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The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic EffectsClick to copy article linkArticle link copied!
- David B. YadenDavid B. YadenDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United StatesCenter for Psychedelic and Consciousness Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, United StatesMore by David B. Yaden
- Roland R. Griffiths*Roland R. Griffiths*Email: [email protected]. Tel.: 410-550-0034.Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United StatesCenter for Psychedelic and Consciousness Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, United StatesDepartment of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United StatesMore by Roland R. Griffiths
Abstract
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Classic psychedelics produce altered states of consciousness that individuals often interpret as meaningful experiences. Across a number of human studies, when the participant-rated intensity of the overall drug effects are statistically controlled for, certain subjective effects predict therapeutic and other desirable outcomes. Underlying neurobiological mechanisms are likely necessary but not sufficient to confer full and enduring beneficial effects. We propose that the subjective effects of psychedelics are necessary for their enduring beneficial effects and that these subjective effects account for the majority of their benefit.
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Introduction
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The classic psychedelics are a structurally diverse group of compounds that are partial agonists at 5-HT2A serotonin receptors and produce a unique profile of subjective effects. (1) These compounds include tryptamines such as psilocybin (the main psychoactive constituent in psychedelic mushrooms), N,N-dimethyltryptamine (DMT, an ingredient of the plant admixture ayahuasca), phenethlyamines such as mescaline (from peyote and other cacti), and the ergotamines (such as lysergic acid diethylamide, LSD). Pharmacological blocking of the 5-HT2A receptor blocks many subjective and other major effects of psychedelics in humans and infrahuman animals. (2)
These classic psychedelics have low toxicity and limited abuse liability, (3) and several recent studies have investigated their treatment potential for mood and substance use disorders. (4−9) While favorable outcomes have been observed when psychedelics are taken under supportive conditions, questions remain regarding their mechanisms of action. Here we argue that some subjective effects occasioned by moderate to high doses of psychedelics in humans are necessary for their full and enduring therapeutic and otherwise beneficial outcomes. In this article, subjective effects refer to first-person experience, which is empirically measured by self-report data. Our view is neatly captured by the thought experiment (which we elaborate on later in this piece): would psychedelics confer their therapeutic benefits if they were administrated to someone who was under heavy sedation? We suspect the answer is no.
Our position contrasts the idea that subjective effects of psychedelics may be irrelevant to their therapeutic effects. The position that subjective effects are irrelevant to therapeutic effects is probably true of many pharmacological treatments. Suggestive evidence supporting this position include studies in which psychedelics have been shown to produce positive effects in a rodent model of depression. (10) Although we cannot completely discount the possibility of subjective drug effects in rodents, it seems unlikely that rodents would have experiences similar to those to which humans attribute deep personal meaning and positive, therapeutically relevant mood and behavioral change after taking a psychedelic. From this perspective, the subjective experiences elicited by psychedelic substances are merely epiphenomena of the underlying neurobiological mechanisms which convey the beneficial effects. For example, psychedelics promote structural and functional neural plasticity in the prefrontal cortex through 5-HT2A receptor-mediated mechanisms, (11) or, to cite another example of a neurobiological model that may not require subjective experience, it is observed that the antidepressant effects of psychedelics are associated with brain network reorganization. (12) While these and other neurobiological mechanisms could plausibly account for some of the therapeutic actions of psychedelics, none rule out an essential mediating role of subjective effects in humans.
Subjective Effects of Psychedelics
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Naturally occurring psychedelics have been used for millennia in some cultures in religious and healing rituals, with an emphasis on the subjective experiences that they produce. (13) The importance of acute subjective effects in therapeutic outcomes has been also been documented in qualitative interview studies of patients treated with psychedelics in contemporary settings. (14,15) There is a great deal of historical, anecdotal, and qualitative data supporting the value of the subjective effects of psychedelics.
The meaning and significance attributed to psychedelic experiences has been well established in laboratory settings. Psilocybin administration studies have repeatedly shown that participants frequently rate their psychedelic experiences as among the most meaningful of their entire lives (5,6,8,16−19) and they are sometimes compared to the birth of a first-born child or death of a parent. Due to their salience, such experiences may serve as narrative “inflection points” in one’s life that could provide an impetus for changing one’s identification with certain patterns of thoughts, feelings, and behaviors.
Several subjective features of psychedelic experiences are measurable through psychometric survey instruments. Building on the foundational scholarship of William James, Walter Stace, Walter Pahnke, and others, (20) the Mystical Experience Questionnaire (MEQ) was developed and subsequently revised and psychometrically validated to provide a self-report measure of the acute effects of psilocybin. (21) This scale includes four subscales: 1, an authoritative sense of unity or connectedness accompanied by feelings of reverence; 2, positively valenced feelings such as love or peace; 3, alterations to the sense of both time and space; and 4, difficulty with putting the experience into words. The MEQ likely taps several different cognitive and affective processes that ongoing psychometric studies are further delineating.
