# publications

publication_date: 2026-01-01
doi: 10.1186/s40359-025-03935-y
pubmed_id: 41484687
source_url: https://doi.org/10.1186/s40359-025-03935-y
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
The effects of psilocybin on psychological distress in cancer patients: a systematic review and meta-analysis.

authors:
Moshfeghinia R, Mostafavi S, Jazi K, Ghasemi AR, Khosravaninezhad Y, Narayanan S, Ahmadi J, Pasalar M.

abstract:
IntroductionPsilocybin may effectively treat psychological distress in cancer patients. A meta-analysis assessed its safety and effectiveness in this context.MethodsA comprehensive search across six databases (Scopus, PsycINFO, PubMed, Cochrane, CINAHL Complete, and Web of Science) was conducted to identify studies on psilocybin's effects on mental health in cancer patients up to November 2024. Both randomized and non-randomized trials were included, assessing anxiety, depression, and other mental outcomes at short-term (2-5 weeks) and long-term (6 months) follow-ups. Study quality was assessed using Cochrane tools, and statistical analyses were performed with Stata version 17.ResultsIn randomized controlled trials (RCTs), psilocybin significantly reduced depressive symptoms, with the Beck Depression Inventory (BDI) (standardized mean difference [SMD] = - 2.87, 95% confidence interval [CI]: - 3.99 to - 1.76, p

keywords:
Humans, Neoplasms, Hallucinogens, Depression, Anxiety, Randomized Controlled Trials as Topic, Psilocybin, Psychological Distress

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

raw_json:
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authors: Sancilio FD, Dariani M, Chavda P, Rajagopal HM, Tomlinson L.
publication_date: 2026-01-01
doi: 10.1080/02791072.2025.2607726
pubmed_id: 41482437
source_url: https://doi.org/10.1080/02791072.2025.2607726
substance_tags: psilocybin,psilocin
topic_tags: Anxiety,Pharmacology,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Daily Administration of Psilocin Mucate (L-130) Produces a Favorable Safety Profile and Anxiolytic Effects in Rodents Exposed to Chronic Unpredictable Mild Stress.

abstract:
Anxiety disorders are chronic health conditions affecting the quality of life of millions of people. Psilocin, the active moiety of psilocybin, provides an anxiolytic effect; however, when orally administered as psilocybin, it only offers a moderate level of bioavailability and less predictable pharmacokinetics, potentially making effects after absorption variable and increasing the risk of adverse hallucinations, depending on the dose. As such, we investigated a recently developed stable salt of psilocin, psilocin mucate (L-130), which delivers increased bioavailability and, thus, more precise control of therapeutic levels. We examined factors related to L-130's safety, as well as its effectiveness in addressing anxiety at a commonly used macro dose level, along with dosing schedules similar to those noted in the literature. Clinical assessments and blood analyses suggest psilocin mucate is safe and has no toxicological effects. Compared to vehicle controls, daily dosing of L-130 led to significant reductions in cortisol levels and improved performances on several anxiety-related behavioral tasks: the Elevated Plus Maze, the Open Field Test, and the Novel Object Recognition Task. However, weekly dosing did not generally produce significant results. Overall, daily dosing of L-130 was able to produce anxiolytic behaviors, but larger studies are needed to determine optimal doses and dosing schedules.

raw_json:
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title: Rural-Urban Disparities in Access to Interventional Psychiatry Treatments among VA Patients.
authors: Shiner B, DuFort V, Peltzman T, Watts BV.
publication_date: 2025-12-31
doi: 10.1037/rmh0000333
pubmed_id: 42267190
source_url: https://doi.org/10.1037/rmh0000333
substance_tags: psilocybin
topic_tags: Depression,PTSD,Veterans
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
abstract:
ObjectiveWhile tele-mental health has improved access to standard medication management and psychotherapy for rural Veterans, implementation of interventional psychiatry treatments will require in-person care, potentially leading to the exacerbation of rural-urban disparities in access to mental health care. We studied the availability of interventional psychiatry treatments, delivered clinically or in the context of a research trial, to rural and urban Veterans.MethodsWe used VA electronic medical record data to measure the use of electroconvulsive therapy (ECT), magnetic seizure therapy (MST), repetitive transcranial magnetic stimulation (rTMS), vagus nerve stimulation (VNS), deep brain stimulation (DBS), ketamine (infusion or nasal spray), stellate ganglion block (SGB), and medication-assisted psychotherapy (AP) protocols including 3,4-methylenedioxy-methamphetamine (MDMA)-AP and psilocybin-AP, as appropriate, for VA patients with major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) from 2017 through 2024. We compared treatment use in rural and micropolitan locations to use in urban locations.ResultsFew patients received any interventional psychiatry treatment across strata. The most common modalities were rTMS, ECT, SGB, DBS, and ketamine. The numbers receiving MST, VNS, MDMA-AP, and psilocybin-AP were too small to report in the micropolitan or rural cells. Micropolitan and rural patients had lower odds of receiving rTMS, ECT, SGB, DBS, and ketamine than urban patients. The largest disparities were for rTMS and ketamine.ConclusionsThere appear to be rural-urban disparities in the emerging field of interventional psychiatry, and the disparities are most pronounced for treatments that require repeated in-person visits such as rTMS and ketamine.

raw_json:
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title: Psychedelics: Future Therapeutics in Major Depression?
authors: Olivier B, Olivier JDA.
publication_date: 2025-12-31
doi: 10.1007/978-981-95-6872-7_25
pubmed_id: 42036582
source_url: https://doi.org/10.1007/978-981-95-6872-7_25
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Treatment-Resistant Depression,Adverse Events
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
abstract:
Major depressive disorder (MDD), including treatment-resistant depression (TRD), is a highly prevalent psychiatric disorder. MDD is associated with severe suffering, burden and large economical costs. Although various conventional antidepressant treatments are available, a large portion of depressed people does not or not adequately respond to the first-line treatments (mostly SSRIs and SNRIs) and a substantial part (ca, 30%) completely fails to respond, leading to TRD. The last two decades of intense research into new drugs for major depression and TRD has led to two lines of development, namely, Typical (or serotonergic) psychedelics (psilocybin, ayahuasca) and atypical (glutamatergic/NMDA) psychedelics (ketamine, esketamine). Both approaches, via a different entrance mechanism, have a fast (immediate) onset, combined with a long-lasting antidepressant action, which cannot be explained by long-term biological presence of the drug in the brain. The psychedelic drugs acutely initiate short-lasting CNS-induced side effects but also lead to activation of downstream cortical processes that underlie the 'lasting' antidepressant effects. In the present chapter, the clinical developments that have led to the marketing of psilocybin and esketamine for major depression disorders has been described. The emergence of fast onset antidepressants for major depression and treatment-resistant depression is a huge step forward in treating major psychiatric disorders. The acute psychotomimetic (psilocybin) or dissociative (esketamine) effects heavily interfere with performing of 'blind' studies, making proper placebo effects challenging. The development of new medicines that are acutely effective in depressive disorders is, however, a real breakthrough in psychiatry, but has also led to a spur of new research activities into new mechanisms involved, and also in developing new research techniques involved in designing proper research methodologies to bring this exciting field into adulthood.

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

raw_json:
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title: New Antidepressant Development in the Treatment of Depression.
authors: Spiti A, Caldirola D, Perna G.
publication_date: 2025-12-31
doi: 10.1007/978-981-95-6872-7_23
pubmed_id: 42036580
source_url: https://doi.org/10.1007/978-981-95-6872-7_23
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
Major depressive disorder (MDD) continues to pose a major therapeutic challenge due to its clinical heterogeneity. This chapter looks at the development of antidepressant treatments, starting with early interventions such as electroconvulsive therapy (ECT), monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). Although these treatments targeted the monoaminergic system, they had significant limitations in terms of safety and efficacy. The introduction of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) improved tolerability but left unmet needs, particularly in terms of treatment resistance and side effects. In response, research has expanded beyond monoamines and focused on new mechanisms. A breakthrough came with N-methyl-D-aspartate (NMDA) receptor antagonists such as ketamine and esketamine, which achieved fast-acting effects and shifted the focus to glutamatergic modulation. Other developments in this area include modulators such as partial agonists, positive allosteric modulators (PAMs), and negative allosteric modulators (NAMs). In addition, gamma-aminobutyric acid (GABA) modulation has gained attention, with neurosteroids such as zurolone (approved for postpartum depression [PPD]) representing a new therapeutic approach. Other new strategies target the opioid system, particularly kappa-opioid receptor (KOR) antagonism, whose role in the treatment of anhedonia and depression is being investigated. Psychedelics, including psilocybin, have come back into focus as potential treatments due to their ability to elicit rapid and sustained antidepressant effects via agonism of the serotonin 2A receptor (5-HT2A), although their efficacy and safety require further research. In addition, innovative treatments targeting orexin, trace amine-associated receptor 1 (TAAR1) and members of the Q subfamily of voltage-gated potassium channels (KCNQ) are also in development. Despite these advances, some challenges remain. These include diagnostic heterogeneity, incomplete understanding of neurobiological mechanisms, limitations of preclinical models, lack of reliable biomarkers, and economic obstacles. Future advances could be driven by artificial intelligence (AI), which has the potential to revolutionize drug discovery, optimize clinical trials, and personalize treatments for patients.

keywords:
Animals, Humans, Antidepressive Agents, Electroconvulsive Therapy, Drug Development, Major Depressive Disorder

topic_tags:
Depression,Addiction,Mechanism of Action,Receptor Pharmacology,Biomarkers,Clinical Trial,Animal Study,Safety,Adverse Events

raw_json:
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title: Contextualizing Violence Risk Associated With Hallucinogens.
authors: Durns T, Iannuzzi G.
publication_date: 2026-01-14
doi: 10.1176/appi.focus.20250027
pubmed_id: 41953889
source_url: https://doi.org/10.1176/appi.focus.20250027
substance_tags: psilocybin
topic_tags: Review Article,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
abstract:
Psilocybin, lysergic acid diethylamide (LSD), and 3,4-methylenedioxymethamphetamine (MDMA) have remerged as agents of psychiatric and cultural relevance. However, public discourse has outpaced empirical understanding of their effects. Although hallucinogens have demonstrated a potential to treat certain mental disorders, their effect on aggression and violence risk remains inconclusive. This article reviews the historical, medical, legal, and cultural contexts of these popular psychedelic and entactogenic compounds. The impact of substance type, dose, set and setting, psychiatric comorbidity, and environmental factors on violence is reviewed. Prevention and response strategies relevant to hallucinogenic compounds are discussed, including harm reduction, risk assessment, and treatment. Individual risk factors that mediate violence risk for people who consume psilocybin, LSD, and MDMA remain an area for further research.

raw_json:
{"europe_pmc_id":"41953889","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Classifying Psychedelic-Related Complications.
authors: Majić T, Gouzoulis-Mayfrank E, Evens R.
publication_date: 2025-12-31
doi: 10.1007/7854_2026_614
pubmed_id: 41749025
source_url: https://doi.org/10.1007/7854_2026_614
keywords: Humans, Hallucinogens
substance_tags: psilocybin
topic_tags: Addiction,Safety,Toxicity
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Classic psychedelics such as psilocybin, lysergic acid diethylamide (LSD), and 5-methoxy-dimethyltryptamine (5-MeO-DMT) have shown promising effects in the treatment of certain mental health conditions. Enthusiastic claims about their therapeutic potential have led to overly optimistic reactions in the media and the public, subsequently resulting in increased use outside of clinical contexts and a heightened rate of psychedelic-related complications. As psychedelics exhibit low toxicity and hardly any habit-forming potential, the typical risks and harms of these substances are often overlooked by mental health professionals and under-assessed in psychedelic research. Similar to the medical history of other psychoactive substances introduced as medicines such as opioids, cocaine, and benzodiazepines, awareness for psychedelic-related complications has emerged with delay. Psychedelics are characterized by a wide range of acute effects on the human psyche and by a particular temporal dynamic in which these effects unfold, including acute, subacute, and long-term effects. Knowledge of how psychedelic effects unfold is not only essential for their use in therapy but also for the understanding and management of risks and complications.Here we provide an overview of complications that may be associated with the use of classic psychedelics, drawing on historical and current classification approaches and using the typical temporal dynamics of drug effects as a guiding thread. We will also discuss to what extent psychedelic-related disorders can be causally and specifically attributed to psychedelic use. Finally, considerations regarding the placement of psychedelic-related disorders within nosological-diagnostic classification systems will be discussed. The increasing interest in using psychedelics within the framework of psychotherapy and the rise of non-medical use underscore the need for a more nuanced classification of psychedelic-related risks and harms. The suggested classification can be used as a comprehensive starting point for the assessment of psychedelic-related complications, contributing to maximizing benefits and minimizing risks of these substances in research, therapy, and beyond.

raw_json:
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title: Psychedelic-Related Psychosis: From Model Psychosis to Psychotherapy.
authors: Bröcker AL, Majić T, Montag C.
publication_date: 2025-12-31
doi: 10.1007/7854_2026_613
pubmed_id: 41749024
source_url: https://doi.org/10.1007/7854_2026_613
keywords: Humans, Psychoses, Substance-Induced, Hallucinogens, Psychotic Disorders, Psychotherapy
substance_tags: psilocybin
topic_tags: General
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Psychotic symptoms are uncommon and non-specific adverse effects of classic (serotonergic) psychedelics such as lysergic acid diethylamide (LSD), psilocybin, and mescaline. They can emerge during the acute phase of psychedelic drug effects, persist into the subacute ("afterglow") period, or, in rare cases, develop into long-term psychotic illness. Across all three scenarios, the symptoms can be deeply distressing due to their rapid changes, unpredictability, and significant adverse behavioral consequences.Psychedelics have a long history of use as research models for schizophrenia because of the phenomenological overlaps between their acute effects and the core symptoms of psychosis. This "model psychosis" paradigm, however, has been widely criticized: although certain acute symptoms may appear similar, the etiology and psychodynamic background of primary psychosis only partially apply to psychedelic-related psychosis. Moreover, it remains unclear whether psychotic symptoms following the use of classic psychedelics differ meaningfully from those associated with other substances, such as dopaminergic stimulants or cannabis.A transient porosity of ego boundaries is a core feature of acute psychedelic states, ranging from heightened feelings of connectedness with oneself and others to complete ego dissolution. These experiences are often perceived as positive and may be followed by a subacute phase characterized by sustained increases in openness to new experiences. In some cases, however, ego dissolution may become fear-inducing and progress from challenging but manageable experiences to paranoid psychotic reactions that require therapeutic guidance and intervention.In this chapter, we examine phenomenological similarities and differences between psychedelic-induced psychosis and primary psychosis. Consistent with current international diagnostic classification systems, we conclude that, with increasing temporal distance from the initial psychedelic "index" experience that predated the symptoms, persisting psychedelic-induced psychotic symptoms become indistinguishable from primary psychosis. Finally, we present a psychodynamic therapeutic approach for schizophrenia-spectrum psychosis that may, to some extent, be adapted to psychotic symptoms observed across all three phases of psychedelic drug effects.

raw_json:
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title: Magic mushrooms and mood: Exploring psilocybin as a depression treatment.
authors: Rasool M, Hannan TM, Imam M.
publication_date: 2025-12-31
doi: 10.47391/jpma.30858
pubmed_id: 41736353
source_url: https://doi.org/10.47391/jpma.30858
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
raw_json:
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title: Single-dose psilocybin promotes cell-type-specific changes of neurons in the orbitofrontal cortex.
authors: Huang Z, Wei X, Wang Y, Tian J, Dong J, Liang B, Lu L, Zhang W.
publication_date: 2026-01-30
doi: 10.1016/j.neurot.2026.e00841
pubmed_id: 41620327
source_url: https://doi.org/10.1016/j.neurot.2026.e00841
substance_tags: psilocybin,psilocin
topic_tags: Depression,Addiction,OCD,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Recent clinical breakthroughs hold great promise for the application of psilocybin in the treatments of psychological disorders, such as depression, addiction, and obsessive-compulsive disorder. Psilocybin is a psychedelic whose metabolite, psilocin, is a 5-HT2A receptor agonist. Nevertheless, the underlying mechanisms for the effects of psilocybin on the brain are not fully illustrated, and cell type-specific and circuit effects of psilocybin are not fully understood. Here, we combined single-nucleus RNA-seq with functional assays to study the long-term effects of psilocybin on the orbitofrontal cortex (OFC) of male mouse, a brain region vulnerable to psychological disorders such as depression. We found that a single dose of psilocybin induced long-term genetic and functional changes in neurons of the OFC, and the layer 5 pyramidal neurons showed the most significant changes. The layer 5 pyramidal neurons in the OFC showed reduced expressions of glutamate receptors and the gene expressions of multiple intercellular signaling pathways involved in the excitatory synapse formation and maintenance after psilocybin injection, which was consistent with the decreased excitatory synaptic transmission of these neurons. Meanwhile, both Parvalbumin- and Somatostatin-positive inhibitory neurons of the OFC showed meager changes after psilocybin injection. Furthermore, knockdown of 5-HT2A receptor in the layer 5 pyramidal neurons but not the Parvalbumin-positive inhibitory neurons abated psilocybin-induced functional changes and the anti-depressant effect. Together, these results showed the cell type-specific mechanisms of psilocybin and shed light on the brain region difference in the effect of psychedelics.

keywords:
Pyramidal Cells, Prefrontal Cortex, Neurons, Animals, Mice, Inbred C57BL, Mice, Receptor, Serotonin, 5-HT2A, Hallucinogens, Male, Serotonin 5-HT2 Receptor Agonists, Psilocybin

raw_json:
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title: Indigenous Knowledge Systems & Psychedelic Science: Towards Ethical and Reciprocal Collaboration.
publication_date: 2026-01-29
doi: 10.1177/02698811251387104
pubmed_id: 41618525
source_url: https://doi.org/10.1177/02698811251387104
keywords: Humans, Banisteriopsis, Hallucinogens, Cooperative Behavior
substance_tags: psilocybin
topic_tags: Spirituality,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
authors:
Magar V, Robbins M, Fernández Lobo Blanco ÓML, Ali IL, Anderson B, Grob C, Henningfield JE, Kryskow P, Kuiper H, Loizaga-Velder A, Rush B, Volat M, Iron Rope S.

abstract:
Indigenous Peoples have cultivated and protected natural psychoactive medicines through ceremony, kinship, and spiritual responsibility across generations, yet their long-standing contributions have often been marginalized through extractive research, commercialization, and policy exclusion. It is Indigenous communities that have stewarded and gained expertise working with psychoactive medicines for centuries, yet they remain underrepresented within the scientific discourse. This commentary advances the case for reciprocal and equitable collaboration in psychedelic science, grounded in Indigenous sovereignty, cultural and intellectual property rights, and governance. Drawing on traditions involving ayahuasca, psilocybin, peyote, and iboga, we illustrate how Indigenous methodologies, including ritual, community-based practices, and ecological approaches, offer insights critical to both safety and efficacy. We argue that research and policy must embed free, prior, and informed consent, equitable benefit-sharing, and Indigenous leadership. Such efforts require moving past tokenistic inclusion toward meaningful collaboration and systemic change in psychedelic research that is both scientifically rigorous and culturally just. We conclude by calling for more formal, transparent, and globally legitimate convening processes, such as those modeled on WHO global consultations, that can bring Indigenous leaders, researchers, and policymakers together in dialogue. These steps represent profound acts of inclusion essential for these medicines to realize their full potential to heal and transform.

raw_json:
{"europe_pmc_id":"41618525","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Freitas da Costa B, Hartmann P, Pagnin D.
publication_date: 2025-12-31
doi: 10.1002/hup.70032
pubmed_id: 41502021
source_url: https://doi.org/10.1002/hup.70032
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Pharmacological Management of Anxiety in End-of-Life Care: A Systematic Review of Benzodiazepines, Opioids, and Psilocybin.

abstract:
ObjectiveAnxiety is common in patients receiving end-of-life care and significantly impacts their quality of life. However, pharmacological management remains challenging due to complex clinical presentations and potential side effects, emphasizing the need for systematically reviewing existing treatments. Here we aim to systematically evaluate the efficacy and safety of pharmacological treatments for anxiety in end-of-life care.DesignSystematic review following PRISMA guidelines, prospectively registered in PROSPERO (CRD42024556913). Comprehensive searches were performed in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. Eligible studies included adults receiving end-of-life care and evaluated pharmacological interventions targeting anxiety.ResultsFive studies met inclusion criteria: two assessing benzodiazepines combined with opioids and three evaluating psilocybin. Both benzodiazepine-opioid combinations and psilocybin reduced anxiety symptoms. Psilocybin studies reported rapid and sustained anxiety relief, with approximately 60%-80% of participants experiencing clinically significant improvements. Both treatment categories showed good tolerability without serious adverse events. However, the evidence base was limited by small sample sizes and narrow study contexts.ConclusionsBenzodiazepine-opioid combinations and psilocybin show promise for anxiety relief in end-of-life patients. Nevertheless, limited high-quality evidence highlights an important research gap. Further robust clinical trials are needed to confirm these findings and guide clinical practice in palliative care.

keywords:
Humans, Benzodiazepines, Analgesics, Opioid, Anti-Anxiety Agents, Terminal Care, Anxiety, Psilocybin

topic_tags:
Anxiety,Addiction,End-of-Life Distress,Clinical Trial,Systematic Review,Review Article,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"41502021","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Advancing treatment paradigms: the role of psilocybin in managing major depressive disorder.
authors: Rasheed S, Arif R, Raza AA, Samadi A.
publication_date: 2025-11-24
doi: 10.1097/ms9.0000000000004349
pubmed_id: 41497122
source_url: https://doi.org/10.1097/ms9.0000000000004349
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Aging,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Psilocybin, a naturally occurring psychedelic compound, has received attention as a novel therapeutic option for major depressive disorder (MDD), particularly in cases where traditional treatments prove ineffective. The study aims to evaluate psilocybin's therapeutic potential by examining its efficacy, safety, and mechanisms of action as well as addressing the societal and regulatory challenges that hinder its broader application. Key objectives include understanding how psilocybin alleviates depressive symptoms, investigating its neurobiological effects, and identifying gaps in current research. The methodology involved analyzing clinical studies conducted between 2014 and 2024, focusing on psilocybin as an intervention, either independently or in conjunction with psychotherapy. Evidence from these studies demonstrates that psilocybin acts on serotonin 5-HT2A receptors, enhancing neuroplasticity and brain connectivity to yield rapid and sustained symptom relief. Despite these promising findings, the use and study of psilocybin remains restricted due to its classification as a Schedule I substance in many countries. Legal prohibitions and societal stigma have significantly delayed progress in exploring psilocybin's therapeutic applications. The findings highlight psilocybin's potential to transform MDD treatment paradigms but emphasize the need to overcome regulatory barriers, conduct larger and more diverse studies, and establish long-term safety and efficacy data. Addressing these challenges is critical for integrating psilocybin into mainstream mental health care and unlocking its full therapeutic potential.

raw_json:
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authors: Moghadam H, Akbari P, Beirami E, Nabavifard S, Ameli A, Valian N.
publication_date: 2025-12-31
doi: 10.1002/jnr.70107
pubmed_id: 41493855
source_url: https://doi.org/10.1002/jnr.70107
substance_tags: psilocybin,psilocin
topic_tags: Depression,Anxiety,Mechanism of Action,Oxidative Stress,Drug Interactions,Inflammation
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
The Effect of Magic Mushroom (Psilocybe azurescens) on Social Interaction, Anxiety- and Depressive-Like Behaviors in Male Rats; the Role of Neuroinflammation, Oxidative Stress, and Neurotrophic Factors.

abstract:
Psilocybin-containing mushrooms, commonly known as magic mushrooms, strongly affect mood, cognition, and behavior. Psilocybe azurescens is a species of psilocybin mushrooms that contains the main active compounds psilocybin and psilocin. Psilocybin mushrooms have been used since ancient times to improve the quality of life. However, their adverse effects have been less studied. This study aimed to investigate, for the first time, the effect of oral consumption of P. azurescens on social behavior, anxiety- and depressive-like behaviors in rats. The underlying mechanisms of these behaviors were also studied. Male Wistar rats received three doses of P. azurescens (10, 100, and 250 mg/kg) by gavage every other day for 14 days. Social interaction, anxiety- and depressive-like behaviors were assessed using the three-chamber, elevated plus maze, and forced swimming tests, respectively. Protein levels of neurotrophic (BDNF and GDNF), neuroinflammatory (IL-6 and TNFα), and oxidative stress (ROS and SOD) factors were measured in the hippocampus, prefrontal cortex (PFC), and amygdala by ELISA technique. The results showed that P. azurescens significantly increased anxiety- and depressive-like behaviors and disrupted social interaction behavior in rats. These effects were accompanied by increased neuroinflammation and oxidative stress and decreased neurotrophic factors in the hippocampus, PFC, and amygdala. This study suggests that the high doses of P. azurescens can cause mood disorders by increasing inflammatory responses and oxidative stress and decreasing the expression of neurotrophic factors.

keywords:
Animals, Rats, Rats, Wistar, Nerve Growth Factors, Behavior, Animal, Depression, Anxiety, Oxidative Stress, Male, Social Interaction, Neuroinflammatory Diseases

raw_json:
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authors: Maltby CJ, Klein AK, Paschen E, Pinto J, Dvorak D, Hedde JR, Hanks AN, Bianchi M, Hughes ZA.
publication_date: 2026-01-05
doi: 10.1177/02698811251395386
pubmed_id: 41493065
source_url: https://doi.org/10.1177/02698811251395386
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Biomarkers,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
An exploration of the relationships between the effects of psilocybin on behavior, 5-HT2A receptor occupancy, and neuroplastic effects in mice.

abstract:
BackgroundPsilocybin has shown rapid and sustained antidepressant effects in patients with major depressive disorder, yet the neurobiological mechanisms underlying these outcomes remain unclear.AimsThis study aimed to bridge clinical and preclinical findings by investigating the relationships between 5-HT2A receptor occupancy (RO) achieved after administration of psilocybin and its effects on behavior and markers of neuroplasticity in mice.MethodsIn vivo 5-HT2A RO was determined via displacement of [3H]MDL-100,907 in the prefrontal cortex (PFC). To relate RO with behavioral outcomes of psilocybin, we assessed the head twitch response (HTR) acutely and investigated behavior in the elevated zero maze (EZM) and forced swim test (FST) 20-24 hours post-drug. Neuroplastic changes were assessed by measuring α-tubulin post-translational modifications (PTMs) and expression of key synaptic proteins in both the PFC and amygdala.ResultsPsilocybin produced dose-dependent 5-HT2A RO (RO₅₀ = 0.88 mg/kg) and an inverted-U dose-response in HTR, with peak effects occurring between ~44% and 62% RO. Behaviorally, a 1.5 mg/kg dose increased the open areas ratio in the EZM, while 3 mg/kg reduced immobility in the FST, 20 and 24 hours after dosing, respectively. Both dose levels shifted α-tubulin PTMs toward a more dynamic microtubule state and selectively increased synaptic marker expression in the PFC, not in the amygdala.ConclusionsThese findings suggest that the therapeutic effects of psilocybin could be mediated by dose- and region-specific enhancement of neuronal plasticity, with distinct signatures associated with anxiolytic-like and antidepressant-like properties.

keywords:
Amygdala, Prefrontal Cortex, Animals, Mice, Inbred C57BL, Mice, Fluorobenzenes, Tubulin, Receptor, Serotonin, 5-HT2A, Hallucinogens, Antidepressive Agents, Behavior, Animal, Protein Processing, Post-Translational, Neuronal Plasticity, Dose-Response Relationship, Drug, Male, Psilocybin

raw_json:
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title: Perceptions of Psilocybin-Assisted Psychotherapy and Standard Interventions for Nicotine Cessation.
authors: Kamilar-Britt P, Oliva AB, Earleywine M.
publication_date: 2025-12-31
doi: 10.1080/02791072.2025.2607724
pubmed_id: 41479153
source_url: https://doi.org/10.1080/02791072.2025.2607724
substance_tags: psilocybin
topic_tags: Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Nicotine dependence remains a leading cause of preventable mortality worldwide. Pharmacotherapy and behavioral interventions offer modest efficacy with limited long-term success. Psilocybin-assisted psychotherapy (PAP) is an emerging approach to nicotine cessation with a growing evidence base. As PAP research expands, understanding how nicotine users' attitudes shape treatment engagement becomes critical. We surveyed daily nicotine users (N = 534) to assess their perceptions and attitudes toward PAP versus standard cessation interventions. Point-biserial correlations and multiple linear regressions examined predictors of treatment interest and credibility. Findings suggest that familiarity with treatment options predicts perceptions of credibility for both interventions (standard: β = 0.16, p

raw_json:
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authors: Dwyer J, Johnston RB, O'Callaghan C, Ross M.
publication_date: 2025-12-09
doi: 10.1016/j.genhosppsych.2025.12.002
pubmed_id: 41418682
source_url: https://doi.org/10.1016/j.genhosppsych.2025.12.002
substance_tags: psilocybin
topic_tags: Anxiety,End-of-Life Distress,Clinical Trial,Review Article,Healthcare Workers
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Stepping back into life: How Psychedelic Assisted Psychotherapy transforms the way of life of the terminally ill.

abstract:
This qualitative study of how successful Psychedelic Assisted Psychotherapy (PAP) transforms the way of life of terminally ill subjects provides new knowledge for researchers and clinicians contemplating its use. Using an interpretive phenomenological approach (IPA) and interviews with subjects before and after PAP from a recent randomised control trial, we find that participants with extreme death anxiety have become displaced from their own life, afraid and alone in an all-encompassing present. PAP can enable them to fully inhabit their life in a more abundant and joyful present, even in the face of death. The psilocybin component is found to be necessary but not sufficient for this achieving this outcome. These novel findings expand our conceptualisation of death anxiety and of the personal transformation that constitutes successful PAP. Clinical trial details Australian New Zealand Clinician Trials Registry. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378101&isReview=true registration: ACTRN12619001225101.

keywords:
Humans, Hallucinogens, Attitude to Death, Anxiety, Psychotherapy, Qualitative Research, Adult, Aged, Middle Aged, Terminally Ill, Female, Male, Psilocybin

raw_json:
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authors: Matos ARS, Silva AC, Rego L, Fernandes R, Gonçalves S.
publication_date: 2025-12-17
doi: 10.1177/02692163251383335
pubmed_id: 41410211
source_url: https://doi.org/10.1177/02692163251383335
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocybin-assisted therapy for individuals with palliative care needs: A systematic review of safety and efficacy.

abstract:
BackgroundPalliative Care is concerned with relieving suffering and improving the quality of life of patients and their families. Currently, questions arise about how to provide patients with good end-of-life care. There has been increasing interest in the beneficial effects of using psilocybin-assisted therapy in patients with severe chronic illnesses near the end of their lives and who present symptoms of depression and/or anxiety.AimExplore the role of psilocybin-assisted therapy in palliative care, synthesizing evidence from clinical trials and longitudinal studies.DesignSystematic review.Data sourcesA bibliographic search was performed in April 2024 in B-on, PubMed, Web of Science, and Scopus. Eligible studies included peer-reviewed quantitative research (RCTs, longitudinal, and observational designs) with adult participants in palliative care settings, examining the efficacy and safety of psilocybin-assisted therapy. Reviews, gray literature, and studies outside the scope of palliative care were excluded.ResultsOf the 215 articles found, six studies (n = 74 participants; age range 22-75 years) met the inclusion criteria. Across randomized and open-label trials, psilocybin-assisted therapy produced clinically significant reductions in depression and anxiety, with 57-79% of participants achieving ⩾ 50% symptom reduction on standardized scales (e.g. HAM-D, HAM-A, BDI, STAI). Improvements were sustained for up to 6-8 months in most trials, and in one follow-up study, for up to 4.5 years. Reported adverse effects were generally mild and transient, including nausea, vomiting, and temporary increases in blood pressure and heart rate; no serious adverse events were observed.ConclusionsPsilocybin-assisted therapy consistently demonstrated efficacy and safety in the reduction of depressive and anxiety symptoms. However, more studies exploring integrating psilocybin-assisted therapy into existing palliative care healthcare systems are needed. This includes investigating the feasibility, acceptability, and cost-effectiveness of integrating psilocybin-assisted therapy into routine clinical practice.

keywords:
Humans, Hallucinogens, Palliative Care, Depression, Anxiety, Quality of Life, Adult, Aged, Middle Aged, Female, Male, Young Adult, Psilocybin

topic_tags:
Depression,Anxiety,End-of-Life Distress,Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article,Observational Study,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"41410211","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin in late-life mental health: Addressing depression, loneliness, and existential anxiety.
authors: Konstantinou GN, Rosenblat J, Hales S, Husain MI, Blumberger DM.
publication_date: 2025-12-08
doi: 10.1016/j.genhosppsych.2025.12.005
pubmed_id: 41401486
source_url: https://doi.org/10.1016/j.genhosppsych.2025.12.005
keywords: Humans, Hallucinogens, Depression, Anxiety, Loneliness, Existentialism, Aging, Aged, Psilocybin
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
The global demographic shift toward aging populations has intensified the need for innovative therapeutic interventions targeting late-life mental health conditions, notably depression, loneliness, and existential distress. Traditional pharmacological treatments often exhibit limited efficacy and poor tolerability in older patients, primarily due to age-related physiological changes and the challenges associated with polypharmacy. Recently, psychedelic-assisted therapy, particularly psilocybin, has gained attention for its potential antidepressant and psychological benefits. This comprehensive review critically evaluates the current evidence supporting psilocybin's effectiveness in older populations and elucidates its neurobiological mechanisms, including serotonergic modulation, enhanced neuroplasticity, and the disruption of maladaptive default mode network activity. Clinical trials in general adult samples demonstrate sustained improvements in depressive symptoms, existential anxiety, and social connectedness following psilocybin administration, suggesting its distinct therapeutic potential beyond conventional treatments. However, geriatric populations are underrepresented in psychedelic research, creating significant knowledge gaps regarding dosing, safety profiles, and long-term outcomes. Pharmacokinetic complexities, cardiovascular risks, and drug interactions necessitate age-specific therapeutic protocols. Ethical considerations, including the complexities of informed consent in cases of cognitive impairment, further underscore the importance of tailored approaches. Future directions must prioritize dedicated geriatric studies that incorporate rigorous safety assessments and integrate findings into existing geriatric care frameworks to fully assess the potential of psilocybin for enhancing late-life mental health and quality of life.

topic_tags:
Depression,Anxiety,Neuroplasticity,Pharmacology,Mechanism of Action,Default Mode Network,Aging,Clinical Trial,Review Article,Safety,Drug Interactions

raw_json:
{"europe_pmc_id":"41401486","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Effects of psychedelic microdosing on cognitive functions: A systematic review and meta-analysis.
authors: Pinhas N, Eidlman N, Barnea A, Peled-Avron L.
publication_date: 2025-11-25
doi: 10.1016/j.neubiorev.2025.106493
pubmed_id: 41314362
source_url: https://doi.org/10.1016/j.neubiorev.2025.106493
keywords: Humans, Lysergic Acid Diethylamide, Hallucinogens, Cognition, Executive Function, Psilocybin
substance_tags: psilocybin
topic_tags: Consciousness,Microdosing,Meta-Analysis,Systematic Review,Review Article
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
abstract:
Microdosing - the practice of consuming extremely low doses of classical psychedelic substances that do not elicit overt psychedelic effects - has gained significant attention as a potential method for enhancing cognitive performance. However, findings from controlled studies remain mixed and inconclusive. This preregistered meta-analysis examined the cognitive effects of classical psychedelic microdosing in 14 different studies (N = 1614), analyzing 59 effect sizes across multiple cognitive domains, spanning both acute (on-drug) and post-acute (off-drug) assessments. Results show a significant decrease in cognitive control, with no detectable effects on other cognitive domains or in general. Neither substance type (psilocybin or LSD), dosage (0.1-0.5 g psilocybin; 6.5-20 µg LSD), nor microdosing duration (1-42 days) emerged as significant moderators. Assessment timing (on- vs. off-drug) likewise did not moderate the effects. These findings suggest that microdosing may disrupt top-down cognitive control processes, aligning with cognitive and neural models of how classical psychedelics alter information processing in the brain to reduce rigidity and enable more fluid states of consciousness. However, better distinguishing between on-drug and off-drug effects is essential for clarifying whether microdosing exerts only transient pharmacological influences or promotes lasting cognitive change. Given the methodological heterogeneity across studies, future research using standardized protocols and mechanistic approaches is needed to fully characterize the cognitive and neural effects of microdosing classical psychedelics.

raw_json:
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authors: Hutchison KE, Hooper JF, Karoly HC.
publication_date: 2025-12-31
doi: 10.1001/jamapsychiatry.2025.3038
pubmed_id: 41191341
source_url: https://doi.org/10.1001/jamapsychiatry.2025.3038
keywords: Humans, Hallucinogens, Public Health, Adult, United States, Psilocybin
substance_tags: psilocybin
topic_tags: Clinical Trial,Review Article,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocybin Outside the Clinic: Public Health Challenges of Increasing Publicity, Accessibility, and Use.

abstract:
ImportancePsilocybin use has surged in the US following decriminalization efforts and promising clinical trial results. Mirroring early cannabis legalization, public access and enthusiasm are outpacing regulatory oversight and scientific understanding, posing potential risks to public health.ObjectiveTo review emerging evidence on the public health implications of unregulated psilocybin mushroom use, including trends in use, product variability, co-use with other substances, and age-related differences in outcomes.Evidence reviewSources included peer-reviewed articles, national surveillance data (eg, poison control center reports), and publicly available chemical testing data from decriminalized jurisdictions. The review emphasizes epidemiological and pharmacological findings published between January 1, 2014, and December 31, 2024, with attention to parallels from cannabis legalization research. Studies were selected based on relevance to nonclinical psilocybin use, product composition, adverse outcomes, and co-use patterns.FindingsPsilocybin mushroom use has sharply increased in the US, particularly among adults aged 19 to 50 years, with more than 7 million individuals reporting use in the past year. This trend has coincided with a substantial increase in poison control center calls related to psychedelics. Testing data from decriminalized regions indicate more than 20-fold variability in psilocybin potency and inconsistent levels of minor tryptamines across mushroom strains. Clinical trial data on synthetic psilocybin do not generalize to public use due to strict participant selection and controlled environments. Co-use with cannabis is common and may increase the risk of adverse events. Evidence also suggests that age may moderate both risks and benefits.Conclusions and relevanceThe expanding use of unregulated psilocybin mushrooms, combined with high variability in composition and common co-use with other substances, raises urgent public health concerns. Existing clinical data are insufficient to guide harm reduction or policy. There is a pressing need to pivot from controlled efficacy trials to real-world research on psilocybin use, including public education, potency testing, and age-specific risk assessment.

