# publications

title: Psilocybin in Palliative Care: An Update.
authors: Whinkin E, Opalka M, Watters C, Jaffe A, Aggarwal S.
publication_date: 2023-04-13
doi: 10.1007/s13670-023-00383-7
pubmed_id: 37305379
source_url: https://doi.org/10.1007/s13670-023-00383-7
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Aging,Emotional Processing,Spirituality,Review Article,Safety,Inflammation
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Purpose of reviewThis review article summarizes clinically and socially relevant developments over the past five years in the therapeutic use of the classical tryptamine psychedelic substance psilocybin, with respect to the common challenges faced by palliative care patients and their care teams. Psilocybin is available in whole fungal and isolated forms but is not yet approved for therapeutic use in the United States. Using targeted database and gray literature searches, and author recall, key sources were identified, reviewed, and synthesized as to the safety and efficacy of psilocybin in palliative care.Recent findingsLife-threatening or life-limiting illnesses and faced by palliative care patients are comorbid with emotional and spiritual distress. Research and field reports reviewed suggest that psilocybin has significant and in some cases, sustained anxiolytic, antidepressant, anti-inflammatory and entheogenic effects with a favorable safety profile. Limitations of the research include the risk for selection bias toward healthy, white, financially privileged individuals, and in general, follow-up timelines too short to appropriately evaluate durability of outcomes in psychospiritual benefits and quality of life.SummaryWhile more research is needed for palliative care populations specifically, reasonable inferences can be made regarding the potential for benefit to palliative care patients from psilocybin's demonstrated anxiolytic, antidepressant, anti-inflammatory and entheogenic effects. However, major legal, ethical and financial barriers to access exist for the general population; obstacles which are likely worsened for geriatric and palliative care patients. Empiric treatment and large-scale controlled trials of psilocybin should be conducted to further investigate the findings of the smaller studies reviewed here across a variety of populations, for a greater understanding of therapeutic benefit and clinically relevant safety criteria, and to support thoughtful legalization and medical access.

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authors: Forstmann M, Kettner HS, Sagioglou C, Irvine A, Gandy S, Carhart-Harris RL, Luke D.
publication_date: 2023-01-04
doi: 10.1177/02698811221146356
pubmed_id: 36601974
source_url: https://doi.org/10.1177/02698811221146356
keywords: Humans, N,N-Dimethyltryptamine, Mescaline, Lysergic Acid Diethylamide, Hallucinogens, Psilocybin
substance_tags: psilocybin
topic_tags: Addiction,Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Among psychedelic-experienced users, only past use of psilocybin reliably predicts nature relatedness.

abstract:
BackgroundPast research reports a positive relationship between experience with classic serotonergic psychedelics and nature relatedness (NR). However, these studies typically do not distinguish between different psychedelic compounds, which have a unique psychopharmacology and may be used in specific contexts and with different intentions. Likewise, it is not clear whether these findings can be attributed to substance use per se or unrelated variables that differentiate psychedelic users from nonusers.AimsThe present study was designed to determine the relative degree to which lifetime experience with different psychedelic substances is predictive of self-reported NR among psychedelic-experienced users.MethodsWe conducted a combined reanalysis of five independent datasets (N = 3817). Using standard and regularized regression analyses, we tested the relationship between degree of experience with various psychedelic substances (binary and continuous) and NR, both within a subsample of psychedelic-experienced participants as well as the complete sample including psychedelic-naïve participants.Results/outcomesAmong people experienced with psychedelics, only past use of psilocybin (versus LSD, mescaline, Salvia divinorum, ketamine, and ibogaine) was a reliable predictor of NR and its subdimensions. Weaker, less reliable results were obtained for the pharmacologically similar N,N-dimethyltryptamine (DMT). Results replicate when including psychedelic-naïve participants. In addition, among people exclusively experience with psilocybin, use frequency positively predicted NR.Conclusions/interpretationResults suggest that experience with psilocybin is the only reliable (and strongest) predictor of NR. Future research should focus on psilocybin when investigating effects of psychedelic on NR and determine whether pharmacological attributes or differences in user expectations/use settings are responsible for this observation.

raw_json:
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authors: Henningfield JE, Ashworth J, Heal DJ, Smith SL.
publication_date: 2022-12-31
doi: 10.1177/02698811221140004
pubmed_id: 36588452
source_url: https://doi.org/10.1177/02698811221140004
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
title:
Psychedelic drug abuse potential assessment for new drug applications and controlled substance scheduling: A United States perspective.

abstract:
BackgroundPsychedelics are an increasingly active area of research and pharmaceutical development. This includes abuse potential assessment to better understand their pharmacological mechanisms and effects and guide controlled substance regulation. Psychedelics pose challenges to abuse assessments to ensure valid, reliable, and generalizable outcomes and safe study conduct.FindingsKey nonclinical techniques, for example, receptor binding and functional assays in vitro, and nonclinical physical dependence determinations, are easily adaptable to psychedelics. However, the entactogens (weak reinforcers) and hallucinogens (non-reinforcers) require more flexible approaches than typically recommended by regulatory agencies. Phase 1 pharmacokinetic/pharmacodynamic safety studies and Phases 2/3 efficacy/safety trials with systematic monitoring of abuse-related adverse events are readily applicable to psychedelics. Human abuse trials require modification because supratherapeutic doses may not be safe and procedures, for example, personal monitors to manage serious adverse events, might bias outcomes.RecommendationsAbuse-related studies for psychedelics requiring approval by Food and Drug Administration and other agencies should take into consideration existing knowledge that will vary from extensive, for example, psilocybin, to zero for novel hallucinogens and entactogens. Many abuse assessments can be reasonably applied to animals and humans without compromising scientific integrity. Modification of existing techniques and incorporating a broader range of nonclinical tests should ensure generalizable outcomes. Human abuse studies merit reconsideration and possible modification to ensure safety and validity for psychedelic drug evaluation. Other nonclinical and clinical methods can provide evaluations of the pharmacological equivalence of test drugs to known drugs of abuse to provide context to the abuse assessment and guide drug scheduling.

keywords:
Animals, Humans, Substance-Related Disorders, Lysergic Acid Diethylamide, Hallucinogens, United States, Controlled Substances, Psilocybin

topic_tags:
Pharmacology,Mechanism of Action,Receptor Pharmacology,Clinical Trial,In Vitro Study,Safety,Adverse Events

raw_json:
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authors: Meccia J, Lopez J, Bagot RC.
publication_date: 2022-12-23
doi: 10.1007/s00213-022-06297-0
pubmed_id: 36564671
source_url: https://doi.org/10.1007/s00213-022-06297-0
keywords: Brain, Animals, Humans, Hallucinogens, Antidepressive Agents, Models, Animal, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Brain Imaging,Mechanism of Action,Aging,Review Article,Animal Study
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Probing the antidepressant potential of psilocybin: integrating insight from human research and animal models towards an understanding of neural circuit mechanisms.

abstract:
Interest in the therapeutic potential of serotonergic psychedelic compounds including psilocybin has surged in recent years. While human clinical research suggests psilocybin holds promise as a rapid and long-lasting antidepressant, little is known about how its acute mechanisms of action mediate enduring alterations in cognition and behavior. Human neuroimaging studies point to both acute and sustained modulation of functional connectivity in key cortically dependent brain networks. Emerging evidence in preclinical models highlights the importance of psilocybin-induced neuroplasticity and alterations in the prefrontal cortex (PFC). Overviewing research in both humans and preclinical models suggests avenues to increase crosstalk between fields. We review how acute modulation of PFC circuits may contribute to long-term structural and functional alterations to mediate antidepressant effects. We highlight the potential for preclinical circuit and behavioral neuroscience approaches to provide basic mechanistic insight into how psilocybin modulates cognitive and affective neural circuits to support further development of psilocybin as a promising new treatment for depression.

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authors: Morton E, Sakai K, Ashtari A, Pleet M, Michalak EE, Woolley J.
publication_date: 2022-12-13
doi: 10.1177/02698811221131997
pubmed_id: 36515370
source_url: https://doi.org/10.1177/02698811221131997
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Clinical Trial,Observational Study,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Risks and benefits of psilocybin use in people with bipolar disorder: An international web-based survey on experiences of 'magic mushroom' consumption.

abstract:
BackgroundPsilocybin, the primary psychoactive component of psychedelic 'magic mushrooms', may have potential for treating depressive symptoms, and consequent applications for bipolar disorder (BD). Knowledge of the risks and benefits of psilocybin in BD is limited to case studies.AimTo support the design of clinical trials, we surveyed experiences of psilocybin use in people with BD.MethodsAn international web-based survey was used to explore experiences of psilocybin use in people with a self-reported diagnosis of BD. Quantitative findings were summarised using descriptive statistics. Qualitative content analysis was used to investigate free-text responses, with a focus on positive experiences of psilocybin use.ResultsA total of 541 people completed the survey (46.4% female, mean 34.1 years old). One-third (32.2%; n = 174) of respondents described new/increasing symptoms after psilocybin trips, prominently manic symptoms, difficulties sleeping and anxiety. No differences in rates of adverse events overall were observed between individuals with BD I compared to BD II. Use of emergency medical services was rare (n = 18; 3.3%), and respondents (even those who experienced adverse effects) indicated that psilocybin use was more helpful than harmful. Quantitative findings elaborated on perceived benefits, as well as the potential for psilocybin trips to contain both positively and negatively received elements.ConclusionsThe subjective benefits of psilocybin use for mental health symptoms reported by survey participants encourage further investigation of psilocybin-based treatments for BD. Clinical trials should incorporate careful monitoring of symptoms, as data suggest that BD symptoms may emerge or intensify following psilocybin use.

keywords:
Humans, Agaricales, Hallucinogens, Risk Assessment, Bipolar Disorder, Internet, Adult, Female, Male, Surveys and Questionnaires, Psilocybin

raw_json:
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title: Psychedelic Drug Legislative Reform and Legalization in the US.
authors: Siegel JS, Daily JE, Perry DA, Nicol GE.
publication_date: 2022-12-31
doi: 10.1001/jamapsychiatry.2022.4101
pubmed_id: 36477830
source_url: https://doi.org/10.1001/jamapsychiatry.2022.4101
substance_tags: psilocybin
topic_tags: Aging,Review Article,Older Adults,Adolescents,Contraindications
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
ImportancePsychedelic drugs are becoming accessible in the US through a patchwork of state legislative reforms. This shift necessitates consensus on treatment models, education and guidance for health care professionals, and planning for implementation and regulation.ObjectiveTo assess trends in psychedelics legislative reform and legalization in the US to provide guidance to health care professionals, policy makers, and the public.Evidence reviewData were compiled from legislative databases (BillTrack50, LexisNexis, and Ballotpedia) from January 1, 2019, to September 28, 2022. Legislation was identified by searching for terms related to psychedelics (eg, psilocybin, MDMA, peyote, mescaline, ibogaine, LSD, ayahuasca, and DMT). Bills were coded by an attorney along 2 axes: which psychedelic drugs would be affected and in what ways (eg, decriminalization, funding for medical research, and right to try). To explore drivers and rates of legislative reform, data were compared with other state indices including 2020 presidential voting margins and marijuana legislative reform.FindingsTwenty-five states have considered 74 bills (69 legislative initiatives, 5 ballot measures); 10 bills were enacted, and 32 were still active. The number of psychedelic reform bills introduced during each calendar year increased steadily from 5 in 2019 to 6 in 2020, 27 in 2021, and 36 in 2022. Nearly all bills specified psilocybin (67 [90%]), and many also included MDMA (3,4-methylenedioxy-methamphetamine; 27 [36%]). While bills varied in their framework, most (43 [58%]) proposed decriminalization, of which few delineated medical oversight (10 of 43 [23%]) or training and/or licensure requirements (15 of 43 [35%]). In general, bills contained less regulatory guidance than the enacted Oregon Measure 109. While early legislative efforts occurred in liberal states, the margin between liberal and conservative states has decreased over time (although the difference was not significant), suggesting that psychedelic drug reform is becoming a bipartisan issue. In addition, an analytic model based on marijuana legalization projected that a majority of states will legalize psychedelics by 2034 to 2037.Conclusions and relevanceLegislative reform for psychedelic drugs has been proceeding in a rapid, patchwork fashion in the US. Further consideration should be given to key health care issues such as establishing (1) standards for drugs procured outside the medical establishment, (2) licensure criteria for prescribers and therapists, (3) clinical and billing infrastructure, (4) potential contraindications, and (5) use in special populations like youths, older adults, and pregnant individuals.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Mescaline, Hallucinogens, Pregnancy, Adolescent, Aged, Educational Status, Female, Psilocybin

raw_json:
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title: Psilocybin mitigates the cognitive deficits observed in a rat model of Fragile X syndrome.
authors: Buzzelli V, Carbone E, Manduca A, Schiavi S, Feo A, Perederiy JV, Ambert KH, Hausman M, Trezza V.
publication_date: 2022-12-04
doi: 10.1007/s00213-022-06286-3
pubmed_id: 36469097
source_url: https://doi.org/10.1007/s00213-022-06286-3
substance_tags: psilocybin
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
RationaleFragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID) and the leading monogenic cause of autism spectrum disorder (ASD). Serotonergic neurotransmission has a key role in the modulation of neuronal activity during development, and therefore, it has been hypothesized to be involved in ASD and co-occurring conditions including FXS. As serotonin is involved in synaptic remodeling and maturation, serotonergic insufficiency during childhood may have a compounding effect on brain patterning in neurodevelopmental disorders, manifesting as behavioral and emotional symptoms. Thus, compounds that stimulate serotonergic signaling such as psilocybin may offer promise as effective early interventions for developmental disorders such as ASD and FXS.ObjectivesThe aim of the present study was to test whether different protocols of psilocybin administration mitigate cognitive deficits displayed by the recently validated Fmr1-Δexon 8 rat model of ASD, which is also a model of FXS.ResultsOur results revealed that systemic and oral administration of psilocybin microdoses normalizes the aberrant cognitive performance displayed by adolescent Fmr1-Δexon 8 rats in the short-term version of the novel object recognition test-a measure of exploratory behavior, perception, and recognition.ConclusionsThese data support the hypothesis that serotonin-modulating drugs such as psilocybin may be useful to ameliorate ASD-related cognitive deficits. Overall, this study provides evidence of the beneficial effects of different schedules of psilocybin treatment in mitigating the short-term cognitive deficit observed in a rat model of FXS.

keywords:
Animals, Rats, Fragile X Syndrome, Serotonin, Cognition, Autism Spectrum Disorder, Psilocybin, Fragile X Messenger Ribonucleoprotein 1

topic_tags:
Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Microdosing,Emotional Processing,Animal Study,Adolescents

raw_json:
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authors: Shukuroglou M, Roseman L, Wall M, Nutt D, Kaelen M, Carhart-Harris R.
publication_date: 2022-11-25
doi: 10.1177/02698811221125354
pubmed_id: 36433778
source_url: https://doi.org/10.1177/02698811221125354
substance_tags: psilocybin
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Changes in music-evoked emotion and ventral striatal functional connectivity after psilocybin therapy for depression.

abstract:
BackgroundMusic listening is a staple and valued component of psychedelic therapy, and previous work has shown that psychedelics can acutely enhance music-evoked emotion.AimsThe present study sought to examine subjective responses to music before and after psilocybin therapy for treatment-resistant depression, while functional magnetic resonance imaging (fMRI) data was acquired.MethodsNineteen patients with treatment-resistant depression received a low oral dose (10 mg) of psilocybin, and a high dose (25 mg) 1 week later. fMRI was performed 1 week prior to the first dosing session and 1 day after the second. Two scans were conducted on each day: one with music and one without. Visual analogue scale ratings of music-evoked 'pleasure' plus ratings of other evoked emotions (21-item Geneva Emotional Music Scale) were completed after each scan. Given its role in musical reward, the nucleus accumbens (NAc) was chosen as region of interest for functional connectivity (FC) analyses. Effects of drug (vs placebo) and music (vs no music) on subjective and FC outcomes were assessed. Anhedonia symptoms were assessed pre- and post-treatment (Snaith-Hamilton Pleasure Scale).ResultsResults revealed a significant increase in music-evoked emotion following treatment with psilocybin that correlated with post-treatment reductions in anhedonia. A post-treatment reduction in NAc FC with areas resembling the default mode network was observed during music listening (vs no music).ConclusionThese results are consistent with current thinking on the role of psychedelics in enhancing music-evoked pleasure and provide some new insight into correlative brain mechanisms.

keywords:
Humans, Hallucinogens, Magnetic Resonance Imaging, Depression, Emotions, Music, Anhedonia, Psilocybin

topic_tags:
Depression,Brain Imaging,Mechanism of Action,Default Mode Network,Aging,Emotional Processing,Treatment-Resistant Depression

raw_json:
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title: Should we be leery of being Leary? Concerns about psychedelic use by psychedelic researchers.
authors: Kious B, Schwartz Z, Lewis B
journal: Journal of psychopharmacology (Oxford, England)
publication_date: 2022-12-31
doi: 10.1177/02698811221133461
pubmed_id: 36377548
source_url: https://pubmed.ncbi.nlm.nih.gov/36377548/
keywords: MDMA, Psychedelic, psilocybin, research ethics
substance_tags: psilocybin
topic_tags: PTSD,Clinical Trial
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"36377548"}
abstract:
Psychedelic research is proceeding rapidly, despite ongoing legal and regulatory barriers and lingering questions about study design, such as the difficulty of ensuring adequate blinding, the relative overrepresentation in studies of participants who have previously used psychedelics, and the importance of personal experience with psychedelics for those who provide psychedelic-assisted therapy. Here we wish to explore a distinct concern: whether personal use of psychedelics by researchers could threaten the objectivity and ethical conduct of psychedelic research itself. In 2020, Anderson et al. suggested that psychedelic use could lead even "conservative individuals to become wildly enthusiastic about the potentials of psychedelics to heal and transform". Recent popular press criticisms of psychedelic science, in particular critiques of the MAPS Phase II and Phase III MDMA-Assisted Therapy trials for PTSD, have also raised questions about whether personal use of psychedelic drugs by psychedelic therapists could compromise scientific objectivity, lead to the exploitation of research subjects, or promote biased reporting of results. Here, we elaborate on and attempt to delimit these concerns, with the goal of informing policy related to psychedelic research and the eventual clinical use of psychedelics. In particular, we explore whether the possibility that psychedelic use can directly and positively affect investigators' enthusiasm about psychedelics themselves raises concerns about bias and scientific integrity. We then discuss several practical strategies to reduce perceived conflict of interest.


title: Body mass index (BMI) does not predict responses to psilocybin.
publication_date: 2022-11-13
doi: 10.1177/02698811221131994
pubmed_id: 36373934
source_url: https://doi.org/10.1177/02698811221131994
keywords: Humans, Serotonin, Hallucinogens, Body Mass Index, Bayes Theorem, Emotions, Psilocybin
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Wellbeing,Emotional Processing,Mystical Experience
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
authors:
Spriggs MJ, Giribaldi B, Lyons T, Rosas FE, Kärtner LS, Buchborn T, Douglass HM, Roseman L, Timmermann C, Erritzoe D, Nutt DJ, Carhart-Harris RL.

abstract:
BackgroundPsilocybin is a serotonin type 2A (5-HT2A) receptor agonist and naturally occurring psychedelic. 5-HT2A receptor density is known to be associated with body mass index (BMI), however, the impact of this on psilocybin therapy has not been explored. While body weight-adjusted dosing is widely used, this imposes a practical and financial strain on the scalability of psychedelic therapy. This gap between evidence and practice is caused by the absence of studies clarifying the relationship between BMI, the acute psychedelic experience and long-term psychological outcomes.MethodData were pooled across three studies using a fixed 25 mg dose of psilocybin delivered in a therapeutic context to assess whether BMI predicts characteristics of the acute experience and changes in well-being 2 weeks later. Supplementing frequentist analysis with Bayes Factors has enabled for conclusions to be drawn regarding the null hypothesis.ResultsResults support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes or emotional breakthroughs during the acute experience. There was weak evidence for greater 'dread of ego dissolution' in participants with lower BMI, however, further analysis suggested BMI did not meaningfully add to the combination of the other covariates (age, sex and study). While mystical-type experiences and emotional breakthroughs were strong predictors of improvements in well-being, BMI was not.ConclusionsThese findings have important implications for our understanding of pharmacological and extra-pharmacological contributors to psychedelic-assisted therapy and for the standardization of a fixed therapeutic dose in psychedelic-assisted therapy.

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title: Psilocin - The "real deal" or an extraction byproduct.
authors: Gutman O, Tenne D, Bretler U.
publication_date: 2022-11-03
doi: 10.1111/1556-4029.15167
pubmed_id: 36333836
source_url: https://doi.org/10.1111/1556-4029.15167
keywords: Substance Abuse Detection, Gas Chromatography-Mass Spectrometry, Psilocybin, Illicit Drugs
substance_tags: psilocybin,psilocin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Most illicit drug casework samples at the Israel Police National Drug Laboratory are found to be mixtures of substances. Some are a mixture of an illicit drug with fillers, and others may contain more than one illicit drug. This study was triggered by a routine gas chromatography-mass spectrometry (GC-MS) analysis of an unusual casework sample. The sample chromatogram showed a mixture of two illicit drugs, 4-acetoxy-DMT and psilocin. Considering the two substances' similar skeletal structure, the authors wondered whether the sample was indeed a mixture of the two substances, or whether perhaps 4-acetoxy-DMT was hydrolyzed to psilocin during the analysis. This study hypothesized that indeed the base used in the pre-injection sample preparation hydrolyzed the ester group on the 4-acetoxy-DMT yielding a hydroxide group. This was tested using several concentrations of ammonium hydroxide and two additional bases - pyridine (a weak base) and sodium hydroxide (a strong base). Results showed that media with a higher pH (induced by the stronger base) yielded a higher psilocin to 4-acetoxy-DMT ratio which is compatible with degradation of 4-acetoxy-DMT. This study also explored the possibility that psilocin was a byproduct of thermal decomposition of 4-acetoxy-DMT and found it thermally stable in the temperature of the GC injection port (200°C). The 4-acetoxy-DMT case demonstrates how pre-injection laboratory procedures can inadvertently modify casework samples. Caution is clearly advisable in selecting reagents and processes in general, and specifically in the case of GC-MS pre-injection procedures conducted to analyze substances like the ones in the present study.

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authors: Jones GM.
publication_date: 2022-10-30
doi: 10.1177/02698811221127304
pubmed_id: 36314881
source_url: https://doi.org/10.1177/02698811221127304
substance_tags: psilocybin
topic_tags: Depression,Observational Study,Drug Interactions
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Race and ethnicity moderate the associations between lifetime psychedelic use (MDMA/ecstasy and psilocybin) and major depressive episodes.

abstract:
BackgroundPsychedelics are receiving renewed attention within Western medicine as they represent potential treatments for many difficult-to-treat mental health disorders. However, psychedelic science is limited in its focus and inclusion of racial and ethnic minorities. Hence, this study examines whether race and ethnicity moderate the associations that naturalistic 3,4-methylenedioxymethamphetamine (MDMA)/ecstasy use and psilocybin use share with major depressive episodes (MDEs).MethodData for this project are from The National Survey on Drug Use and Health (2005-2019). Participants were adults aged 18 years and older (unweighted N = 596,187). This study used multivariable logistic regression to test the interaction between race and ethnicity and MDMA/ecstasy use and psilocybin use for predicting lifetime, past year, and past year severe MDEs.ResultsRace and ethnicity significantly moderated the associations between MDMA/ecstasy use and psilocybin use and MDEs. For White participants, MDMA/ecstasy use and psilocybin use each were associated with lowered odds of all three MDE outcomes (adjusted odds ratio (aOR) range: 0.82-0.92). For Hispanic participants, MDMA/ecstasy use and psilocybin use each conferred lowered odds of only a past year MDE (MDMA/ecstasy aOR: 0.82; psilocybin aOR: 0.79). For Non-Hispanic Racial Minority participants, MDMA/ecstasy and psilocybin use did not confer lowered odds of any MDE outcomes.ConclusionRace and ethnicity have an impact on the associations that psychedelics share with mental health outcomes. Future research should explore the impact of identity and discrimination on the effects of psychedelics and should explore whether these substances can serve as effective treatments for minorities when used in culturally informed contexts.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Adult, Psilocybin, Ethnicity, Major Depressive Disorder

raw_json:
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title: Mescaline: The forgotten psychedelic.
authors: Vamvakopoulou IA, Narine KAD, Campbell I, Dyck JRB, Nutt DJ.
publication_date: 2022-10-13
doi: 10.1016/j.neuropharm.2022.109294
pubmed_id: 36252614
source_url: https://doi.org/10.1016/j.neuropharm.2022.109294
substance_tags: psilocybin
topic_tags: Pharmacology,Mechanism of Action,Receptor Pharmacology,Wellbeing,Review Article,Animal Study
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
IntroductionMescaline (3,4,5-trimethoxyphenethylamine) is one of the oldest hallucinogens, with evidence of use dating back 5700 years. Mescaline is a naturally occurring alkaloid found in cacti, mainly in the peyote cactus (Lophophora williamsii) and in the cacti of the Echinopsis genus. Since the prohibition of psychoactive substances in the early 70s, research on mescaline and other classical psychedelics has been limited.ObjectivesThis article aims to review the pharmacology and behavioural effects of mescaline, focusing on preclinical and clinical research.FindingsMescaline is a serotonin 5HT2A/2C receptor agonist, with its main hallucinogenic effects being mediated via its 5HT2A receptor agonist action. It also exerts effects via agonist binding at α1A/2A noradrenaline and D1/2/3 dopamine receptors. Overall, mescaline has anxiolytic-like effects in animals and increases prosocial behaviour, locomotion, and response reactivity. In humans, mescaline can induce euphoria, hallucinations, improvements in well-being and mental health conditions, and psychotomimetic effects in a naturalistic or religious setting.ConclusionThe pharmacological mechanisms of mescaline are similar to those of other classical psychedelics, like psilocybin and lysergic acid diethylamide (LSD). Mescaline appears to be safe to consume, with most intoxications being mild and easily treatable. Improvement in mental well-being and its ability to overcome alcoholism render mescaline potentially beneficial in clinical settings. This article is part of the Special Issue on 'Psilocybin Research'.

keywords:
Animals, Humans, Memory Disorders, Mescaline, Lysergic Acid Diethylamide, Hallucinogens, Serotonin 5-HT2 Receptor Agonists, Psilocybin

raw_json:
{"europe_pmc_id":"36252614","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The Safety and Efficacy of Psychedelic-Assisted Therapies for Older Adults: Knowns and Unknowns.
authors: Johnston CB, Mangini M, Grob C, Anderson B.
publication_date: 2022-09-05
doi: 10.1016/j.jagp.2022.08.007
pubmed_id: 36184377
source_url: https://doi.org/10.1016/j.jagp.2022.08.007
keywords: Brain, Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Aged, Psilocybin
substance_tags: psilocybin
topic_tags: PTSD,Receptor Pharmacology,Aging,Clinical Trial,Older Adults,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Psychedelics and related compounds have shown efficacy for the treatment of a variety of conditions that are prevalent among older adults, including mood disorders, the psychological distress associated with a serious medical illness, post-traumatic stress disorder (PTSD), and prolonged grief disorder. Psychedelics also have properties that could help provide therapeutic benefits for patients with dementing disorders, as well as promoting personal growth among healthy older adults. This article focuses on psilocybin, a classic psychedelic, and MDMA, a substituted amphetamine with properties similar to classic psychedelics. Both act on the 5HT2A receptor. Psychedelics can be safely administered to healthy adults in controlled conditions. However, both psilocybin and MDMA can increase blood pressure and heart rate, which could be a concern if used in older adults with cardiovascular disease. Very few older adults or patients with serious comorbidities have been included in clinical trials of psychedelics to date, raising the question of how generalizable study results are for the patients that most geropsychiatrists will be treating. Research on the neurophysiologic and mechanistic effects of psychedelics in older adults could also provide insights into the aging brain that could have clinical applications in the future. Given the potential of psychedelic compounds to benefit older adults, more research is needed to establish safety and efficacy among older adults, particularly those with multi-morbidity.

raw_json:
{"europe_pmc_id":"36184377","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Towards an understanding of psychedelic-induced neuroplasticity.
authors: Calder AE, Hasler G.
publication_date: 2022-09-18
doi: 10.1038/s41386-022-01389-z
pubmed_id: 36123427
source_url: https://doi.org/10.1038/s41386-022-01389-z
keywords: Humans, Hallucinogens, Anxiety, Anxiety Disorders, Neuronal Plasticity, Psilocybin
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Classic psychedelics, such as LSD, psilocybin, and the DMT-containing beverage ayahuasca, show some potential to treat depression, anxiety, and addiction. Importantly, clinical improvements can last for months or years after treatment. It has been theorized that these long-term improvements arise because psychedelics rapidly and lastingly stimulate neuroplasticity. The focus of this review is on answering specific questions about the effects of psychedelics on neuroplasticity. Firstly, we review the evidence that psychedelics promote neuroplasticity and examine the cellular and molecular mechanisms behind the effects of different psychedelics on different aspects of neuroplasticity, including dendritogenesis, synaptogenesis, neurogenesis, and expression of plasticity-related genes (e.g., brain-derived neurotrophic factor and immediate early genes). We then examine where in the brain psychedelics promote neuroplasticity, particularly discussing the prefrontal cortex and hippocampus. We also examine what doses are required to produce this effect (e.g., hallucinogenic doses vs. "microdoses"), and how long purported changes in neuroplasticity last. Finally, we discuss the likely consequences of psychedelics' effects on neuroplasticity for both patients and healthy people, and we identify important research questions that would further scientific understanding of psychedelics' effects on neuroplasticity and its potential clinical applications.

topic_tags:
Depression,Anxiety,Addiction,Neuroplasticity,Neurogenesis,Mechanism of Action,Microdosing,Review Article

raw_json:
{"europe_pmc_id":"36123427","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2022-08-16
doi: 10.1177/07067437221111371
pubmed_id: 35975555
source_url: https://doi.org/10.1177/07067437221111371
keywords: Humans, Neoplasms, Hallucinogens, Anxiety, Canada, Psilocybin, Major Depressive Disorder
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: Serotonergic Psychedelic Treatments for Major Depressive Disorder.

authors:
Rosenblat JD, Husain MI, Lee Y, McIntyre RS, Mansur RB, Castle D, Offman H, Parikh SV, Frey BN, Schaffer A, Greenway KT, Garel N, Beaulieu S, Kennedy SH, Lam RW, Milev R, Ravindran AV, Tourjman V, Ameringen MV, Yatham LN, Taylor V.

abstract:
ObjectiveSerotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder.MethodsA systematic review was conducted to identify contemporary clinical trials of serotonergic psychedelics for the treatment of major depressive disorder and cancer-related depression. Studies published between January 1990 and July 2021 were identified using combinations of search terms, inspection of bibliographies and review of other psychedelic reviews and consensus statements. The levels of evidence for efficacy were graded according to the Canadian Network for Mood and Anxiety Treatments criteria.ResultsOnly psilocybin and ayahuasca have contemporary clinical trials evaluating antidepressant effects. Two pilot studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator (escitalopram with supportive psychotherapy) in major depressive disorder, with additional randomized controlled trials showing efficacy specifically in cancer-related depression (Level 3 evidence). There was only one open-label trial of psilocybin in treatment-resistant unipolar depression (Level 4 evidence). Small sample sizes and functional unblinding were major limitations in all studies. Adverse events associated with psychedelics, including psychological (e.g., psychotomimetic effects) and physical (e.g., nausea, emesis and headaches) effects, were generally transient.ConclusionsThere is currently only low-level evidence to support the efficacy and safety of psychedelics for major depressive disorder. In Canada, as of 2022, psilocybin remains an experimental option that is only available through clinical trials or the special access program. As such, Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment and recommends its use primarily within clinical trials, or, less commonly, through the special access program in rare, special circumstances.

topic_tags:
Depression,Anxiety,Headache / Migraine,Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article,Cancer Patients,Treatment-Resistant Depression,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"35975555","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Sustained effects of single doses of classical psychedelics in humans.
authors: Knudsen GM.
publication_date: 2022-06-20
doi: 10.1038/s41386-022-01361-x
pubmed_id: 35729252
source_url: https://doi.org/10.1038/s41386-022-01361-x
keywords: Brain, Humans, Hallucinogens, Personality, Anxiety Disorders, Psilocybin
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
The serotonergic classical psychedelics include compounds that primarily activate the brain's serotonin 2 A receptor (5-HT2AR), such as LSD, psilocybin, and DMT (ayahuasca). The acute effects of these compounds are well-known as are their ability to increase the emotional state both in healthy people and in those with neuropsychiatric disorders. In particular psilocybin, the psychoactive constituent in "magic mushrooms", has shown great potential for treatment of anxiety and depression. A unique and compelling feature of psychedelics is that intake of just a single psychedelic dose is associated with long-lasting effects. This includes effects on personality, e.g., higher openness, and amelioration of depressive symptoms. This review focuses on these stunning effects and summarizes our current knowledge on which behavioral, biochemical, neuroimaging, and electrophysiological data support that the intriguing effects of psychedelics on the human brain and mind are based on neural plasticity. The review also points to so far understudied areas and suggests research questions to be addressed in future studies which potentially can help to understand the intriguing long-term effects after intake of a single (or a few) psychedelic doses.

topic_tags:
Depression,Anxiety,Neuroplasticity,Brain Imaging,Receptor Pharmacology,Aging,Personality Change,Emotional Processing,Review Article

raw_json:
{"europe_pmc_id":"35729252","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: How Important Is a Guide Who Has Taken Psilocybin in Psilocybin-Assisted Therapy for Depression?
authors: Earleywine M, Low F, Altman BR, De Leo J.
publication_date: 2022-03-22
doi: 10.1080/02791072.2022.2047842
pubmed_id: 35318904
source_url: https://doi.org/10.1080/02791072.2022.2047842
keywords: Humans, Antidepressive Agents, Depression, Psychotherapy, Psilocybin, Cognitive Behavioral Therapy
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
Promising outcomes of Psilocybin-Assisted Therapy (PAT) for depression have generated concerted efforts to replicate, extend, and refine protocols to maximize efficacy. Psychotherapy research reveals that clients benefit most when important components of treatment align with their personal preferences. One open question related to PAT concerns the importance of the psilocybin experience of the guides (trained professionals present during acute effects). We sought to assess the importance of a guide who had used psilocybin to potential clients with depressive symptoms. Over 800 MTurk respondents with depressive symptoms rated the import of a guide who had used psilocybin relative to alternative characteristics in guides and cognitive behavioral (CBT) therapists. Importance ratings for guides who had used psilocybin significantly exceeded the "somewhat important" level (50 on a 0-100 scale), other guide-related qualities, and comparable ratings for a cognitive behavioral therapist who shared demographics, had experience with depression and received cognitive therapy personally. People of color (those who are not Caucasian) and those who had previous therapy gave significantly higher importance ratings for guides who had used psilocybin. Participants who chose to list other qualities important for guides listed very similar ones for CBT therapists, often emphasizing proper training and an empathic demeanor. Guides who have used psilocybin, who inform clients of the fact, might have advantages for facilitating PAT's antidepressant effects, as least in a subset of clients.

raw_json:
{"europe_pmc_id":"35318904","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Hodge AT, Sukpraprut-Braaten S, Narlesky M, Strayhan RC.
publication_date: 2022-02-27
doi: 10.1080/02791072.2022.2044096
pubmed_id: 35225726
source_url: https://doi.org/10.1080/02791072.2022.2044096
keywords: Humans, Lysergic Acid Diethylamide, Hallucinogens, Anxiety, Mental Disorders, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Clinical Trial,Systematic Review,Review Article,Safety
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
The Use of Psilocybin in the Treatment of Psychiatric Disorders with Attention to Relative Safety Profile: A Systematic Review.

abstract:
There has been a reemergence of research into the use of substances such as LSD, MDMA, and psilocybin for the treatment of psychiatric disorders. This increase in consideration toward the medicinal use of these compounds has been termed the "Psychedelic Renaissance." This article specifically explores the background of psilocybin, a psychoactive compound that is naturally derived from certain species of fungi. Pubmed was searched by one doctoral-level researcher using specific Boolean operator terms. The results were filtered by title and abstract and 76 articles were screened and analyzed in full detail. Oral psilocybin is showing itself to be clinically efficacious by producing statistically significant reductions in depression and anxiety symptoms over time versus control in multiple clinical trials. It has also been shown to reduce cigarettes per day and drinks per day in patients with substance use disorders. Thus far, there have been no significant adverse clinical events from psilocybin and there also have been no verifiable recorded deaths reported. Larger studies need to be performed before the drug can potentially become approved for use in the general population.

raw_json:
{"europe_pmc_id":"35225726","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Knowledge, Perceptions, and Use of Psychedelics among Individuals with Fibromyalgia.
authors: Glynos NG, Pierce J, Davis AK, McAfee J, Boehnke KF.
publication_date: 2022-01-09
doi: 10.1080/02791072.2021.2022817
pubmed_id: 35001856
source_url: https://doi.org/10.1080/02791072.2021.2022817
substance_tags: psilocybin
topic_tags: Chronic Pain,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Fibromyalgia (FM) is a difficult to treat chronic pain condition for which there is strong interest in alternative treatments. There is growing interest in the potential of psychedelic substances (e.g., psilocybin) in conjunction with psychotherapy to treat chronic pain. Via a cross-sectional, anonymous, online survey, we aimed to characterize knowledge, perceptions, and past use of serotonergic ("classic") and non-serotonergic psychedelics among a population of individuals with FM, and to investigate interest in psychedelic-based FM treatments. Among a North American population of 354 participants with FM, 29.9% reported past use of a psychedelic, with lysergic acid diethylamide (LSD) and psilocybin mushrooms being most commonly used. Perceptions of benefit from psychedelic use were generally neutral (59.4%) or positive (36.8%), with

keywords:
Humans, Fibromyalgia, Lysergic Acid Diethylamide, Hallucinogens, Cross-Sectional Studies, Chronic Pain, Psilocybin

raw_json:
{"europe_pmc_id":"35001856","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Hadar A, David J, Shalit N, Roseman L, Gross R, Sessa B, Lev-Ran S
journal: Journal of psychoactive drugs
publication_date: 2022-12-31
doi: 10.1080/02791072.2021.2022254
pubmed_id: 35000572
source_url: https://pubmed.ncbi.nlm.nih.gov/35000572/
substance_tags: psilocybin
topic_tags: Chronic Pain,Healthcare Workers
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"35000572"}
title:
The Psychedelic Renaissance in Clinical Research: A Bibliometric Analysis of Three Decades of Human Studies with Psychedelics.

abstract:
Psychedelics were used in the treatment of psychiatric conditions prior to their prohibition in the late 1960s. In the past three decades, there is a revived research interest in the therapeutic potential of psychedelic drugs with expected FDA approvals for treatment of various conditions. Given the exponential scientific growth of this field, we sought to characterize, analyze, and visualize trends in its top-cited articles. Bibliometric analyses are quantitative approaches to characterize a scientific field, including evaluation of the impact of academic literature. The bibliometric analysis and visualizations were conducted with R-tools for comprehensive science mapping. The top-cited 100 articles were cited between 82 and 668 times (median 125; mean 158). Fifty-four percent of the T100 articles were produced in the past decade (2010-2020). Network and author impact analysis highlighted key figures and primary collaboration networks within the top 100 publications. UK, USA, Switzerland, Spain, and Brazil lead the field. Results are discussed in terms of research growth, access, diversity, and the distribution of knowledge and experience in the field. These aggregated data and insights on the second wave of psychedelic research facilitate research evaluation, data-driven funding policies, and a practical map for researchers and clinicians entering the field.

