Gukasyan, N., Davis, A. K., Barrett, F. S., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., & Griffiths, R. R.. (2022). Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Journal of Psychopharmacology
Plain numerical DOI: 10.1177/02698811211073759
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“Background: preliminary data suggest that psilocybin-assisted treatment produces substantial and rapid antidepressant effects in patients with major depressive disorder (mdd), but little is known about long-term outcomes. aims: this study sought to examine the efficacy and safety of psilocybin through 12 months in participants with moderate to severe mdd who received psilocybin. methods: this randomized, waiting-list controlled study enrolled 27 patients aged 21–75 with moderate to severe unipolar depression (grid-hamilton depression rating scale (grid-hamd) ⩾ 17). participants were randomized to an immediate or delayed (8 weeks) treatment condition in which they received two doses of psilocybin with supportive psychotherapy. twenty-four participants completed both psilocybin sessions and were followed through 12 months following their second dose. results: all 24 participants attended all follow-up visits through the 12-month timepoint. large decreases from baseline in grid-hamd scores were observed at 1-, 3-, 6-, and 12-month follow-up (cohen d = 2.3, 2.0, 2.6, and 2.4, respectively). treatment response (⩾50% reduction in grid-hamd score from baseline) and remission were 75% and 58%, respectively, at 12 months. there were no serious adverse events judged to be related to psilocybin in the long-term follow-up period, and no participants reported psilocybin use outside of the context of the study. participant ratings of personal meaning, spiritual experience, and mystical experience after sessions predicted increased well-being at 12 months, but did not predict improvement in depression. conclusions: these findings demonstrate that the substantial antidepressant effects of psilocybin-assisted therapy may be durable at least through 12 months following acute intervention in some patients.”
McCulloch, D. E. W., Madsen, M. K., Stenbæk, D. S., Kristiansen, S., Ozenne, B., Jensen, P. S., … Fisher, P. M. D.. (2022). Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals. Journal of Psychopharmacology
Plain numerical DOI: 10.1177/02698811211026454
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“Background: psilocybin is a psychedelic drug that has shown lasting positive effects on clinical symptoms and self-reported well-being following a single dose. there has been little research into the long-term effects of psilocybin on brain connectivity in humans. aim: evaluate changes in resting-state functional connectivity (rsfc) at 1 week and 3 months after one psilocybin dose in 10 healthy psychedelic-naïve volunteers and explore associations between change in rsfc and related measures. methods: participants received 0.2–0.3 mg/kg psilocybin in a controlled setting. participants completed resting-state functional magnetic resonance imaging (fmri) scans at baseline, 1-week and 3-month post-administration and [11c]cimbi-36 pet scans at baseline and 1 week. we examined changes in within-network, between-network and region-to-region rsfc. we explored associations between changes in rsfc and psilocybin-induced phenomenology as well as changes in psychological measures and neocortex serotonin 2a receptor binding. results: psilocybin was well tolerated and produced positive changes in well-being. at 1 week only, executive control network (ecn) rsfc was significantly decreased (cohen’s d = −1.73, pfwe = 0.010). we observed no other significant changes in rsfc at 1 week or 3 months, nor changes in region-to-region rsfc. exploratory analyses indicated that decreased ecn rsfc at 1 week predicted increased mindfulness at 3 months (r = −0.65). conclusions: these findings in a small cohort indicate that psilocybin affects ecn function within the psychedelic ‘afterglow’ period. our findings implicate ecn modulation as mediating psilocybin-induced, long-lasting increases in mindfulness. although our findings implicate a neural pathway mediating lasting psilocybin effects, it is notable that changes in neuroimaging measures at 3 months, when personality changes are observed, remain to be identified.”
Rucker, J. J., Marwood, L., Ajantaival, R. L. J., Bird, C., Eriksson, H., Harrison, J., … Young, A. H.. (2022). The effects of psilocybin on cognitive and emotional functions in healthy participants: Results from a phase 1, randomised, placebo-controlled trial involving simultaneous psilocybin administration and preparation. Journal of Psychopharmacology
Plain numerical DOI: 10.1177/02698811211064720
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“Background: psilocybin, a psychoactive serotonin receptor partial agonist, has been reported to acutely reduce clinical symptoms of depressive disorders. psilocybin’s effects on cognitive function have not been widely or systematically studied. aim: the aim of this study was to explore the safety of simultaneous administration of psilocybin to healthy participants in the largest randomised controlled trial of psilocybin to date. primary and secondary endpoints assessed the short- and longer-term change in cognitive functioning, as assessed by a cambridge neuropsychological test automated battery (cantab) panel, and emotional processing scales. safety was assessed via endpoints which included cognitive function, assessed by cantab global composite score, and treatment-emergent adverse event (teae) monitoring. methods: in this phase 1, randomised, double-blind, placebo-controlled study, healthy participants (n = 89; mean age 36.1 years; 41 females, 48 males) were randomised to receive a single oral dose of 10 or 25 mg psilocybin, or placebo, administered simultaneously to up to six participants, with one-to-one psychological support – each participant having an assigned, dedicated therapist available throughout the session. results: in total, 511 teaes were reported, with a median duration of 1.0 day; 67% of all teaes started and resolved on the day of administration. there were no serious teaes, and none led to study withdrawal. there were no clinically relevant between-group differences in cantab global composite score, cantab cognitive domain scores, or emotional processing scale scores. conclusions: these results indicate that 10 mg and 25 mg doses of psilocybin were generally well tolerated when given to up to six participants simultaneously and did not have any detrimental short- or long-term effects on cognitive functioning or emotional processing. clinical trial registration: eudract (https://www.clinicaltrialsregister.eu/) number: 2018-000978-30.”
Becker, A. M., Holze, F., Grandinetti, T., Klaiber, A., Toedtli, V. E., Kolaczynska, K. E., … Liechti, M. E.. (2022). Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects. Clinical Pharmacology and Therapeutics
Plain numerical DOI: 10.1002/cpt.2487
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“The psychedelic psilocybin is being investigated for the treatment of depression and anxiety. unclear is whether antidepressant treatments interact with psilocybin. the present study used a double-blind, placebo-controlled, crossover design with two experimental test sessions to investigate the response to psilocybin (25 mg) in healthy subjects after pretreatment with escitalopram or placebo. the treatment order was random and counterbalanced. pretreatment consisted of 10 mg escitalopram daily for 7 days, followed by 20 mg daily for 7 days, including the day of psilocybin administration, or 14 days of placebo pretreatment before psilocybin administration. psilocybin treatments were separated by at least 16 days. the outcome measures included self-rating scales that evaluated subjective effects, autonomic effects, adverse effects, plasma brain-derived neurotrophic factor (bdnf) levels, electrocardiogram qtc time, whole-blood htr2a and scl6a4 gene expression, and pharmacokinetics. escitalopram pretreatment had no relevant effect on positive mood effects of psilocybin but significantly reduced bad drug effects, anxiety, adverse cardiovascular effects, and other adverse effects of psilocybin compared with placebo pretreatment. escitalopram did not alter the pharmacokinetics of psilocin. the half-life of psychoactive free (unconjugated) psilocin was 1.8 hours (range 1.1–2.2 hours), consistent with the short duration of action of psilocybin. escitalopram did not alter htr2a or scl6a4 gene expression before psilocybin administration, qtc intervals, or circulating bdnf levels before or after psilocybin administration. further studies are needed with a longer antidepressant pretreatment time and patients with psychiatric disorders to further define interactions between antidepressants and psilocybin.”
Li, N. X., Hu, Y. R., Chen, W. N., & Zhang, B.. (2022). Dose effect of psilocybin on primary and secondary depression: a preliminary systematic review and meta-analysis. Journal of Affective Disorders
Plain numerical DOI: 10.1016/j.jad.2021.09.041
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“Background: previous studies have shown that psilocybin has antidepressant effects. in the current study, we aim to explore the dose effects of psilocybin on primary (major depression patients) and secondary depression (depressed cancer patients). methods: published studies concerning psilocybin for depression were retrieved. in accordance with prisma guidelines, 6 databases (pubmed, embase, web of science, cochrane library, clinicaltrials.gov 2.3 and wanfang database) were searched for research studies published or still in progress from inception to 30 november, 2020, with language restricted to english and chinese. hedges’ g of beck depression inventory (bdi) score changes was calculated as the primary outcome. results: 7 articles were finally included, with a total of 136 participants. in terms of efficacy, hedges’ g was 1.289 (95%ci=[1.020, 1.558], heterogeneity i2=50.995%, p<0.001). as psilocybin dose increases within a certain range, the antidepressive effect declines and then increases, with 30-35 mg/70 kg achieving the optimal therapeutic effect. subgroup analysis suggested that the antidepressive effect of psilocybin was extremely significant at a relatively high dose (30-35mg/70kg: hedges’ g=3.059, 95%ci=[2.269, 3.849], p<0.001), long-term (>1month: hedges’ g=1.123, 95%ci=[0.861, 1.385], p<0.001) and when used in primary depression patients (hedges’ g=2.190, 95%ci=[1.423, 2.957], p<0.001). limitations: only a small number of studies can be identified of variable quality, thus our conclusions remain preliminary. conclusions: our preliminary results have shown that psilocybin exerts a rapid effect in reducing depressive symptom on primary and secondary depression. the optimal dose of psilocybin may be 30-35mg/70kg or higher; future clinical trials are warranted for further evaluation on its effect.”
Marschall, J., Fejer, G., Lempe, P., Prochazkova, L., Kuchar, M., Hajkova, K., & van Elk, M.. (2022). Psilocybin microdosing does not affect emotion-related symptoms and processing: A preregistered field and lab-based study. Journal of Psychopharmacology
Plain numerical DOI: 10.1177/02698811211050556
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“Background: microdoses of psychedelics (i.e. a sub-hallucinogenic dose taken every third day) can reduce symptoms of depression, anxiety and stress according to anecdotal reports and observational studies. research with medium to high doses of psilocybin points towards potential underlying mechanisms, including the modulation of emotion and interoceptive processing. aims: in this preregistered study, we investigated whether psilocybin microdoses alter self-reported interoceptive awareness and whether repeated microdosing over 3 weeks modulates emotion processing and reduces symptoms of anxiety and depression. methods: we used a double-blind, placebo-controlled, within-subject crossover design. participants completed the multidimensional assessment of interoceptive awareness questionnaire 1½ h after self-administering their second dose (or placebo), and the emotional go/no-go task and the shortened depression anxiety stress scale 1½ h after self-administering their seventh dose. results: our confirmatory analyses revealed that psilocybin microdosing did not affect emotion processing or symptoms of anxiety and depression compared with placebo. our exploratory analyses revealed that psilocybin microdosing did not affect self-reported interoceptive awareness, that symptoms of depression and stress were significantly reduced in the first block compared with baseline, that participants broke blind in the second block and that there was no effect of expectations. further research in a substance-naïve population with clinical range anxiety and depressive symptoms is needed to substantiate the potential beneficial effects of microdosing.”
Yu, C. L., Liang, C. S., Yang, F. C., Tu, Y. K., Hsu, C. W., Carvalho, A. F., … Su, K. P.. (2022). Trajectory of Antidepressant Effects after Single-or Two-Dose Administration of Psilocybin: A Systematic Review and Multivariate Meta-Analysis. Journal of Clinical Medicine
Plain numerical DOI: 10.3390/jcm11040938
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“We examined the cardiovascular safety, acceptability, and trajectory of the antidepressant effects of psilocybin after single-or two-dose administration. four major electronic databases were systematically searched. data were pooled using a multivariate random-effects meta-analysis. primary outcomes were changes in depressive symptoms. secondary outcomes were cardiovascular safety and acceptability. ten studies were included. the estimated effect sizes (standardized mean difference (smd) with 95% confidence intervals) for psilocybin were −0.75 (−1.15 to −0.35) on day 1, −1.74 (−2.15 to −1.32) at 1 week, −1.35 (−1.77 to −0.93) at 1 month, −0.91 (−1.31 to −0.51) at 3 months, and −1.12 (−1.56 to −0.68) at 6 months. higher doses and two sessions of psilocybin treatment were significantly associated with superior antidepressant effects. the all-cause discontinuation and heart rate after psilocybin administration were comparable to placebo; meanwhile, psilocybin increased systolic and diastolic blood pressure by 19.00 mmhg and 8.66 mmhg, respectively. there were no significant differences between smd derived from placebo-controlled trials compared to those from pre–post changes and smd in randomized controlled trials (rcts) compared to those in non-rcts. the present study demonstrates that single-or two-dose psilocybin administration has rapid and sustained antidepressant effects for up to 6 months, with favorable cardiovascular safety and acceptability.”