Scores on questionnaires assessing mystical-type experiences are predictive of beneficial outcomes from psychedelics administered in experimental contexts (Figure 1). An initial double-blind study from Johns Hopkins showed that 61% of 36 psychedelic naı̈ve participants met a priori criteria for having a “complete” mystical experience at the end of the psilocybin session day compared to 11% after methylphenidate. (16) Two months after sessions, participants attributed significantly greater positive changes in attitudes about life and self, positive mood, positive behaviors, and positive social effects to experiences during the psilocybin than methylphenidate sessions. Importantly, correlation and regression analyses indicated a central role of the mystical experience assessed on the session day, but not the intensity of the psilocybin experience, in predicting the high ratings of personal meaning assessed at 14 months. (17) For instance, r-values of 0.61 were found between mystical experience scores immediately after psilocybin sessions and the follow-up ratings of the personal meaning of the experience after controlling for three different measures of the intensity of the drug effect. A systematic replication of the first study in 18 healthy participants showed that mystical experience on session days and positive ratings on follow-up increased as an orderly function of psilocybin dose. (18) A further extension of this research explored the role of psilocybin-occasioned mystical experience in combination with meditation on enduring changes in trait measures of prosocial attitudes and behaviors. (19) In that randomized double-blind study, 50 participants received moderate-high doses of psilocybin on each of two sessions while 25 received a low placebo-like dose on both sessions. Overall, 61% of those receiving moderate-high doses of psilocybin had complete mystical experiences in contrast to 4% for those receiving the low placebo-like dose with the same levels of psychological support. Hierarchical regression analysis showed that mystical experience (MEQ scores) on session days contributed significantly (improving the r-square of a model that included only spiritual practices by 0.54) to predicting a composite measure of positive outcomes such as positive attitudes about life, self, mood, and behavior at 6 months.
Figure 1
Figure 1. Left panel shows data from a study (N = 15) of psilocybin on cigarette smoking cessation (replotted from Garcia et al. (22)). Smoking craving data are change scores from pretreatment to the 6-month follow-up. Mystical experience data for each participant are the mean total score on the 43-item version of the Mystical Experience Questionnaire (expressed as a percentage of the maximum possible score) assessed at the end of each of 2 or 3 psilocybin sessions. The middle panel shows data from a study (N = 24) of psilocybin on depression (adapted from Davis et al. (9)). Depression was measured with GRID-Hamilton Depression Rating Scale and expressed as change scores from pretreatment to 4 weeks after the second psilocybin session. Mystical experience data for each participant are the highest of two total scores on the 30-item Mystical Experience Questionnaire (expressed as a percentage of the maximum possible score) assessed at the end of each of two psilocybin sessions. The right panel shows data from a study of (N = 50) of individuals with a life-threatening cancer diagnosis who received either a very low dose or a moderately high dose of psilocybin (Griffiths et al. (5)). Mystical experience data for each participant are the total score on the 30-item Mystical Experience Questionnaire (expressed as a percentage of the maximum possible score) assessed at the end of the first psilocybin session. Anxiety was measured with the Hamilton Anxiety Rating Scale and expressed as a change score from baseline to 5 weeks postsession. More details regarding these images can be found in the citations above describing the original studies.
Mystical-type experience scores on psilocybin session days are also predictive of treatment success at long-term follow-up in clinical studies (see Figure 1). Two double-blind crossover studies showed that psilocybin produced substantial and enduring decreases in symptoms of anxiety and depression among patients with a life-threatening cancer diagnosis. (5,6) In the first of these studies, (5) mean percentage of maximum total possible score on the MEQ was significantly higher immediately after a moderate psilocybin dose (64%) than after a low placebo-like dose (27%). These scores after the first session were significantly correlated with most of the enduring changes in therapeutic outcome measured 5 weeks later. For most measures, this relationship continued to be significant when the intensity of overall psilocybin effect was controlled for in a partial correlation analysis, suggesting that mystical-type experience per se has an important role apart from overall intensity of drug effect. Furthermore, a statistical mediation analysis suggested that mystical-type experience was a mediator in positive therapeutic response. The results of the second of these studies (6) were very similar, with correlation analysis controlling for the intensity of drug effect and a mediation analysis suggesting that mystical experience was a mediator of therapeutic effects. Open-label pilot studies of psilocybin in the treatment of substance dependence and depression have reported data consistent with these findings. In a smoking cessation study, 9 of 15 participants (60%) had a “complete” mystical experience during one or more psilocybin session(s). (22) Results showed significant correlations between mean MEQ total scores assessed on session days and change from baseline in smoking craving scores (r = −0.65) and urine cotinine (r = −0.56) at the 6-month follow-up. Further, those participants who showed stronger mystical experiences on psilocybin sessions were more likely to be successful in biologically assessed smoking abstinence. In a psilocybin study in 20 patients with treatment-resistant depression, a measure assessing oceanic boundlessness (a construct related to mystical experience) on session days correlated with reductions in depression and was a significantly better predictor than subjective measures assessing visual or auditory alterations. (23) Finally, in a psilocybin study in 24 patients with major depressive disorder there was a moderate correlation (r = −0.41) between peak postsession mystical experience ratings and decreases in depression, but no such correlation with postsession challenging experience ratings, thus again suggesting some specificity to mystical-type experiences. (9)