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publication_date: 2025-10-15
doi: 10.1177/02698811251378512
pubmed_id: 41099491
source_url: https://doi.org/10.1177/02698811251378512
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
A novel psychedelic 5-HT2A receptor agonist GM-2505: The pharmacokinetic, safety, and pharmacodynamic profile from a randomized trial healthy volunteer.

authors:
Marek GJ, Makai-Bölöni S, Umbricht D, Christian EP, Winters J, Dvorak D, Raines S, Hughes ZA, Austin EW, Klein AK, Leong W, Krol FJ, Graaf AJV, Juachon MJ, Otto ME, Borghans LGJM, Jacobs G, Kruegel AC, Sporn J.

abstract:
BackgroundThe treatment of major depressive disorder (MDD) with available antidepressant drugs is characterized by considerable ineffectiveness. Classical psychedelics such as psilocybin and N,N-dimethyltryptamine (DMT), which act primarily as 5-hydroxytryptamine 2A (5-HT2A) receptor agonists, have shown preliminary efficacy for inducing long-term remission in MDD after one or two doses. GM-2505 is a novel, 5-HT2A receptor agonist, developed for treating MDD.MethodsIn this single-ascending dose, randomized, placebo-controlled, double-blind study, we characterized GM-2505's safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) profile in 48 healthy participants.ResultsSingle intravenous (IV) doses up to 20 mg demonstrated an acceptable safety profile of mild transient adverse events, short-term, non-clinically significant increases in blood pressure and pulse, and no significant changes in electrocardiographs, consistent with other 5-HT2A receptor agonists. In general, GM-2505 Cmax and AUClast increased dose proportionally, with t1/2 of 40-50 minutes. Generally, dose-dependent effects were observed for neuroendocrine hormones, several neuropsychological and neurophysiological measures, and subjective drug effects. Dose-related effects were also observed in resting-state electroencephalography (rsEEG), with decreased power in the low frequency rsEEG bands (theta and alpha), and increased in the high frequency bands (slow and fast gamma).ConclusionsThese PD findings were similar in nature and magnitude to other 5-HT2A receptor agonists that have been studied clinically. In line with the GM-2505 PK profile, the duration of cardiovascular and subjective effects was shorter than psilocybin but longer than DMT, demonstrating a potentially more practical temporal profile for use in a supervised clinical setting compared to longer-acting 5-HT2A receptor agonists, with an optimal dose range of 10-15 mg IV. Clinical trial (ISRCTN64428072) registration: https://www.isrctn.com/ISRCTN64428072.

keywords:
Humans, Receptor, Serotonin, 5-HT2A, Hallucinogens, Double-Blind Method, Blood Pressure, Dose-Response Relationship, Drug, Adolescent, Adult, Middle Aged, Female, Male, Young Adult, Serotonin 5-HT2 Receptor Agonists, Healthy Volunteers, Major Depressive Disorder

topic_tags:
Depression,Brain Imaging,Pharmacology,Receptor Pharmacology,Clinical Trial,Randomized Controlled Trial,Healthy Volunteers,Adolescents,Safety,Adverse Events

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authors: Heal DJ, Gosden J, Smith SL.
publication_date: 2025-10-15
doi: 10.1177/02698811251382147
pubmed_id: 41099474
source_url: https://doi.org/10.1177/02698811251382147
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Review Article,Abuse Liability
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Mind the gap! Addressing unresolved aspects of abuse potential evaluation and scheduling of classic and novel psychedelic drugs.

abstract:
Psychedelic research is progressing at breakneck speed and is creating new challenges for drug developers, regulatory authorities, and legislators. Most "classic" psychedelics undergoing clinical investigation are C-I controlled drugs with perceived high potential for abuse and no medical use. These and next-generation psychedelic drug-candidates require scientific and clinical assessment of their abuse and dependence potential before transitioning into a controlled drug schedule assigned to clinically approved drugs (C-II to C-V). Food and Drug Administration is likely to undertake the first regulatory assessment of a "classic" psychedelic, and it has led in disseminating advice on how to address the clinical and regulatory challenges. We have built on this foundation by discussing areas of abuse and dependence evaluation procedures that remain unclear or have not previously been covered. Psychedelic drug-candidates can be classified into three categories, that is, "classic" (well-known compounds including psilocybin, N,N-dimethyltryptamine and lysergic acid diethylamide) and "novel" psychedelics (e.g., analogues of known psychedelics), and located between them is what we describe as "grey area" psychedelics (e.g., non-hallucinogenic 5-HT2A agonists). In this review, we set out clear proposals for categorizing psychedelic drug-candidates, describe the development pathway and abuse/dependence testing procedures appropriate to each, and, finally, offer our perspective on how these drugs will be evaluated and scheduled under the auspices of the U.S. Controlled Substances Act. Although we used the United States as a test case, the principles and analyses we used and the screening framework for assessing the abuse potential of psychedelic drug-candidates are universally applicable and can be easily adapted to the regulatory requirements and procedures in other countries.

keywords:
Animals, Humans, Substance-Related Disorders, Hallucinogens, United States Food and Drug Administration, United States

raw_json:
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authors: Hirschfeld T, Blei F, Stegemann L, van der Gouwe D, Smit-Rigter L.
publication_date: 2025-12-31
doi: 10.1007/7854_2025_606
pubmed_id: 41087826
source_url: https://doi.org/10.1007/7854_2025_606
substance_tags: psilocybin
topic_tags: Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Psychedelic Drug Checking: Analytical and Strategic Challenges in Harm Reduction for Classic Psychedelics.

abstract:
Classic psychedelics such as LSD, psilocybin, and DMT from unregulated markets pose considerable risks through unknown adulterants and potencies. In this chapter, we explore the importance of drug checking in minimizing harm among users of classic psychedelics and examine the opportunities and challenges associated with intervention settings, analytical techniques, and risk communication strategies. Gas chromatography (GC) and liquid chromatography (LC) coupled with mass spectrometry (MS) provide the most reliable and comprehensive analysis results for classic psychedelics. However, they are relatively costly, stationary, and require legal permission to obtain reference standards. Combined presumptive tests, such as thin-layer chromatography (TLC) and reagent testing, offer a time-efficient and cost-effective approach to initial substance screening. For certain compounds, Fourier-transform infrared spectroscopy (FTIR) serves as a valuable complementary technique, although potent psychedelics, such as LSD and NBOMe on blotter paper or in diluted solution, and complex botanical matrices challenge its detection limit, requiring the use of multiple analytical methods to confirm results. Such combination can effectively prevent acute risks, while confirmatory instrumental analysis remains essential for ongoing monitoring and public health efforts. Alongside robust testing procedures, drug checking's consultative component is crucial for clarifying analytical constraints, promoting safer use practices, and offering referrals to health services. By identifying mislabeled samples and ensuring tailored risk communication, drug checking not only protects individual users but also informs the public and health professionals regarding dangerous or novel substances. This chapter situates drug checking as a key public health measure that reduces acute harm from misrepresented psychedelic substances while supporting monitoring efforts.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Substance Abuse Detection, Harm Reduction, Drug Contamination, Psilocybin

raw_json:
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publication_date: 2025-08-28
doi: 10.1177/02698811251362390
pubmed_id: 40883964
source_url: https://doi.org/10.1177/02698811251362390
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Investigating the safety and tolerability of single-dose psilocybin for post-traumatic stress disorder: A nonrandomized open-label clinical trial.

authors:
McGowan NM, Rucker JJ, Yehuda R, Agrawal M, Modlin NL, Simmons H, Tofil-Kaluza A, Das S, Goodwin GM.

abstract:
BackgroundPost-traumatic stress disorder (PTSD) is a debilitating condition for which there are few efficacious treatments. Psilocybin is being studied for use in treatment-resistant depression but has not yet been investigated in PTSD.AimsThe trial's primary outcome was to investigate the safety and tolerability of single-dose psilocybin in participants with PTSD.MethodsThis was a Phase 2, nonrandomized, open-label, multicenter trial. Secondary outcomes were changes in PTSD symptoms (Clinician-Administered PTSD Scale for DSM-5 (CAPS-5); PTSD Checklist for DSM-5 (PCL-5)), functional impairment (Sheehan Disability Scale; SDS) and quality of life (EQ-5D-5L index score).ResultsAmongst the 22 participants enrolled (63.6% female; mean (SD) age, 39.0 (7.91) years), there was a total of 117 treatment-emergent adverse events (TEAEs); 70 (59.8%) were reported on administration day, of which 64/70 (91.4%) resolved by the end of the next day. TEAEs commonly included headache (n = 11; 50.0%), nausea (n = 8; 36.4%), crying (n = 6; 27.3%) and fatigue (n = 6; 27.3%). There were no serious TEAEs or TEAEs leading to study withdrawal. Pre-post comparisons indicated a clinically meaningful change from Baseline in mean CAPS-5 total score at Week 4 (-29.9 (14.06)) and Week 12 (-29.5 (15.43)), which was associated with the intensity of psychedelic experience on Day 1. PCL-5 scores showed symptom reduction was rapid and sustained until Week 12. SDS total score and EQ-5D-5L index score showed similar improvements.ConclusionsPsilocybin at a dose of 25 mg, administered with psychological support, may be safe, well-tolerated and associated with symptomatic improvement in adults with PTSD. Further investigation is warranted.Clinical trial registrationClinicalTrials.gov Identifier: NCT05312151(https://clinicaltrials.gov/study/NCT05312151).

keywords:
Humans, Hallucinogens, Treatment Outcome, Stress Disorders, Post-Traumatic, Quality of Life, Adult, Middle Aged, Female, Male, Psilocybin

topic_tags:
Depression,PTSD,Headache / Migraine,Clinical Trial,Treatment-Resistant Depression,Healthcare Workers,Safety,Adverse Events

raw_json:
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authors: Higgins GA, MacMillan C, de Lannoy I, Tyler C, Slassi M.
publication_date: 2025-08-26
doi: 10.1177/02698811251361453
pubmed_id: 40862395
source_url: https://doi.org/10.1177/02698811251361453
substance_tags: psilocybin,psilocin
topic_tags: Receptor Pharmacology,Observational Study,Animal Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Pharmacological characterisation of psilocybin and 5-MeO-DMT discriminative cues in the rat and their translational value for identifying novel psychedelics.

abstract:
Background and aimsDrug discrimination procedures have made important contributions to the pre-clinical investigation of psychedelic drugs, such as psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). One of the most important being to highlight the critical role of central 5-HT2A receptor agonism as a mediator of hallucinogenic activity, and secondly, drugs that fully generalise to a 5-HT2A receptor agonist cued drug discrimination in rodents, may elicit hallucinogenic activity in humans, showing a forward translational value. However, there is relatively little information about how clinical exposures associated with hallucinations back-translate to generalisation profiles in the rat.MethodsThe present series of experiments utilised two cohorts of male Sprague-Dawley rats, one trained to a psilocybin (0.5 mg/kg SC) cue, and the second trained to a 5-MeO-DMT (1 mg/kg SC) cue.ResultsTests of substitution and antagonism supported the primary role of 5-HT2A and 5-HT1A receptors, respectively, in the mediation of each cue. Plasma exposures of psilocin required for generalisation to the psilocybin cue (5-52 ng/mL) overlapped with clinical exposures associated with perceptual effects in humans. With respect to DMT and LSD, higher exposures were required in the rat compared to humans. Time-course studies using an approximate ED90 dose of each psychedelic showed differing temporal profiles in terms of duration of drug-lever generalisation, with LSD > psilocybin > 5-MeO-DMT ⩾ DMT, showing good agreement with clinical experience. With the exception of LSD, there was a good temporal association between plasma exposure and drug lever generalisation. The disconnect noted for LSD is mirrored by similar findings in the clinic.ConclusionsIn summary, the present studies both support and extend the value of the drug discrimination assay as a translational approach to the pre-clinical study of psychedelic drugs.

keywords:
Animals, Humans, Rats, Rats, Sprague-Dawley, N,N-Dimethyltryptamine, Methoxydimethyltryptamines, Lysergic Acid Diethylamide, Receptor, Serotonin, 5-HT2A, Hallucinogens, Cues, Dose-Response Relationship, Drug, Male, Serotonin 5-HT2 Receptor Agonists, Psilocybin, Discrimination, Psychological, Translational Research, Biomedical

raw_json:
{"europe_pmc_id":"40862395","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: The International journal on drug policy
publication_date: 2025-12-31
doi: 10.1016/j.drugpo.2025.104938
pubmed_id: 40803962
source_url: https://pubmed.ncbi.nlm.nih.gov/40803962/
keywords: Harm reduction, Psilocybin, Psychedelics, Qualitative research, Standards of care
substance_tags: psilocybin
topic_tags: Addiction,Safety
study_type: Qualitative Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"40803962"}
title:
Building standards of psychedelic care: Qualitative examination of expert perspectives on safety, inclusion, and accountability.

authors:
Chwyl C, Wilson-Poe AR, Hoffman KA, Bazinet A, Pertl K, Luoma JB, des Jarlais D, Bielavitz S, Korthuis PT

abstract:
There remain significant gaps in knowledge about best practices for facilitated psychedelic care and psychedelic-assisted therapy. To inform the development of service models that support safe and beneficial experiences, this qualitative study explored expert perspectives on current and ideal standards of care, including key practices (e.g., screening, adapting care to diverse contexts) and regulatory and research challenges that influence service delivery. Online focus groups (n = 8) were conducted with a purposive U.S. sample of people with psychedelic content knowledge expertise, including providers (psychiatrists, clinical psychologists, addiction medicine experts, and licensed/unlicensed practitioners) and harm reduction specialists. Transcripts were analyzed through Thematic Analysis team-based coding using a combined inductive-deductive approach within a semantic framework. Participants (N = 38, mean age 47 (SD = 10) years, 53 % women, 84 % white) had an average of 10 years of psychedelic service experience (SD = 11) across diverse settings, including festivals/events, service centers, and clinical, research, ceremonial, community and 'underground' contexts. Five key themes emerged: (1) 'Strengthening Safety through Credibility and Accountability'; (2) 'Advancing Culturally Responsive and Inclusive Psychedelic Care'; (3) 'Healing in Community: The Crucial Role of Ongoing Support and Integration'; (4) 'Ensuring Safe Psychedelic Use: Preparation, Screening, Vulnerability, and Medication Management'; and (5) 'Providing Informed Guidance and Navigating Legal and Informational Gray Areas.' Overall, results underscore the need for stronger provider accountability structures, culturally inclusive practices, accessible and integrated community support, robust safety and screening protocols, and clearer guidelines to help providers navigate legal complexities, ensure safety, and optimize outcomes across diverse populations.


title: Toward Standardized Products Containing Biomass of Psilocybe Cubensis Fungi.
authors: Foster K, Morrison I, Daniel S, Antoine J, Thankappan B, De La Haye W, Tyler M, Grant C, Delgoda R.
publication_date: 2025-12-31
doi: 10.1093/jaoacint/qsaf072
pubmed_id: 40802522
source_url: https://doi.org/10.1093/jaoacint/qsaf072
substance_tags: psilocybin,psilocin
topic_tags: Wellbeing,Clinical Trial,Healthcare Workers
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
BackgroundThe consumption of dried fruiting bodies of Psilocybe cubensis can be traced over centuries, guided by Mesoamerican curanderas, Western medical practitioners, and fungal enthusiasts, all seeking mental wellbeing. There is a notable resurgence in interest both in the fungal biomass and psilocybin, the psychoactive tryptamine, despite the global regulatory restrictions, following enlistment in the UN convention on psychotropic substances.ObjectivesTo evaluate consistency in psilocybin potency and to determine levels of microbial, pesticidal, and heavy metal content in products encompassing biomass of uniformly cultivated P. cubensis.MethodsIn a legally sanctioned, unique laboratory in Jamaica, we cultivated P. cubensis according to published methods, then dried, pulverized, extracted, and tested fruiting bodies for tryptamine content using an Agilent HPLC1290 Infinity assembly. Colony counting was employed for E. coli, yeast, mold, and coliform presence, while a Neogen's Veratox® ELISA assay assessed mycotoxin content. Agilent GCMS and LC assemblies evaluated for pesticidal content while heavy metals (As, Cd, Pb, Hg) were determined using instrumental neutron activation analysis (INAA), energy-dispersive X-ray fluorescence (ED-XRF, and direct mercury analysis (DMA) by thermal decomposition-amalgamation-atomic absorption spectrometry (TDA-AAS), respectively.ResultsMean psilocybin and psilocin content in dried cultivated P. cubensis was 1.14 ± 0.17% by weight; however, there was batch variability, potentiating significant differences in projected dosage, particularly for and above 3 g. The homogenized biomass was deemed safe, with acceptable levels of microbial, mycotoxin, pesticidal, and heavy metal contents, and no significant carcinogenic or other health hazards. Encapsulated biomass stably maintained tryptamine content for 11 months.ConclusionsStandardized, safe biomass suitable for human consumption can be achieved using P. cubensis cultivated under stringent, aseptic conditions. Given the observed variability, it is highly recommended that each batch is tested for tryptamine content. Our results may be useful for policymakers, cultivators, clinicians, and consumers.HighlightsThe present study provides a basis for regular potency testing of P. cubensis biomass and substantiates their potential use in clinical trials as a high-quality, standardized, and safe product.

keywords:
Fungi, Metals, Heavy, Tryptamines, Chromatography, High Pressure Liquid, Biomass, Psilocybe, Psilocybin

raw_json:
{"europe_pmc_id":"40802522","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Prostko S, Wu A, Maddams S, Szpak V, Rosenblum N, Hilt LM, Suzuki J.
publication_date: 2025-05-27
doi: 10.1097/adm.0000000000001517
pubmed_id: 40433994
source_url: https://doi.org/10.1097/adm.0000000000001517
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 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Attitudes Toward Psychedelic Treatments by Individuals With Histories of Substance Use or Psychiatric Disorders: A Survey Study.

abstract:
ObjectivesPsychedelics may be promising treatments for substance use disorders (SUD). This study aims to understand how individuals with alcohol use disorder (AUD), opioid use disorder (OUD), and psychiatric disorders perceive and experience psychedelics for both nonmedical and medical use.MethodsData for this cross-sectional survey study were collected from June 2023 to February 2024 at a large, tertiary hospital through the hospital's patient portal, inpatient floors, and flyers. English-speaking adults with AUD, OUD, and psychiatric disorders were recruited. The response rate was 1.9% and the cooperation rate was 13.7%. The survey collected participants' demographic information, substance use treatment and history, and perceived risks and harms associated with psychedelics and psychedelic treatment.ResultsOf 192 participants surveyed, 66% had previously tried psychedelics, 72.4% believed psychedelics could help patients with SUD or psychiatric disorders, and 69.8% said they would personally try psychedelic-assisted treatment for a SUD or psychiatric condition. Participants were significantly more likely to want to try psychedelic treatment for their own SUD or psychiatric disorder if they had previously used psilocybin (90.0% vs. 47.8%, P

keywords:
Humans, Substance-Related Disorders, Alcoholism, Opioid-Related Disorders, Hallucinogens, Cross-Sectional Studies, Health Knowledge, Attitudes, Practice, Mental Disorders, Adult, Middle Aged, Female, Male, Young Adult, Surveys and Questionnaires

raw_json:
{"europe_pmc_id":"40433994","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Windsor C, Kreynes AE, Chilton JS, Chioffi WA, Niebergall C, Dodds K.
publication_date: 2025-12-31
doi: 10.1093/jaoacint/qsaf007
pubmed_id: 39960890
source_url: https://doi.org/10.1093/jaoacint/qsaf007
keywords: Agaricales, Mycelium, Psychotropic Drugs, Chromatography, Thin Layer, Psilocybe, Psilocybin
substance_tags: psilocybin,psilocin
topic_tags: Addiction
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Development of Psilocybe Mushroom Species Reference Material-Cultivation Parameters and Chemical Profiles.

abstract:
BackgroundPsilocybin-containing mushrooms are gaining the attention of the scientific community due to the potential benefits offered by their psychoactive phytochemicals in the treatment of addiction and various mental health conditions. Although there are hundreds of different Psilocybe species, only a handful have been successfully cultivated under indoor controlled conditions and chemically analyzed.ObjectiveThe goal of this publication is to describe Nammex's ongoing effort to cultivate poorly studied Psilocybe mushroom species and analyze them by high-performance thin-layer chromatography (HPTLC) to identify and quantify important psychoactive compounds.MethodsPure mycelium cultures of Psilocybe species were created from spore prints and tissue of mushrooms collected in the wild. From these mycelia, numerous cultivars were developed and then propagated on various substrates, based on nutritionally supplemented cellulosic materials. Using indoor growth chambers under strictly controlled conditions, mushrooms were produced and prepared for analysis.ResultsSix Psilocybe species (P. zapotecorum, P. natalensis, P. azurescens, P. subaeruginosa, P. cyanescens, and P. stuntzii) were successfully cultivated indoors. Species identity was confirmed through analysis of anatomical and microscopic features, as well as by DNA sequencing. HPTLC was successfully used to quantify psilocybin and psilocin and to identify norbaeocystin, baeocystin, and aeruginascin. P. zapotecorum had the highest psilocybin content (1.89%), and P. stuntzii the lowest (0.45%). Preliminary data showed that psilocybin concentrations remained stable across three successive flushes of P. stuntzii. Storage of fresh mushrooms in a -20 °C freezer prior to freeze-drying drastically reduced psilocybin and increased psilocin levels.ConclusionsThis study successfully demonstrated the cultivation and chemical profiling of multiple Psilocybe species under controlled conditions. The detailed HPTLC analysis revealed species-specific differences in psychoactive compound concentrations. Future research will incorporate advanced techniques, such as HPLC and mass spectrometry, to develop a more comprehensive chemical profile of these mushrooms.HighlightsThis study successfully cultivated and chemically analyzed six Psilocybe species, revealing species-specific differences in psychoactive compound concentrations. Storage conditions, differences between stem and cap, and mushroom developmental stage influenced the composition of psychoactive compounds.

raw_json:
{"europe_pmc_id":"39960890","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Informed Consent in Psychedelic-Assisted Therapy.
authors: Bradberry MM, Appelbaum PS, Gukasyan N.
publication_date: 2025-12-31
doi: 10.1007/7854_2024_559
pubmed_id: 39739178
source_url: https://doi.org/10.1007/7854_2024_559
keywords: Humans, Hallucinogens, Informed Consent
substance_tags: psilocybin
topic_tags: Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
abstract:
Humans have long used classical serotonergic psychedelics, such as psilocybin, for a variety of purposes. Entactogens, such as methylenedioxymethamphetamine (MDMA), emerged during the twentieth century and have likewise seen use in a broad range of settings. Interest has arisen in the use of classical psychedelics and entactogens, together termed "psychedelics," for therapeutic purposes in Western clinical settings. Care in these settings is governed by standards for the communication and assumption of risk in the process of informed consent. Rigorous informed consent standards in psychedelic medicine are not only essential for quality care but also critical to the mitigation of risk, particularly in research settings and for vulnerable individuals. This chapter describes practical elements of informed consent in psychedelic therapy, with a focus on effective communication of the risks and potential benefits of classical psychedelic and entactogen treatments as they are currently understood.

raw_json:
{"europe_pmc_id":"39739178","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-12-09
doi: 10.1177/02698811241303594
pubmed_id: 39655749
source_url: https://doi.org/10.1177/02698811241303594
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Psychedelics as an intervention for psychological, existential distress in terminally ill patients: A systematic review and network meta-analysis.

authors:
Marchi M, Farina R, Rachedi K, Laonigro F, Žuljević MF, Pingani L, Ferrari S, Somers M, Boks MPM, Galeazzi GM.

abstract:
BackgroundThe interest in psychedelics as a therapeutic intervention for existential distress of people with terminal illness grounds on their mechanism of action and effect on the spiritual/existential aspects accompanying end-of-life experiences.AimsThis systematic review and network meta-analysis aimed at examining the efficacy and safety of psychedelic compounds for existential distress in terminally ill people.MethodsPubMed, CINAHL, PsycINFO, EMBASE, and clinicaltrials.gov were searched for randomized controlled trials (RCTs) administering psychedelics for existential distress in people with terminal illnesses. Meta-analysis estimated the standardized mean difference (SMD) and odds ratio (OR), with corresponding 95% confidence intervals (95% CI), between treated and control groups in pairwise and network comparisons, using random-effects models. Post-treatment measures of depression and anxiety, as proxies of existential distress, and tolerability were the primary outcomes.ResultsNine studies, involving 606 participants (362 treated with psychedelics: psilocybin, ketamine, 3,4-methylenedioxymethamphetamine, and lysergic acid diethylamide (LSD)) were included. The meta-analysis supported the efficacy of psychedelics on depression (SMD: -0.80 (95% CI: -0.98, -0.63)) and anxiety (SMD: -0.84 (95% CI: -1.20, -0.48)). Network meta-analysis identified psilocybin as the most effective compound for depression, and LSD for anxiety. However, head-to-head comparison between psychedelics did not reach statistical significance. The rates of treatment discontinuation and adverse events between psychedelics and controls were comparable.ConclusionsPsychedelics, especially psilocybins and LSD, showed promising effects on depression and anxiety in people with terminal illnesses. Limitations include the small number of RCTs, methodological issues related to blinding, and the lack of direct comparisons between psychedelic compounds. Larger studies and comparative research are needed to consolidate these findings.

keywords:
Humans, Hallucinogens, Depression, Stress, Psychological, Anxiety, Terminally Ill, Randomized Controlled Trials as Topic, Psychological Distress, Network Meta-Analysis as Topic

topic_tags:
Depression,Anxiety,End-of-Life Distress,Mechanism of Action,Spirituality,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"39655749","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Syed OA, Petranker R, Fewster EC, Sobolenko V, Beidas Z, Husain MI, Lake S, Lucas P.
publication_date: 2024-11-05
doi: 10.1080/02791072.2024.2424284
pubmed_id: 39503411
source_url: https://doi.org/10.1080/02791072.2024.2424284
substance_tags: psilocybin
topic_tags: Microdosing,Wellbeing,Observational Study,Adolescents
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Global Trends in Psychedelic Microdosing: Demographics, Substance Testing Behavior, and Patterns of Use.

abstract:
Despite psychedelic microdosing being a growing practice, the research on the topic is still in its infancy. While several studies have described the characteristics, motivations and practices of microdosers, the differences between individuals that only microdose and those that use both micro and macrodoses of psychedelics remain unexplored. In an online survey, we collected data of 6193 psychedelic consumers of which 2488 were microdosers of up to 11 different classical and atypical psychedelics. In comparison to respondents that use both microdoses and macrodoses, exclusive microdosers were older in age (46.4 vs. 42.0 years), had a larger proportion of females (68.4% vs. 44.7%), were non-Caucasian (25.4% vs. 14.7%), urban residents (43.9% vs. 38.5%), and had a lower average lifetime use of non-psychedelic substances (3.8 vs. 4.7 substances). Most consumers (52.5%) microdosed psychedelics multiple times a month, commonly using psilocybin (74.5%), LSD (34.4%), and ketamine (15.8%), with most users (64.6%) not testing their substances. The most common reason for microdosing was improving general wellbeing (73.0%), and psychedelics were used for treating several physical and mental health conditions. Additional analyses examined spending habits of consumers. This study adds to the growing literature on the naturalistic use of psychedelic microdosers.

keywords:
Humans, Substance-Related Disorders, Hallucinogens, Substance Abuse Detection, Adolescent, Adult, Middle Aged, Female, Male, Young Adult, Surveys and Questionnaires

raw_json:
{"europe_pmc_id":"39503411","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Masking Influences: A Systematic Review of Placebo Control and Masking in Psychedelic Studies.
authors: Barstowe A, Kajonius PJ.
publication_date: 2024-11-05
doi: 10.1080/02791072.2024.2424272
pubmed_id: 39503404
source_url: https://doi.org/10.1080/02791072.2024.2424272
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
Psychedelic-assisted therapy is becoming increasingly acknowledged as an effective therapeutic intervention for various psychiatric illnesses. However, the evaluation of masking success is rarely reported in trials. The objective of the present systematic review was to evaluate placebo-control and masking in studies exploring psychedelic-assisted therapy. Nine (k = 9) studies dating between January 2010 and March 2023 were retrieved using six databases, following strict inclusion and exclusion criteria. The results show that almost 78% of the studies had, at best, "poor" masking success. At the same time, 60% of active placebo and 75% of inactive placebo studies showed large effect sizes. In other words, masking influences, including benign unmasking, cannot be excluded. We therefore conclude that efficacy of psilocybin, Ayahuasca, or LSD is only one of the possible interpretations of large, positive changes in symptomatology for patients suffering from, for example, alcohol use disorder, anxiety with or without life-threatening disease, anxiety and/or depression with life-threatening cancer, treatment-resistant depression or major depressive disorder. We recommend care be taken to increase successful masking procedures and discuss alternative treatment designs to better control for potential masking influences.

keywords:
Humans, Banisteriopsis, Lysergic Acid Diethylamide, Hallucinogens, Mental Disorders, Placebo Effect, Psilocybin

topic_tags:
Depression,Anxiety,Addiction,End-of-Life Distress,Systematic Review,Review Article,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"39503404","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-10-30
doi: 10.1177/02698811241287542
pubmed_id: 39480198
source_url: https://doi.org/10.1177/02698811241287542
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Psilocybin for major depressive disorder: An updated systematic review and meta-analysis of randomized clinical trials.

authors:
Aghajanian S, Shafiee A, Parvizi Omran S, Rezaei Nejad A, Jafarabady K, Kohandel Gargari O, Rajai S, Mohammadi I, Bahrami Babaheidari T, Bakhtiyari M.

abstract:
BackgroundDue to the unsatisfactory therapeutic effects of current antidepressants, research has been launched into alternative treatment approaches, such as the administration of psychedelics. Psilocybin, a classic hallucinogen, has been shown to exert considerable positive influence on depression symptoms through its serotonergic and glutamatergic effects. This systematic review and meta-analysis aimed to evaluate the effectiveness of psilocybin in treating depression.MethodsA comprehensive search of Medline (via PubMed) and the Cochrane Library databases was conducted to identify relevant studies. Inclusion criteria were applied to select studies that investigated the therapeutic impact of psilocybin on depression. A mixed-effects multi-level model was used to estimate the overall effect size. Effectiveness over time was also investigated as a secondary analysis.ResultsThe results of the primary analysis revealed a large and clinically observable reduction (SMC: -1.24, 95%CI: -1.83 to -0.65, I2level2 = 11.39%, I2level3 = 77.67%) of depressive symptomatology in patients receiving psilocybin in addition to supportive therapy compared to baseline measurements. The decrease was also marked when compared to placebo (p-value = 0.032). The results remained significant even when a secondary analysis assessed the effect in various time intervals since the administration of psilocybin.ConclusionThis systematic review and meta-analysis substantiate the claim that psilocybin is superior in treating depression compared to established psychotherapy alone used for treating depression. This finding warrants further studies with larger sample sizes and across a longer timeframe.

keywords:
Humans, Hallucinogens, Antidepressive Agents, Treatment Outcome, Randomized Controlled Trials as Topic, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,Clinical Trial,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article

raw_json:
{"europe_pmc_id":"39480198","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Anxiety and Affective Symptoms Related to the Use of Classic Psychedelics: A Systematic Review.
authors: Viljoen G, Betzler F
journal: Current topics in behavioral neurosciences
publication_date: 2025-12-31
doi: 10.1007/7854_2024_534
pubmed_id: 39436632
source_url: https://pubmed.ncbi.nlm.nih.gov/39436632/
keywords: Affective disorders, Anxiety, Depression, LSD, Psilocybin, Psychedelics
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Emotional Processing,Systematic Review,Review Article,Safety
study_type: Systematic Review
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"39436632"}
abstract:
There is a large and rapidly growing body of literature investigating the therapeutic effects of classic psychedelics in affective and anxiety disorders, but very few studies have examined the inverse of this, that is, the potential for psychedelics to inflict anxiety and affective symptoms. A systematic literature search was performed and 39 papers were included in the final review to qualitatively synthesize the current literature on anxiety and affective disorders related to the use of classic psychedelics. Persisting disorders were less frequent but generally occurred in individuals who presented with several risk factors (overdose, polydrug use, unstructured recreational setting, psychosocial stress, personal/familial psychiatric histories). When psychedelics were administered in clinical studies under the framework of psychedelic-assisted therapy, the incidence of enduring anxiety and affective symptoms was low. In most cases, acute transient anxiety emerged and resolved during the dosing session without the need for additional treatment interventions. The nuance of such cases is discussed, shedding light on the role of emotional catharsis in the therapeutic process. Several suggestions are proposed to enhance patient safety including strengthening the therapeutic alliance, ensuring adequate mental preparation, acclimating to high doses and providing on-going therapeutic support.


title: Mechanisms of psilocybin on the treatment of posttraumatic stress disorder.
authors: Choi C, Johnson DE, Chen-Li D, Rosenblat J.
publication_date: 2024-10-02
doi: 10.1177/02698811241286771
pubmed_id: 39360403
source_url: https://doi.org/10.1177/02698811241286771
keywords: Animals, Humans, Hallucinogens, Stress Disorders, Post-Traumatic, Psilocybin
substance_tags: psilocybin
topic_tags: PTSD,Pharmacology,Mechanism of Action
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
abstract:
Posttraumatic stress disorder (PTSD) is a condition that can develop after a traumatic event, causing distressing symptoms, including intrusive re-experiencing symptoms, alterations in mood and cognition, and changes in arousal and reactivity. Few treatment options exist for patients who find conventional psychotherapy and pharmacotherapy to be inaccessible, ineffective, or intolerable. We explore psilocybin as a potential treatment option for PTSD by examining the neurobiology of PTSD as well as psilocybin's mechanism of action. Based on both pharmacodynamic and psychoanalytic principles, psilocybin may be an underexplored treatment option for patients with PTSD, though further research is required.

raw_json:
{"europe_pmc_id":"39360403","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Pharmacological Properties of Psychedelics with a Special Focus on Potential Harms.
authors: Holze F, Liechti ME, Müller F.
publication_date: 2025-12-31
doi: 10.1007/7854_2024_510
pubmed_id: 39080236
source_url: https://doi.org/10.1007/7854_2024_510
keywords: Animals, Humans, Tryptamines, Hallucinogens
substance_tags: psilocybin
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Psychedelics are a group of substances within the heterogeneous class of hallucinogenic drugs. Via binding to the serotonin (5-HT) 2A receptor, psychedelics exert profound alterations in various mental domains, including sensation, cognition, emotions, and self-perception. Psychedelics comprise phenethylamines (e.g., mescaline), tryptamines (e.g., psilocybin), and ergolines (e.g., LSD). These drugs have been used recreationally for decades but have also regained attention as potential treatments for various psychiatric as well as neurological illnesses. While psychedelics are generally considered to be relatively safe from a physiological standpoint, especially when compared to other recreational drugs, they are not without risks. The main safety concerns are lasting psychological adverse reactions such as persisting anxiety, dissociation, or flashbacks.This chapter provides a comprehensive overview of the pharmacology of classic psychedelics, including their origins, psychological and autonomic effects, interactions, and potential risks and side effects. Furthermore, the origin, dosing, and consumption methods are discussed. It differentiates psychedelics from other psychoactive drugs, such as MDMA and ketamine, and elaborates on their distinct receptor profiles. Overall, this chapter provides an overview of the pharmacological underpinnings necessary for understanding the harms caused by psychedelic drugs.

topic_tags:
Anxiety,Pharmacology,Receptor Pharmacology,Emotional Processing,Safety,Adverse Events,Drug Interactions

raw_json:
{"europe_pmc_id":"39080236","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Toxicology and Pharmacological Interactions of Classic Psychedelics.
authors: Thomas K.
publication_date: 2025-12-31
doi: 10.1007/7854_2024_508
pubmed_id: 39042251
source_url: https://doi.org/10.1007/7854_2024_508
keywords: Animals, Humans, Lysergic Acid Diethylamide, Hallucinogens, Drug Interactions, Psilocybin
substance_tags: psilocybin
topic_tags: Toxicity,Drug Interactions
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
abstract:
As psychedelics are being investigated for more medical indications, it has become important to characterize the adverse effects and pharmacological interactions with these medications. This chapter will summarize what is known about the toxicology and drug-drug interactions for classic psychedelics, such as LSD, psilocybin, DMT, 5-MeO-DMT, mescaline, 2C-B, Bromo-DragonFLY, and 25X-NBOMe.

raw_json:
{"europe_pmc_id":"39042251","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-12-31
source_url: https://europepmc.org/article/AGR/IND609383879
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocybin: clinical potential, mechanistic insights, and biotechnological advances for scalable production

authors:
Islas-Vargas J, Armenta S, Rivera-Román ÁA, Hernández-León S, Méndez-Hernández JE, Arce-Cervantes O.

abstract:
Psilocybin, a tryptamine-derived alkaloid from Psilocybe mushrooms, has emerged as a high-value biopharmaceutical candidate due to its promising applications in mental health. While clinical studies highlight its rapid and sustained antidepressant effects, current challenges lie in achieving scalable, reproducible, and cost-effective production to meet growing research and therapeutic demand. Traditional extraction from fungal biomass yields low concentrations and requires extensive downstream processing, limiting industrial viability. Chemical synthesis ensures purity but is hindered by high costs and multistep complexity. In contrast, biotechnological approaches have demonstrated significant progress toward sustainable production. Heterologous expression of psilocybin biosynthetic genes in Saccharomyces cerevisiae and Aspergillus nidulans has enabled improved metabolic flux and precursor availability, reaching titers over 200 mg/L under optimized conditions. Moreover, recent engineering Escherichia coli strains has further enhanced catalytic efficiency of key enzymes such as PsiH, achieving production levels up to 2000 mg/L, while simplifying fermentation and purification workflows. These advances establish microbial platforms as a promising route for industrial-scale biosynthesis. Beyond production, psilocybin offers an opportunity to integrate biotechnology with socio-cultural context. In regions where diversity of Psilocybe species and ancestral knowledge converge, the development of biotechnological pipelines could foster innovation in drug discovery, sustainable manufacturing, and policy reform. Overall, psilocybin exemplifies a frontier molecule in biotechnology, where metabolic engineering, synthetic biology, and bioresource valorization converge to transform a natural product into a reproducible, scalable, and globally relevant therapeutic.

raw_json:
{"europe_pmc_id":"IND609383879","source":"AGR","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Dominiak M, Gędek A, Modrzejewski S, Permoda-Pachuta A, Antosik AZ.
publication_date: 2025-12-28
doi: 10.3390/jcm15010253
pubmed_id: 41517502
source_url: https://doi.org/10.3390/jcm15010253
substance_tags: psilocybin
topic_tags: Depression,PTSD,Addiction,Randomized Controlled Trial,Review Article,Safety,Adverse Events
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Efficacy and Safety of Psychedelics in Mental Disorder Cases: An Umbrella Review of Meta-Analyses of Randomized Controlled Trials.

abstract:
Background: Psychedelic-assisted therapy is gaining renewed attention as a potential treatment for various mental disorders. Despite increasing numbers of randomized controlled trials (RCTs) and meta-analyses, a comprehensive synthesis of the evidence across different substances and indications is lacking. This umbrella review aims to evaluate the effectiveness and safety of psychedelic-assisted therapy-primarily psilocybin, MDMA, and LSD-across major psychiatric disorders, including depression, post-traumatic stress disorder (PTSD), and substance use disorders. Methods: We systematically identified and synthesized data from 23 meta-analyses encompassing over 100 primary studies. Outcomes were standardized and re-expressed as Hedges' g to enable cross-study comparisons. Study quality was assessed using AMSTAR2, and certainty of evidence was evaluated via the GRADE framework. Results: The number of identified meta-analyses differed markedly depending on the substance and clinical indication: psilocybin for depression (n = 9) and MDMA for PTSD (n = 10) had the strongest evidence base, while fewer meta-analyses were available for LSD in alcohol use disorder (n = 2) and depression (n = 2), ayahuasca in depression (n = 2), and MDMA in autism spectrum disorder (n = 2). Psilocybin demonstrated large effect sizes in major depression (Hedges' g ≈ 1.05), with some evidence of sustained benefits up to six months. MDMA showed very large effects in reducing PTSD symptoms (Hedges' g ≈ 1.24), often after 2-3 sessions. LSD yielded short-term benefits for alcohol use disorder (OR ≈ 2.0), though effects declined over time. Across studies, adverse events were generally mild and transient, with no consistent signal for serious harm. Considerable methodological variability was observed, including small and sometimes overlapping samples, heterogeneity, risk of bias, and limited long-term data. These constraints should be taken into account when interpreting the overall findings. Conclusions: Current evidence supports the short-term efficacy and safety of psychedelic-assisted therapy for selected psychiatric disorders, particularly depression and PTSD. However, the low methodological quality of studies and most meta-analyses, as well gaps in long-term safety data highlight the need for high-quality studies.

raw_json:
{"europe_pmc_id":"41517502","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Afsharnia S, Liang V, Lunsky Y, Orsini AP, Tint A, Lin HY.
publication_date: 2025-12-25
doi: 10.1371/journal.pmen.0000514
pubmed_id: 41662127
source_url: https://doi.org/10.1371/journal.pmen.0000514
substance_tags: psilocybin
topic_tags: Depression,PTSD,Clinical Trial,Observational Study,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Knowledge, perceptions, and use of psychedelics for mental health among autistic adults: An online survey.