Holze, F., Ley, L., Müller, F., Becker, A. M., Straumann, I., Vizeli, P., … Liechti, M. E.. (2022). Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects. Neuropsychopharmacology
Plain numerical DOI: 10.1038/s41386-022-01297-2
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“Growing interest has been seen in using lysergic acid diethylamide (lsd) and psilocybin in psychiatric research and therapy. however, no modern studies have evaluated differences in subjective and autonomic effects of lsd and psilocybin or their similarities and dose equivalence. we used a double-blind, randomized, placebo-controlled, crossover design in 28 healthy subjects (14 women, 14 men) who underwent five 25 h sessions and received placebo, lsd (100 and 200 µg), and psilocybin (15 and 30 mg). test days were separated by at least 10 days. outcome measures included self-rating scales for subjective effects, autonomic effects, adverse effects, effect durations, plasma levels of brain-derived neurotrophic factor (bdnf), prolactin, cortisol, and oxytocin, and pharmacokinetics. the doses of 100 and 200 µg lsd and 30 mg psilocybin produced comparable subjective effects. the 15 mg psilocybin dose produced clearly weaker subjective effects compared with both doses of lsd and 30 mg psilocybin. the 200 µg dose of lsd induced higher ratings of ego-dissolution, impairments in control and cognition, and anxiety than the 100 µg dose. the 200 µg dose of lsd increased only ratings of ineffability significantly more than 30 mg psilocybin. lsd at both doses had clearly longer effect durations than psilocybin. psilocybin increased blood pressure more than lsd, whereas lsd increased heart rate more than psilocybin. however, both lsd and psilocybin showed comparable cardiostimulant properties, assessed by the rate-pressure product. both lsd and psilocybin had dose-proportional pharmacokinetics and first-order elimination. both doses of lsd and the high dose of psilocybin produced qualitatively and quantitatively very similar subjective effects, indicating that alterations of mind that are induced by lsd and psilocybin do not differ beyond the effect duration. any differences between lsd and psilocybin are dose-dependent rather than substance-dependent. however, lsd and psilocybin differentially increased heart rate and blood pressure. these results may assist with dose finding for future psychedelic research. trial registration: clinicaltrials.gov identifier: nct03604744”
Van Court, R. C., Wiseman, M. S., Meyer, K. W., Ballhorn, D. J., Amses, K. R., Slot, J. C., … Uehling, J. K.. (2022). Diversity, biology, and history of psilocybin-containing fungi: Suggestions for research and technological development. Fungal Biology
Plain numerical DOI: 10.1016/j.funbio.2022.01.003
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“Therapeutic use of psilocybin has become a focus of recent international research, with preliminary data showing promise to address a range of treatment-resistant mental health conditions. however, use of psilocybin as a healing entheogen has a long history through traditional consumption of mushrooms from the genus psilocybe. the forthcoming adoption of new psilocybin-assisted therapeutic practices necessitates identification of preferred sources of psilocybin; consequently, comprehensive understanding of psilocybin-containing fungi is fundamental to consumer safety. here we examine psilocybin producing fungi, discuss their biology, diversity, and ethnomycological uses. we also review recent work focused on elucidation of psilocybin biosynthetic production pathways, especially those from the genus psilocybe, and their evolutionary history. current research on psilocybin therapies is discussed, and recommendations for necessary future mycological research are outlined.”
Pearson, C., Siegel, J., & Gold, J. A.. (2022). Psilocybin-assisted psychotherapy for depression: Emerging research on a psychedelic compound with a rich history. Journal of the Neurological Sciences
Plain numerical DOI: 10.1016/j.jns.2021.120096
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“There is a serious need for novel therapies that treat individuals with depression, including major depressive disorder (mdd) and treatment-resistant depression (trd). an emerging body of research has demonstrated that psychedelic drugs such as psilocybin, combined with supportive psychotherapy, exert rapid and sustained antidepressant effects. the use of psychedelics is not new: they have a rich history with evidence of their use in ritual and medical settings. however, due to political, social, and cultural pressures, their use was limited until modern clinical trials began to emerge in the 2010s. this review provides a comprehensive look at the potential use of psilocybin in the treatment of depression and trd. it includes an overview of the history, pharmacology, and proposed mechanism of psilocybin, and describes several published studies in the last decade which have provided evidence of the efficacy and safety of psilocybin-assisted psychotherapy for individuals with depression. it also includes a discussion of the limitations and barriers of current research on psychedelics. the results of these studies are contextualized within the current treatment landscape through an overview of the pathophysiology of depression and the treatments currently in use, as well as the clinical needs these novel therapies have the promise to fulfill.”
Müller, F., Kraus, E., Holze, F., Becker, A., Ley, L., Schmid, Y., … Borgwardt, S.. (2022). Flashback phenomena after administration of LSD and psilocybin in controlled studies with healthy participants. Psychopharmacology
Plain numerical DOI: 10.1007/s00213-022-06066-z
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“Background: lsd and psilocybin are increasingly used in phase i trials and evaluated as therapeutic agents for mental disorders. the phenomenon of reoccurring drug-like experiences after the acute substance effects have worn off was described for both substances and especially attributed to lsd. according to the dsm-v, the persisting and distressing manifestation of these experiences is called hallucinogen-persisting perception disorder (hppd). data on both conditions is very limited. objective: this study aims to provide descriptive data on reoccurring drug-like experiences after the administration of lsd and psilocybin in controlled studies with healthy participants. methods and materials: data from 142 healthy subjects enrolled in six double-blinded, placebo-controlled, randomized cross-over studies were analyzed. in total, 60 subjects received lsd; 27 subjects received lsd, mdma, and d-amphetamine; 31 subjects received lsd and psilocybin; and 25 subjects received psilocybin and escitalopram. at the end-of-study visit (mean 39.8 days after last study session, sd 37.2), subjects were asked for any reoccurring drug effects since the initial substance effects had worn off. those reporting reoccurring perception changes more than 24 h after administration were contacted for follow-up (mean follow-up duration: 31.2 months, sd 28.6). results: thirteen out of 142 subjects reported reoccurring drug-like experiences (lsd: seven, psilocybin: two, both: four). the reported phenomena were predominantly mild and perceived as neutral to pleasant. flashbacks were mostly of visual nature, lasted for seconds to minutes, and occurred within a week after the last drug administration. two subjects reported distressing experiences that subsided spontaneously. one subject reported brief and pleasant visual perception changes which reoccurred for 7 months. none of the subjects reported impairment in their daily lives. none of the cases met dsm-v criteria for hppd. conclusion: reoccurring drug-like experiences after the administration of lsd and psilocybin are a common phenomenon occurring in up to 9.2% of healthy subjects (7.8% for lsd, 8.3% for psilocybin and 14.3% if both substances are administered). additionally, our work suggests that flashback phenomena are not a clinically relevant problem in controlled studies with healthy participants.”
Mayer, C. E., LeBaron, V. T., & Acquaviva, K. D.. (2022). Exploring the Use of Psilocybin Therapy for Existential Distress: A Qualitative Study of Palliative Care Provider Perceptions. Journal of Psychoactive Drugs
Plain numerical DOI: 10.1080/02791072.2021.1916659
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“There is a growing body of research suggesting that palliative care patients coping with existential distress may benefit from psilocybin. however, there is a large gap regarding the perceptions of palliative care providers who may provide education, counseling services, recommendations, and/or prescriptions for psilocybin if it is decriminalized, commercialized, and/or federally rescheduled and legalized. the aim of this study was to explore the experiences and perceptions of interdisciplinary palliative care providers regarding existential distress and the use of psilocybin therapy. five (n = 5) health care providers from a hospital-based palliative care team completed a semi-structured interview related to their experiences supporting patients with existential distress and their beliefs and attitudes related to psilocybin as a possible treatment modality. a qualitative descriptive approach was used to identify key themes which included: 1) multiple barriers to addressing existential distress at the cultural, institutional/organizational, relational, and individual levels, 2) the duality and power of presence, 3) suffering as an intrinsically subjective phenomenon, and 4) uncertainty about the risks and benefits of psilocybin. to inform an inclusive, safe, and holistic approach, more research is needed regarding the possible integration of psilocybin therapy within palliative care for the treatment of existential distress.”
van Amsterdam, J., & van den Brink, W.. (2022). The therapeutic potential of psilocybin: a systematic review. Expert Opinion on Drug Safety
Plain numerical DOI: 10.1080/14740338.2022.2047929
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“Introduction: psychedelic drugs were used quite extensively before their prohibition in 1968 which delayed research. however, since the 1990s, studies on the potential therapeutic benefits of psychedelics have rapidly increased. areas covered: this systematic review provides an overview of the clinical effects of psilocybin in the treatment of a variety of mental disorders. only (randomized) clinical trials were selected. a total of 11 studies (15 publications) were selected, including seven randomized controlled trials (eight publications) and four single arm open-label studies (seven publications). in total, 488 patients were included in the selected studies: 333 patients treated with psilocybin and 155 patients treated with (active) placebo. in nine studies, psychotherapeutic support was provided as an integral part of the psilocybin treatment. the findings of these studies collectively show that psilocybin has a positive benefit–risk balance in the treatment of various mental disorders with an immediate and prolonged effect following 1–3 doses of psilocybin and a few (serious) adverse events. expert opinion: psilocybin–mostly combined with psychotherapy or psychotherapeutic support–shows a promise as a treatment for various (treatment-resistant) mental disorders. larger double-blind rcts with objective (long-term) outcomes are needed to confirm these findings before standard clinical use of psilocybin can be considered.”
Ling, S., Ceban, F., Lui, L. M. W., Lee, Y., Teopiz, K. M., Rodrigues, N. B., … McIntyre, R. S.. (2022). Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression. CNS Drugs
Plain numerical DOI: 10.1007/s40263-021-00877-y
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“Therapeutic deficiencies with monoaminergic antidepressants invites the need to identify and develop novel rapid-acting antidepressants. hitherto, ketamine and esketamine are identified as safe, well-tolerated rapid-acting antidepressants in adults with treatment-resistant depression, and also mitigate measures of suicidality. psilocybin is a naturally occurring psychoactive alkaloid and non-selective agonist at many serotonin receptors, especially at serotonin 5-ht2a receptors, and is found in the psilocybe genus of mushrooms. preliminary studies with psilocybin have shown therapeutic promise across diverse populations including major depressive disorder. the pharmacodynamic mechanisms mediating the antidepressant and psychedelic effects of psilocybin are currently unknown but are thought to involve the modulation of the serotonergic system, primarily through agonism at the 5-ht2a receptors and downstream changes in gene expression. it is also established that indirect effects on dopaminergic and glutamatergic systems are contributory, as well as effects at other lower affinity targets. along with the direct effects on neurochemical systems, psilocybin alters neural circuitry and key brain regions previously implicated in depression, including the default mode network and amygdala. the aim of this review is to synthesize the current understanding of the receptor pharmacology and neuronal mechanisms underlying the psychedelic and putative antidepressant properties of psilocybin.”
Sarparast, A., Thomas, K., Malcolm, B., & Stauffer, C. S.. (2022). Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review. Psychopharmacology
Plain numerical DOI: 10.1007/s00213-022-06083-y
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“Rationale & objectives: ± 3,4-methylenedioxymethamphetamine (mdma) and psilocybin are currently moving through the us food and drug administration’s phased drug development process for psychiatric treatment indications: posttraumatic stress disorder and depression, respectively. the current standard of care for these disorders involves treatment with psychiatric medications (e.g., selective serotonin reuptake inhibitors), so it will be important to understand drug-drug interactions between mdma or psilocybin and psychiatric medications. methods: in accordance with preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines, we queried the medline database via pubmed for publications of human studies in english spanning between the first synthesis of psilocybin (1958) and december 2020. we used 163 search terms containing 22 psychiatric medication classes, 135 specific psychiatric medications, and 6 terms describing mdma or psilocybin. results: forty publications were included in our systematic review: 26 reporting outcomes from randomized controlled studies with healthy adults, 3 epidemiologic studies, and 11 case reports. publications of studies describe interactions between mdma (n = 24) or psilocybin (n = 5) and medications from several psychiatric drug classes: adrenergic agents, antipsychotics, anxiolytics, mood stabilizers, nmda antagonists, psychostimulants, and several classes of antidepressants. we focus our results on pharmacodynamic, physiological, and subjective outcomes of drug-drug interactions. conclusions: as mdma and psilocybin continue to move through the fda drug development process, this systematic review offers a compilation of existing research on psychiatric drug-drug interactions with mdma or psilocybin.”