keywords:
3, 4-methyl enedioxy methamphetamine, LSD, Lysergic acid diethylamide, MDMA, ayahuasca, bibliometric analysis, drug–psychotherapy combination, psilocybin, psychedelics, research evaluation, scientometrics


title: Linkages between Psychedelics and Meditation in a Population-Based Sample in the United States.
authors: Simonsson O, Goldberg SB
journal: Journal of psychoactive drugs
publication_date: 2022-12-31
doi: 10.1080/02791072.2021.2022816
pubmed_id: 35000559
source_url: https://pubmed.ncbi.nlm.nih.gov/35000559/
keywords: LSD, Psilocybin, Psychedelics, ego dissolution, meditation, mindfulness
substance_tags: psilocybin
topic_tags: Randomized Controlled Trial,Observational Study,Safety
study_type: Randomized Controlled Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"35000559"}
abstract:
There are neurophysiological and phenomenological overlaps between psychedelic and meditative states, but there is little evidence on how exposure to psychedelics might be associated with meditation-related variables. We assessed lifetime classic psychedelic use, ego dissolution during one's most intense experience using a classic psychedelic, and exposure to meditation in a representative sample (n = 953) of American adults. Those who reported experience with meditation were invited to complete a follow-up survey (n = 536, 92.1% response rate) measuring meditation-related variables. Models controlled for a range of potential confounds. Exposure to meditation was associated with lifetime classic psychedelic use and ego dissolution in covariate-adjusted models. In addition, among meditators, greater ego dissolution was associated with more frequent meditation practice. Both lifetime classic psychedelic use and ego dissolution were associated with enlightenment as motivation to practice meditation as well as lower likelihood of overall perceived barriers to meditation practice. Ego dissolution was positively associated with finding meditation more effective. Neither lifetime classic psychedelic use nor ego dissolution was associated with greater likelihood of meditation-related adverse effects. Taken together, results support potential synergy between psychedelics and meditation, but randomized controlled trials are necessary to establish safety and evaluate potential causal relationships.


title: Psilocybin for Depression: From Credibility to Feasibility, What's Missing?
authors: Munafò A, Arillotta D, Mannaioni G, Schifano F, Bernardini R, Cantarella G.
publication_date: 2022-12-30
doi: 10.3390/ph16010068
pubmed_id: 36678564
source_url: https://doi.org/10.3390/ph16010068
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
Psilocybin has been suggested as a promising transdiagnostic treatment strategy for a wide range of psychiatric disorders. Recent findings showed that psychedelic-assisted/"psycholitic" psychotherapy should provide significant and sustained alleviation of depressive symptoms. However, to date, there have been several study limitations (e.g., small sample sizes, blinding, limited follow-up, highly screened treatment populations) and some health/political issues, including practitioners' experience, lack of standardized protocols, psychedelics' legal status, ethical concerns, and potential psychological/psychopathological/medical untoward effects. The focus here is on a range of clinical and methodological issues, also aiming at outlining some possible suggestions. We are confident that newer evidence, more precise protocols, and eventual reclassification policies may allow a better understanding of the real potential of psilocybin as a transdiagnostic therapeutic molecule.

raw_json:
{"europe_pmc_id":"36678564","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A Review of Synthetic Access to Therapeutic Compounds Extracted from.
authors: Serreau R, Amirouche A, Benyamina A, Berteina-Raboin S
journal: Pharmaceuticals (Basel, Switzerland)
publication_date: 2022-12-27
doi: 10.3390/ph16010040
pubmed_id: 36678537
source_url: https://pubmed.ncbi.nlm.nih.gov/36678537/
substance_tags: psilocybin,psilocin
topic_tags: Review Article
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"36678537"}
abstract:
Psychedelics are used for various pathologies of the central nervous system and are currently the subject of much research, some of which relates to the compounds contained in various -type hallucinogenic mushrooms. It is difficult, however, to obtain and purify sufficient quantities of these compounds from fungi to carry out biological studies, hence the need to develop simple and efficient synthetic routes. We review here the various syntheses used to obtain these molecules, focusing first on the classic historical syntheses, then the use of more recent metallo-catalyzed couplings and finally the known biocatalytic methods for obtaining these molecules. Other access routes are certainly possible and should be the subject of future research given the therapeutic interest of these compounds.

keywords:
Psilocybe mushrooms, clinical research, psilocin, psilocybin, psychedelics, synthetic access, tryptamines


publication_date: 2022-11-28
doi: 10.1128/aem.01498-22
pubmed_id: 36445079
source_url: https://doi.org/10.1128/aem.01498-22
keywords: Agaricales, Tryptamines, DNA, Psilocybe, Psilocybin
substance_tags: psilocybin,psilocin
topic_tags: Depression,PTSD,Addiction,End-of-Life Distress,Metabolomics
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
DNA Authentication and Chemical Analysis of Psilocybe Mushrooms Reveal Widespread Misdeterminations in Fungaria and Inconsistencies in Metabolites.

authors:
Bradshaw AJ, Backman TA, Ramírez-Cruz V, Forrister DL, Winter JM, Guzmán-Dávalos L, Furci G, Stamets P, Dentinger BTM.

abstract:
The mushroom genus Psilocybe is best known as the core group of psychoactive mushrooms, yet basic information on their diversity, taxonomy, chemistry, and general biology is still largely lacking. In this study, we reexamined 94 Psilocybe fungarium specimens, representing 18 species, by DNA barcoding, evaluated the stability of psilocybin, psilocin, and their related tryptamine alkaloids in 25 specimens across the most commonly vouchered species (Psilocybe cubensis, Psilocybe cyanescens, and Psilocybe semilanceata), and explored the metabolome of cultivated P. cubensis. Our data show that, apart from a few well-known species, the taxonomic accuracy of specimen determinations is largely unreliable, even at the genus level. A substantial quantity of poor-quality and mislabeled sequence data in public repositories, as well as a paucity of sequences derived from types, further exacerbates the problem. Our data also support taxon- and time-dependent decay of psilocybin and psilocin, with some specimens having no detectable quantities of them. We also show that the P. cubensis metabolome possibly contains thousands of uncharacterized compounds, at least some of which may be bioactive. Taken together, our study undermines commonly held assumptions about the accuracy of names and presence of controlled substances in fungarium specimens identified as Psilocybe spp. and reveals that our understanding of the chemical diversity of these mushrooms is largely incomplete. These results have broader implications for regulatory policies pertaining to the storage and sharing of fungarium specimens as well as the use of psychoactive mushrooms for recreation and therapy. IMPORTANCE The therapeutic use of psilocybin, the active ingredient in "magic mushrooms," is revolutionizing mental health care for a number of conditions, including depression, posttraumatic stress disorder (PTSD), and end-of-life care. This has spotlighted the current state of knowledge of psilocybin, including the organisms that endogenously produce it. However, because of international regulation of psilocybin as a controlled substance (often included on the same list as cocaine and heroin), basic research has lagged far behind. Our study highlights how the poor state of knowledge of even the most fundamental scientific information can impact the use of psilocybin-containing mushrooms for recreational or therapeutic applications and undermines critical assumptions that underpin their regulation by legal authorities. Our study shows that currently available chemical studies are mainly inaccurate, irreproducible, and inconsistent, that there exists a high rate of misidentification in museum collections and public databases rendering even names unreliable, and that the concentration of psilocybin and its tryptamine derivatives in three of the most commonly collected Psilocybe species (P. cubensis, P. cyanescens, and P. semilanceata) is highly variable and unstable in museum specimens spanning multiple decades, and our study generates the first-ever insight into the highly complex and largely uncharacterized metabolomic profile for the most commonly cultivated magic mushroom, P. cubensis.

raw_json:
{"europe_pmc_id":"36445079","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Jones G, Arias D, Nock M.
publication_date: 2022-12-18
doi: 10.1038/s41598-022-25658-5
pubmed_id: 36535992
source_url: https://doi.org/10.1038/s41598-022-25658-5
substance_tags: psilocybin
topic_tags: Observational Study,Adolescents
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Associations between MDMA/ecstasy, classic psychedelics, and suicidal thoughts and behaviors in a sample of U.S. adolescents.

abstract:
Suicide is one of the leading causes of death amongst adolescents and decades of research have failed to curb suicide rates within this population. There is thus a need to better understand factors that correlate with adolescent suicidal thoughts and behaviors (STBs). MDMA/ecstasy and classic psychedelics represent two areas for exploration, as use of these substances has been associated with both increased and lowered odds of STBs. Thus, the goal of this study was to test the associations between MDMA/ecstasy and classic psychedelics (psilocybin, peyote, mescaline, LSD) and STBs in a nationally representative sample of U.S. adolescents. We tested these associations in a sample of adolescents aged 12-17 years old from the National Survey on Drug Use and Health (2004-2019) (N = 262,617) using survey-weighted multivariable logistic regression models. Lifetime psilocybin use was associated with lowered odds of lifetime suicidal thinking, planning, and attempts (aOR range 0.77-0.85). Conversely, LSD was associated with increased odds of these same outcomes (aOR range 1.20-1.35). MDMA/ecstasy, peyote, and mescaline did not share associations with STBs. Our study demonstrates that individual classic psychedelics share varying relationships to STBs among adolescents. Future cross-sectional and longitudinal studies are needed to further elucidate the link between classic psychedelic use and STBs in youth.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Mescaline, Lysergic Acid Diethylamide, Hallucinogens, Cross-Sectional Studies, Adolescent, Child, Suicidal Ideation, Psilocybin

raw_json:
{"europe_pmc_id":"36535992","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Characterization of the Gateway Decarboxylase for Psilocybin Biosynthesis.
authors: Schäfer T, Kramer K, Werten S, Rupp B, Hoffmeister D.
publication_date: 2022-11-21
doi: 10.1002/cbic.202200551
pubmed_id: 36327140
source_url: https://doi.org/10.1002/cbic.202200551
substance_tags: psilocybin
topic_tags: Depression,In Vitro Study
study_type: In Vitro Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
The l-tryptophan decarboxylase PsiD catalyzes the initial step of the metabolic cascade to psilocybin, the major indoleethylamine natural product of the "magic" mushrooms and a candidate drug against major depressive disorder. Unlike numerous pyridoxal phosphate (PLP)-dependent decarboxylases for natural product biosyntheses, PsiD is PLP-independent and resembles type II phosphatidylserine decarboxylases. Here, we report on the in vitro biochemical characterization of Psilocybe cubensis PsiD along with in silico modeling of the PsiD structure. A non-canonical serine protease triad for autocatalytic cleavage of the pro-protein was predicted and experimentally verified by site-directed mutagenesis.

keywords:
Humans, Pyridoxal Phosphate, Carboxy-Lyases, Biological Products, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"36327140","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: DellaCrosse M, Pleet M, Morton E, Ashtari A, Sakai K, Woolley J, Michalak E.
publication_date: 2022-12-13
doi: 10.1371/journal.pone.0279073
pubmed_id: 36516137
source_url: https://doi.org/10.1371/journal.pone.0279073
keywords: Humans, Follow-Up Studies, Bipolar Disorder, Quality of Life, Adult, Self Report, Psilocybin, Mania
substance_tags: psilocybin
topic_tags: Depression,Addiction,Emotional Processing,Clinical Trial,Observational Study,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
"A sense of the bigger picture:" A qualitative analysis of follow-up interviews with people with bipolar disorder who self-reported psilocybin use.

abstract:
ObjectivesPeople with bipolar disorder (BD) spend more time depressed than manic/hypomanic, and depression is associated with greater impairments in psychosocial functioning and quality of life than mania/hypomania. Emerging evidence suggests psilocybin, the psychoactive compound in "magic mushrooms," is a promising treatment for unipolar depression. Clinical trials of psilocybin therapy have excluded people with BD as a precaution against possible adverse effects (e.g., mania). Our study centered the experiences of adults living with BD who consumed psilocybin-containing mushrooms, and aimed to (1) understand its subjective impacts on BD symptoms, (2) deepen understanding of Phase I survey results, and (3) elucidate specific contextual factors associated with adverse reactions in naturalistic settings.MethodsFollowing an international survey (Phase I), follow-up interviews were conducted with 15 respondents (Phase II) to further understand psilocybin use among adults with BD. As part of a larger mixed-methods explanatory sequential design study, reflexive thematic analysis was used to elaborate findings.ResultsThree major themes containing sub-themes were developed. (1) Mental Health Improvements: (1.1) decreased impact and severity of depression, (1.2) increased emotion processing, (1.3) development of new perspectives, and (1.4) greater relaxation and sleep. (2) Undesired Mental Health Impacts: (2.1) changes in sleep, (2.2) increased mania severity, (2.3) hospitalization, and (2.4) distressing sensory experiences. (3) Salient Contextual Factors for psilocybin use included: (3.1) poly-substance use and psilocybin dose, (3.2) solo versus social experiences, and (3.3) pre-psilocybin sleep deprivation.ConclusionOur findings demonstrate both benefits and risks of psilocybin use in this population. Carefully designed clinical trials focused on safety and preliminary efficacy are warranted.

raw_json:
{"europe_pmc_id":"36516137","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Single-dose psilocybin for treatment-resistant obsessive-compulsive disorder: A case report.
authors: Kelmendi B, Kichuk SA, DePalmer G, Maloney G, Ching THW, Belser A, Pittenger C.
publication_date: 2022-12-05
doi: 10.1016/j.heliyon.2022.e12135
pubmed_id: 36536916
source_url: https://doi.org/10.1016/j.heliyon.2022.e12135
substance_tags: psilocybin
topic_tags: OCD,Receptor Pharmacology,Emotional Processing,Case Report
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
Classic psychedelics, such as psilocybin, act on the brain's serotonin system and produce striking psychological effects. Early work in the 1950s and 1960s and more recent controlled studies suggest benefit from psychedelic treatment in a number of conditions. A few case reports in recreational users and a single experimental study suggest benefit in patients with obsessive-compulsive disorder (OCD), but careful clinical data and long-term follow-up have been lacking. Here we describe a case of a patient with refractory OCD treated with psilocybin and followed prospectively for a year, with marked symptomatic improvement. We provide qualitative and quantitative detail of his experience during and after treatment. Improvement in OCD symptoms (YBOCS declined from 24 to 0-2) was accompanied by broader changes in his relationship to his emotions, social and work function, and quality of life. This individual was an early participant in an ongoing controlled study of psilocybin in the treatment of OCD (NCT03356483). These results are preliminary but promising, motivating ongoing investigations of the therapeutic potential of appropriately monitored and supported psychedelic treatment in the treatment of patients with obsessions and compulsions.

raw_json:
{"europe_pmc_id":"36536916","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The economics of psychedelic-assisted therapies: A research agenda.
authors: Marseille E, Bertozzi S, Kahn JG
journal: Frontiers in psychiatry
publication_date: 2021-12-31
doi: 10.3389/fpsyt.2022.1025726
pubmed_id: 36545038
source_url: https://pubmed.ncbi.nlm.nih.gov/36545038/
keywords: MDMA, cost-effectiveness, health economics, psilocybin, psychedelics, psychiatry
substance_tags: psilocybin
topic_tags: Depression,PTSD,Addiction
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"36545038"}
abstract:
After a long hiatus, psychiatry is undergoing a resurgence of interest in psychedelic drugs as therapy for a wide range of mental health disorders Accumulating clinical evidence suggests substantial potential for psychedelics used in a therapeutic context, as treatment for, among other disorders, depression, post-traumatic stress disorder (PTSD), and addictions to tobacco, opioids and alcohol. As soon as 2024, powerful new therapeutic modalities could become available for individuals with mental health problems refractory to traditional therapies. Yet research has lagged on economic considerations, such as costs and cost-effectiveness, the economic effects of widespread implementation, pricing, and economic appraisal's methodological considerations relevant to psychedelic therapies. These issues are critical if psychedelic therapies are to become widely accessible. We describe six types of economic analyses and their rationale for decisions and planning including the needs of health care payers. We also outline desirable features of this research, including scientific rigor, long horizons, equity, and a global view.


authors: Pędzich BD, Medrano M, Buckinx A, Smolders I, De Bundel D.
publication_date: 2022-12-03
doi: 10.3390/ijms232315284
pubmed_id: 36499610
source_url: https://doi.org/10.3390/ijms232315284
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Psychedelic-Induced Serotonin 2A Receptor Downregulation Does Not Predict Swim Stress Coping in Mice.

abstract:
Serotoninergic psychedelics such as psilocybin have been reported to elicit a long-lasting reduction in depressive symptoms. Although the main target for serotoninergic psychedelics, serotonin type 2A receptor (5-HT2A), has been established, the possible mechanism of the antidepressant action of psychedelics remains unknown. Using the mouse forced swim test model, we examined whether the administration of the synthetic serotoninergic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) would modulate 5-HT2A receptor levels in the medial prefrontal cortex (mPFC) and revert stress-induced changes in behavior. Mice subjected to swim stress developed a passive stress-coping strategy when tested in the forced swim test 6 days later. This change in behavior was not associated with the hypothesized increase in 5-HT2A receptor-dependent head twitch behaviors or consistent changes in 5-HT2A receptor levels in the mPFC. When DOI was administered 1 day before the forced swim test, a low dose (0.2 mg/kg i.p.) unexpectedly increased immobility while a high dose (2 mg/kg i.p.) had no significant effect on immobility. Nevertheless, DOI evoked a dose-dependent decrease in 5-HT2A levels in the mPFC of mice previously exposed to swim stress. Our findings do not support the hypothesis that the downregulation of 5-HT2A receptors in the mPFC contributes to the antidepressant-like properties of serotoninergic psychedelics.

keywords:
Animals, Mice, Serotonin, Amphetamines, Receptor, Serotonin, 5-HT2A, Hallucinogens, Antidepressive Agents, Swimming

raw_json:
{"europe_pmc_id":"36499610","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Lower-dose psycholytic therapy - A neglected approach.
authors: Passie T, Guss J, Krähenmann R.
publication_date: 2022-12-01
doi: 10.3389/fpsyt.2022.1020505
pubmed_id: 36532196
source_url: https://doi.org/10.3389/fpsyt.2022.1020505
substance_tags: psilocybin
topic_tags: Personality Change,Mystical Experience,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Lysergic acid diethylamide (LSD) and similar psychoactive drugs have been used in psychotherapy since 1949, when the first clinical study with lower-dose LSD showed therapeutically relevant effects. This caused an intense interest among psychotherapists and researchers, alike, on an international scale. In 1960, the use of serial lower-dose LSD/psilocybin sessions in a psychoanalytical framework, which was dominant at the time, was named "psycholytic therapy". Psycholytic therapy was usually conducted in clinical environments, on both an inpatient and outpatient basis. Psycholytic therapy was developed and established over a 15-year period on the European continent, where it was used at 30 clinical treatment centers and by more than 100 outpatient psychotherapists. Psycholytic approaches were employed minimally in North America, where the psychedelic approach (use of one or two high-dose sessions for "personality-transforming mystical experiences") became the dominant method in use. The leading figure in psycholytic therapy was Professor Hanscarl Leuner in Germany, who laid the ground with his uniquely fine grained analysis of the LSD reaction in a 1962 monograph. He was central in establishing and distributing psycholytic therapy in Europe and abroad. The article provides comprehensive background information and outlines the essential features of psycholytic therapy. Evidence for the efficacy of psycholytic therapy is reviewed and a case for the inclusion of the psycholytic approach in the field of substance-assisted psychotherapy is made.

raw_json:
{"europe_pmc_id":"36532196","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Therapeutic use of psilocybin: Practical considerations for dosing and administration.
authors: MacCallum CA, Lo LA, Pistawka CA, Deol JK.
publication_date: 2022-11-30
doi: 10.3389/fpsyt.2022.1040217
pubmed_id: 36532184
source_url: https://doi.org/10.3389/fpsyt.2022.1040217
substance_tags: psilocybin
topic_tags: Pharmacology,Review Article,Safety,Adverse Events,Drug Interactions,Contraindications
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
The interest in psilocybin as a therapeutic approach has grown exponentially in recent years. Despite increasing access, there remains a lack of practical guidance on the topic for health care professionals. This is particularly concerning given the medical complexity and vulnerable nature of patients for whom psilocybin-assisted psychotherapy may be considered. This article aims to provide health care professionals with an overview of practical considerations for psilocybin therapy, rooted in a patient safety focus. Within this piece we will review basic psilocybin pharmacology and pharmacokinetics, indications, practical therapeutic strategies (e.g., dosing, administration, monitoring) and safety considerations (e.g., contraindications, adverse events, and drug interactions). With this information, our goal is to increase the knowledge and comfort of health care professionals to discuss and counsel their patients on psilocybin therapy, ultimately improving patient care and safety.

raw_json:
{"europe_pmc_id":"36532184","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Barber G, Nemeroff CB, Siegel S.
publication_date: 2022-11-30
doi: 10.1176/appi.ajp.22010073
pubmed_id: 36453037
source_url: https://doi.org/10.1176/appi.ajp.22010073
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
A Case of Prolonged Mania, Psychosis, and Severe Depression After Psilocybin Use: Implications of Increased Psychedelic Drug Availability.

keywords:
Humans, Hallucinogens, Depression, Psychotic Disorders, Psilocybin, Mania, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"36453037","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic-Assisted Therapy for People with Eating Disorders.
authors: Gukasyan N, Schreyer CC, Griffiths RR, Guarda AS
journal: Current psychiatry reports
publication_date: 2022-11-30
doi: 10.1007/s11920-022-01394-5
pubmed_id: 36374357
source_url: https://pubmed.ncbi.nlm.nih.gov/36374357/
keywords: Anorexia nervosa, Eating disorders, Hallucinogens, Psilocybin, Psychedelics, Serotonin
substance_tags: psilocybin
topic_tags: Eating Disorders,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Review Article,Safety
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"36374357"}
abstract:
A growing body of research suggests psychedelic-assisted therapy (PAT) may be safe and effective for a variety of mental health conditions. Among these, eating disorders have been a recent target of interest. This review provides an up-to-date summary of the potential mechanisms and use of PAT in people diagnosed with eating disorders, with a focus on anorexia nervosa.
Classic psychedelics may have transdiagnostic efficacy through several mechanisms relevant to eating disorder pathology. Interest in, and efforts to increase access to PAT are both high. Early clinical trials are focused on establishing the safety and utility of this treatment in eating disorders, and efficacy remains unclear. High-quality published data to support the use of PAT for people with eating disorders remains lacking. Recent studies however suggest PAT has the potential to augment the efficacy of current interventions for these difficult-to-treat conditions.


publication_date: 2022-10-26
doi: 10.1016/j.neuroimage.2022.119716
pubmed_id: 36341951
source_url: https://doi.org/10.1016/j.neuroimage.2022.119716
keywords: Brain, Humans, Hallucinogens, Magnetic Resonance Imaging, Brain Mapping, Consciousness
substance_tags: psilocybin,psilocin
topic_tags: Brain Imaging,Consciousness,Aging,Personality Change
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
Psilocybin modulation of time-varying functional connectivity is associated with plasma psilocin and subjective effects.

authors:
Olsen AS, Lykkebo-Valløe A, Ozenne B, Madsen MK, Stenbæk DS, Armand S, Mørup M, Ganz M, Knudsen GM, Fisher PM.

abstract:
BackgroundPsilocin, the neuroactive metabolite of psilocybin, is a serotonergic psychedelic that induces an acute altered state of consciousness, evokes lasting changes in mood and personality in healthy individuals, and has potential as an antidepressant treatment. Examining the acute effects of psilocin on resting-state time-varying functional connectivity implicates network-level connectivity motifs that may underlie acute and lasting behavioral and clinical effects.AimEvaluate the association between resting-state time-varying functional connectivity (tvFC) characteristics and plasma psilocin level (PPL) and subjective drug intensity (SDI) before and right after intake of a psychedelic dose of psilocybin in healthy humans.MethodsFifteen healthy individuals completed the study. Before and at multiple time points after psilocybin intake, we acquired 10-minute resting-state blood-oxygen-level-dependent functional magnetic resonance imaging scans. Leading Eigenvector Dynamics Analysis (LEiDA) and diametrical clustering were applied to estimate discrete, sequentially active brain states. We evaluated associations between the fractional occurrence of brain states during a scan session and PPL and SDI using linear mixed-effects models. We examined associations between brain state dwell time and PPL and SDI using frailty Cox proportional hazards survival analysis.ResultsFractional occurrences for two brain states characterized by lateral frontoparietal and medial fronto-parietal-cingulate coherence were statistically significantly negatively associated with PPL and SDI. Dwell time for these brain states was negatively associated with SDI and, to a lesser extent, PPL. Conversely, fractional occurrence and dwell time of a fully connected brain state partly associated with motion was positively associated with PPL and SDI.ConclusionOur findings suggest that the acute perceptual psychedelic effects induced by psilocybin may stem from drug-level associated decreases in the occurrence and duration of lateral and medial frontoparietal connectivity motifs. We apply and argue for a modified approach to modeling eigenvectors produced by LEiDA that more fully acknowledges their underlying structure. Together these findings contribute to a more comprehensive neurobiological framework underlying acute effects of serotonergic psychedelics.

raw_json:
{"europe_pmc_id":"36341951","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Strauss D, Ghosh S, Murray Z, Gryzenhout M.
publication_date: 2022-11-03
doi: 10.1007/s13205-022-03355-4
pubmed_id: 36340802
source_url: https://doi.org/10.1007/s13205-022-03355-4
substance_tags: psilocybin,psilocin
topic_tags: Receptor Pharmacology,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
Psilocybin containing mushrooms: a rapidly developing biotechnology industry in the psychiatry, biomedical and nutraceutical fields.

abstract:
Humans have collected and used hallucinogenic mushrooms for ethnic medicinal, recreational, and religious purposes since before recorded history. Currently, the use of these mushrooms is illegal in most countries, but where their use is legal they are applied as self medication. Psilocybin and psilocin, two psychoactive alkaloids, are naturally synthesized by hallucinogenic mushrooms. The chemical structure of these compounds are similar to the neurotransmitter serotonin. Activation of this system by psilocybin and psilocin may produce temporary changes in the brain that induce hallucinations and feelings of euphoria. Adjustment of the serotonin system in this way can moderate symptoms of related mental disorders. This review summarizes relevant and current information regarding the discovery of hallucinogenic mushrooms and their contained psychoactive compounds, the events that lead to their criminalization and decriminilization, and the state of knowledge of psilocybin, psilocin, and derivatives. Last, research on the psychoactive properties of these mushrooms is placed in perspective to possible applications for human dysfunctions.

raw_json:
{"europe_pmc_id":"36340802","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2022-11-01
doi: 10.1016/j.cct.2022.106976
pubmed_id: 36332827
source_url: https://doi.org/10.1016/j.cct.2022.106976
substance_tags: psilocybin
topic_tags: Addiction,Receptor Pharmacology,Randomized Controlled Trial,Safety
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Psilocybin for alcohol use disorder: Rationale and design considerations for a randomized controlled trial.

authors:
O'Donnell KC, Mennenga SE, Owens LT, Podrebarac SK, Baron T, Rotrosen J, Ross S, Forcehimes AA, Bogenschutz MP.

abstract:
Several lines of evidence suggest that classic psychedelics (5-HT2A receptor agonists or partial agonists) such as psilocybin might facilitate behavior change in individuals with substance use disorders. We conducted a multi-site, double-blind, randomized controlled trial (RCT) to assess the effects of psilocybin-assisted psychotherapy in alcohol-dependent volunteers. In addition to a structured 12-week psychotherapy platform, participants (n = 96) were randomly assigned (1:1) to receive either oral psilocybin or an active placebo (oral diphenhydramine) in each of two dosing sessions (at weeks 4 and 8). Initial doses were 25 mg/70 kg psilocybin or 50 mg diphenhydramine, which could be increased in the second session depending on initial response. The psychotherapy platform combined evidence-based, manualized therapy for alcohol dependence with a supportive context for the dosing sessions. All participants were followed in the RCT through week 36. At the end of the RCT, participants who still met safety criteria were offered an open-label psilocybin session. Data collected at screening, baseline and throughout the study included: demographics, measures of alcohol use, subjective response to psilocybin and diphenhydramine, and safety measures. The primary outcome was the proportion of heavy drinking days during the 32 weeks after the first dosing session (i.e., between week 4 and week 36). Secondary outcomes included safety, additional measures of drinking (e.g., abstinence, drinking days, etc.), craving, self-efficacy, and acute effects. We will also explore moderators and mediators of the primary outcome. The primary outcomes will be published elsewhere. In this paper, we describe the protocol and rationale for our design decisions.

keywords:
Humans, Alcoholism, Diphenhydramine, Treatment Outcome, Alcohol Drinking, Randomized Controlled Trials as Topic, Psilocybin

raw_json:
{"europe_pmc_id":"36332827","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Set and setting in microdosing: an oft-overlooked principle.
authors: Hartogsohn I, Petranker R
journal: Psychopharmacology
publication_date: 2022-11-30
doi: 10.1007/s00213-022-06249-8
pubmed_id: 36289109
source_url: https://pubmed.ncbi.nlm.nih.gov/36289109/
keywords: LSD, Microdosing, Psilocybin, Psychedelics, Set and setting
substance_tags: psilocybin
topic_tags: Microdosing,Clinical Trial
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"36289109"}
abstract:
The use of psychedelics for medical and recreational purposes is rising. Contextual factors such as expectancy, intention, and sensory and social environment (set and setting) are widely recognized as moderating the effects of these substances. Nevertheless, clinical trials of microdosing - the ingestion of small, sub-hallucinogenic doses of psychedelics - rarely report their set and setting. This fact suggests that such factors are not considered important in the context of microdosing.
This paper challenges this assumption and makes the case for the crucial relevance of set and setting in microdosing practice. Building on set and setting theory and placebo theory, we explain why set and setting are of crucial importance in the case of microdosing.
This reasoning helps elucidate the role of set and setting in determining the outcomes of microdosing and helps explain some of the contradictory results that have emerged in microdosing research in recent years.
Set and setting are important constructs to be considered especially in the context of microdosing psychedelics. By reporting set and setting, the results of microdosing research can be made more reliable and consistent.


title: Use of plant-based hallucinogens and dissociative agents: U.S. Time Trends, 2002-2019.
authors: Walsh CA, Livne O, Shmulewitz D, Stohl M, Hasin DS.
publication_date: 2022-09-05
doi: 10.1016/j.abrep.2022.100454
pubmed_id: 36119808
source_url: https://doi.org/10.1016/j.abrep.2022.100454
substance_tags: psilocybin
topic_tags: Observational Study,Healthcare Workers
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
AimsInformation on time trends in use of different plant-based hallucinogens is lacking. The current study used nationally representative U.S. data to assess overall and age-specific time trends in the prevalence of lifetime and 12-month use of plant-based hallucinogens and dissociative agents.MethodsParticipants were respondents aged ≥ 12 years (N = 1,006,051) from the National Survey on Drug Use and Health, 2002-2019. Predictors were continuous years. Outcomes included illicit use of peyote, mescaline, psilocybin, ketamine, salvia, and tryptamine. Sociodemographic variables (gender; age; race/ethnicity; educational level; family income) were modeled as covariates. Trends were estimated overall and by age (12-17, 18-25, 26+). Prevalence differences [PDs] were obtained for each category, along with 95 % confidence intervals [CI].ResultsIncreases in lifetime use were observed for psilocybin (2002-2019 PD=+1.61), tryptamine (2006-2014 PD=+0.55; 2015-2019 PD=+0.44), and ketamine (2006-2014 PD=+0.27; 2015-2019 PD=+0.21). Mescaline use decreased (PD = -0.89). While overall lifetime salvia use increased between 2006 and 2014 (PD=+1.81), prevalence did not change between 2015 and 2019. Twelve-month use of tryptamine and ketamine increased between 2006 and 2014 (PD=+0.14; +0.03, respectively). Twelve-month ketamine use also increased from 2015 to 2019 (PD=+0.03). By age, participants aged 12-17 and 18-25 showed decreases in use of most types of hallucinogens, but those age 26+ generally showed increases.ConclusionsWhile use of plant-based hallucinogens and dissociative agents remains rare, lifetime use of ketamine, tryptamine, and psilocybin is increasing in adults. Considering these increases alongside concerns about unsupervised use of illicit products whose dose and composition is uncertain, clinicians and policymakers should remain mindful of the rising rates of illicit use in the general population.

raw_json:
{"europe_pmc_id":"36119808","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The psychedelic renaissance: the next trip for psychiatry?
authors: Kelly JR, Baker A, Babiker M, Burke L, Brennan C, O'Keane V.
publication_date: 2019-09-22
doi: 10.1017/ipm.2019.39
pubmed_id: 31543078
source_url: https://doi.org/10.1017/ipm.2019.39
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
The psychedelic research renaissance is gaining traction. Preliminary clinical studies of the hallucinogenic fungi, psilocybin, with psychological support, have indicated improvements in mood, anxiety and quality of life. A seminal, open-label study demonstrated marked reductions in depression symptoms in participants with treatment-resistant depression (TRD). The associated neurobiological processes involve alterations in brain connectivity, together with altered amygdala and default mode network activity. At the cellular level, psychedelics promote synaptogenesis and neural plasticity. Prompted by the promising preliminary studies, a randomized, double-blind trial has recently been launched across Europe and North America to investigate the efficacy of psilocybin in TRD. One of these centres is based in Ireland - CHO Area 7 and Tallaght University Hospital. The outcome of this trial will determine whether psilocybin with psychological support will successfully translate into the psychiatric clinic for the benefit of patients.

keywords:
Humans, Hallucinogens, Double-Blind Method, Anxiety, Depressive Disorder, Psychiatry, Quality of Life, Randomized Controlled Trials as Topic, Psilocybin

topic_tags:
Depression,Anxiety,Neuroplasticity,Default Mode Network,Randomized Controlled Trial,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"31543078","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Classic psychedelics, health behavior, and physical health.
authors: Simonsson O, Hendricks PS, Chambers R, Osika W, Goldberg SB
journal: Therapeutic advances in psychopharmacology
publication_date: 2021-12-31
doi: 10.1177/20451253221135363
pubmed_id: 36465958
source_url: https://pubmed.ncbi.nlm.nih.gov/36465958/
keywords: BMI, behavior, health, psilocybin, psychedelics
substance_tags: psilocybin
topic_tags: Addiction
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"36465958"}
abstract:
Preliminary evidence suggests that classic psychedelics may be effective in the treatment of some psychiatric disorders, yet little remains known about their effects on health behavior and physical health.
The purpose of this study was to investigate associations of lifetime classic psychedelic use and psychological insight during one's most insightful classic psychedelic experience with health behavior and physical health.
Using data representative of the US population with regard to sex, age, and ethnicity ( = 2822), this study examined associations of lifetime classic psychedelic use and psychological insight with health behavior and physical health.
Lifetime classic psychedelic use was associated with more healthy tobacco-related and diet-related behavior ( = 0.05 and 0.09, respectively). Among lifetime classic psychedelic users ( = 613), greater Psychological Insight Questionnaire (PIQ) total scale, PIQ Avoidance and Maladaptive Patterns (AMP) subscale, and PIQ Goals and Adaptive Patterns (GAP) subscale scores were each associated with higher odds of more healthy exercise-related behavior [adjusted odds ratios (aOR) (95% confidence interval, CI = 1.38 (1.13-1.68), 1.38 (1.13-1.68), and 1.32 (1.10-1.60), respectively] and higher odds of having a healthy body mass index (BMI) [aOR (95% CI) = 1.32 (1.07-1.63), 1.36 (1.10-1.69), and 1.23 (1.01-1.50), respectively], and greater GAP subscale scores were associated with more healthy diet-related behavior ( = 0.10). All PIQ scales were positively associated with some health behavior improvements (overall, diet, exercise) attributed to respondents' most insightful classic psychedelic experience ( = 0.42, 0.18, and 0.17; = 0.40, 0.19, and 0.17; and = 0.40, 0.15, and 0.15, respectively), but only PIQ total scale and AMP subscale scores were positively associated with alcohol-related health behavior improvements ( = 0.13 and 0.16, respectively).
Although these results cannot demonstrate causality, they suggest that psychological insight during a classic psychedelic experience may lead to positive health behavior change and better physical health in some domains, in particular in those related to weight management.


title: Psilocybin as a Treatment for Psychiatric Illness: A Meta-Analysis.
authors: Irizarry R, Winczura A, Dimassi O, Dhillon N, Minhas A, Larice J.
publication_date: 2022-11-21
doi: 10.7759/cureus.31796
pubmed_id: 36569662
source_url: https://doi.org/10.7759/cureus.31796
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Psilocybin is an emerging potential therapy for the treatment of psychiatric illnesses. Microdosing has been shown to result in an overall improvement in patients with anxiety, depression, obsessive-compulsive disorder, post-traumatic stress disorder, and substance abuse. This meta-analysis explores and compiles prior research to make further inferences regarding psilocybin and its use for the treatment of psychiatric illness along with its safety and efficacy. Database searches were conducted to identify peer-reviewed randomized controlled trials and clinical trials mentioning psilocybin use and psychiatric illness. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram was created and analysis was run on the nine articles that met all established inclusion criteria. An event is defined as a participant who showed improvement, in a quantitative method, from baseline after the use of psilocybin. Another analysis was done using depression severity (Quick Inventory of Depressive Symptomatology 16-Item Self Report, QIDS-SR16) at baseline and after the use of psilocybin. Analyses of the original data and the nine articles showed a great deal of heterogeneity with an I2 value of 73.68%, suggesting that the studies in this meta-analysis cannot be considered to be studies of the same population. The Q value of 30.4 was higher than 15.507, which is the critical value for eight degrees of freedom found in a chi-square distribution. This Q value showed a high degree of variation and lacked significance. The second meta-run on QIDS-SR16 scores from three studies showed a Q value of 1.16 which was lower than 5.991, the critical value for two degrees of freedom found in a chi-square distribution. The I2 statistic for this second meta-analysis was -73% which can be equated to zero. This indicated that the data were homogeneous or that there was no observed heterogeneity. Due to low heterogeneity, the fixed-effects model was used. Based on this meta-analysis, psilocybin seems to show symptom improvement in some psychiatric illnesses. The effectiveness of psilocybin microdosing and the use of psilocybin, in general, need to be studied further to determine the efficacy and safety of potential applications in psychiatry.

topic_tags:
Depression,Anxiety,PTSD,OCD,Microdosing,Clinical Trial,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Safety

raw_json:
{"europe_pmc_id":"36569662","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Music programming for psilocybin-assisted therapy: Guided Imagery and Music-informed perspectives.
authors: Messell C, Summer L, Bonde LO, Beck BD, Stenbæk DS.
publication_date: 2022-11-16
doi: 10.3389/fpsyg.2022.873455
pubmed_id: 36467212
source_url: https://doi.org/10.3389/fpsyg.2022.873455
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
The psychedelic drug psilocybin has been successfully explored as a novel treatment for a range of psychiatric disorders. Administration of psilocybin requires careful attention to psychological support and the setting in which the drug is administered. The use of music to support the acute psychoactive effects of psilocybin is recommended in current guidelines, but descriptions of how to compile music programs for the 4-6 h long sessions are still scarce. This article describes the procedural steps and considerations behind the curation of a new music program, the Copenhagen Music Program, tailored to the intensity profile of a medium/high dose psilocybin. The method of Guided Imagery and Music is presented as a music therapeutic framework for choosing and sequencing music in music programming and the Taxonomi of Therapeutic Music is presented as a rating tool to evaluate the music-psychological intensity of music pieces. Practical examples of how to organize the process of music programming are provided along with a full description of the Copenhagen Music Program and its structure. The aim of the article is to inspire others in their endeavours to create music programs for psychedelic interventions, while proposing that an informed music choice may support the therapeutic dynamics during acute effects of psilocybin.