abstract:
Psychedelics such as psilocybin, LSD, and MDMA have shown promise in treating mental health conditions (e.g., depression, post-traumatic stress disorder) among neurotypical individuals, i.e., typically developing individuals without a diagnosed neurodevelopmental condition. However, their therapeutic potential for treating co-occurring mental-health conditions in autistic individuals remains under-explored. Autistic individuals often face co-occurring mental health challenges but are frequently excluded from clinical trials, creating a gap in effective treatments. This study aimed to explore knowledge, perceptions, and experiences of autistic adults regarding psychedelics. In this survey, "psychedelics" included classical psychedelics such as psilocybin and LSD, as well as MDMA. A cross-sectional online survey was conducted with English-speaking autistic adults. We assessed participants' knowledge of psychedelics, willingness to use them for mental health treatment, and any past psychedelic experiences. Data were analyzed using descriptive statistics and chi-square tests to assess group differences. A total of 424 participants began the survey, with 261 completing it. Nearly half resided in Canada. Participants generally viewed psychedelics positively, with 77.8% expressing a willingness to try them, and 69.7% reported past use-most commonly psilocybin mushrooms. Higher doses and highly meaningful experiences correlated with longer-lasting mental health improvements. Barriers included legal concerns, health risks, and logistical challenges. Participants with prior experience reported greater perceived knowledge and lower perceived risks. Autistic adults in this self-selecting sample demonstrated strong interest in psychedelics as potential treatments for mental health, despite significant barriers to access and research participation. These results highlight the importance of considering education, policy reform, and inclusive research practices to ensure that autistic people have opportunities to explore psychedelic therapies. These findings should be interpreted cautiously, as the sample may not be representative of the broader autistic population. Future trials should optimize dosing and explore long-term benefits of psychedelics in this population.

raw_json:
{"europe_pmc_id":"41662127","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin-induced modulation of visual salience processing.
authors: Muller S, Cavanna F, de la Fuente LA, Bruno N, D'Amelio TA, Pallavicini C, Tagliazucchi E.
publication_date: 2025-12-25
doi: 10.1093/nc/niaf060
pubmed_id: 41458361
source_url: https://doi.org/10.1093/nc/niaf060
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Psychedelic compounds significantly reshape conscious perception, yet the implications of these alterations for complex visual-guided behaviors remain poorly understood. We investigated how psilocybin modulates visual salience processing during natural scene perception. Twenty-three participants completed eye-tracking tasks under self-blinded low and high doses of psilocybin, in a naturalistic design with experimental conditions unknown to participants and researchers. Subjects viewed natural scenes while their gaze patterns were recorded and analyzed in relation to normative computational saliency maps generated using a deep learning model of visual attention. Results revealed increased fixation on salient image regions and reduced inter-fixation distance under the high-dose condition, suggesting heightened sensitivity to visual salience and more localized gaze behavior. The Shannon entropy of fixations on high-saliency regions indicated a more exploratory and less predictable visual scanning of the images. Complementary resting-state electroencephalography recordings showed broadband spectral power reductions and increased Lempel-Ziv complexity, with delta power negatively correlating with salience metrics. These findings indicate that psilocybin induces a shift in attentional dynamics, altering gaze behavior, and salience processing during natural scene perception.

raw_json:
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title: Psychedelics as a Therapeutic Opportunity or Threat: A Narrative Review.
publication_date: 2025-12-22
doi: 10.7759/cureus.99942
pubmed_id: 41583322
source_url: https://doi.org/10.7759/cureus.99942
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
authors:
Liszka P, Ogórek A, Olejnik-Chlewicka KM, Puchalski K, Zasiadła M, Patrzykąt KM, Perediatkiewicz J, Urbański W, Łuczak PM, Brodowski J.

abstract:
Classic psychedelics and related substances, such as 3,4-methylenedioxymethamphetamine (MDMA), have again become a focus of interest in psychiatry as potential therapeutic tools. The aim of this paper is to review current data on their mechanisms of action, clinical applications in the treatment of mood and anxiety disorders, addictions and post-traumatic stress disorder (PTSD), as well as to assess safety, drug interactions and long-term complications. Studies indicate that psychedelics act mainly through stimulation of 5-hydroxytryptamine 2A (5-HT2A) receptors, induction of neuroplastic changes and modification of functional brain networks, which may facilitate changes in entrenched cognitive and emotional patterns. Randomized clinical trials with psilocybin have shown a rapid and sustained reduction of depressive symptoms, including in populations with treatment-resistant depression and cancer patients, as well as promising results in the treatment of alcohol use disorders. MDMA, when combined with psychotherapy, has demonstrated substantial therapeutic potential in the treatment of PTSD. The literature indicates that particular caution is required when using these substances in therapy because of the risk of acute and chronic adverse reactions and potential drug interactions, including with serotonergic agents and monoamine oxidase inhibitors (MAOIs). The available findings confirm a substantial, though still only partly explored, therapeutic potential of classic psychedelics and MDMA. At the same time, they emphasize the need for strict control of "set and setting", careful patient selection, further multicentre studies with greater statistical power and longer follow-up before these interventions can be incorporated into routine clinical practice.

topic_tags:
Depression,Anxiety,PTSD,Addiction,Mechanism of Action,Receptor Pharmacology,Emotional Processing,Clinical Trial,Review Article,Cancer Patients,Treatment-Resistant Depression,Safety,Drug Interactions

raw_json:
{"europe_pmc_id":"41583322","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Pargament KI.
publication_date: 2025-12-21
doi: 10.1177/28314425251406613
pubmed_id: 41869009
source_url: https://doi.org/10.1177/28314425251406613
substance_tags: psilocybin
topic_tags: Spirituality
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Psilocybin, Spirituality, and the Potential for Personal Transformation: Commentary on Effects of Psilocybin on Religious and Spiritual Attitudes and Behaviors in Clergy from Various Major World Religions by Griffiths et al.

raw_json:
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authors: de Wit H.
publication_date: 2025-12-21
doi: 10.1177/28314425251409219
pubmed_id: 41869008
source_url: https://doi.org/10.1177/28314425251409219
substance_tags: psilocybin
topic_tags: Spirituality
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Effects of Psilocybin on Religious and Spiritual Attitudes and Behaviors in Clergy from Various Major World Religions, by Griffiths et al.

raw_json:
{"europe_pmc_id":"41869008","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Griffiths RR, Jesse R, Richards WA, Johnson MW, Sepeda ND, Bossis AP, Ross S.
publication_date: 2025-12-21
doi: 10.1089/psymed.2023.0044
pubmed_id: 41869007
source_url: https://doi.org/10.1089/psymed.2023.0044
substance_tags: psilocybin
topic_tags: Wellbeing,Spirituality,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Effects of Psilocybin on Religious and Spiritual Attitudes and Behaviors in Clergy from Various Major World Religions.

abstract:
BackgroundAlthough historical writings, anthropological accounts, and experimental studies document associations between psilocybin use and religion, no prospective experimental study has investigated how the effects of psilocybin are experienced and interpreted by religious clergy. This exploratory study evaluated the overall safety and the acute and enduring effects of psilocybin in clergy.MethodsParticipants were psychedelic-naïve clergy from various major world religions. A randomized, parallel group, waitlist control design was used to assess the effects of two supported psilocybin sessions, with participants receiving 20 and then 20 or 30 mg/70 kg about 1 month later. Outcomes were compared between the Immediate Group (n = 13) and the Delayed Group (n = 16) at 6 months after screening using self-report measures. The effects of psilocybin were also assessed on session days and 4 and 16 months after the second psilocybin session in the 24 participants who completed both sessions.ResultsThe primary outcome assessment at 6 months after screening showed that, compared with the delayed control group, participants who had received psilocybin reported significantly greater positive changes in their religious practices, attitudes about their religion, and effectiveness as a religious leader, as well as in their non-religious attitudes, moods, and behavior. Follow-up assessments showed that positive changes in religious and non-religious attitudes and behavior were sustained through 16 months after the second psilocybin session. At that time, participants rated at least one of their psilocybin experiences to be among the top five most spiritually significant (96%), profoundly sacred (92%), psychologically insightful (83%), and psychologically meaningful (79%) of their lives. Furthermore, 42% rated one of their experiences to be the single most profound of their lifetime. At 16-months follow-up, most (79%) strongly endorsed that the experiences had positive effects on their religious practices (e.g., prayer or meditation) and their daily sense of the sacred, and most (71%) reported positive changes in their appreciation of religious traditions other than their own. Although no serious adverse events were reported, 46% rated a psilocybin experience as among the top five most psychologically challenging of their lives.ConclusionsIn this population of clergy, psilocybin administration was safe and increased multiple domains of overall psychological well-being including positive changes in religious attitudes and behavior as well as their vocation as a religious leader. The study was limited by a waitlist control design, homogenous sample, and the use of some unvalidated outcome measures. Further research with more rigorous control conditions and diverse samples is needed.

raw_json:
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authors: Lorenz J, Hawkins S, McCarthy B.
publication_date: 2025-12-21
doi: 10.1177/28314425251406251
pubmed_id: 41869005
source_url: https://doi.org/10.1177/28314425251406251
substance_tags: psilocybin
topic_tags: Spirituality,Mystical Experience,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Griffiths et al.'s Study of Psilocybin with Religious Professionals: A Theological Response from a Christian Perspective.

abstract:
Griffiths et al.'s recent "Effects of Psilocybin on Religious and Spiritual Attitudes and Behaviors in Clergy from Various Major World Religions" is an important study in the literature on psychedelic medicine and religious experience. In this commentary on the study, we argue: (1) The study design's implicit presupposition of perennialism in its conception of mysticism burdens it with metaphysical and theological freight it doesn't need to support its hypothesis; and (2) Psychedelic usage in pursuit of mysticism, however construed, risks two pathologies-hyper-individualism and idolatry-that religious traditions and communities are well-positioned to counter.

raw_json:
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authors: Brach T.
publication_date: 2025-12-21
doi: 10.1177/28314425251408081
pubmed_id: 41869004
source_url: https://doi.org/10.1177/28314425251408081
substance_tags: psilocybin
topic_tags: Consciousness,Spirituality
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Effects of Psilocybin on Religious and Spiritual Attitudes and Behaviors in Clergy from Various Major World Religions: The Great Promise of Psychedelics: Evolving Human Consciousness.

raw_json:
{"europe_pmc_id":"41869004","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-12-21
doi: 10.1089/psymed.2025.68798.pn
pubmed_id: 41869003
source_url: https://doi.org/10.1089/psymed.2025.68798.pn
substance_tags: psilocybin
topic_tags: Spirituality
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Publisher's Note re: "Effects of Psilocybin on Religious and Spiritual Attitudes and Behaviors in Clergy from Various Major World Religions" (doi: 10.1089/psymed.2023.0044).

raw_json:
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authors: Palitsky R, Grant GH.
publication_date: 2025-12-21
doi: 10.1177/28314425251393983
pubmed_id: 41869002
source_url: https://doi.org/10.1177/28314425251393983
substance_tags: psilocybin
topic_tags: Spirituality
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Using Insights from a Study of Psilocybin with Clergy to Advance Research on Psychedelics, Spirituality, and the Sacred: Commentary on Griffiths et al. (2025).

raw_json:
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journal: Current oncology (Toronto, Ont.)
publication_date: 2025-12-21
doi: 10.3390/curroncol33010007
pubmed_id: 41590327
source_url: https://pubmed.ncbi.nlm.nih.gov/41590327/
substance_tags: psilocybin
topic_tags: Clinical Trial,Randomized Controlled Trial,Cancer Patients,Healthcare Workers
study_type: Randomized Controlled Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"41590327"}
title:
The CAnadian Network for Psychedelic-Assisted Cancer Therapy (CAN-PACT): A Multi-Phase Program Overview.

authors:
Carlson LE, Richardson H, Shore R, Albertyn CP, Balneaves LG, Bates A, Burnell M, Chochinov HM, Clements D, Deleemans J, Horlock H, Mathews J, McKenzie M, Savard C, Soares CN, Tu W, Williams M

abstract:
The CAnadian Network for Psychedelic-Assisted Cancer Therapy (CAN-PACT) was launched in 2025 to address urgent gaps in supportive care for Canadians with cancer experiencing demoralization syndrome (loss of meaning, dysphoria, disheartenment, helplessness, a sense of failure) and related psychosocial distress. CAN-PACT has six major objectives: (1) to develop a national interdisciplinary research and practice network; (2) to set research priorities through structured stakeholder engagement; (3) to develop and provide PAT training and education for clinicians, researchers, and patients; (4) to pilot test the feasibility of intervention and assessment procedures; (5) to conduct a multi-center, randomized controlled trial of PAT for people with advanced cancer; and (6) to inform and influence healthcare policy on PAT in Canada. We discuss the background and need for PAT in cancer, describe challenges currently limiting its use, and outline CAN-PACT's strategy for building capacity, generating Canadian evidence, and preparing the oncology healthcare environment for potential implementation. This manuscript presents a summary overview of CAN-PACT as a multi-objective research program; detailed protocols for each discrete study component will be published separately as the research program progresses. Through environmental scans, national engagement, targeted training, rigorous research, and ongoing collaboration with policymakers, CAN-PACT aims to enable equitable access to safe, evidence-based PAT for people with advanced cancer in Canada's publicly funded cancer centers.

keywords:
cancer, clinical trials, demoralization, fear of death and dying, mindfulness, patient-oriented research, psilocybin, psychedelics


authors: Brett J, Lea T, Knock E, Albert S, Acheson L, Siefried KJ, Job S.
publication_date: 2025-12-21
doi: 10.1111/add.70284
pubmed_id: 41424164
source_url: https://doi.org/10.1111/add.70284
substance_tags: psilocybin
topic_tags: Spirituality
study_type: Qualitative Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
A qualitative analysis of participant expectations and experiences of psilocybin-assisted psychotherapy for methamphetamine use disorder.

abstract:
Background and aimsThere is an urgent unmet need for novel treatments for methamphetamine (MA) use disorder. We explored the qualitative experiences of people participating in a study of psilocybin-assisted psychotherapy (PAT) to treat MA use disorder.Design and settingQualitative study of participants enrolled in a single arm, open-label pilot study of PAT for MA use disorder delivered in an outpatient stimulant treatment program setting in Sydney, Australia.ParticipantsTwelve participants were interviewed before starting PAT and then again one month following PAT.MeasurementsPre-PAT interviews explored participants' experiences of MA use and expectations of receiving PAT. Post-PAT interviews explored participants' experiences of PAT, with a focus on phenomena related to the acute subjective effects of psilocybin, the perceived effects of PAT on MA use, self-perception, beliefs, values, behaviours, interpersonal relationships and spirituality, and acceptability of the intervention. Interviews were audio recorded, transcribed verbatim and analysed using an inductive qualitative approach.FindingsWhile participants generally hoped to have positive outcomes from study participation, their expectations were generally tempered and realistic. Their trial experiences of PAT were often characterised by new understandings of themselves, their narrative histories and interpersonal relationships, all of which were frequently prompted by leaning into vividly presented challenging experiences within the psychedelic experience. This volitional attitude of 'leaning into the obstacle' emerged as a key theme, meriting exploration for its potential to expose the subjective dimension of the psychedelic mechanism of effect. Resolution of this obstacle was associated with a reduction in the salience of methamphetamine. Therapeutic alliance was seen as critical to positive outcomes and was achieved through high levels of concentrated therapeutic attention and intersubjective intimacy between participant and therapist.ConclusionsInterviewed participants in a study of psilocybin-assisted psychotherapy (PAT) for methamphetamine use disorder perceived PAT as an acceptable intervention. Transformation in understandings of self and interpersonal relationships and subsequent reduced salience of methamphetamine use often occurred through confronting psychic obstacles in the context of high levels of therapeutic support from study therapists.

raw_json:
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publication_date: 2025-11-21
doi: 10.1016/j.pnpbp.2025.111565
pubmed_id: 41285295
source_url: https://doi.org/10.1016/j.pnpbp.2025.111565
substance_tags: psilocybin
topic_tags: Depression,Treatment-Resistant Depression
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Cognitive outcomes following psilocybin-assisted therapy in treatment-resistant depression: A post-hoc analysis of a randomized, waitlist-controlled trial.

authors:
Johnson DE, Meshkat S, Kaczmarek ES, Rabin JS, Brudner RM, Chisamore N, Doyle Z, Bawks J, Riva-Cambrin J, Mansur RB, Lipsitz O, McIntyre RS, Lanctôt KL, Rosenblat JD.

abstract:
BackgroundCognitive difficulties within treatment-resistant unipolar and bipolar depression (TRD; TRBD) often do not improve with conventional pharmacotherapies. Psilocybin-assisted psychotherapy (PAP) has shown promise as a novel intervention for TRD; however, few studies have assessed its effects on cognition in this population.MethodsThis retrospective post hoc analysis included 26 adults with TRD or TRBD from an open-label trial of PAP. Cognition was assessed with the Digit Symbol Substitution Test (DSST) and Trail Making Test Part A and B (TMT-A/B) at baseline, one-day, and two-weeks post-treatment. Linear mixed models (LMMs) evaluated change over time, and reliable change indices (RCIs) with binomial tests assessed whether the proportion of participants showing meaningful improvement exceeded chance.ResultsSignificant improvements were observed on all cognitive measures over time (all p

keywords:
Humans, Hallucinogens, Treatment Outcome, Retrospective Studies, Cognition, Neuropsychological Tests, Adult, Middle Aged, Waiting Lists, Female, Male, Depressive Disorder, Treatment-Resistant, Psilocybin

raw_json:
{"europe_pmc_id":"41285295","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-10-22
doi: 10.1016/j.pnpbp.2025.111541
pubmed_id: 41138900
source_url: https://doi.org/10.1016/j.pnpbp.2025.111541
keywords: Humans, Hallucinogens, Research Design, Clinical Trials as Topic, Psilocybin
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Adverse event reporting and management in psilocybin therapy clinical trials: A systematic review to guide clinical and research protocol development.

authors:
Bukovsky D, Amaev A, Song J, Kyte S, Carmona-Torres E, Ueno F, Deluca V, Strafella AP, Husain MI, Graff-Guerrero A, Gerretsen P.

abstract:
Psilocybin, a psychedelic prodrug, has gained renewed interest for its potential to treat various psychiatric disorders, including depression, anxiety, and substance use disorders. While promising, concerns remain regarding its safety profile and the management of potential adverse events (AEs). This systematic review aimed to evaluate the incidence, nature, and severity of adverse events and serious adverse events (SAEs) associated with psilocybin use across diverse clinical populations. A comprehensive search was conducted across MEDLINE, Embase, and APA PsycInfo via the OVID platform, from database inception to June 5, 2024. A total of 42 clinical studies (N = 1068 participants) met inclusion criteria, all of which reported on AEs and/or SAEs following psilocybin administration. All studies were deemed to have a high risk of bias due to concerns regarding blinding. We synthesized information on common, uncommon, and SAEs, instances of suicidal ideation, methods of measuring AEs, and AEs requiring medical intervention. Reported AEs included headache, transient increases in blood pressure, and nausea, which typically resolved on their own. In rare instances, medical intervention was required. SAEs were reported infrequently in 2 of 42 studies and were limited to participants with underlying depressive disorders (e.g., suicidal behaviour, hospitalization). Overall, psilocybin appears to have a favourable safety profile when administered in controlled settings. Based on our findings, we provide an outline of commonly reported AEs, uncommon AEs, SAEs, and considerations for future clinical and research protocols.

topic_tags:
Depression,Anxiety,Addiction,Headache / Migraine,Clinical Trial,Systematic Review,Review Article,Safety,Adverse Events

raw_json:
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title: Psilocybin reporting in media (PRiMe) for the treatment of depression.
authors: Brar G, Burke T, Gribben AD, Harrington C, Thuery G, Kelly JR.
publication_date: 2025-12-17
doi: 10.1017/ipm.2025.10142
pubmed_id: 41410115
source_url: https://doi.org/10.1017/ipm.2025.10142
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
ObjectivesInterest in psilocybin as a treatment for depression has risen over the past decade, fuelled by promising clinical trials and a rapidly evolving regulatory landscape. Media coverage plays a critical role in shaping public perceptions, yet little is known about how psilocybin is portrayed in global anglophone online news for the treatment of depression.MethodsThis study examines the comprehensiveness and sentiment of English-language online news articles (n = 125) discussing psilocybin as a treatment for depression from January 2000 to May 2024. Articles were sourced from the top 30 global anglophone news outlets, assessed using a 13-item instrument for comprehensiveness, and analysed for sentiment across five thematic categories. A separate sub-analysis was completed for Irish media.ResultsFindings indicate a significant increase in coverage over time, with 43.2% of articles published between 2022 and 2024, predominantly from the USA (68%). While 90.4% of articles cited researchers, fewer addressed risks (47.2%), long-term evidence (46.4%), or patient perspectives (25%). Sentiment analysis revealed a very positive sentiment across articles which was 2.27 on a scale from -5 (most negative) to + 5 (most positive) (SD1.33), with no significant changes over the time period. Reporting on psilocybin's onset and duration of effects increased significantly, reflecting growing clinical evidence. However, coverage remains concentrated in prominent outlets, with limited attention to patient experiences and long-term safety.ConclusionsThese findings highlight the media's role in shaping discourse on emerging treatments and suggest a need for more balanced reporting to align public understanding with scientific evidence. This study provides a foundation for future research on media portrayals of psilocybin and implications for public perception and policy.

raw_json:
{"europe_pmc_id":"41410115","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Which Psychotherapy Model Should be Used in Psilocybin Treatment for Depression?
authors: Koning E, Bacchi P, Chaves C, Gomes FA, Brietzke E.
publication_date: 2025-12-16
doi: 10.47626/2237-6089-2025-1197
pubmed_id: 41405984
source_url: https://doi.org/10.47626/2237-6089-2025-1197
substance_tags: psilocybin
topic_tags: Depression,Psychological Flexibility,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
ObjectiveUnipolar and bipolar depression severely impact millions of individuals worldwide, with a significant subset of cases remaining unresponsive to conventional treatments. Psilocybin-assisted psychotherapy (PAP) has demonstrated therapeutic efficacy; however, the optimal psychotherapeutic approach remains undefined, ranging from unstructured models rooted in historical practices to modern frameworks that are structurally tailored for depression. This narrative review proposes a conceptualization of psychotherapeutic models employed in existing interventional trials of PAP for depression and provides a preliminary comparison of their main characteristics and evidence for efficacy.MethodsThe online databases PubMed, PsycINFO, and Google Scholar were searched for interventional trials evaluating PAP for individuals with unipolar or bipolar depression.ResultsA total of 38 publications were reviewed, contributing to the conceptualization of two main types of psychotherapy models: 1) 'Specific' approaches (most commonly Acceptance and Commitment Therapy and Perceptual-Control Therapy) and 2) 'Non-specific' models of psychological support. Both models emphasize the critical role of the therapeutic alliance, yet differ in mechanistic focus, with specific models being developed to enhance psychological flexibility and non-specific models emphasizing the concept of the 'inner-healer.' Importantly, critical gaps in the literature were identified, including methodological limitations of current evidence and the need for standardized reporting guidelines.ConclusionAlthough each PAP model differs, both may have clinical relevance in depression treatment. Future work should explore the standardized reporting of psychological interventions in PAP and comparative study designs to better evaluate non-specific and specific models and inform treatment guidelines.

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publication_date: 2025-12-14
doi: 10.1192/bjo.2025.10895
pubmed_id: 41392767
source_url: https://doi.org/10.1192/bjo.2025.10895
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocybin-assisted psychotherapy for treatment-resistant obsessive-compulsive disorder: protocol for an open-label pilot study.

authors:
Ledwos N, Baer J, Husain MI, Blumberger DM, Patterson R, Hollingdrake E, Cheung E, Hawco C, Zrenner C, Zrenner B, Feusner JD, Rossell SL, Castle DJ, Zai G.

abstract:
BackgroundObsessive-compulsive disorder (OCD) is a debilitating mental disorder commonly treated with selective serotonin reuptake inhibitors, atypical antipsychotic augmentation and cognitive-behavioural therapy. However, up to 60% of people with OCD do not respond to these treatments. Therefore, a novel intervention, psilocybin-assisted psychotherapy (PAP), is an option of interest. Moreover, there is a need to better understand the mechanisms underpinning PAP's effect on OCD symptoms.AimsWe aimed to (a) establish the feasibility, tolerability and safety of administering PAP to adults with treatment-resistant OCD; (b) provide preliminary data on the clinical effects of PAP for treatment-resistant OCD, to inform the design of larger clinical trials; and (c) compare neuroimaging and neurophysiological markers pre- and post-PAP in treatment-resistant OCD.MethodIn this 12-week open-label trial, ten adults with treatment-resistant OCD will receive one 25 mg dose of psilocybin combined with psychological support. Feasibility, tolerability and safety will be assessed throughout. Clinical outcomes will be measured with the Yale-Brown Obsessive-Compulsive Scale. Exploratory measures will include brain imaging examining changes in dynamic connectivity from pre to post treatment, electroencephalogram to investigate changes in brain dynamics associated with psilocybin under acute conditions, and transcranial magnetic stimulation-electroencephalogram measures between baseline, provocation of OCD symptoms and up to 1-week post-dose.ResultsThe study will provide important preliminary data on the feasibility and efficacy of PAP in adults with treatment-resistant OCD, as well as inform our understanding of neurobiological mechanisms.ConclusionsThe findings of the study will inform the design of larger randomised controlled trials and advance the field of psychedelic-assisted therapies.

topic_tags:
OCD,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Biomarkers,Aging,Clinical Trial,Randomized Controlled Trial,Safety

raw_json:
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authors: Kittur ME, Burgos M LA, Jones BDM, Blumberger DM, Mulsant BH, Rosenblat JD, Husain MI.
publication_date: 2025-07-17
doi: 10.1016/j.jad.2025.119952
pubmed_id: 40684956
source_url: https://doi.org/10.1016/j.jad.2025.119952
keywords: Humans, Hallucinogens, Mental Disorders, Psychotherapy, Clinical Trials as Topic, Psilocybin
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Mapping psilocybin therapy: A systematic review of therapeutic frameworks, adaptations, and standardization across contemporary clinical trials.

abstract:
Accumulating evidence suggests that psilocybin can produce rapid and sustained clinical benefits when administered in conjunction with psychological support. Though non-pharmacological procedures are considered integral, the field lacks therapeutic guidelines and little is known about current practices. This systematic review sought to provide a comprehensive and cross-diagnostic synthesis of current psilocybin therapy (PT) protocols across contemporary mental health related trials. Primary objectives were to define and compare PT models with respect to overall therapeutic framework, evidence-based psychotherapeutic adaptations, and therapeutic standardization measures. Database search identified 22 recent trials assessing psilocybin as treatment for major and treatment-resistant depression, medical condition-related distress, substance use, obsessive-compulsive disorders, and eating disorders. Cross-diagnostic review revealed broad consistency in therapeutic structure (i.e. before, during, and after psilocybin treatment), session themes, and external context during drug administration. However, trials varied in therapeutic intensity, diagnostic adaptations, and incorporation of evidence-based psychotherapies. Less than half of reviewed trials reported standardization measures such as manualized procedures, PT-specific training, or adherence and fidelity monitoring. With non-pharmacological treatment mechanisms still unclear, results highlight potential confounds and standardization gaps that undermine the replicability and generalizability of recent psilocybin interventions. Until adjunctive support protocols are adequately operationalized, mechanistic insight and uptake into clinical practice will remain a challenge.

topic_tags:
Depression,Addiction,OCD,Eating Disorders,Mechanism of Action,Clinical Trial,Systematic Review,Review Article,Treatment-Resistant Depression

raw_json:
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authors: Bender DA, Nayak SM, Siegel JS, Hellerstein DJ, Ercal BC, Lenze EJ.
publication_date: 2025-05-05
doi: 10.1176/appi.psychotherapy.20240025
pubmed_id: 40326007
source_url: https://doi.org/10.1176/appi.psychotherapy.20240025
substance_tags: psilocybin
topic_tags: Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
The Role of Touch in Psychedelic Therapy: Perspectives From a Survey of Practitioners in Research Settings.

abstract:
ObjectivePsychedelic therapies are promising new treatment options in psychiatry. Including the use of physical touch as part of treatment is an area of debate. This study aimed to characterize the viewpoints of practitioners on the use of touch in psychedelic therapy.MethodsAn anonymous survey was distributed via e-mail to the contacts listed on ClinicalTrials.gov for trials of psilocybin and lysergic acid diethylamide, via e-mail to personal contacts of the current authors, and through snowball sampling. Survey items focused on topics related to the facilitation of psychedelic treatments. The survey included Likert-scale, free-response, and demographic items.ResultsForty respondents completed the survey. The respondents had overseen an average of 41.4 psychedelic sessions (range 2-200 sessions), had varying educational backgrounds (doctorate in medicine or osteopathic medicine, 43%; other degree, 58%), and were affiliated with ≥16 institutions worldwide. Seventy percent of the respondents agreed that therapeutic touch was a crucial component of psychedelic therapy, although a majority felt that specific forms of touch (bodywork, 63%; full-body contact, 98%) were inappropriate. Free-response analysis indicated that 96% of the respondents supported touch of the patient's hand and 58% supported touching of the shoulder. Unprompted, 63% of respondents emphasized the importance of consent.ConclusionsClassical psychedelic practitioners in research settings believed that physical touch is an important part of psychedelic therapy. However, they also emphasized the importance of professional boundaries. These findings may inform the future practice of psychedelic therapy.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Therapeutic Touch, Attitude of Health Personnel, Mental Disorders, Adult, Middle Aged, Female, Male, Surveys and Questionnaires, Psilocybin

raw_json:
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publication_date: 2025-12-12
doi: 10.1007/s00213-025-06983-9
pubmed_id: 41389223
source_url: https://doi.org/10.1007/s00213-025-06983-9
substance_tags: psilocybin
topic_tags: Brain Imaging,Consciousness,Biomarkers,Aging,Emotional Processing,Healthy Volunteers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Regional specificity of the cingulate cortex thickness association with the intensity of psilocybin experience: a replication study.

authors:
Greguš D, Hlinka J, Tylš F, Viktorin V, Viktorinová M, Bravermanová A, Androvičová R, Andrashko V, Korčák J, Nikolič M, Adámek P, Beneš M, Páleníček T, Horáček J.

abstract:
RATIONALE: Individual variability in psilocybin response is a major challenge for psychedelic-assisted therapy, with structural brain features potentially serving as predictive biomarkers. (Lewis et al. Biomedicines 8(2):34 2020) reported that rostral anterior cingulate cortex thickness predicted emotional experiences under psilocybin, suggesting cortical morphometry as a marker of psychedelic responsivity. OBJECTIVES: This study sought to replicate and extend these findings by examining associations between cingulate thickness and psilocybin-induced altered states of consciousness using comprehensive assessment and rigorous statistical control. METHODS: Twenty-five healthy participants underwent a double-blind, placebo-controlled crossover design with psilocybin (0.26 mg/kg) and placebo. High-resolution T1-weighted magnetic resonance imaging (MRI) measured cortical thickness across cingulate subregions. Subjective effects were assessed with the Altered States of Consciousness (ASC) questionnaire. Analyses applied false discovery rate (FDR) correction for multiple comparisons. RESULTS: The primary Lewis et al. finding-that rostral anterior cingulate cortex thickness predicts emotional psilocybin responses-showed a comparable effect size (β = 0.523 vs. their range 0.324-0.572) that did not achieve statistical significance (p = 0.297), likely reflecting limited statistical power given our smaller sample (N = 25 vs. N = 55). We identified an anterior-posterior gradient in cingulate thickness that significantly predicted psychedelic experience intensity (r = 0.676, FDR p = 0.0004). CONCLUSIONS: Findings indicate that spatial organization within the cingulate cortex provides a neuroanatomical marker of variability in psychedelic response. Results highlight the importance of organizational patterns within the cingulate cortex, rather than focal regional measures, when predicting psychedelic effects.

raw_json:
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authors: Renner AC, Kargbo RB.
publication_date: 2025-11-09
doi: 10.1021/acsmedchemlett.5c00661
pubmed_id: 41404010
source_url: https://doi.org/10.1021/acsmedchemlett.5c00661
substance_tags: psilocin
topic_tags: Pharmacology,Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Engineering the Next Generation of Psychedelic Therapeutics through Serotonergic Precision and Pharmacokinetic Control.

abstract:
Recent patents unveil a new wave of psychedelic analogs optimized for 5-HT2A receptor modulation, reduced adverse effects, and tunable duration of action. By refining DMT and psilocin scaffolds through prodrug design, fluorination, and structure-activity exploration, these innovations promise safer, shorter-acting psychedelic medicines that align with clinical workflow and improve therapeutic predictability for psychiatric disorders.

raw_json:
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publication_date: 2025-12-09
doi: 10.3389/fpsyt.2025.1726818
pubmed_id: 41450831
source_url: https://doi.org/10.3389/fpsyt.2025.1726818
substance_tags: psilocybin
topic_tags: OCD,Mechanism of Action,Emotional Processing
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Acute and post-dosing effects of single-dose psilocybin for obsessive-compulsive disorder in a randomized, double-blind, placebo-controlled trial: an interpretative phenomenological analysis.

authors:
Ching THW, Stahnke B, Shnayder S, Agin-Liebes G, Adams TG, Amoroso L, Baiz O, Belser A, Bohner C, Burke M, D'Amico E, DePalmer G, Eilbott J, Fram G, Grazioplene R, Hokanson J, Jankovsky A, Kichuk SA, Martins B, Purohit P, Schaer H, Sierra YP, Witherow C, Pittenger C, Kelmendi B.

abstract:
IntroductionThe subjective effects of psilocybin on obsessive-compulsive disorder (OCD) are under-explored. Therefore, we conducted a qualitative study of participant experiences from the first randomized placebo-controlled trial of single-dose psilocybin combined with unstructured and non-directive support for individuals with treatment-refractory OCD. Our research explored how participants experienced acute and post-dosing effects, the interrelationships between these effects, and participants' perspectives on therapeutic change.Materials and methodsWe conducted qualitative interviews with 12 participants approximately one month after psilocybin dosing; (six who received psilocybin in the initial randomized placebo-controlled phase, six who received open-label psilocybin following unblinding). We analyzed interview transcripts via interpretative phenomenological analysis (IPA) and engaged in consensus decision-making to arrive at 100% intercoder agreement in the process of abstracting codes into higher-order themes.ResultsFour major themes (and several subthemes) emerged from our analysis: 1) Influences on Psilocybin Experience (i.e., Set, Setting); 2) Acute Effects (i.e., Acute perceptual effects, Acute [meta]cognitive effects, Acute emotional effects, Acute impact of OCD, Other acute effects); 3) Post-Dosing Changes in OCD (i.e., Post-dosing changes in symptoms, Post-dosing changes in perceptions of OCD); as well as 4) Post-Dosing Changes Beyond OCD Symptoms (i.e., Post-dosing [meta]cognitive changes, Other post-dosing changes). Meaningful interrelationships among codes, subthemes, and themes were the norm.DiscussionOur findings highlight the moderate to strong influences of set and setting in the nature and trajectory of participants' psilocybin experiences. We also uncovered acute, synergistic visual/perceptual, emotional/psychological, and physiological/somatic effects that map onto those commonly reported in prior psilocybin trials for other closely related indications. However, these acute effects tended to occur at lower intensities (i.e., 'partial' experiences) potentially due to acute interference by OCD symptoms. Certain acute and post-dosing (meta)cognitive and behavioral effects also map onto putative mechanisms of action in evidence-based psychotherapy for OCD (e.g., exposure and response prevention [ERP] and acceptance and commitment therapy [ACT]). These findings yielded hypotheses for future investigation, and point toward potential integration of psilocybin with structured psychotherapy approaches for OCD.

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publication_date: 2025-12-09
doi: 10.1523/jneurosci.0652-25.2025
pubmed_id: 41213805
source_url: https://doi.org/10.1523/jneurosci.0652-25.2025
substance_tags: psilocybin,psilocin
topic_tags: Addiction,Mechanism of Action,Receptor Pharmacology,Animal Study,Drug Interactions
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
The Psychedelic Psilocin Suppresses Activity of Central Amygdala Corticotropin-Releasing Factor Receptor 1 Neurons and Decreases Ethanol Drinking in Female Mice.

authors:
Magee SN, Sereno AC, Echeveste-Sanchez M, Shannon EG, Mohsin A, Mott SE, Faccidomo SP, Hodge CW, Herman MA.

abstract:
Alcohol use disorder (AUD) is a highly prevalent disorder with limited therapeutic options. The central amygdala (CeA) is a critical brain region as dysregulation within the CeA and the corticotropin-releasing factor (CRF) system are associated with AUD pathology. CeA CRF1 receptors regulate alcohol drinking and have served as a therapeutic target in alcohol treatment. One emerging potential therapeutic for AUD is psilocybin. Psilocybin has been shown to decrease drinking in some clinical studies; however, the effects are variable and the underlying mechanisms are poorly understood. Psilocybin engages many brain regions, including the CeA, and may produce therapeutic effects on drinking through interactions with CeA CRF1 neurons. The current study explores the effects of psilocin, the active metabolite of psilocybin, on voluntary ethanol drinking and CeA CRF1 activity to understand potential mechanisms underlying the therapeutic effects of psilocin. Psilocin acutely decreased ethanol consumption in mice exposed to two different models of chronic ethanol exposure without producing changes in locomotor behavior. Psilocin increased CeA activation and decreased relative CRF1 activation in CeA subregions from ethanol-naive female CRF1:GFP mice. These results were also observed in chronic ethanol-exposed mice at 24 and 72 h withdrawal timepoints. Psilocin increased corticosterone at 24 h withdrawal but not at 72 h withdrawal. Collectively, these results demonstrate that psilocin engages CeA circuitry and decreases relative CRF1 activation, in parallel with acute reductions in drinking. These results contribute to our understanding of the mechanisms underlying the actions of psilocin and inform the interpretation of therapeutic effects in clinical studies.

keywords:
Neurons, Animals, Mice, Inbred C57BL, Mice, Ethanol, Receptors, Corticotropin-Releasing Hormone, Hallucinogens, Alcohol Drinking, Female, Central Amygdaloid Nucleus, Psilocybin, CRF Receptor, Type 1

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publication_date: 2025-12-04
doi: 10.1016/j.eclinm.2025.103692
pubmed_id: 41497513
source_url: https://doi.org/10.1016/j.eclinm.2025.103692
substance_tags: psilocybin
topic_tags: Depression,PTSD,Mechanism of Action,Clinical Trial,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Investigational psilocybin treatment for post-traumatic stress disorder: a qualitative study of participant experience, trauma engagement, and differences from standard treatment.

authors:
Modlin NL, Williamson V, Goodwin GM, Malievskaia E, Atli M, Elek Z, Gaillard A, Koelpin D, Cleare A, Agrawal M, Yehuda R, Kirlic N, Rucker J.

abstract:
BackgroundPost-traumatic stress disorder (PTSD) is a debilitating condition leading to significant personal and societal burden. Standard treatments frequently demonstrate limited efficacy, leading to persistent symptoms and high dropout rates. Psilocybin has shown promise in treating depression, a condition that is often comorbid with PTSD. We aimed to explore participant experiences of psilocybin treatment for PTSD, emphasising the role of monitoring and support for safety, direct and indirect engagement with trauma-related material during psilocybin treatment, and differences between psilocybin and standard treatments.MethodsThis qualitative study was nested within a quantitative, open-label phase 2 trial assessing the safety and tolerability of COMP360 psilocybin in adults with PTSD. Eligible participants were adults (18 years or older) who met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for PTSD secondary to a traumatic event experienced in adulthood. Recruitment was conducted at three sites across two countries: two in the United States and one in the United Kingdom. Enrolled participants underwent standardised preparation, a single psilocybin administration session, and follow-up integration sessions. Semi-structured interviews were conducted before, the day after, and 12 weeks post-treatment. Data were analysed using reflexive thematic analysis, which is a distinct and theoretically grounded approach to co-construction of recurring themes pertaining to participants' preparedness for treatment, how participants' index trauma presented during treatment, and how psilocybin compared to standard treatments. The quantitative phase 2 trial, which the present qualitative study is nested within, is registered with ClinicalTrials.gov, NCT05312151.FindingsBetween June 10, 2022, and Feb 12, 2024, 21 participants were enrolled and participated in this qualitative sub-study and completed the in-person qualitative interviews. The analysis revealed four core themes: (1) non-pharmacological factors for psychological safety and trust, (2) the experiential nature of psilocybin treatment, (3) engagement with trauma-related material during psilocybin treatment, and (4) comparative reflections on prior therapies and psilocybin treatment. Emphasising safety, treatment education, and informed consent, the treatment facilitated an experience of both direct and indirect engagement with trauma-related material during psilocybin treatment. Unlike standard treatments requiring direct confrontation with trauma memories, psilocybin appears to enable a broader, indirect engagement with traumatic material via a range of affective, somatic and self-transcendent experiences (e.g., moments of perceived unity, dissolution of self, or felt connection with a larger whole).InterpretationOur qualitative findings suggests that psilocybin treatment, when administered with standardised preparation and treatment support, may offer a meaningful therapeutic opportunity for Patients with PTSD. Future work should include larger controlled studies and use mixed methods to explore how symptom change, functional outcomes, and patient narratives interact.FundingCompass Pathways, plc.