In addition to mystical-type experiences, meaningful insights and belief changes are also frequently cited as fundamentally important to enduring positive outcomes in anecdotal descriptions of psychedelic treatments. For example, in a study of successful smoking cessation after psilocybin treatment, participants reported gaining vivid insights into self-identity and reasons for smoking along with strengthened belief that they had the ability remain abstinent. (8,15) In a double-blind study comparing psilocybin and dextromethorphan, psychological or personal insight rated after sessions increased as a function of psilocybin dose and was identified as an important domain associated with motivation to use psilocybin. (24) Although experiences of insight may sometimes overlap with mystical-type experience, a statistical path analysis of cross-sectional survey data suggests that insightful and mystical experiences independently mediate positive therapeutic outcomes on depression, anxiety, and substance use after psychedelics. (25−27) A prospective survey study that assessed respondents before and after taking a psychedelic in a noncontrolled, naturalistic manner showed that a measure of “emotional breakthrough,” likely related to psychological insight, predicted well-being 2 weeks later after controlling for mystical and challenging types of experiences. (23) A recent open label study of psilocybin in depression (N = 24) showed a strong correlation (r = 0.60) between ratings of psychological insight the day after the session and decreases in depression 4 weeks later. (9)
Proposal for a Critical Test of the Relevance of Subjective Effects
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Although preliminary, the foregoing experimental observations make a case that some subjective effects occasioned by moderate to high doses of psychedelics play a key role in their enduring beneficial effects. It is our contention that the only definitive study to disprove the importance of such subjective effects would be one in which a psychedelic was administered to individuals who were rendered fully unconscious (e.g., via deep anesthesia) and who subsequently reported no memory for a psychedelic-like experience. Although we think it to be highly unlikely, if full and lasting therapeutic efficacy remained under these conditions, we would concede that the subjective effects are irrelevant.
Conclusion
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Based on the results from experimental studies of moderate to high dose psychedelics we believe that the case for subjective effects playing a major role in enduring beneficial effects is compelling. Across a number of studies, when the intensity of the subjective psychedelic effect is controlled, certain subjective effects predict desirable outcomes. Underlying neurobiological-based mechanisms are undoubtedly necessary but likely not sufficient to confer full beneficial effects. In the nonsubjective anesthesia test that we describe, we would not be surprised to see some therapeutic effects but that they would be of lower magnitude and/or more transient. We suspect that the proportion of the long-term beneficial outcomes that are mediated through subjective effects is substantial, accounting for the majority of the lasting beneficial effects of psychedelics. For an alternative perspective, please see a companion Viewpoint in this issue. (28)
Author Information
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- David B. Yaden - Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States; Center for Psychedelic and Consciousness Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, United States;
http://orcid.org/0000-0002-9604-6227
Acknowledgments
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We thank Chris Letheby (University of Western Australia), Albert Garcia-Romeu (Johns Hopkins University School of Medicine), Brian D. Earp (Yale University), Derek E. Anderson (Boston University), and Chaz Firestone (Johns Hopkins University) for their helpful comments and suggestions. Support for Drs. D. Yaden and Griffiths through the Johns Hopkins Center for Psychedelic and Consciousness Research was provided by Tim Ferriss, Matt Mullenweg, Blake Mycoskie, Craig Nerenberg, and the Steven and Alexandra Cohen Foundation.
References
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This article references 28 other publications.
- 1Nichols, D. E. (2018) (2016). Psychedelics. Pharmacol. Rev. 68 (2), 264– 355, DOI: 10.1124/pr.115.011478Google ScholarThere is no corresponding record for this reference.
- 2Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F., Bäbler, A., Vogel, H., and Hell, D. (1998) Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. NeuroReport 9 (17), 3897– 3902, DOI: 10.1097/00001756-199812010-00024Google Scholar3Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2A agonist actionVollenweider, Franz X.; Vollenweider-Scherpenhuyzen, Margreet F. I.; Babler, Andreas; Vogel, Helen; Hell, DanielNeuroReport (1998), 9 (17), 3897-3902CODEN: NERPEZ; ISSN:0959-4965. (Lippincott Williams & Wilkins)Psilocybin, an indoleamine hallucinogen, produces a psychosis-like syndrome in humans that resembles first episodes of schizophrenia. In healthy human volunteers, the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone but were increased by the dopamine antagonist and typical antipsychotic haloperidol. These data are consistent with animal studies and provide the first evidence in humans that psilocybin-induced psychosis is due to serotonin-2A receptor activation, independently of dopamine stimulation. Thus, serotonin-2A overactivity may be involved in the pathophysiol. of schizophrenia and serotonin-2A antagonism may contribute to therapeutic effects of antipsychotics.