raw_json:
{"europe_pmc_id":"36467212","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Shahar O, Botvinnik A, Esh-Zuntz N, Brownstien M, Wolf R, Lotan A, Wolf G, Lerer B, Lifschytz T.
publication_date: 2022-11-15
doi: 10.3390/ijms232214148
pubmed_id: 36430623
source_url: https://doi.org/10.3390/ijms232214148
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Role of 5-HT2A, 5-HT2C, 5-HT1A and TAAR1 Receptors in the Head Twitch Response Induced by 5-Hydroxytryptophan and Psilocybin: Translational Implications.

abstract:
There is increasing interest in the therapeutic potential of psilocybin. In rodents, the serotonin precursor, 5-hydroxytryptophan (5-HTP) and psilocybin induce a characteristic 5-HT2A receptor (5-HT2AR)-mediated head twitch response (HTR), which is correlated with the human psychedelic trip. We examined the role of other serotonergic receptors and the trace amine -associated receptor 1 (TAAR1) in modulating 5-HTP- and psilocybin-induced HTR. Male C57BL/6J mice (11 weeks, ~30 g) were administered 5-HTP, 50-250 mg/kg i.p., 200 mg/kg i.p. after pretreatment with 5-HT/TAAR1 receptor modulators, psilocybin 0.1-25.6 mg/kg i.p. or 4.4 mg/kg i.p., immediately preceded by 5-HT/TAAR1 receptor modulators. HTR was assessed in a custom-built magnetometer. 5-HTP and psilocybin induced a dose-dependent increase in the frequency of HTR over 20 min with attenuation by the 5-HT2AR antagonist, M100907, and the 5-HT1AR agonist, 8-OH-DPAT. The 5-HT2CR antagonist, RS-102221, enhanced HTR at lower doses but reduced it at higher doses. The TAAR1 antagonist, EPPTB, reduced 5-HTP- but not psilocybin-induced HTR. We have confirmed the key role of 5-HT2AR in HTR, an inhibitory effect of 5-HT1AR, a bimodal contribution of 5-HT2CR and a role of TAAR1 in modulating HTR induced by 5-HTP. Compounds that modulate psychedelic-induced HTR have important potential in the emerging therapeutic use of these compounds.

keywords:
Animals, Mice, Inbred C57BL, Humans, Mice, Serotonin, 5-Hydroxytryptophan, Hallucinogens, Male, Psilocybin

raw_json:
{"europe_pmc_id":"36430623","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Extensive Collection of Psychotropic Mushrooms with Determination of Their Tryptamine Alkaloids.
authors: Gotvaldová K, Borovička J, Hájková K, Cihlářová P, Rockefeller A, Kuchař M.
publication_date: 2022-11-14
doi: 10.3390/ijms232214068
pubmed_id: 36430546
source_url: https://doi.org/10.3390/ijms232214068
keywords: Agaricales, Tryptamines, Organophosphorus Compounds, Alkaloids, Indoles, Organophosphates
substance_tags: psilocybin,psilocin
topic_tags: Microdosing,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
Since not only psilocybin (PSB) but also PSB-containing mushrooms are used for psychedelic therapy and microdosing, it is necessary to know their concentration variability in wild-grown mushrooms. This article aimed to determine the PSB, psilocin (PS), baeocystin (BA), norbaeocystin (NB), and aeruginascin (AE) concentrations in a large sample set of mushrooms belonging to genera previously reported to contain psychotropic tryptamines. Ultra-high performance liquid chromatography coupled with tandem mass spectrometry was used to quantify tryptamine alkaloids in the mushroom samples. Most mushroom collections were documented by fungarium specimens and/or ITS rDNA/LSU/EF1-α sequencing. Concentrations of five tryptamine alkaloids were determined in a large sample set of 226 fruiting bodies of 82 individual collections from seven mushroom genera. For many mushroom species, concentrations of BA, NB, and AE are reported for the first time. The highest PSB/PS concentrations were found in Psilocybe species, but no tryptamines were detected in the P. fuscofulva and P. fimetaria collections. The tryptamine concentrations in mushrooms are extremely variable, representing a problem for mushroom consumers due to the apparent risk of overdose. The varied cocktail of tryptamines in wild mushrooms could influence the medicinal effect compared to therapy with chemically pure PSB, posing a serious problem for data interpretation.

raw_json:
{"europe_pmc_id":"36430546","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2022-08-12
doi: 10.1016/j.neuropharm.2022.109214
pubmed_id: 35973601
source_url: https://doi.org/10.1016/j.neuropharm.2022.109214
substance_tags: psilocybin
topic_tags: Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Policy considerations that support equitable access to responsible, accountable, safe, and ethical uses of psychedelic medicines.

authors:
Belouin SJ, Averill LA, Henningfield JE, Xenakis SN, Donato I, Grob CS, Berger A, Magar V, Danforth AL, Anderson BT.

abstract:
There is mounting evidence suggesting psychedelic and entactogen medicines (namely psilocybin and 3,4-methylenedioxymethamphetamine [MDMA]), in conjunction with proper psychosocial support, hold the potential to provide safe, rapid acting, and robust clinical improvements with durable effects. In the US, both psilocybin and MDMA have been granted Breakthrough Therapy designations by the US Food and Drug Administration and may potentially receive full FDA approval with similar regulatory considerations occurring in multiple countries. At the same time, regulatory changes are poised to increase access to legal or decriminalized psychedelic use in various non-medical settings. This review provides a brief discussion on the historical use of psychedelic medicines, the status of the empirical evidence, and numerous significant policy considerations that must be thoughtfully addressed regarding standards-of-practice, consumer protection, engagement of communities, safeguarding access for all, and developing data standards, which supports the responsible, accountable, safe, and ethical uses of these medicines in clinical, faith-based, and other contexts. We provide suggestions for how public health and harm reduction can be supported through a public-private partnership that engages a community of stakeholders from various disciplines in the co-creation and dissemination of best practices and public policies.

keywords:
Humans, Substance Withdrawal Syndrome, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Policy, Psilocybin

raw_json:
{"europe_pmc_id":"35973601","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2022-11-01
doi: 10.1021/acsptsci.2c00177
pubmed_id: 36407948
source_url: https://doi.org/10.1021/acsptsci.2c00177
substance_tags: psilocybin,psilocin
topic_tags: Receptor Pharmacology,Animal Study,In Vitro Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice.

authors:
Glatfelter GC, Pottie E, Partilla JS, Sherwood AM, Kaylo K, Pham DNK, Naeem M, Sammeta VR, DeBoer S, Golen JA, Hulley EB, Stove CP, Chadeayne AR, Manke DR, Baumann MH.

abstract:
4-Phosphoryloxy-N,N-dimethyltryptamine (psilocybin) is a naturally occurring tertiary amine found in many mushroom species. Psilocybin is a prodrug for 4-hydroxy-N,N-dimethyltryptamine (psilocin), which induces psychedelic effects via agonist activity at the serotonin (5-HT) 2A receptor (5-HT2A). Several other 4-position ring-substituted tryptamines are present in psilocybin-containing mushrooms, including the secondary amine 4-phosphoryloxy-N-methyltryptamine (baeocystin) and the quaternary ammonium 4-phosphoryloxy-N,N,N-trimethyltryptamine (aeruginascin), but these compounds are not well studied. Here, we investigated the structure-activity relationships for psilocybin, baeocystin, and aeruginascin, as compared to their 4-acetoxy and 4-hydroxy analogues, using in vitro and in vivo methods. Broad receptor screening using radioligand binding assays in transfected cells revealed that secondary and tertiary tryptamines with either 4-acetoxy or 4-hydroxy substitutions display nanomolar affinity for most human 5-HT receptor subtypes tested, including the 5-HT2A and the serotonin 1A receptor (5-HT1A). The same compounds displayed affinity for 5-HT2A and 5-HT1A in mouse brain tissue in vitro and exhibited agonist efficacy in assays examining 5-HT2A-mediated calcium mobilization and β-arrestin 2 recruitment. In mouse experiments, only the tertiary amines psilocin, psilocybin, and 4-acetoxy-N,N-dimethyltryptamine (psilacetin) induced head twitch responses (ED50 0.11-0.29 mg/kg) indicative of psychedelic-like activity. Head twitches were blocked by 5-HT2A antagonist pretreatment, supporting 5-HT2A involvement. Both secondary and tertiary amines decreased body temperature and locomotor activity at higher doses, the effects of which were blocked by 5-HT1A antagonist pretreatment. Across all assays, the pharmacological effects of 4-acetoxy and 4-hydroxy compounds were similar, and these compounds were more potent than their 4-phosphoryloxy counterparts. Importantly, psilacetin appears to be a prodrug for psilocin that displays substantial serotonin receptor activities of its own.

raw_json:
{"europe_pmc_id":"36407948","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin in Treatment-Resistant Depression.
authors: Madras BK.
publication_date: 2022-10-31
doi: 10.1056/nejme2210975
pubmed_id: 36322849
source_url: https://doi.org/10.1056/nejme2210975
keywords: Humans, Hallucinogens, Depression, Depressive Disorder, Treatment-Resistant, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Treatment-Resistant Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
{"europe_pmc_id":"36322849","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.
publication_date: 2022-10-31
doi: 10.1056/nejmoa2206443
pubmed_id: 36322843
source_url: https://doi.org/10.1056/nejmoa2206443
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Treatment-Resistant Depression
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
authors:
Goodwin GM, Aaronson ST, Alvarez O, Arden PC, Baker A, Bennett JC, Bird C, Blom RE, Brennan C, Brusch D, Burke L, Campbell-Coker K, Carhart-Harris R, Cattell J, Daniel A, DeBattista C, Dunlop BW, Eisen K, Feifel D, Forbes M, Haumann HM, Hellerstein DJ, Hoppe AI, Husain MI, Jelen LA, Kamphuis J, Kawasaki J, Kelly JR, Key RE, Kishon R, Knatz Peck S, Knight G, Koolen MHB, Lean M, Licht RW, Maples-Keller JL, Mars J, Marwood L, McElhiney MC, Miller TL, Mirow A, Mistry S, Mletzko-Crowe T, Modlin LN, Nielsen RE, Nielson EM, Offerhaus SR, O'Keane V, Páleníček T, Printz D, Rademaker MC, van Reemst A, Reinholdt F, Repantis D, Rucker J, Rudow S, Ruffell S, Rush AJ, Schoevers RA, Seynaeve M, Shao S, Soares JC, Somers M, Stansfield SC, Sterling D, Strockis A, Tsai J, Visser L, Wahba M, Williams S, Young AH, Ywema P, Zisook S, Malievskaia E.

abstract:
BackgroundPsilocybin is being studied for use in treatment-resistant depression.MethodsIn this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits).ResultsA total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P

keywords:
Humans, Antidepressive Agents, Treatment Outcome, Double-Blind Method, Depression, Adult, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"36322843","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin reduces symptoms in treatment resistant depression, trial results show.
authors: Iacobucci G.
publication_date: 2022-11-01
doi: 10.1136/bmj.o2623
pubmed_id: 36411539
source_url: https://doi.org/10.1136/bmj.o2623
keywords: Humans, Hallucinogens, Depressive Disorder, Treatment-Resistant, Psilocybin
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
raw_json:
{"europe_pmc_id":"36411539","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: [Treatment-resistant depression. From classification to new therapies.]
authors: Paganin W, Signorini S, Signorini S, Leccese V, Sciarretta A.
publication_date: 2022-10-31
doi: 10.1708/3922.39072
pubmed_id: 36503940
source_url: https://doi.org/10.1708/3922.39072
substance_tags: psilocybin
topic_tags: Depression,Aging,Treatment-Resistant Depression,Healthcare Workers,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
AimsThis paper aims to investigate the advances in recent years in the recognition and therapy of treatment-resistant depression starting from the concepts of: depressive disorder, resistance and pseudoresistance to drug treatment in depression, and appropriate treatments of treatment-resistant depression.MethodsAn extensive research was carried out on scientific databases such as: PubMed, PsychInfo and Cochrane Library, until May 2022, using the keywords "major depression", "treatment-resistant depression", "staging", "instrumental therapies for resistant depression", "esketamine" and "psilocybin".ResultsSubjects who do not respond to antidepressants show a form of treatment resistance that requires an approach with additional pharmacological and/or instrumental therapies. Recently, esketamine and psilocybin are of particular interest among clinicians, and instrumental treatments such as: vagus nerve stimulation, deep brain stimulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, epidural cortical stimulation, and electro convulsive therapy, are being added to them.Discussion and conclusionsTreatment-resistant depression has increasingly become a public health problem due to the significant number of relapses, hospitalizations and mortality it entails, with increased demand for the use of more drugs, therapeutic resources by health services, and loss of quality of life for patients. Treatment-resistant depression needs to be addressed through the creation of dedicated study protocols. Future research should focus on the need to establish operational, valid and appropriate criteria, both on the psychopathological, clinical governance and therapeutic levels, focusing on the latest therapies in order to provide reliable data on the benefits, risks and costs associated with their use.

keywords:
Humans, Ketamine, Quality of Life, Transcranial Direct Current Stimulation, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"36503940","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2022-11-22
doi: 10.1111/head.14420
pubmed_id: 36416492
source_url: https://doi.org/10.1111/head.14420
keywords: Humans, Cluster Headache, Headache, Treatment Outcome, Double-Blind Method, Psilocybin
substance_tags: psilocybin
topic_tags: Headache / Migraine,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Exploratory investigation of a patient-informed low-dose psilocybin pulse regimen in the suppression of cluster headache: Results from a randomized, double-blind, placebo-controlled trial.

authors:
Schindler EAD, Sewell RA, Gottschalk CH, Luddy C, Flynn LT, Zhu Y, Lindsey H, Pittman BP, Cozzi NV, D'Souza DC.

abstract:
ObjectiveUsing a patient-informed regimen, we conducted an exploratory randomized, double-blind, placebo-controlled study to systematically investigate the effects of psilocybin in cluster headache.BackgroundSustained reductions in cluster headache burden after limited quantities of psilocybin-containing mushrooms are anecdotally reported, although to date there are no controlled studies investigating these effects.MethodsParticipants were randomized to receive psilocybin (0.143 mg/kg) or placebo (microcrystalline cellulose) in a pulse of three doses, each ~5 days apart. Participants maintained headache diaries starting 2 weeks before and continuing through 8 weeks after the first drug session. A total of 16 participants were randomized to receive experimental drug and 14 were included in the final analysis.ResultsIn the 3 weeks after the start of the pulse regimen, the change in cluster attack frequency was 0.03 (95% confidence interval [CI] -2.6 to 2.6) attacks/week with placebo (baseline 8.9 [95% CI3.8 to 14.0]) and -3.2 (95% CI -8.3 to 1.9) attacks/week with psilocybin (baseline 9.6 [95% CI5.6 to 13.6]; p = 0.251). Group difference in change from baseline had a moderate effect size (d = 0.69). The effect size was small in episodic participants (d = 0.35) but large in chronic participants (d = 1.25), which remained over the entire 8-week period measured (d = 0.81). Changes in cluster attack frequency were not correlated with the intensity of acute psychotropic effects during psilocybin administration. Psilocybin was well-tolerated without any unexpected or serious adverse events.ConclusionsFindings from this initial, exploratory study provide valuable information for the development of larger, more definitive studies. Efficacy outcomes were negative, owing in part to the small number of participants. The separation of acute psychotropic effects and lasting therapeutic effects underscores the need for further investigation into the mechanism(s) of action of psilocybin in headache disorders.

raw_json:
{"europe_pmc_id":"36416492","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Patchett-Marble R, O'Sullivan S, Tadwalkar S, Hapke E.
publication_date: 2022-10-31
doi: 10.46747/cfp.6811823
pubmed_id: 36376043
source_url: https://doi.org/10.46747/cfp.6811823
keywords: Humans, Agaricales, Neoplasms, Lung Neoplasms, Palliative Care, Stress, Psychological, Psilocybin
substance_tags: psilocybin
topic_tags: End-of-Life Distress
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Psilocybin mushrooms for psychological and existential distress: Treatment for a patient with palliative lung cancer.

raw_json:
{"europe_pmc_id":"36376043","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Classic psychedelics and alcohol use disorders: A systematic review of human and animal studies.
authors: Calleja-Conde J, Morales-García JA, Echeverry-Alzate V, Bühler KM, Giné E, López-Moreno JA.
publication_date: 2022-10-31
doi: 10.1111/adb.13229
pubmed_id: 36301215
source_url: https://doi.org/10.1111/adb.13229
keywords: Animals, Humans, Alcoholism, Mescaline, Lysergic Acid Diethylamide, Hallucinogens, Psilocybin
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by acting mainly on 5-HT2A receptors. Recently, the interest of psychedelics as pharmacological treatment for psychiatric disorders has increased significantly, including their use on problematic use of alcohol. This systematic review is aimed to analyse the last two decades of studies examining the relationship between classic psychedelics and alcohol consumption. We searched PubMed and PsycInfo for human and preclinical studies published between January 2000 to December 2021. The search identified 639 publications. After selection, 27 studies were included. Human studies (n = 20) generally show promising data and seem to indicate that classic psychedelics could help reduce alcohol consumption. Nevertheless, some of these studies present methodological concerns such as low number of participants, lack of control group or difficulty in determining the effect of classic psychedelics in isolation. On the other hand, preclinical studies (n = 7) investigating the effect of these compounds on voluntary alcohol consumption are scarce and show some conflicting data. Among these compounds, psilocybin seems to show the most consistent data indicating that this compound could be a potential candidate to treat alcohol use disorders. In the absence of understanding the biological and/or psychological mechanisms, more studies including methodological quality parameters are needed to finally determine the effects of classic psychedelics on alcohol consumption.

topic_tags:
Addiction,Mechanism of Action,Receptor Pharmacology,Consciousness,Systematic Review,Review Article,Animal Study

raw_json:
{"europe_pmc_id":"36301215","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Are Magic Mushrooms Really Magic?: Psilocybin in the Treatment of Depression.
authors: Balon R.
publication_date: 2022-10-15
doi: 10.1097/jcp.0000000000001610
pubmed_id: 36251379
source_url: https://doi.org/10.1097/jcp.0000000000001610
keywords: Humans, Hallucinogens, Depression, Psilocybe, Psilocybin
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
raw_json:
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authors: Ledwos N, Rosenblat JD, Blumberger DM, Castle DJ, McIntyre RS, Mulsant BH, Husain MI.
publication_date: 2022-10-02
doi: 10.1097/jcp.0000000000001608
pubmed_id: 36193898
source_url: https://doi.org/10.1097/jcp.0000000000001608
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
A Critical Appraisal of Evidence on the Efficacy and Safety of Serotonergic Psychedelic Drugs as Emerging Antidepressants: Mind the Evidence Gap.

abstract:
Purpose/backgroundThere has been resurgence of interest in the therapeutic use of serotonergic ("classic") psychedelics in major depressive disorder (MDD) and end-of-life distress. This commentary offers a critical appraisal of current evidence for antidepressant effects of classic psychedelics from contemporary clinical trials and highlights pitfalls that should be addressed before clinical translation.Methods/proceduresA narrative review was conducted to identify clinical trials of serotonergic psychedelics for the treatment of MDD and end-of-life distress. Trials published between January 1990 and May 2022 were identified on PubMed using combinations of search terms.Findings/resultsPsilocybin, lysergic acid diethylamide, and ayahuasca have clinical trials to evaluate antidepressant effects. Two studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression. Similar results were seen in lysergic acid diethylamide for end-of-life distress. Small randomized clinical trials (RCTs) of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator in MDD, with additional RCTs showing efficacy in end-of-life distress. Adverse events associated with psychedelics were reported as mild and transient. Small homogenous samples, expectancy bias, functional unblinding, and lack of consensus and standardization of psychotherapy are major limitations of all studies.Implications/conclusionsGiven the methodological limitations of published RCTs, the evidence supporting the efficacy and safety of serotonergic psychedelics for depression is currently of low level. Future research should assess the role of expectancy and psychedelic effects in moderating and mediating treatment response. Innovative trial designs are needed to overcome functional unblinding. For now, psychedelics should remain experimental interventions used within clinical trials.

keywords:
Humans, Banisteriopsis, Death, Lysergic Acid Diethylamide, Serotonin Agents, Hallucinogens, Antidepressive Agents, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,End-of-Life Distress,Receptor Pharmacology,Clinical Trial,Randomized Controlled Trial,Review Article,Treatment-Resistant Depression,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"36193898","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2022-08-16
doi: 10.1016/j.neuropharm.2022.109220
pubmed_id: 35987353
source_url: https://doi.org/10.1016/j.neuropharm.2022.109220
substance_tags: psilocybin
topic_tags: Mechanism of Action,Consciousness,Spirituality,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Psychedelic drug abuse potential assessment research for new drug applications and Controlled Substances Act scheduling.

authors:
Henningfield JE, Coe MA, Griffiths RR, Belouin SJ, Berger A, Coker AR, Comer SD, Heal DJ, Hendricks PS, Nichols CD, Sapienza F, Vocci FJ, Zia FZ.

abstract:
New medicines containing classic hallucinogenic and entactogenic psychedelic substance are under development for various psychiatric and neurological disorders. Many of these, including psilocybin, lysergic acid diethylamide (LSD), and 3,4-methylenedioxymethamphetamine (MDMA) are Schedule I controlled substances of the United States Controlled Substances Act (US CSA), and similarly controlled globally. The implications of the CSA for research and medicines development, the path to approval of medicines, and their subsequent removal from Schedule I in the US are discussed. This entire process occurs within the framework of the CSA in the US and its counterparts internationally in accordance with international drug control treaties. Abuse potential related research in the US informs the eight factors of the CSA which provide the basis for rescheduling actions that must occur upon approval of a drug that contains a Schedule I substance. Abuse-related research also informs drug product labeling and the risk evaluation and mitigation strategies (REMS) will likely be required for approved medicines. Human abuse potential studies typically employed in CNS drug development may be problematic for substances with strong hallucinogenic effects such as psilocybin, and alternative strategies are discussed. Implications for research, medicinal development, and controlled substance scheduling are presented in the context of the US CSA and FDA requirements with implications for global regulation. We also discuss how abuse-related research can contribute to understanding mechanisms of action and therapeutic effects as well as the totality of the effects of the drugs on the brain, behavior, mood, and the constructs of spirituality and consciousness.

keywords:
Humans, Substance-Related Disorders, Lysergic Acid Diethylamide, Hallucinogens, United States, Controlled Substances, Psilocybin

raw_json:
{"europe_pmc_id":"35987353","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2022-08-07
doi: 10.1007/s00213-022-06187-5
pubmed_id: 35939083
source_url: https://doi.org/10.1007/s00213-022-06187-5
keywords: Humans, Hallucinogens, Emotions, Surveys and Questionnaires, Psilocybin, Major Depressive Disorder
substance_tags: psilocybin
topic_tags: Depression,Emotional Processing,Clinical Trial,Randomized Controlled Trial,Observational Study
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
The Watts Connectedness Scale: a new scale for measuring a sense of connectedness to self, others, and world.

authors:
Watts R, Kettner H, Geerts D, Gandy S, Kartner L, Mertens L, Timmermann C, Nour MM, Kaelen M, Nutt D, Carhart-Harris R, Roseman L.

abstract:
RationaleA general feeling of disconnection has been associated with mental and emotional suffering. Improvements to a sense of connectedness to self, others and the wider world have been reported by participants in clinical trials of psychedelic therapy. Such accounts have led us to a definition of the psychological construct of 'connectedness' as 'a state of feeling connected to self, others and the wider world'. Existing tools for measuring connectedness have focused on particular aspects of connectedness, such as 'social connectedness' or 'nature connectedness', which we hypothesise to be different expressions of a common factor of connectedness. Here, we sought to develop a new scale to measure connectedness as a construct with these multiple domains. We hypothesised that (1) our scale would measure three separable subscale factors pertaining to a felt connection to 'self', 'others' and 'world' and (2) improvements in total and subscale WCS scores would correlate with improved mental health outcomes post psychedelic use.ObjectivesTo validate and test the 'Watts Connectedness Scale' (WCS).MethodsPsychometric validation of the WCS was carried out using data from three independent studies. Firstly, we pooled data from two prospective observational online survey studies. The WCS was completed before and after a planned psychedelic experience. The total sample of completers from the online surveys was N = 1226. Exploratory and confirmatory factor analysis were performed, and construct and criterion validity were tested. A third dataset was derived from a double-blind randomised controlled trial (RCT) comparing psilocybin-assisted therapy (n = 27) with 6 weeks of daily escitalopram (n = 25) for major depressive disorder (MDD), where the WCS was completed at baseline and at a 6-week primary endpoint.ResultsAs hypothesised, factor analysis of all WCS items revealed three main factors with good internal consistency. WCS showed good construct validity. Significant post-psychedelic increases were observed for total connectedness scores (η2 = 0.339, p

raw_json:
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authors: Berens N, Kim SY.
publication_date: 2022-07-10
doi: 10.1016/j.jagp.2022.07.003
pubmed_id: 35927119
source_url: https://doi.org/10.1016/j.jagp.2022.07.003
keywords: Humans, Ketamine, Suicide, Assisted, Depression, Ethical Analysis, Physicians, Female, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,End-of-Life Distress,Case Report,Healthcare Workers
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Rapid-Response Treatments for Depression and Requests for Physician-Assisted Death: An Ethical Analysis.

abstract:
Depression is common at the end of life, and there is longstanding concern that it may affect terminally ill patients' decisions to request physician-assisted death (PAD). However, it is difficult for clinicians to determine the role of depression in a patient's PAD request. A recent case series described rapid responses to intranasal ketamine in three patients with terminal illness and comorbid depression who had requested PAD. One patient withdrew her request (which, in retrospect, had been driven by her depression) while the others maintained their requests; in all three, the rapid relief clarified the role of depression in the patients' decision-making. In addition to ketamine, there are other emerging rapid-response treatments for depression, including psilocybin with psychological support and functional connectivity-guided transcranial magnetic stimulation. We examine three key ethical implications of such treatments: their role in clarifying the decision-making capacity of depressed patients requesting PAD; the potential tension between the legal definition of irremediability in some jurisdictions and the ethical obligations of clinicians; and the likely obstacles to treatment access and their implications for equal respect for autonomy of patients.

raw_json:
{"europe_pmc_id":"35927119","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Raut SB, Marathe PA, van Eijk L, Eri R, Ravindran M, Benedek DM, Ursano RJ, Canales JJ, Johnson LR.
publication_date: 2022-04-26
doi: 10.1016/j.pharmthera.2022.108195
pubmed_id: 35489438
source_url: https://doi.org/10.1016/j.pharmthera.2022.108195
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Mechanism of Action,Clinical Trial,Animal Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation.

abstract:
Post-traumatic stress disorder (PTSD), characterized by abnormally persistent and distressing memories, is a chronic debilitating condition in need of new treatment options. Current treatment guidelines recommend psychotherapy as first line management with only two drugs, sertraline and paroxetine, approved by U.S. Food and Drug Administration (FDA) for treatment of PTSD. These drugs have limited efficacy as they only reduce symptoms related to depression and anxiety without producing permanent remission. PTSD remains a significant public health problem with high morbidity and mortality requiring major advances in therapeutics. Early evidence has emerged for the beneficial effects of psychedelics particularly in combination with psychotherapy for management of PTSD, including psilocybin, MDMA, LSD, cannabinoids, ayahuasca and ketamine. MDMA and psilocybin reduce barrier to therapy by increasing trust between therapist and patient, thus allowing for modification of trauma related memories. Furthermore, research into the memory reconsolidation mechanisms has allowed for identification of various pharmacological targets to disrupt abnormally persistent memories. A number of pre-clinical and clinical studies have investigated novel and re-purposed pharmacological agents to disrupt fear memory in PTSD. Novel therapeutic approaches like neuropeptide Y, oxytocin, cannabinoids and neuroactive steroids have also shown potential for PTSD treatment. Here, we focus on the role of fear memory in the pathophysiology of PTSD and propose that many of these new therapeutic strategies produce benefits through the effect on fear memory. Evaluation of recent research findings suggests that while a number of drugs have shown promising results in preclinical studies and pilot clinical trials, the evidence from large scale clinical trials would be needed for these drugs to be incorporated in clinical practice.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Cannabinoids, Fear, Stress Disorders, Post-Traumatic, United States, Psilocybin

raw_json:
{"europe_pmc_id":"35489438","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Altman BR, Earleywine M, De Leo J.
publication_date: 2022-01-02
doi: 10.1080/02791072.2021.2020382
pubmed_id: 34979875
source_url: https://doi.org/10.1080/02791072.2021.2020382
keywords: Humans, Female, Psilocybin, Cognitive Behavioral Therapy
substance_tags: psilocybin
topic_tags: Depression,Healthcare Workers,Adverse Events
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Exploring the Credibility of Psilocybin-assisted Therapy and Cognitive-behavioral Therapy for Depression.

abstract:
Depression treatments succeed with many but leave others unimproved, and they can generate concerns about side effects, time, and cost. Psilocybin has generated media attention and empirical support for antidepressant effects, but lay impressions of its effectiveness are unclear. Although perceptions of treatment credibility contribute to outcome, beliefs about the credibility of psilocybin-assisted therapy (PAT) among potential patients remain uninvestigated, especially relative to cognitive-behavioral therapy (CBT), a common, empirically-validated approach. The present study examined credibility ratings for CBT and PAT among individuals reporting depressive symptoms. Participants (N = 803) from Amazon's MTurk platform reported demographics, depressive symptoms, and psychotherapy experience, then read data-based vignettes describing each therapy and rated their credibility. Individuals rated CBT as more credible than PAT. Those with therapy experience rated CBT as more credible than those without. Men and lifetime hallucinogen users rated PAT more credible than women and non-users, but few other predictors accounted for much variance in credibility. Results suggest that potential clients appear cautious about PAT. As continued work examines the effectiveness of psychedelic-assisted interventions, researchers and clinicians must consider patients' beliefs about treatments as potential predictors of outcomes. Additionally, the paradigm used here might have potential for examining credibility of many interventions.

raw_json:
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authors: Mohamed A, Touheed S, Ahmed M, Hor M, Fatima S
journal: Cureus
publication_date: 2022-09-30
doi: 10.7759/cureus.30919
pubmed_id: 36465766
source_url: https://pubmed.ncbi.nlm.nih.gov/36465766/
substance_tags: psilocybin
topic_tags: PTSD,Aging,Review Article
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"36465766"}
title:
The Efficacy of Psychedelic-Assisted Therapy in Managing Post-traumatic Stress Disorder (PTSD): A New Frontier?

abstract:
Post-traumatic stress disorder (PTSD) is a significant public health concern for which existing therapies are only marginally effective. Indisputably, the primary line of treatment for PTSD is psychotherapy, according to current treatment guidelines. However, PTSD continues to be a chronic condition even after psychotherapy, with high psychiatric and medical illness rates. There is a dire need to search for new compounds and approaches for managing PTSD. The usage of psychedelic substances is a potential new method. This article reviews the efficacy of psychedelic-assisted therapy in treating PTSD and improving patient outcomes. It will examine current research on the topic and evaluate the benefits and drawbacks of different therapies. The current evidence for the use of four different types of psychedelics (3,4-methylenedioxymethamphetamine, ketamine, classical psychedelics, and cannabis) in the treatment of PTSD will be reviewed. It will also include an overview of the therapeutic justification, context of use, and level of evidence available for each drug. Several questions are formulated that could be studied in future research in order to gain a better understanding of the topic.

keywords:
cannabinoids, dmt, hallucinogens, ketamine, lsd, mdma, post traumatic stress disorder, psilocybin, psychedelic-assisted therapy, ptsd


authors: Li SN, Xu F, Long P, Liu F, Zhang P, Fan YG, Chen ZH.
publication_date: 2022-10-30
doi: 10.3389/fmicb.2022.1021583
pubmed_id: 36386664
source_url: https://doi.org/10.3389/fmicb.2022.1021583
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Five new species of Inosperma from China: Morphological characteristics, phylogenetic analyses, and toxin detection.

abstract:
Many species of Inosperma cause neurotoxic poisoning in humans after consumption around the world. However, the toxic species of Inosperma and its toxin content remain unclear. In the present study, we proposed five new Inosperma species from China, namely, I. longisporum, I. nivalellum, I. sphaerobulbosum, I. squamulosobrunneum, and I. squamulosohinnuleum. Morphological and molecular phylogenetic analyses based on three genes (ITS, nrLSU, rpb2) revealed that these taxa are independent species. A key to 17 species of Inosperma in China is provided. In addition, targeted screening for the most notorious mushroom neurotoxins, muscarine, psilocybin, ibotenic acid, and muscimol, in these five new species was performed by using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Our results show that the neurotoxin contents in these five species varied: I. sphaerobulbosum contains none of the tested neurotoxins; I. nivalellum is muscarine positive; I. longisporum and I. squamulosohinnuleum contain both ibotenic acid and muscimol, and I. squamulosobrunneum only contains muscimol; psilocybin was not detected in these five new species.

raw_json:
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title: Electrical spiking of psilocybin fungi.
authors: Gandia A, Adamatzky A.
publication_date: 2022-10-23
doi: 10.1080/19420889.2022.2136118
pubmed_id: 36311546
source_url: https://doi.org/10.1080/19420889.2022.2136118
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Psilocybin fungi, aka "magic" mushrooms, are well known for inducing colorful and visionary states of mind. Such psychoactive properties and the ease of cultivating their basidiocarps within low-tech setups make psilocybin fungi promising pharmacological tools for mental health applications. Understanding of the intrinsic electrical patterns occurring during the mycelial growth can be utilized for better monitoring the physiological states and needs of these species. In this study we aimed to shed light on this matter by characterizing the extra-cellular electrical potential of two popular species of psilocybin fungi: Psilocybe tampanensis and P. cubensis. As in previous experiments with other common edible mushrooms, the undisturbed fungi have shown to generate electric potential spikes and trains of spiking activity. This short analysis provides a proof of intrinsic electrical communication in psilocybin fungi, and further establishes these fungi as a valuable tool for studying fungal electro-physiology.

raw_json:
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authors: Gaddis A, Lidstone DE, Nebel MB, Griffiths RR, Mostofsky SH, Mejia AF, Barrett FS.
publication_date: 2022-07-01
doi: 10.1016/j.neuroimage.2022.119434
pubmed_id: 35792293
source_url: https://doi.org/10.1016/j.neuroimage.2022.119434
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivity.

abstract:
BackgroundClassic psychedelics, such as psilocybin and LSD, and other serotonin 2A receptor (5-HT2AR) agonists evoke acute alterations in perception and cognition. Altered thalamocortical connectivity has been hypothesized to underlie these effects, which is supported by some functional MRI (fMRI) studies. These studies have treated the thalamus as a unitary structure, despite known differential 5-HT2AR expression and functional specificity of different intrathalamic nuclei. Independent Component Analysis (ICA) has been previously used to identify reliable group-level functional subdivisions of the thalamus from resting-state fMRI (rsfMRI) data. We build on these efforts with a novel data-maximizing ICA-based approach to examine psilocybin-induced changes in intrathalamic functional organization and thalamocortical connectivity in individual participants.MethodsBaseline rsfMRI data (n=38) from healthy individuals with a long-term meditation practice was utilized to generate a statistical template of thalamic functional subdivisions. This template was then applied in a novel ICA-based analysis of the acute effects of psilocybin on intra- and extra-thalamic functional organization and connectivity in follow-up scans from a subset of the same individuals (n=18). We examined correlations with subjective reports of drug effect and compared with a previously reported analytic approach (treating the thalamus as a single functional unit).ResultsSeveral intrathalamic components showed significant psilocybin-induced alterations in spatial organization, with effects of psilocybin largely localized to the mediodorsal and pulvinar nuclei. The magnitude of changes in individual participants correlated with reported subjective effects. These components demonstrated predominant decreases in thalamocortical connectivity, largely with visual and default mode networks. Analysis in which the thalamus is treated as a singular unitary structure showed an overall numerical increase in thalamocortical connectivity, consistent with previous literature using this approach, but this increase did not reach statistical significance.ConclusionsWe utilized a novel analytic approach to discover psilocybin-induced changes in intra- and extra-thalamic functional organization and connectivity of intrathalamic nuclei and cortical networks known to express the 5-HT2AR. These changes were not observed using whole-thalamus analyses, suggesting that psilocybin may cause widespread but modest increases in thalamocortical connectivity that are offset by strong focal decreases in functionally relevant intrathalamic nuclei.

keywords:
Thalamus, Cerebral Cortex, Neural Pathways, Humans, Serotonin, Magnetic Resonance Imaging, Rest, Psilocybin

raw_json:
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authors: Jensen ME, Jensen ME, Stenbæk DS, Juul TS, Fisher PM, Ekstrøm CT, Knudsen GM, Fink-Jensen A.
publication_date: 2022-10-13
doi: 10.1136/bmjopen-2022-066019
pubmed_id: 36241352
source_url: https://doi.org/10.1136/bmjopen-2022-066019
substance_tags: psilocybin,psilocin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin-assisted therapy for reducing alcohol intake in patients with alcohol use disorder: protocol for a randomised, double-blinded, placebo-controlled 12-week clinical trial (The QUANTUM Trip Trial).

abstract:
IntroductionAlcohol use disorder is a difficult-to-treat psychiatric disorder and a major burden on public health. Existing treatment efficacy is moderate, and relapse rates are high. Preliminary findings suggest that psilocybin, a psychedelic compound, can safely and reliably occasion highly meaningful experiences that may spur a positive change in drinking behaviour when administered in a therapeutic context. However, the efficacy of a single psilocybin administration and its potential neurobiological underpinnings still remain unknown.Methods and analysisTo establish efficacy, we will investigate the effects of psilocybin-assisted therapy versus placebo in a randomised, double-blinded, placebo-controlled 12-week clinical trial. Ninety treatment-seeking patients, aged 20-70 years, diagnosed with alcohol use disorder will be recruited from the community via advertisement and referrals from general practitioners or specialised treatment units. The psilocybin or placebo will be administered in accordance with a protocol for psychological support before, during and after the dosing. Outcome assessments will be carried out 1, 4, 8 and 12 weeks postdosing. The primary outcome is reduction in the percentage of heavy drinking days from baseline to follow-up at 12 weeks. Key secondary outcomes are as follows: (1) total alcohol consumption, (2) phosphatidyl-ethanol, an objective biomarker for alcohol, (3) plasma psilocin, the active metabolite, to establish a possible therapeutic range, (4) the acute subjective drug experience as a possible predictor of treatment outcome and (5) neuronal response to alcohol cues and cognitive flexibility within corticostriatal pathways by use of functional MR brain imaging 1-week postdosing.Ethics and disseminationEthical approval has been obtained from the Committee on Health Research Ethics of the Capital Region of Denmark (H-20043832). All patients will be provided oral and written information about the trial before screening. The study results will be disseminated by peer-review publications and conference presentations.Trial registration numberEudraCT 2020-000829-55 and NCT05416229.