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authors: Dodds C, Dawson R, Lim A, Tye S, Nasrallah F.
publication_date: 2025-12-03
doi: 10.1177/20451253251396255
pubmed_id: 41362593
source_url: https://doi.org/10.1177/20451253251396255
substance_tags: psilocybin
topic_tags: PTSD,Neuroplasticity,Mechanism of Action,Review Article,Healthcare Workers
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Novel psychedelic interventions for post-traumatic stress disorder and their promise for precision medicine.

abstract:
Novel interventions for post-traumatic stress disorder (PTSD) leverage the psychoactive properties of psychedelic compounds, such as ketamine, 3,4-methylenedioxymethamphetamine and psilocybin, which may overcome limitations of conventional treatments. Through the modulation of pathways involved in synaptic plasticity, psychedelic interventions are believed to enhance the mechanisms underlying memory processing and extinction. Multi-modal approaches to patient care can use existing treatments in combination with psychedelics to improve the efficacy of current psychotherapies, producing rapid and lasting improvement to chronic physiological and psychological symptoms. Modern methods for predicting treatment response will allow clinicians to personalise psychedelic interventions to the individual, capitalising on quantitative evidence to provide precision medical care. This review serves to identify limitations of the current treatment paradigm for PTSD, highlight how emerging psychedelic interventions may offer a solution to these considerations and explore the promise of precision medicine approaches for the future of PTSD treatment.

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authors: Kangaslampi S, Wolff M, Doss MK, Kloft-Heller L, Otgaar H.
publication_date: 2025-12-03
doi: 10.1186/s40337-025-01484-8
pubmed_id: 41345723
source_url: https://doi.org/10.1186/s40337-025-01484-8
substance_tags: psilocybin
topic_tags: Eating Disorders,Case Report
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Questioning the recovery of dissociated traumatic memories under psilocybin: comment on "Therapeutic emergence of dissociated traumatic memories during psilocybin treatment for anorexia nervosa".

abstract:
In their recent case report article, Peck and colleagues suggested that two patients recovered dissociated traumatic memories during psilocybin treatment for anorexia nervosa. These case reports are of clinical and scientific interest and confirm that psychedelics may induce vivid memory-like experiences. However, the reports warrant scrutiny. Here, based on what is known about recovered memories and the effects of psychedelics, we argue that the authors may not have adequately considered alternative explanations. The cases do not necessarily demonstrate that psilocybin induces recovery of dissociated traumatic memories or could treat dissociative amnesia. We further caution against the authors' suggestion of explicitly preparing patients for the emergence of forgotten material.

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authors: Machado T, Rodrigues ASL, Costa J.
publication_date: 2025-12-02
doi: 10.1177/20451253251397590
pubmed_id: 41356122
source_url: https://doi.org/10.1177/20451253251397590
substance_tags: psilocybin
topic_tags: Meta-Analysis,Systematic Review,Review Article
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Comment on: Effect of psilocybin therapy on suicidal ideation, attempts, and deaths in people with psychiatric diagnoses: a systematic review and meta-analysis.

raw_json:
{"europe_pmc_id":"41356122","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kleditzsch N, Gattuso JJ, Hannan AJ, Renoir T.
publication_date: 2025-11-30
doi: 10.1111/ejn.70351
pubmed_id: 41365493
source_url: https://doi.org/10.1111/ejn.70351
substance_tags: psilocybin,psilocin
topic_tags: Depression,Anxiety,Receptor Pharmacology,Animal Study,Treatment-Resistant Depression
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Acute Blockade of the Serotonin Transporter With Low Doses of Escitalopram Does Not Alter the Behavioural Responses to Acute Psilocybin.

abstract:
The psychedelic psilocybin has gained popularity in recent years as a therapy for treatment-resistant depression and has been reported to reduce symptoms of depression and anxiety. Psilocybin's active metabolite, psilocin, possesses a binding affinity for serotonin receptors as well as for the serotonin transporter (5-HTT). We recently reported that in contrast to wild-type mice, psilocybin did not induce hyperlocomotion and head-twitch responses in mice genetically lacking 5-HTT, suggesting an involvement of 5-HTT in mediating these effects. To further assess the specific role of 5-HTT in psilocybin's acute behavioural effects, we treated C57BL/6 mice with the highly selective 5-HTT inhibitor escitalopram (2.5-5 mg/kg, i.p.) prior to psilocybin administration (1 mg/kg, i.p.), and measured acute behavioural effects including head-twitch response and locomotor activity. We found that acute psilocybin administration increased locomotor activity and induced head twitches, and that escitalopram did not alter these effects. Our study using low doses of escitalopram reveals no direct involvement of 5-HTT in mediating the acute effects of psilocybin in mice, and instead suggests that developmental changes and varying serotonin levels may rather explain the absence of psilocybin's acute behavioural effects previously reported in the 5-HTT homozygous knockout mice.

keywords:
Animals, Mice, Inbred C57BL, Mice, Citalopram, Hallucinogens, Behavior, Animal, Locomotion, Male, Serotonin Plasma Membrane Transport Proteins, Psilocybin, Escitalopram, Selective Serotonin Reuptake Inhibitors

raw_json:
{"europe_pmc_id":"41365493","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Sudden Loss of Consciousness Following Psilocybin Ingestion.
authors: Downey AE, Tai ML, Bradley ER, Woolley JD.
publication_date: 2025-11-30
doi: 10.1176/appi.ajp.20250037
pubmed_id: 41320824
source_url: https://doi.org/10.1176/appi.ajp.20250037
substance_tags: psilocybin
topic_tags: Consciousness
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
raw_json:
{"europe_pmc_id":"41320824","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin reduces comorbid chronic pain and depression in mice.
authors: Ferreira J.
publication_date: 2025-11-30
doi: 10.1038/s41684-025-01663-9
pubmed_id: 41298885
source_url: https://doi.org/10.1038/s41684-025-01663-9
substance_tags: psilocybin
topic_tags: Depression,Chronic Pain,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
raw_json:
{"europe_pmc_id":"41298885","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-11-06
doi: 10.1016/j.euroneuro.2025.09.011
pubmed_id: 41205366
source_url: https://doi.org/10.1016/j.euroneuro.2025.09.011
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Efficacy, all-cause discontinuation, and safety of serotonergic psychedelics and MDMA to treat mental disorders: A living systematic review with meta-analysis.

authors:
Højlund M, Kafali HY, Kırmızı B, Fusar-Poli P, Correll CU, Cortese S, Sabé M, Fiedorowicz J, Saraf G, Zein J, Berk M, Husain MI, Rosenblat JD, Rubaiyat R, Corace K, Wong S, Hatcher S, Kaluzienski M, Yatham LN, Cipriani A, Gosling CJ, Carhart-Harris R, Tanuseputro P, Myran DT, Fabiano N, Moher D, Mayo LM, Nicholls SG, White T, Prisco M, Radua J, Vieta E, Ladha KS, Katz J, Veroniki AA, Solmi M.

abstract:
Serotonergic psychedelics and 3,4-methylendioxtmethamphetamine (MDMA) are promising treatments for mental disorders with a continuously evolving evidence base. We searched Pubmed/Scopus/clinical trial registries up to 08july2025 for double-blind randomized controlled trials (RCTs) testing MDMA or serotonergic psychedelics in patients with mental disorders. Primary outcomes were change in disease-specific symptoms and all-cause discontinuation. Standardized mean differences (SMD) and relative risk (RR) were estimated using random-effects meta-analysis. Risk of bias (RoB) was assessed with Cochrane's RoB-tool version 2 and certainty of evidence with GRADE. The review is maintained as living systematic review (https://ebipsyche-database.org/). We included 30 RCTs (1480 participants; female=45.8 %; with psychological support=83.3 %; high RoB=83.3 %). In post-traumatic stress disorder (PTSD), MDMA reduced PTSD symptoms compared to any control (k = 11; SMD=-0.85 [-1.09; -0.60]; I2=0 %; GRADE=low). In major depressive disorder (MDD), psilocybin/ayahuasca/LSD reduced depressive symptoms (k = 8; SMD=-0.62 [-0.97; -0.28]; I2=55 %; GRADE=very low). In anxiety disorders, both MDMA and serotonergic psychedelics reduced anxiety symptoms (SMDMDMA=-1.18 [-2.04; -0.32]; I2=0 %; k = 2; GRADE=low and SMDserotonergic=-0.88 [-1.70; -0.06]; I2=54 %;k = 5; GRADE=very low). In alcohol use disorder, neither psilocybin nor LSD reduced abstinence rates (k = 6; RR=1.42 [0.89; 2.26]; I2=7 %; GRADE=very low). In attention-deficit hyperactivity disorder (ADHD), LSD did not reduce ADHD symptoms (k = 1; SMD=0.22 [-0.32; 0.76]; GRADE=very low). Moderate certainty in evidence was only found for MDMA on PTSD symptoms when compared to placebo. MDMA/serotonergic psychedelics were not associated with higher risk of all-cause discontinuation (RRMDMA=0.74 [0.32; 1.72]; RRserotonergic=0.81 [0.56; 1.15]). Overall, MDMA/serotonergic psychedelics are promising for the treatment of PTSD, MDD, and anxiety disorders with moderate to large effect sizes. Pragmatic trials, long-term, head-to-head trials exploring the role of psychological support, aiming to identify predictors of response, and accounting for expectancy and functional unblinding are needed. Studies addressing these limitations will likely be required for regulatory approval of psychedelic drugs.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Serotonin Agents, Hallucinogens, Treatment Outcome, Mental Disorders, Randomized Controlled Trials as Topic

topic_tags:
Depression,Anxiety,PTSD,Addiction,Receptor Pharmacology,Clinical Trial,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Safety

raw_json:
{"europe_pmc_id":"41205366","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: García-Cabrerizo R, Beruete-Fresnillo I, Bergas-Cladera P, García-Fuster MJ.
publication_date: 2025-10-29
doi: 10.1016/j.biopha.2025.118720
pubmed_id: 41172953
source_url: https://doi.org/10.1016/j.biopha.2025.118720
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Neurogenesis,Biomarkers,Observational Study,Adolescents
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocybin as a fast-acting and long-lasting antidepressant for adolescence: Proposing NeuroD1 as a biomarker of its long-term plasticity.

abstract:
Adolescent depression is a significant public health concern, yet treatment options remain limited, particularly due to age- and sex-related differences in antidepressant efficacy. This study explored for the first time the potential antidepressant-like response of psilocybin in adolescence by examining acute, repeated and persistent effects in Sprague-Dawley rats of both sexes, as measured under the stress of the forced-swim test. As compared to other studies, we relied on a more translational approach by administering psilocybin orally (oral gavage, o.g.), while elucidating its hallucinogenic-like potential through head-twitch responses. Finally, hippocampal neurogenesis markers were evaluated as potential biomarkers of psilocybin's antidepressant-like responses in adolescence (1- and 16-days post-treatment). The main results showed that: (1) acute psilocybin (1 mg/kg, 30 min) induced subjective hallucinogenic effects, as measured by head-twitch responses, independently of the route of administration (i.p. vs. o.g.), and without changing locomotor activity; (2) acute psilocybin (0.3 and 1 mg/kg, o.g., 30 min) exerted a rapid antidepressant-like response that coincided with the course of hallucinogenic-like responses; (3) repeated psilocybin (0.3 and 1 mg/kg, 7 days, 1 dose/day, o.g.) induced an antidepressant-like response while increased several hippocampal neurogenesis markers (Ki-67: cell proliferation, NeuroD1: neural progenitors and BrdU: cell survival) as measured 1-day post-treatment; and (4) the long-lasting antidepressant-like effects of psilocybin (observed up to 15-days post-treatment) paralleled hippocampal NeuroD1 regulation. Interestingly these effects were observed for rats independently of sex (mixed-sex cohort). To the best of our knowledge, these results are the first ones to underscore oral psilocybin's potential as a fast-acting and long-lasting antidepressant during adolescence, a developmental stage marked by high vulnerability to depression and reduced response to conventional treatments, while also proposing NeuroD1 as a putative biomarker of its long-term plasticity.

keywords:
Hippocampus, Animals, Rats, Rats, Sprague-Dawley, Hallucinogens, Antidepressive Agents, Behavior, Animal, Depression, Neuronal Plasticity, Female, Male, Neurogenesis, Biomarkers, Psilocybin, Doublecortin Protein, Basic Helix-Loop-Helix Proteins

raw_json:
{"europe_pmc_id":"41172953","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Du X, Liu J, Wang X, Wang X.
publication_date: 2025-09-29
doi: 10.1038/s41380-025-03291-8
pubmed_id: 41028569
source_url: https://doi.org/10.1038/s41380-025-03291-8
substance_tags: psilocybin
topic_tags: Consciousness,Creativity,Spirituality
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
The transformational power of psychedelics: catalysts for creativity, consciousness, and mental health.

abstract:
Psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), ketamine, and N,N-dimethyltryptamine (DMT), have captured the attention of scientists, artists, and seekers alike for their profound ability to alter consciousness and inspire creativity. The concept of "creation" encompasses multiple interpretations-ranging from generating novel ideas to fostering personal transformation. This perspective explores how psychedelics interact with the concept of creation, examining their role in enhancing artistic inspiration, facilitating spiritual experiences, and driving therapeutic breakthroughs in mental health treatment. By integrating findings from neurobiological research, clinical applications, and cultural analysis, we offer a holistic view of how psychedelics may catalyze innovative modes of thinking and awaken the mind's creative and transformative potential. As these substances gain prominence as tools for reshaping our understanding of consciousness and psychological healing, their broader integration into society requires careful consideration of legal complexities, ethical responsibilities, and cultural contexts to ensure their use is evidence-based, respectful, and responsibly guided.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Mental Health, Consciousness, Creativity, Psilocybin

raw_json:
{"europe_pmc_id":"41028569","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin inhibits formalin-induced nociception through 5-hydroxytryptamine 2A receptor in rats.
authors: Inan S, Morris P, Rawls SM, Daws S.
publication_date: 2025-09-24
doi: 10.1097/fbp.0000000000000856
pubmed_id: 41017560
source_url: https://doi.org/10.1097/fbp.0000000000000856
substance_tags: psilocybin
topic_tags: Chronic Pain,Receptor Pharmacology,Inflammation
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Psilocybin is found in a family of mushrooms commonly known as Psilocybe. We aimed to study the antinociceptive efficacy of psilocybin using formalin-induced noxious stimuli, a model that comprises both acute and persistent pain in rats. Adult male Sprague-Dawley rats were used. Psilocybin (0.1, 0.3, and 1 mg/kg, IP) or vehicle was administered, and 6 h later, formalin (5%, 50 µL, subcutaneous) was injected into the hindpaw, and the number of flinches and time spent for licking were recorded for 0-10 and 20-60 min for acute and tonic phases, respectively. Another set of rats was used to examine if the antinociceptive effect of psilocybin is via 5-hydroxytryptamine 2a receptor (5-HT2A R). For this aim, rats were pretreated with volinanserin (0.1 mg/kg, highly selective 5-HT2A R antagonist) or vehicle 30 min before psilocybin (0.3 mg/kg). Six hours later, formalin was injected, and the number of flinches and time spent for licking were recorded. Psilocybin (0.1 and 0.3 mg/kg) significantly reduced flinching and licking behaviors in both acute and late pain phases and pretreatment with volinanserin blocked the antinociceptive effect of psilocybin. Our results suggest that psilocybin produces an analgesic effect for acute and tonic inflammatory pain, at least in part, by activating 5-HT2A R.

keywords:
Animals, Rats, Rats, Sprague-Dawley, Pain, Disease Models, Animal, Formaldehyde, Fluorobenzenes, Piperidines, Receptor, Serotonin, 5-HT2A, Analgesics, Hallucinogens, Pain Measurement, Dose-Response Relationship, Drug, Male, Serotonin 5-HT2 Receptor Antagonists, Nociception, Psilocybin

raw_json:
{"europe_pmc_id":"41017560","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Gattuso JJ, Kong G, Bezcioglu B, Lu D, Ekwudo MN, Wilson C, Gubert C, Hannan AJ, Renoir T.
publication_date: 2025-09-11
doi: 10.1016/j.neuropharm.2025.110679
pubmed_id: 40940205
source_url: https://doi.org/10.1016/j.neuropharm.2025.110679
substance_tags: psilocybin
topic_tags: OCD,Pharmacology,Animal Study,Microbiome
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Corrigendum to "Chronic psilocybin administration increases sociability and alters the gut microbiome in male wild-type mice but not in a preclinical model of obsessive-compulsive disorder" [Neuropharmacology 279 (2025) 110648].

raw_json:
{"europe_pmc_id":"40940205","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-11-30
doi: 10.1038/s41380-025-03231-6
pubmed_id: 40913115
source_url: https://doi.org/10.1038/s41380-025-03231-6
substance_tags: psilocybin
topic_tags: Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Correction: Short- and long-term modulation of rat prefrontal cortical activity following single doses of psilocybin.

authors:
Purple RJ, Gupta R, Thomas CW, Golden CT, Palomero-Gallagher N, Carhart-Harris R, Froudist-Walsh S, Jones MW.

raw_json:
{"europe_pmc_id":"40913115","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Brownstien M, Lazar M, Botvinnik A, Pogodin I, Lifschytz T, Lerer B.
publication_date: 2025-09-02
doi: 10.1038/s41380-025-03173-z
pubmed_id: 40897865
source_url: https://doi.org/10.1038/s41380-025-03173-z
substance_tags: psilocybin
topic_tags: OCD
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Reply to Gattuso et al.: "Comments on 'Striking long-term beneficial effects of single-dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming' by Brownstien et al. (2024)".

raw_json:
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publication_date: 2025-08-25
doi: 10.1038/s41380-025-03182-y
pubmed_id: 40858779
source_url: https://doi.org/10.1038/s41380-025-03182-y
substance_tags: psilocybin
topic_tags: Neuroplasticity,Brain Imaging,Biomarkers,Aging,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Short- and long-term modulation of rat prefrontal cortical activity following single doses of psilocybin.

authors:
Purple RJ, Gupta R, Thomas CW, Golden CT, Palomero-Gallagher N, Carhart-Harris R, Froudist-Walsh S, Jones MW.

abstract:
We quantify cellular- and circuit-resolution neural network dynamics following therapeutically relevant doses of the psychedelic psilocybin. Using chronically implanted Neuropixels probes, we recorded local field potentials (LFP) alongside action potentials from hundreds of neurons spanning infralimbic, prelimbic and cingulate subregions of the medial prefrontal cortex of freely-behaving adult rats. Psilocybin (0.3 mg/kg or 1 mg/kg i.p.) unmasked 100 Hz high frequency oscillations that were most pronounced within the infralimbic cortex, persisted for approximately 1 h post-injection and were accompanied by decreased net neuronal firing rates and reduced spike-train complexity. These acute effects were more prominent during resting behaviour than during performance of a sustained attention task. LFP1-, 2- and 6-days post-psilocybin showed gradually-emerging increases in beta and low-gamma (20-60 Hz) power, specific to the infralimbic cortex. These findings reveal features of psychedelic action not readily detectable in human brain imaging, implicating infralimbic network oscillations as potential biomarkers of psychedelic-induced network plasticity over multi-day timescales.

keywords:
Prefrontal Cortex, Neurons, Animals, Rats, Rats, Sprague-Dawley, Hallucinogens, Action Potentials, Time Factors, Male, Psilocybin

raw_json:
{"europe_pmc_id":"40858779","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Drewko AJ, Habets RLP, Brunt TM.
publication_date: 2025-08-22
doi: 10.1038/s41380-025-03169-9
pubmed_id: 40849544
source_url: https://doi.org/10.1038/s41380-025-03169-9
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Above the threshold, beyond the trip: the role of the 5-HT2A receptor in psychedelic-induced neuroplasticity and antidepressant effects.

abstract:
Serotonergic psychedelics, including the recreationally used psilocybin and LSD, have become promising therapeutic agents for the treatment of treatment-resistant depression. While it is generally agreed that they exhibit their antidepressant effects by inducing rapid and sustained neuroplasticity, the molecular mechanisms responsible are widely debated. In particular, the role of the serotonin 5-HT2A receptor, known to mediate the hallucinogenic effects of psychedelics, is under scrutiny. However, many studies remain in conflict on whether action at the receptor is also required for neuroplastic effects. In this narrative review, we examine the available evidence for the involvement of the 5-HT2A receptor in neuroplasticity induction and the possibly antidepressant effects of psychedelics. Firstly, we review the role of decreased neuroplasticity in depression, the evidence for dendrito-, spino- and synaptogenesis promotion by psychedelics, and for its possible regional selectivity. We then discuss the current knowledge on psychedelic action at the 5-HT2A receptor, including its role in promoting hallucinogenic effects. Finally, we critically assess the studies testing the necessity for 5-HT2A signalling for neuroplastic effects and present a model of molecular mechanisms responsible for psychedelic-induced neuroplasticity.

keywords:
Brain, Animals, Humans, Lysergic Acid Diethylamide, Receptor, Serotonin, 5-HT2A, Hallucinogens, Antidepressive Agents, Depression, Neuronal Plasticity, Serotonin 5-HT2 Receptor Agonists, Psilocybin

topic_tags:
Depression,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Review Article,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"40849544","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Between enhancement and risk: A critical review of psychedelic microdosing.
authors: Totomanova I, Haijen ECHM, Hurks PPM, Ramaekers JG, Kuypers KPC.
publication_date: 2025-08-05
doi: 10.1016/j.copsyc.2025.102129
pubmed_id: 40834796
source_url: https://doi.org/10.1016/j.copsyc.2025.102129
substance_tags: psilocybin
topic_tags: Anxiety,Microdosing,Review Article,Observational Study,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Microdosing psychedelics, the regular use of low doses of LSD or psilocybin, have attracted growing public and scientific interest. This review synthesizes findings from 57 human studies on psychological and physiological outcomes in clinical and non-clinical populations. Reported benefits include improved mood, enhanced cognition, social functioning, and mental health, although findings are inconsistent and largely self-reported. Adverse effects such as anxiety, physical discomfort, and cognitive disruption are also frequently reported. Outcomes appear to be highly individual and shaped by user expectations, context, and baseline state. Notably, many experimental studies focus on the acute effects of single low doses, whereas observational studies reflect repeated use and generally report more benefits, while experimental trials tend to yield more null findings. Differences between observational and experimental findings highlight the need for rigorous, placebo-controlled research. While microdosing shows potential in some studies, current evidence remains inconclusive and warrants caution.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Affect, Cognition, Dose-Response Relationship, Drug, Psilocybin

raw_json:
{"europe_pmc_id":"40834796","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Exploring the therapeutic potential of psychedelics in treating substance use disorders.
authors: Li Y, Li H, Wang H, Wang X.
publication_date: 2025-08-18
doi: 10.1038/s41380-025-03168-w
pubmed_id: 40830580
source_url: https://doi.org/10.1038/s41380-025-03168-w
keywords: Animals, Humans, Substance-Related Disorders, Hallucinogens, Psilocybin
substance_tags: psilocybin
topic_tags: Addiction,Neuroplasticity,Clinical Trial,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
abstract:
Psychedelics, particularly psilocybin, have garnered significant attention as potential therapeutic tools for treating substance use disorders (SUDs), such as those related to alcohol, nicotine, heroin (an opioid), or cocaine. Traditional treatments often fall short, leading to high relapse rates and an urgent need for innovative approaches. This article explores the emerging role of psychedelics in SUDs therapy, highlighting their ability to disrupt maladaptive neural circuits, promote neuroplasticity, and facilitate profound psychological insights that address the root causes of SUDs. Clinical trials demonstrate promising results across various forms of SUDs, with psilocybin-assisted therapy showing significant reductions in substance use and improved mental health outcomes. Despite the potential, challenges such as legal barriers, safety concerns, and the need for more rigorous research remain. The future of psychedelics in SUDs treatment is cautiously optimistic, with the possibility of transforming the field of SUDs therapy and offering hope to millions of individuals struggling with SUDs.

raw_json:
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authors: Gillespie CM, Bering JM.
publication_date: 2025-07-22
doi: 10.1016/j.jagp.2025.07.003
pubmed_id: 40829966
source_url: https://doi.org/10.1016/j.jagp.2025.07.003
keywords: Humans, Hallucinogens, Aged, Social Stigma, Depressive Disorder, Treatment-Resistant, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Aging,Older Adults,Treatment-Resistant Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Avoiding Stigma and Sensationalism in Therapeutic Psilocybin Communications: Considerations for Reaching Older Patients.

abstract:
Psilocybin's efficacy as a treatment for treatment-resistant depression (TRD) has led to a wave of new legislation permitting its usage in medical settings. Older adults are affected disproportionately by TRD and may be especially good candidates for this promising treatment. However, due to the drug's past (and present) illicit status and exposure to historic antidrug messaging, older prospective patients may hold more stigmatized attitudes towards this treatment than those who are younger. Stigma and sensationalism pose special challenges for the dissemination of effective, accurate information about therapeutic psilocybin, with recent "hype" around the drug treatment possibly further alienating these individuals. Because current clinical communication strategies may be inadvertently reinforcing negative attitudes about psychedelics rather than reducing them, we offer some general communication guidelines for therapeutic psilocybin geared towards the older patient profile.

raw_json:
{"europe_pmc_id":"40829966","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: [Psilocybin in the setting of treatment-resistant unipolar depression: A case report].
authors: Dumenil M, Cordova G, El-Hage W.
publication_date: 2025-05-22
doi: 10.1016/j.encep.2025.02.007
pubmed_id: 40413068
source_url: https://doi.org/10.1016/j.encep.2025.02.007
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
abstract:
BackgroundCurrent antidepressants have shown certain limitations in the treatment of unipolar depression. Their long onset of action, interactions, and side effects are obstacles to achieving lasting remission of this prevalent, often chronic or recurrent, pathology. Faced with this clinical necessity, research efforts have intensified in recent years around psychedelic drugs, with a particular focus on the mental health benefits of psilocybin. To illustrate this promising approach, we present here the clinical vignette of a student living in France for whom psilocybin led to complete remission after recurrent depressive episodes and a two-year course of Escitalopram.Case presentationJuan, a Mexican student, decided to move to France in 2015 to further his education and broaden his horizons. Since his degree in physiotherapy from Mexico did not qualify him to practice in France, he began studying Biology from 2016 to 2020. Unfortunately, during this period, Juan experienced his first episode of major unipolar depression, marked by feelings of incompetence and academic stagnation. In March 2017, he started an initial course of Escitalopram at 5mg, which provided some relief from his depressive symptoms but did not completely alleviate his anxiety and ruminative thoughts. The treatment was discontinued after three months due to a summer travel plan. By January 2018, he encountered a more intense depressive episode for which he resumed Escitalopram at an increased dose of 10mg. He continued this treatment until August 2019, although it again proved insufficient for full symptom relief. In January 2020, he faced his most challenging relapse, sometimes unable to get out of bed for weeks. This led him to resume Escitalopram, this time at 15mg, but he struggled with significant side effects, including nausea, fatigue, and numbness. Seeking alternative solutions, in the summer of 2020 Juan tried a non-conventional approach in Mexico using psilocybin, a compound found in hallucinogenic mushrooms, under the supervision of a shaman. Following the first administration in July, he noticed a rapid partial improvement in his symptoms; a second administration two weeks later resulted in a full remission of his depressive symptoms. Juan described his experience as profoundly healing, gaining an inner peace and a deep understanding of his struggles. Since 2020, he has remained in full remission without the need for antidepressants. This case highlights the potential role of psilocybin in addressing treatment-resistant depression and the importance of further research into alternative therapeutic options.DiscussionPsilocybin, a 5-HT2A serotonergic receptor agonist, affects cortical neural networks by reducing amygdala reactivity to negative emotions and altering brain connectivity. According to David Nutt's drug harm scale, psilocybin ranks among the least dangerous substances with a relatively low potential for dependence. Despite its potential benefits, responsible and supervised use is essential. Under carefully prepared conditions, psilocybin's psychedelic effects can promote healing by facilitating introspection and altering depressive brain functioning. In April 2021, a double-blind, randomized trial by a British team at Imperial College London compared psilocybin to Escitalopram, revealing higher response and remission rates for psilocybin: 70% of psilocybin-treated patients experienced a reduction of over 50 % in depression levels, compared to 48 % of those on antidepressants-a 22 % increase. However, with only 59 subjects and a 6-week Escitalopram treatment for the control group, further research with larger samples and extended treatment durations is essential.ConclusionThe psychedelic experience appears to have significantly accelerated Juan's clinical remission, enabling him to regain control over his life after years of depression. Although multiple factors may have contributed to Juan's recovery-including his course of Escitalopram-psychedelic effects seem to have served as a powerful tool in overcoming his depression. This case suggests additional therapeutic potentials worth exploring, such as the reduction of alcohol consumption.

keywords:
Humans, Hallucinogens, France, Male, Depressive Disorder, Treatment-Resistant, Psilocybin, Escitalopram, Major Depressive Disorder

topic_tags:
Depression,Anxiety,Receptor Pharmacology,Emotional Processing,Case Report,Treatment-Resistant Depression,Adverse Events,Drug Interactions

raw_json:
{"europe_pmc_id":"40413068","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Domżalska M, Kwiatkowska J, Cichoń I, Sokołowska E.
publication_date: 2025-11-25
doi: 10.1038/s41598-025-29642-7
pubmed_id: 41290975
source_url: https://doi.org/10.1038/s41598-025-29642-7
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 06:48:04
last_checked: 2026-07-01 11:22:00
title:
A comparative assessment of the antidepressant efficacy of ketamine, psilocybin, and fluoxetine in a chronic stress model.

abstract:
Depression is a debilitating mental disorder affecting millions worldwide, yet current pharmacological treatments, such as selective serotonin reuptake inhibitors (SSRIs), often exhibit delayed onset and limited efficacy. The chronic social defeat (CSD) stress model in mice is a well-established preclinical paradigm for inducing depression-like behaviors and evaluating antidepressants effectiveness. This study compared the efficacy of both acute and chronic fluoxetine with acute ketamine and psilocybin treatment in male C57BL/6J mice subjected to CSD. Fluoxetine showed no significant effects 24 h after a single dose or following 7 days of repeated administration; antidepressant-like effects only appeared after 14 days of continuous treatment. In contrast, a single dose of either ketamine or psilocybin significantly reversed social avoidance behavior at 24 h, with sustained effects observed at 7- and 14-days post-treatment. These findings suggest that ketamine and psilocybin elicit rapid and durable, antidepressant-like responses in this preclinical model, in contrast to traditional SSRIs, like fluoxetine, which requires extended treatment duration, mirroring clinical efficacy patterns. The results support the utility of the CSD model in evaluating antidepressant efficacy and highlight the therapeutic potential of fast-acting agents such as ketamine and psilocybin as alternatives to conventional treatments for major depressive disorder.

keywords:
Animals, Mice, Inbred C57BL, Mice, Disease Models, Animal, Fluoxetine, Ketamine, Antidepressive Agents, Behavior, Animal, Depression, Stress, Psychological, Male, Psilocybin, Social Defeat

raw_json:
{"europe_pmc_id":"41290975","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Novel qNMR Method to Quantify Psilocybin and Psilocin in Psychedelic Mushrooms.
authors: Rodríguez L, Morera G, Lupo S, Davyt D, Carrera I, Hernández Dossi G.
publication_date: 2025-11-09
doi: 10.1021/acsomega.5c07092
pubmed_id: 41322617
source_url: https://doi.org/10.1021/acsomega.5c07092
substance_tags: psilocybin,psilocin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Psychedelic mushrooms of the Psilocybe genus contain the psychoactive tryptamines psilocybin and psilocin, compounds currently under clinical investigation for the treatment of depression and other psychiatric conditions. However, the accurate quantification of these alkaloids in fungal matrices remains analytically challenging. Here, we report an optimized extraction protocol and a robust, nondestructive quantification method based on quantitative nuclear magnetic resonance (qNMR) spectroscopy. Using a combination of 1H- and 31P NMR, we achieved simultaneous detection and quantification of psilocin and psilocybin in dried Psilocybe cubensis samples with high accuracy and reproducibility. Our method revealed significant variability in tryptamine content and psilocybin-to-psilocin ratios among user-provided and laboratory-grown samples, underscoring the potential influence of storage conditions on alkaloid stability. Compared with conventional chromatographic approaches, qNMR offers a rapid and calibration-free alternative for the routine analysis of psychedelic fungi. This approach may facilitate quality control in emerging clinical and regulatory contexts of psychedelic mushrooms.

raw_json:
{"europe_pmc_id":"41322617","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kruger DJ, Mersereau G, Sullivan A, Barron J, Herberholz M, Pouyan N, Aday JS, Boehnke KF.
publication_date: 2025-11-24
doi: 10.1186/s12954-025-01337-2
pubmed_id: 41291774
source_url: https://doi.org/10.1186/s12954-025-01337-2
substance_tags: psilocybin
topic_tags: Clinical Trial,Observational Study,Adolescents,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Best practices for first psychedelic experiences: harm reduction advice from the psychedelic community.

abstract:
BackgroundThe use of psychedelics is currently increasing in the United States. Awareness of clinical trials investigating the therapeutic applications of psychedelics may result in a record number of people who use psychedelics for the first-time. This study aimed to develop a harm-reduction resource to facilitate safe and successful psychedelic experiences outside of regulated clinical and research settings. We employed a community-based approach to crowdsource practical recommendations for first-time psychedelic experiences from the psychedelic community.MethodsWe conducted an online survey with 581 individuals who reported psychedelic use (N = 581) on recommendations for people using psychedelics for the first-time, following the principles of community-based collaborative research. The survey assessed recommendations for and against specific psychedelics for first-time experiences, recommendations for and against combinations of psychedelics, and other advice for first-time experiences. Open-ended follow-up questions were included to understand participants' reasons for their recommendations. An experienced qualitative researcher and two qualitative coders analyzed responses to open-ended items.ResultsMost participants recommended psilocybin for first-time psychedelic experiences, approximately half recommended cannabis, and a third recommended MDMA/MDA (3,4-methylenedioxymethamphetamine/3,4-methylenedioxyamphetamine, ecstasy, molly). These substances were favored for their moderate intensity, dose-dependent effects, precise dosing, and relatively short duration of effects. Conversely, substances such as ayahuasca, DMT (N,N-dimethyltryptamine), 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), and Salvia divinorum or salvinorin A were not recommended due to their intensity, mental and physical health risks, and safety concerns. Participants advised against mixing psychedelics with alcohol, stimulants, antidepressants, and narcotics/opiates. Additional recommendations included embracing the experience, learning about the substance and its effects, and setting intentions for the experience.ConclusionsGiven the growing interest in psychedelics despite limited legal access and systematic education available, it is crucial to inform the public about practices that minimize risks. This project compiled recommendations from individuals who self-identified being experienced with psychedelics. The active involvement of the psychedelic community may enhance research quality and public trust in the findings.

keywords:
Humans, Hallucinogens, Harm Reduction, Dose-Response Relationship, Drug, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, United States, Female, Male, Practice Guidelines as Topic, Young Adult, Surveys and Questionnaires, Community Participation

raw_json:
{"europe_pmc_id":"41291774","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin alters visual contextual computations.
authors: Aqil M, de Hollander G, Vreugdenhil N, Knapen T, Dumoulin SO.
publication_date: 2025-11-20
doi: 10.1038/s41467-025-65150-y
pubmed_id: 41271688
source_url: https://doi.org/10.1038/s41467-025-65150-y
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Psilocybin alters perception and brain dynamics. Here, we investigate the effects of psilocybin using psychophysics, ultra-high field functional MRI, and computational modeling. We find that psilocybin alters contextual perception in the Ebbinghaus illusion, as well as contextual modulation in cortical responses to visual stimuli. We propose a computational model capable of capturing and linking these changes. Leveraging vision as a beachhead, our findings highlight the alteration of contextual computations as a potential general mechanism underlying psychedelic action.

keywords:
Brain, Humans, Illusions, Hallucinogens, Magnetic Resonance Imaging, Photic Stimulation, Visual Perception, Psychophysics, Computer Simulation, Adult, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"41271688","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin and Chronic Pain: A New Perspective for Future Pain Therapists?
authors: Natoli S, Cuomo A, Marchesini M, Luongo L, Lo Bianco G, Guardamagna VA, Yamaguchi S.
publication_date: 2025-11-19
doi: 10.3390/medsci13040277
pubmed_id: 41283278
source_url: https://doi.org/10.3390/medsci13040277
keywords: Animals, Humans, Analgesics, Hallucinogens, Quality of Life, Chronic Pain, Psilocybin
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
BackgroundChronic pain affects nearly one in five adults worldwide and remains a major healthcare burden due to its persistence, multidimensional impact, and resistance to conventional therapies. The opioid crisis has further highlighted the urgent need for safer and more effective alternatives. Psilocybin, a serotonergic psychedelic compound, has re-emerged as a potential therapeutic option for chronic pain given its effects on neuroplasticity, neuroinflammation, and emotional regulation.MethodsThis narrative review synthesized evidence from published preclinical and clinical studies. The focus was on the mechanisms of action of psilocybin, animal models of neuropathic and inflammatory pain, and early human trials exploring its effects on pain, mood, and quality of life.ResultsPreclinical studies demonstrated that psilocybin promotes synaptogenesis via BDNF-TrkB signalling, modulates 5-HT2A receptor activity, and reduces neuroinflammatory processes, leading to persistent analgesic and anxiolytic effects. Animal models of chemotherapy-induced neuropathy and inflammatory pain showed long-lasting antinociceptive responses. Clinical studies, though limited, reported improvements in depression, anxiety, resilience, and quality of life in patients with advanced cancer and chronic conditions, with preliminary evidence of analgesic benefit.ConclusionsPsilocybin shows promise as a multidimensional therapy for chronic pain, addressing both sensory and affective components. However, ethical issues, safety concerns, and regulatory barriers necessitate careful management, and robust randomized controlled trials are essential to confirm efficacy and guide clinical translation.

topic_tags:
Depression,Anxiety,Addiction,Chronic Pain,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Resilience,Emotional Processing,Randomized Controlled Trial,Review Article,Animal Study,Safety,Inflammation

raw_json:
{"europe_pmc_id":"41283278","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Sex-specific role of the 5-HT2A receptor in psilocybin-induced extinction of opioid reward.
publication_date: 2025-11-19
doi: 10.1038/s41467-025-64887-w
pubmed_id: 41266307
source_url: https://doi.org/10.1038/s41467-025-64887-w
substance_tags: psilocybin
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
authors:
Jaster AM, Hadlock TM, Buzzi B, Maltman JL, Silva GM, Saha S, Koseli E, Pondelick AM, Thakur N, Zhang X, Li G, Ledesma-Corvi S, Moore KN, Peterson HR, Fujita B, Zylko AL, Lewis MR, Poklis JL, Halquist MS, Wolstenholme JT, Selley DE, Hamilton PJ, Lu C, Damaj MI, González-Maeso J.