Sherwood, A. M., Kargbo, R. B., Kaylo, K. W., Cozzi, N. V., Meisenheimer, P., & Kaduk, J. A.. (2022). Psilocybin: Crystal structure solutions enable phase analysis of prior art and recently patented examples. Acta Crystallographica Section C: Structural Chemistry
Plain numerical DOI: 10.1107/S2053229621013164
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“Psilocybin {systematic name: 3-[2-(dimethylamino)ethyl]-1h-indol-4-yl dihydrogen phosphate} is a zwitterionic tryptamine natural product found in numerous species of fungi known for their psychoactive properties. following its structural elucidation and chemical synthesis in 1959, purified synthetic psilocybin has been evaluated in clinical trials and has shown promise in the treatment of various mental health disorders. in a recent process-scale crystallization investigation, three crystalline forms of psilocybin were repeatedly observed: hydrate a, polymorph a, and polymorph b. the crystal structure for hydrate a was solved previously by single-crystal x-ray diffraction. this article presents new crystal structure solutions for the two anhydrates, polymorphs a and b, based on rietveld refinement using laboratory and synchrotron x-ray diffraction data, and density functional theory (dft) calculations. utilizing the three solved structures, an investigation was conducted via rietveld method (rm) based quantitative phase analysis (qpa) to estimate the contribution of the three different forms in powder x-ray diffraction (pxrd) patterns provided by different sources of bulk psilocybin produced between 1963 and 2021. over the last 57 years, each of these samples quantitatively reflect one or more of the hydrate and anhydrate polymorphs. in addition to quantitatively evaluating the composition of each sample, this article evaluates correlations between the crystal forms present, corresponding process methods, sample age, and storage conditions. furthermore, revision is recommended on characterizations in recently granted patents that include descriptions of crystalline psilocybin inappropriately reported as a single-phase ‘isostructural variant.’ rietveld refinement demonstrated that the claimed material was composed of approximately 81% polymorph a and 19% polymorph b, both of which have been identified in historical samples. in this article, we show conclusively that all published data can be explained in terms of three well-defined forms of psilocybin and that no additional forms are needed to explain the diffraction patterns.”
Roscoe, J., & Lozy, O.. (2022). Can psilocybin be safely administered under medical supervision? A systematic review of adverse event reporting in clinical trials. Drug Science, Policy and Law
Plain numerical DOI: 10.1177/20503245221085222
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“This systematic review investigates whether clinical trials of psilocybin support criterion number three of the drug’s schedule i designation: there is a lack of accepted safety for use of the drug or other substance under medical supervision. data were collected by using the pubmed database and conducting a search on november 24, 2021, with the search term psilocybin and applying the clinical trial filter. only primary reports on the sole administration of psilocybin by a medical professional were included for analysis, excluding trials wherein psilocybin was not administered, trials wherein psilocybin was exclusively co-administered with other drugs, articles that were not clinical trials, and articles that were repeat analyses of already included trials. 52 included publications were closely examined for reports of adverse events, drug tolerability, and drug safety. zero of these articles reported psilocybin to be unsafe, while 27 of the included trials suggested that psilocybin is safe to administer under proper medical supervision.”
Jones, G. M., & Nock, M. K.. (2022). Lifetime use of MDMA/ecstasy and psilocybin is associated with reduced odds of major depressive episodes. Journal of Psychopharmacology
Plain numerical DOI: 10.1177/02698811211066714
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“Background: depression is a major mental health issue worldwide, with high rates of chronicity and non-recovery associated with the condition. existing treatments such as antidepressant medication and psychological treatments have modest effectiveness, suggesting the need for alternative interventions. aim: the aim of this study was to examine the relationships between mdma (3,4-methylenedioxymethamphetamine)/ecstasy and psilocybin use and major depressive episodes (mdes). methods: this observational study used data from a large (n = 213,437) nationally representative sample of us adults to test the association of lifetime use of mdma/ecstasy, psilocybin and other classic psychedelics (lysergic acid diethylamide (lsd), peyote, mescaline), other illegal substances (e.g. cocaine, phencyclidine (pcp)), and legal/medicinal substances of misuse (e.g. pain relievers, tranquilizers) with lifetime, past year, and past year severe mdes. results: results revealed that lifetime mdma/ecstasy use was associated with significantly lowered odds of a lifetime mde (adjusted odds ratio (aor) = 0.84; p < 0.001), past year mde (aor = 0.84; p < 0.001), and past year severe mde (aor = 0.82; p < 0.001). psilocybin was associated with significantly lowered odds of a past year mde (aor = 0.90; p < 0.05) and past year severe mde (aor = 0.87; p < 0.05). all other substances either shared no relationship with a mde or conferred increased odds of an mde. conclusions: these results suggest that mdma/ecstasy and psilocybin use is associated with lower risk of depression. experimental studies are needed to test whether there is a causal association between use of these compounds and the alleviation of depressive symptoms.”
Popik, P., Hogendorf, A., Bugno, R., Khoo, S. Y. S., Zajdel, P., Malikowska-Racia, N., … Golebiowska, J.. (2022). Effects of ketamine optical isomers, psilocybin, psilocin and norpsilocin on time estimation and cognition in rats. Psychopharmacology
Plain numerical DOI: 10.1007/s00213-021-06020-5
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“Rationale: ketamine and psilocybin belong to the rapid-acting antidepressants but they also produce psychotomimetic effects including timing distortion. it is currently debatable whether these are essential for their therapeutic actions. as depressed patients report that the ‘time is dragging,’ we hypothesized that ketamine and psilocybin-like compounds may produce an opposite effect, i.e., time underestimation, purportedly contributing to their therapeutic properties. objectives: timing was tested following administration of (r)- and (s)-ketamine, and psilocybin, psilocin, and norpsilocin in the discrete-trial temporal discrimination task (tdt) in male rats. timing related to premature responses, and cognitive and unspecific effects of compounds were tested in the 5-choice serial reaction time task (5-csrtt) in the standard 1-s, and ‘easier’ 2-s stimulus duration conditions, as well as in the viti variant promoting impulsive responses. results: (s)-ketamine (15 but not 3.75 or 7.5 mg/kg) shifted psychometric curve to the right in tdt and reduced premature responses in 5-csrtt, suggesting expected time underestimation, but it also decreased the accuracy of temporal discrimination and increased response and reward latencies, decreased correct responses, and increased incorrect responses. while (r)-ketamine did not affect timing and produced no unspecific actions, it reduced incorrect responses in tdt and increased accuracy in 5-csrtt, suggesting pro-cognitive effects. psilocin and psilocybin produced mainly unspecific effects in both tasks, while norpsilocin showed no effects. conclusions: time underestimation produced by (s)-ketamine could be associated with its antidepressant effects; however, it was accompanied with severe behavioral disruption. we also hypothesize that behavioral disruption produced by psychedelics objectively reflects their psychotomimetic-like actions.”
Adams, A. M., Anas, N. A., Sen, A. K., Hinegardner-Hendricks, J. D., O’Dell, P. J., Gibbons, W. J., … Jones, J. A.. (2022). Development of an E. coli-based norbaeocystin production platform and evaluation of behavioral effects in rats. Metabolic Engineering Communications
Plain numerical DOI: 10.1016/j.mec.2022.e00196
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“Interest in the potential therapeutic efficacy of psilocybin and other psychedelic compounds has escalated significantly in recent years. to date, little is known regarding the biological activity of the psilocybin pathway intermediate, norbaeocystin, due to limitations around sourcing the phosphorylated tryptamine metabolite for in vivo testing. to address this limitation, we first developed a novel e. coli platform for the rapid and scalable production of gram-scale amounts of norbaeocystin. through this process we compare the genetic and fermentation optimization strategies to that of a similarly constructed and previously reported psilocybin producing strain, uncovering the need for reoptimization and balancing upon even minor genetic modifications to the production host. we then perform in vivo measurements of head twitch response to both biosynthesized psilocybin and norbaeocystin using both a cell broth and water vehicle in long-evans rats. the data show a dose response to psilocybin while norbaeocystin does not elicit any pharmacological response, suggesting that norbaeocystin and its metabolites may not have a strong affinity for the serotonin 2a receptor. the findings presented here provide a mechanism to source norbaeocystin for future studies to evaluate its disease efficacy in animal models, both individually and in combination with psilocybin, and support the safety of cell broth as a drug delivery vehicle.”
Teixeira, P. J., Johnson, M. W., Timmermann, C., Watts, R., Erritzoe, D., Douglass, H., … Carhart-Harris, R. L.. (2022). Psychedelics and health behaviour change. Journal of Psychopharmacology
Plain numerical DOI: 10.1177/02698811211008554
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“Healthful behaviours such as maintaining a balanced diet, being physically active and refraining from smoking have major impacts on the risk of developing cancer, diabetes, cardiovascular diseases and other serious conditions. the burden of the so-called ‘lifestyle diseases’—in personal suffering, premature mortality and public health costs—is considerable. consequently, interventions designed to promote healthy behaviours are increasingly being studied, e.g., using psychobiological models of behavioural regulation and change. in this article, we explore the notion that psychedelic substances such as psilocybin could be used to assist in promoting positive lifestyle change conducive to good overall health. psilocybin has a low toxicity, is non-addictive and has been shown to predict favourable changes in patients with depression, anxiety and other conditions marked by rigid behavioural patterns, including substance (mis)use. while it is still early days for modern psychedelic science, research is advancing fast and results are promising. here we describe psychedelics’ proposed mechanisms of action and research findings pertinent to health behaviour change science, hoping to generate discussion and new research hypotheses linking the two areas. therapeutic models including psychedelic experiences and common behaviour change methods (e.g., cognitive behaviour therapy, motivational interviewing) are already being tested for addiction and eating disorders. we believe this research may soon be extended to help promote improved diet, exercise, nature exposure and also mindfulness or stress reduction practices, all of which can contribute to physical and psychological health and well-being.”
Coppola, M., Bevione, F., & Mondola, R.. (2022). Psilocybin for Treating Psychiatric Disorders: A Psychonaut Legend or a Promising Therapeutic Perspective?. Journal of Xenobiotics
Plain numerical DOI: 10.3390/jox12010004
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“Psychedelics extracted from plants have been used in religious, spiritual, and mystic practices for millennia. in 1957, dr. hofmann identified and synthesized the prodrug psilocybin, a substance present in more than 200 species of psychedelic mushrooms. although there were limitations related to the scientific design of many studies, clinical observations performed during the 1950s and 1960s showed a potential therapeutic effect of psilocybin for patients affected by depressive symptoms, anxiety, and conversion disorder. psilocybin was classed as a schedule i substance in 1970, but the fascination with psychedelics has remained almost unchanged over time, promoting a new scientific interest starting in the 1990s. recent studies have provided further evidence supporting the suggestive hypothesis of the therapeutic use of psilocybin for treating various psychiatric disorders, including pathological anxiety, mood depressive disorder, and addiction.”
Plotnik, L., Gibbs, G., & Graham, T.. (2022). Psilocybin Conspectus: Status, Production Methods, and Considerations. International Journal of Medicinal Mushrooms
Plain numerical DOI: 10.1615/IntJMedMushrooms.2021041921
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“Psilocybin is a psychoactive alkaloid that is produced naturally by approximately 200 species of mush-rooms. the potential medical use of this molecule for the treatment of mental illness is gaining renewed momentum. as demand grows and clinical trials progress, appropriate methods for producing a quality pharmaceutical product are needed. this review highlights the methods currently available, such as the prominent synthetic method and its biosyn-thetic alternatives, as well as others on the near horizon. this article further seeks to discuss the rapid and evolving nature of the psilocybin industry in the 21st century.”
Hodge, A. T., Sukpraprut-Braaten, S., Narlesky, M., & Strayhan, R. C.. (2022). The Use of Psilocybin in the Treatment of Psychiatric Disorders with Attention to Relative Safety Profile: A Systematic Review. Journal of Psychoactive Drugs
Plain numerical DOI: 10.1080/02791072.2022.2044096
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“There has been a reemergence of research into the use of substances such as lsd, mdma, and psilocybin for the treatment of psychiatric disorders. this increase in consideration toward the medicinal use of these compounds has been termed the ‘psychedelic renaissance.’ this article specifically explores the background of psilocybin, a psychoactive compound that is naturally derived from certain species of fungi. pubmed was searched by one doctoral-level researcher using specific boolean operator terms. the results were filtered by title and abstract and 76 articles were screened and analyzed in full detail. oral psilocybin is showing itself to be clinically efficacious by producing statistically significant reductions in depression and anxiety symptoms over time versus control in multiple clinical trials. it has also been shown to reduce cigarettes per day and drinks per day in patients with substance use disorders. thus far, there have been no significant adverse clinical events from psilocybin and there also have been no verifiable recorded deaths reported. larger studies need to be performed before the drug can potentially become approved for use in the general population.”