- 3Johnson, M. W., Hendricks, P. S., Barrett, F. S., and Griffiths, R. R. (2019) Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacol. Ther. 197, 83– 102, DOI: 10.1016/j.pharmthera.2018.11.010Google Scholar4Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network functionJohnson, Matthew W.; Hendricks, Peter S.; Barrett, Frederick S.; Griffiths, Roland R.Pharmacology & Therapeutics (2019), 197 (), 83-102CODEN: PHTHDT; ISSN:0163-7258. (Elsevier)The purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are serotonin 2A receptor (5-HT2AR) agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been administered as sacraments since ancient times. They were of prominent interest within psychiatry and neuroscience in the 1950s to 1960s, and during this time contributed to the emergence of the field of mol. neuroscience. Promising results were reported for treatment of both end-of-life psychol. distress and addiction, and classic psychedelics served as tools for studying the neurobiol. bases of psychol. disorders. Moreover, classic psychedelics were shown to occasion mystical experiences, which are subjective experiences reported throughout different cultures and religions involving a strong sense of unity, among other characteristics. However, the recreational use of classic psychedelics and their assocn. with the counterculture prompted an end to human research with classic psychedelics in the early 1970s. We provide the most comprehensive review of epidemiol. studies of classic psychedelics to date. Notable among these are a no. of studies that have suggested the possibility that nonmedical naturalistic (non-lab.) use of classic psychedelics is assocd. with pos. mental health and prosocial outcomes, although it is clear that some individuals are harmed by classic psychedelics in non-supervised settings. We then review recent therapeutic studies suggesting efficacy in treating psychol. distress assocd. with life-threatening diseases, treating depression, and treating nicotine and alc. addictions. We also describe the construct of mystical experience, and provide a comprehensive review of modern studies investigating classic psychedelic-occasioned mystical experiences and their consequences. These studies have shown classic psychedelics to fairly reliably occasion mystical experiences. Moreover, classic-psychedelic-occasioned mystical experiences are assocd. with improved psychol. outcomes in both healthy volunteer and patient populations. Finally, we review neuroimaging studies that suggest neurobiol. mechanisms of classic psychedelics. These studies have also broadened our understanding of the brain, the serotonin system, and the neurobiol. basis of consciousness. Overall, these various lines of research suggest that classic psychedelics might hold strong potential as therapeutics, and as tools for exptl. investigating mystical experiences and behavioral-brain function more generally.
- 4Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A., Wilcox, C. E., Barbosa, P. C. R., and Strassman, R. J. (2015) Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J. Psychopharmacol. 29 (3), 289– 299, DOI: 10.1177/0269881114565144Google Scholar5Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept studyBogenschutz, Michael P.; Forcehimes, Alyssa A.; Pommy, Jessica A.; Wilcox, Claire E.; Barbosa, P. C. R.; Strassman, Rick J.Journal of Psychopharmacology (London, United Kingdom) (2015), 29 (3), 289-299CODEN: JOPSEQ; ISSN:0269-8811. (Sage Publications Ltd.)Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clin. relevant effects in alc. and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alc. dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alc.-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alc. dependence received orally administered psilocybin in one or two supervised sessions in addn. to Motivational Enhancement Therapy and therapy sessions devoted to prepn. for and debriefing from the psilocybin sessions. Participants' responses to psilocybin were qual. similar to those described in other populations. Abstinence did not increase significantly in the first 4 wk of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 wk. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5-8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms.
- 5Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., Cosimano, M. P., and Klinedinst, M. A. (2016) Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J. Psychopharmacol. 30 (12), 1181– 1197, DOI: 10.1177/0269881116675513Google Scholar6Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trialGriffiths, Roland R.; Johnson, Matthew W.; Carducci, Michael A.; Umbricht, Annie; Richards, William A.; Richards, Brian D.; Cosimano, Mary P.; Klinedinst, Margaret A.Journal of Psychopharmacology (London, United Kingdom) (2016), 30 (12), 1181-1197CODEN: JOPSEQ; ISSN:0269-8811. (Sage Publications Ltd.)Cancer patients often develop chronic, clin. significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 wk between sessions and a 6-mo follow-up. Instructions to participants and staff minimized expectancy effects. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-mo follow-up, these changes were sustained, with about 80% of participants continuing to show clin. significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.
- 6Ross, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., Mennenga, S. E, Belser, A., Kalliontzi, K., Babb, J., Su, Z., Corby, P., and Schmidt, B. L (2016) Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J. Psychopharmacol. 30 (12), 1165– 1180, DOI: 10.1177/0269881116675512Google Scholar7Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trialRoss, Stephen; Bossis, Anthony; Guss, Jeffrey; Agin-Liebes, Gabrielle; Malone, Tara; Cohen, Barry; Mennenga, Sarah E.; Belser, Alexander; Kalliontzi, Krystallia; Babb, James; Su, Zhe; Corby, Patricia; Schmidt, Brian L.Journal of Psychopharmacology (London, United Kingdom) (2016), 30 (12), 1165-1180CODEN: JOPSEQ; ISSN:0269-8811. (Sage Publications Ltd.)Background: Clin. significant anxiety and depression are common in patients with cancer, and are assocd. with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. Methods: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 wk. Results: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-mo follow-up, psilocybin was assocd. with enduring anxiolytic and anti-depressant effects (approx. 60-80% of participants continued with clin. significant redns. in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. Conclusions: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychol. distress.