abstract:
Emerging evidence suggests that classical psychedelics may offer therapeutic potential for opioid use disorder (OUD) by alleviating key hallmarks such as altered reward processing and dependence. However, the mechanisms behind these effects remain unclear. Our data demonstrate that a single administration of the psychedelic psilocybin (PSI) reduces conditioned behavior and withdrawal induced by the opioid oxycodone (OXY) in male mice but not in females, and this effect is mediated via the 5-HT2A receptor (5-HT2AR). We show that the sex-specific attenuation of OXY preference is driven by 5-HT2AR activation in frontal cortex pyramidal neurons projecting to the nucleus accumbens (NAc). Additionally, PSI modulates epigenomic regulation following repeated OXY exposure and induces sex-specific NAc dendritic structural plasticity independently of 5-HT2AR. Notably, female frontal cortex and NAc show fewer changes at gene enhancer regions in response to PSI, repeated OXY, or combined PSI-OXY treatment compared to males, with the frontal cortex exhibiting more pronounced sex differences than the NAc at the epigenomic level. Together, these results provide new insights into the neural and epigenetic mechanisms of psychedelic-induced plasticity in OUD, while also highlighting sex differences in PSI's modulation of reward pathways and its therapeutic potential.

keywords:
Pyramidal Cells, Nucleus Accumbens, Frontal Lobe, Animals, Mice, Inbred C57BL, Mice, Receptor, Serotonin, 5-HT2A, Analgesics, Opioid, Hallucinogens, Reward, Epigenesis, Genetic, Sex Characteristics, Female, Male, Extinction, Psychological, Psilocybin

topic_tags:
Addiction,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Epigenetics,Animal Study,Genomics

raw_json:
{"europe_pmc_id":"41266307","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Pharmacotherapy to Prevent Alcohol Relapse in Alcohol-Associated Liver Disease.
authors: Zhang W, Hwang SY, Luther J.
publication_date: 2025-11-18
doi: 10.1007/s11894-025-01026-x
pubmed_id: 41258558
source_url: https://doi.org/10.1007/s11894-025-01026-x
substance_tags: psilocybin
topic_tags: Addiction,Receptor Pharmacology,Review Article
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Purpose of reviewAlcohol use disorder (AUD) drives alcohol-associated liver disease (ALD), and relapsing after abstinence remains a significant challenge before and after transplantation. This review summarizes evidence for pharmacotherapies in relapse prevention and their integration into ALD care.Recent findingsNaltrexone and acamprosate reduce the relapse in the general AUD population, though data in ALD are limited. Baclofen is the only drug tested in randomized trials in cirrhosis, with early benefit but mixed results in later studies. Gabapentin and topiramate are promising off-label options. Emerging agents include glucagon-like peptide-1 (GLP-1) receptor agonists, psilocybin, and fibroblast growth factor-21 (FGF21) analogs, all showing early signals in reducing alcohol use. Despite guideline support, pharmacotherapy is underutilized in ALD due to lack of insight, stigma, provider inexperience, and fragmented care. Integrated programs across the disease spectrum demonstrate feasibility and may improve pharmacotherapy uptake. Pharmacotherapy is effective yet underused for relapse prevention in ALD. Integration with behavioral interventions and multidisciplinary care is essential to expand access, evaluate novel therapies, and improve patient outcomes.

keywords:
Humans, Liver Diseases, Alcoholic, Alcoholism, Recurrence, Naltrexone, Alcohol Deterrents, Secondary Prevention, Acamprosate

raw_json:
{"europe_pmc_id":"41258558","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Agrawal R, Gillie D, Mungenast A, Chytil M, Engel S, Wu MC, Rasmussen K, Salinas E, Olson DE.
publication_date: 2025-10-12
doi: 10.1021/acschemneuro.5c00667
pubmed_id: 41078264
source_url: https://doi.org/10.1021/acschemneuro.5c00667
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Pharmacology,Animal Study,Safety
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Zalsupindole is a Nondissociative, Nonhallucinogenic Neuroplastogen with Therapeutic Effects Comparable to Ketamine and Psychedelics.

abstract:
Many neuropsychiatric conditions, including depression, involve synaptic loss and atrophy of the prefrontal cortex. The rapid regrowth of cortical neurons has been hypothesized to explain the rapid and enduring therapeutic effects of psychedelics and the dissociative anesthetic ketamine. However, safety concerns related to hallucinogenic/dissociative properties have limited the addressable patient population that could potentially be treated with these compounds. Thus, substantial efforts have focused on the development of neuroplastogens─compounds that can produce similar effects on structural and functional neuroplasticity as well as rapid and sustained therapeutic behavioral effects without inducing hallucinations or dissociation. Here, we describe the preclinical pharmacology and efficacy of zalsupindole─the first neuroplastogen to be administered to patients with major depressive disorder. Despite lacking any of the acute cellular and behavioral characteristics of hallucinogenic/dissociative compounds, zalsupindole produced robust effects on structural and functional neuroplasticity in the prefrontal cortex of rats as well as sustained antidepressant-like responses. These effects were comparable to or greater than those of ketamine, psilocybin, and N,N-dimethyltryptamine, suggesting that zalsupindole might represent a safer and more scalable neuroplasticity-promoting compound for treating conditions like depression.

keywords:
Prefrontal Cortex, Animals, Humans, Rats, Rats, Sprague-Dawley, Ketamine, Indoles, Hallucinogens, Antidepressive Agents, Neuronal Plasticity, Male, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"41078264","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Synaptic priming: A framework for pharmacotherapy in depression.
authors: Brown KA, Ajibola MI, Medeiros GC, Gould TD.
publication_date: 2025-10-07
doi: 10.1016/j.neuron.2025.09.010
pubmed_id: 41067229
source_url: https://doi.org/10.1016/j.neuron.2025.09.010
keywords: Synapses, Animals, Humans, Ketamine, Antidepressive Agents, Depression, Neuronal Plasticity
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Pharmacology,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Recent antidepressant drug development focuses on a next generation of drugs to rapidly relieve symptoms. Yet, how ketamine, the prototype rapid-acting antidepressant, maintains symptom relief days after drug elimination, and how repeated doses sustain longer-lasting therapeutic effects, remains unclear. Derived from elements of metaplasticity (synaptic priming), this review discusses a framework in which rapid-acting antidepressants prime synapses such that subsequent doses evoke stronger plasticity. Within this framework, we describe how the indirect relationship between ketamine's pharmacokinetics and sustained antidepressant pharmacodynamics reveals a dosing model (primer pharmacology) that can be harnessed to fine-tune therapeutic outcomes. This review also explores how plasticity machinery engaged by antidepressant pharmacotherapies overlaps with priming induced by contextual conditions relevant to depression (e.g., stress and psychotherapy), suggesting innovative opportunities for treatment strategies with emerging primers (e.g., psychedelics such as psilocybin). The integration of synaptic priming with primer pharmacology reveals a model to guide clinical and translational work in psychiatry.

raw_json:
{"europe_pmc_id":"41067229","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Gattuso JJ, Kong G, Bezcioglu B, Lu D, Ekwudo MN, Wilson C, Gubert C, Hannan AJ, Renoir T.
publication_date: 2025-08-20
doi: 10.1016/j.neuropharm.2025.110648
pubmed_id: 40849086
source_url: https://doi.org/10.1016/j.neuropharm.2025.110648
substance_tags: psilocybin
topic_tags: Depression,Anxiety,OCD,Mechanism of Action,Receptor Pharmacology,Animal Study,Microbiome
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Chronic psilocybin administration increases sociability and alters the gut microbiome in male wild-type mice but not in a preclinical model of obsessive-compulsive disorder.

abstract:
Psilocybin, a serotonergic compound that produces psychedelic effects primarily through activation of the 5-HT2A receptor, has shown promise in treating neuropsychiatric conditions, including obsessive-compulsive disorder (OCD). However, the effects of chronic psilocybin administration on gut function, microbiota, and behavioural phenotypes remain understudied. The present study investigated the effects of chronic psilocybin (0.1 and 1 mg/kg, oral gavage) on gut and behavioural measures in wild-type (WT) and SAPAP3 knockout (KO) mice, a model of OCD-like phenotypes. We present novel evidence that SAPAP3 KO mice exhibit social deficits, and that chronic psilocybin increases sociability in male WT mice. Although no therapeutic effects were observed at either dose on anxiety-, compulsive-, or depressive-like behaviour, chronic psilocybin also did not induce psychosis-like behaviours. A dose-dependent effect of psilocybin was observed on gut motility. Although chronic administration did not significantly alter overall gut microbiome diversity, reductions in Lactobacillus murinus, Lactobacillus animalis, and Alistipes dispar were observed in male WT mice, but not in KO mice or female mice. Integrative analysis revealed that a microbial cluster, comprising Lactobacillus and Alistipes species, correlated with locomotion, head-twitch response and gut motility, effectively differentiating psilocybin-treated mice from vehicle controls. This suggests a potential host-microbiome feedback mechanism regulating host serotonin signalling, linked to central and peripheral 5-HT2A receptor activation. Additionally, separate microbial clusters were associated with startle response and sociability, indicating that psilocybin may engage distinct neural pathways to mediate these behaviours. These findings highlight the importance of considering the microbiome and sex in future psychedelic research and open new avenues for exploring the microbiota-gut-brain axis as a target for future therapeutic strategies.

keywords:
Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Disease Models, Animal, Nerve Tissue Proteins, Hallucinogens, Social Behavior, Obsessive-Compulsive Disorder, Female, Male, Gastrointestinal Microbiome, Psilocybin

raw_json:
{"europe_pmc_id":"40849086","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Age- and estrous-dependent effects of psilocybin in rats.
publication_date: 2025-07-29
doi: 10.1016/j.neuropharm.2025.110619
pubmed_id: 40744407
source_url: https://doi.org/10.1016/j.neuropharm.2025.110619
substance_tags: psilocybin
topic_tags: Anxiety,Animal Study,Adolescents,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
authors:
Zylko AL, Rakoczy RJ, Roberts BF, Wilson M, Powell A, Page A, Heitkamp M, Feist D, Jones JA, McMurray MS.

abstract:
Psilocybin, a psychedelic compound in "magic" mushrooms, has promise as a novel treatment for psychiatric disorders, many of which are more prevalent in females and have onsets during adolescence. However, there is a lack of research about how factors such as sex and age affect responses to psilocybin, as well as potential safety concerns with developmental exposure. The primary objectives of this preclinical study were to determine if psilocybin-induced head twitch responses differ between adolescent and adult rats, and if estrous phase contributes to variation in female head twitch responses. Secondarily, this study sought to determine if treatment with psilocybin during adolescence has long-term effects on anxiety-associated behaviors and behavioral flexibility. Results showed that 1 mg/kg intragastric psilocybin failed to elicit head twitch responses in adolescents (P35 and P45) but elicited robust responses in adult rats. Further, adolescent psilocybin exposure did not cause long-term differences in performance on the elevated zero maze or probabilistic reversal learning tasks. Lastly, adult females in diestrus showed increased head twitch responses after 1 mg/kg psilocybin compared to females in proestrus. Collectively, these results highlight the existence of age- and sex-dependent differences in the effects of psychedelics, while finding no long-term effects on selected behaviors after adolescent exposure. These findings have implications on psychedelic study design, emphasizing the need for inclusive research considering age, sex, and hormonal status.

keywords:
Animals, Rats, Rats, Sprague-Dawley, Hallucinogens, Maze Learning, Reversal Learning, Age Factors, Estrous Cycle, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"40744407","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Luo W, Dai Q, van Beek TA, Zuilhof H, Chen B, Chen Z, Salentijn GI.
publication_date: 2025-10-31
source_url: https://europepmc.org/article/AGR/IND609225828
substance_tags: psilocin
topic_tags: General
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Paper spray and direct mushroom spray mass spectrometry methods for the analysis of psycho-neurological disorder toxins

abstract:
Fast screening approaches based on paper spray ionization were developed to identify psycho-neurological disorders mushrooms. Directly spraying from mushroom tissue already allowed direct identification of muscarine, psilocin, and ibotenic acid within 2-3 min. For quantitative analysis of the more challenging ibotenic acid, a new anion-exchange modified paper spray tandem mass spectrometry (AEPS-MS/MS) method was established to increase selectivity and sensitivity. The developed method was benchmarked against HPLC-MS/MS (with detection limits of 0.009 μg mL⁻¹) and could reach detection limits of 1.3 μg mL⁻¹ for ibotenic acid spiked in mushroom extract, with acceptable accuracy (−14.0 % to +5.1 %) and precision (10.8 % to 18.0 %). In addition, the developed method was compared with solid-phase extraction coupled with PS-MS/MS (with detection limits of 2.8 μg mL⁻¹). Finally, the AEPS-MS/MS was applied for the quantitative analysis of ibotenic acid in Amanita griseopantherina, matching results from HPLC-MS/MS.

raw_json:
{"europe_pmc_id":"IND609225828","source":"AGR","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-06-08
doi: 10.1016/j.jad.2025.119655
pubmed_id: 40499827
source_url: https://doi.org/10.1016/j.jad.2025.119655
substance_tags: psilocybin
topic_tags: Depression,Treatment-Resistant Depression,Veterans
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Long-term outcomes of single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression - 12-month data from an open-label pilot study.

authors:
Ellis S, Bostian C, Donnelly A, Feng W, Eisen K, Lean M, Conlan E, Ostacher M, Aaronson S, Suppes T.

abstract:
BackgroundOne-third of Veterans with major depressive disorder suffer from treatment-resistant depression (TRD). This is the first study to evaluate the long-term outcomes of psilocybin in Veterans with severe TRD.MethodsThis paper presents 12-month results from an open-label pilot study assessing the effects of 25 mg psilocybin in Veterans with severe TRD, defined as a major depressive episode failing to respond to ≥5 treatments, or lasting >2 years. 10 out of 15 participants completed the 12-month follow-up. Depression severity was measured by Montgomery-Åsberg Depression Rating scale (MADRS) at 6, 9, and 12 months posttreatment. Response was defined as ≥50 % reduction in MADRS, and remission as ≤10 MADRS score.ResultsDepression scores show significant reductions from Baseline across all timepoints. However, there was an increase in MADRS scores from short-term timepoints (Weeks 3 and 12) to Month 12. Of 10 participants, at Month 6, 80 % met response and 50 % met remission criteria for the MADRS. At Month 9, acute responses began to wane. At Month 12, 40 % maintained response and 30 % maintained remission.LimitationsLimitations include the small sample size and the uncontrolled, unblinded design.ConclusionsIn this first-of-kind study on long-term effects of psilocybin for Veterans with severe TRD, depression scores showed significant sustained reductions up to 12-months. However, the antidepressant effects began to wane at 6 months, and then more substantially after 9 months, although these increases in MADRS did not reach statistical significance. Further research is needed.Trial registrationClinicalTrials.gov Identifier: NCT04433858.

keywords:
Humans, Hallucinogens, Treatment Outcome, Follow-Up Studies, Pilot Projects, Psychiatric Status Rating Scales, Adult, Middle Aged, Veterans, United States, Female, Male, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"40499827","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Assessing the Potential Cardiovascular Risk of Microdosing the Psychedelic LSD in Mice.
publication_date: 2025-08-21
doi: 10.1021/acsptsci.5c00202
pubmed_id: 41789300
source_url: https://doi.org/10.1021/acsptsci.5c00202
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Microdosing,Emotional Processing,Animal Study,Safety
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
authors:
Effinger DP, Schalk SS, King JL, Wallingford JR, O'Connell CK, Calderon JR, Kopecky BJ, McCorvy JD, Thompson SM.

abstract:
Microdosing, the prolonged ingestion of psychedelics at subhallucinogenic doses, has gained popularity for its perceived cognitive and emotional benefits. Psychedelics have high affinity for 5-HT2B receptors, a receptor known to cause human heart disease with strong chronic activation. We investigated the effects of microdosed psychedelics on cardiovascular health in mice using echocardiography after chronically administering either serotonin or d-fenfluramine as positive controls or lysergic acid diethylamide (LSD) at two subhallucinogenic doses. Serotonin produced significant ventricular thickening at 4- and 8-weeks, and d-fenfluramine caused aortic valve regurgitation at 4-weeks. No significant changes were observed in any vehicle or LSD group. We determined the affinity and potency of LSD, psilocybin, and norfenfluramine at mouse and human 5-HT2BRs and observed no significant differences. We calculated that levels of 5-HT2B activation by low-dose LSD were substantial, but short-lived, compared to the cardiotoxin d-fenfluramine. Together, these data provide no evidence of ventricular or valvular remodeling associated with prolonged administration of low-dose LSD in mice.

raw_json:
{"europe_pmc_id":"41789300","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: McHerron D, Barber M, Ham R, Liknaitzky P, Carter A, Gardner J
journal: Therapeutic advances in psychopharmacology
publication_date: 2024-12-31
doi: 10.1177/20451253251377191
pubmed_id: 41244962
source_url: https://pubmed.ncbi.nlm.nih.gov/41244962/
substance_tags: psilocybin
topic_tags: Aging,Clinical Trial
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"41244962"}
title:
The ethical use of therapeutic touch in psychedelic-assisted therapy: a qualitative study of researcher perspectives and experiences.

abstract:
Physical touch is often included as a supportive or therapeutic tool in psychedelic-assisted therapy (PAT), involving instrumental forms of physical contact, supportive touch and somatic techniques. However, participants under the influence of psychedelics have reduced capacity to provide consent, are more suggestible and may experience and interpret therapeutic touch in ways they did not expect prior to taking the drug. Yet little research has been conducted on the considerations and approaches to therapeutic touch in clinical trials of PAT.
This study explored the experiences and perspectives of PAT researchers on the use and consent to therapeutic touch in clinical trials of PAT.
A qualitative study using semi-structured interviews.
Sixteen PAT researchers involved in clinical trials of PAT were interviewed. Reflexive thematic analysis was used to analyse the data. The reporting of this study conforms to the Consolidated Criteria for Reporting Qualitative Research Checklist (COREQ).
Three themes were uncovered through reflexive thematic analysis: (1) flexible frameworks, (2) therapeutic alliance and (3) boundary management. Researchers discussed consent challenges across the broad spectrum of physical contact existing in PAT protocols at the time. Researchers indicated that consent to therapeutic touch should be established prior to the dosing sessions and continually managed throughout the course of treatment. Flexibility in consent protocols enabled researchers to interpret and approach consent through the development of a strong therapeutic alliance; however, flexibility could also lead to challenges in boundary management. Researchers emphasised the need for greater ethical guidance in instances where trial participants change their established preferences during dosing sessions, and limits on expanding consent after drug administration.
Clear guidelines for obtaining consent, managing changing preferences and training on the management of boundary transgressions were viewed as essential for ethical research and practice of PAT.

keywords:
MDMA, ethics, informed consent, psilocybin, psychedelic-assisted therapy, psychedelics, therapeutic touch


authors: Martens MAG, Cunha BG, Erritzoe D, Nutt D, Carhart-Harris R, Harmer CJ.
publication_date: 2025-11-12
doi: 10.1038/s41398-025-03693-w
pubmed_id: 41257994
source_url: https://doi.org/10.1038/s41398-025-03693-w
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Emotional Processing,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Negative affective bias in depression following treatment with psilocybin or escitalopram - a secondary analysis from a randomized trial.

abstract:
Recent clinical trial data suggests that ratings on depression scales are lowered after psilocybin therapy compared to placebo, though it is unclear what neuropsychological mechanisms underpin these effects. This study compared psilocybin, with an established antidepressant, escitalopram, to investigate whether there are shared or distinct effects on emotional information processing. Patients with long-standing moderate-to-severe depression were randomly and double-blindly assigned in a 1:1 ratio to receive either 1) two doses of 25 mg of psilocybin, 3-weeks apart, plus 6-weeks of daily placebo (psilocybin group N = 30); or 2) two doses of 1 mg of psilocybin 3-weeks apart plus 6-weeks of daily oral escitalopram (escitalopram group N = 29); all patients received the same psychological support. Behavioural measures of affective bias as well as subjective measures of depression were collected at baseline and at the primary 6-week endpoint, using an established computerised task (Facial Emotion Recognition Task) and Quick Inventory of Depressive Symptomatology, respectively. Change in affective bias was further correlated with change in depression scores measured concurrently as well as at 1-month post-trial follow-up (week-10), corrected for baseline depression severity. Negative bias in facial expression recognition decreased after both treatments to a comparable level. Concurrently, change in negative affective bias was not associated with change in depression. Longitudinally, a decrease in the misclassification of positive faces as negative was associated with a decrease in depression scores at week-10 for the escitalopram group only. Therefore, a more positive behavioural bias in emotional processing was seen following psilocybin and citalopram compared to baseline. This highlights the potential for at least some overlap in cognitive mechanisms across two distinct treatments, which is noteworthy given the short dosing regimen with psilocybin.

keywords:
Humans, Citalopram, Hallucinogens, Treatment Outcome, Double-Blind Method, Depression, Affect, Adult, Middle Aged, Female, Male, Facial Recognition, Psilocybin, Escitalopram, Secondary Data Analysis

raw_json:
{"europe_pmc_id":"41257994","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Novel Psilocin Derivatives as Serotonergic Psychedelic Agents for Treating CNS Disorders.
authors: Sabnis RW.
publication_date: 2025-10-21
doi: 10.1021/acsmedchemlett.5c00608
pubmed_id: 41256997
source_url: https://doi.org/10.1021/acsmedchemlett.5c00608
substance_tags: psilocin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Provided herein are novel psilocin derivatives as serotonergic psychedelic agents, pharmaceutical compositions, use of such compounds in treating central nervous system (CNS) disorders, and processes for preparing such compounds.

raw_json:
{"europe_pmc_id":"41256997","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Stabilizing Psilocybin Pharmacology and Tuning Safety with Atypical Antipsychotic Cotherapy.
authors: Renner AC, Kargbo RB.
publication_date: 2025-10-09
doi: 10.1021/acsmedchemlett.5c00595
pubmed_id: 41256989
source_url: https://doi.org/10.1021/acsmedchemlett.5c00595
substance_tags: psilocybin,psilocin
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
A crystalline cocrystal of psilocin and psilocybin enhances exposure, neuroplasticity biomarkers, and functional activity, while adjunctive atypical antipsychotics modulate serotonergic signaling to mitigate 5-HT2B-linked safety concerns. Together, these inventions advance formulation, mechanistic selectivity, and translational biomarkersoffering a chemistry-enabled path to scalable psychedelic therapy with improved cardiac safety and durable neuroplastic responses across organoid and animal models.

topic_tags:
Neuroplasticity,Pharmacology,Mechanism of Action,Receptor Pharmacology,Biomarkers,Animal Study,Safety

raw_json:
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title: Toward Precision Psychedelic Therapies: Chemical, Computational, and Neuromodulatory Innovations.
authors: Renner AC, Kargbo RB.
publication_date: 2025-10-08
doi: 10.1021/acsmedchemlett.5c00597
pubmed_id: 41256977
source_url: https://doi.org/10.1021/acsmedchemlett.5c00597
substance_tags: psilocin
topic_tags: Neuroplasticity,Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
abstract:
Recent patents disclose complementary strategies to optimize psychedelic-assisted therapy. Novel psilocin prodrugs improve pharmacokinetics and stability, while digital systems enable cognitive state monitoring during treatment. Parallel advances in combining neuroplastogen drugs with transcranial electrical stimulation highlight a model-driven approach to enhance and personalize neural plasticity. Together, these innovations converge on a precision framework for treating neuropsychiatric disorders.

raw_json:
{"europe_pmc_id":"41256977","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Oo AP, Tseu S, Ponnusamy A.
publication_date: 2025-11-11
doi: 10.7759/cureus.96718
pubmed_id: 41393631
source_url: https://doi.org/10.7759/cureus.96718
substance_tags: psilocybin
topic_tags: Addiction,Brain Imaging,Aging,Randomized Controlled Trial,Toxicity
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Acute Kidney Failure and Myocarditis Triggered by Magic Mushroom Toxicity in a Patient With Prior Cocaine Exposure.

abstract:
Magic mushroom poisoning can be associated with acute kidney injury (AKI), primarily due to ischemic acute tubular necrosis (ATN). Additionally, the use of cocaine can lead to both venous and arterial thrombosis through its vasoconstrictive and prothrombotic effects. In this article, a middle-aged gentleman with a previous history of cocaine use was admitted with severe anuric AKI requiring dialysis after magic mushroom poisoning. He developed supraventricular tachycardia (SVT) with significantly raised troponin T and severe left ventricular dysfunction, which was thought to be due to myocarditis induced by magic mushrooms. In addition, imaging revealed extensive thrombosis in multiple blood vessels, including the abdominal aorta, superior mesenteric artery (SMA), and bilateral iliac arteries, resulting in right kidney infarction and a pulmonary embolism in the right lower lobe. There is also a possibility that psilocybin-containing magic mushrooms may induce vasoconstriction, which could theoretically contribute to thrombotic events. However, direct evidence linking psilocybin to thrombosis remains limited.

raw_json:
{"europe_pmc_id":"41393631","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Mehtani NJ, Mian MN, Agin-Liebes G, Coker AR, Huebner C, Anderson BT, Mitchell JM.
publication_date: 2025-11-09
doi: 10.1080/02791072.2025.2583960
pubmed_id: 41214462
source_url: https://doi.org/10.1080/02791072.2025.2583960
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Wellbeing,Spirituality,Safety
study_type: Qualitative Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Psychedelic Augmentation of 12-Step Engagement: A Novel, Accessible Approach to Enhance Community-Based Recovery from Substance Use Disorders.

abstract:
Amid an evolving psychedelic drug policy landscape and limitations of existing substance use disorder (SUD) treatments, a novel addiction recovery paradigm has emerged involving augmentation of 12-Step program engagement with therapeutic psychedelic use. A preliminary qualitative analysis was initiated to describe this movement by examining real-world experiences of participants in remission from alcohol, opioid, and stimulant use disorders. Between November 2022 and February 2023, data collection was piloted with nine individuals reporting ayahuasca, ibogaine, psilocybin, and/or peyote use in combination with 12-Step engagement. Participants were intentionally recruited through a community partner to explore this emerging phenomenon; findings are not intended to generalize to broader 12-Step communities. Motivations included challenges with sobriety, psychological distress during abstinence, dissatisfaction with existing SUD treatments, and the relative accessibility of this community-based approach compared to clinical care. Participants highlighted reduced SUD-related cravings, psychospiritual mechanisms of behavior change, and synergistic effects of psychedelics with Steps 2, 4, and 11. Tensions with abstinence-oriented philosophies were acknowledged, and risks related to unsupervised psychedelic use were central to participants' narratives; however, participants ultimately found that psychedelics enhanced their recovery by deepening actionable Step-work and improving psychosocial well-being. Pilot findings underscore a need for further research into this low-cost, accessible approach.

raw_json:
{"europe_pmc_id":"41214462","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Dissimilar Reactions and Enzymes for Psilocybin Biosynthesis in Inocybe and Psilocybe Mushrooms.
authors: Schäfer T, Haun F, Rupp B, Hoffmeister D.
publication_date: 2025-09-20
doi: 10.1002/anie.202512017
pubmed_id: 40977073
source_url: https://doi.org/10.1002/anie.202512017
keywords: Agaricales, Methyltransferases, Psilocybe, Psilocybin
substance_tags: psilocybin
topic_tags: Mechanism of Action,In Vitro Study
study_type: In Vitro Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine, 1) is the main indolethyl-amine natural product of psychotropic (so-called "magic") mushrooms. The majority of 1-producing species belongs to the eponymous genus Psilocybe, for which the biosynthetic events, beginning from l-tryptophan (2), and the involved enzymes have thoroughly been characterized. Some Inocybe (fiber cap) species, among them Inocybe corydalina, produce 1 as well. In product formation assays, we characterized four recombinantly produced biosynthesis enzymes of this species in vitro: IpsD, a pyridoxal-5'-phosphate-dependent l-tryptophan decarboxylase, the kinase IpsK, and two near-identical methyltransferases, IpsM1 and IpsM2. The fifth enzyme, the insoluble monooxygenase IpsH, was analyzed in silico. Surprisingly, none of the reactions intrinsic to the 1 pathway in Psilocybe species takes place in I. corydalina. Contrasting the situation in Psilocybe, the Inocybe pathway is branched and leads to baeocystin (4-phosphoryloxy-N-methyltryptamine, 3) as a second end product. Our results demonstrate that mushrooms recruited distantly or entirely unrelated enzymes to evolve the metabolic capacity for 1 biosynthesis twice independently.

raw_json:
{"europe_pmc_id":"40977073","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Zech JM, Richard J, Jones GM
journal: Journal of psychoactive drugs
publication_date: 2025-11-08
doi: 10.1080/02791072.2025.2583967
pubmed_id: 41208129
source_url: https://pubmed.ncbi.nlm.nih.gov/41208129/
keywords: AUD, Alcohol, LSD, MDMA, ketamine, psilocybin
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Randomized Controlled Trial,Safety
study_type: Randomized Controlled Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"41208129"}
title:
The Relationship Between Psychedelic Use and Alcohol Use Disorder in a Nationally Representative Sample.

abstract:
Psychedelic-assisted interventions are emerging as potential treatments for substance use disorders, including alcohol use disorder (AUD). While recent randomized controlled trials suggest efficacy for certain psychedelics and related compounds in treating AUD, the impact of naturalistic psychedelic use on problematic alcohol consumption remains underexplored. This study examines associations between psychedelic use and AUD in a nationally representative sample ( = 139,524). Logistic regression was used to examine the association between AUD and past-year use of LSD, MDMA, and ketamine, controlling for demographics and comorbid substance use. Past-year LSD use was significantly associated with lower odds of AUD (adjusted odds ratio [aOR] = 0.70, =.006). However, use of MDMA (aOR = 1.17, =.229) and ketamine (aOR = 1.28, =.235) was not associated with AUD. In a quasi-Poisson regression analysis, past-year LSD use was found to be associated with 15.7% fewer AUD symptoms (IRR = 0.84, 95% CI: 0.72 - 0.98, =.033), but neither past-year MDMA nor past-year ketamine use were significantly associated with AUD symptoms (MDMA: IRR = 0.97, 95% CI: 0.83 - 1.13, =.731; ketamine: IRR = 1.21, 95% CI: 0.93 - 1.57, =.139). Taken together, these findings indicate differential associations between specific psychedelics and AUD, with LSD use linked to a reduced risk of AUD. The results underscore the need for further research into the mechanisms by which LSD may influence alcohol use and AUD risk.


authors: Fadahunsi N, Lund J, Breum AW, Mathiesen CV, Larsen IB, Knudsen GM, Klein AB, Clemmensen C.
publication_date: 2025-11-05
doi: 10.1038/s41398-025-03729-1
pubmed_id: 41198613
source_url: https://doi.org/10.1038/s41398-025-03729-1
substance_tags: psilocybin
topic_tags: Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Correction: Acute and long-term effects of psilocybin on energy balance and feeding behavior in mice.

raw_json:
{"europe_pmc_id":"41198613","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Soltanzadeh M, Wang Z, Allohverdi SG, Charlton CE, Schmidt A, Vollenweider FX, Diaconescu AO.
publication_date: 2025-11-04
doi: 10.1007/s00213-025-06952-2
pubmed_id: 41191045
source_url: https://doi.org/10.1007/s00213-025-06952-2
substance_tags: psilocybin
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Divergent effects of ketamine and psilocybin on EEG power spectral density in a mismatch negativity paradigm.

abstract:
RationaleKetamine and psilocybin have demonstrated therapeutic potential for mental disorders, including major depressive disorder, yet they engage distinct mechanisms of action. Ketamine, a dissociative hallucinogen, acts by blocking N-methyl-D-aspartate receptors (NMDAR), whereas psilocybin primarily targets serotonin receptors. These divergent mechanisms are reflected in their electrophysiological biomarkers.ObjectivesThis study aimed to investigate the divergent effects of ketamine and psilocybin on different elements of the EEG frequency spectrum, focusing on aperiodic components as an indicator of excitation-inhibition balance in the neural circuitry.MethodsWe re-analyzed a previously acquired EEG dataset from healthy volunteers using a placebo-controlled within-subject crossover design (Schmidt et al., Neuropsychopharmacology 37(4):865-875 2012). Participants received either placebo or S-ketamine (N=19) and placebo or psilocybin (N=16) during an auditory roving paradigm. Spectral parameters including periodic and aperiodic were extracted and partial least squares analysis was employed.ResultsKetamine significantly altered the offset and slope of the EEG spectrum, suggesting a disruption in excitatory-inhibitory balance. While both drugs commonly reduced alpha power in similar regions, beta band activity was decreased exclusively under ketamine.ConclusionsThese findings highlight ketamine's unique effects on aperiodic EEG components, reinforcing its role as a neurochemical model of prodromal psychosis. Psilocybin's effects appear distinct, emphasizing its targeted influence on oscillatory activity.

topic_tags:
Depression,Brain Imaging,Pharmacology,Mechanism of Action,Receptor Pharmacology,Biomarkers,Healthy Volunteers

raw_json:
{"europe_pmc_id":"41191045","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin and chronic neuropathic pain: a systematic review.
publication_date: 2025-11-04
doi: 10.1136/rapm-2024-105532
pubmed_id: 39106989
source_url: https://doi.org/10.1136/rapm-2024-105532
keywords: Humans, Neuralgia, Hallucinogens, Treatment Outcome, Pain Management, Chronic Pain, Psilocybin
substance_tags: psilocybin
topic_tags: Chronic Pain,Aging,Systematic Review,Review Article,Safety
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
authors:
Jevotovsky DS, Chopra H, Pak DJ, Durbhakula S, Shustorovich A, Juneja T, Broachwala MY, AlFarra T, Silver C, Kreitzer G, Oreoluwa P, Weissman BB, AlFarra A, Mayrsohn BG, Orhurhu V, Emerick T, Furnish T, Castellanos JP.

abstract:
Background/importanceChronic pain affects many people globally, requiring alternative management strategies. Psilocybin is gaining attention for its potential in chronic pain management despite being classified as Schedule I.ObjectiveThis systematic review critically evaluates the evidence for psilocybin, a Schedule I substance, in the treatment of chronic pain. The exact purpose of the review is to assess the impact of psilocybin on chronic pain relief, focusing on dosing protocols, treated conditions, and patient outcomes.Evidence reviewA comprehensive review of PubMed, CINAHL, Web of Science, Cochrane Library, and EMBASE was conducted up to January 2024. Eligibility criteria included studies evaluating psilocybin for chronic pain management. The risk of bias was assessed using the MASTER (MethodologicAl STandards for Epidemiological Research) scale, and the strength of evidence was graded using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation).FindingsThe review identified 28 relevant studies focusing on dosing, treated conditions, and outcomes. The majority of the included studies (76.2%) were of low or very low quality. Several studies with moderate-to-low-quality evidence utilized a 0.14 mg/kg dosing protocol. The findings suggest promise for the use of psilocybin in chronic pain relief, though the quality of evidence is generally low.ConclusionsThe current research shows potential for psilocybin as a treatment option for chronic pain relief. However, methodological issues and a lack of high-quality evidence underscore the need for further investigations with standardized protocols. Despite these limitations, the potential for psilocybin in chronic pain management is encouraging.Prospero registration numberCRD42023493823.

raw_json:
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title: A Tragedy of Errors: The State of Psychedelic Research in the Treatment of Alcohol Use Disorder.
authors: Srivastava AB, Gold MS
journal: Brain sciences
publication_date: 2025-11-03
doi: 10.3390/brainsci15111190
pubmed_id: 41300197
source_url: https://pubmed.ncbi.nlm.nih.gov/41300197/
substance_tags: psilocybin
topic_tags: Addiction,Brain Imaging,Aging,Spirituality,Mystical Experience,Review Article
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"41300197"}
abstract:
The past two decades have seen the reemergence of research investigating the therapeutic potential of psychedelic drugs across neuropsychiatric illnesses. One condition, alcohol use disorder (AUD), is of relevance given the broad public health implications and both limited effectiveness and attrition associated with currently available treatments. While emerging research has suggested that the benefits of psychedelic drugs in the treatment of AUD may be considerable, several fundamental aspects of this work limit the conclusions that can be drawn. These limitations include those that apply to research involving psychedelics generally-including functional unblinding and the role and definition of "psychedelic assisted psychotherapy" and some unique to AUD, including the nature of the mystical experience and how it relates to the "spiritual experience" as described in the literature of Alcoholics Anonymous (AA), of which the history of psychedelic research in AUD is closely intertwined. Additionally, current mechanistic neuroimaging studies examining the therapeutic effects of psychedelics in AUD are limited by design and do not directly interrogate the cognitive and circuit-level processes likely underlying treatment response. This review describes these limitations in detail by bridging historical, conceptual, and mechanistic aspects of psychedelic research in AUD and offers suggestions for future studies, the results of which may more clearly specify the role and utility of psychedelic drugs in the treatment of AUD.

keywords:
alcohol use disorder, alcoholics anonymous, cognitive control, dorsolateral prefrontal cortex, psilocybin, psychedelic


publication_date: 2025-11-03
doi: 10.1017/neu.2025.10042
pubmed_id: 41186141
source_url: https://doi.org/10.1017/neu.2025.10042
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging,Personality Change,Randomized Controlled Trial,Observational Study,Safety
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocybin-assisted physiotherapy for refractory motor functional neurological disorder: protocol for a randomised dose-comparison pilot study.

authors:
Bhagavan C, Bryson A, Carter O, Nielsen G, Berlowitz D, Issak S, Braat S, Zaloumis S, Attard Z, Eleftheriadis D, Oliver G, Mayne D, Roebuck G, Rucker J, Butler M, Kanaan R.

abstract:
BackgroundMotor functional neurological disorder (FND) is a common illness associated with significant functional impairment. There are no effective pharmacotherapies, and despite the early promise of physiotherapy studies, many suffer disabling symptoms in the long term. There is a theoretical rationale for combining psychedelics with physiotherapy; however, the potential benefit of this approach and optimal treatment model remains unexplored. Here, we present the protocol for the first study investigating the tolerability, feasibility, and potential efficacy of two distinct treatment regimens of psilocybin-assisted physiotherapy for refractory motor FND: a moderate dose that incorporates movement tasks during the acute drug effects versus a standard dose alone.MethodsTwenty-four participants with refractory motor FND will be randomised in a 1:1 ratio to either (1) psilocybin 15 mg, with movement tasks conducted during the acute drug effects, or (2) psilocybin 25 mg alone. All participants will receive two sessions of FND-specific physiotherapy pre-dosing, six sessions of physiotherapy post-dosing, and undergo follow-up visits one week and four weeks following their final physiotherapy session. A battery of outcome measures will be completed as scheduled, assessing tolerability, feasibility, motor FND symptom severity, psychiatric and physical symptoms, quality of life, treatment expectations, intensity of the acute drug effects, personality, motor function, force-matching performance, resting-state and task-based brain imaging, and subjective experiences of the study treatment.DiscussionThese findings will assist the design of an adequately powered randomised controlled trial in this cohort. The findings may also inform the feasibility of psychedelic treatment in related functional and neuropsychiatric disorders.

keywords:
Humans, Hallucinogens, Treatment Outcome, Pilot Projects, Adult, Middle Aged, Female, Male, Physical Therapy Modalities, Randomized Controlled Trials as Topic, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"41186141","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Marinis J, Clarke ST, Guerin AA, Guastella AJ, Bedi G.
publication_date: 2025-11-02
doi: 10.1192/bjo.2025.10847
pubmed_id: 41178084
source_url: https://doi.org/10.1192/bjo.2025.10847
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Reporting of side-effects in clinical trials of psilocybin-assisted psychotherapy for psychiatric conditions: systematic review.