Kisely, S., Connor, M., Somogyi, A. A., & Siskind, D.. (2022). A systematic literature review and meta-analysis of the effect of psilocybin and methylenedioxymethamphetamine on mental, behavioural or developmental disorders. Australian and New Zealand Journal of Psychiatry
Plain numerical DOI: 10.1177/00048674221083868
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“Objectives: there is an increasing interest in combining psilocybin or methylenedioxymethamphetamine with psychological support in treating psychiatric disorders. although there have been several recent systematic reviews, study and participant numbers have been limited, and the field is rapidly evolving with the publication of more studies. we therefore conducted a systematic review of pubmed, medline, psycinfo, the cochrane central register of controlled trials, embase, and cinahl for randomised controlled trials of methylenedioxymethamphetamine and psilocybin with either inactive or active controls. methods: outcomes were psychiatric symptoms measured by standardised, validated and internationally recognised instruments at least 2 weeks following drug administration, quality was independently assessed using the cochrane risk of bias assessment tool and grading of recommendations assessment, development and evaluation framework. results: there were eight studies on methylenedioxymethamphetamine and six on psilocybin. diagnoses included post-traumatic stress disorder, long-standing/treatment-resistant depression, obsessive-compulsive disorder, social anxiety in adults with autism, and anxiety or depression in life-threatening disease. the most information and strongest association was for the change in methylenedioxymethamphetamine scores compared to active controls in post-traumatic stress disorder (k = 4; standardised mean difference = −0.86; 95% confidence interval = [−1.23, −0.50]; p < 0.0001). there were also small benefits for social anxiety in adults with autism. psilocybin was superior to wait-list but not niacin (active control) in life-threatening disease anxiety or depression. it was equally as effective as escitalopram in long-standing depression for the primary study outcome and superior for most of the secondary outcomes in analyses uncorrected for multiple comparisons. both agents were well tolerated in supervised trials. trial quality varied with only small proportions of potential participants included in the randomised phase. overall certainty of evidence was low or very low using the grading of recommendations assessment, development and evaluation framework. conclusion: methylenedioxymethamphetamine and psilocybin may show promise in highly selected populations when administered in closely supervised settings and with intensive support.”
McCulloch, D. E.-W., Grzywacz, M. Z., Madsen, M. K., Jensen, P. S., Ozenne, B., Armand, S., … Stenbæk, D. S.. (2022). Psilocybin-Induced Mystical-Type Experiences are Related to Persisting Positive Effects: A Quantitative and Qualitative Report. Frontiers in Pharmacology
Plain numerical DOI: 10.3389/fphar.2022.841648
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“ Psychedelic drugs such as psilocybin have shown substantial promise for the treatment of several psychiatric conditions including mood and addictive disorders. they also have the remarkable property of producing persisting positive psychological changes in healthy volunteers for at least several months. in this study (nct03289949), 35 medium-high doses of psilocybin were administered to 28 healthy volunteers (12 females). by the end of the dosing day, participants reported the intensity of their acute experience using the 30-item mystical experience questionnaire (meq) and an open-form qualitative report from home. persisting psychological effects attributed to the psilocybin experience were measured using the persisting effects questionnaire (peq) 3-months after administration. using a linear latent-variable model we show that the meq total score is positively associated with the later emergence of positive peq effects ( p = 3 × 10 −5 ). moreover, the meq subscales ‘positive mood’ ( p corr = 4.1 × 10 −4 ) and ‘mysticality’ ( p corr = 2.0 × 10 −4 ) are associated with positive peq whereas the subscales ‘transcendence of time and space’ ( p corr = 0.38) and ‘ineffability’ ( p corr = 0.45) are not. using natural language pre-processing, we provide the first qualitative descriptions of the ‘complete mystical experience’ induced by orally administered psilocybin in healthy volunteers, revealing themes such as a sense of connection with the universe, familial love, and the experience of profound beauty. combining qualitative and quantitative methods, this paper expands understanding of the acute psilocybin induced experience in healthy volunteers and suggests an importance of the type of experience in predicting lasting positive effects. ”
Khan, F. I., Hassan, F., & Lai, D.. (2022). In Silico Studies on Psilocybin Drug Derivatives Against SARS-CoV-2 and Cytokine Storm of Human Interleukin-6 Receptor. Frontiers in Immunology
Plain numerical DOI: 10.3389/fimmu.2021.794780
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“Various metabolites identified with therapeutic mushrooms have been found from different sources and are known to have antibacterial, antiviral, and anticancer properties. over thousands soil growth-based mushroom metabolites have been discovered, and utilized worldwide to combat malignancy. in this study, psilocybin-mushroom that contains the psychedelic compounds such as psilacetin, psilocin, and psilocybine were screened and found to be inhibitors of sars-cov-2 mprotease. it has been found that psilacetin, psilocin, and psilocybine bind to mprotease with −6.0, −5.4, and −5.8 kcal/mol, respectively. additionally, the psilacetin was found to inhibit human interleukin-6 receptors to reduce cytokine storm. the binding of psilacetin to mprotease of sars-cov-2 and human interleukin-6 receptors changes the structural dynamics and gibbs free energy patterns of proteins. these results suggested that psilocybin-mushroom could be utilized as viable potential chemotherapeutic agents for sars-cov-2.”
Petranker, R., Anderson, T., Maier, L. J., Barratt, M. J., Ferris, J. A., & Winstock, A. R.. (2022). Microdosing psychedelics: Subjective benefits and challenges, substance testing behavior, and the relevance of intention. Journal of Psychopharmacology
Plain numerical DOI: 10.1177/0269881120953994
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“Background: microdosing psychedelics is the practice of taking small, sub-hallucinogenic doses of lysergic acid diethylamide or psilocybin-containing mushrooms. despite its surging popularity, little is known about the specific intentions to start microdosing and the effects of this practice. aims: first, we aimed to replicate previous findings regarding the subjective benefits and challenges reported for microdosing. second, we assessed whether people who microdose test their substances before consumption. third, we examined whether having an approach-intention to microdosing was predictive of more reported benefits. methods: the global drug survey runs the world’s largest online drug survey. participants who reported last year use of lysergic acid diethylamide or psilocybin in the global drug survey 2019 were offered the opportunity to answer a sub-section on microdosing. results: data from 6753 people who reported microdosing at least once in the last 12 months were used for analyses. our results suggest a partial replication of previously reported benefits and challenges among the present sample often reporting enhanced mood, creativity, focus and sociability. counter to our prediction, the most common challenge participants associated with microdosing was ‘none’. as predicted, most participants reported not testing their substances. counter to our hypothesis, approach-intention – microdosing to approach a desired goal – predicted less rather than more benefits. we discuss alternate frameworks that may better capture the reasons people microdose. conclusion: our results suggest the perceived benefits associated with microdosing greatly outweigh the challenges. microdosing may have utility for a variety of uses while having minimal side effects. double-blind, placebo-controlled experiments are required to substantiate these reports.”
Altman, B. R., Earleywine, M., & De Leo, J.. (2022). Exploring the Credibility of Psilocybin-assisted Therapy and Cognitive-behavioral Therapy for Depression. Journal of Psychoactive Drugs
Plain numerical DOI: 10.1080/02791072.2021.2020382
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“Depression treatments succeed with many but leave others unimproved, and they can generate concerns about side effects, time, and cost. psilocybin has generated media attention and empirical support for antidepressant effects, but lay impressions of its effectiveness are unclear. although perceptions of treatment credibility contribute to outcome, beliefs about the credibility of psilocybin-assisted therapy (pat) among potential patients remain uninvestigated, especially relative to cognitive-behavioral therapy (cbt), a common, empirically-validated approach. the present study examined credibility ratings for cbt and pat among individuals reporting depressive symptoms. participants (n = 803) from amazon’s mturk platform reported demographics, depressive symptoms, and psychotherapy experience, then read data-based vignettes describing each therapy and rated their credibility. individuals rated cbt as more credible than pat. those with therapy experience rated cbt as more credible than those without. men and lifetime hallucinogen users rated pat more credible than women and non-users, but few other predictors accounted for much variance in credibility. results suggest that potential clients appear cautious about pat. as continued work examines the effectiveness of psychedelic-assisted interventions, researchers and clinicians must consider patients’ beliefs about treatments as potential predictors of outcomes. additionally, the paradigm used here might have potential for examining credibility of many interventions.”
Jones, G. M., & Nock, M. K.. (2022). Psilocybin use is associated with lowered odds of crime arrests in US adults: A replication and extension. Journal of Psychopharmacology
Plain numerical DOI: 10.1177/02698811211058933
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“Background: the united states boasts the largest prison population in the world, conferring significant direct and indirect costs (e.g. lost wages for the incarcerated, increased morbidity/mortality, etc.) to society. recidivism rates are high for the imprisoned and most interventions to reduce criminality are minimally effective. thus, in addition to the need for criminal justice reform, there is a need to better understand factors linked to lowered criminal behavior. aim: the aim of this study was to assess the relationships between the use of classic psychedelic substances (psilocybin, lsd, peyote, and mescaline) and past year arrests for various crimes (i.e. property, violence, alcohol and substance use, miscellaneous crimes). methods: this study used nationally representative data from the national survey on drug use and health (nsduh) (2015–2019) (n = 211,549) to test the aforementioned associations. results: lifetime psilocybin use was associated with lowered odds of seven of 11 past year arrest variables (adjusted odds ratio (aor) range = 0.30–0.73). peyote was associated with reduced odds of motor vehicle theft (aor = 0.30) and driving under the influence (aor = 0.52), and mescaline was associated with reduced odds of drug possession/sale (aor = 0.51). virtually all other substances either shared no relationship to our outcomes or conferred higher odds of arrest. conclusion: this study suggests that use of classic psychedelic substances is associated with lowered odds of crime arrests. future research should explore whether causal factors and/or third variable factors (e.g. personality, political orientation) underlie the relationship between classic psychedelic use and reduced criminal behavior.”
Duerler, P., Brem, S., Fraga-González, G., Neef, T., Allen, M., Zeidman, P., … Preller, K. H.. (2022). Psilocybin Induces Aberrant Prediction Error Processing of Tactile Mismatch Responses – A Simultaneous EEG-FMRI Study. Cerebral Cortex
Plain numerical DOI: 10.1093/cercor/bhab202
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“As source of sensory information, the body provides a sense of agency and self/non-self-discrimination. the integration of bodily states and sensory inputs with prior beliefs has been linked to the generation of bodily self-consciousness. the ability to detect surprising tactile stimuli is essential for the survival of an organism and for the formation of mental body representations. despite the relevance for a variety of psychiatric disorders characterized by altered body and self-perception, the neurobiology of these processes is poorly understood. we therefore investigated the effect of psilocybin (psi), known to induce alterations in self-experience, on tactile mismatch responses by combining pharmacological manipulations with simultaneous electroencephalography-functional magnetic resonance imaging (eeg-fmri) recording. psi reduced activity in response to tactile surprising stimuli in frontal regions, the visual cortex, and the cerebellum. furthermore, psi reduced tactile mismatch negativity eeg responses at frontal electrodes, associated with alterations of body- and self-experience. this study provides first evidence that psi alters the integration of tactile sensory inputs through aberrant prediction error processing and highlights the importance of the 5-ht2a system in tactile deviancy processing as well as in the integration of bodily and self-related stimuli. these findings may have important implications for the treatment of psychiatric disorders characterized by aberrant bodily self-awareness.”