- 7Carhart-Harris, R. L, Bolstridge, M., Rucker, J., Day, C. M J, Erritzoe, D., Kaelen, M., Bloomfield, M., Rickard, J. A, Forbes, B., Feilding, A., Taylor, D., Pilling, S., Curran, V. H, and Nutt, D. J (2016) Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry 3 (7), 619– 627, DOI: 10.1016/S2215-0366(16)30065-7Google Scholar8Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility studyCarhart-Harris Robin L; Bolstridge Mark; Day Camilla M J; Erritzoe David; Kaelen Mendel; Nutt David J; Rucker James; Bloomfield Michael; Rickard James A; Forbes Ben; Feilding Amanda; Taylor David; Pilling Steve; Curran Valerie HThe lancet. Psychiatry (2016), 3 (7), 619-27 ISSN:.BACKGROUND: Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. METHODS: In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797. FINDINGS: Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference -11·8, 95% CI -9·15 to -14·35, p=0·002, Hedges' g=3·1) and 3 months (-9·2, 95% CI -5·69 to -12·71, p=0·003, Hedges' g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted. INTERPRETATION: This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach. FUNDING: Medical Research Council.
- 8Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P., and Griffiths, R. R. (2014) Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J. Psychopharmacol. 28 (11), 983– 992, DOI: 10.1177/0269881114548296Google Scholar9Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addictionJohnson, Matthew W.; Garcia-Romeu, Albert; Cosimano, Mary P.; Griffiths, Roland R.Journal of Psychopharmacology (London, United Kingdom) (2014), 28 (11), 983-992, 10 pp.CODEN: JOPSEQ; ISSN:0269-8811. (Sage Publications Ltd.)Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To det. the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-wk smoking cessation treatment protocol. Participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. Biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-mo follow-up. The obsd. smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacol. therapies (typically <35%). Although the open-label design does not allow for definitive conclusions regarding the efficacy of psilocybin, these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models. The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction.
- 9Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., and Griffiths, R. R. Effects of psilocybin-assisted therapy for major depressive disorder: A randomized clinical trial. JAMA Psychiatry , 2020, online. DOI: 10.1001/jamapsychiatry.2020.3285Google ScholarThere is no corresponding record for this reference.
- 10Hibicke, M., Landry, A. N., Kramer, H. M., Talman, Z. K., and Nichols, C. D. (2020) Psychedelics, but not ketamine, produce persistent antidepressant-like effects in a rodent experimental system for the study of depression. ACS Chem. Neurosci. 11 (6), 864– 871, DOI: 10.1021/acschemneuro.9b00493Google Scholar11Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of DepressionHibicke, Meghan; Landry, Alexus N.; Kramer, Hannah M.; Talman, Zoe K.; Nichols, Charles D.ACS Chemical Neuroscience (2020), 11 (6), 864-871CODEN: ACNCDM; ISSN:1948-7193. (American Chemical Society)Psilocybin shows efficacy to alleviate depression in human clin. trials for six or more months after only one or two treatments. Another hallucinogenic drug, esketamine, has recently been U.S. Food and Drug Administration (FDA)-approved as a rapid-acting antidepressant. The mechanistic basis for the antidepressant effects of psilocybin and ketamine appear to be conserved. The efficacy of these two medications has not, however, been directly compared either clin. or preclinically. Further, whether or not a profound subjective existential experience is necessary for psilocybin to have antidepressant effects is unknown. To address these questions, we tested psilocybin, lysergic acid diethylamide (LSD), and ketamine in a rat model for depression. As in humans, a single administration of psilocybin or LSD produced persistent antidepressant-like effects in our model. In contrast, ketamine produced only a transient antidepressant-like effect. Our results indicate that classic psychedelics may have therapeutic efficacy that is more persistent than that of ketamine, and also suggest that a subjective existential experience may not be necessary for therapeutic effects.
- 11Ly, C., Greb, A. C., Cameron, L. P., Wong, J. M., Barragan, E. V., Wilson, P. C., Burbach, K. F., Soltanzadeh Zarandi, S., Sood, A., Paddy, M. R., Duim, W. C., Dennis, M. Y., McAllister, A. K., Ori-McKenney, K. M., Gray, J. A., and Olson, D. E. (2018) Psychedelics promote structural and functional neural plasticity. Cell Rep. 23 (11), 3170– 3182, DOI: 10.1016/j.celrep.2018.05.022Google Scholar12Psychedelics Promote Structural and Functional Neural PlasticityLy, Calvin; Greb, Alexandra C.; Cameron, Lindsay P.; Wong, Jonathan M.; Barragan, Eden V.; Wilson, Paige C.; Burbach, Kyle F.; Soltanzadeh Zarandi, Sina; Sood, Alexander; Paddy, Michael R.; Duim, Whitney C.; Dennis, Megan Y.; McAllister, A. Kimberley; Ori-McKenney, Kassandra M.; Gray, John A.; Olson, David E.Cell Reports (2018), 23 (11), 3170-3182CODEN: CREED8; ISSN:2211-1247. (Cell Press)Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiol. of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse no. and function, as measured by fluorescence microscopy and electrophysiol. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clin. effectiveness of these compds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chem. efforts focused on developing plasticity-promoting compds. as safe, effective, and fast-acting treatments for depression and related disorders.