keywords:
Humans, Alcoholism, Ethanol, Hallucinogens, Treatment Outcome, Double-Blind Method, Alcohol Drinking, Randomized Controlled Trials as Topic, Psilocybin

topic_tags:
Addiction,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Clinical Trial,Randomized Controlled Trial,Review Article

raw_json:
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title: Potential Therapeutic Effects of Psilocybin: A Systematic Review.
authors: Goel DB, Zilate S.
publication_date: 2022-10-11
doi: 10.7759/cureus.30214
pubmed_id: 36381758
source_url: https://doi.org/10.7759/cureus.30214
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
Psilocybin is a plant alkaloid that is derived from precursors of tryptamine and is present in many different types of mushrooms. It has been utilized by indigenous peoples of Central and South America for centuries in a ceremonial setting to promote spiritual experiences. Indigenous societies have long employed psilocybin and other 5-HT2A agonist classic psychedelics in their rites. They were a focus in psychiatry in the middle of the 20th century as both experimental medicines and tools for studying brain function. Due to the fact that traditional psychedelics were being used for purposes other than medical research and in connection with the burgeoning counterculture by the late 1960s and early 1970s, these scientific investigations fell out of favor. However, thanks to a number of encouraging studies that validated the earlier research, interest in traditional psychedelics has surged among scientists in the 21st century. In this review, we examine therapeutic studies on psilocybin, the traditional psychedelic that has received the lion's share of recent attention. According to three controlled studies, psilocybin may reduce symptoms of depression and anxiety in the context of cancer-related psychological discomfort for at least six months after a single acute treatment for mood and anxiety disorders. Three months after two acute doses, individuals in a small, open-label study with treatment-resistant depression reported fewer depressive and anxiety symptoms. Small, open-label pilot studies on addiction have demonstrated encouraging success rates for alcohol and cigarette addiction. The review also briefly discusses the synthesis, mechanism of action, effects, molecular pharmacology, adverse effects, and contraindications of psilocybin.

topic_tags:
Depression,Anxiety,Addiction,Pharmacology,Mechanism of Action,Receptor Pharmacology,Aging,Spirituality,Systematic Review,Review Article,Cancer Patients,Treatment-Resistant Depression,Contraindications

raw_json:
{"europe_pmc_id":"36381758","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Sottile RJ, Vida T.
publication_date: 2022-10-11
doi: 10.3389/fpsyt.2022.991753
pubmed_id: 36311515
source_url: https://doi.org/10.3389/fpsyt.2022.991753
substance_tags: psilocybin
topic_tags: Anxiety,PTSD,Mechanism of Action,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
A proposed mechanism for the MDMA-mediated extinction of traumatic memories in PTSD patients treated with MDMA-assisted therapy.

abstract:
Post-traumatic stress disorder (PTSD) is a devastating psychiatric disorder afflicting millions of people around the world. Characterized by severe anxiety, intrusive thoughts, pervasive nightmares, an assortment of somatic symptoms, associations with severe long-term health problems, and an elevated risk of suicide, as much as 40-70% of patients suffer from refractory disease. 3,4-Methylenedioxy-methamphetamine (MDMA), like classic psychedelics such as psilocybin, have been used to enhance the efficacy of psychotherapy almost since their discovery, but due to their perceived potential for abuse and inclusion on USFDA (United States Food and Drug Administration) schedule 1, research into the mechanism by which they produce improvements in PTSD symptomology has been limited. Nevertheless, several compelling rationales have been explored, with the pro-social effects of MDMA thought to enhance therapeutic alliance and thus facilitate therapist-assisted trauma processing. This may be insufficient to fully explain the efficacy of MDMA in the treatment of psychiatric illness. Molecular mechanisms such as the MDMA mediated increase of brain-derived neurotrophic factor (BDNF) availability in the fear memory learning pathways combined with MDMA's pro-social effects may provide a more nuanced explanation for the therapeutic actions of MDMA.

raw_json:
{"europe_pmc_id":"36311515","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Jones GM, Nock MK.
publication_date: 2022-10-09
doi: 10.1038/s41598-022-18645-3
pubmed_id: 36216840
source_url: https://doi.org/10.1038/s41598-022-18645-3
substance_tags: psilocybin
topic_tags: Observational Study,Drug Interactions
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Race and ethnicity moderate the associations between lifetime psychedelic use (MDMA and psilocybin) and psychological distress and suicidality.

abstract:
Psychedelic compounds have been linked to salutary mental health outcomes in both naturalistic and clinical settings; however, current research on psychedelics suffers from a lack of inclusion and focus on racial and ethnic minorities. Thus, the goal of our study was to assess whether race and ethnicity moderate the associations that naturalistic lifetime MDMA (3,4-Methylenedioxymethamphetamine) use and psilocybin use share with past month psychological distress and past year suicidality (ideation and planning). Using data from the National Survey on Drug Use and Health (NSDUH) (2008-2019) (N = 484,732), we conducted survey-weighted multivariable logistic regression to conduct interaction tests and to assess the associations that MDMA use and psilocybin use share with the aforementioned outcomes for each racial and ethnic group. Race and ethnicity significantly moderated the associations between MDMA and psilocybin use and psychological distress and suicidality. For White participants, MDMA and psilocybin use conferred lowered odds of all distress and suicidality outcomes. For racial and ethnic minority participants, the associations between psychedelic use and suicidality were far fewer. These findings invite further research into the impact of race, ethnicity, and other identity factors (e.g., socioeconomic status, sexual/gender minority status) on the effects of psychedelic substances.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Suicide, Minority Groups, Psilocybin, Psychological Distress, Ethnicity

raw_json:
{"europe_pmc_id":"36216840","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin: a revolution in psychedelic medicines in the US?
authors: Silberner J.
publication_date: 2022-10-05
doi: 10.1136/bmj.o2178
pubmed_id: 36202403
source_url: https://doi.org/10.1136/bmj.o2178
keywords: Humans, Lysergic Acid Diethylamide, Hallucinogens, Emotions, Psilocybin
substance_tags: psilocybin
topic_tags: Emotional Processing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
{"europe_pmc_id":"36202403","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Søndergaard A, Madsen MK, Ozenne B, Armand S, Knudsen GM, Fisher PM, Stenbæk DS.
publication_date: 2022-10-04
doi: 10.3389/fpsyg.2022.948729
pubmed_id: 36275302
source_url: https://doi.org/10.3389/fpsyg.2022.948729
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Mystical Experience,Healthy Volunteers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Lasting increases in trait mindfulness after psilocybin correlate positively with the mystical-type experience in healthy individuals.

abstract:
BackgroundPsilocybin-induced mystical-type experiences are associated with lasting positive psychological outcomes. Recent studies indicate that trait mindfulness is increased 3 months after psilocybin intake, preceded by decreases in neocortical serotonin 2A receptor (5-HT2AR) binding. However, the association between psilocybin-induced mystical-type experiences and subsequent changes in trait mindfulness remains unexplored, as does the association between pre-drug trait mindfulness and 5-HT2AR binding in the healthy brain.AimWe evaluated whether psilocybin induced lasting increases in trait mindfulness in healthy volunteers, and whether the mystical-type experience was associated with this increase. We further examined the association between pre-drug trait mindfulness and 5-HT2AR binding in neocortex and selected frontolimbic regions.Materials and methodsForty-six medium-high dose psilocybin sessions were conducted in 39 healthy individuals. The mystical-type experience was measured with the Mystical Experience Questionnaire (MEQ) at the end of the session. Trait mindfulness was measured using the Mindful Attention and Awareness Scale (MAAS) at baseline and 3 months after the psilocybin session. Thirty-two of the participants completed pre-drug [11C]-Cimbi-36 positron emission tomography (PET) to assess 5-HT2AR binding in neocortex and, post-hoc, in the frontolimbic regions amygdala, frontal cortex, and anterior cingulate cortex.ResultsThe MAAS score was significantly increased at 3-month follow-up (p = 3.24 × 10-6), a change positively associated with the MEQ score (p = 0.035). Although the association between pre-drug MAAS score and neocortex 5-HT2AR binding was not significant (p = 0.24), post-hoc analyses revealed a significant negative association between MAAS and right amygdala 5-HT2AR binding (pFWER = 0.008).ConclusionWe here show that lasting changes in trait mindfulness following psilocybin administration are positively associated with intensity of the mystical-type experience, suggesting that the acute phenomenology of psilocybin facilitates a shift in awareness conducive for mindful living. We furthermore show that higher pre-drug trait mindfulness is associated with reduced 5-HT2AR binding in the right amygdala.

raw_json:
{"europe_pmc_id":"36275302","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Chinese Cordyceps: Bioactive Components, Antitumor Effects and Underlying Mechanism-A Review.
authors: Liu Y, Guo ZJ, Zhou XW
journal: Molecules (Basel, Switzerland)
publication_date: 2022-10-03
doi: 10.3390/molecules27196576
pubmed_id: 36235111
source_url: https://pubmed.ncbi.nlm.nih.gov/36235111/
keywords: Chinese Cordyceps, antitumor, bioactive components, immunomodulatory, mechanism
substance_tags: psilocybin
topic_tags: Mechanism of Action,Review Article,Immune Function
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 06:54:13
raw_json: {"pubmed_id":"36235111"}
abstract:
Chinese Cordyceps is a valuable source of natural products with various therapeutic effects. It is rich in various active components, of which adenosine, cordycepin and polysaccharides have been confirmed with significant immunomodulatory and antitumor functions. However, the underlying antitumor mechanism remains poorly understood. In this review, we summarized and analyzed the chemical characteristics of the main components and their pharmacological effects and mechanism on immunomodulatory and antitumor functions. The analysis revealed that Chinese Cordyceps promotes immune cells' antitumor function by via upregulating immune responses and downregulating immunosuppression in the tumor microenvironment and resetting the immune cells' phenotype. Moreover, Chinese Cordyceps can inhibit the growth and metastasis of tumor cells by death (including apoptosis and autophagy) induction, cell-cycle arrest, and angiogenesis inhibition. Recent evidence has revealed that the signal pathways of mitogen-activated protein kinases (MAPKs), nuclear factor kappaB (NF-κB), cysteine-aspartic proteases (caspases) and serine/threonine kinase Akt were involved in the antitumor mechanisms. In conclusion, Chinese Cordyceps, one type of magic mushroom, can be potentially developed as immunomodulator and anticancer therapeutic agents.


title: Psilocybin for Treatment of Alcohol Use Disorder.
authors: Slomski A.
publication_date: 2022-09-30
doi: 10.1001/jama.2022.15436
pubmed_id: 36194230
source_url: https://doi.org/10.1001/jama.2022.15436
keywords: Humans, Alcoholism, Hallucinogens, Alcohol Drinking, Psilocybin
substance_tags: psilocybin
topic_tags: Addiction
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
{"europe_pmc_id":"36194230","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2022-10-02
doi: 10.3389/fpsyt.2022.990405
pubmed_id: 36262632
source_url: https://doi.org/10.3389/fpsyt.2022.990405
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
title:
3,4-Methylenedioxy methamphetamine, synthetic cathinones and psychedelics: From recreational to novel psychotherapeutic drugs.

authors:
López-Arnau R, Camarasa J, Carbó ML, Nadal-Gratacós N, Puigseslloses P, Espinosa-Velasco M, Urquizu E, Escubedo E, Pubill D.

abstract:
The utility of classical drugs used to treat psychiatric disorders (e.g., antidepressants, anxiolytics) is often limited by issues of lack of efficacy, delayed onset of action or side effects. Psychoactive substances have a long history of being used as tools to alter consciousness and as a gateway to approach the unknown and the divinities. These substances were initially obtained from plants and animals and more recently by chemical synthesis, and its consumption evolved toward a more recreational use, leading to drug abuse-related disorders, trafficking, and subsequent banning by the authorities. However, these substances, by modulation of certain neurochemical pathways, have been proven to have a beneficial effect on some psychiatric disorders. This evidence obtained under medically controlled conditions and often associated with psychotherapy, makes these substances an alternative to conventional medicines, to which in many cases the patient does not respond properly. Such disorders include post-traumatic stress disease and treatment-resistant depression, for which classical drugs such as MDMA, ketamine, psilocybin and LSD, among others, have already been clinically tested, reporting successful outcomes. The irruption of new psychoactive substances (NPS), especially during the last decade and despite their recreational and illicit uses, has enlarged the library of substances with potential utility on these disorders. In fact, many of them were synthetized with therapeutic purposes and were withdrawn for concrete reasons (e.g., adverse effects, improper pharmacological profile). In this review we focus on the basis, existing evidence and possible use of synthetic cathinones and psychedelics (specially tryptamines) for the treatment of mental illnesses and the properties that should be found in NPS to obtain new therapeutic compounds.

topic_tags:
Depression,PTSD,Mechanism of Action,Consciousness,Review Article,Treatment-Resistant Depression,Adverse Events

raw_json:
{"europe_pmc_id":"36262632","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2022-10-02
doi: 10.1038/s41467-022-33578-1
pubmed_id: 36192411
source_url: https://doi.org/10.1038/s41467-022-33578-1
substance_tags: psilocybin
topic_tags: Brain Imaging,Receptor Pharmacology,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain's control energy landscape.

authors:
Singleton SP, Luppi AI, Carhart-Harris RL, Cruzat J, Roseman L, Nutt DJ, Deco G, Kringelbach ML, Stamatakis EA, Kuceyeski A.

abstract:
Psychedelics including lysergic acid diethylamide (LSD) and psilocybin temporarily alter subjective experience through their neurochemical effects. Serotonin 2a (5-HT2a) receptor agonism by these compounds is associated with more diverse (entropic) brain activity. We postulate that this increase in entropy may arise in part from a flattening of the brain's control energy landscape, which can be observed using network control theory to quantify the energy required to transition between recurrent brain states. Using brain states derived from existing functional magnetic resonance imaging (fMRI) datasets, we show that LSD and psilocybin reduce control energy required for brain state transitions compared to placebo. Furthermore, across individuals, reduction in control energy correlates with more frequent state transitions and increased entropy of brain state dynamics. Through network control analysis that incorporates the spatial distribution of 5-HT2a receptors (obtained from publicly available positron emission tomography (PET) data under non-drug conditions), we demonstrate an association between the 5-HT2a receptor and reduced control energy. Our findings provide evidence that 5-HT2a receptor agonist compounds allow for more facile state transitions and more temporally diverse brain activity. More broadly, we demonstrate that receptor-informed network control theory can model the impact of neuropharmacological manipulation on brain activity dynamics.

keywords:
Brain, Humans, Serotonin, Lysergic Acid Diethylamide, Receptor, Serotonin, 5-HT2A, Hallucinogens, Serotonin 5-HT2 Receptor Agonists, Psilocybin

raw_json:
{"europe_pmc_id":"36192411","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Effects of classic psychedelic drugs on turbulent signatures in brain dynamics.
publication_date: 2022-09-30
doi: 10.1162/netn_a_00250
pubmed_id: 38800462
source_url: https://doi.org/10.1162/netn_a_00250
substance_tags: psilocybin
topic_tags: Mechanism of Action,Default Mode Network
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
authors:
Cruzat J, Perl YS, Escrichs A, Vohryzek J, Timmermann C, Roseman L, Luppi AI, Ibañez A, Nutt D, Carhart-Harris R, Tagliazucchi E, Deco G, Kringelbach ML.

abstract:
Psychedelic drugs show promise as safe and effective treatments for neuropsychiatric disorders, yet their mechanisms of action are not fully understood. A fundamental hypothesis is that psychedelics work by dose-dependently changing the functional hierarchy of brain dynamics, but it is unclear whether different psychedelics act similarly. Here, we investigated the changes in the brain's functional hierarchy associated with two different psychedelics (LSD and psilocybin). Using a novel turbulence framework, we were able to determine the vorticity, that is, the local level of synchronization, that allowed us to extend the standard global time-based measure of metastability to become a local-based measure of both space and time. This framework produced detailed signatures of turbulence-based hierarchical change for each psychedelic drug, revealing consistent and discriminate effects on a higher level network, that is, the default mode network. Overall, our findings directly support a prior hypothesis that psychedelics modulate (i.e., "compress") the functional hierarchy and provide a quantification of these changes for two different psychedelics. Implications for therapeutic applications of psychedelics are discussed.

raw_json:
{"europe_pmc_id":"38800462","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Microdosing with classical psychedelics: Research trajectories and practical considerations.
authors: Wong A, Raz A.
publication_date: 2022-10-30
doi: 10.1177/13634615221129115
pubmed_id: 36317302
source_url: https://doi.org/10.1177/13634615221129115
keywords: Humans, Lysergic Acid Diethylamide, Hallucinogens, Mental Health, United States, Psilocybin
substance_tags: psilocybin
topic_tags: Consciousness,Microdosing,Creativity,Healthcare Workers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Microdosing-the intermittent ingestion of minute, sub-hallucinogenic amounts of psychedelic substances, repeatedly and over time-has become a widespread, albeit largely understudied, phenomenon. Regulations around using psychedelics at any dose-micro, mini, macro, or mega-pose all sorts of difficulties for those who wish to systematically study the effects of Schedule I drugs, especially in the United States. Microdosers commonly claim that taking a sub-hallucinogenic (pre-hallucinogenic or sub-perceptual) dose improves higher brain functions, including creativity, productivity, and mood. If true, these results would provide an important experimental edge in distinguishing psychosocial effects (e.g. caused by expectation) from those related to the active psychedelic ingredient. In this critical integrative synthesis, we explore the psychobiological science of dose amounts and how it informs microdosing with classical psychedelics (e.g. lysergic acid diethylamide [LSD] and psilocybin) to highlight and fuel research into questions (e.g. in cognitive neuroscience, consciousness studies, and metacognition). We sketch the hurdle-laden regulatory landscape and the procedures that shroud research with Schedule I drugs. Finally, we offer some future directions relevant to both scholars and clinicians in the social and behavioral sciences as well as in mental health and neurological science.

raw_json:
{"europe_pmc_id":"36317302","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic medicine at a crossroads: Advancing an integrative approach to research and practice.
authors: Gobbi G, Inserra A, Greenway KT, Lifshitz M, Kirmayer LJ
journal: Transcultural psychiatry
publication_date: 2022-09-30
doi: 10.1177/13634615221119388
pubmed_id: 36263521
source_url: https://pubmed.ncbi.nlm.nih.gov/36263521/
keywords: LSD, Psychedelics, consciousness, context, culture, ketamine, psilocybin, psychotherapy
substance_tags: psilocybin
topic_tags: Mechanism of Action,Consciousness,Spirituality,Adverse Events
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"36263521"}
abstract:
Psychedelics have been already used by human societies for more than 3000 years, mostly in religious and healing context. The renewed interest in the potential application of psychedelic compounds as novel therapeutics has led to promising preliminary evidence of clinical benefit in some psychiatric disorders. Despite these promising results, the potential for large-scale clinical application of these profoundly consciousness-altering substances, in isolation from the sociocultural contexts in which they were traditionally used, raises important concerns. These concerns stem from the recognition that the mechanisms of therapeutic action of psychedelics are not entirely dependent on neurobiology, but also on the psychological, social and spiritual processes for their efficacy. For these reasons, physicians or psychotherapists involved in psychedelic-assisted psychotherapy need training in ways to accompany patients through this experience to promote positive outcomes and address potential side effects. Psychedelic therapies may foster the emergence of a novel paradigm in psychiatry that integrates psychopharmacological, psychotherapeutic, and cultural interventions for patients with mental health issues.


authors: Dupuis D, Veissière S.
publication_date: 2022-10-18
doi: 10.1177/13634615221131465
pubmed_id: 36263513
source_url: https://doi.org/10.1177/13634615221131465
keywords: Humans, Substance-Related Disorders, Hallucinogens, Anxiety, Anxiety Disorders, Psychotherapy
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Mechanism of Action,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Culture, context, and ethics in the therapeutic use of hallucinogens: Psychedelics as active super-placebos?

abstract:
Following decades of prohibition and widespread concern about their mind-altering properties, there is increasing public, scholarly, and clinical interest in the therapeutic potential of psychedelic substances. Serotonergic substances in particular (DMT, psilocybin, and LSD) are now being tested as treatments for such ailments as depression, anxiety, and substance use disorder. This thematic issue of Transcultural Psychiatry presents articles that investigate the cultural assumptions, political dimensions, and clinical and ethical implications that arise from this renewed interest. After reviewing ongoing debates on therapeutic mechanisms of action and the importance of context, we argue that psychedelics can be conceptualized as "active super-placebos"-that is, substances that enhance ritual, symbolic, and interpersonal therapeutic processes by increasing suggestibility and the influence of extra-pharmacological, "non-specific" factors. Rather than simply freeing up habitual constraints on perception, the articles in this issue support the claim that psychedelic encounters typically entail processes of sense-making, crystallization of meaning, and enculturation into contextually mediated assumptive worlds (or ideologies) and behaviours that necessarily install novel constraints with potentially maladaptive consequences. We highlight the importance of clinical and epistemic integrity in the framing of psychedelic therapies. The importance of structuring and providing oversight for the therapeutic context raises difficult questions about the search for appropriate forms of epistemic authority that are at once respectful of the plural cultural origins of psychedelic rituals and mindful of best practices and standards in clinical care.

raw_json:
{"europe_pmc_id":"36263513","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Animal Behavior in Psychedelic Research.
authors: Odland AU, Kristensen JL, Andreasen JT.
publication_date: 2022-09-30
doi: 10.1124/pharmrev.122.000590
pubmed_id: 36180111
source_url: https://doi.org/10.1124/pharmrev.122.000590
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
abstract:
Psychedelic-assisted psychotherapy holds great promise in the treatment of mental health disorders. Research into 5-hydroxytryptamine 2A receptor (5-HT2AR) agonist psychedelic compounds has increased dramatically over the past two decades. In humans, these compounds produce drastic effects on consciousness, and their therapeutic potential relates to changes in the processing of emotional, social, and self-referential information. The use of animal behavior to study psychedelics is under debate, and this review provides a critical perspective on the translational value of animal behavior studies in psychedelic research. Acute activation of 5-HT2ARs produces head twitches and unique discriminative cues, disrupts sensorimotor gating, and stimulates motor activity while inhibiting exploration in rodents. The acute treatment with psychedelics shows discrepant results in conventional rodent tests of depression-like behaviors but generally induces anxiolytic-like effects and inhibits repetitive behavior in rodents. Psychedelics impair waiting impulsivity but show discrepant effects in other tests of cognitive function. Tests of social interaction also show conflicting results. Effects on measures of time perception depend on the experimental schedule. Lasting or delayed effects of psychedelics in rodent tests related to different behavioral domains appear to be rather sensitive to changes in experimental protocols. Studying the effects of psychedelics on animal behaviors of relevance to effects on psychiatric symptoms in humans, assessing lasting effects, publishing negative findings, and relating behaviors in rodents and humans to other more translatable readouts, such as neuroplastic changes, will improve the translational value of animal behavioral studies in psychedelic research. SIGNIFICANCE STATEMENT: Psychedelics like LSD and psilocybin have received immense interest as potential new treatments of psychiatric disorders. Psychedelics change high-order consciousness in humans, and there is debate about the use of animal behavior studies to investigate these compounds. This review provides an overview of the behavioral effects of 5-HT2AR agonist psychedelics in laboratory animals and discusses the translatability of the effects in animals to effects in humans. Possible ways to improve the utility of animal behavior in psychedelic research are discussed.

keywords:
Animals, Humans, Serotonin, Lysergic Acid Diethylamide, Anti-Anxiety Agents, Hallucinogens, Behavior, Animal, Psilocybin

topic_tags:
Depression,Anxiety,Receptor Pharmacology,Consciousness,Emotional Processing,Review Article,Drug Interactions

raw_json:
{"europe_pmc_id":"36180111","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The Emerging Field of Psychedelic Psychotherapy.
authors: Barber GS, Aaronson ST.
publication_date: 2022-09-20
doi: 10.1007/s11920-022-01363-y
pubmed_id: 36129571
source_url: https://doi.org/10.1007/s11920-022-01363-y
substance_tags: psilocybin
topic_tags: Depression,PTSD,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Purpose of reviewFew treatments are available for patients with mood disorders or post-traumatic stress disorder (PTSD) who have already failed multiple interventions. After several decades when research into psychedelics was effectively halted by federal legislation, the past several years have shown the re-emergence of thoughtful investigations studying the utility of compounds such as 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin.Recent findingsSeveral studies have coupled the safe administration of psychedelic compounds in a controlled environment after several hours of preparation of study participants and followed by multiple sessions to integrate the psychedelic experience. The improvement participants experience appear related to the often profound perspective changes experienced and seem unlike the improvements seen in the currently available care paradigms. Studies cited include treatment resistant depression, end of life despair, and PTSD. Psychedelic psychotherapy, a unique remarriage of biological therapy and psychotherapy, has the potential to transform mental health care.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Stress Disorders, Post-Traumatic, Psychotherapy, Psilocybin

raw_json:
{"europe_pmc_id":"36129571","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2022-09-11
doi: 10.1007/s40263-022-00944-y
pubmed_id: 36097251
source_url: https://doi.org/10.1007/s40263-022-00944-y
keywords: Humans, Hallucinogens, Psilocybin
substance_tags: psilocybin
topic_tags: Randomized Controlled Trial,Systematic Review,Review Article
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
A Research Domain Criteria (RDoC)-Guided Dashboard to Review Psilocybin Target Domains: A Systematic Review.

authors:
Pouyan N, Halvaei Khankahdani Z, Younesi Sisi F, Lee Y, Rosenblat JD, Teopiz KM, Lui LMW, Subramaniapillai M, Lin K, Nasri F, Rodrigues N, Gill H, Lipsitz O, Cao B, Ho R, Castle D, McIntyre RS.

abstract:
BackgroundPreliminary results from randomized controlled studies as well as identified molecular, cellular, and circuit targets of select psychedelics (e.g., psilocybin) suggest that their effects are transdiagnostic. In this review, we exploit the Research Domain Criteria (RDoC) transdiagnostic framework, to synthesize extant literature on psilocybin.ObjectiveWe aimed to identify RDoC-based effects of psilocybin and vistas for future mechanistic and interventional research.MethodsA systematic search in electronic databases (i.e., PubMed, Scopus, PsycINFO, and Web of Science) performed in January and February 2021 identified English articles published between 1990 and 2020 reporting the effects of psilocybin on mental health measures. Data from included articles were retrieved and organized according to the RDoC bio-behavioral matrix and its constituent six main domains, namely: positive valence systems, negative valence systems, cognitive systems, social processes, sensorimotor systems, and arousal and regulatory systems.ResultsThe preponderance of research with psilocybin has differentially reported beneficial effects on positive valence systems, negative valence system, and social process domains. The data from the included studies support both short-term (23 assessments) and long-term (15 assessments) beneficial effects of psilocybin on the positive valence systems. While 12 of the extracted outcome measures suggest that psilocybin use is associated with increases in the "fear" construct of the negative valence systems domain, 19 findings show no significant effects on this construct, and seven parameters show lowered levels of the "sustained threat" construct in the long term. Thirty-four outcome measures revealed short-term alterations in the social systems' construct namely, "perception and understanding of self," and "social communications" as well as enhancements in "perception and understanding of others" and "affiliation and attachment". The majority of findings related to the cognitive systems' domain reported dyscognitive effects. There have been relatively few studies reporting outcomes of psilocybin on the remaining RDoC domains. Moreover, seven of the included studies suggest the transdiagnostic effects of psilocybin. The dashboard characterization of RDoC outcomes with psilocybin suggests beneficial effects in the measures of reward, threat, and arousal, as well as general social systems.ConclusionsPsilocybin possesses a multi-domain effectiveness. The field would benefit from highly rigorous proof-of-mechanism research to assess the effects of psilocybin using the RDoC framework. The combined effect of psilocybin with psychosocial interventions with RDoC-based outcomes is a priority therapeutic vista.

raw_json:
{"europe_pmc_id":"36097251","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Why Otolaryngologists Should Be Interested in Psychedelic Medicine.
authors: Asher BF
journal: Otolaryngologic clinics of North America
publication_date: 2022-09-30
doi: 10.1016/j.otc.2022.06.002
pubmed_id: 36088153
source_url: https://pubmed.ncbi.nlm.nih.gov/36088153/
keywords: Ketamine, MDMA, Psilocybin, Psychedelic
substance_tags: psilocybin
topic_tags: Contraindications
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"36088153"}
abstract:
As psychedelic medicine is becoming mainstream, physicians need to know something about these medications, their indications, contraindications, and potential for research. This article is a brief overview of the subject with some ideas of how psychedelic medicines can impact the practice of Otolaryngology-Head and Neck Surgery.


title: Expectancy in placebo-controlled trials of psychedelics: if so, so what?
authors: Butler M, Jelen L, Rucker J
journal: Psychopharmacology
publication_date: 2022-09-30
doi: 10.1007/s00213-022-06221-6
pubmed_id: 36063208
source_url: https://pubmed.ncbi.nlm.nih.gov/36063208/
keywords: Clinical trials, Expectancy, Placebo, Psilocybin, Psychoactive medication
substance_tags: psilocybin
topic_tags: Clinical Trial,Randomized Controlled Trial
study_type: Randomized Controlled Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"36063208"}
abstract:
Modern psychedelic research remains in an early phase, and the eventual introduction of psychedelics into clinical practice remains in doubt. In this piece, we discuss the role of blinding and expectancy in psychedelic trials, and place this in a broader historical and contemporary context of blinding in trials across the rest of healthcare. We suggest that premature and uncritical promotion ('hype') of psychedelics as medicines is not only misleading, but also directly influences participant expectancy in ongoing psychedelic trials. We argue that although psychedelic trials are likely to significantly overestimate treatment effects by design due to unblinding and expectancy effects, this is not a unique situation. Placebo-controlled RCTs are not a perfect fit for all therapeutics, and problems in blinding should not automatically disqualify medications from licencing decisions. We suggest that simple practical measures may be (and indeed already are) taken in psychedelic trials to partially mitigate the effects of expectancy and unblinding, such as independent raters and active placebos. We briefly suggest other alternative trial methodologies which could be used to bolster RCT results, such as naturalistic studies. We conclude that the results of contemporary placebo-controlled RCTs of psychedelics should neither be dismissed due to imperfections in design, nor should early data be taken as firm evidence of effectiveness.


authors: Erkizia-Santamaría I, Alles-Pascual R, Horrillo I, Meana JJ, Ortega JE.
publication_date: 2022-08-29
doi: 10.1016/j.biopha.2022.113612
pubmed_id: 36049313
source_url: https://doi.org/10.1016/j.biopha.2022.113612
substance_tags: psilocybin,psilocin
topic_tags: Mechanism of Action,Receptor Pharmacology,Animal Study,In Vitro Study,Adverse Events
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Serotonin 5-HT2A, 5-HT2c and 5-HT1A receptor involvement in the acute effects of psilocybin in mice. In vitro pharmacological profile and modulation of thermoregulation and head-twich response.

abstract:
The psychedelic 5-HT2A receptor (5HT2AR) agonist psilocybin (or the active metabolite psilocin) has emerged as potential useful drug for various neuropsychiatric diseases, with a rapid onset of therapeutic activity. However, the mechanisms responsible for such effects remain incompletely characterized. We aimed to study in vitro pharmacological profile and in vivo acute mechanism of psilocin/psilocybin. Competition binding studies with psilocin were performed in brain and cell cultures. The role of 5HT2AR, 5-HT2C receptors (5HT2CR) and 5-HT1A receptors (5HT1AR) on the psychosis-like head-twitch response (HTR) and on body temperature in mice after psilocybin administration were evaluated. Psilocin showed similar affinities for 5HT2AR (Ki: 120-173 nM), 5HT2CR (Ki: 79-311 nM) and 5-HT1AR (Ki: 152-146 nM) in human and mice brain. Psilocybin induced a dose-dependent HTR (maximal effect 17.07 ± 1.31 at 1 mg/kg i.p.) that was completely suppressed by the 5HT2AR antagonist MDL11939 (1 mg/kg). Higher doses of psilocybin (3 mg/kg) induced lower HTR (9.00 ± 0.53). The 5HT2CR antagonist SB242084 (0.1 mg/kg) increased HTR exerted by psilocybin (3 mg/kg). Psilocybin significantly raised core body temperature at low dose (0.125 mg/kg) (Emax=0.67 ± 0.15 °C), whereas a significant decrease was induced by doses over 1 mg/kg (Emax = -1.31 ± 0.16 °C). Pre-treatment with the 5HT1AR antagonist WAY100635 reversed the decrease of body temperature after psilocybin (1 mg/kg), causing hyperthermia (Emax = 0.94 ± 0.26 °C). The present work provides key findings on the 5HT2AR, 5-HT2CR and 5HT1AR involvement in the acute central effects of psilocybin. The results may be relevant for understanding the mechanism of action underlying the therapeutic effects and side effects of this psychedelic drug.

keywords:
Animals, Humans, Mice, Serotonin, Receptor, Serotonin, 5-HT1A, Hallucinogens, Body Temperature Regulation, Psilocybin

raw_json:
{"europe_pmc_id":"36049313","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Macrodosing to microdosing with psychedelics: Clinical, social, and cultural perspectives.
authors: Kaypak AC, Raz A.
publication_date: 2022-08-28
doi: 10.1177/13634615221119386
pubmed_id: 36031848
source_url: https://doi.org/10.1177/13634615221119386
substance_tags: psilocybin
topic_tags: Microdosing,Creativity,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
To date, the clinical and scientific literature has best documented the effects of classical psychedelics, such as lysergic acid diethylamide (LSD), psilocybin, and dimethyltryptamine (DMT), in typical quantities most often associated with macrodosing. More recently, however, microdosing with psychedelics has emerged as a social trend and nascent therapeutic intervention. This variation in psychedelic practice refers to repeat, intermittent ingestion of less-than-macrodose amounts that do not cause the effects associated with full-blown "trips". Microdosing paves the road to incorporating psychedelic drugs into a daily routine while maintaining, or even improving, cognitive and mental function. Unlike macrodosing with psychedelics, the influence of microdosing remains mostly unexplored. And yet, despite the paucity of formal studies, many informal accounts propose that microdosing plays an important role as both a therapeutic intervention (e.g., in mental disorders) and enhancement tool (e.g., recreationally-to boost creativity, improve cognition, and drive personal growth). In response to this relatively new practice, we provide an integrative synthesis of the clinical, social, and cultural dimensions of microdosing. We describe some of the overarching context that explains why this practice is increasingly in vogue, unpack potential benefits and risks, and comment on sociocultural implications. In addition, this article considers the effects that macro- and microdoses have on behavior and psychopathology in light of their dosage characteristics and contexts of use.

keywords:
Humans, N,N-Dimethyltryptamine, Lysergic Acid Diethylamide, Hallucinogens, Mental Disorders, Psilocybin

raw_json:
{"europe_pmc_id":"36031848","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Breeksema JJ, Kuin BW, Kamphuis J, van den Brink W, Vermetten E, Schoevers RA.
publication_date: 2022-08-25
doi: 10.1177/02698811221116926
pubmed_id: 36017784
source_url: https://doi.org/10.1177/02698811221116926
substance_tags: psilocybin
topic_tags: Anxiety,Headache / Migraine,Clinical Trial,Systematic Review,Review Article,Adverse Events
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review.

abstract:
IntroductionSmall-scale clinical studies with psychedelic drugs have shown promising results for the treatment of several mental disorders. Before psychedelics become registered medicines, it is important to know the full range of adverse events (AEs) for making balanced treatment decisions.ObjectiveTo systematically review the presence of AEs during and after administration of serotonergic psychedelics and 3,4-methyenedioxymethamphetamine (MDMA) in clinical studies.MethodsWe systematically searched PubMed, PsycINFO, Embase, and ClinicalTrials.gov for clinical trials with psychedelics since 2000 describing the results of quantitative and qualitative studies.ResultsWe included 44 articles (34 quantitative + 10 qualitative), describing treatments with MDMA and serotonergic psychedelics (psilocybin, lysergic acid diethylamide, and ayahuasca) in 598 unique patients. In many studies, AEs were not systematically assessed. Despite this limitation, treatments seemed to be overall well tolerated. Nausea, headaches, and anxiety were commonly reported acute AEs across diagnoses and compounds. Late AEs included headaches (psilocybin, MDMA), fatigue, low mood, and anxiety (MDMA). One serious AE occurred during MDMA administration (increase in premature ventricular contractions requiring brief hospitalization); no other AEs required medical intervention. Qualitative studies suggested that psychologically challenging experiences may also be therapeutically beneficial. Except for ayahuasca, a large proportion of patients had prior experience with psychedelic drugs before entering studies.ConclusionsAEs are poorly defined in the context of psychedelic treatments and are probably underreported in the literature due to study design (lack of systematic assessment of AEs) and sample selection. Acute challenging experiences may be therapeutically meaningful, but a better understanding of AEs in the context of psychedelic treatments requires systematic and detailed reporting.

keywords:
Humans, Banisteriopsis, Headache, N-Methyl-3,4-methylenedioxyamphetamine, Lysergic Acid Diethylamide, Hallucinogens, Psilocybin

raw_json:
{"europe_pmc_id":"36017784","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2022-09-30
doi: 10.1001/jamapsychiatry.2022.2096
pubmed_id: 36001306
source_url: https://doi.org/10.1001/jamapsychiatry.2022.2096
substance_tags: psilocybin
topic_tags: Addiction,Clinical Trial,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial.

authors:
Bogenschutz MP, Ross S, Bhatt S, Baron T, Forcehimes AA, Laska E, Mennenga SE, O'Donnell K, Owens LT, Podrebarac S, Rotrosen J, Tonigan JS, Worth L.

abstract:
ImportanceAlthough classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown.ObjectiveTo evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy.Design, setting, and participantsIn this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following the first dose of study medication. The study was conducted at 2 academic centers in the US. Participants were recruited from the community between March 12, 2014, and March 19, 2020. Adults aged 25 to 65 years with a DSM-IV diagnosis of alcohol dependence and at least 4 heavy drinking days during the 30 days prior to screening were included. Exclusion criteria included major psychiatric and drug use disorders, hallucinogen use, medical conditions that contraindicated the study medications, use of exclusionary medications, and current treatment for AUD.InterventionsStudy medications were psilocybin, 25 mg/70 kg, vs diphenhydramine, 50 mg (first session), and psilocybin, 25-40 mg/70 kg, vs diphenhydramine, 50-100 mg (second session). Psychotherapy included motivational enhancement therapy and cognitive behavioral therapy.Main outcomes and measuresThe primary outcome was percentage of heavy drinking days, assessed using a timeline followback interview, contrasted between groups over the 32-week period following the first administration of study medication using multivariate repeated-measures analysis of variance.ResultsA total of 95 participants (mean [SD] age, 46 [12] years; 42 [44.2%] female) were randomized (49 to psilocybin and 46 to diphenhydramine). One participant (1.1%) was American Indian/Alaska Native, 3 (3.2%) were Asian, 4 (4.2%) were Black, 14 (14.7%) were Hispanic, and 75 (78.9%) were non-Hispanic White. Of the 95 randomized participants, 93 received at least 1 dose of study medication and were included in the primary outcome analysis. Percentage of heavy drinking days during the 32-week double-blind period was 9.7% for the psilocybin group and 23.6% for the diphenhydramine group, a mean difference of 13.9%; (95% CI, 3.0-24.7; F1,86 = 6.43; P =.01). Mean daily alcohol consumption (number of standard drinks per day) was also lower in the psilocybin group. There were no serious adverse events among participants who received psilocybin.Conclusions and relevancePsilocybin administered in combination with psychotherapy produced robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy. These results provide support for further study of psilocybin-assisted treatment for AUD.Trial registrationClinicalTrials.gov Identifier: NCT02061293.