abstract:
BackgroundPsilocybin-assisted psychotherapy (PAP) has gained attention as a promising intervention for conditions including depression, anxiety and post-traumatic stress disorder, but understanding of its side-effects is limited. This review evaluates the quality of side-effects reporting in PAP trials, to guide treatment, policy and research.AimsTo assess side-effects reporting quality in PAP trials for psychiatric conditions, comparing published articles and ClinicalTrials.gov records.MethodA PROSPERO-registered review (no. CRD42023458960) included English-language PAP trials (2005-2024) identified via Embase, CENTRAL, PubMed and reference searches. Reporting quality was assessed using the CONSORT Harms extension, categorised as either high (17-21), moderate (12-16), low (7-11) or very low (0-6). Randomised controlled trials underwent risk of bias analysis, and descriptive statistics compared side-effects across sources.ResultsTwenty-four trials were included. Reporting quality was high in six studies, moderate in four, low in nine and very low in five. All randomised controlled trials (n = 9) showed high risk of bias for side-effects outcomes. Variability in reporting hindered comparisons between articles and ClinicalTrials.gov, underscoring the need for standardisation. Overall, there was no evidence of systematic underreporting of side-effects in published articles compared with trial registers.ConclusionsSide-effects reporting in PAP trials is inconsistent but is improving over time. Existing evidence has a high risk of bias. Future trials should align with best-practice guidelines for side-effects reporting. Discussions with patients should prioritise findings from high-quality studies and emphasise the current uncertainty regarding PAP side-effects.

topic_tags:
Depression,Anxiety,PTSD,Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article,Safety

raw_json:
{"europe_pmc_id":"41178084","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-10-10
doi: 10.1016/j.genhosppsych.2025.10.010
pubmed_id: 41109203
source_url: https://doi.org/10.1016/j.genhosppsych.2025.10.010
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Cancer Patients,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Set and setting in psilocybin-assisted therapy: A qualitative study of patients with cancer and depression.

authors:
Beaussant Y, Tarbi E, Nigam K, Miner S, Sager Z, Sanders J, Ljuslin M, Guérin B, Sholevar R, Roddy K, Tulsky JA, Agrawal M.

abstract:
BackgroundPsilocybin-assisted therapy (PAT) shows promise for cancer-related depression, yet little research has examined how therapeutic context shapes patient experiences. While set (mindset) and setting (environment) are considered central to psychedelic treatment, empirical evidence on their role in PAT acceptability remains limited. This study explores factors influencing the acceptability of PAT from the perspective of patients with cancer and depression.MethodsWe conducted semi-structured interviews with participants in a clinical trial of psilocybin-assisted therapy. Using template analysis, we examined themes related to the acceptability of the experience and the surrounding therapeutic environment.ResultsParticipants (n = 28) described the psilocybin experience as intense and demanding, with therapeutic benefits closely tied to their ability to "surrender"-a term used to describe accepting and remaining open to the experience's intensity and unpredictability. A safe, supportive, and ethical environment was critical in fostering trust and engagement. Preparation and integration were key to maximizing benefit. Music played a significant but variable role, sometimes enhancing and other times distracting. While the clinical setting provided safety, ceremonial elements added meaning for many.ConclusionsFindings highlight how therapeutic structure, preparation, and setting shape PAT acceptability, supporting the need for patient-centered approaches to optimize care and outcomes.

keywords:
Humans, Neoplasms, Hallucinogens, Depression, Qualitative Research, Adult, Aged, Middle Aged, Patient Acceptance of Health Care, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"41109203","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-10-12
doi: 10.1038/s41593-025-02069-z
pubmed_id: 41083844
source_url: https://doi.org/10.1038/s41593-025-02069-z
substance_tags: psilocybin
topic_tags: Brain Imaging,Receptor Pharmacology,Aging,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Psychedelic 5-HT2A receptor agonism alters neurovascular coupling and differentially affects neuronal and hemodynamic measures of brain function.

authors:
Padawer-Curry JA, Krentzman OJ, Kuo CC, Wang X, Bice AR, Nicol GE, Snyder AZ, Siegel JS, McCall JG, Bauer AQ.

abstract:
Human neuroimaging studies report that psychedelics induce serotonin-2A receptor-dependent changes in functional brain reorganization, presumably reflecting neuromodulation. However, these studies often overlook the potent vasoactive effects of serotonin. Here we identified psilocybin-induced alterations in hemodynamic response functions during human functional magnetic resonance imaging, suggesting potential disruptions in neurovascular coupling. We then used wide-field optical imaging in awake Thy1-jRGECO1a mice to determine whether psychedelic-induced changes in hemodynamics arise from neuronal, vascular or neurovascular effects. Exposure to the psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) differentially altered coupling between cortical excitatory neuronal versus hemodynamic activity, both during whisker stimulation and in the resting state. Furthermore, DOI resulted in discordant changes between neuronal-based versus hemodynamic-based assessments of functional connectivity. A selective serotonin-2A receptor antagonist (MDL100907) reversed many of the effects of DOI. Our results demonstrate a dissociation between DOI-induced neuronal and hemodynamic signals, indicating a need to consider neurovascular effects of psychedelics when interpreting blood-based measures of brain function.

keywords:
Brain, Neurons, Animals, Mice, Inbred C57BL, Mice, Transgenic, Humans, Mice, Amphetamines, Receptor, Serotonin, 5-HT2A, Hallucinogens, Magnetic Resonance Imaging, Adult, Female, Male, Hemodynamics, Serotonin 5-HT2 Receptor Agonists, Serotonin 5-HT2 Receptor Antagonists, Neurovascular Coupling, Psilocybin

raw_json:
{"europe_pmc_id":"41083844","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Ostuni S, Voto P, Birkebak J, Meyer MGE, Geurin Z, Slot JC.
publication_date: 2025-10-06
doi: 10.1080/00275514.2025.2552612
pubmed_id: 41056483
source_url: https://doi.org/10.1080/00275514.2025.2552612
keywords: Agaricales, Fruiting Bodies, Fungal, Spores, Fungal, DNA, Fungal, Microscopy, Phylogeny, Florida
substance_tags: psilocybin
topic_tags: Genomics
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Panaeolus oligotrophus: A new species from central Florida, with notes on Panaeolus pumilus and Crucispora rhombisperma.

abstract:
Panaeolus oligotrophus sp. nov., a species macromorphologically resembling Panaeolus cinctulus, was collected in central Florida. Its macro- and micromorphological features are described and compared with all other known Panaeolus species. Color photos of the fruiting bodies and micrographs of key microscopic features are provided, along with an updated phylogenetic analysis. A microscopic reexamination of the holotype of Panaeolus pumilus supports its synonymy with P. cinctulus. The potential for psilocybin production by P. oligotrophus was determined by the characterization of the psilocybin gene cluster through whole genome sequencing. Phylogenetic and morphological evidence also supports the placement of Crucispora rhombisperma within Panaeolus, for which the new combination Panaeolus rhombispermus is proposed. This paper makes two interesting additions to the genus Panaeolus: P. rhombispermus introduces the novelty of an extremely differentiated spore morphology, and Panaeolus oligotrophus provides a rare example of Panaeolus in the underexplored niche of oligonutritive sandy soil.

raw_json:
{"europe_pmc_id":"41056483","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-09-22
doi: 10.1016/j.eclinm.2025.103517
pubmed_id: 41048658
source_url: https://doi.org/10.1016/j.eclinm.2025.103517
substance_tags: psilocybin
topic_tags: Depression,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Considerations and cautions for the integration of psilocybin into routine clinical care: a consensus statement from the US National Network of Depression Centers' Task Group on Psychedelics and Related Compounds.

authors:
Hosein MM, Reid MJ, Walser S, Charney S, Fonzo GA, Lewis BR, Yaden DB, Suppes T, Cordner ZA, Barrett FS.

abstract:
The potential for psilocybin, and other psychedelic drugs, to fulfil a much needed and potentially transformative class of psychiatric treatments has garnered significant attention. Consequently, there has been a great deal of interest and investment in accelerating its development and potential implementation in routine clinical practice. However, the expanding scope of scientific discovery, heightened media coverage, and commercial interests in the field risk outpacing the rate of developments in the necessary guidelines and infrastructure required for integration of psilocybin into clinical practice. The US National Network of Depression Centers (NNDC) Task Group on Psychedelics and Related Compounds-comprising psychiatrists, psychologists, neuroscientists, psychedelic researchers, and leaders in healthcare consulting affiliated with the NNDC-developed this consensus statement as a summary of clinical expertise and opinion on the matter, to recognise psilocybin's therapeutic potential while also emphasising the need for further research and careful consideration before the integration of psilocybin into routine clinical care. We outline the current state of the science on psilocybin, incorporating articles published through April 2025. We identify key areas for further research and frame them within the context of therapeutic and ethical implications surrounding psilocybin's use in future clinical practice. We highlight the need for further research to address gaps in understanding of therapeutic dosage, efficacy across diverse populations, and long-term safety. Finally, we propose an agenda which calls for diversification of funding, collaborative research efforts, standardised training for healthcare providers, and careful consideration of ethical dilemmas inherent in the theorised clinical use of psilocybin. Crucially, we advocate for a balanced approach that prioritises rigorous scientific standards while considering the urgency of the need for better treatment options, ensuring equitable access and safety as the field progresses. We acknowledge that the single-country focus of the NNDC may limit the generalisability of recommendations to international contexts with differing healthcare systems and regulatory landscapes.

raw_json:
{"europe_pmc_id":"41048658","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Hammo A, Wisser S, Cichon J.
publication_date: 2025-10-01
doi: 10.1038/s41593-025-02068-0
pubmed_id: 41039182
source_url: https://doi.org/10.1038/s41593-025-02068-0
substance_tags: psilocybin,psilocin
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Single-dose psilocybin rapidly and sustainably relieves allodynia and anxiodepressive-like behaviors in mouse models of chronic pain.

abstract:
Chronic pain and mood disorders co-occur, exacerbate one another and share neurobiological mechanisms, but whether a single intervention could promptly alleviate both conditions remains unclear. Here, in two chronic pain models, we show that a single dose of psilocybin induces a rapid and sustained reversal of both mechanical allodynia and anxiodepression-like states in adult male and female mice. Using local psilocin injections, the key active metabolite of psilocybin, we show that the engagement of prefrontal cortical circuits is critical for the concurrent alleviation of both conditions. Two-photon calcium imaging reveals that psilocin rapidly normalizes chronic pain-associated hyperactivity in anterior cingulate cortex layer 2/3 pyramidal neurons. Pharmacologic manipulations with full agonists of 5-HT2A and 5-HT1A receptors replicated some, but not all, of psilocin's cellular and behavioral effects, suggesting that psilocin's actions arise from partial agonism at these receptors within shared circuits governing pain and mood processing.

keywords:
Prefrontal Cortex, Animals, Mice, Inbred C57BL, Mice, Hyperalgesia, Disease Models, Animal, Hallucinogens, Behavior, Animal, Anxiety, Female, Male, Chronic Pain, Psilocybin

topic_tags:
Depression,Anxiety,Chronic Pain,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Animal Study

raw_json:
{"europe_pmc_id":"41039182","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Characteristics of Ongoing Clinical Trials of Psychogenic Substances for Psychiatric Disorders.
authors: Havlik JL, Isaac S, Raman P, Tran N, Hidalgo K, Suppes T.
publication_date: 2025-09-24
doi: 10.1097/jcp.0000000000002095
pubmed_id: 40994136
source_url: https://doi.org/10.1097/jcp.0000000000002095
substance_tags: psilocybin
topic_tags: Depression,PTSD,Addiction,Emotional Processing,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
abstract:
BackgroundWith a rapid rise in clinical trials investigating psychogenic substances, the field faces considerable concerns regarding transparency and conflicts of interest. This study aims to systematically characterize ongoing NIH-registered clinical trials investigating psychogenic substances for psychiatric disorders as of late 2024, including research protocols, institutional settings, and funding sources.ProceduresThis cross-sectional analysis evaluated ongoing trials from ClinicalTrials.gov that studied psychogenic substances-defined as compounds significantly affecting perception, cognition, or emotion-for psychiatric conditions. Data collected included substance class, targeted diagnoses, trial phase, geographic location, study design (eg, blinding), recruitment status, and funding sources.FindingsA total of 181 trials met the inclusion criteria, with the majority in phase 2 (n=93; 51.4%) or phase 1 (n=33; 18.2%). The most frequently studied substances were psilocybin (n=64; 35.4%) and ketamine (n=61; 33.7%). Trials were notably concentrated within a small number of leading academic institutions. Most trials (n=148; 81.2%) listed their funding source as "other," of which 127 (86.4%) were sponsored by universities or university-affiliated institutions. Blinding was not reported in 38.7% (n=70) of trials. The primary conditions studied were major depressive disorder (n=94; 51.9%), posttraumatic stress disorder (n=38; 21.0%), and alcohol use disorder (n=21; 11.6%).ImplicationsOngoing clinical trials of psychogenic substances for psychiatric disorders are largely concentrated at select institutions and primarily focus on psilocybin and ketamine. The majority lack clear disclosure of funding sources, highlighting a need for enhanced transparency to build trust and facilitate the ethical advancement of this rapidly evolving area of psychiatric research.

keywords:
Humans, Ketamine, Cross-Sectional Studies, Mental Disorders, Research Design, Conflict of Interest, United States, Clinical Trials as Topic, Psilocybin

raw_json:
{"europe_pmc_id":"40994136","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Emerging mechanisms of psilocybin-induced neuroplasticity.
authors: Sonda S, Pendin D, Comai S, De Martin S, Manfredi P, Mattarei A.
publication_date: 2025-09-14
doi: 10.1016/j.tips.2025.08.012
pubmed_id: 40957728
source_url: https://doi.org/10.1016/j.tips.2025.08.012
keywords: Animals, Humans, Hallucinogens, Neuronal Plasticity, Psilocybin
substance_tags: psilocybin,psilocin
topic_tags: Depression,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Review Article,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Psilocybin, a serotonergic psychedelic, is gaining attention for its rapid and sustained therapeutic effects in depression and other hard-to-treat neuropsychiatric conditions, potentially through its capacity to enhance neuronal plasticity. While its neuroplastic and therapeutic effects are commonly attributed to serotonin 2A (5-HT2A) receptor activation, emerging evidence reveals a more nuanced pharmacological profile involving multiple serotonin receptor subtypes and nonserotonergic targets such as TrkB. This review integrates current findings on the molecular interactome of psilocin (psilocybin active metabolite), emphasizing receptor selectivity, biased agonism, and intracellular receptor localization. Together, these insights offer a refined framework for understanding psilocybin's enduring effects and guiding the development of next-generation neuroplastogens with improved specificity and safety.

raw_json:
{"europe_pmc_id":"40957728","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Vohryzek J, Luppi AI, Atasoy S, Deco G, Carhart-Harris RL, Timmermann C, Kringelbach ML.
publication_date: 2025-09-11
doi: 10.1038/s41386-025-02190-4
pubmed_id: 40940591
source_url: https://doi.org/10.1038/s41386-025-02190-4
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Consciousness,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
N,N-dimethyltryptamine effects on connectome harmonics, subjective experience and comparative psychedelic experiences.

abstract:
Exploring the intricate relationship between brain's structure and function, and how this affects subjective experience is a fundamental pursuit in neuroscience. Psychedelic substances offer a unique insight into the influences of specific neurotransmitter systems on perception, cognition and consciousness. Specifically, their impact on brain function propagates across the structural connectome - a network of white matter pathways linking different regions. To comprehensively grasp the effects of psychedelic compounds on brain function, we used a theoretically rigorous framework known as connectome harmonic decomposition. This framework provides a robust method to characterize how brain function intricately depends on the organized network structure of the human connectome. We show that the connectome harmonic repertoire under N,N-dimethyltryptamine (DMT) is reshaped in line with other reported psychedelic compounds - psilocybin, lysergic acid diethylamide (LSD) and ketamine. Furthermore, we show that the repertoire entropy of connectome harmonics increases under DMT, as with those other psychedelics. Importantly, we demonstrate for the first time that measures of energy spectrum difference and repertoire entropy of connectome harmonics index the intensity of subjective experience of the participants in a time-resolved manner reflecting close coupling between connectome harmonics and subjective experience.

keywords:
Brain, Nerve Net, Humans, N,N-Dimethyltryptamine, Ketamine, Lysergic Acid Diethylamide, Hallucinogens, Magnetic Resonance Imaging, Adult, Female, Male, Young Adult, Connectome, Psilocybin

raw_json:
{"europe_pmc_id":"40940591","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The therapeutic use of psychedelic drugs: Legal, policy, and neuroscientific perspectives.
authors: Rahmani S, Crupi R, Riley AL, Davidson T
journal: Pharmacology, biochemistry, and behavior
publication_date: 2025-10-31
doi: 10.1016/j.pbb.2025.174087
pubmed_id: 40849009
source_url: https://pubmed.ncbi.nlm.nih.gov/40849009/
keywords: Drug law, Drug policy, Medical ethics, Psilocybin, Psychedelics
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Mechanism of Action,Safety
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"40849009"}
abstract:
After many years of stigma and neglect, there is a resurgence of interest in the therapeutic use of psychedelic drugs. Anecdotal and evidence-based reports indicate psychedelics as a possible treatment for depression, anxiety, PTSD, substance abuse, and other disorders resistant to conventional medical interventions. The available data, however, are limited and the use of psychedelic substances in therapy remains controversial. This paper presents a collection of reports based on the talks of eighteen renowned experts in science, policy, and law who spoke at a recent symposium organized by American University's Center for Neuroscience and Behavior titled "The Therapeutic Uses of Psychedelic Drugs: Legal, Policy, and Neuroscientific Perspectives." These speakers presented their ideas and perspectives concerning (a) the safety and effectiveness of psychedelic-assisted therapies; (b) the brain systems on which psychedelic drugs act; (c) ethical issues for both research and clinical settings; (d) pathways to increasing access to psychedelics for medical and nonmedical purposes; (e) federal and state regulation of psychedelic drugs for research, therapy, and nonmedical uses; and (f) procedures and requirements for psychedelic drug patents and commercialization. In considering these topics, each speaker strove to make their views accessible to diverse audiences of professionals outside of their own disciplines. This paper aims to faithfully convey the substance of each talk, while also providing additional context and updates relevant to the presentations. The symposium revealed the potential of psychedelics for treating psychiatric and behavioral disorders and the scientific, legal, and policy challenges that must be met to realize this potential.


authors: Koenig HG.
publication_date: 2025-08-19
doi: 10.1177/00912174251369880
pubmed_id: 40833259
source_url: https://doi.org/10.1177/00912174251369880
substance_tags: psilocybin
topic_tags: Depression,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Psilocybin-assisted psychotherapy, combined antipsychotic and antidepressant treatment for bipolar depression, duration of birth control pill use and risk of depression, handgrip strength and cognitive function, mood disorders in epilepsy, and mental health issues among physicians.

raw_json:
{"europe_pmc_id":"40833259","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The emotional architecture of the psychedelic brain.
authors: Moujaes F, Rieser NM, Belinger L, Herdener M, Zahid Z, Preller KH
journal: Trends in cognitive sciences
publication_date: 2025-10-31
doi: 10.1016/j.tics.2025.07.006
pubmed_id: 40830011
source_url: https://pubmed.ncbi.nlm.nih.gov/40830011/
keywords: amygdala, depression, mood, neuroplasticity, psilocybin, psychedelics
substance_tags: psilocybin
topic_tags: Depression,Chronic Pain,Neuroplasticity,Mechanism of Action,Emotional Processing,Review Article
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"40830011"}
abstract:
Serotonergic psychedelics are being explored as treatments for a range of psychiatric conditions. Promising results in mood disorders indicate that their effects on emotional processing may play a central role in their therapeutic potential. However, mechanistic and clinical studies paint a complex picture of the impact of psychedelics on emotions and mood. Here, we review recent findings on the effects of psychedelics on emotion, emotional empathy, and mood. We discuss how psychedelics may impact long-term emotion management strategies, the significance of challenging experiences, and neuroplastic changes. More precise characterization of emotional states and greater attention to the temporal dynamics of psychedelic-induced effects will be critical for clarifying their mechanisms of action and optimizing their therapeutic impact.


authors: Joga R, Yerram S, Patnam JD, Choudhary KK, Varpe P, Raghuvanshi RS, Srivastava S.
publication_date: 2025-07-07
doi: 10.1016/j.healthpol.2025.105392
pubmed_id: 40694950
source_url: https://doi.org/10.1016/j.healthpol.2025.105392
substance_tags: psilocybin
topic_tags: Depression,PTSD,Clinical Trial,Review Article,Treatment-Resistant Depression,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Unraveling the policies, legislations, and regulations of psychedelics in Australia, Canada, Netherlands, New Zealand, and India.

abstract:
BackgroundResearch into psychedelics has gained renewed interest due to their potential to address psychiatric, neurological, and other peripheral conditions. These substances offer long-term therapeutic benefits, contrasting with the side effects and limitations of current psychiatric medicines.ObjectiveThis study examines the legislations and regulatory frameworks for psychedelics in Australia, Canada, The Netherlands, New Zealand, and India, highlighting their varied approaches to legalization, medical use, and integration into healthcare systems.MethodsA comparative analysis of the regulatory landscapes in the selected countries was conducted, focusing on policies, clinical trial practices, and the ethical considerations surrounding psychedelics. Data were drawn from government documents, regulatory databases, and peer-reviewed literature.ResultsAustralia legalized MDMA for post-traumatic stress disorder and psilocybin for treatment-resistant depression, establishing a structured prescription system for authorized psychiatrists. Canada and The Netherlands supports therapeutic use through regulated clinical trials and limited exemptions under strict controls, reflecting cautious but progressive approaches. New Zealand demonstrates exploratory interest in psychedelics within a controlled regulatory framework. India maintains stringent prohibitions with severe penalties for possession and use, despite emerging research indicating potential medical benefits.ConclusionsAustralia, Canada, The Netherlands, and New Zealand have taken pioneering steps in integrating psychedelics into medical practice, guided by evolving scientific evidence and ethical considerations. In contrast, India's conservative regulatory stance highlights significant barriers to exploring the medical potential of psychedelics. As global perspectives shift, balancing scientific advancements with robust regulatory measures will be crucial for shaping public health policies and fostering therapeutic innovation.

keywords:
Humans, Hallucinogens, Legislation, Drug, Health Policy, Canada, India, Australia, Netherlands, New Zealand

raw_json:
{"europe_pmc_id":"40694950","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-06-03
doi: 10.1007/s12035-025-05097-9
pubmed_id: 40461729
source_url: https://doi.org/10.1007/s12035-025-05097-9
keywords: Animals, Humans, Nervous System Diseases, Hallucinogens, Mental Disorders
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Psychedelics in the Treatment of Neurologic and Psychiatric Disorders: Coincidence or a New Point of View.

authors:
Lashgari NA, Khalaji M, Rana P, Badrabadi F, Rahnama M, Nasoori H, Momeni Roudsari N, Khosravi Nia MM, Shafaroodi H.

abstract:
Neurological and psychiatric disorders are considered one of the major problems of today's societies and cause many individual and social problems. Current treatments are effective, but due to their burdens, there is always an effort to introduce novel treatments. Psychedelics, a diverse group of psychoactive compounds, including LSD, psilocybin, DMT, MDMA, and ketamine, have shown potential in modulating neurologic and psychiatric disorders due to several mechanisms. This review investigates the therapeutic potential of psychedelics in both neurologic and neuropsychiatric disorders due to their several mechanisms such as anti-inflammatory, anti-oxidative, and biological properties. This study was conducted across major databases, such as PubMed, Scopus, Web of Science, Google Scholar, and Medline, due to the systematically searched literature including clinical, preclinical, and in vitro studies. Psychedelic compounds such as psilocybin, LSD, and MDMA have demonstrated beneficial effects across various models of neuropsychiatric and neurologic disorders, including depression, PTSD, Alzheimer's disease, and Parkinson's disease. These effects are mediated through multiple mechanisms, including anti-inflammatory actions (e.g., downregulation of cytokines such as IL-6 and TNF-α), antioxidant activity (e.g., induction of SOD), and enhancement of neuroplasticity through increased expression of brain-derived neurotrophic factor such as BDNF. Additionally, psychedelics modulate key neurotransmitter systems, notably increasing synaptic levels of serotonin and dopamine, which are critically involved in mood regulation and cognitive function. Compared to conventional treatments, psychedelics offer faster onset, durable effects, and possible disease-modifying properties, making them promising candidates for future neurotherapeutics.

topic_tags:
Depression,PTSD,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Review Article,Animal Study,In Vitro Study,Inflammation

raw_json:
{"europe_pmc_id":"40461729","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Swieczkowski D, Kwaśny A, Pruc M, Gaca Z, Szarpak L, Cubała WJ.
publication_date: 2025-04-24
doi: 10.1177/00912174251337572
pubmed_id: 40279353
source_url: https://doi.org/10.1177/00912174251337572
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Psilocybin-assisted psychotherapy as a rapid-acting treatment for cancer-related depression and anxiety: Evidence from a network meta-analysis.

abstract:
ObjectiveTo evaluate psilocybin's efficacy in reducing depressive and anxiety symptoms in cancer patients based on randomized controlled trials (RCTs).MethodsThis systematic review and network meta-analysis (NMA) followed PRISMA and Cochrane Handbook guidelines. PubMed, Embase and Cochrane Library data up to July 2024 were analyzed. Two RCTs met the inclusion criteria. Changes in Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) scores were assessed on day 1 and on 2-week follow-up. The risk of bias was evaluated with the Cochrane Risk of Bias Tool 2.0.ResultsPsilocybin significantly reduced BDI scores at day 1 post-administration (MD = 2.26; P = 0.01), though effects were not sustained at 2 weeks. STAI state scores showed substantial reductions at both day 1 (MD = 11.52; P < 0.001) and 2 weeks (MD = 12.66; P < 0.001). STAI trait scores also improved on both day 1 and day 14. The highest psilocybin dose (0.3 mg/kg) was the most effective, with SUCRA values of 87.81% (BDI), 91.58% (STAI state), and 94.2% (STAI trait).ConclusionsFindings suggest psilocybin may rapidly reduce depressive and anxiety symptoms in cancer patients, but methodological limitations, including the small number of trials, necessitate cautious interpretation. Larger, high-quality RCTs are needed to verify its clinical potential.

keywords:
Humans, Neoplasms, Hallucinogens, Depression, Anxiety, Psychotherapy, Randomized Controlled Trials as Topic, Psilocybin, Outcome Assessment, Health Care

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

raw_json:
{"europe_pmc_id":"40279353","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: [Acceptance of psilocybin-assisted therapy in German-speaking countries].
authors: Hartter N, Däumichen M, Schmidt C, Wolff M, Gründer G, Jungaberle H.
publication_date: 2025-02-11
doi: 10.1007/s00115-024-01792-5
pubmed_id: 39937287
source_url: https://doi.org/10.1007/s00115-024-01792-5
substance_tags: psilocybin
topic_tags: Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
BackgroundClinical studies with psilocybin in combination with psychotherapy show promising results for the treatment of various mental disorders; however, there still exists a lack of knowledge, rejection and prejudice towards this new form of therapy among doctors, psychotherapists and patients. The aim of this study was to gain a representative impression, as far as possible, of the level of information and attitudes towards the implementation of psilocybin-assisted therapy (PAT) among mental health experts, patients and the general population.MethodsAn online survey was used to collect information on the attitudes and knowledge of 1456 participants and to test the effect of a brief intervention. Results were determined using analyses of variance and regression models.ResultsRegression analyses showed that a higher knowledge score and self-assessed level of knowledge, own treatment experience and also own experience with psychedelics predicted more positive attitudes towards the introduction of PAT, F(8, 1447) = 154.646, p

keywords:
Humans, Hallucinogens, Treatment Outcome, Combined Modality Therapy, Attitude of Health Personnel, Health Knowledge, Attitudes, Practice, Mental Disorders, Psychotherapy, Adult, Aged, Middle Aged, Patient Acceptance of Health Care, Germany, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"39937287","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Glynos NG, Baker A, Aday JS, Pouyan N, Barron J, Herberholz M, Kruger D, Boehnke KF.
publication_date: 2024-09-18
doi: 10.1080/02791072.2024.2405685
pubmed_id: 39297183
source_url: https://doi.org/10.1080/02791072.2024.2405685
substance_tags: psilocybin
topic_tags: Personality Change,Observational Study,Safety
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Going Underground: Demographics, Services, and Best Practices Endorsed by Practitioners Providing Support for Naturalistic Psychedelic Use.

abstract:
Psychedelic-assisted therapy (PAT) has shown preliminary efficacy for psychiatric and physical health conditions. Although some people report naturalistic psychedelic use with so-called "underground" practitioners, little is known about PAT that occurs outside of controlled clinical settings or perspectives of these practitioners. We conducted an anonymous online survey of individuals who reported providing psychedelic support services (e.g. trip sitting and/or preparatory/follow-up psychotherapy) in naturalistic settings. We investigated demographics, including education and licensing, details about services provided, and reported client outcomes. Among 107 participants, 40.2% held a full or in-progress license and 44.9% had not obtained a relevant graduate degree. Almost all participants reported pre-screening clients before treatment, offering preparation, integration, and trip-sitting services, and most employed a range of therapeutic modalities, centering primarily on non-directive approaches. Participants reported that clients most commonly consumed psilocybin, and treated numerous conditions, primarily aligning with indications targeted in psychedelic clinical research. Perceptions of clients' symptom changes were largely positive, although a small proportion reported worsened personality disorder symptoms. Further research delineating client and practitioner perspectives of naturalistic PAT services is warranted, and such work may shed light on the benefits and risks specific to naturalistic PAT as well as inform best practices for practitioners.

keywords:
Humans, Hallucinogens, Psychotherapy, Adult, Middle Aged, Female, Male, Young Adult, Surveys and Questionnaires

raw_json:
{"europe_pmc_id":"39297183","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-10-30
doi: 10.1038/s41398-025-03654-3
pubmed_id: 41173871
source_url: https://doi.org/10.1038/s41398-025-03654-3
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Psychedelics and ketamine/esketamine in depressive disorders: biological mechanisms and associated neuroimaging and clinical changes.

authors:
d'Andrea G, Chiappini S, Ciavoni L, Tucci R, Martino F, Semeraro FM, Di Battista D, Mosca A, Miuli A, Di Carlo F, Russo M, Di Petta G, Fornaro M, Pettorruso M, Sensi SL, Martinotti G.

abstract:
BackgroundOver the past ten years, several psychedelic compounds, including tryptamines like lysergic acid diethylamide/LSD, psilocybin, ayahuasca, and dimethyltryptamine/DMT, have been tested in clinical trials for a range of psychiatric conditions, such as anxiety and depression. While these compounds are relatively available for treatment, ketamine and its S(+) enantiomer, esketamine, are increasingly used to manage treatment-resistant depression. The biological mechanisms set in motion by these compounds are still largely unexplored. Preliminary data indicate modulatory activity of distinct brain networks and selected neurotransmitter pathways (i.e., glutamate, serotonin).ObjectiveThis systematic review investigates functional changes in neural activity generated by these compounds (i.e., LSD, psilocybin, ayahuasca, and DMT or ketamine/esketamine) in depressive disorders. Studies involving different techniques (i.e. Positron Emission Tomography/PET, Single Photon Emission Computed Tomography/SPECT, functional Magnetic Resonance Imaging/fMRI and MRI) were included.MethodA literature search was conducted following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines of 2015. The search was performed using PubMed Web of Science and Scopus databases, taking into consideration publications up to March 2022, without any time restrictions.ResultsThe search produced a final set of 49 articles. Most were related to ketamine/esketamine (n = 44). A smaller number (n = 5) pertained to psychedelic tryptamines (one on ayahuasca and four on psilocybin). From the total of 49 studies, 9 were randomized-controlled trials, 25 were open-label studies, 4 were double-blind trials, 8 were observational studies, and 3 cross-over studies.ConclusionsPsylocibin seems to reset Default Mode Network (DMN) activity, thereby reducing depressive symptoms with long-term and sustainable antidepressant efficacy. Compared to psychedelics, ketamine exhibits a more specific action on networks involving prefrontal areas that act indirectly on the DMN. This effect may help explain ketamine's anti-anhedonic activity and its critical role in increasing cognitive control over emotional stimuli, thus reducing negative mood stages.

keywords:
Brain, Humans, Ketamine, Hallucinogens, Depressive Disorder, Neuroimaging, Depressive Disorder, Treatment-Resistant

topic_tags:
Depression,Anxiety,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Aging,Emotional Processing,Clinical Trial,Systematic Review,Review Article,Observational Study,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"41173871","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-10-27
doi: 10.1186/s40814-025-01706-5
pubmed_id: 41152967
source_url: https://doi.org/10.1186/s40814-025-01706-5
substance_tags: psilocybin
topic_tags: Clinical Trial,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy for patients with advanced cancer: protocol for a multi-method feasibility trial.

authors:
Richardson C, Chan C, Macgregor E, Hare C, Hannon B, Black S, Schneider E, Buchman D, Wang S, Rac V, Abrahamyan L, Huszti E, Nissim R, Li M, Zimmermann C, Hapke E, Rosenbaum D, Hales S.

abstract:
BackgroundIndividuals with advanced cancer often experience high levels of distress for which there are few standardized treatment approaches. Our multidisciplinary team has combined existing evidence-based approaches into Psilocybin-assisted Existential, Attachment, and RelationaL (PEARL) therapy. PEARL therapy combines elements from psilocybin-assisted psychotherapy, including preparatory therapy sessions, a high-dose psilocybin session, and integration sessions, with important elements from evidence-based psychotherapies designed for patients with advanced cancer.MethodThis open-label, single-arm clinical trial will assess the acceptability, feasibility, and safety of PEARL therapy among 15 patients with advanced cancer, using qualitative and quantitative methodologies. Participants will complete self-report questionnaires at four time points pre- and post-intervention, as well as a qualitative interview one month after PEARL completion. Feasibility will be evaluated in terms of recruitment, retention, and adherence rates, while safety will be assessed based on the number of participants experiencing no serious adverse events.DiscussionThis study will yield important information about the acceptability and feasibility of PEARL therapy and contribute to growing research around the efficacy of psychedelic-assisted therapies. PEARL therapy has the potential to improve quality of life among those with advanced disease, and careful research is needed to guide public policy, legislation, therapist training, and clinical guidelines.Trial registrationNCT06416085; 2024-07-16.

raw_json:
{"europe_pmc_id":"41152967","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Provider perspectives on challenges in treatment during psychedelic therapy.
authors: Bender DA, Nayak SM, Siegel JS, Hellerstein DJ, Ercal BC, Lenze EJ.
publication_date: 2025-10-26
doi: 10.1007/s00213-025-06907-7
pubmed_id: 41139739
source_url: https://doi.org/10.1007/s00213-025-06907-7
substance_tags: psilocybin
topic_tags: PTSD,Aging,Clinical Trial,Review Article,Observational Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
RationalePsychedelic treatments are considered to involve unique treatment challenges relative to other psychiatric interventions, though these are typically not explored in detail within clinical trial reports.ObjectivesTo determine the types of challenges that providers encounter while administering psychedelic drugs in research settings and to assess provider opinions on safeguards that may be pursued to improve outcomes.MethodsAn anonymous survey was distributed via email to contacts listed on clinicaltrials.gov. for clinical trials of psilocybin and LSD, personal contacts of authors, and through snowball sampling. Free response items were reviewed using qualitative thematic analysis.Results40 qualified respondents completed the survey. Respondents came from varying educational backgrounds (42.5% M.D./D.O., 57.5% other degrees) and practiced in at least 4 countries, 11 U.S. states, and 16 institutions. Respondents had overseen a total of 1656 psychedelic sessions (average = 41.4). Thematic analysis of free response descriptions pertaining to challenges in psychedelic therapy produced 11 distinct themes, with the most commonly reported challenges being intense dysphoria during treatment sessions (42% of respondents), disappointment with the intervention (25% of respondents), and re-engaging with traumatic experience (17% of respondents). 70% of respondents felt that individuals with PTSD or prior trauma warrant additional psychological support. Respondents recommended 9.8 h of total psychological support for individuals with serious mental illness receiving psychedelic treatment for the first time.ConclusionsPsychedelic providers encounter a variety of challenges over the course of psychedelic treatments. These potentialities should be considered during the development of psychological support protocols for clinical trials and any future clinical guidelines.

raw_json:
{"europe_pmc_id":"41139739","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: High Risk, Low Key: The New Face of Drug Use.
authors: Burmeister JR, Jung JK.
publication_date: 2024-12-31
doi: 10.1177/29768357251389682
pubmed_id: 41180078
source_url: https://doi.org/10.1177/29768357251389682
substance_tags: psilocybin
topic_tags: Addiction,Microdosing,Wellbeing,Adolescents,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
In today's rapidly evolving substance use landscape, the traditional image of drug consumption is being replaced by a subtler, more socially accepted aesthetic. High Risk, Low Key: The New Face of Drug Use explores how modern intoxicants, from THC-infused beverages to microdosed psilocybin and nitrous oxide canisters, are increasingly marketed as wellness products rather than recreational drugs. This shift, driven by cultural, technological, and mental health trends, has led to the normalization and concealment of daily drug use, especially among youth. Cannabis, once emblematic of rebellion, is now branded as organic and therapeutic, despite rising potency and associated risks. Meanwhile, legal gray-area substances like kratom and nitrous oxide offer easily accessible highs with potentially serious health consequences. The rise of self-medication, fueled by online platforms and a mental health crisis, further blurs the line between therapy and abuse. Digital platforms now serve as decentralized drug markets, contributing to the fentanyl crisis through counterfeit pills. This article calls for a new framework to address these trends, one that includes updated education, regulation, and clinical tools responsive to a generation navigating a silent, rebranded drug crisis.

raw_json:
{"europe_pmc_id":"41180078","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Keighley EE, Abo Hamza E, Bedewy DA, Nalla S, Moustafa AA.
publication_date: 2025-10-22
doi: 10.3390/healthcare13212668
pubmed_id: 41228035
source_url: https://doi.org/10.3390/healthcare13212668
substance_tags: psilocybin
topic_tags: Addiction,Clinical Trial,Meta-Analysis,Systematic Review,Review Article
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
A Systematic Review and Meta-Analysis Investigating the Efficacy of Various Psychedelic Drugs for the Treatment of Substance Use Disorder.

abstract:
Objectives: This study investigates psychedelic drugs to treat substance use disorder (SUD). Researchers have recently begun conducting clinical trials of psychedelic treatment for SUD. The current meta-analysis investigates the extent of efficacy in alleviating SM behaviours (P) using psychedelic therapy (I), concurrent with determining which psychedelic enables the greatest effect (C) as a treatment tool for reducing SUD (O). Methods: The inclusion criteria in this study include evaluating the efficacy of LSD, psilocybin, ketamine, or ibogaine in human beings with an SUD. The exclusion criteria include studies on rodents, patients with schizophrenia, case studies, incomplete or ongoing trials, and studies with insufficient quantitative data. The search criteria obtained 1278 articles, acquired through PubMed and PsycINFO. After excluding literature, 30 papers were kept in the final meta-analysis. A random-effects model analysis was applied to investigate individual psychedelic interventions, with a corresponding combined psychedelic intervention analysis. Results: The results favoured psychedelics as an SM treatment, with ibogaine evidencing the most prominent. We also found a non-significant difference between the effectiveness of psychedelic treatment paired with psychotherapy and psychedelic treatment alone. This study aims to contribute knowledge to future clinical research on the psychedelic treatment of SUD.