- 12Carhart-Harris, R. L. (2018) The entropic brain-revisited. Neuropharmacology 142, 167– 178, DOI: 10.1016/j.neuropharm.2018.03.010Google Scholar13The entropic brain - revisitedCarhart-Harris, Robin L.Neuropharmacology (2018), 142 (), 167-178CODEN: NEPHBW; ISSN:0028-3908. (Elsevier B.V.)The entropic brain hypothesis proposes that within upper and lower limits, after which consciousness may be lost, the entropy of spontaneous brain activity indexes the informational richness of conscious states. Here the hypothesis is revisited four years on from its original publication. It is shown that the principle that the entropy of brain activity is elevated in the psychedelic state is increasingly well supported by sep. and independent studies and analyses, and evidence for greater brain criticality under psychedelics is also highlighted. It is argued that heightened brain criticality enables the brain to be more sensitive to intrinsic and extrinsic perturbations which may translate as a heightened susceptibility to "set" and "setting". This updated version of the original entropic brain hypothesis now offers more concrete information on specific measures of brain entropy and suggests new studies to scrutinise it further, as well as examine its utility for describing and informing the treatment of psychiatric and neurol. conditions such as depression and disorders of consciousness.
- 13Schultes, R. E. (1969) Hallucinogens of plant origin. Science 163, 245, DOI: 10.1126/science.163.3864.245Google Scholar14Hallucinogens of plant originSchultes R EScience (New York, N.Y.) (1969), 163 (3864), 245-54 ISSN:0036-8075.There is no expanded citation for this reference.
- 14Belser, A. B., Agin-Liebes, G., Swift, T. C., Terrana, S., Devenot, N., Friedman, H. L., Guss, J., Bossis, A., and Ross, S. (2017) Patient experiences of psilocybin-assisted psychotherapy: an interpretative phenomenological analysis. J. Humanist Psychol 57 (4), 354– 388, DOI: 10.1177/0022167817706884Google ScholarThere is no corresponding record for this reference.
- 15Noorani, T., Garcia-Romeu, A., Swift, T. C., Griffiths, R. R., and Johnson, M. W. (2018) Psychedelic therapy for smoking cessation: qualitative analysis of participant accounts. J. Psychopharmacol. 32 (7), 756– 769, DOI: 10.1177/0269881118780612Google Scholar16Psychedelic therapy for smoking cessation: Qualitative analysis of participant accountsNoorani Tehseen; Noorani Tehseen; Garcia-Romeu Albert; Swift Thomas C; Griffiths Roland R; Johnson Matthew W; Swift Thomas C; Swift Thomas C; Griffiths Roland RJournal of psychopharmacology (Oxford, England) (2018), 32 (7), 756-769 ISSN:.BACKGROUND: Recent pilot trials suggest feasibility and potential efficacy of psychedelic-facilitated addiction treatment interventions. Fifteen participants completed a psilocybin-facilitated smoking cessation pilot study between 2009 and 2015. AIMS: The aims of this study were as follows: (1) to identify perceived mechanisms of change leading to smoking cessation in the pilot study; (2) to identify key themes in participant experiences and long-term outcomes to better understand the therapeutic process. METHODS: Participants were invited to a retrospective follow-up interview an average of 30 months after initial psilocybin sessions. Semi-structured interviews were conducted with 12 of the 15 participants. Data were analysed using thematic analysis. RESULTS: Participants reported gaining vivid insights into self-identity and reasons for smoking from their psilocybin sessions. Experiences of interconnectedness, awe, and curiosity persisted beyond the duration of acute drug effects. Participants emphasised that the content of psilocybin experiences overshadowed any short-term withdrawal symptoms. Preparatory counselling, strong rapport with the study team, and a sense of momentum once engaged in the study treatment were perceived as vital additional factors in achieving abstinence. In addition, participants reported a range of persisting positive changes beyond smoking cessation, including increased aesthetic appreciation, altruism, and pro-social behaviour. CONCLUSIONS: The findings highlight the value of qualitative research in the psychopharmacological investigation of psychedelics. They describe perceived connections between drug- and non-drug factors, and provide suggestions for future research trial design and clinical applications.
- 16Griffiths, R. R., Richards, W. A., McCann, U., and Jesse, R. (2006) Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology 187 (3), 268– 283, DOI: 10.1007/s00213-006-0457-5Google Scholar17Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significanceGriffiths, R. R.; Richards, W. A.; McCann, U.; Jesse, R.Psychopharmacology (Berlin, Germany) (2006), 187 (3), 268-283CODEN: PSCHDL; ISSN:0033-3158. (Springer GmbH)Rationale Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects. Objectives This double-blind study evaluated the acute and longer-term psychol. effects of a high dose of psilocybin relative to a comparison compd. administered under comfortable, supportive conditions. Materials and methods The participants were hallucinogen-naive adults reporting regular participation in religious or spiritual activities. Two or three sessions were conducted at 2-mo intervals. Thirty volunteers received orally administered psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) in counterbalanced order. To obscure the study design, six addnl. volunteers received methylphenidate in the first two sessions and unblinded psilocybin in a third session. The 8-h sessions were conducted individually. Volunteers were encouraged to close their eyes and direct their attention inward. Study monitors rated volunteers' behavior during sessions. Volunteers completed questionnaires assessing drug effects and mystical experience immediately after and 2 mo after sessions. Community observers rated changes in the volunteer's attitudes and behavior. Results Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 mo, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained pos. changes in attitudes and behavior consistent with changes rated by community observers. Conclusions When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences. The ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.