keywords:
Humans, Alcoholism, Diphenhydramine, Hallucinogens, Treatment Outcome, Double-Blind Method, Alcohol Drinking, Psychotherapy, Adult, Middle Aged, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"36001306","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Prevalence and associations of classic psychedelic-related seizures in a population-based sample.
authors: Simonsson O, Goldberg SB, Chambers R, Osika W, Long DM, Hendricks PS
journal: Drug and alcohol dependence
publication_date: 2022-09-30
doi: 10.1016/j.drugalcdep.2022.109586
pubmed_id: 35981469
source_url: https://pubmed.ncbi.nlm.nih.gov/35981469/
keywords: Adverse, LSD, Psilocybin, Psychedelics, Risk, Seizures
substance_tags: psilocybin
topic_tags: Addiction,Safety
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"35981469"}
abstract:
Previous studies have reported links between classic psychedelic use and seizures, but little remains known about prevalence and potential risk factors of classic psychedelic-related seizures.
Using a sample representative of the US adult population with regard to sex, age, and ethnicity (N = 2822), this study examined the prevalence and potential risk factors of classic psychedelic-related seizures, in a subsample of respondents who reported lifetime classic psychedelic use (n = 613).
Among those who reported lifetime classic psychedelic use, 1.5 % reported classic psychedelic-related seizures, a statistic that comports with the prevalence of epilepsy in the US population. Among those who reported seizures while using a classic psychedelic, almost half reported co-use of antidepressants, mood stabilizers, or opioid replacement therapies at the time of the seizures. Notably, classic psychedelic-related seizures were more commonly reported in certain respondents, especially those with a personal or family history of epilepsy.
These results suggest that classic psychedelic use could increase the risk of seizures in certain populations, particularly those with a personal or family history of epilepsy.


title: New investigational agents for the treatment of major depressive disorder.
authors: Pochwat B, Krupa AJ, Siwek M, Szewczyk B
journal: Expert opinion on investigational drugs
publication_date: 2022-09-30
doi: 10.1080/13543784.2022.2113376
pubmed_id: 35975761
source_url: https://pubmed.ncbi.nlm.nih.gov/35975761/
keywords: NMDA, Rapid-acting antidepressant, depression, ketamine, psilocybin, serotonin
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Receptor Pharmacology,Review Article
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"35975761"}
abstract:
Pharmacotherapy of depression is characterized by the delayed onset of action, chronic treatment requirements, and insufficient effectiveness. Ketamine, with its rapid action and long-lasting effects, represents a breakthrough in the modern pharmacotherapy of depression.
The current review summarizes the latest findings on the mechanism of the antidepressant action of ketamine and its enantiomers and metabolites. Furthermore, the antidepressant potential of psychedelics, non-hallucinogenic serotonergic modulators, and metabotropic glutamate receptor ligands was discussed.
Recent data indicated that to achieve fast and long-acting antidepressant-like effects, compounds must induce durable effects on the architecture and density of dendritic spines in brain regions engaged in mood regulation. Such mechanisms underlie the actions of ketamine and psychedelics. These compounds trigger hallucinations; however, it is thought that these effects might be essential for their antidepressant action. Behavioral studies with serotonergic modulators affecting 5-HT1A (biased agonists), 5-HT4 (agonists), and 5-HT-7 (antagonists) receptors exert rapid antidepressant-like activity, but they seem to be devoid of these effects. Another way to avoid psychomimetic effects and achieve the desired rapid antidepressant-like effects is combined therapy. In this respect, ligands of metabotropic receptors show some potential.


authors: Barnett BS, Ziegler K, Doblin R, Carlo AD
journal: Journal of psychopharmacology (Oxford, England)
publication_date: 2022-09-30
doi: 10.1177/02698811221117536
pubmed_id: 35971893
source_url: https://pubmed.ncbi.nlm.nih.gov/35971893/
keywords: LSD, MDMA, Psychedelic, cancer, leukemia, lymphoma, psilocybin
substance_tags: psilocybin
topic_tags: Case Report,Observational Study,In Vitro Study
study_type: Case Report
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"35971893"}
title:
Is psychedelic use associated with cancer?: Interrogating a half-century-old claim using contemporary population-level data.

abstract:
In 1967, concerns about the carcinogenic potential of psychedelics arose after a study reported chromosomal damage in human leukocytes following in vitro lysergic acid (LSD) exposure. Worries were further heightened by subsequent reports of leukemia and other cancers in LSD users. Additional investigations of psychedelics' effects on chromosomes were published over the next decade, with the majority suggesting these concerns were unfounded. However, the relationship between psychedelics and cancer has been explored only minimally from an epidemiological perspective.
To determine whether associations exist between psychedelic use and either lifetime cancer or hematologic cancer diagnoses.
We analyzed data from adult participants in the 2015-2019 administrations of the National Survey on Drug Use and Health for associations between lifetime use of psychedelics and lifetime diagnosis of either any cancer or hematologic cancer.
We identified no associations between lifetime psychedelic use and either lifetime cancer diagnosis or hematologic cancer diagnosis. Sub-analyses of lifetime lysergamide, phenethylamine, and tryptamine use also revealed no associations with lifetime cancer or hematologic cancer diagnosis.
While laboratory studies and case reports from the 1960s and 1970s generated concerns about psychedelics' carcinogenic potential, this analysis of recent epidemiological data does not support an association between psychedelic use and development of cancer in general or hematologic cancer. Important study limitations to consider include a lack of information about psychedelic dosage, number of lifetime psychedelic exposures, and the temporal relationship between psychedelic use and cancer diagnosis.


authors: Levin A, Nagib PB, Deiparine S, Gao T, Mitchell J, Davis AK.
publication_date: 2022-08-10
doi: 10.1016/j.drugpo.2022.103816
pubmed_id: 35964449
source_url: https://doi.org/10.1016/j.drugpo.2022.103816
substance_tags: psilocybin
topic_tags: Aging,Observational Study,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Inconsistencies between national drug policy and professional beliefs about psychoactive drugs among psychiatrists in the United States.

abstract:
BackgroundEvidence points to an incongruence between international drug policy and expert opinion about safety, abuse potential, and therapeutic potential of specific drugs. However, no prior studies have directly explored psychiatrists' attitudes about the current drug schedule. Therefore, we examined whether American psychiatrists' perceptions of four psychoactive drugs differed from those indicated by their schedules.MethodsA quasi-experimental online survey of a convenience sample of psychiatrists in the United States (N=181; Mean age=48.7; Female=35%). Participants were randomized to receive 1-of-4 vignettes, each depicting a depressed patient reporting relief from symptoms after non-prescribed psychoactive drug use (i.e., psilocybin [Schedule I], methamphetamine [SchedII], ketamine [SchedIII], or alprazolam [SchedIV]). Participants responded to questions related to this clinical scenario and then rated the safety, therapeutic, and abuse potentials of these four drugs and alcohol.ResultsThere were significant differences by vignette condition in mean likelihood ratings of: warning against engaging in drug use again (p

keywords:
Humans, Methamphetamine, Ketamine, Alprazolam, Psychotropic Drugs, Psychiatry, Public Policy, Middle Aged, United States, Female, Psilocybin

raw_json:
{"europe_pmc_id":"35964449","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin Efficacy and Mechanisms of Action in Major Depressive Disorder: a Review.
authors: Prouzeau D, Conejero I, Voyvodic PL, Becamel C, Abbar M, Lopez-Castroman J.
publication_date: 2022-08-11
doi: 10.1007/s11920-022-01361-0
pubmed_id: 35953638
source_url: https://doi.org/10.1007/s11920-022-01361-0
keywords: Humans, Hallucinogens, Antidepressive Agents, Psilocybin, Major Depressive Disorder
substance_tags: psilocybin
topic_tags: Depression,End-of-Life Distress,Mechanism of Action,Clinical Trial,Review Article,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
Purpose of the reviewWe aim to provide an overview of the current state of knowledge about the efficacy of psilocybin in the treatment of depression, as well as its mechanisms of action.Recent findingsPsilocybin has a large, rapid, and persistent clinical effect in the treatment of resistant or end-of-life depression. Tolerance is good, with mild side effects limited to a few hours after dosing. The studies conducted to date have had small sample sizes. One clinical trial has been conducted against a reference treatment (escitalopram) without showing a significant superiority of psilocybin in the main outcome. The neurobiological mechanisms, mostly unknown, differ from those of SSRI antidepressants. Psilocybin represents a promising alternative in the treatment of depression. Further research with larger sample sizes, particularly against reference treatments, is needed to better understand the neurobiological factors of its effects and to investigate its potential for use in everyday practice.

raw_json:
{"europe_pmc_id":"35953638","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Pilc A, Machaczka A, Kawalec P, Smith JL, Witkin JM.
publication_date: 2022-08-21
doi: 10.1080/17460441.2022.2111415
pubmed_id: 35934973
source_url: https://doi.org/10.1080/17460441.2022.2111415
substance_tags: psilocybin
topic_tags: Depression,Pharmacology,Mechanism of Action,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Where do we go next in antidepressant drug discovery? A new generation of antidepressants: a pivotal role of AMPA receptor potentiation and mGlu2/3 receptor antagonism.

abstract:
IntroductionMajor depressive disorder remains a prevalent world-wide health problem. Currently available antidepressant medications take weeks of dosing, do not produce antidepressant response in all patients, and have undesirable ancillary effects.Areas coveredThe present opinion piece focuses on the major inroads to the creation of new antidepressants. These include N-methyl-D-aspartate (NMDA) receptor antagonists and related compounds like ketamine, psychedelic drugs like psilocybin, and muscarinic receptor antagonists like scopolamine. The preclinical and clinical pharmacological profile of these new-age antidepressant drugs is discussed.Expert opinionPreclinical and clinical data have accumulated to predict a next generation of antidepressant medicines. In contrast to the current standard of care antidepressant drugs, these compounds differ in that they demonstrate rapid activity, often after a single dose, and effects that outlive their presence in brain. These compounds also can provide efficacy for treatment-resistant depressed patients. The mechanism of action of these compounds suggests a strong glutamatergic component that involves the facilitation of AMPA receptor function. Antagonism of mGlu2/3 receptors is also relevant to the antidepressant pharmacology of this new class of drugs. Based upon the ongoing efforts to develop these new-age antidepressants, new drug approvals are predicted in the near future.

keywords:
Humans, Ketamine, Scopolamine, Receptors, AMPA, Receptors, N-Methyl-D-Aspartate, Antidepressive Agents, Depression, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"35934973","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Meyer TD, Meir P, Lex C, Soares JC.
publication_date: 2022-07-15
doi: 10.1016/j.psychres.2022.114727
pubmed_id: 35878481
source_url: https://doi.org/10.1016/j.psychres.2022.114727
keywords: Humans, Hallucinogens, Emotions, Mental Health, Psilocybe, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Emotional Processing,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Magic Mushrooms - an exploratory look at how mental health professionals feel and think about Psilocybin.

abstract:
Psilocybin recently received breakthrough status by the FDA for its use in treatment of depression. We therefore investigated mental health professionals' (MHPs) opinions on Psilocybin (n = 155). Overall, attitudes were neutral but self-rated knowledge of Psilocybin was low. The term used in the survey, 'Psilocybin' or 'Magic Mushrooms', did not significantly affect their responses. Some variables (i.e., gender, attitudes towards medical cannabis, and personal history of psychedelic usage) were associated with ratings of Psilocybin. These results provide a baseline of MHPs' thoughts on Psilocybin and what should be considered in the future if it is FDA-approved.

raw_json:
{"europe_pmc_id":"35878481","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Dworkin RH, Anderson BT, Andrews N, Edwards RR, Grob CS, Ross S, Satterthwaite TD, Strain EC
journal: The journal of pain
publication_date: 2022-09-30
doi: 10.1016/j.jpain.2022.05.003
pubmed_id: 35643270
source_url: https://pubmed.ncbi.nlm.nih.gov/35643270/
keywords: Chronic pain, LSD, clinical trials, psilocybin, psychedelics
substance_tags: psilocybin
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"35643270"}
title:
If the Doors of Perception Were Cleansed, Would Chronic Pain be Relieved? Evaluating the Benefits and Risks of Psychedelics.

abstract:
Psychedelic substances have played important roles in diverse cultures, and ingesting various plant preparations to evoke altered states of consciousness has been described throughout recorded history. Accounts of the subjective effects of psychedelics typically focus on spiritual and mystical-type experiences, including feelings of unity, sacredness, and transcendence. Over the past 2 decades, there has been increasing interest in psychedelics as treatments for various medical disorders, including chronic pain. Although concerns about adverse medical and psychological effects contributed to their controlled status, contemporary knowledge of psychedelics suggests that risks are relatively rare when patients are carefully screened, prepared, and supervised. Clinical trial results have provided support for the effectiveness of psychedelics in different psychiatric conditions. However, there are only a small number of generally uncontrolled studies of psychedelics in patients with chronic pain (eg, cancer pain, phantom limb pain, migraine, and cluster headache). Challenges in evaluating psychedelics as treatments for chronic pain include identifying neurobiologic and psychosocial mechanisms of action and determining which pain conditions to investigate. Truly informative proof-of-concept and confirmatory randomized clinical trials will require careful selection of control groups, efforts to minimize bias from unblinding, and attention to the roles of patient mental set and treatment setting. PERSPECTIVE: There is considerable promise for the use of psychedelic therapy for pain, but evidence-based recommendations for the design of future studies are needed to ensure that the results of this research are truly informative.

topic_tags:
Chronic Pain,Headache / Migraine,Mechanism of Action,Consciousness,Spirituality,Mystical Experience,Clinical Trial,Safety


authors: Timmermann C, Watts R, Dupuis D
journal: Transcultural psychiatry
publication_date: 2022-09-30
doi: 10.1177/13634615221082796
pubmed_id: 35313754
source_url: https://pubmed.ncbi.nlm.nih.gov/35313754/
keywords: ayahuasca, know-how, neurophenomenology, psilocybin, psychedelic therapy, revelations
substance_tags: psilocybin
topic_tags: Safety
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"35313754"}
title:
Towards psychedelic apprenticeship: Developing a gentle touch for the mediation and validation of psychedelic-induced insights and revelations.

abstract:
A striking feature of psychedelics is their ability to increase attribution of truth and meaningfulness to specific contents and ideas experienced, which may persist long after psychedelic effects have subsided. We propose that processes underlying conferral of meaning and truth in psychedelic experiences may act as a double-edged sword: while these may drive important therapeutic benefits, they also raise important considerations regarding the validation and mediation of knowledge gained during these experiences. Specifically, the ability of psychedelics to induce noetic feelings of revelation may enhance the significance and attribution of reality to specific beliefs, worldviews, and apparent memories which might exacerbate the risk of iatrogenic complications that other psychotherapeutic approaches have historically faced, such as false memory syndrome. These considerations are timely, as the use of psychedelics is becoming increasingly mainstream, in an environment marked by the emergence of strong commercial interest for psychedelic therapy. We elaborate on these ethical challenges via three examples illustrating issues of validation and mediation in therapeutic, neo-shamanic and research contexts involving psychedelic use. Finally, we propose a pragmatic framework to attend to these challenges based on an ethical approach which considers the embeddedness of psychedelic experiences within larger historical and cultural contexts, their intersubjective character and the use of practices which we conceptualise here as forms of. This notion of goes beyond current approaches of and by stressing the central importance of validation practices based on by an experienced therapist or guide.


authors: Psiuk D, Nowak EM, Dycha N, Łopuszańska U, Kurzepa J, Samardakiewicz M.
publication_date: 2022-09-27
doi: 10.3390/ijms231911450
pubmed_id: 36232748
source_url: https://doi.org/10.3390/ijms231911450
substance_tags: psilocybin
topic_tags: Depression,Systematic Review,Review Article
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Esketamine and Psilocybin-The Comparison of Two Mind-Altering Agents in Depression Treatment: Systematic Review.

abstract:
This publication discusses two compounds belonging to the psychoactive substances group which are studied in the context of depression treatment-psilocybin and esketamine. The former is a naturally occurring psychedelic. The latter was invented in the laboratory exactly 60 years ago. Although the substances were controversial in the past, recent studies indicate the potential of those substances as novel antidepressant agents. The PubMed/MEDLINE database was used to identify articles for systematic review, using the following search terms: (depression) AND (psilocybin) OR (ketamine). From 617 items, only 12 articles were obtained in the final analyses. Three articles were devoted to psilocybin in depression treatment and nine to esketamine. In most studies, esketamine showed a significant reduction in both depressive symptoms and suicidal ideation shortly after intake and after a month of treatment compared to baseline and to standard-of-care antidepressant agents. Psilocybin's antidepressive effects occurred one day after intake and after 6-7 weeks of treatment and were maintained for up to 6 or 8 months of follow-up. One study indicated that psilocybin's effects are comparable with and may be superior to escitalopram treatment. Both esketamine and psilocybin demonstrated rapid and long-term effects in reducing depression symptoms and, after overcoming some limitations, may be considered as novel antidepressant agents in future.

keywords:
Humans, Ketamine, Hallucinogens, Antidepressive Agents, Depression, Depressive Disorder, Treatment-Resistant, Psilocybin

raw_json:
{"europe_pmc_id":"36232748","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Differences across sexes on head-twitch behavior and 5-HT2A receptor signaling in C57BL/6J mice.
authors: Jaster AM, Younkin J, Cuddy T, de la Fuente Revenga M, Poklis JL, Dozmorov MG, González-Maeso J.
publication_date: 2022-08-09
doi: 10.1016/j.neulet.2022.136836
pubmed_id: 35963476
source_url: https://doi.org/10.1016/j.neulet.2022.136836
substance_tags: psilocybin
topic_tags: Depression,Addiction,Pharmacology,Mechanism of Action,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
abstract:
Psychedelics, also known as classical hallucinogens, affect processes related to perception, cognition and sensory processing mostly via the serotonin 5-HT2A receptor (5-HT2AR). This class of psychoactive substances, which includes lysergic acid diethylamide (LSD), psilocybin, mescaline and the substituted amphetamine 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), is receiving renewed attention for their potential therapeutic properties as it relates to psychiatric conditions such as depression and substance use disorders. Current studies focused on the potentially clinical effects of psychedelics on human subjects tend to exclude sex as a biological variable. Much of the understanding of psychedelic pharmacology is derived from rodent models, but most of this preclinical research has only focused on male mice. Here we tested the effects of DOI on head-twitch behavior (HTR) - a mouse behavioral proxy of human psychedelic potential - in male and female mice. DOI elicited more HTR in female as compared to male C57BL/6J mice, a sex-specific exacerbated behavior that was not observed in 129S6/SvEv animals. Volinanserin (or M100907) - a 5-HT2AR antagonist - fully prevented DOI-induced HTR in male and female C57BL/6J mice. Accumulation of inositol monophosphate (IP1) in the frontal cortex upon DOI administration showed no sex-related effect in C57BL/6J mice. However, the pharmacokinetic properties of DOI differed among sexes - brain and plasma concentrations of DOI were lower 30 and 60 min after drug administration in female as compared to male C57BL/6J mice. Together, these results suggest strain-dependent and sex-related differences in the behavioral and pharmacokinetic profiles of the 5-HT2AR agonist DOI in C57BL/6J mice, and support the importance of studying sex as a biological variable in preclinical psychedelic research.

keywords:
Animals, Mice, Inbred C57BL, Humans, Mice, Serotonin, Amphetamine, Fluorobenzenes, Piperidines, Receptor, Serotonin, 5-HT2A, Hallucinogens, Behavior, Animal, Female, Male

raw_json:
{"europe_pmc_id":"35963476","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic drugs for psychiatric disorders.
authors: da Costa SC, Oesterle T, Rummans TA, Richelson E, Gold M.
publication_date: 2022-07-04
doi: 10.1016/j.jns.2022.120332
pubmed_id: 35841696
source_url: https://doi.org/10.1016/j.jns.2022.120332
keywords: Humans, Alcoholism, Lysergic Acid Diethylamide, Hallucinogens, Mental Disorders, Psilocybin
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
abstract:
Existing pharmacological treatments for psychiatric disorders have demonstrated limited efficacy, delayed onset of action, and significant burden of side effects. Recent findings from human studies with psychedelics have shown promise, demonstrating rapid and sustained clinical benefits of these compounds for a variety of psychiatric disorders. Classical psychedelics have a rich history and some of these compounds have been used in shamanic and spiritual ceremonies for millennia. The psychoactive effects of these drugs, particularly on human consciousness, have generated great scientific curiosity, and early research on psychedelics suggested their clinical benefits for psychiatric conditions, including alcohol use disorders and anxiety and depressive symptoms in terminal illness and life-threatening conditions. Since the 1990s, after a period of dormancy that followed the criminalization of psychedelic drugs since the Controlled Substance Act of 1970, the continued interest in their unique psychoactive effects along with the pursuit for novel and more effective treatments in psychiatry have led to a renewed interest in research on these compounds. While preliminary findings on psychedelics are encouraging, current evidence is still insufficient to support extensive use of these drugs routinely. Long-term safety and efficacy of these compounds remain unclear, and several clinical trials are underway and may add clarity to these questions. Therefore, this article intends to provide an overview of the evidence to date on psychedelic drugs - particularly psilocybin, MDMA, and LSD - for the treatment of psychiatric disorders.

topic_tags:
Depression,Anxiety,Addiction,End-of-Life Distress,Consciousness,Aging,Spirituality,Clinical Trial,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"35841696","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: Cureus
publication_date: 2022-08-31
doi: 10.7759/cureus.29167
pubmed_id: 36259015
source_url: https://pubmed.ncbi.nlm.nih.gov/36259015/
keywords: clinical trials, major depressive disorder, mdma, post traumatic stress disorder, psilocybin
substance_tags: psilocybin
topic_tags: Depression,PTSD,Addiction,Receptor Pharmacology,Clinical Trial
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"36259015"}
title:
The Use of Psychedelics in the Treatment of Medical Conditions: An Analysis of Currently Registered Psychedelics Studies in the American Drug Trial Registry.

authors:
Kurtz JS, Patel NA, Gendreau JL, Yang C, Brown N, Bui N, Picton B, Harris M, Hatter M, Beyer R, Sahyouni R, Diaz-Aguilar LD, Castellanos J, Schuster N, Abraham ME

abstract:
Although early therapeutic research on psychedelics dates back to the 1940s, this field of investigation was met with many cultural and legal challenges in the 1970s. Over the past two decades, clinical trials using psychedelics have resumed. Therefore, the goal of this study was to (1) better characterize the recent uptrend in psychedelics in clinical trials and (2) identify areas where potentially new clinical trials could be initiated to help in the treatment of widely prevalent medical disorders. A systematic search was conducted on the clinicaltrials.gov database for all registered clinical trials examining the use of psychedelic drugs and was both qualitatively and quantitatively assessed. Analysis of recent studies registered in clinicaltrials.gov was performed using Pearson's correlation coefficient testing. Statistical analysis and visualization were performed using R software. In totality, 105 clinical trials met this study's inclusion criteria. The recent uptrend in registered clinical trials studying psychedelics (p = 0.002) was similar to the uptrend in total registered clinical trials in the registry (p < 0.001). All trials took place from 2007 to 2020, with 77.1% of studies starting in 2017 or later. A majority of clinical trials were in phase 1 (53.3%) or phase 2 (25.7%). Common disorders treated include substance addiction, post-traumatic stress disorder, and major depressive disorder. Potential research gaps include studying psychedelics as a potential option for symptomatic treatment during opioid tapering. There appears to be a recent uptrend in registered clinical trials studying psychedelics, which is similar to the recent increase in overall trials registered. Potentially, more studies could be performed to evaluate the potential of psychedelics for symptomatic treatment during opioid tapering and depression refractory to selective serotonin reuptake inhibitors.


title: Association between Lifetime Classic Psychedelic Use and Sick Leave in a Population-Based Sample.
authors: Mellner C, Dahlen M, Simonsson O
journal: International journal of environmental research and public health
publication_date: 2022-09-08
doi: 10.3390/ijerph191811353
pubmed_id: 36141631
source_url: https://pubmed.ncbi.nlm.nih.gov/36141631/
substance_tags: psilocybin
topic_tags: Mechanism of Action,Observational Study,Safety
study_type: Observational Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"36141631"}
abstract:
Absenteeism from work due to illness, and related costs, has increased steadily during the past decades. In recent years, there has been a reemergence of research on the therapeutic effects of classic psychedelics showing associations with both physical and mental health. However, the association between classic psychedelics and sick leave remains unknown. The aim of this study is to investigate the association between lifetime classic psychedelic use and sick leave in the past 30 days among adults in the United States ( = 407,717), using data from the National Survey on Drug Use and Health (2005-2019), weighted to be representative of the US adult population.
The primary analysis was conducted using multiple linear regression, controlling for sociodemographic characteristics, risky behavior, and use of other substances.
There was a significant and negative association between lifetime classic psychedelic use and sick leave in the past 30 days (B = -0.09, < 0.01) when adjusting for all control variables.
These findings suggest that classic psychedelics could potentially lead to reduced sick leave and associated costs in the general population, but more research is needed to investigate potential causal pathways of classic psychedelics on sick leave and evaluate possible mechanisms.

keywords:
LSD, health economics, psilocybin, psychedelics, public health, sickness absence, sickness absenteeism


title: Psilocybin therapy reduces heavy drinking.
authors: O'Leary K.
publication_date: 2022-09-07
doi: 10.1038/d41591-022-00093-1
pubmed_id: 36076081
source_url: https://doi.org/10.1038/d41591-022-00093-1
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
{"europe_pmc_id":"36076081","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Skepticism about Recent Evidence That Psilocybin "Liberates" Depressed Minds.
authors: Doss MK, Barrett FS, Corlett PR.
publication_date: 2022-08-23
doi: 10.1021/acschemneuro.2c00461
pubmed_id: 36001741
source_url: https://doi.org/10.1021/acschemneuro.2c00461
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Receptor Pharmacology,Aging,Drug Interactions
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
A recent paper in Nature Medicine found that psilocybin therapy in patients with depression decreased brain network modularity (measured with task-free functional magnetic resonance imaging), an effect supposedly not found with the selective serotonin reuptake inhibitor S-citalopram. This decrease in network modularity also correlated with depression. Here, we raise several issues with this paper, including inconsistencies in reports of the primary clinical outcome, statistical flaws including a one-tailed test, nonsignificant interaction, and regression to the mean, the ambiguity and overinterpretation of "resting state" data, and a missing reference for a conceptually similar study that exemplifies why a one-tailed test cannot be justified. Together, these issues make us question the uniqueness and impact of these findings, as well as the unwarranted media hype that they generated.

keywords:
Brain, Humans, Citalopram, Magnetic Resonance Imaging, Psilocybin, Selective Serotonin Reuptake Inhibitors

raw_json:
{"europe_pmc_id":"36001741","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Effects of psilocybin versus escitalopram on rumination and thought suppression in depression.
authors: Barba T, Buehler S, Kettner H, Radu C, Cunha BG, Nutt DJ, Erritzoe D, Roseman L, Carhart-Harris R.
publication_date: 2022-09-05
doi: 10.1192/bjo.2022.565
pubmed_id: 36065128
source_url: https://doi.org/10.1192/bjo.2022.565
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Drug Interactions
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
BackgroundMajor depressive disorder is often associated with maladaptive coping strategies, including rumination and thought suppression.AimsTo assess the comparative effect of the selective serotonin reuptake inhibitor escitalopram, and the serotonergic psychedelic psilocybin (COMP360), on rumination and thought suppression in major depressive disorder.MethodBased on data derived from a randomised clinical trial (N = 59), we performed exploratory analyses on the impact of escitalopram versus psilocybin (i.e. condition) on rumination and thought suppression from 1 week before to 6 weeks after treatment inception (i.e. time), using mixed analysis of variance. Condition responder versus non-responder subgroup analyses were also done, using the standard definition of ≥50% symptom reduction.ResultsA time×condition interaction was found for rumination (F(1, 56) = 4.58, P = 0.037) and thought suppression (F(1,57) = 5.88, P = 0.019), with post hoc tests revealing significant decreases exclusively in the psilocybin condition. When analysing via response, a significant time×condition×response interaction for thought suppression (F(1,54) = 8.42, P = 0.005) and a significant time×response interaction for rumination (F(1,54) = 23.50, P < 0.001) were evident. Follow-up tests revealed that decreased thought suppression was exclusive to psilocybin responders, whereas rumination decreased in both responder groups. In the psilocybin arm, decreases in rumination and thought suppression correlated with ego dissolution and session-linked psychological insight.ConclusionsThese data provide further evidence on the therapeutic mechanisms of psilocybin and escitalopram in the treatment of depression.

raw_json:
{"europe_pmc_id":"36065128","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Clifton JM, Belcher AM, Greenblatt AD, Welsh CM, Cole TO, Davis AK.
publication_date: 2022-08-04
doi: 10.1556/2054.2022.00214
pubmed_id: 36686617
source_url: https://doi.org/10.1556/2054.2022.00214
substance_tags: psilocybin
topic_tags: Addiction,Observational Study,Safety
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Psilocybin use patterns and perception of risk among a cohort of Black individuals with Opioid Use Disorder.

abstract:
Background and aimsThere is growing evidence that psilocybin, a serotonergic psychedelic substance, may be useful in the treatment of substance use disorders. However, there is a lack of data on the beliefs and attitudes towards psilocybin amongst Black individuals diagnosed with Opioid Use Disorder (OUD). This study characterized psilocybin use patterns and perception of risk amongst a cohort of Black individuals diagnosed with OUD.MethodsUsing a convenience sampling approach, patients were recruited from an urban methadone treatment program and paid five dollars to complete an anonymous phone-based survey.ResultsTwenty-eight patients participated (mean age 53.8; N = 28; 35.7% female). Most (N = 23; 82.1%) had "heard of" psilocybin mushrooms before taking the survey, but only five (N = 5; 17.8%) had ever used them. More than 80% perceived a risk or were "unsure" of the risk for sixteen of the seventeen items queried about psilocybin. Approximately half (N = 15; 53.6%) were willing to try therapy incorporating psilocybin and half (N = 14; 50%) said they would be more likely to try if it were FDA approved for OUD. Most (N = 18; 64.3%) preferred to stay on methadone treatment alone, 32.1% (N = 9) wanted to try treatment with both psilocybin and methadone, and only one participant opted for psilocybin treatment without methadone.ConclusionMany Black individuals with Opioid Use Disorder perceive psilocybin as dangerous and may be hesitant to try psilocybin treatment. Culturally informed treatment models, educational interventions and community outreach programs should be developed to increase racial/ethnic minority representation in psilocybin research and treatment.

raw_json:
{"europe_pmc_id":"36686617","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Use of psychedelics in the Czech Republic: results of recent population surveys.
authors: Chomynová P, Kočárová R, Kňažek F, Plevková M, Bláhová B, Valeš K, Mravčík V.
publication_date: 2022-08-31
doi: 10.21101/cejph.a7079
pubmed_id: 36239361
source_url: https://doi.org/10.21101/cejph.a7079
substance_tags: psilocybin
topic_tags: Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
abstract:
ObjectivesDifferent psychoactive substances are widely used in today's society. So far limited data are available on the use of psychedelics in the general population. The main aim of this study is to estimate the numbers of users of substances with psychedelic properties (classical psychedelics, cannabis, ecstasy, and ketamine) in the Czech Republic.MethodsData from two samples enrolled in representative cross-sectional questionnaire surveys in the Czech adult population in 2016 (n = 2,785) and 2018 (n = 1,665) were analysed. Prevalence rates were extrapolated to estimate numbers of current, i.e., last-year, users of psychedelics, and their socio-demographic profiles were compared with non-users and users of cannabis.ResultsAn estimated 5-6% of the Czech adult population (350-430 thousand people) used classical psychedelics (LSD, psilocybin mushrooms, ayahuasca) in their lifetime, increasing up to 28-30% when cannabis is included (1.9-2.1 million users). Current use of classical psychedelics reached 0.7-1.9% (50-130 thousand people), and 9-11% (590-750 thousand users) when cannabis was included. Users of psychedelics were more often males, of younger age and single.ConclusionsNo significant socio-demographic differences were found between users of classical psychedelics and recreational cannabis users, however, differences were significant when compared to non-users and users of other illicit drugs. Findings should further serve to inform drug policy and social and healthcare systems in respect to the use of psychedelics.

keywords:
Humans, Cannabis, Substance-Related Disorders, Ketamine, Lysergic Acid Diethylamide, Hallucinogens, Cross-Sectional Studies, Adult, Czech Republic, Male, Psilocybin, Illicit Drugs

raw_json:
{"europe_pmc_id":"36239361","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: [The use of psilocybin for treatment-resistant depression].
authors: Johannesdottir A, Sigurdsson E.
publication_date: 2022-08-31
doi: 10.17992/lbl.2022.09.706
pubmed_id: 36040772
source_url: https://doi.org/10.17992/lbl.2022.09.706
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
The hallucinogen psilocybin is a potential novel treatment for treatment-resistant depression (TRD). Our goal is to review current knowledge on psilocybin and its efficacy in TRD. Literature searches were done on PubMed, Web of Science and Google Scholar, references reviewed in identified articles and other articles found on the website of COMPASS Pathways. Psilocybin treatment consists usually of a single oral administration of 25 mg of psilocybin along with psychological support for 5-8 hours during the ensuing hallucinogenic trip. Common side-effects include headache, nausea, fatigue and insomnia. A systematic review has demonstrated significant antidepressant efficacy in certain groups and a double-blind randomized study found antidepressant efficacy of psilocybin comparable to the SSRI escitalopram. In the phase 2 study of COMPASS Pathways, the psilocybin-COMP360 treatment led to a rapid response and remission as early as three weeks following the treatment for around one third of participants. Recent studies have shown that psilocybin significantly decreases the severity of depressive symptoms and is generally well tolerated. Further research will reveal whether it will be granted a license to treat treatment-resistant depression in the near future. There remains an urgent need for novel treatments for those who do not respond to current antidepressant therapies.

keywords:
Humans, Hallucinogens, Antidepressive Agents, Depression, Randomized Controlled Trials as Topic, Depressive Disorder, Treatment-Resistant, Psilocybin

topic_tags:
Depression,Headache / Migraine,Mechanism of Action,Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"36040772","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics as preventive treatment in headache and chronic pain disorders.
authors: Schindler EAD.
publication_date: 2022-06-15
doi: 10.1016/j.neuropharm.2022.109166
pubmed_id: 35718005
source_url: https://doi.org/10.1016/j.neuropharm.2022.109166
keywords: Humans, Headache, Hallucinogens, Chronic Pain, Psilocybin
substance_tags: psilocybin
topic_tags: Chronic Pain,Headache / Migraine,Mechanism of Action,Review Article,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
The effects of psychedelic drugs in headache and chronic pain disorders have been reported for several decades, and now controlled studies are emerging. The existing evidence supports a lasting therapeutic benefit after limited dosing, a unique feature of the drug class that distinguishes it from conventional treatment. This commentary summarizes these reports of preventive effects of psychedelic drugs in headache and chronic pain disorders. The recently published controlled trial of psilocybin in migraine is reviewed, including its limitations. Several neurobiological targets of psychedelics that are related to headache and chronic pain are highlighted, though a clear separation of acute and lasting effects is key in uncovering the unique clinical effects of this drug class. Considerable investigation is required before the effects, safety, and mechanism of action of psychedelics in headache and chronic pain disorders can be known.

raw_json:
{"europe_pmc_id":"35718005","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Natural language signatures of psilocybin microdosing.
publication_date: 2022-06-08
doi: 10.1007/s00213-022-06170-0
pubmed_id: 35676541
source_url: https://doi.org/10.1007/s00213-022-06170-0
substance_tags: psilocybin
topic_tags: Microdosing,Wellbeing,Creativity
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
authors:
Sanz C, Cavanna F, Muller S, de la Fuente L, Zamberlan F, Palmucci M, Janeckova L, Kuchar M, Carrillo F, García AM, Pallavicini C, Tagliazucchi E.

abstract:
RationaleSerotonergic psychedelics are being studied as novel treatments for mental health disorders and as facilitators of improved well-being, mental function, and creativity. Recent studies have found mixed results concerning the effects of low doses of psychedelics ("microdosing") on these domains. However, microdosing is generally investigated using instruments designed to assess larger doses of psychedelics, which might lack sensitivity and specificity for this purpose.ObjectivesDetermine whether unconstrained speech contains signatures capable of identifying the acute effects of psilocybin microdoses.MethodsNatural speech under psilocybin microdoses (0.5 g of psilocybin mushrooms) was acquired from thirty-four healthy adult volunteers (11 females: 32.09 ± 3.53 years; 23 males: 30.87 ± 4.64 years) following a double-blind and placebo-controlled experimental design with two measurement weeks per participant. On Wednesdays and Fridays of each week, participants consumed either the active dose (psilocybin) or the placebo (edible mushrooms). Features of interest were defined based on variables known to be affected by higher doses: verbosity, semantic variability, and sentiment scores. Machine learning models were used to discriminate between conditions. Classifiers were trained and tested using stratified cross-validation to compute the AUC and p-values.ResultsExcept for semantic variability, these metrics presented significant differences between a typical active microdose and the inactive placebo condition. Machine learning classifiers were capable of distinguishing between conditions with high accuracy (AUC [Formula: see text] 0.8).ConclusionsThese results constitute first evidence that low doses of serotonergic psychedelics can be identified from unconstrained natural speech, with potential for widely applicable, affordable, and ecologically valid monitoring of microdosing schedules.

keywords:
Humans, Hallucinogens, Double-Blind Method, Language, Mental Disorders, Adult, Female, Male, Creativity, Psilocybin

raw_json:
{"europe_pmc_id":"35676541","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Magic mushroom extracts in lipid membranes.
authors: Nguyen TQT, Lund FW, Zanjani AAH, Khandelia H.
publication_date: 2022-05-09
doi: 10.1016/j.bbamem.2022.183957
pubmed_id: 35561790
source_url: https://doi.org/10.1016/j.bbamem.2022.183957
keywords: Serotonin, Lipids, Hallucinogens, Protein Binding, Psilocybe
substance_tags: psilocybin,psilocin
topic_tags: Depression,Addiction,Receptor Pharmacology,Treatment-Resistant Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
The active hallucinogen of magic mushrooms, psilocin, is being repurposed to treat nicotine addiction and treatment-resistant depression. Psilocin belongs to the tryptamine class of psychedelic compounds which include the hormone serotonin. It is believed that psilocin exerts its effect by binding to the serotonin 5-HT2A receptor. However, recent in-vivo evidence suggests that psilocin may employ a different mechanism to exert its effects. Membrane-mediated receptor desensitization of neurotransmitter receptors is one such mechanism. We compare the impact of the neutral and charged versions of psilocin and serotonin on the properties of zwitterionic and anionic lipid membranes using molecular dynamics simulations and calorimetry. Both compounds partition to the lipid interface and induce membrane thinning. The tertiary amine in psilocin, as opposed to the primary amine in serotonin, limits psilocin's impact on the membrane although more psilocin partitions into the membrane than serotonin. Calorimetry corroborates that both compounds induce a classical melting point depression like anesthetics do. Our results also lend support to a membrane-mediated receptor-binding mechanism for both psilocin and serotonin and provide physical insights into subtle chemical changes that can alter the membrane-binding of psychedelic compounds.