Barrett, F. S., Zhou, Y., Carbonaro, T. M., Roberts, J. M., Smith, G. S., Griffiths, R. R., & Wong, D. F.. (2022). Human Cortical Serotonin 2A Receptor Occupancy by Psilocybin Measured Using [11C]MDL 100,907 Dynamic PET and a Resting-State fMRI-Based Brain Parcellation. Frontiers in Neuroergonomics
Plain numerical DOI: 10.3389/fnrgo.2021.784576
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“ Psilocybin (a serotonin 2a, or 5-ht 2a , receptor agonist) has shown preliminary efficacy as a treatment for mood and substance use disorders. the current report utilized positron emission tomography (pet) with the selective 5-ht 2a receptor inverse agonist radioligand [ 11 c]mdl 100,907 (a.k.a. m100,907) and cortical regions of interest (rois) derived from resting-state functional connectivity-based brain parcellations in 4 healthy volunteers (2 females) to determine regional occupancy/target engagement of 5-ht 2a receptors after oral administration of a psychoactive dose of psilocybin (10 mg/70 kg). average 5-ht 2a receptor occupancy across all rois was 39.5% (± 10.9% sd). three of the rois with greatest occupancy (between 63.12 and 74.72% occupancy) were within the default mode network (subgenual anterior cingulate and bilateral angular gyri). however, marked individual variability in regional occupancy was observed across individuals. these data support further investigation of the relationship between individual differences in the acute and enduring effects of psilocybin and the degree of regional 5-ht 2a receptor occupancy. ”
Hase, A., Erdmann, M., Limbach, V., & Hasler, G.. (2022). Analysis of recreational psychedelic substance use experiences classified by substance. Psychopharmacology
Plain numerical DOI: 10.1007/s00213-022-06062-3
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“Rationale and objectives: differences among psychedelic substances regarding their subjective experiences are clinically and scientifically interesting. quantitative linguistic analysis is a powerful tool to examine such differences. this study compared five psychedelic substance report groups and a non-psychedelic report group on quantitative linguistic markers of psychological states and processes derived from recreational use-based online experience reports. methods: using 2947 publicly available online reports, we compared ayahuasca and n,n-dimethyltryptamine (dmt, analyzed together), ketamine, lysergic acid diethylamide (lsd), 3,4-methylenedioxymethamphetamine (mdma), psilocybin (mushroom), and antidepressant drug use experiences. we examined word frequencies related to various psychological states and processes and semantic proximity to psychedelic and mystical experience scales. results: linguistic markers of psychological function indicated distinct effect profiles. for example, mdma experience reports featured an emotionally intensifying profile accompanied by many cognitive process words and dynamic-personal language. in contrast, ayahuasca and dmt experience reports involved relatively little emotional language, few cognitive process words, increased analytical thinking-associated language, and the most semantic similarity with psychedelic and mystical experience descriptions. lsd, psilocybin mushroom, and ketamine reports showed only small differences on the emotion-, analytical thinking-, psychedelic, and mystical experience-related language outcomes. antidepressant reports featured more negative emotional and cognitive process-related words, fewer positive emotional and analytical thinking-related words, and were generally not similar to mystical and psychedelic language. conclusion: this article addresses an existing research gap regarding the comparison of different psychedelic drugs on linguistic profiles of psychological states, processes, and experiences. the large sample of experience reports involving multiple psychedelic drugs provides valuable information that would otherwise be difficult to obtain. the results could inform experimental research into psychedelic drug effects in healthy populations and clinical trials for psychedelic treatments of psychiatric problems.”
Jones, G. M., & Nock, M. K.. (2022). MDMA/ecstasy use and psilocybin use are associated with lowered odds of psychological distress and suicidal thoughts in a sample of US adults. Journal of Psychopharmacology
Plain numerical DOI: 10.1177/02698811211058923
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“Background: suicide is one of the leading causes of death worldwide and rates within the united states have risen over the past two decades. hence, there is a critical need for novel tools to treat suicidal ideation and related mental health conditions. 3,4-methylenedioxymethamphetamine (mdma)/ecstasy and classic psychedelics may be two such tools. aims: the aim of this study was to assess non-causal associations between mdma/ecstasy and classic psychedelic use and psychological distress and suicide risk. methods: in this study, we examined the aforementioned associations among 484,732 adult participants in the national survey on drug use and health (2008–2019). results: lifetime mdma/ecstasy use was associated with reduced odds of past year suicidal thinking (10% reduced odds; odds ratio (or) = 0.90; 95% confidence interval, ci = (0.84–0.97); p < 0.01) and past year suicidal planning (or = 0.88; 95% ci = (0.78–0.99); p < 0.05). furthermore, lifetime psilocybin use was associated with reduced odds of past month psychological distress (or = 0.78; 95% ci = (0.73–0.84); p < 0.001) and past year suicidal thinking (or = 0.90; 95% ci = (0.83–0.96); p < 0.01). finally, lysergic acid diethylamide (lsd) was associated with increased odds of past year suicidal thinking (or = 1.07; 95% ci = (1.00–1.15); p < 0.05). conclusion: mdma/ecstasy and psilocybin use are associated with reduced odds of suicidal thinking and related outcomes—though experimental studies are needed to determine whether these associations are causal. these findings call for more research into the efficacy of mdma/ecstasy and classic psychedelics for treating psychological distress and suicidal thoughts and behaviors, and for updated drug legislation that allows for further investigation into these substances.”
Leger, R. F., & Unterwald, E. M.. (2022). Assessing the effects of methodological differences on outcomes in the use of psychedelics in the treatment of anxiety and depressive disorders: A systematic review and meta-analysis. Journal of Psychopharmacology
Plain numerical DOI: 10.1177/02698811211044688
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“Background: classical psychedelics are a group of drugs which act as agonists on the serotonin-2a (5-ht2a) receptor. evidence suggests they may have a uniquely rapid and enduring positive effect on mood. however, marked heterogeneity between methodological designs in this emerging field remains a significant concern. aims: to determine how differences in the type of psychedelic agent used and the number of dosing sessions administered affect subjects’ depression and anxiety outcomes and adverse drug reactions (adr). methods: this review collected and screened 1591 records from the medline and web of science databases for clinical trials reporting objective data on mood for subjects with a known anxiety or depression. results: after screening, nine clinical trials met inclusion criteria. meta-analysis of these studies showed significant, large positive effect sizes for measures of anxiety (cohen’s d = 1.26) and depression (cohen’s d = 1.38) overall. these positive effects were also significant at acute (⩽1 week) and extended (>1 week) time points. no significant differences were observed between trials using different psychedelic agents (psilocybin, ayahuasca or lysergic acid diethylamide (lsd)), however, a significant difference was observed in favour of trials with multiple dosing sessions. no serious adr were reported. conclusion: psilocybin, ayahuasca and lsd all appear to be effective and relatively safe agents capable of producing rapid and sustained improvements in anxiety and depression. moreover, the findings of the present analysis suggest that they may show a greater efficacy when given to patients over multiple sessions as compared to the more common single session used in many of the existing trials.”
Mertens, L. J., Koslowski, M., Betzler, F., Evens, R., Gilles, M., Jungaberle, A., … Gründer, G.. (2022). Methodological challenges in psychedelic drug trials: Efficacy and safety of psilocybin in treatment-resistant major depression (EPIsoDE) – Rationale and study design. Neuroscience Applied
Plain numerical DOI: 10.1016/j.nsa.2022.100104
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“Psychedelics such as psilocybin have recently gained remarkable interest in both the specialist literature and the lay press because studies suggest that these substances may have great therapeutic potential in various psychiatric disorders, including major depression. however, clinical trials with psychedelic drugs pose particular methodological challenges to researchers, some of which differ considerably from those with other psychotropic drugs. these include the problem of successful blinding, which can hardly be guaranteed in clinical trials with psychedelic substances and – directly related – the high risk of expectation bias and nocebo effects. some of these challenges are being addressed in the given clinical trial on the efficacy and safety of psilocybin in treatment-resistant major depression. it is a phase ii randomized, double-blind, active placebo-controlled parallel group trial with 144 patients. the rationale, the study design, and the core features of the study are presented here. the trial (episode trial; eudract number: 2019-003984-24; nct04670081) is funded by the german federal ministry of education and research (bmbf 01en2006 a/b).”
Wolff, M., Mertens, L. J., Walter, M., Enge, S., & Evens, R.. (2022). The Acceptance/Avoidance-Promoting Experiences Questionnaire (APEQ): A theory-based approach to psychedelic drugs’ effects on psychological flexibility. Journal of Psychopharmacology
Plain numerical DOI: 10.1177/02698811211073758
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“Background: many benefits and some harms associated with psychedelic use could be attributable to these drugs’ acceptance/avoidance-promoting effects and corresponding changes in psychological flexibility. underlying psychological mechanisms are insufficiently understood. aim: the purpose of this study was the validation of a psychological model of acceptance/avoidance-promoting psychedelic experiences, which included the development of a theory-based self-report instrument: the acceptance/avoidance-promoting experiences questionnaire (apeq). its two main scales, acceptance-related experience (ace) and avoidance-related experience (ave), represent the theorized model’s core constructs. we aimed to test the model’s central assumptions of complementarity (ace and ave may occur alternatingly but not simultaneously, and are therefore empirically independent), intertwinedness (subaspects within ace and ave are mutually contingent and therefore highly inter-correlated), context-dependence (ace and ave depend on context factors) and interaction (longer-term outcomes depend on the interplay between ace and ave). method: a bilingual retrospective online survey including 997 english- and 836 german-speaking participants. each participant reported on one psychedelic experience occasioned by lysergic acid diethylamide (lsd), psilocybin, mescaline, or ayahuasca. results: whereas ace and ave were found to be relatively independent aspects of participants’ reported psychedelic experiences (complementarity), their subaspects were mostly distinguishable but strongly correlated among each other (intertwinedness). therapeutic, escapist, and hedonic use motives were differentially associated with ace and ave (context-dependence), which were in turn associated with retrospective changes in psychological flexibility following participants’ reported experiences. the positive association between ace and increased psychological flexibility was significantly moderated by ave (interaction). conclusion: these results provide an initial validation of the apeq and its underlying theoretical model, suggesting the two can help clarify the psychological mechanisms of psychedelic-induced benefits and harms. both should be further investigated in prospective-longitudinal and clinical studies.”
Miceli McMillan, R., & Jordens, C.. (2022). Psychedelic-assisted psychotherapy for the treatment of major depression: a synthesis of phenomenological explanations. Medicine, Health Care and Philosophy
Plain numerical DOI: 10.1007/s11019-022-10070-7
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“Psychedelic-assisted psychotherapy (pap) combines the use of psychedelic compounds, such as psilocybin, with psychotherapy. pap has shown some promise as a novel treatment for major depressive disorder (mdd), and empirical research suggests that its efficacy turns on the altered states induced by psychedelic compounds. in this paper we draw on the literature of phenomenology to explain the therapeutic potential of psychedelic experiences. svenaeus characterises mental illness as a form of suffering that entails three distinct but related experiences of alienation or ‘unhomelike being-in-the-world’: (1) illness suffering, which relates to embodiment; (2) existential suffering, which relates to self-narratives, and (3) political suffering, which relates to social relationships. ratcliffe further characterises the experience of mdd in phenomenological terms as a loss of pre-intentional possibility that manifests as excessive noematic feeling in the experience of embodiment, restrictive narratives in the construction of self, and disconnectedness in experience of the social world. we contend that pap ameliorates the suffering associated with mdd by inducing and consolidating a state of broadened pre-intentional possibility—one that entails sudden, profound and enduring changes in embodiment, self-narratives, and social experience. we argue further that this phenomenological account is consistent with a bio-psycho-social model of mental health and illness, and we frame it as an argument supporting the plausibility of recent claims about treatment success. this helps to justify ongoing future empirical research in this setting.”
Kargbo, R. B., Sherwood, A. M., Meisenheimer, P., Lenoch, K., & Abebe, S.. (2022). Psilocybin: Characterization of the metastable zone width (MSZW), control of anhydrous polymorphs, and particle size distribution (PSD). ACS Omega
Plain numerical DOI: 10.1021/acsomega.1c06708
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“Psilocybin, a serotonergic agonist, was granted a ‘breakthrough therapy’ status by the food and drug administration for clinical trials involving major depressive disorder and treatment-resistant depression. the direct phosphorylation of psilocin to psilocybin that uses a fast crystallization associated with a kinetically controlled process resulted in a smaller particle size distribution. herein, the measurement of the metastable zone width (mszw) and nucleation induction enabled a thermodynamically controlled crystallization process, which leads to the formation of a crystal structure with stronger interactions, controlled particle size distribution (psd), and improved impurity profile. employing a high-resolution inline microscopy viewer allowed the real-time monitoring of the crystallization process and the measurement of the particle size. we also present a comprehensive study of the formation of polymorph b (trihydrate), polymorph a (anhydrate), and polymorph h (anhydrate) using water recrystallization, which indicates that the formation of polymorph b (trihydrate) is independent of the crystallization method. however, polymorphs a and h are dependent on the mode of drying: drying at room temperature under vacuum gives rise to mainly polymorph a, and when heated even at relatively low temperatures, a mixture of polymorphs a and h beings to form.”
Gründer, G., Brand, M., Kärtner, L., Scharf, D., Schmitz, C., Spangemacher, M., & Mertens, L. J.. (2022). Are psychedelics fast acting antidepressant agents?. Nervenarzt
Plain numerical DOI: 10.1007/s00115-021-01255-1
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“Background: psychedelics, such as psilocybin represent one of the most promising current therapeutic approaches in psychiatry. objective: psychedelics seem to have not only potent antidepressant effects. do they also work particularly quickly, i.e. within one day? material and methods: the available literature on clinical studies of psychedelics in depressive syndromes is presented both from the period up to the prohibition of these substances in the late 1960s as well as after the resumption of research in the 2000s. one focus is the speed of onset of antidepressant action. results: only the clinical studies published since 2016 that meet modern methodological standards have also systematically examined the speed of the antidepressant onset of action. the published studies, which were almost exclusively carried out with psilocybin, so far show small sample sizes (the total number of patients with depression treated in published clinical studies is < 200) and some of them have methodological weaknesses; however, they suggest a pronounced and very rapid onset of action within one day for depression, treatment-resistant depression and depression in the context of life-threatening cancer. conclusion: the available studies indicate a potent, rapid onset and in many cases long-lasting antidepressant effect over several months. the currently conducted studies with three-digit patient numbers will provide final information about the potential of psilocybin for depression.”