raw_json:
{"europe_pmc_id":"41228035","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Home-based psilocybin-assisted therapy for a patient with advanced cancer: A case report.
authors: Farzin H, Koren B, Ferrier H, Sanders JJ, Garel N.
publication_date: 2025-10-22
doi: 10.1017/s1478951525100941
pubmed_id: 41127918
source_url: https://doi.org/10.1017/s1478951525100941
substance_tags: psilocybin
topic_tags: Depression,Anxiety,End-of-Life Distress,Wellbeing,Spirituality,Case Report
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
ObjectivesPsychospiritual distress affects many patients with cancer, contributing to diminished quality of life, decreased survival and a desire for hastened death. The current standard of care, which primarily consists of antidepressants and psychotherapy, has demonstrated only modest benefits. Psilocybin-assisted therapy (PAT) has shown evidence of rapid, durable, and significant effects on measures of both depression and anxiety in this patient population.MethodsA 51-year-old man diagnosed with metastatic lung cancer, referred to palliative care (PC) with a prognosis of less than 6 months, experienced depression and anxiety in the context of demoralization and existential distress. His suffering persisted despite psychotherapy and treatment with 100 mg of sertraline. He was granted access to PAT through Health Canada's Special Access Program (SAP) and was treated with 25 mg of oral psilocybin in a homecare setting, with preparative and integrative therapy prior to and following the PAT session.ResultsPAT was well tolerated, with significant decreases in both anxiety and depression. The patient subjectively reported a sustained reduction in suffering and improved well-being at 2 months post-intervention.Significance of resultsPAT, when utilized within an appropriate therapeutic framework, may be safely delivered at home and may serve as an effective and long-lasting treatment for symptoms of anxiety and depression associated with psychospiritual symptoms of existential distress in PC. Future studies should examine differences in outcomes between clinical and homecare settings for PAT, and could include creating practice guidelines and protocols for home-based PAT.

keywords:
Humans, Neoplasms, Lung Neoplasms, Hallucinogens, Palliative Care, Depression, Anxiety, Middle Aged, Home Care Services, Male, Psilocybin

raw_json:
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authors: Li R, Yan H, Chen Y, Liu Y, Tang L, Yu J, Liu J, Wang H, Wang S, Cheng J.
publication_date: 2025-10-13
doi: 10.1021/acs.jmedchem.5c02045
pubmed_id: 41087124
source_url: https://doi.org/10.1021/acs.jmedchem.5c02045
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 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Structure-Guided Design of Novel 5-HT2A Partial Agonists as Psychedelic Analogues with Antidepressant Effects.

abstract:
Depression is primarily treated with selective serotonin reuptake inhibitors (SSRIs), which are limited by delayed onset of effects and low rates of remission. Recent studies showed that serotonergic psychedelics such as psilocybin can reduce depressive symptoms both rapidly and enduringly. Such effects have been associated with the activation of the serotonin 2A (5-HT2A) receptor in the central nervous system, which has prompted medicinal chemistry studies of novel 5-HT2A agonists. In this study, we designed and synthesized novel 5-HT2A partial agonists based on the structures of the antipsychotic drug aripiprazole and our previously reported lead compound IHCH-7086. Two series of new compounds were synthesized, a number of which exhibited potent 5-HT2A partial agonist activity in G protein coupling and β-arrestin2 recruitment assays. Compound 28c exhibited antidepressant effects in the mouse tail-suspension test without inducing head-twitch responses, supplementing the growing reservoir of nonhallucinogenic 5-HT2A agonists.

keywords:
Animals, Humans, Mice, Receptor, Serotonin, 5-HT2A, Hallucinogens, Antidepressive Agents, Structure-Activity Relationship, Drug Design, Male, Serotonin 5-HT2 Receptor Agonists

raw_json:
{"europe_pmc_id":"41087124","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-10-15
doi: 10.1177/20451253251384513
pubmed_id: 41122434
source_url: https://doi.org/10.1177/20451253251384513
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Biological markers of treatment response to serotonergic psychedelic therapies: a systematic review.

authors:
Wong S, Jones BDM, Thiyagarajah MT, Sabbah SG, Thompson C, Solmi M, Umer M, Zrenner C, Voineskos D, Rosenblat JD, Mulsant BH, Blumberger DM, Husain MI.

abstract:
BackgroundResults from contemporary clinical trials of serotonergic psychedelic therapies have led to an increasing focus on their potential clinical use across mental disorders. However, studies examining mechanisms of clinical response to psychedelic therapy in psychiatric populations are limited. This review aimed to synthesize evidence from studies examining biomarkers of clinical response to psychedelic therapies.Data sources and methodsA systematic search of four databases (MedLine, PsycInfo, EMBASE, and Web of Science) for studies investigating treatment response to psychedelic therapies in psychiatric populations that included both clinical outcomes and a related biomarker was conducted on January 10, 2024. Studies were included if they reported on prospective clinical trials involving the use of a psychedelic in participants diagnosed with any Diagnostic and Statistical Manual or International Classification of Diseases mental disorder, where a biological marker was measured and evaluated in association with treatment response.ResultsNine studies investigating the effects of Ayahuasca and psilocybin in major depressive disorder and treatment-resistant depression were included in this review. Several potential biomarkers of response were explored through neuroimaging and blood samples, with significant associations found for serum brain-derived neurotrophic factor, serum C-reactive protein, cerebral activation of the amygdala, and functional connectivity between regions such as the ventromedial prefrontal cortex, anterior cingulate cortex, and posterior cingulate cortex.ConclusionResults of small studies suggest associations between several putative biomarkers and treatment response to psychedelic therapies. Future trials of psychedelic therapies should integrate biomarker assessment in longitudinal designs to advance the understanding of their mechanism of action in mental disorders.Trial registrationThis study protocol was registered to PROSPERO under the number CRD42021291171.

topic_tags:
Depression,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Clinical Trial,Systematic Review,Review Article,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"41122434","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: bioRxiv
publication_date: 2025-10-13
doi: 10.1101/2025.10.12.681880
source_url: https://doi.org/10.1101/2025.10.12.681880
substance_tags: psilocybin
topic_tags: Brain Imaging
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Intravenous Administration of Serotonergic Psychedelics Produce Short-lasting Changes in Sleep-Wake Behavior and High Gamma Functional Connectivity in Rats

authors:
Kolbman N, Huels ER, Nelson A, Summerfield R, Byraju K, Groenhout T, Liu T, Hudetz AG, Vanini G, Pal D.

abstract:
Background and Purpose Given the increase in recreational psychedelic use and ongoing efforts to explore psychedelics as therapeutic agents for mental health disorders, there is an urgent need to understand the effect of psychedelics such as psilocybin and N,N-dimethyltryptamine (DMT) on sleep-wake states, which share a bidirectional relationship with mental health. Here, we investigated the effects of intravenous psilocybin and DMT on sleep-wake states and EEG spectral power and functional connectivity in rats. Experimental Approach Sprague Dawley rats (n=25, 13 male) were surgically instrumented to record high-density EEG (27 electrodes) and EMG during 12-h light and 12-h dark cycle after intravenous psilocybin (2.5 mg/kg, 10 mg/kg), DMT (3.75 mg/kg, 7.5 mg/kg) or 0.9% saline. The EEG/EMG data were scored in 4-second epochs into wake, slow-wave sleep (SWS), and rapid eye movement (REM) sleep. EEG spectral power and corticocortical coherence, a surrogate for functional connectivity, were computed in 12-second epochs. Key Results Psilocybin and DMT delayed the onset of SWS and REM sleep, and caused a short-lasting increase in wakefulness and decrease in SWS. Psilocybin also produced a 1) decrease in REM sleep, 2) decrease in theta power and coherence and increase in high gamma power and coherence during wake and SWS, and 3) increase in high gamma coherence during REM sleep. DMT increased gamma coherence only during wakefulness. Conclusions and Implications Serotonergic psychedelics have minimal effects on sleep-wake states. The enhanced high gamma functional connectivity suggests that the psychedelic-induced changes in EEG/neural dynamics can occur independent of the arousal states.

raw_json:
{"europe_pmc_id":"PPR1100688","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: Psychopharmacology
publication_date: 2025-10-10
doi: 10.1007/s00213-025-06913-9
pubmed_id: 41073618
source_url: https://pubmed.ncbi.nlm.nih.gov/41073618/
keywords: Citizen science, Mental health, Microdosing, Psilocybin, Psychedelics
substance_tags: psilocybin
topic_tags: Microdosing,Observational Study
study_type: Observational Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"41073618"}
title:
Daily self-assessment within a regimen of microdosing indicates enhanced psychological functioning on microdosing days relative to non-microdosing days.

authors:
St Pierre M, Argento E, Cates J, Kryskow P, Harvey K, Stamets P, Santos-Brault E, Paschall SA, Kuypers KPC, Rootman J, Walsh Z

abstract:
Repeated self-administration of small doses of psychedelics, known as microdosing, has been associated with perceived improvements in psychological functioning. However, few studies have examined effects at the daily level.
Drawing on data from a naturalistic, prospective, international survey of adults who microdose (N = 1435), we assessed self-reported within-person changes between microdosing days and non-microdosing days across six domains of psychological functioning.
Using multi-level modeling, we identified higher (p
Given the observational and exploratory nature of this study, these findings should be interpreted with caution; nonetheless, the prospective data provides valuable real-time insights while reducing recall bias.


authors: Razidlo J, Cataldo N, Wenthur CJ.
publication_date: 2025-09-10
doi: 10.1021/acsptsci.5c00462
pubmed_id: 41244305
source_url: https://doi.org/10.1021/acsptsci.5c00462
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 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocybin Enhances Cued Fear Extinction and Extinction Recall in Stress-Naïve, Acutely Stressed, and Chronically Stressed Mice.

abstract:
Serotonergic psychedelics have shown promise in clinical trials for treating an array of mental health disorders, including depression, anxiety, and post-traumatic stress disorder. Despite these findings, our understanding of how these drugs mechanistically exert their therapeutic effects remains incomplete. While researchers have regularly employed rodent preclinical models to assess such mechanisms, many of these findings arise from stress-naïve animals. Given that prior environmental stress is a critical component for the mental health disorders being studied in clinical trials of psychedelics, understanding the performance of these drugs in animals previously exposed to acute or chronic stress is of strong translational relevance. In this study, we examined the effects of psilocybin in male mice that were stress-naïve, as well as in those that underwent either single-prolonged stress (SPS) or chronic restraint stress (CRS). The effects of these treatments on corticosterone release, extinction of freezing behavior, and recall of extinction in Pavlovian fear conditioning were examined for each group. We observed that psilocybin challenge transiently increased serum corticosterone in stress-naïve mice relative to saline; however, this effect was not observed in SPS and CRS animals. Interestingly, psilocybin treatment enhanced fear extinction and promoted extinction recall 24 h later not only in stress-naïve animals but also in stressed animals. These findings indicate psilocybin's ability to acutely enhance fear extinction and promote enhanced extinction recall across animals with diverse environmental stress experiences prior to exposure.

raw_json:
{"europe_pmc_id":"41244305","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Moskovitz M
journal: ACS pharmacology & translational science
publication_date: 2025-10-09
doi: 10.1021/acsptsci.5c00583
pubmed_id: 41098559
source_url: https://pubmed.ncbi.nlm.nih.gov/41098559/
keywords: Lysergic acid diethylamide (LSD), Music, Psilocybin, Psychedelic assisted therapy (PAT)
substance_tags: psilocybin
topic_tags: Review Article
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"41098559"}
title:
The Research Deficit and Expert Disagreement Regarding Music Selection for Psychedelic Assisted Therapy.

abstract:
Prior research has determined that music plays a central role in psychedelic assisted therapy (PAT). While there is a general consensus of the importance of music during PAT, there are only three empirical studies published to date that directly investigate which type of music might best support PAT. Importantly, no review to date has critically analyzed these studies and identified the gaps. Careful examination reveals these studies have important limitations and the findings lack alignment with other publications and existing recommendations. Additionally, our understanding of guidelines seems to be not much different from when this research started in 1970. This paper summarizes the common impacts of music during PAT, reviews what we know about music selection and guidelines for PAT, and makes suggestions of priorities for future research.


publication_date: 2025-10-05
doi: 10.1038/s41398-025-03611-0
pubmed_id: 41052972
source_url: https://doi.org/10.1038/s41398-025-03611-0
substance_tags: psilocybin,psilocin
topic_tags: Neuroplasticity,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psychedelic compounds directly excite 5-HT2A layer V medial prefrontal cortex neurons through 5-HT2A Gq activation.

authors:
Schmitz GP, Chiu YT, Foglesong ML, Magee SN, MacKinnon M, König GM, Kostenis E, Hsu LM, Shih YI, Roth BL, Herman MA.

abstract:
Psilocybin, and its active metabolite psilocin, have seen renewed interest due to studies suggesting potential therapeutic utility. 5-Hydroxytryptamine2A receptors (5-HT2ARs) are primary mediators of the psychoactive effects of psychedelics in animals and humans, but the underlying neurobiological mechanisms remain poorly understood. Functional magnetic resonance imaging identified significant psilocin-induced increases in medial prefrontal cortex (mPFC) activity, a site of enriched 5-HT2AR expression. We identified a population of 5-HT2AR neurons in the prelimbic/anterior cingulate mPFC. Psilocin and the 5-HT2AR-selective compound 25-CN-NBOH increased excitability, and stimulated firing across a range of current injections in these neurons that was both 5-HT2AR and Gαq dependent. Similar effects were observed with a novel, non-hallucinogenic psychedelic compound. These findings provide valuable insight into the specific role of 5-HT2AR-containing neurons in psychedelic-associated plasticity in mPFC regions that are likely implicated in the clinical effects of psychedelics and further identify membrane-bound 5-HT2ARs and subsequent intracellular Gαq signaling as therapeutic targets.

keywords:
Gyrus Cinguli, Prefrontal Cortex, Neurons, Animals, Rats, GTP-Binding Protein alpha Subunits, Gq-G11, Receptor, Serotonin, 5-HT2A, Hallucinogens, Magnetic Resonance Imaging, Male, Serotonin 5-HT2 Receptor Agonists, Psilocybin

raw_json:
{"europe_pmc_id":"41052972","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Visual Hallucinations in Serotonergic Psychedelics and Lewy Body Diseases
journal: PsyArXiv
publication_date: 2025-07-14
source_url: https://osf.io/preprints/psyarxiv/7x8q4_v3
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Review Article,Animal Study
study_type: Review Article
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"7x8q4_v3","version":3,"reviews_state":"accepted"}
abstract:
Background and Hypothesis Visual hallucinations (VH) are a core symptom of both Lewy body diseases (LBDs; e.g., Parkinson’s disease and dementia with Lewy bodies) and serotonergic psychedelics (SPs; e.g., psilocybin and mescaline). While these classes of VH differ in etiology, shared pathways are suggested by overlapping phenomenology and neural mechanisms. This review explores similarities and differences in VH between LBDs and SPs, focusing on phenomenology, cortical function, and serotonergic modulation. Study Design This narrative review synthesizes findings from neurology, cognitive neuroscience, and systems neuroscience to compare VH in LBDs and SPs. The literature includes studies with both human subjects and animal models that examine cortical activity patterns, neuromodulatory mechanisms, and VH phenomenology. Study Results Both LBDs and SPs exhibit distinct visual aberrations, ranging from minor metamorphopsias to complex hallucinations. Specific classes of VH in LBDs resemble those induced by SPs (e.g., illusory motion and entity encounters), suggesting shared neural mechanisms. Neuroimaging studies indicate a common pattern of hyperactive associative cortex and hypoactive sensory cortex. At the neuromodulator level, SP-induced VH involves serotonin 2A and 1A receptor (5-HT₂AR and 5-HT₁AR) modulation, while in LBDs, 5-HT₂AR upregulation correlates with increased VH, and its inhibition (e.g., with pimavanserin) reduces VH. Two shared cortical signatures are highlighted: reduced visual evoked responses and shifts toward visual excitation. Conclusions Examining cortical and neuromodulatory similarities between LBD- and SP-induced VH may elucidate the link between visual degradation, excitation, and hallucinogenesis. Future research should employ real-time neuroimaging of discrete hallucinatory episodes to identify shared mechanisms and develop targeted interventions for LBD hallucinations.

keywords:
Excitatory/Inhibitory Balance, Hallucinogenesis, Phenomenology, Sensory Deprivation, Serotonin Receptors, Visual Hierarchy, Psychiatry, Neuroscience, Cognitive Neuroscience, Systems Neuroscience, Clinical Neuroscience


title: Harm reduction practises for users of psychedelic drugs: a scoping review.
authors: Dutton C, North E, Chun Tie Y, Oliva J, Skeffington P
journal: Harm reduction journal
publication_date: 2025-10-02
doi: 10.1186/s12954-025-01264-2
pubmed_id: 41044617
source_url: https://pubmed.ncbi.nlm.nih.gov/41044617/
keywords: Benefit enhancement, Hallucinogens, Harm reduction strategies, Naturalistic use, Psilocybin, Risks
substance_tags: psilocybin
topic_tags: Review Article,Safety
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"41044617"}
abstract:
Psychedelic use in naturalistic settings in Australia is increasing. Although the risks and harms of psychedelics from a physical perspective are low, psychedelic drugs carry a unique psychological risk profile which is increased in uncontrolled settings. Harm reduction support services align with the Australian Government's Federal Drug strategy, which includes harm reduction as the third pillar in the overall harm minimisation approach to drug use for the period of 2017-2026. This study examined the harm reduction behaviours which users of psychedelics in naturalistic settings currently use, and any harm reduction interventions which have been developed for this population. A scoping review was undertaken using online databases, Psychinfo, Medline, CINAHL and Scopus. Articles were included if they explored or informed harm reduction practices for users of psychedelic drugs in naturalistic settings, which included articles that investigated motivations for psychedelic use. Twenty-seven papers were included, which contained only four intervention-based studies. Harm reduction or benefit enhancing strategies were categorised into three themes: before psychedelic use, during psychedelic experience and after the experience (integration). The review found that users of psychedelic drugs in naturalistic settings employ several different harm minimisation strategies, predominantly before and during use. Motivation for use, social setting and dosage amount were all found to influence the strategies used. There were a limited number of evaluated interventions for users of psychedelics in naturalistic settings, identifying the need for further research in this area. Challenges for harm reduction campaigns such as low uptake of drug checking services and low trust in government institutions were identified. Further research needs to consider the differing motivations of psychedelic users and recognise strategies that promote benefit enhancement and reduce risk.


title: Psychedelic-induced behavioral and developmental effects on zebrafish: a systematic review.
authors: de Oliveira AL, de Oliveira DP, Dos Santos RG, Hallak JEC.
publication_date: 2025-10-19
doi: 10.1016/j.pnpbp.2025.111534
pubmed_id: 41125218
source_url: https://doi.org/10.1016/j.pnpbp.2025.111534
keywords: Animals, Zebrafish, Hallucinogens, Behavior, Animal
substance_tags: psilocybin,psilocin
topic_tags: Anxiety,Mechanism of Action,Systematic Review,Review Article,Animal Study,Toxicity
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Psychedelics are mind-altering substances that have shown promising effects in the treatment of neuropsychiatric disorders owing to their antidepressant, anxiolytic and antiaddictive effects. However, data on their developmental toxicity is scarce, which might hinder its therapeutic suitability, and preclinical data on their behavioral effects is mainly restricted to rodents. In this context, zebrafish emerge as vertebrate model, since it shows well conserved genetic, neurodevelopment, molecular and physiological pathways that are comparable to humans. Additionally, high fecundity, clear embryo visualization, fast development and good nervous system homology make it an interesting model in assessing developmental toxicity and behavior. Thus, we conducted a systematic review of the articles which evaluated these parameters after psychedelic exposure. Thirteen articles were included of which nine focused on adult behavioral alterations and four on developmental toxicity. Substances used included ayahuasca, dimethyltryptamine (DMT), ibogaine, lysergic acid diethylamide (LSD), methylenedioxymethamphetamine (MDMA), mescaline, noribogaine, psilocybin and psilocin. Overall, psychedelics did not elicit morphological abnormalities in embryo-larvae, although ayahuasca induced edemas and increased mortality at high concentrations. Ibogaine, MDMA and LSD were associated with locomotor impairments after exposure during development. DMT, psilocybin and psilocin elicited an anxiolytic effect on larvae, while LSD, MDMA, mescaline and noribogaine reduced anxiety in adult fish. Altogether, psychedelics present a safe toxicological profile at low concentrations in zebrafish, but it is yet unclear whether they induce offspring's neurodevelopment deficits. Further studies are warranted to elucidate the extent of these adverse effects and if they persist during development.

raw_json:
{"europe_pmc_id":"41125218","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-10-09
doi: 10.1016/j.pnpbp.2025.111522
pubmed_id: 41077262
source_url: https://doi.org/10.1016/j.pnpbp.2025.111522
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Differential effects of psilocybin and lisuride on serotonin and dopamine neuronal activity and behavior.

authors:
Richardson B, Inserra A, Pileggi M, Prud'Homme T, Bruno V, Wan-Yan-Chan D, Shareghi-Ghahreman I, Nasini S, Strand T, Leyton M, Sonenberg N, De Gregorio D, Sprouse J, Bambico FR, Gobbi G.

abstract:
Psilocybin and lisuride are 5-HT2A receptor agonists, but only psilocybin elicits the head twitch response (HTR) in rodents, a behavior commonly used as a proxy for hallucinogenic activity. This study aimed to compare their effects on serotonin (5-HT) and dopamine (DA) neuronal activity, as well as related behavioral outcomes, to elucidate the mechanisms underlying their divergent effects. Adult male C57BL/6N mice were administered intraperitoneal injections of psilocybin (0.3-3 mg/kg), lisuride (0.1-0.5 mg/kg), or vehicle. In vivo electrophysiological recordings were performed in the dorsal raphe nucleus (DRN) and substantia nigra (SN) to monitor 5-HT and DA neuronal firing. MDL100907 (0.2 mg/kg) pretreatment was used to determine 5-HT2A receptor specificity. Behavioral assessments included HTR testing 10 min post-injection, followed by either the forced swim test (FST), open field test (OFT), or elevated plus maze (EPM) at 20 min post-injection. Psilocybin-induced inhibition, but not lisuride-induced inhibition, of 5-HT neuron firing was blocked by MDL100907. Both drugs reduced DA neuron firing, however, lisuride's effect was more sensitive to 5-HT2A receptor antagonism. Psilocybin elicited HTR, while lisuride did not. In the FST, only high-dose lisuride reduced immobility time. Both drugs reduced locomotor activity in the OFT and EPM. Principal Component Analysis (PCA) sufficiently separated the effects of each drug from each other, indicating distinct effect profiles. Although both drugs target 5-HT2A receptors, they engage distinct neurobiological pathways. Psilocybin produces psychedelic-like, 5-HT-dominant effects, whereas lisuride displays DA-linked improvements in coping behavior, informing future development of serotonergic therapeutics.

keywords:
Substantia Nigra, Animals, Mice, Inbred C57BL, Mice, Dopamine, Serotonin, Lisuride, Hallucinogens, Behavior, Animal, Motor Activity, Action Potentials, Dose-Response Relationship, Drug, Male, Serotonin 5-HT2 Receptor Agonists, Dopaminergic Neurons, Dorsal Raphe Nucleus, Psilocybin

raw_json:
{"europe_pmc_id":"41077262","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Meikle S, Carter O, Liknaitzky P, Johansen L, Iyer R, Strauss N, Williams M, Castle D, Rossell SL.
publication_date: 2025-10-01
doi: 10.1177/20451253251377187
pubmed_id: 41050149
source_url: https://doi.org/10.1177/20451253251377187
substance_tags: psilocybin
topic_tags: Depression,Spirituality,Clinical Trial,Treatment-Resistant Depression,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocybin with psychotherapeutic support for treatment-resistant depression: a pilot clinical trial.

abstract:
BackgroundDepressive disorders are a major global health challenge, with many individuals unresponsive to existing treatments. Novel psychedelic therapies show promise but require further research.ObjectivesThis study aimed to evaluate the feasibility, safety and effectiveness of psilocybin with psychotherapeutic support for treatment-resistant depression (TRD), investigate predictors of treatment outcomes and deepen understanding of individual variability in response.DesignOpen-label, single-arm pilot trial with mixed-methods assessment.MethodsTreatment consisted of two 25 mg psilocybin sessions, alongside three preparatory and six integration sessions. Depression severity was assessed using the self-rated Quick Inventory of Depressive Symptomatology at 3 weeks (primary endpoint) and at 20 weeks post-dose 2 (long-term follow-up). Potential predictors of clinical outcomes were evaluated using questionnaires, and qualitative interviews were used to capture individual experiences.ResultsAt the aggregate level, a clinically meaningful reduction in depressive symptoms was observed at the primary endpoint (mean change = -7.14; p = 0.02; Hedges' g = -1.27; 95% CI [-2.40, -0.37]) and maintained long-term. Individual participant data revealed diverse response patterns. Two participants displayed a sustained treatment response, three relapsed, and two exhibited no substantial improvement. Exploratory analyses identified mindset prior to dosing, spiritual experiences and perceptual shifts during dosing as predictors of treatment trajectory, while treatment expectations were not a reliable predictor. Adverse events were largely consistent with previous studies, with no serious adverse events.ConclusionFindings add to the growing evidence base for psilocybin therapy and provide direction for further research on individual variability in response to better tailor treatments and enhance efficacy.Trial registrationAustralian New Zealand Clinical Trials Registry (ACTRN12621001097831).

raw_json:
{"europe_pmc_id":"41050149","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin-assisted psychotherapy in adults with depression - A literature review.
authors: Dorczok MC, Mittmann G, Ettl T, Steiner-Hofbauer V.
publication_date: 2025-09-22
doi: 10.1016/j.pnpbp.2025.111508
pubmed_id: 40998282
source_url: https://doi.org/10.1016/j.pnpbp.2025.111508
keywords: Humans, Hallucinogens, Treatment Outcome, Depression, Psychotherapy, 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 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
BackgroundPsilocybin-Assisted Psychotherapy (PAP) has gained increasing attention in recent years as a potential treatment for depression, particularly in cases resistant to conventional therapies. This article aims to assess the efficacy of PAP in adults with various forms of depression by conducting a comprehensive review of the available literature.MethodA systematic search was conducted across several major databases (PubMed and Ebsco Host (incl. MEDLINE Ultimate, eBook Clinical Collection, DynaMed, APA PsycARTICLES, APA PsycINFO, Psychology & Behavioral Sciences Collection), focusing on studies that investigated the effects of psilocybin in a therapeutic setting.ResultsThe overall systematic literature search identified 139 items, of which seven were selected for detailed analysis. The studies employed different dosing regimens and varied in their methodologies of psychological support before, during, and after psilocybin administration. Most studies found significant improvements in depression symptoms after administration of Psilocybin and sustained antidepressant effects up to twelve months post-treatment. Response and remission rates were consistently high across studies.ConclusionsPAP combined with structured psychological support shows sustained reductions in depressive symptoms for treatment-resistant depression and major depressive disorder. Higher doses generally yield stronger benefits. While PAP holds significant potential as a holistic treatment, methodological limitations, such as heterogeneity in study designs, inconsistent levels of psychological support and difficulties in blinding due to the nature of the drug's effect, highlight the need for more standardized protocols in future studies to ensure reliable outcomes. More research is needed to better understand the mechanisms underlying its therapeutic effects.

raw_json:
{"europe_pmc_id":"40998282","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: [Role of psychedelics in psychiatry: a true therapeutic revolution or a trend?]
authors: Sabé M, Seragnoli F, Penzenstadler L, Thorens G.
publication_date: 2025-09-30
pubmed_id: 41575100
source_url: https://europepmc.org/article/MED/41575100
keywords: Humans, Hallucinogens, Mental Disorders, Psychiatry
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
abstract:
Role of psychedelics in psychiatryA TRUE THERAPEUTIC REVOLUTION OR A TREND? Psychedelics, long marginalized, are now gaining renewed interest in psychiatry for their therapeutic potential. Substances like psilocybin, LSD, and MDMA are being studied for treating conditions such as treatment-resistant depression, post-traumatic stress disorder (PTSD), and anxiety in palliative care. The FDA granted psilocybin "breakthrough therapy" status for certain indications in psychiatry, and progress has been made in Phase 3 clinical trials. However, the use of psychedelics carries risks, especially with non-medical use, including side effects. Stigmatization, their illegal status in many countries, and high costs limit accessibility. Despite promising results, the integration of these substances in psychiatry remains uncertain and raises ethical and societal concerns.

topic_tags:
Depression,Anxiety,PTSD,End-of-Life Distress,Clinical Trial,Treatment-Resistant Depression,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"41575100","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: Nature
publication_date: 2025-09-30
doi: 10.1038/s41586-025-09671-y
pubmed_id: 41023408
source_url: https://pubmed.ncbi.nlm.nih.gov/41023408/
substance_tags: psilocybin
topic_tags: Receptor Pharmacology
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"41023408"}
title:
Publisher Correction: Psilocybin's lasting action requires pyramidal cell types and 5-HT2A receptors.

authors:
Shao LX, Liao C, Davoudian PA, Savalia NK, Jiang Q, Wojtasiewicz C, Tan D, Nothnagel JD, Liu RJ, Woodburn SC, Bilash OM, Kim H, Che A, Kwan AC


authors: He Z, Tang R, Feng M, Li X, Zhang C, Li J.
publication_date: 2025-09-14
doi: 10.1080/15563650.2025.2552438
pubmed_id: 40948398
source_url: https://doi.org/10.1080/15563650.2025.2552438
keywords: Humans, Mushroom Poisoning, Hallucinogens, China, Psilocybe, Psilocybin
substance_tags: psilocybin
topic_tags: Case Report,Safety
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Dynamic myocardial injury and variable hallucination latency in Psilocybe keralensis poisoning: a molecularly confirmed case series from China.

abstract:
IntroductionPsychoactive Psilocybe spp. mushrooms pose significant public health risks. We report a cluster of Psilocybe keralensis poisonings in Chengdu, China, highlighting its unique clinical features and cardiovascular complications.Case seriesFour patients ingested 16-90 g of wild mushrooms (misidentified as an edible species, but later molecularly confirmed as Psilocybe keralensis). Prodromal symptoms (e.g., dizziness) emerged within 5-20 min, but the onset of hallucinations varied widely (10-180 min). All patients developed hypertension (systolic blood pressure >150 mmHg), with one patient exhibiting rapid blood pressure elevation to 182/110 mmHg at 4 h post-ingestion, which was accompanied by evidence of myocardial injury (peak cardiac troponin T concentration 188.70 pg/mL [reference range

raw_json:
{"europe_pmc_id":"40948398","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Serotonin 5-HT2C Receptor Signaling Analysis Reveals Psychedelic Biased Agonism.
publication_date: 2025-09-12
doi: 10.1021/acschemneuro.5c00647
pubmed_id: 40944639
source_url: https://doi.org/10.1021/acschemneuro.5c00647
substance_tags: psilocin
topic_tags: Depression,Mechanism of Action,Receptor Pharmacology,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
authors:
Bonniwell EM, Alabdali R, Hennessey JJ, McKee JL, Cavalco NG, Lammers JC, Moore EJ, Franchini L, Orlandi C, McCorvy JD.

abstract:
The serotonin 2C receptor (5-HT2C) is a G protein-coupled receptor implicated in multiple physiological and psychological processes and has been investigated as a therapeutic target for neuropsychiatric conditions such as obesity, drug abuse, and depression. With renewed interest in serotonergic psychedelics for treating depression, 5-HT2C may contribute to psychedelic-induced therapeutic effects. Despite earlier evidence of 5-HT2C G protein coupling promiscuity, the full signaling landscape remains incompletely characterized, which may help explain the limited efficacy and potential cancer risks associated with lorcaserin. Here, we provide a comprehensive analysis of 5-HT2C signaling, confirming and building upon previous findings that the receptor engages Gi/o/z and G12/13 proteins in addition to its primary Gq/11 pathway, and that it preferentially recruits β-arrestin2 over β-arrestin1. We also show that increased RNA editing of the receptor attenuates signaling across all G protein pathways, particularly for G12/13, while preserving β-arrestin recruitment. Profiling of both 5-HT2C-selective and psychedelic ligands reveals diverse signaling profiles, with serotonergic psychedelics such as LSD and psilocin exhibiting a striking Gq/11 bias due to minimal secondary G protein activation. Altogether, this work provides a foundation for incorporating a broader view of 5-HT2C signaling modalities into future investigations of 5-HT2C drug development efforts.

keywords:
Animals, Humans, Receptor, Serotonin, 5-HT2C, Hallucinogens, Signal Transduction, HEK293 Cells, Serotonin 5-HT2 Receptor Agonists, beta-Arrestin 2

raw_json:
{"europe_pmc_id":"40944639","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Concomitant use of antidepressants and classic psychedelics: A scoping review.
authors: Tap SC, Thomas K, Páleníček T, Stenbæk DS, Oliveira-Maia AJ, van Dalfsen JH, Schoevers RA.
publication_date: 2025-09-11
doi: 10.1177/02698811251368360
pubmed_id: 40937732
source_url: https://doi.org/10.1177/02698811251368360
keywords: Humans, Serotonin Syndrome, Hallucinogens, Antidepressive Agents, Mental Disorders
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology,Review Article,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
Classic psychedelics are increasingly studied as potential treatments for different psychiatric disorders. Current research protocols often require patients to discontinue antidepressants (ADs) for at least 2 weeks before psychedelic administration to decrease the risk of serotonin syndrome and limit their effect on efficacy and the acute subjective effects of psychedelics. Moreover, the discontinuation of ADs represents a significant burden to patients that could also worsen their depression status and increase suicidal ideation. Together, this suggests that the general recommendation for AD discontinuation might be unnecessary and even detrimental to the therapeutic efficacy of psychedelics. In this scoping review, we summarise the existing literature on the concomitant use of conventional ADs with classic psychedelics in humans with the aims to assess safety, tolerability, efficacy, and subjective effects. Following PRISMA-ScR guidelines, we searched MEDLINE, Embase, and Scopus databases to retrieve relevant literature from inception to March 3, 2025. Data were systematically charted from included studies. We included 18 studies and found that the concomitant use of ADs and classic psychedelics is generally safe and tolerable, with no increased risk of serotonin syndrome, particularly for psilocybin. Some studies reported significant improvements in depression and other mental health symptoms. While some evidence indicates a potential attenuation of acute subjective psychedelic effects, this was not observed in all studies. Accordingly, we conclude that the use of ADs can be maintained to enhance patient access to psychedelic treatments and avoid the risk of AD discontinuation syndrome. Finally, this review highlights limitations and several knowledge gaps in the current literature that need to be addressed in future randomized double-blind, placebo-controlled trials.

raw_json:
{"europe_pmc_id":"40937732","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: US Poison Center Encounters for Psilocybin-Related Exposures: 2013-2022.
authors: Montoy JCC, Wang RC, Coker AR, Smollin CG, Anderson BT.
publication_date: 2025-08-29
doi: 10.1016/j.acepjo.2025.100231
pubmed_id: 40927687
source_url: https://doi.org/10.1016/j.acepjo.2025.100231
substance_tags: psilocybin
topic_tags: Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
ObjectivesGiven the increasing use of psilocybin-containing substances across a variety of use settings, understanding the potential risks is imperative for informing public health policy, health care providers, and consumers. Poison centers (PCs) receive calls following exposures to potential toxins to support the detection, prevention, and treatment of toxin-related health emergencies. This report assesses trends in PC encounters of psilocybin and a subset of other comparator substances.MethodsA retrospective study of PC encounters documenting exposure to psilocybin, other psychedelic substances (lysergic acid diethylamide, mescaline/peyote, and hallucinogenic plants), or toxic plants and mushrooms from 2013 to 2022 was performed. The primary outcome was the occurrence of psilocybin-related encounters, with and without other coingestants. Psilocybin-related encounters were presented overall and stratified by age groups, and the clinical outcomes were described.ResultsThere were 6933 PC encounters for psilocybin-containing substances between 2013 and 2022. PC encounters for psilocybin-containing substances (alone or with coingestants) increased over time-from 477 in 2013 to 1441 in 2022. Psilocybin-related encounters increased over the study period among all age groups (years) and were most common in the 18 to 24 and 25 to 44 year-old age groups. Across all years, the number of psilocybin-related encounters was similar to those for lysergic acid diethylamide and mescaline/peyote, and far lower than those for other mushrooms and toxic plants.ConclusionFrom 2013 to 2022, there was a 3-fold increase in psilocybin-related PC encounters, nearly all of which occurred since 2019. A similar pattern was not observed with other substances. Although the number of encounters remains low, this trend could continue as psilocybin use increases.

raw_json:
{"europe_pmc_id":"40927687","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-09-30
doi: 10.1016/s2352-4642(25)00208-1
pubmed_id: 40908054
source_url: https://doi.org/10.1016/s2352-4642(25)00208-1
substance_tags: psilocybin
topic_tags: Anxiety,PTSD,Review Article,Adolescents,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Clinical psychedelic research in adolescents: a scoping review and overview of ethical considerations.

authors:
Rajwani K, Jacobs E, Bruce L, Hokanson J, Almonte MT, Feroz F, Waldman E, Cheung K, Levy N, Savulescu J, Singh I, Yaden DB, Earp BD.

abstract:
The potential use of psychedelic-assisted therapy for adolescents with mental illness has sparked both interest and concern. Modern psychedelic research has focused on adults, and adolescents younger than 18 years are typically excluded due to ethical and legal challenges. To explore whether adolescents have been included in 21st century psychedelic research, we conducted a scoping review of the medical literature from January, 2000, to April, 2025. Three trial registrations and one trial plan showed involvement of participants younger than 18 years, but none of these trials were completed and no trial findings have been published. The proposed studies would investigate 3,4-methylenedioxymethamphetamine (MDMA)-assisted or psilocybin-assisted psychotherapy as an intervention for adolescents with post-traumatic stress disorder, autism with social anxiety, or self-harm. Ethical approval and recruitment details were inconsistently reported. This scarcity of data highlights a major evidence gap that could hinder informed care. Given that many medications are used off-label in adolescents, we argue for cautious, ethically grounded research-starting with older adolescents with the highest foreseeable benefit-risk ratio due to special circumstances-to better understand the potential risks and benefits of psychedelic therapies for this vulnerable population.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Mental Disorders, Psychotherapy, Biomedical Research, Adolescent, Psilocybin

raw_json:
{"europe_pmc_id":"40908054","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-08-15
doi: 10.1016/j.psychres.2025.116697
pubmed_id: 40840197
source_url: https://doi.org/10.1016/j.psychres.2025.116697
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Endocannabinoids, depression, and treatment resistance: Perspectives on effective therapeutic interventions.

authors:
Rosa I, Padula LP, Semeraro F, Marrangone C, Inserra A, De Risio L, Boffa M, Zoratto F, Borgi M, Guidotti R, Lorenzo GD, D'Addario C, Pettorruso M, Martinotti G.

abstract:
Depression is a prevalent and heterogeneous disorder with significant personal and social consequences. The rise of treatment-resistant depression (TRD) challenges traditional approaches and underscores the need for a broader neurobiological perspective. When monoaminergic modulation proves insufficient, clinical guidelines increasingly turn to non-monoaminergic interventions such as neuromodulation techniques and glutamatergic agents, which operate through distinct mechanisms. Despite their heterogeneity, these treatments may act on shared final pathways that differ from those of conventional antidepressants. Among these pathways, the endocannabinoid system (ECS) has emerged as a critical mood regulator and a potential mediator of antidepressant effects. This narrative review draws from preclinical and clinical literature to explore the role of the ECS in depression and its involvement in various non-monoaminergic treatments effective in TRD. Evidence suggests that physical interventions like repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT), as well as glutamatergic and serotonergic agents such as ketamine, esketamine, and psychedelics, influence ECS components. rTMS and ECT elevate levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), correlating with clinical improvement. Ketamine and esketamine modulate CB1 receptors and other ECS targets, contributing to their rapid effects. Psilocybin restores 2-AG and enhances CB1 expression in mood-related brain regions, while LSD affects the broader endocannabinoidome in the prefrontal cortex and hippocampus. These findings suggest that ECS modulation may constitute a unifying mechanism through which diverse, non-monoaminergic interventions exert antidepressant effects in TRD, positioning the ECS as a promising target of novel treatment strategies for individuals who do not respond to conventional treatments.