raw_json:
{"europe_pmc_id":"35561790","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Fitzpatrick CM, Anderson BT, Agin-Liebes G, Guydish J.
publication_date: 2022-01-26
doi: 10.1080/02791072.2021.1983673
pubmed_id: 35083957
source_url: https://doi.org/10.1080/02791072.2021.1983673
substance_tags: psilocybin
topic_tags: OCD,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
title:
Comment and Response: (Lugo-Radillo & Cortez-Lopez, 2020) Long-Term Amelioration of OCD Symptoms in a Patient with Chronic Consumption of Psilocybin-Containing Mushrooms.

keywords:
Humans, Agaricales, Substance-Related Disorders, Hallucinogens, Obsessive-Compulsive Disorder, Review Literature as Topic, Psilocybin

raw_json:
{"europe_pmc_id":"35083957","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Lehto RH, Miller M, Sender J.
publication_date: 2021-09-05
doi: 10.1177/08980101211039086
pubmed_id: 34482761
source_url: https://doi.org/10.1177/08980101211039086
keywords: Humans, Neoplasms, Anxiety, Mental Health, Psychotherapy, Psilocybin
substance_tags: psilocybin
topic_tags: Anxiety,Consciousness,Aging,Spirituality,Review Article,Healthcare Workers
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
The Role of Psilocybin-Assisted Psychotherapy to Support Patients With Cancer: A Critical Scoping Review of the Research.

abstract:
Treatments for addressing psychiatric mental health issues in vulnerable patients with cancer are established. Yet, many patients persist with unrelenting psychological difficulties despite intervention. There is growing interest in the role of psilocybin-assisted psychotherapy for managing treatment-resistant mental health challenges in patients with cancer. Psilocybin is a naturally occurring compound derived from certain mushroom species that can induce entheogenic experiences or an altered state of consciousness. Reed's Self-Transcendence Theory provides a holistic lens to examine existential concerns and mental health in individuals who perceive their illness as potentially life threatening, such as those with cancer. This scoping literature review used Arksey and O'Malley's template to evaluate research examining psilocybin-assisted psychotherapy for patients with cancer. Eight articles met inclusion/exclusion criteria (four quantitative, two mixed methods, and two qualitative). Review findings indicated that the majority of patient experiences were positive, centering on themes of death acceptance, reflection, and broadened spirituality. Although psilocybin-assisted psychotherapy is in early stages of clinical testing, it thus shows promise for carefully screened patients with cancer who have persistent existential suffering. It will be critical for investigators to tailor this emerging intervention to select patients and for clinicians to be engaged in assessment of outcomes and efficacy.

raw_json:
{"europe_pmc_id":"34482761","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Davis AK, Agin-Liebes G, España M, Pilecki B, Luoma J
journal: Journal of psychoactive drugs
publication_date: 2021-12-31
doi: 10.1080/02791072.2021.1971343
pubmed_id: 34468293
source_url: https://pubmed.ncbi.nlm.nih.gov/34468293/
keywords: Psychedelics, hallucinogens, psilocybin, psychologists, survey
substance_tags: psilocybin
topic_tags: Observational Study,Safety
study_type: Observational Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"34468293"}
title:
Attitudes and Beliefs about the Therapeutic Use of Psychedelic Drugs among Psychologists in the United States.

abstract:
Psychologists are a vital component of mental health treatment and their perceptions of psychedelic-assisted therapy are critical for future implementation. This cross-sectional quasi-experimental electronic survey study explored the attitudes about psychedelics used in treatment among 366 clinical psychologists in the United States. Participants expressed cautiously favorable attitudes toward therapeutic psychedelic experiences but indicated concern about possible psychiatric and neurocognitive risks. Most participants indicated that they lack an understanding of the full range of effects of psychedelics, would need to seek out additional consultation, and endorsed positive beliefs in the potential of psychedelic treatment and the need for further research. Overall, this research identified the need to increase education and training about psychedelics for psychologists in order to help increase knowledge and reduce stigma about psychedelic therapies.


authors: Yan YY, Zhang YZ, Vauras J, Zhao LN, Fan YG, Li HJ, Xu F.
publication_date: 2022-08-29
doi: 10.3897/mycokeys.92.86277
pubmed_id: 36761319
source_url: https://doi.org/10.3897/mycokeys.92.86277
substance_tags: psilocybin,psilocin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
﻿ Pseudospermaarenarium (Inocybaceae), a new poisonous species from Eurasia, based on morphological, ecological, molecular and biochemical evidence.

abstract:
In this study, Pseudospermaarenarium is proposed as a new species, based on morphological, ecological, molecular and biochemical evidence. The new species grows on sandy ground under Populus and Pinussylvestris in north-western China and northern Europe, respectively. It is characterised by the combination of the robust habit, nearly glabrous pileus, large cylindrical basidiospores, thin-walled cheilocystidia and ecological associations with Populusalba × P.berolinensis and Pinussylvestris and unique phylogenetic placement. Additionally, a comprehensive toxin determination of the new species using ultra-high performance liquid chromatography-tandem mass spectrometry was conducted. Results showed that it was a muscarine-positive species. The content were approximately five times higher in the pilei [4012.2 ± 803.1-4302.3 ± 863.2 mg/kg (k = 2, p = 95%)] than in the stipes [850.4 ± 171.1-929.1 ± 184.2 mg/kg (k = 2, p = 95%)], demonstrating the severity of mushroom poisoning when patients consumed different parts of the poisonous mushroom. Amatoxins, phallotoxins, ibotenic acid, muscimol, psilocybin and psilocin were not detected.

raw_json:
{"europe_pmc_id":"36761319","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Sweeney MM, Nayak S, Hurwitz ES, Mitchell LN, Swift TC, Griffiths RR.
publication_date: 2022-08-23
doi: 10.1371/journal.pone.0271926
pubmed_id: 36001643
source_url: https://doi.org/10.1371/journal.pone.0271926
substance_tags: psilocybin
topic_tags: Spirituality,Mystical Experience,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Comparison of psychedelic and near-death or other non-ordinary experiences in changing attitudes about death and dying.

abstract:
Both psychedelic drug experiences and near-death experiences can occasion changes in perspectives on death and dying, but there have been few direct comparisons of these phenomena. This study directly compared psychedelic occasioned and non-drug experiences which altered individuals' beliefs about death. Individuals who reported an experience that altered their beliefs about death occasioned by either a psychedelic drug or a near-death or other non-ordinary experience completed an online survey. Circumstances of the experience, mystical and near-death subjective features, changes in attitudes about death, and other persisting effects were evaluated. The study sample (n = 3192) included five groups: non-drug near-death or other non-ordinary experiences (n = 933), and drug experiences occasioned by lysergic acid diethylamide (LSD) (n = 904), psilocybin (n = 766), ayahuasca (n = 282), or N,N-dimethyltryptamine (DMT) (n = 307). Analyses of differences in experiences were adjusted statistically for demographic differences between groups. Compared to the psychedelic groups, the non-drug group was more likely to report being unconscious, clinically dead, and that their life was in imminent danger. The groups were remarkably similar in the reported changes in death attitudes attributed to the experience, including a reduced fear of death and high ratings of positive persisting effects and personal meaning, spiritual significance, and psychological insight. Although both psychedelic and non-drug participants showed robust increases on standardized measures of mystical and near-death experiences, these measures were significantly greater in the psychedelic participants. Non-drug participants were more likely to rate their experiences as the single most meaningful of their lives. Comparing across psychedelic substances, ayahuasca and DMT groups tended report stronger and more positive enduring consequences of the experience than the psilocybin and LSD groups, which were largely indistinguishable. These data provide a detailed characterization and comparison of psychedelic occasioned and non-drug experiences that changed attitudes about death and suggest the importance of future prospective psychedelic administration studies.

keywords:
Humans, Banisteriopsis, N,N-Dimethyltryptamine, Lysergic Acid Diethylamide, Hallucinogens, Phobic Disorders, Psilocybin

raw_json:
{"europe_pmc_id":"36001643","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Yao S, Wei C, Lin H, Zhang P, Liu Y, Deng Y, Huang Q, Xie B.
publication_date: 2022-08-17
doi: 10.3390/jof8080870
pubmed_id: 36012858
source_url: https://doi.org/10.3390/jof8080870
substance_tags: psilocybin
topic_tags: Depression,Pharmacology,Mechanism of Action,Transcriptomics
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Cystathionine Gamma-Lyase Regulate Psilocybin Biosynthesis in Gymnopilus dilepis Mushroom via Amino Acid Metabolism Pathways.

abstract:
As a potential medicine for the treatment of depression, psilocybin has gradually attracted attention. To elucidate the molecular mechanism regulating psilocybin synthesis in Gymnopilus dilepis, ultra-performance liquid chromatography (UPLC) was used to detect the changes in psilocybin content after S-adenosyl-l-homocysteine (SAH) treatment and the changes of psilocybin content in different parts (stipe and pileus), and RNA-Seq was used to explore the mechanism of psilocybin content changes. In this study, the psilocybin content in G. dilepis mycelia treated with SAH was significantly lower than that in the control group, and the content of psilocybin in the stipe was significantly higher than that in the pileus. Transcriptome analysis revealed that differential expression genes (DEGs) were associated with cysteine and methionine metabolism. In particular, the transcription levels of genes encoding Cystathionine gamma-lyase (CTH) in different treatments and different parts were positively correlated with psilocybin content. In addition, we found that the exogenous addition of CTH activity inhibitor (DL-propargylglycine, PAG) could reduce the content of psilocybin and L-serine, and the content of psilocybin and L-serine returned to normal levels after L-cysteine supplementation, suggesting that psilocybin synthesis may be positively correlated with L-cysteine or CTH, and L-cysteine regulates the synthesis of psilocybin by affecting L-serine and 4-hydroxy-L-tryptophan. In conclusion, this study revealed a new molecular mechanism that affects psilocybin biosynthesis, which can provide a theoretical basis for improving psilocybin synthesis and the possibility for the development of biomedicine.

raw_json:
{"europe_pmc_id":"36012858","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Gumpper RH, Fay JF, Roth BL.
publication_date: 2022-07-31
doi: 10.1016/j.celrep.2022.111211
pubmed_id: 35977511
source_url: https://doi.org/10.1016/j.celrep.2022.111211
keywords: Receptors, Serotonin, Protein Isoforms, RNA, Messenger, Signal Transduction, RNA Editing
substance_tags: psilocin
topic_tags: Mechanism of Action,Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Molecular insights into the regulation of constitutive activity by RNA editing of 5HT2C serotonin receptors.

abstract:
RNA editing is a process by which post-transcriptional changes of mRNA nucleotides alter protein function through modification of the amino acid content. The 5HT2C serotonin receptor, which undergoes 32 distinct RNA-editing events leading to 24 protein isoforms, is a notable example of this process. These 5HT2C isoforms display differences in constitutive activity, agonist/inverse agonist potencies, and efficacies. To elucidate the molecular mechanisms responsible for these effects of RNA editing, we present four active-state 5HT2C-transducer-coupled structures of three representative isoforms (INI, VGV, and VSV) with the selective drug lorcaserin (Belviq) and the classic psychedelic psilocin. We also provide a comprehensive analysis of agonist activation and constitutive activity across all 24 protein isoforms. Collectively, these findings reveal a unique hydrogen-bonding network located on intracellular loop 2 that is subject to RNA editing, which differentially affects GPCR constitutive and agonist signaling activities.

raw_json:
{"europe_pmc_id":"35977511","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Review of potential psychedelic treatments for PTSD.
authors: Henner RL, Keshavan MS, Hill KP.
publication_date: 2022-05-29
doi: 10.1016/j.jns.2022.120302
pubmed_id: 35700643
source_url: https://doi.org/10.1016/j.jns.2022.120302
substance_tags: psilocybin
topic_tags: PTSD,Mechanism of Action,Clinical Trial,Review Article,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
abstract:
Post-traumatic stress disorder (PTSD) is a debilitating mental illness with limited treatment options and a high treatment dropout rate. Psychedelics, often in combination with psychotherapy, are now under investigation as a potential treatment option for a variety of psychiatric conditions including PTSD. This paper reviews the proposed mechanism of action for 3,4-Methylenedioxymethamphetamine (MDMA) and classical psychedelics such as psilocybin in treating PTSD, along with available clinical evidence, safety and side effects. MDMA-assisted psychotherapy is in FDA phase III clinical trials for PTSD and is purported to work by way of increased empathy and decreased amygdala activation during the therapeutic encounter and trauma processing. Classical psychedelics may create change by a subjective transformative experience along with an observable process of brain network alterations, though these substances have not been clinically studied in the context PTSD. In recent human-subject studies MDMA-assisted therapy resulted in significant improvement in PTSD symptoms with a good safety and side effect profile. There is not yet direct clinical evidence for classical psychedelics in treating PTSD, but the evidence supports such a trial. The studies to date have been relatively small, and participants are wellscreened for potential co-morbidities which could increase the risks of psychedelic treatment. Nonetheless, the data is promising for psychedelic-assisted treatment to become a much-needed treatment option for PTSD.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Combined Modality Therapy, Stress Disorders, Post-Traumatic, Psychotherapy

raw_json:
{"europe_pmc_id":"35700643","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Ortiz CE, Dourron HM, Sweat NW, Garcia-Romeu A, MacCarthy S, Anderson BT, Hendricks PS.
publication_date: 2022-05-12
doi: 10.1016/j.neuropharm.2022.109127
pubmed_id: 35577136
source_url: https://doi.org/10.1016/j.neuropharm.2022.109127
keywords: Humans, Hallucinogens, Mental Disorders, Psychotherapy, Vulnerable Populations, Psilocybin
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Special considerations for evaluating psilocybin-facilitated psychotherapy in vulnerable populations.

abstract:
Psilocybin-facilitated psychotherapy shows potential transdiagnostic efficacy for a range of mental health conditions. Though vulnerable populations bear disproportionate mental health burden, they have been largely neglected in the clinical psilocybin literature. However, if the field is to best respond to the diverse needs of individuals from vulnerable populations, care must be taken to ensure these individuals are represented in the empirical research. This report calls attention to this concern by detailing the challenges and opportunities associated with evaluating psilocybin-facilitated psychotherapy in vulnerable populations. First, we show how working with vulnerable populations must be considered in the context of an often-problematic past and differential exposure to and experience with classic psychedelics. We then provide actionable recommendations for future research testing psilocybin-facilitated psychotherapy in vulnerable populations, including an emphasis on recruitment strategies, the appropriate communication and assessment of subjective effects, building therapeutic alliance, multicultural competence, and flexible study designs. On these premises we call for future work in this area, underscoring that there is vast room for improvement and expansion in this rapidly advancing field of study.

raw_json:
{"europe_pmc_id":"35577136","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Acute and long-term effects of psilocybin on energy balance and feeding behavior in mice.
authors: Fadahunsi N, Lund J, Breum AW, Mathiesen CV, Larsen IB, Knudsen GM, Klein AB, Clemmensen C.
publication_date: 2022-08-10
doi: 10.1038/s41398-022-02103-9
pubmed_id: 35953488
source_url: https://doi.org/10.1038/s41398-022-02103-9
substance_tags: psilocybin
topic_tags: Addiction,Neuroplasticity,Pharmacology,Consciousness,Microdosing,Animal Study,Transcriptomics
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
Psilocybin and other serotonergic psychedelics have re-emerged as therapeutics for neuropsychiatric disorders, including addiction. Psilocybin induces long-lasting effects on behavior, likely due to its profound ability to alter consciousness and augment neural connectivity and plasticity. Impaired synaptic plasticity in obesity contributes to 'addictive-like' behaviors, including heightened motivation for palatable food, and excessive food seeking and consumption. Here, we evaluate the effects of psilocybin on feeding behavior, energy metabolism, and as a weight-lowering agent in mice. We demonstrate that a single dose of psilocybin substantially alters the prefrontal cortex transcriptome but has no acute or long-lasting effects on food intake or body weight in diet-induced obese mice or in genetic mouse models of obesity. Similarly, sub-chronic microdosing of psilocybin has no metabolic effects in obese mice and psilocybin does not augment glucagon-like peptide-1 (GLP-1) induced weight loss or enhance diet-induced weight loss. A single high dose of psilocybin reduces sucrose preference but fails to counter binge-like eating behavior. Although these preclinical data discourage clinical investigation, there may be nuances in the mode of action of psychedelic drugs that are difficult to capture in rodent models, and thus require human evaluation to uncover.

keywords:
Animals, Humans, Mice, Obesity, Weight Loss, Hallucinogens, Feeding Behavior, Energy Metabolism, Psilocybin

raw_json:
{"europe_pmc_id":"35953488","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2021-12-31
doi: 10.1177/24705470221115342
pubmed_id: 35936944
source_url: https://doi.org/10.1177/24705470221115342
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Mechanism of Action,Aging,Systematic Review,Review Article
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Neuroimaging Correlates of Treatment Response with Psychedelics in Major Depressive Disorder: A Systematic Review.

authors:
Kuburi S, Di Passa AM, Tassone VK, Mahmood R, Lalovic A, Ladha KS, Dunlop K, Rizvi S, Demchenko I, Bhat V.

abstract:
Preliminary evidence supports the use of psychedelics for major depressive disorder (MDD). However, less attention has been given to the neural mechanisms behind their effects. We conducted a systematic review examining the neuroimaging correlates of antidepressant response following psychedelic interventions for MDD. Through MEDLINE, Embase, and APA PsycINFO, 187 records were identified and 42 articles were screened. Six published studies and one conference abstract were included. Five ongoing trials were included from subjective outcomesTrials.gov. Our search covered several psychedelics, though included studies were specific to psilocybin, ayahuasca, and lysergic acid diethylamide. Three psilocybin studies noted amygdala activity and functional connectivity (FC) alterations that correlated with treatment response. Two psilocybin studies reported that FC changes in the medial and ventromedial prefrontal cortices correlated with treatment response. Two trials from a single study reported global decreases in brain network modularity which correlated with antidepressant response. One ayahuasca study reported increased activity in the limbic regions following treatment. Preliminary evidence suggests that the default mode and limbic networks may be a target for future research on the neural mechanisms of psychedelics. More data is required to corroborate these initial findings as the evidence summarized in this review is based on four datasets.

raw_json:
{"europe_pmc_id":"35936944","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Microdosing with psilocybin mushrooms: a double-blind placebo-controlled study.
publication_date: 2022-08-01
doi: 10.1038/s41398-022-02039-0
pubmed_id: 35918311
source_url: https://doi.org/10.1038/s41398-022-02039-0
keywords: Humans, Agaricales, Hallucinogens, Double-Blind Method, Motivation, Psilocybin
substance_tags: psilocybin
topic_tags: Brain Imaging,Microdosing,Wellbeing,Creativity
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
authors:
Cavanna F, Muller S, de la Fuente LA, Zamberlan F, Palmucci M, Janeckova L, Kuchar M, Pallavicini C, Tagliazucchi E.

abstract:
The use of low sub-perceptual doses of psychedelics ("microdosing") has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies severely limits our knowledge of microdosing and its effects. Moreover, research conducted in standard laboratory settings could fail to capture the motivation of individuals engaged or planning to engage in microdosing protocols, thus underestimating the likelihood of positive effects on creativity and cognitive function. We recruited 34 individuals starting to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled experimental design, we investigated the acute and short-term effects of 0.5 g of dried mushrooms on subjective experience, behavior, creativity (divergent and convergent thinking), perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, but only for participants who correctly identified their experimental condition. These changes were accompanied by reduced EEG power in the theta band, together with preserved levels of Lempel-Ziv broadband signal complexity. For all other measurements there was no effect of microdosing except for few small changes towards cognitive impairment. According to our findings, low doses of psilocybin mushrooms can result in noticeable subjective effects and altered EEG rhythms, but without evidence to support enhanced well-being, creativity and cognitive function. We conclude that expectation underlies at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.

raw_json:
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authors: Makin S.
publication_date: 2022-07-31
doi: 10.1038/scientificamerican0822-12
pubmed_id: 39016786
source_url: https://doi.org/10.1038/scientificamerican0822-12
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Mushrooms' Legal Trip: As psilocybin research ramps up, the drug's status under the law is shifting.

raw_json:
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title: Antidepressant effects of a psychedelic experience in a large prospective naturalistic sample.
journal: Journal of psychopharmacology (Oxford, England)
publication_date: 2022-07-31
doi: 10.1177/02698811221101061
pubmed_id: 35924888
source_url: https://pubmed.ncbi.nlm.nih.gov/35924888/
keywords: Psychedelics, anxiety, depression, mystical experience, psilocybin
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Emotional Processing,Mystical Experience,Observational Study
study_type: Observational Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"35924888"}
authors:
Nygart VA, Pommerencke LM, Haijen E, Kettner H, Kaelen M, Mortensen EL, Nutt DJ, Carhart-Harris RL, Erritzoe D

abstract:
Over the last two decades, a number of studies have highlighted the potential of psychedelic therapy. However, questions remain to what extend these results translate to naturalistic samples, and how contextual factors and the acute psychedelic experience relate to improvements in affective symptoms following psychedelic experiences outside labs/clinics. The present study sought to address this knowledge gap.
Here, we aimed to investigate changes in anxiety and depression scores before versus after psychedelic experiences in naturalistic contexts, and how various pharmacological, extrapharmacological and experience factors related to outcomes.
Individuals who planned to undergo a psychedelic experience were enrolled in this online survey study. Depressive symptoms were assessed at baseline and 2 and 4 weeks post-psychedelic experience, with self-rated Quick Inventory of Depressive Symptomatology (QIDS-SR-16) as the primary outcome. To facilitate clinical translation, only participants with depressive symptoms at baseline were included. Sample sizes for the four time points were = 302, = 182, = 155 and = 109, respectively.
Relative to baseline, reductions in depressive symptoms were observed at 2 and 4 weeks. A medicinal motive, previous psychedelic use, drug dose and the type of acute psychedelic experience (i.e. specifically, having an emotional breakthrough) were all significantly associated with changes in self-rated QIDS-SR-16.
These results lend support to therapeutic potential of psychedelics and highlight the influence of pharmacological and non-pharmacological factors in determining response. Mindful of a potential sample and attrition bias, further controlled and observational longitudinal studies are needed to test the replicability of these findings.


title: From Mushrooms to Myolysis: A Case of Rhabdo in Psilocybin-Induced Mood and Psychotic Disorder.
authors: Suleiman M, Basu A, Belal S, Jacob T.
publication_date: 2022-07-31
doi: 10.1097/nmd.0000000000001489
pubmed_id: 35900779
source_url: https://doi.org/10.1097/nmd.0000000000001489
keywords: Humans, Agaricales, Rhabdomyolysis, Substance-Related Disorders, Psychotic Disorders, Psilocybin
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Microdosing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
AbstractThe involvement of certain recreational drugs, namely, hallucinogens, in the development of hyperactive syndromes is well known, but not well studied. In this report, we expand on this relationship by documenting the development of substance-induced psychosis in a young patient who used a large amount of psilocybin and developed symptoms of a first psychotic and manic episode, complicated by violent behavior and rhabdomyolysis. We further evaluate the association between psilocybin use and rhabdomyolysis and explore this understudied phenomenon and differentiate it from the diagnoses of other hyperactive syndromes seen in psychiatry. This case exemplifies the need for increased vigilance in psilocybin microdosing therapy and for physicians to be mindful of how each patient responds to its use to prevent life-threatening hyperactive syndromes in its wake.

raw_json:
{"europe_pmc_id":"35900779","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Self-Reported Efficacy of Treatments in Cluster Headache: a Systematic Review of Survey Studies.
authors: Rusanen SS, De S, Schindler EAD, Artto VA, Storvik M.
publication_date: 2022-06-26
doi: 10.1007/s11916-022-01063-5
pubmed_id: 35759175
source_url: https://doi.org/10.1007/s11916-022-01063-5
substance_tags: psilocybin
topic_tags: Headache / Migraine,Systematic Review,Review Article,Observational Study
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Purpose of reviewThe use and efficacy of various substances in the treatment of CH have been studied in several retrospective surveys. The aim of the study is to systematically review published survey studies to evaluate the reported efficacies of both established and unconventional substances in abortive and prophylactic treatment of both episodic and chronic CH, specifically assessing the consistency of the results.Recent findingsNo systematic review have been conducted of these studies previously. A systematic literature search with a set of search terms was conducted on PubMed. Retrospective surveys that quantified the self-reported efficacy of two or more CH treatments, published in English during 2000-2020, were included. Several key characteristics and results of the studies were extracted. A total of 994 articles were identified of which 9 were found to be eligible based on the selection criteria. In total, 5419 respondents were included. Oxygen and subcutaneous triptan injections were most reported as effective abortive treatments, while psilocybin and lysergic acid diethylamide were most commonly reported as effective prophylactic treatments. The reported efficacy of most substances was consistent across different studies, and there were marked differences in the reported efficacies of different substances. The reported order of efficacy is generally in agreement with clinical studies. The findings suggest that retrospective surveys can be used to obtain supporting information on the effects of various substances used in the treatment of CH and to form hypotheses about novel treatment methods. The consistently reported efficacy of psilocybin and LSD in prophylactic treatment indicates need for clinical studies.

keywords:
Humans, Cluster Headache, Lysergic Acid Diethylamide, Retrospective Studies, Self Report, Surveys and Questionnaires, Psilocybin

raw_json:
{"europe_pmc_id":"35759175","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Felsch CL, Kuypers KPC.
publication_date: 2022-06-05
doi: 10.1016/j.neubiorev.2022.104724
pubmed_id: 35679988
source_url: https://doi.org/10.1016/j.neubiorev.2022.104724
keywords: Humans, Meditation, Fear, Mindfulness, Psilocybin, Phobia, Social
substance_tags: psilocybin
topic_tags: Anxiety,Mechanism of Action,Systematic Review,Review Article
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Don't be afraid, try to meditate- potential effects on neural activity and connectivity of psilocybin-assisted mindfulness-based intervention for social anxiety disorder: A systematic review.

abstract:
BackgroundCurrent first-line treatment for social anxiety disorder (SAD), one of the most prevalent anxiety disorders, is limited in its efficacy. Hence, novel treatment approaches are urgently needed. The current review suggests a combination of meditation-based interventions and the administration of a psychedelic as a future alternative treatment approach. While both separate treatments show promise in the treatment of (other) clinical conditions, their combination has not yet been investigated in the treatment of psychopathologies.AimWith a systematic literature review, we aim to identify the potential mechanisms by which combined psilocybin and mindfulness treatment could adjust anomalous neural activity underlying SAD and exert therapeutic effects.ResultsThirty experimental studies investigating the neural effects of meditation or psilocybin treatment in healthy and patient samples were included. Findings suggest that psilocybin-assisted meditation interventions might change cognitive processes like biased attention to threat linked to SAD by modulating connectivity of the salience network, balancing the activity and connectivity of cortical-midline structures, and increasing frontoparietal control over amygdala reactivity.ConclusionsFuture studies should investigate whether psilocybin-assisted mindfulness-based intervention can provide therapeutic benefits to SAD patients who are do not remit following conventional therapy.

raw_json:
{"europe_pmc_id":"35679988","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Phosphate moiety in FDA-approved pharmaceutical salts and prodrugs.
authors: Fulmali A, Bharate SS.
publication_date: 2022-06-01
doi: 10.1002/ddr.21953
pubmed_id: 35656613
source_url: https://doi.org/10.1002/ddr.21953
keywords: Phosphates, Salts, Pyrrolidinones, Indoles, Leucine, Prodrugs, Solubility
substance_tags: psilocybin
topic_tags: Pharmacology,Review Article,Toxicity
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
The salification and prodrug approaches modulate the physicochemical properties and absorption, distribution, metabolism, excretion, and toxicity parameters of drugs and lead candidates. The "phosphate" is one of the key counterions/promoiety used in the salt formation and prodrug synthesis. Salification with phosphoric acid enhances the aqueous solubility and thereby facilitates the administration of a drug by the parenteral route. Phosphate moiety in prodrug synthesis mainly improves permeability by lipophilic substitution. Histamine phosphate is the first phosphate salt, and hydrocortisone phosphate was the first prodrug approved by FDA in 1939 and 1952, respectively. The orange book enlists 12 phosphate salts and 17 phosphate prodrugs. Phosphate prodrugs, namely combretastatin A-4 diphosphate, combretastatin A-4 phosphate, lufotrelvir, TP-1287, pyridoxal phosphate, riboflavin phosphate, and psilocybin are clinical candidates. This review focuses on the FDA-approved phosphate salts and prodrugs from 1939 to 2021. The biopharmaceutical advantage of phosphate salts and prodrugs over the parent molecule is also deliberated.

raw_json:
{"europe_pmc_id":"35656613","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Postpartum depression: A role for psychedelics?
authors: Jairaj C, Rucker JJ.
publication_date: 2022-05-29
doi: 10.1177/02698811221093793
pubmed_id: 35638179
source_url: https://doi.org/10.1177/02698811221093793
substance_tags: psilocybin
topic_tags: Depression,Aging,Review Article,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
BackgroundPostpartum depression (PPD) is a major public health concern and has, at its core, a sense of maternal 'disconnection' - from the self, the infant, and the support system. While PPD bears similarities with MDD, there is increasing evidence for its distinct nature, especially with the unique aspect of the mother-infant relationship. Current treatment modalities for PPD, largely based on those used in major depressive disorder (MDD), have low remission rates with emerging evidence for treatment resistance. It is, therefore, necessary to explore alternative avenues of treatment for PPD.ObjectiveIn this narrative review, we outline the potential therapeutic rationale for serotonergic psychedelics in the treatment of PPD, and highlight safety and pragmatic considerations for the use of psychedelics in the postpartum period.MethodsWe examined the available evidence for the treatment of PPD and the evidence for psychedelics in the treatment of MDD. We explored safety considerations in the use of psychedelics in the postpartum period.ResultsThere is increasing evidence for safety, and encouraging signals for efficacy, of psilocybin in the treatment of MDD. Psilocybin has been shown to catalyse a sense of 'reconnection' in participants with MDD. This effect in PPD, by fostering a sense of 'reconnection' for the mother, may allow for improved mood and maternal sensitivity towards the infant, which can positively impact maternal role gratification and the mother-infant relationship.ConclusionPsychedelic assisted therapy in PPD may have a positive effect on the mother-infant dyad and warrants further examination.

keywords:
Humans, Depression, Postpartum, Hallucinogens, Mothers, Female, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"35638179","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Polito V, Liknaitzky P
journal: Neuroscience and biobehavioral reviews
publication_date: 2022-07-31
doi: 10.1016/j.neubiorev.2022.104706
pubmed_id: 35609684
source_url: https://pubmed.ncbi.nlm.nih.gov/35609684/
keywords: Hallucinogen, LSD, Low dose, Microdosing, Psilocybin, Psychedelics, Systematic review
substance_tags: psilocybin
study_type: Systematic Review
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:39
raw_json: {"pubmed_id":"35609684"}
title:
The emerging science of microdosing: A systematic review of research on low dose psychedelics (1955-2021) and recommendations for the field.

abstract:
The use of low doses of psychedelic substances (microdosing) is attracting increasing interest. This systematic review summarises all empirical microdosing research to date, including a set of infrequently cited studies that took place prior to prohibition. Specifically, we reviewed 44 studies published between 1955 and 2021, and summarised reported effects across six categories: mood and mental health; wellbeing and attitude; cognition and creativity; personality; changes in conscious state; and neurobiology and physiology. Studies showed a wide range in risk of bias, depending on design, age, and other study characteristics. Laboratory studies found changes in pain perception, time perception, conscious state, and neurophysiology. Self-report studies found changes in cognitive processing and mental health. We review data related to expectation and placebo effects, but argue that claims that microdosing effects are largely due to expectancy are premature and possibly wrong. In addition, we attempt to clarify definitional inconsistencies in the microdosing literature by providing suggested dose ranges across different substances. Finally, we provide specific design suggestions to facilitate more rigorous future research.

topic_tags:
Chronic Pain,Consciousness,Microdosing,Wellbeing,Personality Change,Creativity,Systematic Review,Review Article,Safety


title: Analytical profile, in vitro metabolism and behavioral properties of the lysergamide 1P-AL-LAD.
publication_date: 2022-05-28
doi: 10.1002/dta.3281
pubmed_id: 35524430
source_url: https://doi.org/10.1002/dta.3281
keywords: Animals, Humans, Mice, Lysergic Acid Diethylamide, Hallucinogens, Prodrugs, Chromatography, Liquid
substance_tags: psilocybin
topic_tags: Pharmacology,Receptor Pharmacology,Animal Study,In Vitro Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
authors:
Brandt SD, Kavanagh PV, Westphal F, Pulver B, Schwelm HM, Whitelock K, Stratford A, Auwärter V, Halberstadt AL.

abstract:
Lysergic acid diethylamide (LSD) is known to induce powerful psychoactive effects in humans, which cemented its status as an important tool for clinical research. A range of analogues and derivatives has been investigated over the years, including those classified as new psychoactive substances. This study presents the characterization of the novel lysergamide N,N-diethyl-1-propanoyl-6-(prop-2-en-1-yl)-9,10-didehydroergoline-8β-carboxamide (1P-AL-LAD) using various mass spectrometric, gas- and liquid chromatographic and spectroscopic methods. In vitro metabolism studies using pooled human liver microsomes (pHLM) confirmed that 1P-AL-LAD converted to AL-LAD as the most abundant metabolite consistent with the hypothesis that 1P-AL-LAD may act as a prodrug. Fourteen metabolites were detected in total; metabolic reactions included hydroxylation of the core lysergamide ring structure or the N6 -allyl group, formation of dihydrodiol metabolites, N-dealkylation, N1 -deacylation, dehydrogenation, and combinations thereof. The in vivo behavioral activity of 1P-AL-LAD was evaluated using the mouse head twitch response (HTR), a 5-HT2A -mediated head movement that serves as a behavioral proxy in rodents for human hallucinogenic effects. 1P-AL-LAD induced a dose-dependent increase in HTR counts with an inverted U-shaped dose-response function, similar to lysergic acid diethylamide (LSD), psilocybin, and other psychedelics. Following intraperitoneal injection, the median effective dose (ED50 ) for 1P-AL-LAD was 491 nmol/kg, making it almost three times less potent than AL-LAD (174.9 nmol/kg). Previous studies have shown that N1 -substitution disrupts the ability of lysergamides to activate the 5-HT2A receptor; based on the in vitro metabolism data, 1P-AL-LAD may induce the HTR because it acts as a prodrug and is metabolized to AL-LAD after administration to mice.

raw_json:
{"europe_pmc_id":"35524430","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Girn M, Roseman L, Bernhardt B, Smallwood J, Carhart-Harris R, Nathan Spreng R.
publication_date: 2022-04-24
doi: 10.1016/j.neuroimage.2022.119220
pubmed_id: 35483649
source_url: https://doi.org/10.1016/j.neuroimage.2022.119220
keywords: Brain, Humans, Lysergic Acid Diethylamide, Serotonin Agents, Hallucinogens, Psilocybin
substance_tags: psilocybin
topic_tags: Brain Imaging,Receptor Pharmacology,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex.

abstract:
Lysergic acid diethylamide (LSD) and psilocybin are serotonergic psychedelic compounds with potential in the treatment of mental health disorders. Past neuroimaging investigations have revealed that both compounds can elicit significant changes to whole-brain functional organization and dynamics. A recent proposal linked past findings into a unified model and hypothesized reduced whole-brain hierarchical organization as a key mechanism underlying the psychedelic state, but this has yet to be directly tested. We applied a non-linear dimensionality reduction technique previously used to map hierarchical connectivity gradients to assess cortical organization in the LSD and psilocybin state from two previously published pharmacological resting-state fMRI datasets (N = 15 and 9, respectively). Results supported our primary hypothesis: The principal gradient of cortical connectivity, describing a hierarchy from unimodal to transmodal cortex, was significantly flattened under both drugs relative to their respective placebo conditions. Between-condition contrasts revealed that this was driven by a reduction of functional differentiation at both hierarchical extremes - default and frontoparietal networks at the upper end, and somatomotor at the lower. Gradient-based connectivity mapping indicated that this was underpinned by a disruption of modular unimodal connectivity and increased unimodal-transmodal crosstalk. Results involving the second and third gradient, which, respectively represent axes of sensory and executive differentiation, also showed significant alterations across both drugs. These findings provide support for a recent mechanistic model of the psychedelic state relevant to therapeutic applications of psychedelics. More fundamentally, we provide the first evidence that macroscale connectivity gradients are sensitive to an acute pharmacological manipulation, supporting a role for psychedelics as scientific tools to perturb cortical functional organization.

raw_json:
{"europe_pmc_id":"35483649","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kopra EI, Ferris JA, Winstock AR, Young AH, Rucker JJ.
publication_date: 2022-04-06
doi: 10.1177/02698811221084063
pubmed_id: 35388724
source_url: https://doi.org/10.1177/02698811221084063
keywords: Humans, Agaricales, Hallucinogens, Psilocybe, Psilocybin
substance_tags: psilocybin
topic_tags: Anxiety,Spirituality,Observational Study,Safety
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Adverse experiences resulting in emergency medical treatment seeking following the use of magic mushrooms.

abstract:
BackgroundPsilocybin-containing mushrooms are used for recreational, spiritual, self-development and therapeutic purposes. However, physiologically relatively nontoxic, adverse reactions are occasionally reported.AimsThis study investigated the 12-month prevalence and nature of magic mushroom-related adverse reactions resulting in emergency medical treatment seeking in a global sample of people reporting magic mushroom use.MethodsWe use data from the 2017 Global Drug Survey - a large anonymous online survey on patterns of drug use conducted between November 2016 and January 2017.ResultsOut of 9233 past year magic mushroom users, 19 (0.2%) reported having sought emergency medical treatment, with a per-event risk estimate of 0.06%. Young age was the only predictor associated with higher risk of emergency medical presentations. The most common symptoms were psychological, namely anxiety/panic and paranoia/suspiciousness. Poor 'mindset', poor 'setting' and mixing substances were most reported reasons for incidents. All but one respondent returned back to normality within 24 h.ConclusionsThe results confirm psilocybin mushrooms are a relatively safe drug, with serious incidents rare and short lasting. Providing harm-reduction information likely plays a key role in preventing adverse effects. More research is needed to examine the detailed circumstances and predictors of adverse reactions including rarer physiological reactions.

raw_json:
{"europe_pmc_id":"35388724","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: Journal of palliative medicine
publication_date: 2022-07-31
doi: 10.1089/jpm.2022.0036
pubmed_id: 35285721
source_url: https://pubmed.ncbi.nlm.nih.gov/35285721/
substance_tags: psilocybin
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:39
raw_json: {"pubmed_id":"35285721"}
title:
Top Ten Tips Palliative Care Clinicians Should Know About Psychedelic-Assisted Therapy in the Context of Serious Illness.