Earleywine, M., Low, F., Altman, B. R., & De Leo, J.. (2022). How Important Is a Guide Who Has Taken Psilocybin in Psilocybin-Assisted Therapy for Depression?. Journal of Psychoactive Drugs
Plain numerical DOI: 10.1080/02791072.2022.2047842
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“ABSTRACT promising outcomes of psilocybin-assisted therapy (pat) for depression have generated concerted efforts to replicate, extend, and refine protocols to maximize efficacy. psychotherapy research reveals that clients benefit most when important components of treatment align with their personal preferences. one open question related to pat concerns the importance of the psilocybin experience of the guides (trained professionals present during acute effects). we sought to assess the importance of a guide who had used psilocybin to potential clients with depressive symptoms. over 800 mturk respondents with depressive symptoms rated the import of a guide who had used psilocybin relative to alternative characteristics in guides and cognitive behavioral (cbt) therapists. importance ratings for guides who had used psilocybin significantly exceeded the ‘somewhat important’ level (50 on a 0–100 scale), other guide-related qualities, and comparable ratings for a cognitive behavioral therapist who shared demographics, had experience with depression and received cognitive therapy personally. people of color (those who are not caucasian) and those who had previous therapy gave significantly higher importance ratings for guides who had used psilocybin. participants who chose to list other qualities important for guides listed very similar ones for cbt therapists, often emphasizing proper training and an empathic demeanor. guides who have used psilocybin, who inform clients of the fact, might have advantages for facilitating pat’s antidepressant effects, as least in a subset of clients. (psycinfo database record (c) 2022 apa, all rights reserved) (source: journal abstract)”
Sarris, J., Rubiano, D. P., Day, K., Galvao-Coelho, N. L., & Perkins, D.. (2022). Psychedelic medicines for mood disorders: Current evidence and clinical considerations. Current Opinion in Psychiatry
Plain numerical DOI: 10.1097/YCO.0000000000000759
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“Purpose of review despite advances in treatment modalities for mood disorders over recent decades, further therapeutic options are still required. increased research is occurring, with the pursuit of psychedelic-based pharmacotherapies for a range of mood disorders and other conditions. recent findings serotonergic psychedelics have been found to modulate brain networks underlying various psychiatric disorders, as well promoting neurogenesis and neuroplasticity. randomized placebo-controlled trials have found psilocybin with psychological support effective at treating depression, including treatment-resistant depression; with emergent research also signalling n,n-dimethyltryptamine/ayahuasca also as a potential option for the treatment of depression. lysergic acid diethylamide has been found to have anxiolytic effects, whereas 3,4-methylenedioxymethamphetamine (mdma) has been used effectively to treat posttraumatic stress disorder (ptsd), with phase iii clinical trial evidence. microdosing of psychedelics is a growing phenomenon that has shown benefits in some preclinical data; however, a recent self-directed controlled trial reported no evidence of improved mood. summary current research with medicinal psychedelics, usually as an adjunct to psychotherapy, has shown encouraging results in treating mood disorders. however, there are challenges regarding blinding and sample sizes remain small, and there have been no definitive phase iii studies (aside from mdma for ptsd). further work exploring novel formulations, interface with pharmacogenomics and the microbiome, and inflammatory pathways can be advised.”
McClure-Begley, T. D., & Roth, B. L.. (2022). The promises and perils of psychedelic pharmacology for psychiatry. Nature Reviews Drug Discovery
Plain numerical DOI: 10.1038/s41573-022-00421-7
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“Psychedelic drugs including psilocybin, n,nʹ-dimethyltryptamine (dmt) and lysergic acid diethylamide (lsd) are undergoing a renaissance as potentially useful drugs for various neuropsychiatric diseases, with a rapid onset of therapeutic activity. notably, phase ii trials have shown that psilocybin can produce statistically significant clinical effects following one or two administrations in depression and anxiety. these findings have inspired a ‘gold rush’ of commercial interest, with nearly 60 companies already formed to explore opportunities for psychedelics in treating diverse diseases. additionally, these remarkable phenomenological and clinical observations are informing hypotheses about potential molecular mechanisms of action that need elucidation to realize the full potential of this investigative space. in particular, despite compelling evidence that the 5-ht2a receptor is a critical mediator of the behavioural effects of psychedelic drugs, uncertainty remains about which aspects of 5-ht2a receptor activity in the central nervous system are responsible for therapeutic effects and to what degree they can be isolated by developing novel chemical probes with differing specificity and selectivity profiles. here, we discuss this emerging area of therapeutics, covering both controversies and areas of consensus related to the opportunities and perils of psychedelic and psychedelic-inspired therapeutics. we highlight how basic science breakthroughs can guide the discovery and development of psychedelic-inspired medications with the potential for improved efficacy without hallucinogenic or rewarding actions.”
Vollenweider, F. X., & Smallridge, J. W.. (2022). Classic Psychedelic Drugs: Update on Biological Mechanisms. Pharmacopsychiatry
Plain numerical DOI: 10.1055/a-1721-2914
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“Renewed interest in the effects of psychedelics in the treatment of psychiatric disorders warrants a better understanding of the neurobiological mechanisms underlying the effects of these substances. during the past two decades, state-of-the-art studies of animals and humans have yielded new important insights into the molecular, cellular, and systems-level actions of psychedelic drugs. these efforts have revealed that psychedelics affect primarily serotonergic receptor subtypes located in cortico-thalamic and cortico-cortical feedback circuits of information processing. psychedelic drugs modulate excitatory-inhibitory balance in these circuits and can participate in neuroplasticity within brain structures critical for the integration of information relevant to sensation, cognition, emotions, and the narrative of self. neuroimaging studies showed that characteristic dimensions of the psychedelic experience obtained through subjective questionnaires as well as alterations in self-referential processing and emotion regulation obtained through neuropsychological tasks are associated with distinct changes in brain activity and connectivity patterns at multiple-system levels. these recent results suggest that changes in self-experience, emotional processing, and social cognition may contribute to the potential therapeutic effects of psychedelics.”
Zeifman, R. J., Singhal, N., Breslow, L., & Weissman, C. R.. (2022). Correction: On the Relationship between Classic Psychedelics and Suicidality: A Systematic Review (ACS Pharmacology and Translational Science (2021) 4:2 (436-451) DOI: 10.1021/acsptsci.1c00024). ACS Pharmacology and Translational Science
Plain numerical DOI: 10.1021/acsptsci.2c00014
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“Upon further review, we identified two suicidality-related events that were not described in the original manuscript. both of these events were deemed not attributable to the administration of a psychedelic by the authors of the primary outcome trials. one completed suicide was reported by griffiths et al. (2016) 11 days following the administration of a very low dose (placebo-like) of psilocybin (1 mg/70 kg psilocybin). importantly, this individual was not administered an ‘active’ dose of psilocybin during the course of the study.1 one suicide attempt was reported by anderson et al. (2020) approximately 2 months after the administration of an active dose of psilocybin (21−25.2 mg/70 kg).2 for further details, see the supporting information of the respective manuscripts. although these events are likely not attributable to psychedelic therapy itself, they point to the importance of closely attending to safety within psychedelic therapy and research.”
Bender, D., & Hellerstein, D. J.. (2022). Assessing the risk–benefit profile of classical psychedelics: a clinical review of second-wave psychedelic research. Psychopharmacology
Plain numerical DOI: 10.1007/s00213-021-06049-6
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“Rationale: a broad reassessment of the potential benefits of psychedelic drugs has led to the initiation of multiple major clinical trials in an effort to advance their status to become fda-approved medications, as well as local legislative efforts to legalize or decriminalize their use. objectives: to use recently published data to assess potential risks and benefits of psychedelic drugs as therapeutics, as well as to synthesize what is currently known in order to generate fruitful future research directions. methods: a review of studies conducted since 1991 identified 14 clinical trials of classical psychedelics, including 11 of psilocybin (n = 257 participants), 1 of lysergic acid diethylamide (n = 12 participants), and 2 of ayahuasca (n = 46 participants). other published studies (e.g., of healthy volunteers, survey studies, case reports, neuroimaging) were also considered for review. results: published studies since 1991 largely support the hypothesis that small numbers of treatments with psychedelic-assisted psychotherapy can offer significant and sustained alleviation to symptoms of multiple psychiatric conditions. no serious adverse events attributed to psychedelic therapy have been reported. existing studies have several limitations, including small sample sizes, inherent difficulty in blinding, relatively limited follow-up, and highly screened treatment populations. conclusions: substantial data have been gathered in the past 30 years suggesting that psychedelics are a potent treatment for a variety of common psychiatric conditions, though the ideal means of employing these substances to minimize adverse events and maximize therapeutic effects remains controversial. unique factors related to study design are vital for clinical researchers in the field to address.”
Glynos, N. G., Pierce, J., Davis, A. K., McAfee, J., & Boehnke, K. F.. (2022). Knowledge, Perceptions, and Use of Psychedelics among Individuals with Fibromyalgia. Journal of Psychoactive Drugs
Plain numerical DOI: 10.1080/02791072.2021.2022817
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“Fibromyalgia (fm) is a difficult to treat chronic pain condition for which there is strong interest in alternative treatments. there is growing interest in the potential of psychedelic substances (e.g., psilocybin) in conjunction with psychotherapy to treat chronic pain. via a cross-sectional, anonymous, online survey, we aimed to characterize knowledge, perceptions, and past use of serotonergic (‘classic’) and non-serotonergic psychedelics among a population of individuals with fm, and to investigate interest in psychedelic-based fm treatments. among a north american population of 354 participants with fm, 29.9% reported past use of a psychedelic, with lysergic acid diethylamide (lsd) and psilocybin mushrooms being most commonly used. perceptions of benefit from psychedelic use were generally neutral (59.4%) or positive (36.8%), with <3% reporting negative impacts on overall health or pain symptoms. among 12 participants who used psychedelics with intentions of treating chronic pain, 11 reported improved symptoms. regardless of past use, the majority of participants believed that psychedelics have potential for chronic pain treatments and would be willing to participate in a psychedelic-based clinical trial for their pain. these findings support the need for additional studies to understand the potential and effectiveness of psychedelic substances in managing fm symptoms.”
Petranker, R., Kim, J., & Anderson, T.. (2022). Microdosing as a Response to the Meaning Crisis: A Qualitative Analysis. Journal of Humanistic Psychology
Plain numerical DOI: 10.1177/00221678221075076
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“The use of psychedelic substances in both humanistic and mainstream clinical research has been increasing in the last decade. in particular, the practice of microdosing—ingesting sub-hallucinogenic doses of psychedelics—has been increasing in popularity, but large-scale qualitative analyses are still uncommon. this study attempted to recognize emergent themes in qualitative reports regarding the experience of microdosing to enrich the theoretical landscape in psychedelic research and propose future research directions for both basic and clinical research. participants were people who reported microdosing at least once in the last year; they described their experiences using an online survey. data from 118 informative responses suggested four main emergent themes: reasons for microdosing, the practice of microdosing itself, outcomes linked to microdosing, and meta-commentary about microdosing. we use meaning-making theory and propose that, even at low doses, psychedelic substances can provide a sense of meaning. our results suggest that many of the reported benefits occur regardless of motivation to microdose and are likely due to the enhanced psychological flexibility and a sense of connectedness made possible due to the use of psychedelics. double-blind, placebo-controlled experiments are required to substantiate these reports.”
Cao, D., Yu, J., Wang, H., Luo, Z., Liu, X., He, L., … Wang, S.. (2022). Structure-based discovery of nonhallucinogenic psychedelic analogs. Science
Plain numerical DOI: 10.1126/science.abl8615
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“Drugs that target the human serotonin 2a receptor (5-ht2ar) are used to treat neuropsychiatric diseases; however, many have hallucinogenic effects, hampering their use. here, we present structures of 5-ht2ar complexed with the psychedelic drugs psilocin (the active metabolite of psilocybin) and d-lysergic acid diethylamide (lsd), as well as the endogenous neurotransmitter serotonin and the nonhallucinogenic psychedelic analog lisuride. serotonin and psilocin display a second binding mode in addition to the canonical mode, which enabled the design of the psychedelic ihch-7113 (a substructure of antipsychotic lumateperone) and several 5-ht2ar b-arrestin-biased agonists that displayed antidepressant-like activity in mice but without hallucinogenic effects. the 5-ht2ar complex structures presented herein and the resulting insights provide a solid foundation for the structure-based design of safe and effective nonhallucinogenic psychedelic analogs with therapeutic effects.”