keywords:
Animals, Humans, Antidepressive Agents, Endocannabinoids, Electroconvulsive Therapy, Transcranial Magnetic Stimulation, Depressive Disorder, Treatment-Resistant

topic_tags:
Depression,Mechanism of Action,Receptor Pharmacology,Review Article,Animal Study,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"40840197","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The polypharmacology of psychedelics reveals multiple targets for potential therapeutics.
publication_date: 2025-07-17
doi: 10.1016/j.neuron.2025.06.012
pubmed_id: 40683247
source_url: https://doi.org/10.1016/j.neuron.2025.06.012
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Headache / Migraine,Pharmacology,Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
authors:
Jain MK, Gumpper RH, Slocum ST, Schmitz GP, Madsen JS, Tummino TA, Suomivuori CM, Huang XP, Shub L, DiBerto JF, Kim K, DeLeon C, Krumm BE, Fay JF, Keiser M, Hauser AS, Dror RO, Shoichet B, Gloriam DE, Nichols DE, Roth BL.

abstract:
The classical psychedelics (+)-lysergic acid diethylamide (LSD), psilocybin, and mescaline exert their psychedelic effects via activation of the 5-HT2A serotonin receptor (5-HT2AR). Recent clinical studies have suggested that classical psychedelics may additionally have therapeutic potential for many neuropsychiatric conditions including depression, anxiety, migraine and cluster headaches, drug abuse, and post-traumatic stress disorder. In this study, we investigated the pharmacology of 41 classical psychedelics from the tryptamine, phenethylamine, and lysergamide chemical classes. We profiled these compounds against 318 human G-protein-coupled receptors (GPCRs) to elucidate their target profiles, and in the case of LSD, against more than 450 human kinases. We found that psychedelics have potent and efficacious actions at nearly every serotonin, dopamine, and adrenergic receptor. We quantified their activation for multiple transducers and found that psychedelics stimulate multiple 5-HT2AR transducers, each of which correlates with psychedelic drug-like actions in vivo. Our results suggest that multiple molecular targets likely contribute to the actions of psychedelics.

keywords:
Animals, Humans, Tryptamines, Lysergic Acid Diethylamide, Receptors, G-Protein-Coupled, Receptor, Serotonin, 5-HT2A, Hallucinogens, Polypharmacology

raw_json:
{"europe_pmc_id":"40683247","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Informed Consent Documents from Psychedelic Clinical Trials: A Descriptive Ethical Analysis.
authors: Cheung K, Propes C, Graziosi M, Patch K, Yaden DB.
publication_date: 2025-07-15
doi: 10.1080/23294515.2025.2526339
pubmed_id: 40668936
source_url: https://doi.org/10.1080/23294515.2025.2526339
substance_tags: psilocybin
topic_tags: Consciousness,Clinical Trial,Review Article,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
abstract:
BackgroundClassic psychedelics, such as psilocybin and LSD, evoke certain kinds of altered states of consciousness. Specific features of the experience, such as its allegedly ineffable nature, have been discussed as posing challenges to the informed consent process. A growing call for tailored informed consent documents (ICDs) in the psychedelic bioethics literature raises the question of how closely ICDs used in contemporary psychedelic trials reflect the concrete suggestions and proposals offered by psychedelic bioethicists.MethodsIn this article, we review ICDs from psilocybin clinical trials in the United States. Using a content analysis approach, we provide a systematic qualitative description of the ICDs which comprise our final sample (N = 28; 28 clinical trials across 13 unique sites). Coders demonstrated good reliability (κ =.683).ResultsQualitative analyses revealed that most of the coding aligned with expectations based upon the psychedelics bioethics literature, such as the emphasis on mental health risks and physical risks in ICDs. Notably, psychedelic-specific codes (e.g., ineffability, therapeutic touch) did not appear as frequently in ICDs.ConclusionsScholars in psychedelic bioethics have called for the inclusion of a variety of potential risks and benefits in ICDs. It will be important to continue debating which elements are worth including in ICDs such that potential research participants are presented with the most salient factors relevant to their decision about joining a study. We provide a table of best practices applied by our sample of ICDs.

keywords:
Humans, Hallucinogens, Informed Consent, Consent Forms, United States, Clinical Trials as Topic, Psilocybin

raw_json:
{"europe_pmc_id":"40668936","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Larsen JK, Kølbæk P, Østergaard SD.
publication_date: 2025-07-09
doi: 10.1080/08039488.2025.2529449
pubmed_id: 40635579
source_url: https://doi.org/10.1080/08039488.2025.2529449
substance_tags: psilocybin
topic_tags: Review Article,Adolescents,Adverse Events
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Treatment with LSD and psilocybin at the department of psychiatry at Frederiksberg Hospital in Denmark from 1960 to 1973: an analysis of 324 cases.

abstract:
BackgroundRecent studies have suggested that psychedelics such as lysergic acid diethylamide (LSD) and psilocybin might benefit patients with mental illness. This revival calls for revisiting the field's past experiences with these agents. From 1960 to 1973, many patients were treated with LSD and/or psilocybin at the Department of Psychiatry at Frederiksberg Hospital in Denmark. Here, we analyze the case material/medical records of 324 of these patients. Specifically, we aimed to estimate whether patients who applied for reparatory compensation (applicants; n = 93) as per the Danish LSD Damages Law had worse responses and were more affected by adverse events related to psychedelic treatment than those who did not (non-applicants; n = 231).Materials and methodsData from the LSD archive at Frederiksberg City Archives were reviewed, and data regarding patient characteristics and LSD/psilocybin treatment (dose, effect, and adverse events) were extracted. Data were compared between applicants and non-applicants using independent samples t-tests, Mann-Whitney U tests, chi-square tests, and Fisher's exact tests, as appropriate.ResultsApplicants were treated with higher LSD doses (median LSD dose-index: 31 vs. 21, p = 0.040) and received more treatments (median: 14 vs. 10, p = 0.005) than the non-applicants. Treatment responses did not differ significantly between applicants and non-applicants. Flashbacks were registered for a larger fraction of the applicants compared to non-applicants (18.2% vs. 5.2%, p

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Mental Disorders, Adolescent, Adult, Middle Aged, Denmark, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"40635579","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The therapeutic potential of psilocybin beyond psychedelia through shared mechanisms with ketamine.
authors: Park D, Lee G, Lee WG, Kim B, Lee Y, Kim JW.
publication_date: 2025-07-06
doi: 10.1038/s41380-025-03100-2
pubmed_id: 40624295
source_url: https://doi.org/10.1038/s41380-025-03100-2
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Review Article,Animal Study
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Major depressive disorder is a debilitating condition, with many patients unresponsive to conventional monoaminergic antidepressants. Rapid-acting antidepressants such as ketamine and psilocybin offer promising alternatives, relieving symptoms within hours. Ketamine, an NMDA receptor antagonist, and psilocybin, a serotonergic psychedelic primarily targeting 5-HT2A receptors, both enhance synaptic plasticity in mood-regulating circuits through distinct mechanisms. This review synthesizes recent clinical and preclinical findings on ketamine and psilocybin, emphasizing their molecular targets, circuit-level effects, and converging downstream pathways. A key shared mechanism involves BDNF-TrkB signaling, which promotes spinogenesis and synaptogenesis critical for sustained antidepressant efficacy. We also discuss 5-HT2A receptor biased agonism as a potential strategy to dissociate psilocybin's therapeutic effects from its hallucinogenic actions. By comparing their mechanistic profiles, we identify both overlapping and distinct features that may inform the development of next-generation rapid-acting antidepressants. Understanding how serotonergic, glutamatergic, and neurotrophic systems converge may guide the development of fast-acting, durable, and non-hallucinogenic antidepressants.

keywords:
Animals, Humans, Ketamine, Brain-Derived Neurotrophic Factor, Receptor, Serotonin, 5-HT2A, Receptors, N-Methyl-D-Aspartate, Hallucinogens, Antidepressive Agents, Signal Transduction, Neuronal Plasticity, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"40624295","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-06-30
doi: 10.1016/j.comppsych.2025.152619
pubmed_id: 40618640
source_url: https://doi.org/10.1016/j.comppsych.2025.152619
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Single-dose (10 mg) psilocybin reduces symptoms in adults with obsessive-compulsive disorder: A pharmacological challenge study.

authors:
Pellegrini L, Fineberg NA, O'Connor S, De Souza AMFLP, Godfrey K, Reed S, Peill J, Healy M, Rohani-Shukla C, Lee H, Carhart-Harris R, Robbins TW, Nutt D, Erritzoe D.

abstract:
BackgroundObsessive-compulsive disorder (OCD) is a common and disabling condition. A large proportion of patients fail to respond to first-line treatment with serotonin reuptake inhibitors either selective serotonin reuptake inhibitors (SSRIs) or clomipramine. Preliminary evidence suggests psilocybin, a serotonin receptor agonist, might be efficacious. We conducted a pharmacological challenge study to investigate the efficacy and mechanisms of effect of psilocybin in OCD. This analysis reports the clinical outcomes only.MethodsParticipants with a diagnosis of OCD of at least moderate severity, received two single doses of oral psilocybin, 1 mg followed by 10 mg, administered in fixed order separated by 4 weeks. On the day of dosing, they were treated in a day-care facility in the presence of clinicians experienced in the use of psychedelics for treating mental disorders. Psychological support was provided before, during and after dosing. Participants and raters were blinded to the order of treatment. They were assessed on the day before each dose (baseline 1, 2), on the day of dosing and at intervals over a 4-week period afterward using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) (primary clinical outcome) and secondary clinical outcomes including the Montgomery-Åsberg Depression Rating Scale (MADRS). Adverse effects were also recorded.ResultsNineteen adult participants (aged 20-60) entered the study and 18 completed all assessments. Clinical outcomes following 1 mg and 10 mg psilocybin were compared using a linear mixed-effects model and ANOVA. A significant between-dosage effect favouring 10 mg psilocybin was found one-week after dosing on the Y-BOCS (Cohen's d = 0.82, p = 0.002). In particular, the effect one-week after dosing was statistically significant on the compulsion subscale of the Y-BOCS (Cohen's d: 0.74, p = 0.003), compared to obsession (Cohen's d: 0.50, p = 0.06). The effect diminished over the subsequent 3 weeks. No effect of psilocybin was detected on the MADRS. Psilocybin was well tolerated, with few adverse events reported at both dosages and no serious adverse events.ConclusionsIn this study, which was limited by a small sample size and the absence of randomisation, a 10 mg dose of oral psilocybin was found to be well-tolerated and potentially efficacious in patients with OCD. Psilocybin produced a rapid-onset, moderate to large effect on compulsive symptoms, which lasted up to one week after dosing. Future randomised placebo-controlled clinical trials investigating a longer course of multiple weekly doses of 10 mg psilocybin are indicated in OCD and in other obsessive-compulsive and related disorders characterised by compulsions.

keywords:
Humans, Hallucinogens, Treatment Outcome, Obsessive-Compulsive Disorder, Psychiatric Status Rating Scales, Adult, Middle Aged, Female, Male, Young Adult, Psilocybin

topic_tags:
Depression,OCD,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Healthcare Workers,Adverse Events

raw_json:
{"europe_pmc_id":"40618640","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Borgogna NC, Owen T, Petrovitch D, Vaughn J, Johnson DAL, Pagano LA, Aita SL, Hill BD.
publication_date: 2025-09-30
doi: 10.1007/s00213-025-06818-7
pubmed_id: 40381005
source_url: https://doi.org/10.1007/s00213-025-06818-7
substance_tags: psilocybin
topic_tags: Depression,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Correction to: Incremental efficacy systematic review and meta-analysis of psilocybin-for-depression RCTs.

raw_json:
{"europe_pmc_id":"40381005","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: McGriff SA, Hecker JC, Maitland AD, Partilla JS, Baumann MH, Glatfelter GC.
publication_date: 2025-05-16
doi: 10.1007/s00213-025-06795-x
pubmed_id: 40381003
source_url: https://doi.org/10.1007/s00213-025-06795-x
substance_tags: psilocybin
topic_tags: Animal Study,Drug Interactions
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Psychedelic-like effects induced by 2,5-dimethoxy-4-iodoamphetamine, lysergic acid diethylamide, and psilocybin in male and female C57BL/6J mice.

abstract:
RationaleThe head twitch response (HTR) is a spontaneously occurring behavior in mice that is increased in frequency by serotonergic psychedelics. The mouse HTR is often used as a proxy for psychedelic-like drug effects, but limited information is available about sex differences in HTRs evoked by various classes of psychedelics (i.e., phenethylamines, lysergamides, tryptamines).Objective and methodsTo examine potential sex differences in responsiveness to structurally-distinct psychedelics, acute effects of subcutaneous 2,5-dimethoxy-4-iodo-amphetamine (DOI, 0.03-10 mg/kg), lysergic acid diethylamide (LSD, 0.003-1 mg/kg), and 4-phosphoryloxy-N,N-dimethyltryptamine (psilocybin, 0.03-10 mg/kg) on HTRs were compared in male and female C57BL/6J mice. For comparison, effects of the drugs on locomotor activity and body temperature were also determined.ResultsDrug potencies for inducing HTRs were similar in males and females for all drugs, with only LSD exhibiting detectable differences due to increased maximal counts in females. Importantly, the maximum number of HTRs observed for all drugs was higher in females, with significant differences between sexes for DOI and LSD. Dose x sex interactions for the dose-response data were statistically significant for psilocybin and LSD, with females displaying more HTRs after the highest or peak doses of all drugs. The acute effects of drugs on locomotion and temperature varied by drug, but were similar in both sexes.ConclusionsThe present results overall show no substantial sex differences in the potencies to induce HTRs for DOI, LSD, and psilocybin in C57BL/6J mice. However, females uniformly displayed more HTRs at high doses administered across chemotypes. The results further suggest that commonly used doses of psychedelics induce comparable psychedelic-like effects in male and female C57BL/6J mice, but modest differences may emerge at high doses.

keywords:
Animals, Mice, Inbred C57BL, Mice, Amphetamines, Lysergic Acid Diethylamide, Hallucinogens, Sex Factors, Sex Characteristics, Dose-Response Relationship, Drug, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"40381003","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Incremental efficacy systematic review and meta-analysis of psilocybin-for-depression RCTs.
authors: Borgogna NC, Owen T, Petrovitch D, Vaughn J, Johnson DAL, Pagano LA, Aita SL, Hill BD.
publication_date: 2025-04-22
doi: 10.1007/s00213-025-06788-w
pubmed_id: 40266291
source_url: https://doi.org/10.1007/s00213-025-06788-w
keywords: Humans, Hallucinogens, Depression, Randomized Controlled Trials as Topic, Psilocybin
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
RationalePsilocybin is a potentially paradigm-shifting depression intervention. We conducted a systematic review and meta-analysis of psilocybin-for-depression randomized controlled trials (RCTs).ObjectivesSystematically assess harm reporting, risk of bias, action mechanism specification, and incremental therapeutic effect sizes in the psilocybin-for-depression RCT literature.MethodsAssessed databases included PsycINFO, CINAHL, Embase, Medline, Web of Science, and Scopus. Search terms "Psilocybin" or "Psychedelic" were paired with "Depression", and "Randomized Controlled Trial" or "RCT".ResultsWe identified k = 9 RCTs (k = 10 subgroups) involving n = 602 participants (56% psilocybin). Five studies had low/very low harm quality reporting, opposed to two with high. Most studies demonstrated a high risk of bias. Therapeutic mechanisms of action (MoAs) were discussed in varying detail but rarely assessed in original publications. Psilocybin was moderately superior to controls at reducing depression (g = 0.62; 95% CI = 0.27, 0.98). Effects were heterogenous (τ =.47). Smaller studies evidenced stronger effects that favored psilocybin (Egger's b0 = 3.63, p =.014). Almost all studies documented financial conflicts of interests.ConclusionPsilocybin demonstrates significant depression reduction relative to controls. However, researchers, clinicians, and stakeholders should consider several contextual factors. Effects were moderate and attenuated in larger and better-controlled studies. Harms reporting and risk of bias was high, though partly driven by unique challenges of psilocybin research. MoAs were variably specified but rarely assessed; suggesting it is unclear how depression is reduced. We advise researchers conduct RCTs with active control conditions, larger samples, and include MoA assessments. Independent RCTs from researchers without financial conflicts of interest are needed.

topic_tags:
Depression,Mechanism of Action,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Healthcare Workers,Safety

raw_json:
{"europe_pmc_id":"40266291","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-04-14
doi: 10.1007/s00210-025-04152-5
pubmed_id: 40232378
source_url: https://doi.org/10.1007/s00210-025-04152-5
substance_tags: psilocybin,psilocin
topic_tags: Mechanism of Action,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocin alleviates acute itch in mice: possible involvement of 5-HT2A receptors and kynurenine pathway.

authors:
Afrooghe A, Ahmadi E, Lesani A, Mehranjani MS, Elahi M, Babaei M, Shayan M, Shafaroodi H, Jafari RM, Foroumadi A, Manavi MA, Dehpour AR.

abstract:
We aimed to investigate whether psilocin, the bioactive metabolite of the well-known psychedelic, psilocybin, may have antipruritic effects in mice by interfering with the kynurenine pathway and interacting with 5-HT2A receptors. Eight mice were randomly assigned to each of the study groups receiving either normal saline, compound 48/80, psilocin (0.3, 1, and 3 mg/kg), or psilocin (1 mg/kg) + 1-MT (0.3 mg/kg). The scratching bouts were documented in each group. The hallucinogenic properties of psilocin were documented using the head-twitch response (HTR) test. To confirm their involvement, we also quantified the expression levels of TNF-α, TLR-4, indoleamine-2,3-dioxygenase (IDO), and 5-HT2A receptors across various study groups. We found that psilocin (1 mg/kg) exerted the most significant antipruritic and hallucinogenic effects (P

keywords:
Animals, Mice, Pruritus, Kynurenine, Tumor Necrosis Factor-alpha, Receptor, Serotonin, 5-HT2A, Hallucinogens, Antipruritics, Signal Transduction, Male, Indoleamine-Pyrrole 2,3,-Dioxygenase, Toll-Like Receptor 4, Psilocybin, Polycyclic Sesquiterpenes

raw_json:
{"europe_pmc_id":"40232378","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-03-24
doi: 10.1177/07067437251328316
pubmed_id: 40129307
source_url: https://doi.org/10.1177/07067437251328316
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Comparing Antidepressant Effects of Psilocybin-Assisted Psychotherapy in Individuals That Were Unmedicated at Initial Screening Versus Individuals Discontinuing Medications for Study Participation: Comparaison des effets antidépresseurs de la psychothérapie assistée par la psilocybine (PAP) chez les personnes non médicamentées à la sélection initiale et les personnes ayant arrêté les médicaments pour participer à l'étude.

authors:
Chisamore N, Kaczmarek ES, Doyle Z, Johnson DE, Weiglein G, Meshkat S, Brudner RM, Blainey MG, Riva-Cambrin J, McIntyre RS, Rosenblat JD.

abstract:
ObjectiveTo compare changes in depression, anxiety, and suicidality symptoms after a single 25 mg oral dose of psilocybin between treatment-resistant depression participants not on antidepressants at screening to participants that discontinued antidepressant medications leading up to receiving psilocybin-assisted psychotherapy (PAP).MethodsParticipants (n = 27) received at least one 25 mg dose of psilocybin accompanied by psychotherapy as part of an exploratory analysis from an open-label, randomized, waitlist-controlled clinical trial. The primary outcome of changes in depression symptoms was measured by the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary outcomes included changes in anxiety symptom severity (Generalized Anxiety Disorder 7-Item [GAD-7]), suicidal ideation (MADRS Item-10), self-reported depression symptoms (Quick Inventory for Depression Symptomology [QIDS-SR]), and intensity of psychedelic experience (Mystical Experience Questionnaire 30-item [MEQ30]). Patients were separated into two groups for analysis; those who were unmedicated at initial screening versus participants that had to taper off antidepressant medications to be eligible for the trial. A mixed analysis of variance was used to evaluate clinical outcomes over time from baseline to 2 months post-dose.ResultsNo significant differences were found between medication discontinued (n = 18) and unmedicated at screening (UAS) (n = 9) groups in clinician rated depression (p = 0.759), self-reported depression (p = 0.215), anxiety (p = 0.178), and suicidality (p = 0.882) symptoms over time, with both groups having clinically significant benefits on all outcomes assessed. Both groups also had a similar intensity of psychedelic experience (p = 0.191).ConclusionComparable improvements were observed in depression and anxiety and symptoms between antidepressant discontinued and UAS patients. These findings contrast with and contribute to the growing literature on the effects of medication tapering leading up to PAP. Further clinical research is needed to directly compare efficacy across medication statuses, in addition to evaluating psychedelic effects in individuals continuing antidepressants during PAP.

keywords:
Humans, Hallucinogens, Antidepressive Agents, Combined Modality Therapy, Psychotherapy, Adult, Middle Aged, Female, Male, Suicidal Ideation, Depressive Disorder, Treatment-Resistant, Psilocybin, Outcome Assessment, Health Care

topic_tags:
Depression,Anxiety,Mystical Experience,Clinical Trial,Treatment-Resistant Depression,Healthcare Workers

raw_json:
{"europe_pmc_id":"40129307","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics and autobiographical memory - Six open questions
journal: PsyArXiv
publication_date: 2025-03-10
source_url: https://osf.io/preprints/psyarxiv/su7ch_v2
substance_tags: psilocybin
topic_tags: Pharmacology
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"su7ch_v2","version":2,"reviews_state":"accepted"}
abstract:
Rationale Since the earliest LSD research, psychedelics have been claimed to enhance autobiographical memory. Revisiting and processing autobiographical memories has further been suggested to be a major component of the therapeutic action of psychedelics. However, modern psychedelic research has largely neglected autobiographical elements of psychedelic experiences, and many vital questions remain unanswered. Objectives We present and discuss six open questions related to psychedelics and autobiographical memory: 1. Do psychedelics enhance autobiographical recall? 2. Is recall and processing of significant autobiographical (e.g., traumatic) memories a common part of psychedelic experiences? 3. Do psychedelics promote the development of false or inaccurate memories? 4. How do autobiographical memories change if they are recalled and reconsolidated under the effects of psychedelics? 5. What are memories of psychedelic experiences like? 6. Are autobiographical experiences under psychedelics of particular importance for their therapeutic effects? Results We present the background and current limited state of evidence for each question and provide suggestions on how future studies could best address them. Conclusions Besides advancing basic research, answering these pressing questions is highly relevant for the possible therapeutic use of psychedelics, both in terms of developing and optimizing new interventions and for avoiding iatrogenic harms. Ideally, future psychedelic-assisted interventions could harness the possible synergies between the effects of psychedelics and existing memory-based therapies. Keywords: Psychedelics, autobiographical memory, LSD, psilocybin

keywords:
autobiographical memory, LSD, psilocybin, psychedelics, Social and Behavioral Sciences, Clinical Psychology, Psychopharmacology


publication_date: 2025-09-14
doi: 10.1021/acsomega.5c05606
pubmed_id: 41048717
source_url: https://doi.org/10.1021/acsomega.5c05606
substance_tags: psilocybin,psilocin
topic_tags: Safety,Toxicity
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Multianalytical Investigation of Psilocybe cubensis Mushrooms: Physicochemical Characterization and Biological Evaluation of Psilocybin and Psilocin Compounds.

authors:
Pereira Galdino T, Bisneto ABM, Pedro MDS, de Oliveira LC, Luz MA, de Lima AGB, Silva SML, Fook MVL.

abstract:
Mental disorders of the global population have been evaluated statistically by decades. Psilocybin has medicinal properties with potential pharmaceutical applications for treatment of psychological disorders. This component is present naturally in mushrooms of the Psilocybe genus and is primarily responsible for their psychoactive properties. It exhibits a low risk of acute toxicity and has shown no evidence of neurotoxicity, carcinogenicity, or mutagenicity in current toxicological assessments. This study aimed to develop an active pharmaceutical ingredient (API) derived from Psilocybe mushrooms for application in the management of mental health disorders. The primary objectives include extraction of bioactive compounds, quantitative analysis, and evaluation of their physicochemical and biological properties. Following the extraction procedures, the experiments achieved yields of approximately 20%, demonstrating effective isolation of the target compounds. The presence of alkaloids was confirmed through phytochemical screening and validated by high-performance liquid chromatography (HPLC) analysis. The obtained API exhibited thermal and spectroscopic characteristics consistent with those of edible mushroom extracts, enabling a comprehensive understanding of its physicochemical behavior. Additionally, analytical assays demonstrated high solubility, low toxicity, and compliance with acceptable limits for heavy metal content and microbial load, including aerobic microorganisms, fungi, and yeasts. Quantitative HPLC analysis revealed psilocybin and psilocin contents of 3.26 and 0.34%, respectively, supporting the formulation of drug delivery systems with standardized concentrations of psilocybin. The results indicated that the extracted API is stable, highly pure, and compatible with polymeric matrices for controlled release applications. Furthermore, the assays confirmed high solubility in polar solvents and minimal risk of adverse effects. In conclusion, the study showed that the development of a psilocybin- and psilocin-based API is feasible and represents a significant advancement in the treatment of mental disorders, standing out as a promising solution in the pursuit of innovative therapeutic alternatives.

raw_json:
{"europe_pmc_id":"41048717","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-09-29
doi: 10.1038/s41467-025-64371-5
pubmed_id: 41027992
source_url: https://doi.org/10.1038/s41467-025-64371-5
substance_tags: psilocybin
topic_tags: Anxiety,Pharmacology,Receptor Pharmacology,Animal Study,Safety
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocybin during the postpartum period induces long-lasting adverse effects in both mothers and offspring.

authors:
Hatzipantelis CJ, Liu M, Love A, Leventhal SJ, Maera H, Viswanathan S, Avetisyan E, Belinsky L, Rangel MM, Jain NJ, Kelly M, Copeland C, Khatib YA, Fiehn O, Olson DE, Stolzenberg DS.

abstract:
Psilocybin increases social connectedness and has strong clinical transdiagnostic efficacy for mental illness, making it a candidate treatment to reduce maternal disconnect, anxiety, and blunted affect seen in peripartum mood disorders. However, the efficacy and safety of psilocybin in peripartum mood disorders has not been investigated. We used a social stress model to examine the effects of psilocybin in parous mice and their offspring. Social stress induced maternal withdrawal and increased stress-related behaviors - none of which were ameliorated by psilocybin. Weeks later, psilocybin-treated dams were more anxious, regardless of stress exposure. In contrast, psilocybin-treated virgin females were unaffected. Though reproductive status did not affect psilocybin pharmacokinetics, serotonin receptor transcription and 5-HT2A receptor-dependent responses were reduced in dams. Offspring exposed to maternal psilocybin during breastfeeding exhibited anhedonia in adulthood. Here, we show that both parous parents and their children may be uniquely vulnerable to psychedelic treatment during the postpartum period.

keywords:
Animals, Mice, Inbred C57BL, Mice, Receptor, Serotonin, 5-HT2A, Hallucinogens, Behavior, Animal, Stress, Psychological, Anxiety, Maternal Behavior, Mothers, Postpartum Period, Pregnancy, Female, Male, Anhedonia, Psilocybin

raw_json:
{"europe_pmc_id":"41027992","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Egger K, Meling D, Polat F, Seifritz E, Avram M, Scheidegger M.
publication_date: 2025-09-28
doi: 10.1162/imag.a.907
pubmed_id: 41035622
source_url: https://doi.org/10.1162/imag.a.907
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Aging,Wellbeing,Emotional Processing,Randomized Controlled Trial
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Meditation, psychedelics, and brain connectivity: A randomized controlled resting-state fMRI study of N,N-dimethyltryptamine and harmine in a meditation retreat.

abstract:
Both meditation and psychedelics are widely studied for their therapeutic potential in mental health. Recent research suggests potential synergies between mindfulness practice and psychedelics, though empirical studies have primarily focused on psilocybin. This study investigates the distinct and combined effects of mindfulness practice and an ayahuasca-inspired formulation containing N,N-dimethyltryptamine (DMT) and harmine on brain functional connectivity (FC), with implications for advancing clinical interventions. In this double-blind, placebo-controlled pharmaco-functional magnetic resonance imaging (fMRI) study, 40 meditation practitioners participated in a 3-day meditation retreat. They were randomized to receive either placebo or buccal DMT-harmine (120 mg each) and underwent fMRI scans 2 days before and after administration. Neural changes were assessed using multiple connectivity metrics, including within- and between-network connectivity, network and global connectivity, and cortical gradient analyses. Within-group changes showed that meditators in the placebo group exhibited increased network segregation across several resting-state networks, while the DMT-harmine group showed increased FC within the visual network (VIS) and between VIS and attention networks. Between-group differences similarly showed increased FC between VIS and the salience network (SAL) in the DMT-harmine group compared with placebo post-retreat. No evidence of prolonged cortical gradient disruption, which is characteristic of acute psychedelic action, was observed. This suggests a return to typical brain organization shortly after the experience. These findings reveal distinct neural mechanisms underlying meditation and psychedelic-augmented meditation. While meditation alone reduced FC between networks, DMT-harmine increased within- and between-network connectivity. Given the potential of meditation and psychedelics for improving mental health, further exploration of their synergistic potential in clinical contexts is warranted. This study advances the understanding of how psychedelics and mindfulness practice shape brain function, offering insights into their complementary roles in emotional and psychological well-being.

raw_json:
{"europe_pmc_id":"41035622","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-09-28
doi: 10.47626/1516-4446-2025-4316
pubmed_id: 41024388
source_url: https://doi.org/10.47626/1516-4446-2025-4316
substance_tags: psilocybin
topic_tags: OCD,Genomics
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Real-world use of classic and non-classic psychedelics in Hispanic/Latino adults with Obsessive-Compulsive Disorder: International findings from the LATINO Study.

authors:
Mathai DS, Robinson JO, Wagner K, Neitzke-Spruill L, Berrones D, Anderberg JL, Frederick RM, Cruz VZ, Muñoz JS, Latin American Trans-Ancestry INitiative for OCD genomics, Brazilian Obsessive-Compulsive Spectrum Disorder Working Group, Rodriguez CI, Averill LA, Crowley JJ, Storch EA, McGuire AL.

abstract:
ObjectiveDespite growing research on the potential mental health benefits of psychedelics, there has been limited study of these drugs in populations with obsessive-compulsive disorder (OCD) and with Hispanic and Latin American (H/L) ancestry.MethodsDemographic and clinical assessments were conducted as part of the Latin American Trans-ancestry Initiative for OCD genomics (LATINO) Study in H/L participants with OCD living throughout the Americas. Self-reported data on the prevalence of naturalistic psychedelic use and associated outcomes on OCD symptoms were collected in a subsample of 2,639 adults. Descriptive statistics and regression analyses were used to assess psychedelic use, predictors of use, and predictors of OCD symptom change attributed to psychedelics.ResultsAcross 11 countries, 9% of respondents reported using psychedelics or related substances for treatment. Most respondents (72%) had received traditionally available treatments for OCD (e.g., psychiatric medication and/or psychotherapy). Psilocybin, LSD, and MDMA were the most used psychedelics. Psychedelic users compared to non-users were more likely to be male, have received non-ERP therapy for OCD, and have a comorbid psychiatric diagnosis. Outcomes of psychedelic use for OCD-related symptoms varied widely by drug and were difficult to predict but were reported as most favorable for "classic" serotonergic psychedelics.ConclusionsReal-world evidence suggests that H/L adults are exploring psychedelics as a treatment for OCD, though further work is needed to establish the conditions for safe and effective use in this population. Increased research and practical harm reduction in this area is critical as public interest in psychedelic drugs continues to surge.

raw_json:
{"europe_pmc_id":"41024388","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Ethical issues with psychedelic-assisted treatments in psychiatry: A systematic scoping review.
authors: Caporuscio C, Poppe C, Gieselmann A, Repantis D.
publication_date: 2025-09-28
doi: 10.1017/s0033291725101761
pubmed_id: 41017267
source_url: https://doi.org/10.1017/s0033291725101761
keywords: Humans, Hallucinogens, Mental Disorders, Psychiatry
substance_tags: psilocybin
topic_tags: Wellbeing,Clinical Trial,Review Article,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Based on promising preliminary results from clinical trials, it seems likely that psychedelic substances (classic serotonergic psychedelics, such as psilocybin, and entactogens, such as MDMA) will be introduced into psychiatry as psychedelic-assisted therapy. This also raises a range of ethical questions that urgently need to be addressed before widespread roll-out in society. This scoping review fills a gap in the literature by providing an overview of these ethical issues using a systematic search, presentation, and descriptive analysis of ethical issues in psychedelic-assisted treatments. It includes peer-reviewed studies pertaining to human study participants and psychiatric patients (population), which discuss ethical issues (concept) of psychedelic treatments (context) in clinical trials and other clinical applications. The systematic search included several databases: MEDLINE, PsycInfo, CINAHL, HeinOnline, and PsycArticles. The search strategy, including all identified keywords and index terms, was adapted for each included database. The search was completed in June 2025 and studies published until then in any language were included. After an iterative process of inductive and deductive coding of ethical issues, the scoping review comprises seven themes related to the ethics of psychedelic-assisted treatments: (1) safety and patient well-being, (2) therapeutic relationships, (3) informed consent, (4) equity and access, (5) research ethics, (6) special contexts, and (7) societal and cultural implications. The results can be used to inform and stimulate further discussion and in-depth research on the ethics of psychedelic-assisted treatments, possibly leading to more nuanced debate surrounding a safer and more ethical implementation of psychedelic-assisted treatments in the future.

raw_json:
{"europe_pmc_id":"41017267","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Knock E, Siefried KJ, Bedi G, Albert S, Day RO, Ezard N, Ross M, Liknaitzky P, Brett J.
publication_date: 2025-09-19
doi: 10.1111/add.70187
pubmed_id: 40974259
source_url: https://doi.org/10.1111/add.70187
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Headache / Migraine,Randomized Controlled Trial,Safety,Adverse Events
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocybin-assisted psychotherapy for methamphetamine use disorder: A pilot open-label safety and feasibility study.

abstract:
Background & aimsThere are few effective treatments for methamphetamine use disorder, despite increasing global demand. Here, we assessed the safety and feasibility of outpatient psilocybin-assisted psychotherapy for methamphetamine use disorder.DesignSingle arm, open label pilot study.SettingOutpatient public stimulant treatment program at St. Vincent's Hospital, Sydney, Australia.ParticipantsWe recruited 15 participants that were ≥25 years old, seeking treatment for methamphetamine use, using methamphetamine ≥4 days/month at screening, and without serious mental illness or contraindicated medical conditions or medications.InterventionParticipants received three preparatory psychotherapy sessions over two weeks before a single psilocybin dosing session (25 mg oral), followed by two integration psychotherapy sessions over one week. Psychotherapy included elements of motivational enhancement and acceptance and commitment therapy. Participants were followed for 90 days post psilocybin-assisted psychotherapy session.MeasurementsPrimary endpoints were safety (as measured by adverse events over the trial and vital signs during psilocybin dosing) and feasibility (as measured by enrolment and dropout rates), and secondary endpoints included measuring self-reported methamphetamine and other illicit drug use, drug craving, depression, anxiety, stress and quality of life measures.FindingsOf 56 participants pre-screened, 15 were eligible and enrolled, 14 completed the intervention and 13 completed 90-day post-dose follow-up.". No serious adverse events (AEs) occurred, and the seven treatment related AEs were self-limiting and mild to moderate in severity. AEs included hypertension during the dosing session and headache (n = 4), nausea (n = 1) and noise sensitivity (n = 1) within the week following the dose. Methamphetamine use (over the prior 28 days) was observed to be lower at screening (median 12 days, IQR7-16, n = 15) relative to day 28 (median 0 days, IQR0-2, n = 13) and 90 (median 2 days, IQR1-4, n = 14) post psilocybin. Methamphetamine craving was also observed to be lower while quality of life, depression, anxiety, and stress were observed to be higher at days 28 and 90 follow-up relative to baseline.ConclusionsPsilocybin assisted psychotherapy for methamphetamine use disorder was feasible to implement in an outpatient setting and did not appear to generate safety concerns. A larger randomised controlled trial is required to confirm efficacy and safety.

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title: Advancing drug safety in psychiatry: insights from pharmacogenomics of hypersensitivity reactions.
authors: Alhaj HA, Samara J, Alnamous A, Karima R, Saber-Ayad M.
publication_date: 2025-09-18
doi: 10.3389/fphar.2025.1651898
pubmed_id: 41050417
source_url: https://doi.org/10.3389/fphar.2025.1651898
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
Drug hypersensitivity reactions (DHRs) to psychiatric medications represent a significant clinical challenge, often resulting in treatment discontinuation, poor adherence, and compromised patient outcomes. Pharmacogenomics has emerged as a promising field for understanding and mitigating these adverse effects by identifying genetic predispositions that affect drug metabolism, immune responses, and individual susceptibility. This narrative review explores the multifaceted mechanisms underlying DHRs, with a focus on immunological pathways, particularly T cell-mediated responses, drug metabolite formation, and genetic risk factors. Among these, human leukocyte antigen (HLA) alleles and polymorphisms in cytochrome P450 (CYP450) enzymes are critical contributors to hypersensitivity development. We provide a comprehensive analysis of pharmacogenomic associations with commonly prescribed psychiatric drugs, including anticonvulsants (e.g., carbamazepine, lamotrigine), selective serotonin reuptake inhibitors (SSRIs), and novel agents such as vortioxetine, psilocybin, and esketamine. Additionally, we examine antipsychotics, including clozapine and newer agents like aripiprazole, brexpiprazole, and cariprazine, highlighting specific gene-drug interactions and known risk alleles such as HLA-B*15:02, HLA-A*31:01, and variants in CYP2D6 and CYP1A2. These findings underscore the value of pharmacogenomic testing in predicting and preventing serious DHRs, such as Stevens-Johnson Syndrome, toxic epidermal necrolysis, agranulocytosis, and hepatotoxicity. The review also addresses clinical implementation, discussing the role of pre-emptive genetic screening, emerging guidelines from international consortia such as CPIC and DPWG, and real-world challenges, including variability in test accessibility, ethical concerns, and a lack of standardized protocols across regions. Recent advances in next-generation sequencing and multiomic approaches offer new opportunities to improve predictive accuracy and personalize psychiatric treatment further. Finally, we highlight the importance of population-specific research and global collaboration to close the evidence gap, particularly in underrepresented regions like the Middle East. This review emphasizes the transformative potential of pharmacogenomics in optimizing psychiatric drug therapy, enhancing safety, and ultimately improving patient-centered care.

topic_tags:
Pharmacology,Mechanism of Action,Receptor Pharmacology,Review Article,Safety,Toxicity,Drug Interactions,Genomics,Immune Function

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authors: Calin A, Burlec AF, Mircea C, Macovei I, Hancianu M, Corciova A.
publication_date: 2025-09-18
doi: 10.3390/jcm14186613
pubmed_id: 41010814
source_url: https://doi.org/10.3390/jcm14186613
substance_tags: psilocybin
topic_tags: Mechanism of Action,Clinical Trial,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Evolution and Comparative Analysis of Clinical Trials on Psilocybin in the Treatment of Psychopathologies: Trends in the EU and the US.

abstract:
Background/Objectives: This study examines the development of clinical trials investigating psilocybin for the treatment of psychopathologies, with a comparative focus on the United States (US) and the European Union (EU). The objective is to identify regional differences in trial progression, research infrastructure, and regulatory frameworks. Methods: A mixed-methods approach was applied, combining case studies, qualitative and quantitative research. Key variables included trial phase, geographical distribution, demographic factors, funding, governmental support, and public health policies. Results: The US demonstrated a substantially higher number of psilocybin trials across both early and advanced phases. This reflects a strong research infrastructure, growing financial investment, and increasing interest in psychedelic-assisted therapies. In contrast, the EU showed fewer trials and slower advancement, reflecting a more cautious stance that emphasizes patient safety and therapeutic efficacy. These divergences are shaped by differences in regulation, funding mechanisms, and sociocultural attitudes toward psychedelics in psychiatry. Conclusion: This comparative analysis highlights the uneven pace of psilocybin research across different regions. It also emphasizes the importance of international collaboration, harmonization of public health policies, and the development of standardized procedures prioritizing safety and effectiveness. Integrating psilocybin-assisted interventions into psychiatric practice has the potential to expand treatment options and strengthen mental health care, but coordinated global efforts are essential to ensure both scientific rigor and patient protection.

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