authors:
Rosa WE, Sager Z, Miller M, Bernstein I, Doerner Rinaldi A, Addicott K, Ljuslin M, Adrian C, Back AL, Beachy J, Bossis AP, Breitbart WS, Cosimano MP, Fischer SM, Guss J, Knighton E, Phelps J, Richards BD, Richards WA, Tulsky JA, Williams MT, Beaussant Y

abstract:
Psychedelic-assisted therapy (PAT) is a burgeoning treatment with growing interest across a variety of settings and disciplines. Empirical evidence supports PAT as a novel therapeutic approach that provides safe and effective treatment for people suffering from a variety of diagnoses, including treatment-resistant depression, substance use disorder, and post-traumatic stress disorder. Within the palliative care (PC) field, one-time PAT dosing may lead to sustained reductions in anxiety, depression, and demoralization-symptoms that diminish the quality of life in both seriously ill patients and those at end of life. Despite a well-noted psychedelic renaissance in scholarship and a renewed public interest in the utilization of these medicines, serious illness-specific content to guide PAT applications in hospice and PC clinical settings has been limited. This article offers 10 evidence-informed tips for PC clinicians synthesized through consultation with interdisciplinary and international leading experts in the field with aims to: (1) familiarize PC clinicians and teams with PAT; (2) identify the unique challenges pertaining to this intervention given the current legalities and logistical barriers; (3) discuss therapeutic competencies and considerations for current and future PAT use in PC; and (4) highlight critical approaches to optimize the safety and potential benefits of PAT among patients with serious illness and their caregivers.

keywords:
LSD, MDMA, anxiety treatment, demoralization, depression, palliative care, psilocybin, psychedelic-assisted therapy, psychedelics, serious illness

topic_tags:
Depression,Anxiety,PTSD,Addiction,End-of-Life Distress,Treatment-Resistant Depression,Healthcare Workers,Safety


authors: Rootman JM, Kiraga M, Kryskow P, Harvey K, Stamets P, Santos-Brault E, Kuypers KPC, Walsh Z.
publication_date: 2022-07-27
doi: 10.1038/s41598-022-17428-0
pubmed_id: 35902723
source_url: https://doi.org/10.1038/s41598-022-17428-0
substance_tags: psilocybin
topic_tags: Microdosing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
title:
Author Correction: Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls.

raw_json:
{"europe_pmc_id":"35902723","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Golden CT, Chadderton P.
publication_date: 2022-07-25
doi: 10.1038/s41598-022-16325-w
pubmed_id: 35882885
source_url: https://doi.org/10.1038/s41598-022-16325-w
keywords: Gyrus Cinguli, Neurons, Animals, Rodentia, Mice, Wakefulness, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,PTSD,Mechanism of Action,Default Mode Network,Animal Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Psilocybin reduces low frequency oscillatory power and neuronal phase-locking in the anterior cingulate cortex of awake rodents.

abstract:
Psilocybin is a hallucinogenic compound that is showing promise in the ability to treat neurological conditions such as depression and post-traumatic stress disorder. There have been several investigations into the neural correlates of psilocybin administration using non-invasive methods, however, there has yet to be an invasive study of the mechanism of action in awake rodents. Using multi-unit extracellular recordings, we recorded local field potential and spiking activity from populations of neurons in the anterior cingulate cortex of awake mice during the administration of psilocybin (2 mg/kg). The power of low frequency bands in the local field potential was found to significantly decrease in response to psilocybin administration, whilst gamma band activity trended towards an increase. The population firing rate was found to increase overall, with just under half of individual neurons showing a significant increase. Psilocybin significantly decreased the level of phase modulation of cells with each neural frequency band except high-gamma oscillations, consistent with a desynchronization of cortical populations. Furthermore, bursting behavior was altered in a subset of cells, with both positive and negative changes in the rate of bursting. Neurons that increased their burst firing following psilocybin administration were highly likely to transition from a phase-modulated to a phase unmodulated state. Taken together, psilocybin reduces low frequency oscillatory power, increases overall firing rates and desynchronizes local neural activity. These findings are consistent with dissolution of the default mode network under psilocybin, and may be indicative of disruption of top-down processing in the acute psychedelic state.

raw_json:
{"europe_pmc_id":"35882885","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Editorial: Psychedelic sociality: Pharmacological and extrapharmacological perspectives.
authors: Roseman L, Preller KH, Fotiou E, Winkelman MJ
journal: Frontiers in pharmacology
publication_date: 2021-12-31
doi: 10.3389/fphar.2022.979764
pubmed_id: 35935854
source_url: https://pubmed.ncbi.nlm.nih.gov/35935854/
substance_tags: psilocybin
topic_tags: Pharmacology,Receptor Pharmacology
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:39
raw_json: {"pubmed_id":"35935854"}
keywords:
5-HT2A receptor, LSD, biopsychosocial, culture, interdisciplinary research, psilocybin, set and setting, social pharmacology


authors: Glatfelter GC, Pham DNK, Walther D, Golen JA, Chadeayne AR, Baumann MH, Manke DR.
publication_date: 2022-07-04
doi: 10.1021/acsomega.2c03476
pubmed_id: 35874244
source_url: https://doi.org/10.1021/acsomega.2c03476
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Animal Study,In Vitro Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
title:
Synthesis, Structural Characterization, and Pharmacological Activity of Novel Quaternary Salts of 4-Substituted Tryptamines.

abstract:
Aeruginascin (4-phosphoryloxy-N,N,N-trimethyltryptammonium) is an analogue of psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) that has been identified in several species of psilocybin-containing mushrooms. Our team previously reported the synthesis, structural characterization, and biological activity of the putative metabolite of aeruginascin (4-hydroxy-N,N,N-trimethyltryptammonium; 4-HO-TMT) and its potential prodrug (4-acetoxy-N,N,N-trimethyltryptammonium; 4-AcO-TMT). Here, we report the synthesis, structural characterization, and pharmacological activity of several quaternary tryptammonium analogues of 4-HO-TMT and 4-AcO-TMT, namely, 4-hydroxy-N,N-dimethyl-N-ethyltryptammonium (4-HO-DMET), 4-hydroxy-N,N-dimethyl-N-n-propyltryptammonium (4-HO-DMPT), and 4-hydroxy-N,N-dimethyl-N-isopropyltryptammonium (4-HO-DMiPT), as well as their hypothesized prodrugs 4-acetoxy-N,N-dimethyl-N-ethyltryptammonium (4-AcO-DMET), 4-acetoxy-N,N-dimethyl-N-n-propyltryptammonium (4-AcO-DMPT), and 4-acetoxy-N,N-dimethyl-N-isopropyltryptammonium (4-AcO-DMiPT). Compounds were synthesized using established methods, and structures were characterized by single-crystal X-ray diffraction. Test compounds were screened for in vitro pharmacological activity at a variety of receptors and transporters to determine potential targets of action. None of the compounds exhibited measurable affinity for the serotonin 2A receptor (5-HT2A), but several analogues had low micromolar affinity (K i) for the serotonin 1D receptor (5-HT1D) and serotonin 2B receptor (5-HT2B), where they appeared to be weak partial agonists with low micromolar potencies. Importantly, 4-HO-DMET, 4-HO-DMPT, and 4-HO-DMiPT displayed sub-micromolar affinity for the serotonin transporter (SERT; 370-890 nM). The same 4-hydroxy analogues had low to sub-micromolar potencies (IC50) for inhibition of 5-HT uptake at SERT in transfected cells (3.3-12.3 μM) and rat brain tissue (0.31-3.5 μM). Overall, our results show that quaternary tryptammonium analogues do not target 5-HT2A sites, suggesting the compounds lack psychedelic-like subjective effects. However, certain 4-hydroxy quaternary tryptammonium analogues may provide novel templates for exploring structure-activity relationships for selective actions at SERT.

raw_json:
{"europe_pmc_id":"35874244","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Genetic Survey of Psilocybe Natural Products.
publication_date: 2022-06-08
doi: 10.1002/cbic.202200249
pubmed_id: 35583969
source_url: https://doi.org/10.1002/cbic.202200249
keywords: Hallucinogens, Biological Products, Psilocybe
substance_tags: psilocybin,psilocin
topic_tags: Observational Study,Genomics,Metabolomics
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
authors:
Dörner S, Rogge K, Fricke J, Schäfer T, Wurlitzer JM, Gressler M, Pham DNK, Manke DR, Chadeayne AR, Hoffmeister D.

abstract:
Psilocybe magic mushrooms are best known for their main natural product, psilocybin, and its dephosphorylated congener, the psychedelic metabolite psilocin. Beyond tryptamines, the secondary metabolome of these fungi is poorly understood. The genomes of five species (P. azurescens, P. cubensis, P. cyanescens, P. mexicana, and P. serbica) were browsed to understand more profoundly common and species-specific metabolic capacities. The genomic analyses revealed a much greater and yet unexplored metabolic diversity than evident from parallel chemical analyses. P. cyanescens and P. mexicana were identified as aeruginascin producers. Lumichrome and verpacamide A were also detected as Psilocybe metabolites. The observations concerning the potential secondary metabolome of this fungal genus support pharmacological and toxicological efforts to find a rational basis for yet elusive phenomena, such as paralytic effects, attributed to consumption of some magic mushrooms.

raw_json:
{"europe_pmc_id":"35583969","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A Single Method for 127 Recommended and Additional DUID Drugs in Blood and Urine by LC-MS-MS.
authors: Farley M, Tran H, Towler S, Gevorkyan J, Pearring S, Rodda LN.
publication_date: 2022-06-30
doi: 10.1093/jat/bkab075
pubmed_id: 34159389
source_url: https://doi.org/10.1093/jat/bkab075
substance_tags: psilocin
topic_tags: Addiction,Safety,Toxicity
study_type: Qualitative Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Driving under the influence of drug (DUID) cases continue to challenge forensic toxicologists as both the volume and complexity of casework increases. Comprehensive DUID testing should also meet the drafted Academy Standards Board (ASB)/ American National Standard Institute (ANSI) standard and the National Safety Council's Alcohol, Drugs and Impairment Division (NSC-ADID) recommendations. A simple method using protein precipitation followed by filtration extraction with an 8 minute run time by liquid chromatography-tandem mass spectrometry (LC-MS-MS) was developed, and a comprehensive ASB/ANSI validation was performed. Target drugs and metabolites were quantitatively assessed in blood and qualitatively assessed in urine. Included were 127 target analytes including cannabinoids (12), amphetamines (11), cocaine and metabolites (6), benzodiazepines (36), Z-drugs (5), opioids (27), anticonvulsants (3), first-generation antihistamines (6), muscle relaxants (2), dissociatives and hallucinogens (6), barbiturates (10), and miscellaneous substances (3). Limits of detection are appropriate for DUID and other forensic casework such as drug-facilitated crime (DFC) and postmortem investigations. To demonstrate applicability, 78 proficiency test blood and urine samples and 1,645 blood and urine samples from authentic cases samples demonstrated effective detection of target analytes in forensic casework. By increasing the analytical scope of multiple drug classes via a single method, this technique detects drugs that may have previously gone undetected, such as flualprazolam, etizolam, mitragynine, gamma-hydroxybutyric acid and psilocin and improves laboratory efficiency by reducing the number of tests required. The described method is, to the authors' best knowledge, the only published single procedure to meet all drugs listed in the drafted ASB/ANSI standard and recommended Tier 1 and traditional drugs from Tier 2 for DUID screening, while also achieving many drug scope and sensitivity recommendations for DFC and postmortem testing.

keywords:
Amphetamines, Cannabinoids, Chromatography, Liquid, Substance Abuse Detection, Tandem Mass Spectrometry, Forensic Toxicology

raw_json:
{"europe_pmc_id":"34159389","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics, Mystical Experience, and Therapeutic Efficacy: A Systematic Review.
authors: Ko K, Knight G, Rucker JJ, Cleare AJ.
publication_date: 2022-07-11
doi: 10.3389/fpsyt.2022.917199
pubmed_id: 35923458
source_url: https://doi.org/10.3389/fpsyt.2022.917199
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Mystical Experience,Systematic Review,Review Article,Cancer Patients
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
The mystical experience is a potential psychological mechanism to influence outcome in psychedelic therapy. It includes features such as oceanic boundlessness, ego dissolution, and universal interconnectedness, which have been closely linked to both symptom reduction and improved quality of life. In this review, 12 studies of psychedelic therapy utilizing psilocybin, ayahuasca, or ketamine were analyzed for association between mystical experience and symptom reduction, in areas as diverse as cancer-related distress, substance use disorder, and depressive disorders to include treatment-resistant. Ten of the twelve established a significant association of correlation, mediation, and/or prediction. A majority of the studies are limited, however, by their small sample size and lack of diversity (gender, ethnic, racial, educational, and socioeconomic), common in this newly re-emerging field. Further, 6 out of 12 studies were open-label in design and therefore susceptible to bias. Future studies of this nature should consider a larger sample size with greater diversity and thus representation by use of randomized design. More in-depth exploration into the nature of mystical experience is needed, including predictors of intensity, in order to maximize its positive effects on treatment outcome benefits and minimize concomitant anxiety. Systematic Review Registration: PROSPERO, identifier CRD42021261752.

raw_json:
{"europe_pmc_id":"35923458","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kiraga MK, Kuypers KPC, Uthaug MV, Ramaekers JG, Mason NL.
publication_date: 2022-07-06
doi: 10.3389/fpsyt.2022.883869
pubmed_id: 35873251
source_url: https://doi.org/10.3389/fpsyt.2022.883869
substance_tags: psilocybin,psilocin
topic_tags: Anxiety,Mechanism of Action,Personality Change,Observational Study,Healthy Volunteers
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Decreases in State and Trait Anxiety Post-psilocybin: A Naturalistic, Observational Study Among Retreat Attendees.

abstract:
Anxiety disorders are the most common type of psychiatric disorders among Western countries. Evidence-based treatment modalities including pharmacological and cognitive-behavioral therapy result in deficient treatment responses. Historical and recent research suggests psychedelic drugs may be efficacious in alleviating anxiety-related symptoms among healthy and clinical populations. The main aim of the present study was investigation of the effects of psilocybin-containing truffles, when taken in a supportive group setting, on ratings of state and trait anxiety across self-reported healthy volunteers. Attendees of psilocybin ceremonies were asked to complete a test battery at three separate occasions: before the ceremony (baseline), the morning after, and 1 week after the ceremony. The test battery included questionnaires assessing state and trait anxiety (State-Trait Anxiety Inventory), mindfulness capacities (Five Facet Mindfulness Questionnaire), and personality (Big Five Inventory). Additionally, the psychedelic experience was quantified with the Persisting Effects Questionnaire and the Ego Dissolution Inventory. The total amount of psilocybin-containing truffles consumed by each participant was recorded, and a sample of the truffles was analyzed to determine psilocin concentrations. Fifty-two attendees (males = 25; females = 25; others = 2) completed parts of the baseline assessment, 46 (males = 21; females = 24; others = 1) completed assessments the morning after the ceremony, and 23 (males = 10; females = 13) completed assessments at the 1-week follow-up. Average psilocin consumption across individuals was 27.1 mg. The morning after the ceremony, we observed medium reductions in anxiety measures (both state and trait) compared to baseline ( d ¯ = 6.4; p < 0.001 and d ¯ = 6; p = 0.014, respectively), which persisted over a 1-week period post-ceremony ( d ¯ = 6.7; p = 0.001 and d ¯ = 8.6; p = 0.004, respectively). At 1 week post-ceremony, the non-judging facet of the mindfulness scale was increased ( d ¯ = 1.5; p = 0.03), while the personality trait neuroticism decreased ( d ¯ = 5.2; p = 0.005), when compared to baseline. Additionally, we found ratings of ego dissolution (mean: 59.7, SD: 28.3) and changes in neuroticism to be the strongest predictors of reductions in state and trait anxiety, respectively. In sum, results suggest rapid and persisting (up to 1 week) anxiolytic effects in individuals with sub-clinical anxiety symptoms, which are related to the acute experience of ego dissolution, as well as lasting changes in trait neuroticism. Results also add support to the feasibility and potential efficacy of group sessions with psychedelics. To understand whether these effects extend to wider populations suffering from heightened anxiety, and the mechanisms involved, further experimental research is needed.

raw_json:
{"europe_pmc_id":"35873251","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics in the treatment of unipolar and bipolar depression.
authors: Bosch OG, Halm S, Seifritz E.
publication_date: 2022-07-04
doi: 10.1186/s40345-022-00265-5
pubmed_id: 35788817
source_url: https://doi.org/10.1186/s40345-022-00265-5
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
This is a narrative review about the role of classic and two atypical psychedelics in the treatment of unipolar and bipolar depression. Since the 1990s, psychedelics experience a renaissance in biomedical research. The so-called classic psychedelics include lysergic acid diethylamide (LSD), psilocybin, mescaline and ayahuasca. Characteristic effects like alterations in sensory perception, as well as emotion- and self-processing are induced by stimulation of serotonin 2A receptors in cortical areas. The new paradigm of psychedelic-assisted psychotherapy suggests a therapeutic framework in which a safely conducted psychedelic experience is integrated into a continuous psychotherapeutic process. First randomized, controlled trials with psilocybin show promising efficacy, tolerability, and adherence in the treatment of unipolar depression. On the other hand, classic psychedelics seem to be associated with the induction of mania, which is an important issue to consider for the design of research and clinical protocols. So called atypical psychedelics are a heterogeneous group with overlapping subjective effects but different neurobiological mechanisms. Two examples of therapeutic value in psychiatry are 3,4-methyl​enedioxy​methamphetamine (MDMA) and ketamine. Since 2020 the ketamine enantiomer esketamine has been granted international approval for treatment-resistant unipolar depression, and also first evidence exists for the therapeutic efficacy of ketamine in bipolar depression. Whether psychedelics will fulfil current expectations and find their way into broader clinical use will depend on future rigorous clinical trials with larger sample sizes. A well-considered therapeutic and legal framework will be crucial for these substances to create new treatment settings and a potential paradigm shift.

topic_tags:
Depression,Mechanism of Action,Receptor Pharmacology,Emotional Processing,Clinical Trial,Review Article,Safety

raw_json:
{"europe_pmc_id":"35788817","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Assessment of Bioactivity-Modulating Pseudo-Ring Formation in Psilocin and Related Tryptamines.
authors: Lenz C, Dörner S, Trottmann F, Hertweck C, Sherwood A, Hoffmeister D.
publication_date: 2022-05-17
doi: 10.1002/cbic.202200183
pubmed_id: 35483009
source_url: https://doi.org/10.1002/cbic.202200183
keywords: Humans, Tryptamines, Hallucinogens, Prodrugs, Psilocybin, Major Depressive Disorder
substance_tags: psilocybin,psilocin
topic_tags: Depression,Pharmacology,Consciousness,Drug Interactions
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Psilocybin (1) is the major alkaloid found in psychedelic mushrooms and acts as a prodrug to psilocin (2, 4-hydroxy-N,N-dimethyltryptamine), a potent psychedelic that exerts remarkable alteration of human consciousness. In contrast, the positional isomer bufotenin (7, 5-hydroxy-N,N-dimethyltryptamine) differs significantly in its reported pharmacology. A series of experiments was designed to explore chemical differences between 2 and 7 and specifically to test the hypothesis that the C-4 hydroxy group of 2 significantly influences the observed physical and chemical properties through pseudo-ring formation via an intramolecular hydrogen bond (IMHB). NMR spectroscopy, accompanied by quantum chemical calculations, was employed to compare hydrogen bond behavior in 4- and 5-hydroxylated tryptamines. The results provide evidence for a pseudo-ring in 2 and that sidechain/hydroxyl interactions in 4-hydroxytryptamines influence their oxidation kinetics. We conclude that the propensity to form IMHBs leads to a higher number of uncharged species that easily cross the blood-brain barrier, compared to 7 and other 5-hydroxytryptamines, which cannot form IMHBs. Our work helps understand a fundamental aspect of the pharmacology of 2 and should support efforts to introduce it (via the prodrug 1) as an urgently needed therapeutic against major depressive disorder.

raw_json:
{"europe_pmc_id":"35483009","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Self-administration of Psilocybin in the Setting of Treatment-resistant Depression.
authors: Lyons A.
publication_date: 2022-06-30
pubmed_id: 36204170
source_url: https://europepmc.org/article/MED/36204170
substance_tags: psilocybin
topic_tags: Depression,Microdosing,Randomized Controlled Trial,Treatment-Resistant Depression,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
BackgroundPatients diagnosed with major depressive disorder (MDD) who fail to respond to two or more antidepressants are often considered to have treatment-resistant depression (TRD). Many of the current options for TRD have significant side effect profiles, are expensive, and are difficult to access. There has been a revival of psychedelic research in recent years that shows promising results in the treatment of TRD.Case presentationHere, the case of a 43-year-old man with TRD is presented. TRD symptoms were greatly interfering with his life. He underwent psychological testing, lab work, adequate trials of numerous medications, transcranial magnetic stimulation (TMS), and electroconvulsive therapy, all without adequate relief of his symptoms. The patient began self-administering a microdosing regimen of psilocybin and experienced significant improvement of MDD symptoms, as characterized by Hamilton Depression Rating Scale (HDRS).DiscussionIn recent years, multiple randomized, controlled trials (RCTs) have shown the benefit of psilocybin in the treatment of varying types of depression. One trial evaluated psilocybin and escitalopram as treatments for depression, and psilocybin was found to be superior.ConclusionThis case suggests the possible benefit of psilocybin in the setting of TRD, as outlined in recent research. Additional research is needed to confirm these observations.

raw_json:
{"europe_pmc_id":"36204170","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Classic Psychedelics and Human-Animal Relations.
authors: Pöllänen E, Osika W, Stenfors CUD, Simonsson O
journal: International journal of environmental research and public health
publication_date: 2022-06-30
doi: 10.3390/ijerph19138114
pubmed_id: 35805769
source_url: https://pubmed.ncbi.nlm.nih.gov/35805769/
keywords: LSD, human–animal relations, nature, psilocybin, psychedelics
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:39
raw_json: {"pubmed_id":"35805769"}
abstract:
Previous research has found associations between classic psychedelic use and nature-relatedness, but the link between classic psychedelic use and human−animal relations remains largely unexplored. Using data representative of the US adult population, with regard to age, sex and ethnicity (N = 2822), this pre-registered study assessed lifetime classic psychedelic use, ego dissolution during respondents’ most intense experience using a classic psychedelic, and three measures related to human−animal relations: speciesism, animal solidarity and desire to help animals. The results showed that lifetime classic psychedelic use was negatively associated with speciesism (β = −0.07, p = 0.002), and positively associated with animal solidarity (β = 0.04, p = 0.041), but no association was found with desire to help animals (β = 0.01, p = 0.542). Ego dissolution during the respondents’ most intense experience using a classic psychedelic was negatively associated with speciesism (β = −0.17, p < 0.001), and positively associated with animal solidarity (β = 0.18, p < 0.001) and desire to help animals (β = 0.10, p = 0.007). The findings indicate that classic psychedelics and ego dissolution may have an impact on human−animal relations. As these results cannot demonstrate causality, however, future studies should use longitudinal research designs to further explore the potential causal link between classic psychedelic use and human−animal relations.


authors: Smausz R, Neill J, Gigg J.
publication_date: 2022-05-29
doi: 10.1177/02698811221092508
pubmed_id: 35638159
source_url: https://doi.org/10.1177/02698811221092508
keywords: Brain, Humans, Hallucinogens, Emotions, Electrophysiology, Psilocybin
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
title:
Neural mechanisms underlying psilocybin's therapeutic potential - the need for preclinical in vivo electrophysiology.

abstract:
Psilocybin is a naturally occurring psychedelic compound with profound perception-, emotion- and cognition-altering properties and great potential for treating brain disorders. However, the neural mechanisms mediating its effects require in-depth investigation as there is still much to learn about how psychedelic drugs produce their profound and long-lasting effects. In this review, we outline the current understanding of the neurophysiology of psilocybin's psychoactive properties, highlighting the need for additional preclinical studies to determine its effect on neural network dynamics. We first describe how psilocybin's effect on brain regions associated with the default-mode network (DMN), particularly the prefrontal cortex and hippocampus, likely plays a key role in mediating its consciousness-altering properties. We then outline the specific receptor and cell types involved and discuss contradictory evidence from neuroimaging studies regarding psilocybin's net effect on activity within these regions. We go on to argue that in vivo electrophysiology is ideally suited to provide a more holistic, neural network analysis approach to understand psilocybin's mode of action. Thus, we integrate information about the neural bases for oscillatory activity generation with the accumulating evidence about psychedelic drug effects on neural synchrony within DMN-associated areas. This approach will help to generate important questions for future preclinical and clinical studies. Answers to these questions are vital for determining the neural mechanisms mediating psilocybin's psychotherapeutic potential, which promises to improve outcomes for patients with severe depression and other difficulty to treat conditions.

topic_tags:
Depression,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Consciousness,Aging,Emotional Processing,Review Article,Animal Study

raw_json:
{"europe_pmc_id":"35638159","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2021-06-09
source_url: https://osf.io/preprints/psyarxiv/64kyg_v1
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Biomarkers,Aging,Clinical Trial,Review Article
study_type: Clinical Trial
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"64kyg_v1","version":1,"reviews_state":"accepted"}
title:
Psychedelic resting-state neuroimaging: a review and perspective on balancing replication and novel analyses

abstract:
Clinical research into serotonergic psychedelic drugs including psilocybin, LSD and N,N-DMT (e.g., in ‘ayahuasca’) is expanding rapidly and clinical trials across a range of psychiatric conditions have shown promising efficacy, with larger trials ongoing. Resting-state functional magnetic resonance imaging (fMRI) has emerged as a brain imaging strategy commonly used to identify associated neural mechanisms in both clinical and healthy populations. To date, 42 research articles have been published analysing resting-state fMRI data from 17 unique datasets involving the administration of a psychedelic drug. This provides a promising foundation for resolving imaging markers of the perceptual and clinical effects of psychedelics. Here we review the existing psychedelic resting-state fMRI literature through a lens that brings attention to emerging variation in core methodological decisions and promote strategies that aim to strengthen the field. We find a large degree of heterogeneity across the existing literature, with nearly all studies varying in data processing and analysis or drug evaluated. Two datasets are the foundation of more than half of the published literature, and terms such as “entropy” are often used to denote distinct metrics across studies. In light of these observations, we offer suggestions for future studies that we hope encourages coherence in the field. As a budding field of interest, psychedelic resting-state imaging will benefit from the development of novel models, hypotheses and quantification methods that may expand our understanding of the neural mechanisms mediating the intriguing acute perceptual and lasting clinical effects. Our review of the existing literature suggests that the psychedelic resting-state brain imaging field is at a crossroads at which it must also consider the critical importance of consistency and replicability to effectively converge on stable representations of the neural effects of psychedelics.

keywords:
ayahuasca, DMT, entropy, fMRI, LSD, neuroimaging, neuroscience, psilocybin, psychedelic, replication, resting-state, review, Neuroscience, Computational Neuroscience, Systems Neuroscience, Clinical Neuroscience


publication_date: 2022-04-25
doi: 10.1016/j.psychres.2022.114577
pubmed_id: 35580433
source_url: https://doi.org/10.1016/j.psychres.2022.114577
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Aging,Review Article,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
The Effects of Psilocybin in Adults with Major Depressive Disorder and the General Population: Findings from Neuroimaging Studies.

authors:
Gill H, Puramat P, Patel P, Gill B, Marks CA, Rodrigues NB, Castle D, Cha DS, Mansur RB, Rosenblat JD, McIntyre RS.

abstract:
The use of psilocybin as treatment for major depressive disorder (MDD) has been examined as a promising alternative to traditional first-line options. We reviewed existing literature to provide a synthesis of the extant neuroimaging observations with psilocybin, and to identify putative therapeutic targets for target engagement studies with psilocybin, and potentially other psychedelics. We assessed neuroimaging observations with psilocybin among participants with MDD and healthy populations. A systematic search was conducted on PubMed, Google Scholar and PsycINFO from database inception to November 17th, 2021. The study quality (i.e., risk of bias) was assessed using the revised Cochrane risk-of-bias tool for randomized trials. A total of ten studies evaluated psilocybin in healthy populations and three studies assessed psilocybin in MDD participants using neuroimaging techniques. Following psilocybin administration, a decrease in amygdala activity and a reduction in depressive symptoms was observed in two studies. Changes in functional connectivity and activation of prefrontal limbic structures, specifically the ventral medial prefrontal cortex and amygdala, was seen in healthy populations. There was high heterogeneity in methodology (e.g., dosing schedule and imaging methods) amongst included studies. Longitudinal studies are needed to further elucidate psilocybin treatment for MDD, its long-term effects and the possibility of sustained therapeutic effects.

keywords:
Amygdala, Humans, Hallucinogens, Magnetic Resonance Imaging, Adult, Neuroimaging, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"35580433","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Zhai W, Li L, Zhao J, Xiang P, Liu M, Shi Y, Dang Y.
publication_date: 2022-03-28
doi: 10.1002/dta.3255
pubmed_id: 35312166
source_url: https://doi.org/10.1002/dta.3255
substance_tags: psilocybin,psilocin
topic_tags: Pharmacology,Biomarkers,Epigenetics,Clinical Trial,In Vitro Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Tentative identification of in vitro metabolites of O-acetylpsilocin (psilacetin, 4-AcO-DMT) by UHPLC-Q-Orbitrap MS.

abstract:
4-Acetoxy-N,N-dimethyltryptamine (4-AcO-DMT, psilacetin, O-acetylpsilocin) is a synthetic tryptamine with psychedelic properties. Psilacetin may also act as precursor drug of psilocin, similar to psilocybin, but little is known about its metabolism. In this study, the phase I and phase II in vitro metabolism of 4-AcO-DMT was investigated with pooled human liver microsomes, and the reaction mixture was analyzed using liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry. Fifteen metabolites were formed after incubation of pooled human liver microsomes with 4-AcO-DMT (12 phase I metabolites and 3 phase II metabolites). The proposed metabolite structures were based on accurate mass analysis and MS/MS fragmentation patterns. The biotransformations included hydrolysis, hydroxylation, N-demethylation, oxidation, and conjugation with glucuronic acid. The hydrolysis metabolite was the most abundant compound. For the development of new methods for the identification of 4-AcO-DMT consumption, the beta-hydroxylation metabolite of 4-AcO-DMT (M2-1) is recommended as a biomarker. The data reported in this work might be applicable to metabolic transformation of 4-AcO-DMT in vivo and also forensically helpful.

keywords:
Microsomes, Liver, Humans, Tryptamines, Chromatography, Liquid, Chromatography, High Pressure Liquid, Tandem Mass Spectrometry

raw_json:
{"europe_pmc_id":"35312166","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Sakurai H, Yonezawa K, Tani H, Mimura M, Bauer M, Uchida H.
publication_date: 2022-01-18
doi: 10.1055/a-1714-9097
pubmed_id: 35045580
source_url: https://doi.org/10.1055/a-1714-9097
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
title:
Novel Antidepressants in the Pipeline (Phase II and III): A Systematic Review of the US Clinical Trials Registry.

abstract:
IntroductionThere is an imminent need for faster-acting and more effective antidepressants beyond the monoaminergic hypothesis.MethodsWe systematically searched the US Clinical Trials registry for antidepressant compounds with completed phase II and III trials. Compounds that demonstrated significant superiority over placebo in the primary outcome measure in the latest phase of phase II and III trials were identified. The collateral information was gathered via a PubMed search and press releases.ResultsNine compounds were identified. AXS-05 (a combination of dextromethorphan and bupropion) and ansofaxine hydrochloride showed a positive result over placebo in a phase III study for major depressive disorder or treatment-resistant depression. MIJ821, nitrous oxide, psilocybin, ayahuasca, facial injection of botulinum toxin A, prasterone, and casopitant demonstrated at least one positive result in phase II trials. Ayahuasca showed a greater response rate than placebo at week one, indicating the rapid antidepressant effect.DiscussionThese new compounds with novel mechanisms of action are expected to provide a greater variety of treatment options for depression if preliminary positive results are confirmed.

keywords:
Humans, Antidepressive Agents, Registries, Clinical Trials, Phase II as Topic, Depressive Disorder, Treatment-Resistant, Major Depressive Disorder

topic_tags:
Depression,Mechanism of Action,Clinical Trial,Systematic Review,Review Article,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"35045580","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A systematic literature review of clinical trials and therapeutic applications of ibogaine.
authors: Köck P, Froelich K, Walter M, Lang U, Dürsteler KM.
publication_date: 2021-12-29
doi: 10.1016/j.jsat.2021.108717
pubmed_id: 35012793
source_url: https://doi.org/10.1016/j.jsat.2021.108717
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
abstract:
BackgroundIboga and its primary alkaloids, ibogaine and noribogaine, have been of interest to researchers and practitioners, mainly due to their putative efficacy in treating substance use disorders (SUDs). For many SUDs, still no effective pharmacotherapies exist. Distinct psychoactive and somatic effects of the iboga alkaloids set them apart from classic hallucinogens like LSD, mescaline, and psilocybin.AimsThe study team performed this systematic review focusing on clinical data and therapeutic interventions involving ibogaine and noribogaine.MethodsThe team conducted a search for all publications up to December 7, 2020, using PubMed and Embase following PRISMA guidelines.ResultsIn total, we identified 743 records. In this review, we consider 24 studies, which included 705 individuals receiving ibogaine or noribogaine. This review includes two randomized, double-blind, controlled clinical trials, one double-blind controlled clinical trial, 17 open-label studies or case series (including observational or retrospective studies), three case reports, and one retrospective survey. The published data suggest that ibogaine is an effective therapeutic intervention within the context of SUDs, reducing withdrawal symptoms and craving. Data also point toward a beneficial impact on depressive and trauma-related psychological symptoms. However, studies have reported severe medical complications and deaths, which seem to be associated with neuro- and cardiotoxic effects of ibogaine. Two of these fatalities were described in the 24 studies included in this review.ConclusionTreatment of SUDs and persisting comorbidities requires innovative treatment approaches. Rapid-onset therapies such as the application of ibogaine may offer novel treatment opportunities for specific individuals. Rigorous study designs within medical settings are necessary to warrant safe application, monitoring, and, possibly, medical intervention.

keywords:
Humans, Substance-Related Disorders, Substance Withdrawal Syndrome, Alkaloids, Ibogaine, Hallucinogens, Retrospective Studies, Randomized Controlled Trials as Topic, Observational Studies as Topic

topic_tags:
Depression,Addiction,Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article,Case Report,Observational Study

raw_json:
{"europe_pmc_id":"35012793","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic-inspired approaches for treating neurodegenerative disorders.
authors: Saeger HN, Olson DE
journal: Journal of neurochemistry
publication_date: 2022-06-30
doi: 10.1111/jnc.15544
pubmed_id: 34816433
source_url: https://pubmed.ncbi.nlm.nih.gov/34816433/
substance_tags: psilocybin
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:39
raw_json: {"pubmed_id":"34816433"}
abstract:
Psychedelics are increasingly being recognized for their potential to treat a wide range of brain disorders including depression, post-traumatic stress disorder (PTSD), and substance use disorder. Their broad therapeutic potential might result from an ability to rescue cortical atrophy common to many neuropsychiatric and neurodegenerative diseases by impacting neurotrophic factor gene expression, activating neuronal growth and survival mechanisms, and modulating the immune system. While the therapeutic potential of psychedelics has not yet been extended to neurodegenerative disorders, we provide evidence suggesting that approaches based on psychedelic science might prove useful for treating these diseases. The primary target of psychedelics, the 5-HT receptor, plays key roles in cortical neuron health and is dysregulated in Alzheimer's disease. Moreover, evidence suggests that psychedelics and related compounds could prove useful for treating the behavioral and psychological symptoms of dementia (BPSD). While more research is needed to probe the effects of psychedelics in models of neurodegenerative diseases, the robust effects of these compounds on structural and functional neuroplasticity and inflammation clearly warrant further investigation.

keywords:
Alzheimer's disease, BPSD, ayahuasca, frontotemporal dementia, neurodegeneration, neuroplasticity, psilocybin, psychedelic, psychoplastogen

topic_tags:
Depression,PTSD,Addiction,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Inflammation,Immune Function


title: Molecular insights into psychedelic drug action.
authors: Slocum ST, DiBerto JF, Roth BL.
publication_date: 2021-11-30
doi: 10.1111/jnc.15540
pubmed_id: 34797943
source_url: https://doi.org/10.1111/jnc.15540
keywords: Lysergic Acid Diethylamide, Hallucinogens, United States, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Review Article,Treatment-Resistant Depression
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
A confluence of factors has renewed interest in the scientific understanding and translational potential of psychedelic drugs such as lysergic acid diethylamide (LSD), mescaline, and psilocybin: the desire for additional approaches to mental health care, incremental progress in basic and clinical research, and the reconsideration and relaxation of existing drug policies. With the United States Food and Drug Administration's designation of psilocybin as a "Breakthrough Therapy" for treatment-resistant depression, a new path has been forged for the conveyance of psychedelics to the clinic. Essential to the further development of such applications, however, is a clearer understanding of how these drugs exert their effects at the molecular level. Here we review the current knowledge regarding the molecular details of psychedelic drug actions and suggest that these discoveries can facilitate new insights into their hallucinogenic and therapeutic mechanisms.

raw_json:
{"europe_pmc_id":"34797943","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kozlowska U, Nichols C, Wiatr K, Figiel M.
publication_date: 2021-10-21
doi: 10.1111/jnc.15509
pubmed_id: 34519052
source_url: https://doi.org/10.1111/jnc.15509
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
From psychiatry to neurology: Psychedelics as prospective therapeutics for neurodegenerative disorders.

abstract:
The studies of psychedelics, especially psychedelic tryptamines like psilocybin, are rapidly gaining interest in neuroscience research. Much of this interest stems from recent clinical studies demonstrating that they have a unique ability to improve the debilitating symptoms of major depressive disorder (MDD) long-term after only a single treatment. Indeed, the Food and Drug Administration (FDA) has recently designated two Phase III clinical trials studying the ability of psilocybin to treat forms of MDD with "Breakthrough Therapy" status. If successful, the use of psychedelics to treat psychiatric diseases like depression would be revolutionary. As more evidence appears in the scientific literature to support their use in psychiatry to treat MDD on and substance use disorders (SUD), recent studies with rodents revealed that their therapeutic effects might extend beyond treating MDD and SUD. For example, psychedelics may have efficacy in the treatment and prevention of brain injury and neurodegenerative diseases such as Alzheimer's Disease. Preclinical work has highlighted psychedelics' ability to induce neuroplasticity and synaptogenesis, and neural progenitor cell proliferation. Psychedelics may also act as immunomodulators by reducing levels of proinflammatory biomarkers, including IL-1β, IL-6, and tumor necrosis factor-α (TNF-α). Their exact molecular mechanisms, and induction of cellular interactions, especially between neural and glial cells, leading to therapeutic efficacy, remain to be determined. In this review, we discuss recent findings and information on how psychedelics may act therapeutically on cells within the central nervous system (CNS) during brain injuries and neurodegenerative diseases.

keywords:
Humans, Neurodegenerative Diseases, Substance-Related Disorders, Hallucinogens, Psychiatry, Neurology, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,Addiction,Neuroplasticity,Mechanism of Action,Biomarkers,Clinical Trial,Review Article,Animal Study,Drug Interactions,Inflammation

raw_json:
{"europe_pmc_id":"34519052","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin: A brief overview for psychiatric mental health nurse practitioners.
authors: Fradkin D.
publication_date: 2021-06-07
doi: 10.1111/ppc.12888
pubmed_id: 34101846
source_url: https://doi.org/10.1111/ppc.12888
keywords: Humans, Substance-Related Disorders, Hallucinogens, Mental Health, Nurse Practitioners, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
The use of psychedelics, such as psilocybin, has emerged in recent literature as a novel therapeutic treatment for various psychiatric disorders, including substance use, depression, and anxiety. While international and domestic trials are currently underway, there is data demonstrating both the relative safety and potential efficacy of psilocybin. Psychiatric mental health nurse practitioners are essential mental health providers that may be at the forefront of delivering these new treatment modalities. Therefore, they must be aware of the psychopharmacological and psychotherapeutic tenets of psilocybin to be prepared to treat patients.