- 17Griffiths, R. R., Richards, W. A., Johnson, M. W., McCann, U. D., and Jesse, R. (2008) Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J. Psychopharmacol. 22 (6), 621– 632, DOI: 10.1177/0269881108094300Google Scholar18Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months laterGriffiths, R. R.; Richards, W. A.; Johnson, M. W.; McCann, U. D.Journal of Psychopharmacology (London, United Kingdom) (2008), 22 (6), 621-632CODEN: JOPSEQ; ISSN:0269-8811. (Sage Publications Ltd.)Psilocybin has been used for centuries for religious purposes; however, little is known scientifically about its long-term effects. We previously reported the effects of a double-blind study evaluating the psychol. effects of a high psilocybin dose. This report presents the 14-mo follow-up and examines the relationship of the follow-up results to data obtained at screening and on drug session days. Participants were 36 hallucinogen-naive adults reporting regular participation in religious/spiritual activities. Oral psilocybin (30 mg/70 kg) was administered on one of two or three sessions, with methylphenidate (40 mg/70 kg) administered on the other session(s). During sessions, volunteers were encouraged to close their eyes and direct their attention inward. At the 14-mo follow-up, 58% and 67%, resp., of volunteers rated the psilocybin-occasioned experience as being among the five most personally meaningful and among the five most spiritually significant experiences of their lives; 64% indicated that the experience increased well-being or life satisfaction; 58% met criteria for having had a "complete" mystical experience. Correlation and regression analyses indicated a central role of the mystical experience assessed on the session day in the high ratings of personal meaning and spiritual significance at follow-up. Of the measures of personality, affect, quality of life and spirituality assessed across the study, only a scale measuring mystical experience showed a difference from screening. When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences that, at 14-mo follow-up, were considered by volunteers to be among the most personally meaningful and spiritually significant of their lives.
- 18Griffiths, R. R., Johnson, M. W., Richards, W. A., Richards, B. D., McCann, U., and Jesse, R. (2011) Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology 218 (4), 649– 665, DOI: 10.1007/s00213-011-2358-5Google Scholar19Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effectsGriffiths, Roland R.; Johnson, Matthew W.; Richards, William A.; Richards, Brian D.; McCann, Una; Jesse, RobertPsychopharmacology (Heidelberg, Germany) (2011), 218 (4), 649-665CODEN: PSCHDL; ISSN:0033-3158. (Springer)Rationale: This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting pos. effects on attitudes, mood, and behavior. Objectives: This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions. Methods: Participants were 18 adults (17 hallucinogen-naive). Five 8-h sessions were conducted individually for each participant at 1-mo intervals. Participants were randomized to receive the four active doses in either ascending or descending order (nine participants each). Placebo was scheduled quasi-randomly. During sessions, volunteers used eyeshades and were instructed to direct their attention inward. Volunteers completed questionnaires assessing effects immediately after and 1 mo after each session, and at 14 mo follow-up. Results: Psilocybin produced acute perceptual and subjective effects including, at 20 and/or 30 mg/70 kg, extreme anxiety/fear (39% of volunteers) and/or mystical-type experience (72% of volunteers). One month after sessions at the two highest doses, volunteers rated the psilocybin experience as having substantial personal and spiritual significance, and attributed to the experience sustained pos. changes in attitudes, mood, and behavior, with the ascending dose sequence showing greater pos. effects. At 14 mo, ratings were undiminished and were consistent with changes rated by community observers. Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose, with the lowest dose showing significant effects. Conclusions: Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting pos. effects on attitudes, mood, and behavior. Implications for therapeutic trials are discussed.