Koslowski, M., Johnson, M. W., Gründer, G., & Betzler, F.. (2022). Novel Treatment Approaches for Substance Use Disorders: Therapeutic Use of Psychedelics and the Role of Psychotherapy. Current Addiction Reports
Plain numerical DOI: 10.1007/s40429-021-00401-8
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“Purpose of review: the use of psychedelics in a therapeutical setting has been reported for the treatment of various diagnoses in recent years. however, as psychedelic substances are still commonly known for their (illicit) recreational use, it may seem counterintuitive to use psychedelic therapy to treat substance use disorders. this review aims to discuss how psychedelics can promote and intensify psychotherapeutic key processes, in different approaches like psychodynamic and cognitive behavioral therapy, with a spotlight on the treatment of substance use disorders (sud). recent findings: there is promising evidence of feasibility, safety, and efficacy of psychedelic therapy in sud. in the whole process of former and current psychedelic therapy regimes that have shown to be safe and efficacious, various psychotherapeutic elements, both psychodynamic and behavioral as well as other approaches, can be identified, while a substantial part of the assumed mechanism of action, the individual psychedelic experience, cannot be distinctly classified to just one approach. summary: psychedelic therapy consists of a complex interaction of pharmacological and psychological processes. when administered in well-defined conditions, psychedelics can serve as augmentation of different psychotherapy interventions in the treatment of sud and other mental disorders, regardless of their theoretical origin.”
Schimmel, N., Breeksema, J. J., Smith-Apeldoorn, S. Y., Veraart, J., van den Brink, W., & Schoevers, R. A.. (2022). Psychedelics for the treatment of depression, anxiety, and existential distress in patients with a terminal illness: a systematic review. Psychopharmacology
Plain numerical DOI: 10.1007/s00213-021-06027-y
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“Background: terminally ill patients may experience existential distress, depression, or anxiety, limiting quality of life in the final stage. existing psychotherapeutic or pharmacological interventions have (time) limited efficacy. psychedelic treatment may be a safe and effective alternative treatment option. aim: systematically review studies on psychedelic treatment with and without psychotherapy for existential distress, depression, and anxiety in terminally ill patients. methods: medline, psycinfo, and embase were searched for original-data studies on the treatment of depression, anxiety, and existential distress with classical or a-typical psychedelics in patients with a terminal illness, using preferred reporting items for systematic reviews and meta-analyses guidelines. results: a total of 1850 records were screened, and 33 articles were included in this review: 14 studies on classical psychedelics (dpt, lsd, and psilocybin) and 19 studies on atypical psychedelics (mdma and ketamine). results of early pre-post studies are promising but have serious methodological flaws. recent (controlled) trials with lsd, psilocybin, ketamine, and mdma are of higher methodological quality and indicate positive effects on existential and spiritual well-being, quality of life, acceptance, and reduction of anxiety and depression with few adverse and no serious adverse effects. conclusions: both classical and a-typical psychedelics are promising treatment options in patients with terminal illness. to draw final conclusions on effectiveness and safety of psychedelics, we need larger high-quality studies for classical psychedelics and mdma. ketamine studies should pay more attention to existential dimensions of well-being and the psychotherapeutic context of the treatment.”
Dworatzyk, K., Jansen, T., & Schmidt, T. T.. (2022). Phenomenological assessment of psychedelics induced experiences: Translation and validation of the German Challenging Experience Questionnaire (CEQ) and Ego-Dissolution Inventory (EDI). PLoS ONE
Plain numerical DOI: 10.1371/journal.pone.0264927
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“Several measures have been designed to assess subjective experiences induced by psychedelic substances or other mind-altering drugs as well as non-pharmacological methods. recently, two self-report questionnaires have been introduced to measure acute adverse effects following psilocybin ingestion and the phenomenon of ego-dissolution associated with the use of psychedelics, respectively. the 26-item challenging experience questionnaire assesses multiple facets of psilocybin induced experiences on seven subscales, whereas the 8-item ego-dissolution inventory consists of a unidimensional scale. in the present study, these questionnaires were translated into german and their psychometric properties then evaluated in an online survey on psychedelics induced experiences. confirmatory factor analysis suggested an acceptable fit of the 7-factor structure of the german challenging experience questionnaire with overall good internal consistency for all subscales. the factor structure did not differ based on gender or prior struggle with a psychiatric disorder, furthering the evidence of internal validity. correlations with the state-trait-anxiety inventory and the altered states of consciousness rating scale demonstrated convergent validity. confirmatory factor analysis did not support the hypothesized single-factor structure of the german ego-dissolution inventory and exploratory factor analysis suggested an alternative factor structure, where only five items loaded onto a common factor that was interpreted as ego-dissolution. internal consistency of this 5-item measure was high and correlation with selected items of the mystical experience questionnaire and altered states of consciousness rating scale supported convergent validity. translation and validation of these questionnaires contribute to the advancement of common standards in the psychological and neuroscientific study of altered states of consciousness.”
Elman, I., Pustilnik, A., & Borsook, D.. (2022). Beating pain with psychedelics: Matter over mind?. Neuroscience and Biobehavioral Reviews
Plain numerical DOI: 10.1016/j.neubiorev.2021.12.005
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“Basic pain research has shed light on key cellular and molecular mechanisms underlying nociceptive and phenomenological aspects of pain. despite these advances, we still yearn for the discovery of novel therapeutic strategies to address the unmet needs of about 70 % of chronic neuropathic pain patients whose pain fails to respond to opioids as well as to other conventional analgesic agents. importantly, a substantial body of clinical observations over the past decade cumulatively suggests that the psychedelic class of drugs may possess heuristic value for understanding and treating chronic pain conditions. the present review presents a theoretical framework for hitherto insufficiently understood neuroscience-based mechanisms of psychedelics’ potential analgesic effects. to that end, searches of pubmed-indexed journals were performed using the following medical subject headings’ terms: pain, analgesia, inflammatory, brain connectivity, ketamine, psilocybin, functional imaging, and dendrites. recursive sets of scientific and clinical evidence extracted from this literature review were summarized within the following key areas: (1) studies employing psychedelics for alleviation of physical and emotional pain; (2) potential neuro-restorative effects of psychedelics to remediate the impaired connectivity underlying the dissociation between pain-related conscious states/cognitions and the subcortical activity/function leading to the eventual chronicity through immediate and long-term effects on dentritic plasticity; (3) anti-neuroinflammatory and pro-immunomodulatory actions of psychedelics as the may pertain to the role of these factors in the pathogenesis of neuropathic pain; (4) safety, legal, and ethical consideration inherent in psychedelics’ pharmacotherapy. in addition to direct beneficial effects in terms of reduction of pain and suffering, psychedelics’ inclusion in the analgesic armamentarium will contribute to deeper and more sophisticated insights not only into pain syndromes but also into frequently comorbid psychiatric condition associated with emotional pain, e.g., depressive and anxiety disorders. further inquiry is clearly warranted into the above areas that have potential to evolve into further elucidate the mechanisms of chronic pain and affective disorders, and lead to the development of innovative, safe, and more efficacious neurobiologically-based therapeutic approaches.”
Simonsson, O., & Goldberg, S. B.. (2022). Linkages between Psychedelics and Meditation in a Population-Based Sample in the United States. Journal of Psychoactive Drugs
Plain numerical DOI: 10.1080/02791072.2021.2022816
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“There are neurophysiological and phenomenological overlaps between psychedelic and meditative states, but there is little evidence on how exposure to psychedelics might be associated with meditation-related variables. we assessed lifetime classic psychedelic use, ego dissolution during one’s most intense experience using a classic psychedelic, and exposure to meditation in a representative sample (n = 953) of american adults. those who reported experience with meditation were invited to complete a follow-up survey (n = 536, 92.1% response rate) measuring meditation-related variables. models controlled for a range of potential confounds. exposure to meditation was associated with lifetime classic psychedelic use and ego dissolution in covariate-adjusted models. in addition, among meditators, greater ego dissolution was associated with more frequent meditation practice. both lifetime classic psychedelic use and ego dissolution were associated with enlightenment as motivation to practice meditation as well as lower likelihood of overall perceived barriers to meditation practice. ego dissolution was positively associated with finding meditation more effective. neither lifetime classic psychedelic use nor ego dissolution was associated with greater likelihood of meditation-related adverse effects. taken together, results support potential synergy between psychedelics and meditation, but randomized controlled trials are necessary to establish safety and evaluate potential causal relationships.”
Toby, B. H.. (2022). Crystallographic hallucinations. Acta Crystallographica Section C: Structural Chemistry
Plain numerical DOI: 10.1107/S2053229622000511
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Jaster, A. M., Elder, H., Marsh, S. A., de la Fuente Revenga, M., Negus, S. S., & González-Maeso, J.. (2022). Effects of the 5-HT2A receptor antagonist volinanserin on head-twitch response and intracranial self-stimulation depression induced by different structural classes of psychedelics in rodents. Psychopharmacology
Plain numerical DOI: 10.1007/s00213-022-06092-x
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“Background: clinical studies suggest that psychedelics exert robust therapeutic benefits in a number of psychiatric conditions including substance use disorder. preclinical studies focused on safety and efficacy of these compounds are necessary to determine the full range of psychedelics’ effects. objectives: the present study explores the behavioral pharmacology of structurally distinct psychedelics in paradigms associated with serotonin 2a receptor (5-ht2ar) activation and behavioral disruption in two rodent models. utilizing the selective 5-ht2ar antagonist volinanserin, we aimed to provide further pharmacological assessment of psychedelic effects in rodents. methods: we compared volinanserin (0.0001–0.1 mg/kg) antagonism of the phenethylamine 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (doi, 1.0 mg/kg) and the ergoline lysergic acid diethylamide (lsd, 0.32 mg/kg) in preclinical assays predictive of hallucinations (head-twitch response or htr in mice) and behavioral disruption (intracranial self-stimulation or icss in rats). volinanserin antagonism of the phenethylamine mescaline, the tryptamine psilocybin, and the k-opioid receptor agonist salvinorin a was also evaluated in the rat icss assay. results: volinanserin had similar potency, effectiveness, and time-course to attenuate doi–induced htr in mice and icss depression in rats. volinanserin completely blocked lsd–induced htr in mice, but not lsd–induced icss depression in rats. volinanserin also reversed icss depression by mescaline, but it was only partially effective to reduce the effects of psilocybin, and it exacerbated icss depression by salvinorin a. conclusion: although hallucination-related htr behavior induced by phenethylamine, ergoline, and tryptamine psychedelics appears to be 5-ht2ar-mediated, the receptor(s) responsible for behavioral disruptive effects may differ among these three structural classes.”
Hammel, R. L., Gulliver, B. J., Sukich, S. N., & Abraham, S. P.. (2022). The Role ofPsychedelics in Managing Anxiety, Depression, and Flashbacks of Individuals withPost-Traumatic Stress Disorder. International Journal of Science and Research Methodology
Plain numerical DOI: 10.25166/ijsrm/2022.20.3.2
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“Background: the impact of psychedelic treatment on patients with posttraumatic stress disorder (ptsd) has become more intriguing to the psychiatric field. because of the stigma surrounding illicit drug use, the scientific communities were unable to conduct thorough studies regarding the effects of psychedelics on the brain. these drugs could help many people with mental illnesses that have not found adequate success with typical treatments. in recent years, there have been studies conducted to examine the use of psychedelics for the treatment of psychiatric disorders such as ptsd. purpose: the purpose of this review was to bring awareness to the effectiveness of long-forbidden psychedelic treatments such as psilocybin. method: using a review of scholarly articles, this paper examines the effects of psilocybin on anxiety, depression, and flashbacks in patients with ptsd. findings: findings indicate a therapeutic effect on patients with ptsd when using psilocybin. conclusion: based on these findings, the medical community should take steps toward novelty treatments for psychiatric diagnoses; however, further studies may be implicated. stigma against this class of medications remains an issue.”