raw_json:
{"europe_pmc_id":"34101846","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Rootman JM, Kiraga M, Kryskow P, Harvey K, Stamets P, Santos-Brault E, Kuypers KPC, Walsh Z.
publication_date: 2022-06-29
doi: 10.1038/s41598-022-14512-3
pubmed_id: 35773270
source_url: https://doi.org/10.1038/s41598-022-14512-3
keywords: Hallucinogens, Self Administration, Affect, Mental Health, Psilocybin
substance_tags: psilocybin
topic_tags: Aging,Microdosing,Observational Study,Older Adults
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls.

abstract:
Psilocybin microdosing involves repeated self-administration of mushrooms containing psilocybin at doses small enough to not impact regular functioning. Microdose practices are diverse and include combining psilocybin with substances such as lion's mane mushrooms (Hericium erinaceus; HE) and niacin (vitamin-B3). Public uptake of microdosing has outpaced evidence, mandating further prospective research. Using a naturalistic, observational design, we followed psilocybin microdosers (n = 953) and non-microdosing comparators (n = 180) for approximately 30 days and identified small- to medium-sized improvements in mood and mental health that were generally consistent across gender, age and presence of mental health concerns, as we all as improvements in psychomotor performance that were specific to older adults. Supplementary analyses indicated that combining psilocybin with HE and B3 did not impact changes in mood and mental health. However, among older microdosers combining psilocybin, HE and B3 was associated with psychomotor improvements relative to psilocybin alone and psilocybin and HE. Our findings of mood and mental health improvements associated with psilocybin microdosing add to previous studies of psychedelic microdosing by using a comparator group and by examining the consistency of effects across age, gender, and mental health. Findings regarding the combination of psilocybin, HE and B3 are novel and highlight the need for further research to confirm and elucidate these apparent effects.

raw_json:
{"europe_pmc_id":"35773270","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: 3,4-Methylenedioxymethamphetamine (MDMA)-Assisted Therapy in Hawaii: A Brief Review.
authors: Inouye A, Wolfgang A.
publication_date: 2022-06-27
doi: 10.7759/cureus.26402
pubmed_id: 35915689
source_url: https://doi.org/10.7759/cureus.26402
substance_tags: psilocybin
topic_tags: Depression,PTSD,Clinical Trial,Review Article,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
The Food and Drug Administration (FDA) granted breakthrough therapy status to 3,4-methyl​enedioxy​methamphetamine-assisted therapy (MDMA-AT) in 2017 due to preliminary evidence supporting its efficacy and safety in treating post-traumatic stress disorder (PTSD). A series of six phase-II clinical trials studying MDMA-AT for treatment-resistant PTSD found that 54% of MDMA-AT full-dose participants no longer met the diagnosis of PTSD after two MDMA sessions, compared to 23% in the control group. In the first phase-III clinical trial, 67% no longer met the criteria for PTSD after three sessions. The effects are durable, with 67% no longer diagnosable after one year and 74% at nearly four years. The MDMA-AT is being fast-tracked for potential FDA approval by 2023. In 2021, Hawaii's Senate Bill 738 unsuccessfully proposed that psilocybin be removed from the Schedule I controlled substances list due to its clinical efficacy for major depressive disorder. Methyl​enedioxy​methamphetamine is also a Schedule I controlled substance and has proven to be a treatment option that could potentially benefit the people of Hawaii.

raw_json:
{"europe_pmc_id":"35915689","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Vorobyeva N, Kozlova AA.
publication_date: 2022-06-27
doi: 10.3389/fphar.2022.927984
pubmed_id: 35837277
source_url: https://doi.org/10.3389/fphar.2022.927984
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Addiction,Receptor Pharmacology,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Three Naturally-Occurring Psychedelics and Their Significance in the Treatment of Mental Health Disorders.

abstract:
Classical psychedelics represent a family of psychoactive substances with structural similarities to serotonin and affinity for serotonin receptors. A growing number of studies have found that psychedelics can be effective in treating various psychiatric conditions, including post-traumatic stress disorder, major depressive disorder, anxiety, and substance use disorders. Mental health disorders are extremely prevalent in the general population constituting a major problem for the public health. There are a wide variety of interventions for mental health disorders, including pharmacological therapies and psychotherapies, however, treatment resistance still remains a particular challenge in this field, and relapse rates are also quite high. In recent years, psychedelics have become one of the promising new tools for the treatment of mental health disorders. In this review, we will discuss the three classic serotonergic naturally occurring psychedelics, psilocybin, ibogaine, and N, N-dimethyltryptamine, focusing on their pharmacological properties and clinical potential. The purpose of this article is to provide a focused review of the most relevant research into the therapeutic potential of these substances and their possible integration as alternative or adjuvant options to existing pharmacological and psychological therapies.

raw_json:
{"europe_pmc_id":"35837277","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Wang Q, Ren Y, Cui Y, Gao B, Zhang H, Jiang Q, Loor JJ, Deng Z, Xu C.
publication_date: 2022-06-26
doi: 10.3389/fvets.2022.852321
pubmed_id: 35832333
source_url: https://doi.org/10.3389/fvets.2022.852321
substance_tags: psilocybin
topic_tags: Pharmacology,Mechanism of Action
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
title:
Bacillus subtilis Produces Amino Acids to Stimulate Protein Synthesis in Ruminal Tissue Explants via the Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Beta-Serine/Threonine Kinase-Mammalian Target of Rapamycin Complex 1 Pathway.

abstract:
BackgroundBacillus subtilis is a probiotic strain that is widely used as a feed supplement for ruminants. In this study, one B. subtilis strain isolated from the ruminal fluid of Holstein dairy cows was used for an ex vivo study with ruminal tissue explants. The main goal was to assess the potential endosymbiotic links between B. subtilis and the ruminal epithelium using molecular analyses and amino acid profiling. The explant culture protocol was first optimized to determine the ideal conditions in terms of tissue viability before performing the actual experiments involving active and inactive bacteria with or without protein synthesis inhibitors, such as LY294002 (phosphatidylinositol 3-kinase inhibitor) or rapamycin [mammalian target of rapamycin (mTOR) inhibitor].ResultsThe mRNA levels of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PIK3CB), serine/threonine kinase (AKT), mTOR, P70S6K1, and eukaryotic translation initiation factor 4E binding protein 1 were the highest (p < 0.01), while those of programmed cell death 4 were the lowest when the tissue was incubated with 107 of B. subtilis. Compared with the inactivated bacteria, the expression levels of PIK3CB and AKT, and overall changes in mTOR and P70S6K1 were greater in rumen explants with living bacteria (p < 0.05). With an increase in B. subtilis concentration, the trends of protein and corresponding gene changes were consistent. There were differences in the concentrations of individual amino acids in the supernatants of living and inactivated bacterial culture groups, with most amino acids enriched in pathways, such as aminoacyl tRNA biosynthesis, cyanoamino acid metabolism, monobactam biosynthesis, or glycine, serine, and threonine metabolism. The addition of psilocybin upregulated the expression levels of PIK3CB and AKT. A significant decrease (p < 0.05) in PIK3CB and mTOR protein expression levels was detected after the addition of LY294002 and rapamycin. In addition, These responses were associated with the downregulation (p < 0.05) of AKT and P70S6K protein expression levels.ConclusionsWe confirmed that the in vivo ruminal tissue culture system is a suitable model for studying probiotic-induced alterations in tissue function. As such, this study provides a means for future mechanistic studies related to microbial regulation and the dietary supply of proteins. In addition, living and inactivated B. subtilis can promote protein synthesis in ruminal tissue explants by altering the expression levels of related factors in the PIK3CB-AKT-mTORC1 pathway, which could further aid in optimizing the feed efficiency and increasing the use of inactivated bacteria as additives in dairy cow farming.

raw_json:
{"europe_pmc_id":"35832333","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Jones G, Lipson J, Nock MK.
publication_date: 2022-06-21
doi: 10.1038/s41598-022-14809-3
pubmed_id: 35732796
source_url: https://doi.org/10.1038/s41598-022-14809-3
keywords: Humans, Tobacco Use Disorder, Mescaline, Hallucinogens, Smoking Cessation, Adult, Psilocybin
substance_tags: psilocybin
topic_tags: Addiction,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Associations between classic psychedelics and nicotine dependence in a nationally representative sample.

abstract:
Tobacco use is the single largest cause of preventable death worldwide, but none of the established treatments aimed at smoking cessation work for a majority of smokers. As such, there is an urgent need for interventions capable of reliably treating nicotine addiction. The use of classic psychedelics has been associated with lower odds of many forms of substance dependence. Here we tested whether lifetime use of classic psychedelics (tryptamine, lysergamide, and phenethylamine) is associated with lower odds of current nicotine dependence. We tested these associations in a sample of 214,505 adult participants in the National Survey on Drug Use and Health (2015-2019) using multivariable logistic regression models. Lifetime psilocybin use was associated with reduced odds of odds of current nicotine dependence (aOR 0.87-0.93). Lifetime use of peyote and mescaline also conferred reduced odds of multiple subdomains of a main nicotine dependence measure (Nicotine Dependence Syndrome Scale [NDSS]) (aOR 0.79-0.91). Conversely, lifetime use of LSD was associated with increased odds of nicotine dependence (aOR 1.17-1.24). Psilocybin, mescaline, and peyote use are associated with lowered odds of nicotine dependence. Experimental studies are needed to establish whether these associations are causal. These results make the case for further research into the efficacy of both tryptamine and phenethylamine psychedelics in promoting smoking cessation.

raw_json:
{"europe_pmc_id":"35732796","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2022-06-18
doi: 10.3390/jpm12061004
pubmed_id: 35743788
source_url: https://doi.org/10.3390/jpm12061004
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Emotional Processing,Healthy Volunteers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Psilocybin-Mediated Attenuation of Gamma Band Auditory Steady-State Responses (ASSR) Is Driven by the Intensity of Cognitive and Emotional Domains of Psychedelic Experience.

authors:
Viktorin V, Griškova-Bulanova I, Voicikas A, Dojčánová D, Zach P, Bravermanová A, Andrashko V, Tylš F, Korčák J, Viktorinová M, Koudelka V, Hájková K, Kuchař M, Horáček J, Brunovský M, Páleníček T.

abstract:
Psilocybin is a classical serotoninergic psychedelic that induces cognitive disruptions similar to psychosis. Gamma activity is affected in psychosis and is tightly related to cognitive processing. The 40 Hz auditory steady-state responses (ASSR) are frequently used as indicators to test the ability to generate gamma activity. Based on previous literature, we studied the impact of psilocybin on 40 Hz ASSR in healthy volunteers. The study was double blind and placebo controlled with a crossover design. A sample of 20 healthy subjects (10M/10F) received psilocybin orally 0.26 mg/kg or placebo. Participants were measured four times in total, one time before ingestion of psilocybin/placebo and one time after ingestion, during the peak of intoxication. A series of 500 ms click trains were used for stimulation. Psilocybin induced a psychedelic effect and decreased 40 Hz ASSR phase-locking index compared to placebo. The extent of the attenuation was related to Cognition and Affect on the Hallucinogen Rating Scale. The current study shows that psilocybin lowers the synchronization level and the amplitude of 40 Hz auditory steady-state responses, which yields further support for the role of gamma oscillations in cognitive processing and its disturbance.

raw_json:
{"europe_pmc_id":"35743788","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2022-06-15
doi: 10.3390/ijms23126713
pubmed_id: 35743159
source_url: https://doi.org/10.3390/ijms23126713
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Receptor Pharmacology,Animal Study,Toxicity
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Effect of Psilocybin and Ketamine on Brain Neurotransmitters, Glutamate Receptors, DNA and Rat Behavior.

authors:
Wojtas A, Bysiek A, Wawrzczak-Bargiela A, Szych Z, Majcher-Maślanka I, Herian M, Maćkowiak M, Gołembiowska K.

abstract:
Clinical studies provide evidence that ketamine and psilocybin could be used as fast-acting antidepressants, though their mechanisms and toxicity are still not fully understood. To address this issue, we have examined the effect of a single administration of ketamine and psilocybin on the extracellular levels of neurotransmitters in the rat frontal cortex and reticular nucleus of the thalamus using microdialysis. The genotoxic effect and density of glutamate receptor proteins was measured with comet assay and Western blot, respectively. An open field test, light-dark box test and forced swim test were conducted to examine rat behavior 24 h after drug administration. Ketamine (10 mg/kg) and psilocybin (2 and 10 mg/kg) increased dopamine, serotonin, glutamate and GABA extracellular levels in the frontal cortex, while psilocybin also increased GABA in the reticular nucleus of the thalamus. Oxidative DNA damage due to psilocybin was observed in the frontal cortex and from both drugs in the hippocampus. NR2A subunit levels were increased after psilocybin (10 mg/kg). Behavioral tests showed no antidepressant or anxiolytic effects, and only ketamine suppressed rat locomotor activity. The observed changes in neurotransmission might lead to genotoxicity and increased NR2A levels, while not markedly affecting animal behavior.

keywords:
Brain, Animals, Rats, gamma-Aminobutyric Acid, Ketamine, Receptors, Glutamate, DNA, Neurotransmitter Agents, Antidepressive Agents, Behavior, Animal, Psilocybin

raw_json:
{"europe_pmc_id":"35743159","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Hibicke M, Nichols CD.
publication_date: 2022-06-14
doi: 10.1038/s41598-022-14165-2
pubmed_id: 35705666
source_url: https://doi.org/10.1038/s41598-022-14165-2
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Validation of the forced swim test in Drosophila, and its use to demonstrate psilocybin has long-lasting antidepressant-like effects in flies.

abstract:
Psilocybin has been shown to be a powerful, long-lasting antidepressant in human clinical trials and in rodent models. Although rodents have commonly been used to model psychiatric disorders, Drosophila have neurotransmitter systems similar to mammals and many comparable brain structures involved in similar behaviors. The forced swim test (FST), which has been used extensively to evaluate compounds for antidepressant efficacy, has recently been adapted for Drosophila. The fly FST has potential to be a cost-effective, high-throughput assay for evaluating potential antidepressants. For this study we pharmacologically validated the fly FST using methamphetamine, DL-α-methyltyrosine, and the antidepressant citalopram. While methamphetamine and DL-α-methyltyrosine altered overall locomotor activity in the Drosophila Activity Monitor System (DAMS), they had no significant impact on measures of immobility in the FST. Conversely, chronic citalopram decreased measures of immobility in the FST in both sexes without increasing DAMS activity. We used the validated FST to evaluate the antidepressant-like effects of high (3.5 mM) and low (0.03 mM) doses of psilocybin. Both doses of psilocybin significantly reduced measures of immobility in male flies, but not females. 0.03 mM had an effect size comparable to chronic citalopram, and 3.5 mM had an effect size approximately twice that of chronic citalopram.

keywords:
Animals, Mammals, Humans, Drosophila, Methamphetamine, Citalopram, alpha-Methyltyrosine, Antidepressive Agents, Motor Activity, Swimming, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"35705666","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Polo-Castellano C, Álvarez JÁ, Palma M, Barbero GF, Ayuso J, Ferreiro-González M.
publication_date: 2022-06-01
doi: 10.3390/jof8060598
pubmed_id: 35736081
source_url: https://doi.org/10.3390/jof8060598
substance_tags: psilocybin,psilocin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Optimization through a Box-Behnken Experimental Design of the Microwave-Assisted Extraction of the Psychoactive Compounds in Hallucinogenic Fungi (Psylocibe cubensis).

abstract:
Hallucinogenic fungi, mainly those from the Psilocybe genus, are being increasingly consumed even though there is no control on their culture conditions. Due to the therapeutic potential as antidepressants and anxiolytics of the alkaloids that they produce (psilocin and psilocybin), some form of control on their production would be highly recommended. Prior to identifying their optimal culture condition, a methodology that allows their study is required. Microwave-assisted extraction method (MAE) is a technique that has proven its efficiency to extract different compounds from solid matrices. For this reason, this study intends to optimize a MAE method to extract the alkaloids found in Psylocibe cubensis. A surface-response Box-Behnken design has been employed to optimize such extraction method and significantly reduce time and other resources in the extraction process. Based on the Box-Behnken design, 50 °C temperature, 60% methanol as extraction solvent, 0.6 g:10 mL sample mass:solvent ratio and 5 min extraction time, were established as optimal conditions. These mild conditions, combined with a rapid and efficient UHPLC analysis result in a practical and economical methodology for the extraction of psilocin and psilocybin from Psylocibe cubensis.

raw_json:
{"europe_pmc_id":"35736081","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Rossi GN, Hallak JEC, Bouso Saiz JC, Dos Santos RG.
publication_date: 2022-04-26
doi: 10.1080/14740338.2022.2066650
pubmed_id: 35426754
source_url: https://doi.org/10.1080/14740338.2022.2066650
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Clinical Trial,Randomized Controlled Trial,Safety,Adverse Events
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Safety issues of psilocybin and LSD as potential rapid acting antidepressants and potential challenges.

abstract:
IntroductionA limited number of preliminary open-label (n = 3) and placebo-controlled clinical trials (n = 5) have suggested psilocybin and LSD as potential rapid antidepressants. In this context, there is a growing need to verify and document their safety and tolerability as therapeutic agents, discuss the challenges associated with their administration, and develop safety protocols for their use as next-generation therapeutic agents.Areas coveredWe have analyzed all randomized, double-blind, and controlled trials that assessed the antidepressant effects of psilocybin and LSD in clinical populations to date, taking special attention to adverse events (AEs) related to their use. Prevalence, significance, and mechanisms of action related to AEs were systematically extracted, analyzed, and discussed.Expert opinionThere were no serious AEs related to psilocybin and LSD administration. Most AEs were expected, manageable, and transient. Nevertheless, safety and tolerability concerns regarding some effects, such as dissociation, paranoia, and confusion, remain. Thus, randomized controlled trials with bigger samples are warranted to confirm their therapeutic effects and further investigate their safety and tolerability.

keywords:
Humans, Lysergic Acid Diethylamide, Antidepressive Agents, Randomized Controlled Trials as Topic, Psilocybin

raw_json:
{"europe_pmc_id":"35426754","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Husain MI, Umer M, Mulsant BH
journal: Expert opinion on drug safety
publication_date: 2022-05-31
doi: 10.1080/14740338.2022.2063274
pubmed_id: 35387542
source_url: https://pubmed.ncbi.nlm.nih.gov/35387542/
substance_tags: psilocybin
topic_tags: Depression,PTSD,Addiction,Safety
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:39
raw_json: {"pubmed_id":"35387542"}
title:
Can the revival of serotonergic psychedelic drugs as treatments for mental disorders help to characterize their risks and benefits?

keywords:
MDMA, Psychedelics, major depressive disorder, post-traumatic stress disorder, psilocybin, psychotherapy, substance use disorders


authors: van den Berg M, Magaraggia I, Schreiber R, Hillhouse TM, Porter JH
journal: Psychopharmacology
publication_date: 2022-05-31
doi: 10.1007/s00213-022-06106-8
pubmed_id: 35348806
source_url: https://pubmed.ncbi.nlm.nih.gov/35348806/
substance_tags: psilocybin
topic_tags: Depression,Pharmacology,Mystical Experience,Treatment-Resistant Depression
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:39
raw_json: {"pubmed_id":"35348806"}
title:
How to account for hallucinations in the interpretation of the antidepressant effects of psychedelics: a translational framework.

abstract:
Recent trials with psychedelics in major depressive disorder and treatment-resistant depression showed remarkable improvements in depressive symptoms that can last for up to several months after even a single administration. The lack of an appropriate placebo control group-as patients are often able to discriminate the subjective effects of the drug-and an incomplete understanding of the role of the hallucinogenic and mystical experience, hampers the interpretation of these therapeutic effects.
To control for these factors, we developed a translational framework based on establishing pharmacokinetic/pharmacodynamic (PK/PD) relationships in rodents and humans for hallucinogenic (i.e., discriminative stimulus effects in rodents and humans; head twitch responses in rodents; questionnaires in humans) and therapeutic effects. For the latter, we selected the pattern separation and attentional set-shifting tasks as measures for cognitive flexibility because of their high translational value. We predict that these PK/PD analyses will lead to a more objective evaluation of improvements in patients compared to relying only on the currently used self-reported questionnaires. We hypothesize that-if the role of the hallucinogenic experience is not central in the antidepressant effects of psychedelics-the ED's for the therapeutic effects will be significantly lower than for the hallucinogenic and mystical effects.
Our framework will help to inform future studies that aim at the elucidation of the mechanism(s) of action of psychedelics in depression, and the role of the acute subjective and/or hallucinogenic experience in their effects.

keywords:
Cognitive flexibility, Depression, Drug discrimination, Head twitch response (HTR), Lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), Pattern separation (PS), Psilocybin, Psychedelics


publication_date: 2022-03-11
doi: 10.1016/j.mec.2022.e00196
pubmed_id: 35310468
source_url: https://doi.org/10.1016/j.mec.2022.e00196
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Animal Study,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Development of an E. coli-based norbaeocystin production platform and evaluation of behavioral effects in rats.

authors:
Adams AM, Anas NA, Sen AK, Hinegardner-Hendricks JD, O'Dell PJ, Gibbons WJ, Flower JE, McMurray MS, Jones JA.

abstract:
Interest in the potential therapeutic efficacy of psilocybin and other psychedelic compounds has escalated significantly in recent years. To date, little is known regarding the biological activity of the psilocybin pathway intermediate, norbaeocystin, due to limitations around sourcing the phosphorylated tryptamine metabolite for in vivo testing. To address this limitation, we first developed a novel E. coli platform for the rapid and scalable production of gram-scale amounts of norbaeocystin. Through this process we compare the genetic and fermentation optimization strategies to that of a similarly constructed and previously reported psilocybin producing strain, uncovering the need for reoptimization and balancing upon even minor genetic modifications to the production host. We then perform in vivo measurements of head twitch response to both biosynthesized psilocybin and norbaeocystin using both a cell broth and water vehicle in Long-Evans rats. The data show a dose response to psilocybin while norbaeocystin does not elicit any pharmacological response, suggesting that norbaeocystin and its metabolites may not have a strong affinity for the serotonin 2A receptor. The findings presented here provide a mechanism to source norbaeocystin for future studies to evaluate its disease efficacy in animal models, both individually and in combination with psilocybin, and support the safety of cell broth as a drug delivery vehicle.

raw_json:
{"europe_pmc_id":"35310468","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The promises and perils of psychedelic pharmacology for psychiatry.
authors: McClure-Begley TD, Roth BL.
publication_date: 2022-03-16
doi: 10.1038/s41573-022-00421-7
pubmed_id: 35301459
source_url: https://doi.org/10.1038/s41573-022-00421-7
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Pharmacology,Mechanism of Action,Receptor Pharmacology,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Psychedelic drugs including psilocybin, N,N'-dimethyltryptamine (DMT) and lysergic acid diethylamide (LSD) are undergoing a renaissance as potentially useful drugs for various neuropsychiatric diseases, with a rapid onset of therapeutic activity. Notably, phase II trials have shown that psilocybin can produce statistically significant clinical effects following one or two administrations in depression and anxiety. These findings have inspired a 'gold rush' of commercial interest, with nearly 60 companies already formed to explore opportunities for psychedelics in treating diverse diseases. Additionally, these remarkable phenomenological and clinical observations are informing hypotheses about potential molecular mechanisms of action that need elucidation to realize the full potential of this investigative space. In particular, despite compelling evidence that the 5-HT2A receptor is a critical mediator of the behavioural effects of psychedelic drugs, uncertainty remains about which aspects of 5-HT2A receptor activity in the central nervous system are responsible for therapeutic effects and to what degree they can be isolated by developing novel chemical probes with differing specificity and selectivity profiles. Here, we discuss this emerging area of therapeutics, covering both controversies and areas of consensus related to the opportunities and perils of psychedelic and psychedelic-inspired therapeutics. We highlight how basic science breakthroughs can guide the discovery and development of psychedelic-inspired medications with the potential for improved efficacy without hallucinogenic or rewarding actions.

keywords:
Humans, Lysergic Acid Diethylamide, Receptor, Serotonin, 5-HT2A, Hallucinogens, Mental Disorders, Psychiatry, Psilocybin

raw_json:
{"europe_pmc_id":"35301459","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review.
authors: Sarparast A, Thomas K, Malcolm B, Stauffer CS.
publication_date: 2022-03-06
doi: 10.1007/s00213-022-06083-y
pubmed_id: 35253070
source_url: https://doi.org/10.1007/s00213-022-06083-y
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
Rationale & objectives ± 3,4-Methylenedioxymethamphetamine (MDMA) and psilocybin are currently moving through the US Food and Drug Administration's phased drug development process for psychiatric treatment indications: posttraumatic stress disorder and depression, respectively. The current standard of care for these disorders involves treatment with psychiatric medications (e.g., selective serotonin reuptake inhibitors), so it will be important to understand drug-drug interactions between MDMA or psilocybin and psychiatric medications.MethodsIn accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we queried the MEDLINE database via PubMed for publications of human studies in English spanning between the first synthesis of psilocybin (1958) and December 2020. We used 163 search terms containing 22 psychiatric medication classes, 135 specific psychiatric medications, and 6 terms describing MDMA or psilocybin.ResultsForty publications were included in our systematic review: 26 reporting outcomes from randomized controlled studies with healthy adults, 3 epidemiologic studies, and 11 case reports. Publications of studies describe interactions between MDMA (N = 24) or psilocybin (N = 5) and medications from several psychiatric drug classes: adrenergic agents, antipsychotics, anxiolytics, mood stabilizers, NMDA antagonists, psychostimulants, and several classes of antidepressants. We focus our results on pharmacodynamic, physiological, and subjective outcomes of drug-drug interactions.ConclusionsAs MDMA and psilocybin continue to move through the FDA drug development process, this systematic review offers a compilation of existing research on psychiatric drug-drug interactions with MDMA or psilocybin.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Stress Disorders, Post-Traumatic, Psychotherapy, Drug Interactions, Adult, Psilocybin

topic_tags:
Depression,PTSD,Pharmacology,Receptor Pharmacology,Randomized Controlled Trial,Systematic Review,Review Article,Case Report,Drug Interactions

raw_json:
{"europe_pmc_id":"35253070","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Popik P, Hogendorf A, Bugno R, Khoo SY, Zajdel P, Malikowska-Racia N, Nikiforuk A, Golebiowska J.
publication_date: 2022-03-01
doi: 10.1007/s00213-021-06020-5
pubmed_id: 35234983
source_url: https://doi.org/10.1007/s00213-021-06020-5
keywords: Animals, Humans, Rats, Serotonin, Ketamine, Antidepressive Agents, Cognition, Male, Psilocybin
substance_tags: psilocybin,psilocin
topic_tags: Depression,Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
Effects of ketamine optical isomers, psilocybin, psilocin and norpsilocin on time estimation and cognition in rats.

abstract:
RationaleKetamine and psilocybin belong to the rapid-acting antidepressants but they also produce psychotomimetic effects including timing distortion. It is currently debatable whether these are essential for their therapeutic actions. As depressed patients report that the "time is dragging," we hypothesized that ketamine and psilocybin-like compounds may produce an opposite effect, i.e., time underestimation, purportedly contributing to their therapeutic properties.ObjectivesTiming was tested following administration of (R)- and (S)-ketamine, and psilocybin, psilocin, and norpsilocin in the discrete-trial temporal discrimination task (TDT) in male rats. Timing related to premature responses, and cognitive and unspecific effects of compounds were tested in the 5-choice serial reaction time task (5-CSRTT) in the standard 1-s, and "easier" 2-s stimulus duration conditions, as well as in the vITI variant promoting impulsive responses.Results(S)-ketamine (15 but not 3.75 or 7.5 mg/kg) shifted psychometric curve to the right in TDT and reduced premature responses in 5-CSRTT, suggesting expected time underestimation, but it also decreased the accuracy of temporal discrimination and increased response and reward latencies, decreased correct responses, and increased incorrect responses. While (R)-ketamine did not affect timing and produced no unspecific actions, it reduced incorrect responses in TDT and increased accuracy in 5-CSRTT, suggesting pro-cognitive effects. Psilocin and psilocybin produced mainly unspecific effects in both tasks, while norpsilocin showed no effects.ConclusionsTime underestimation produced by (S)-ketamine could be associated with its antidepressant effects; however, it was accompanied with severe behavioral disruption. We also hypothesize that behavioral disruption produced by psychedelics objectively reflects their psychotomimetic-like actions.

raw_json:
{"europe_pmc_id":"35234983","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Jaster AM, Elder H, Marsh SA, de la Fuente Revenga M, Negus SS, González-Maeso J.
publication_date: 2022-03-01
doi: 10.1007/s00213-022-06092-x
pubmed_id: 35233648
source_url: https://doi.org/10.1007/s00213-022-06092-x
substance_tags: psilocybin
topic_tags: Depression,Addiction,Pharmacology,Receptor Pharmacology,Animal Study,Safety
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Effects of the 5-HT2A receptor antagonist volinanserin on head-twitch response and intracranial self-stimulation depression induced by different structural classes of psychedelics in rodents.

abstract:
BackgroundClinical studies suggest that psychedelics exert robust therapeutic benefits in a number of psychiatric conditions including substance use disorder. Preclinical studies focused on safety and efficacy of these compounds are necessary to determine the full range of psychedelics' effects.ObjectivesThe present study explores the behavioral pharmacology of structurally distinct psychedelics in paradigms associated with serotonin 2A receptor (5-HT2AR) activation and behavioral disruption in two rodent models. Utilizing the selective 5-HT2AR antagonist volinanserin, we aimed to provide further pharmacological assessment of psychedelic effects in rodents.MethodsWe compared volinanserin (0.0001-0.1 mg/kg) antagonism of the phenethylamine 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1.0 mg/kg) and the ergoline lysergic acid diethylamide (LSD, 0.32 mg/kg) in preclinical assays predictive of hallucinations (head-twitch response or HTR in mice) and behavioral disruption (intracranial self-stimulation or ICSS in rats). Volinanserin antagonism of the phenethylamine mescaline, the tryptamine psilocybin, and the k-opioid receptor agonist salvinorin A was also evaluated in the rat ICSS assay.ResultsVolinanserin had similar potency, effectiveness, and time-course to attenuate DOI-induced HTR in mice and ICSS depression in rats. Volinanserin completely blocked LSD-induced HTR in mice, but not LSD-induced ICSS depression in rats. Volinanserin also reversed ICSS depression by mescaline, but it was only partially effective to reduce the effects of psilocybin, and it exacerbated ICSS depression by salvinorin A.ConclusionAlthough hallucination-related HTR behavior induced by phenethylamine, ergoline, and tryptamine psychedelics appears to be 5-HT2AR-mediated, the receptor(s) responsible for behavioral disruptive effects may differ among these three structural classes.

keywords:
Animals, Rodentia, Mice, Rats, Tryptamines, Serotonin, Phenethylamines, Mescaline, Fluorobenzenes, Lysergic Acid Diethylamide, Piperidines, Receptor, Serotonin, 5-HT2A, Hallucinogens, Depression, Self Stimulation, Psilocybin

raw_json:
{"europe_pmc_id":"35233648","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The therapeutic potential of psilocybin: a systematic review.
authors: van Amsterdam J, van den Brink W.
publication_date: 2022-03-01
doi: 10.1080/14740338.2022.2047929
pubmed_id: 35225143
source_url: https://doi.org/10.1080/14740338.2022.2047929
substance_tags: psilocybin
topic_tags: Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article,Safety,Adverse Events
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
IntroductionPsychedelic drugs were used quite extensively before their prohibition in 1968 which delayed research. However, since the 1990s, studies on the potential therapeutic benefits of psychedelics have rapidly increased.Areas coveredThis systematic review provides an overview of the clinical effects of psilocybin in the treatment of a variety of mental disorders. Only (randomized) clinical trials were selected. A total of 11 studies (15 publications) were selected, including seven randomized controlled trials (eight publications) and four single arm open-label studies (seven publications). In total, 488 patients were included in the selected studies: 333 patients treated with psilocybin and 155 patients treated with (active) placebo. In nine studies, psychotherapeutic support was provided as an integral part of the psilocybin treatment. The findings of these studies collectively show that psilocybin has a positive benefit-risk balance in the treatment of various mental disorders with an immediate and prolonged effect following 1-3 doses of psilocybin and a few (serious) adverse events.Expert opinionPsilocybin - mostly combined with psychotherapy or psychotherapeutic support - shows a promise as a treatment for various (treatment-resistant) mental disorders. Larger double-blind RCTs with objective (long-term) outcomes are needed to confirm these findings before standard clinical use of psilocybin can be considered.

keywords:
Humans, Hallucinogens, Double-Blind Method, Mental Disorders, Randomized Controlled Trials as Topic, Psilocybin

raw_json:
{"europe_pmc_id":"35225143","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Maia LO, Beaussant Y, Garcia ACM.
publication_date: 2022-02-10
doi: 10.1016/j.jpainsymman.2022.01.024
pubmed_id: 35157985
source_url: https://doi.org/10.1016/j.jpainsymman.2022.01.024
keywords: Humans, Lysergic Acid Diethylamide, Hallucinogens, Anxiety, Psilocybin
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
title:
The Therapeutic Potential of Psychedelic-assisted Therapies for Symptom Control in Patients Diagnosed With Serious Illness: A Systematic Review.

abstract:
ContextPeople affected by serious illness usually experience suffering in its various dimensions, not only in the physical but also in the psychosocial and spiritual aspects. The interest in psychedelic-assisted therapies as a potential new therapeutic modality has increased since evidence suggests a significant impact of their use on the outcomes of patients with serious illness.ObjectivesTo systematically review the available evidence on the effects of psychedelic-assisted therapies for symptom control in patients diagnosed with serious illness.MethodsThe protocol of this systematic review has been prepared according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. This review included randomized and non-randomized controlled trials published in peer-reviewed scientific journals. A comprehensive search for studies was carried out in the main scientific databases, including Web of Science, Scopus, Cochrane Library, PsycINFO, PubMed, CINAHL, and EMBASE. There were no limitations regarding the year or language of publication.ResultsThe sample was composed of 20 studies. The results suggest positive effects of psychedelic-assisted therapies for symptom control in patients diagnosed with serious illness, with considerable safety of use. Most studies have been conducted with lysergic acid diethylamide, psilocybin, and N,N-dipropyltryptamine in cancer patients. The adverse effects reported were of physical and/or psychological nature and of mild to moderate intensity, transient, and self-resolutive.ConclusionThe evaluated evidence suggests positive effects of psychedelic-assisted therapies for symptom control in patients diagnosed with serious illness, especially regarding symptoms of psychological and spiritual nature.

topic_tags:
Anxiety,Spirituality,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Cancer Patients,Safety

raw_json:
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authors: Müller F, Kraus E, Holze F, Becker A, Ley L, Schmid Y, Vizeli P, Liechti ME, Borgwardt S.
publication_date: 2022-01-24
doi: 10.1007/s00213-022-06066-z
pubmed_id: 35076721
source_url: https://doi.org/10.1007/s00213-022-06066-z
substance_tags: psilocybin
topic_tags: Clinical Trial,Healthy Volunteers
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Flashback phenomena after administration of LSD and psilocybin in controlled studies with healthy participants.

abstract:
BackgroundLSD and psilocybin are increasingly used in phase I trials and evaluated as therapeutic agents for mental disorders. The phenomenon of reoccurring drug-like experiences after the acute substance effects have worn off was described for both substances and especially attributed to LSD. According to the DSM-V, the persisting and distressing manifestation of these experiences is called hallucinogen-persisting perception disorder (HPPD). Data on both conditions is very limited.ObjectiveThis study aims to provide descriptive data on reoccurring drug-like experiences after the administration of LSD and psilocybin in controlled studies with healthy participants.Methods and materialsData from 142 healthy subjects enrolled in six double-blinded, placebo-controlled, randomized cross-over studies were analyzed. In total, 60 subjects received LSD; 27 subjects received LSD, MDMA, and D-amphetamine; 31 subjects received LSD and psilocybin; and 25 subjects received psilocybin and escitalopram. At the end-of-study visit (mean 39.8 days after last study session, SD37.2), subjects were asked for any reoccurring drug effects since the initial substance effects had worn off. Those reporting reoccurring perception changes more than 24 h after administration were contacted for follow-up (mean follow-up duration: 31.2 months, SD28.6).ResultsThirteen out of 142 subjects reported reoccurring drug-like experiences (LSD: seven, psilocybin: two, both: four). The reported phenomena were predominantly mild and perceived as neutral to pleasant. Flashbacks were mostly of visual nature, lasted for seconds to minutes, and occurred within a week after the last drug administration. Two subjects reported distressing experiences that subsided spontaneously. One subject reported brief and pleasant visual perception changes which reoccurred for 7 months. None of the subjects reported impairment in their daily lives. None of the cases met DSM-V criteria for HPPD.ConclusionReoccurring drug-like experiences after the administration of LSD and psilocybin are a common phenomenon occurring in up to 9.2% of healthy subjects (7.8% for LSD, 8.3% for psilocybin and 14.3% if both substances are administered). Additionally, our work suggests that flashback phenomena are not a clinically relevant problem in controlled studies with healthy participants.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Diagnostic and Statistical Manual of Mental Disorders, Healthy Volunteers, Psilocybin

raw_json:
{"europe_pmc_id":"35076721","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Miceli McMillan R, Jordens C.
publication_date: 2022-01-21
doi: 10.1007/s11019-022-10070-7
pubmed_id: 35064398
source_url: https://doi.org/10.1007/s11019-022-10070-7
keywords: Humans, Hallucinogens, Depression, Psychotherapy, Psilocybin, Major Depressive Disorder
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
title:
Psychedelic-assisted psychotherapy for the treatment of major depression: a synthesis of phenomenological explanations.

abstract:
Psychedelic-assisted Psychotherapy (PAP) combines the use of psychedelic compounds, such as psilocybin, with psychotherapy. PAP has shown some promise as a novel treatment for Major Depressive Disorder (MDD), and empirical research suggests that its efficacy turns on the altered states induced by psychedelic compounds. In this paper we draw on the literature of phenomenology to explain the therapeutic potential of psychedelic experiences. Svenaeus characterises mental illness as a form of suffering that entails three distinct but related experiences of alienation or "unhomelike being-in-the-world": (1) illness suffering, which relates to embodiment; (2) existential suffering, which relates to self-narratives, and (3) political suffering, which relates to social relationships. Ratcliffe further characterises the experience of MDD in phenomenological terms as a loss of pre-intentional possibility that manifests as excessive noematic feeling in the experience of embodiment, restrictive narratives in the construction of self, and disconnectedness in experience of the social world. We contend that PAP ameliorates the suffering associated with MDD by inducing and consolidating a state of broadened pre-intentional possibility-one that entails sudden, profound and enduring changes in embodiment, self-narratives, and social experience. We argue further that this phenomenological account is consistent with a bio-psycho-social model of mental health and illness, and we frame it as an argument supporting the plausibility of recent claims about treatment success. This helps to justify ongoing future empirical research in this setting.

raw_json:
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