Barnett, B. S., Parker, S. E., & Weleff, J.. (2022). United States National Institutes of Health grant funding for psychedelic-assisted therapy clinical trials from 2006–2020. International Journal of Drug Policy
Plain numerical DOI: 10.1016/j.drugpo.2021.103473
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“Background: medicine is currently experiencing a ‘psychedelic renaissance’, said by many to have commenced in 2006. since then, clinical trials have consistently demonstrated promising findings for psychedelic-assisted therapies in the treatment of various mental health conditions and addictions. while most of this work has been privately funded, governmental biomedical research funding bodies in countries such as australia, canada, israel, new zealand, and the united kingdom have begun supporting it. given that the united states national institutes of health (nih) is the largest public funder of biomedical research in the world, it is important to understand the degree to which the organization is supporting clinical trials of psychedelic-assisted therapies. we are unaware of existing literature quantifying direct nih grant support for psychedelic-assisted therapy clinical trials, so we sought to answer this important question by searching all nih grants awarded since the beginning of the psychedelic renaissance. methods: we queried nih reporter, nih’s grant database, for grants awarded from 2006-2020 mentioning the psychedelics 3,4-methylenedioxymethamphetamine (mdma), 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt), ayahuasca, dimethyltryptamine (dmt), ibogaine, lysergic acid (lsd), mescaline, peyote, and psilocybin. we manually reviewed resulting grants to determine whether they directly funded psychedelic-assisted therapy clinical trials. results: we identified zero nih grants directly funding psychedelic-assisted therapy clinical trials during the study period. conclusion: while governmental biomedical research funding bodies in other countries have begun funding clinical trials of psychedelic-assisted therapies during the psychedelic renaissance, nih has yet to directly fund a single psychedelic-assisted therapy clinical trial. concerns about risks related to psychedelics, a federal law preventing promotion of legalization of schedule 1 drugs, and prioritization of grants for other types of studies on psychedelics may explain the dearth of nih funding for psychedelic-assisted therapy clinical trials.”
Averill, L. A., & Abdallah, C. G.. (2022). Investigational drugs for assisting psychotherapy for posttraumatic stress disorder (PTSD): emerging approaches and shifting paradigms in the era of psychedelic medicine. Expert Opinion on Investigational Drugs
Plain numerical DOI: 10.1080/13543784.2022.2035358
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Strickland, J. C., & Johnson, M. W.. (2022). Human behavioral pharmacology of psychedelics. In Advances in Pharmacology
Plain numerical DOI: 10.1016/bs.apha.2021.10.003
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“The past decade has witnessed a rapid growth of research on the basic science and clinical understanding of psychedelics. this chapter provides an overview of the human behavioral pharmacology of psychedelics focusing on three prototypic classic psychedelics—psilocybin, lysergic acid diethylamide (lsd), and dimethyltryptamine (dmt). a brief historical overview of the classic psychedelics and naming and drug classification is first specified. next, special considerations in the conduct of human behavioral pharmacology work with psychedelics is described including the role of set and setting, mystical experience measurement, the use of effective blinding and placebos, and the abuse liability of psychedelics. following, a description of the subjective, physiological, and clinical effects of psilocybin, lsd, and dmt is provided. this body of work clearly documents a unique and complex collection of subjective effects following psychedelic use, both during acute drug administration and as related to long-term behavior change following use. clinical research demonstrates potential therapeutic utility with early phase clinical trials showing positive and enduring effects in many difficult-to-treat conditions including treatment-resistant depression, alcohol use disorder, and cigarette smoking. future work in this newly reemerged field is needed to reveal mechanisms of behavior change in psychedelic drug action. behavioral pharmacology is ultimately well served to provide this direction answering questions at the intersection of environment and pharmacology.”
Lahood, G.. (2022). The mushroom, the frog, and the rainbow of desire: A participatory-psychedelic spiritual emergence.. The International Journal of Transpersonal Studies
Plain numerical DOI: 10.24972/ijts.2019.38.2.182
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“This article will explore a spiritual emergency through a myth or fairy tale that emerged at the same time i had a frightening brush with death. two days before the accident i had ingested psilocybin mushrooms. michael washburn, among other transpersonal theorists, will be used to interpret, amplify and re-frame this potential ‘psychotic episode’ with ‘borderline features’ into something more, perhaps, on the threshold of a shamanic initiation in a liminal state. the mythic sequence in my story anticipates the death-rebirth (perinatal pattern) and evolution of consciousness in the lsd research of stanislav grof; an evolution given epic participatory elucidation by richard tarnas; and an evolution consummated in the erotic desire for nature found in the panpsychism of freya mathews.”
Elcock, C.. (2022). Psychedelic philanthropy: The nonprofit sector and Timothy Leary’s 1960s psychedelic movement. Journal of the History of the Behavioral Sciences
Plain numerical DOI: 10.1002/jhbs.22083
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“Little has been written on the financial support behind timothy leary’s unorthodox research into mind-altering drugs like lsd and psilocybin and his subsequent psychedelic movement. indeed several individuals and organizations helped the psychedelic cause by directly funding leary’s ventures, offering legal and logistic assistance, and organizing fund-raising campaigns. i argue that classic philanthropic attitudes and wealthy patrons played a major supporting role for leary’s psychedelic movement in the first part of the decade and that the changes in leary’s research objectives and his transition from academic to lsd guru were accompanied by changes in the patterns of support that occurred throughout the 1960s. this paper also connects leary’s legal troubles in the second part of the decade with the rise of the movement to legalize cannabis and points to historical continuity by looking at contemporary endeavors to fund psychedelic research.”
Schlag, A. K., Aday, J., Salam, I., Neill, J. C., & Nutt, D. J.. (2022). Adverse effects of psychedelics: From anecdotes and misinformation to systematic science. Journal of Psychopharmacology
Plain numerical DOI: 10.1177/02698811211069100
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“Background: despite an increasing body of research highlighting their efficacy to treat a broad range of medical conditions, psychedelic drugs remain a controversial issue among the public and politicians, tainted by previous stigmatisation and perceptions of risk and danger. objective: this narrative review examines the evidence for potential harms of the classic psychedelics by separating anecdotes and misinformation from systematic research. methods: taking a high-level perspective, we address both psychological and psychiatric risks, such as abuse liability and potential for dependence, as well as medical harms, including toxicity and overdose. we explore the evidence base for these adverse effects to elucidate which of these harms are based largely on anecdotes versus those that stand up to current scientific scrutiny. results: our review shows that medical risks are often minimal, and that many – albeit not all – of the persistent negative perceptions of psychological risks are unsupported by the currently available scientific evidence, with the majority of reported adverse effects not being observed in a regulated and/or medical context. conclusions: this highlights the importance for clinicians and therapists to keep to the highest safety and ethical standards. it is imperative not to be overzealous and to ensure balanced media reporting to avoid future controversies, so that much needed research can continue.”
Matzopoulos, R., Morlock, R., Morlock, A., Lerer, B., & Lerer, L.. (2022). Psychedelic Mushrooms in the USA: Knowledge, Patterns of Use, and Association With Health Outcomes. Frontiers in Psychiatry
Plain numerical DOI: 10.3389/fpsyt.2021.780696
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“Introduction: popular media coverage of psychedelics use, growing research into this class of compounds for psychiatry and decriminalization initiatives, are transforming the public perception of psychedelics. however, little is known about levels of knowledge and psychedelic mushroom (pm) use among american adults. methods: we examined pm use and various measures of health status, quality of life, and self-reported mental health outcome measures obtained through a national on-line, cross-sectional survey of adults with a demographic composition representative of the us adult population by region, gender, age, and race (weighted n = 251,297,495) from november 2020–march 2021. results: general mental health and well-being were popular reasons for pm use (63.6%), although use for medically-diagnosed (31.8%) and self-diagnosed (19.0%) conditions was also common. pm users reported more depression and anxiety as reflected in higher gad-7 and phq-9 scores. factors predictive of pm use included being male [or 1.54 95%ci 1.09–2.15] and having higher charlson comorbidity index scores [or 1.42; 95%ci 1.22–1.65]. self-reported pm use was less likely among participants with health insurance [or = 0.50 (0.35–0.72)], increased age [or = 0.92 (0.90–0.93)] and, relative to those living in the west us census region, living in the northeast [or = 0.27 (0.15–0.50)], midwest [or = 0.34 (0.20–0.56)], and south [or = 0.38 (0.26–0.55)]. discussion and conclusions: a significant number of americans are already ‘self-medicating’ with pm and as growing positive media coverage of psychedelics drives public interest in the health benefits of pm, this number will increase. the association between pm use and poor mental health requires further research to inform policy.”
Hearn, B. G., Brubaker, M. D., & Richardson, G.. (2022). Counselors’ attitudes toward psychedelics and their use in therapy. Journal of Counseling and Development
Plain numerical DOI: 10.1002/jcad.12429
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“The ‘“psychedelic renaissance”’ is generating new evidence for psychedelics’ potential to treat numerous mental and substance use disorders. in particular, the united states food and drug administration is poised to approve psychedelic drugs 3,4 methylenedioxymethamphetamine (mdma) and psilocybin for the use in psychedelic-assisted therapy (pat). this renaissance has led to substantial public attention toward psychedelics, state and local changes to the legal status of psychedelics, and recent increases in the rate of psychedelic use among united states adults. despite these advancements, the counseling profession has remained relatively disengaged from the research and general discourse surrounding psychedelics and pat. in response to this gap, this study presents the results of a survey of counseling professionals’ attitudes toward psychedelics and pats. results suggest counselors’ attitudes toward psychedelic use and pats are mixed, unless they are medically supervised. furthermore, most counselors see potential in pat and the need for additional research.”
Markopoulos, A., Inserra, A., De Gregorio, D., & Gobbi, G.. (2022). Evaluating the Potential Use of Serotonergic Psychedelics in Autism Spectrum Disorder. Frontiers in Pharmacology
Plain numerical DOI: 10.3389/fphar.2021.749068
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“Recent clinical and preclinical evidence points towards empathogenic and prosocial effects elicited by psychedelic compounds, notably the serotonin 5-ht2a agonists lysergic acid diethylamide (lsd), psilocybin, n,n-dimethyltryptamine (dmt), and their derivatives. these findings suggest a therapeutic potential of psychedelic compounds for some of the behavioural traits associated with autism spectrum disorder (asd), a neurodevelopmental condition characterized by atypical social behaviour. in this review, we highlight evidence suggesting that psychedelics may potentially ameliorate some of the behavioural atypicalities of asd, including reduced social behaviour and highly co-occurring anxiety and depression. next, we discuss dysregulated neurobiological systems in asd and how they may underlie or potentially limit the therapeutic effects of psychedelics. these phenomena include: 1) synaptic function, 2) serotonergic signaling, 3) prefrontal cortex activity, and 4) thalamocortical signaling. lastly, we discuss clinical studies from the 1960s and 70s that assessed the use of psychedelics in the treatment of children with asd. we highlight the positive behavioural outcomes of these studies, including enhanced mood and social behaviour, as well as the adverse effects of these trials, including increases in aggressive behaviour and dissociative and psychotic states. despite preliminary evidence, further studies are needed to determine whether the benefits of psychedelic treatment in asd outweigh the risks associated with the use of these compounds in this population, and if the 5-ht2a receptor may represent a target for social-behavioural disorders.”
Johnson, S., & Black, Q. C.. (2022). Classic Psychedelics as a Psychotherapeutic Aid in the Treatment of Stimulant Use Disorder: a Case Report. International Journal of Mental Health and Addiction
Plain numerical DOI: 10.1007/s11469-020-00398-7
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“Despite nascent research supporting the efficacy of classic psychedelics as a psychotherapeutic aid for the treatment of substance abuse, to date, there is limited published research exploring their use in the treatment of stimulant use disorder and dual diagnosis. a 22-year-old male with a history of mood disorder and polysubstance use presented to a private australian mental health clinic. while undergoing psychological treatment for mood and stimulant use disorder, this patient reported significant benefit from his use of classic psychedelics. following consumption of 3.5 grams of psilocybin-containing mushrooms, he decided to seek out psychotherapy for the first time. throughout treatment, subjective reports of his classic psychedelic use, which among others, included two occasions of having consumed 200 μg of lysergic acid diethylamide and 100 mg of dimethyltryptamine, were recorded and a psychometric tool used to capture mystical experiences was administered. as treatment progressed, the patient reported being better able to consolidate his therapeutic gains through the integration of insights obtained through his use of classic psychedelics, ultimately remaining abstinent from all stimulant drugs. the results of this case report suggest that classic psychedelics may be effective psychotherapeutic aids to be used in traditional substance abuse treatment programs. it is hoped that this case report will inform future research in this field.”
Holze, F., Ley, L., Müller, F., Nimmy, V., Eckert, A., & Liechti, M. E.. (2022). Comparison of subjective, autonomic, and endocrine effects of LSD and psilocybin in healthy subjects. Neuroscience Applied
Plain numerical DOI: 10.1016/j.nsa.2022.100075
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