- 19Griffiths, R. R., Johnson, M. W., Richards, W. A., Richards, B. D., Jesse, R., MacLean, K. A., Barrett, F. S., Cosimano, M. P., and Klinedinst, M. A. (2018) Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors. J. Psychopharmacol. 32 (1), 49– 69, DOI: 10.1177/0269881117731279Google Scholar20Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviorsGriffiths, Roland R.; Johnson, Matthew W.; Richards, William A.; Richards, Brian D.; Jesse, Robert; MacLean, Katherine A.; Barrett, Frederick S.; Cosimano, Mary P.; Klinedinst, Maggie A.Journal of Psychopharmacology (London, United Kingdom) (2018), 32 (1), 49-69CODEN: JOPSEQ; ISSN:0269-8811. (Sage Publications Ltd.)Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examd. enduring changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were randomized to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2) with moderate-level ("std.") support for spiritual-practice (LD-SS); (2) high-dose (20 and 30 mg/70 kg on sessions 1 and 2, resp.) with std. support (HD-SS); and (3) high-dose (20 and 30 mg/70kg on sessions 1 and 2, resp.) with high support for spiritual practice (HD-HS). Psilocybin was administered double-blind and instructions to participants/staff minimized expectancy confounds. Psilocybin was administered 1 and 2 mo after spiritual-practice initiation. Outcomes at 6 mo included rates of spiritual practice and persisting effects of psilocybin. Compared with low-dose, high-dose psilocybin produced greater acute and persisting effects. At 6 mo, compared with LD-SS, both high-dose groups showed large significant pos. changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings. Determinants of enduring effects were psilocybin-occasioned mystical-type experience and rates of meditation/spiritual practices. Psilocybin can occasion enduring trait-level increases in prosocial attitudes/behaviors and in healthy psychol. functioning. Trial Registration ClinicalTrials.gov Identifier NCT00802282.
- 20Yaden, D. B., Haidt, J., Hood, R. W., Jr, Vago, D. R., and Newberg, A. B. (2017) The varieties of self-transcendent experience. Rev. Gen Psychol 21 (2), 143– 160, DOI: 10.1037/gpr0000102Google ScholarThere is no corresponding record for this reference.
- 21Barrett, F. S., Johnson, M. W., and Griffiths, R. R. (2015) Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin. J. Psychopharmacol. 29 (11), 1182– 1190, DOI: 10.1177/0269881115609019Google Scholar22Validation of the revised mystical experience questionnaire in experimental sessions with psilocybinBarrett, Frederick S.; Johnson, Matthew W.; Griffiths, Roland R.Journal of Psychopharmacology (London, United Kingdom) (2015), 29 (11), 1182-1190CODEN: JOPSEQ; ISSN:0269-8811. (Sage Publications Ltd.)The 30-item revised Mystical Experience Questionnaire (MEQ30) was previously developed within an online survey of mystical-type experiences occasioned by psilocybin-contg. mushrooms. The rated experiences occurred on av. eight years before completion of the questionnaire. The current paper validates the MEQ30 using data from exptl. studies with controlled doses of psilocybin. Data were pooled and analyzed from five lab. expts. in which participants (n = 184) received a moderate to high oral dose of psilocybin (at least 20 mg/70 kg). Results of confirmatory factor anal. demonstrate the reliability and internal validity of the MEQ30. Structural equation models demonstrate the external and convergent validity of the MEQ30 by showing that latent variable scores on the MEQ30 pos. predict persisting change in attitudes, behavior, and well-being attributed to experiences with psilocybin while controlling for the contribution of the participant-rated intensity of drug effects. These findings support the use of the MEQ30 as an efficient measure of individual mystical experiences. A method to score a "complete mystical experience" that was used in previous versions of the mystical experience questionnaire is validated in the MEQ30, and a stand-alone version of the MEQ30 is provided for use in future research.
- 22Garcia-Romeu, A., Griffiths, R., and Johnson, M. (2015) Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Curr. Drug Abuse Rev. 7 (3), 157– 164, DOI: 10.2174/1874473708666150107121331Google ScholarThere is no corresponding record for this reference.
- 23Roseman, L., Nutt, D. J., and Carhart-Harris, R. L. (2018) Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression. Front. Pharmacol. 8, 974, DOI: 10.3389/fphar.2017.00974Google ScholarThere is no corresponding record for this reference.
- 24Carbonaro, T. M., Johnson, M. W., and Griffiths, R. R. (2020) Subjective features of the psilocybin experience that may account for its self-administration by humans: A double-blind comparison of psilocybin and dextromethorphan. Psychopharmacology 237, 2293– 2304, DOI: 10.1007/s00213-020-05533-9Google Scholar25Subjective features of the psilocybin experience that may account for its self-administration by humans: a double-blind comparison of psilocybin and dextromethorphanCarbonaro, Theresa M.; Johnson, Matthew W.; Griffiths, Roland R.Psychopharmacology (Heidelberg, Germany) (2020), 237 (8), 2293-2304CODEN: PSCHDL; ISSN:0033-3158. (Springer)Objective: New data are presented from a study of psilocybin and DXM relevant to understanding the features of psilocybin subjective effects that may account for its higher rates of non-medical use. Methods: Single, acute oral doses of psilocybin (10, 20, 30 mg/70 kg), DXM (400 mg/70 kg), and placebo were administered under double-blind conditions to 20 healthy participants with histories of hallucinogen use. Results: High doses of both drugs produced similar time courses and increases in participant ratings of peak overall drug effect strength. Nine subjective effect domains are proposed to be related to the reinforcing effects of psilocybin: liking, visual effects, pos. mood, insight, pos. social effects, increased awareness of beauty (both visual and music), awe/amazement, meaningfulness, and mystical experience. For most ratings, (1) psilocybin and DXM both produced effects significantly greater than placebo; (2) psilocybin showed dose-related increases; 3, DXM was never significantly higher than psilocybin; (4) the two highest psilocybin doses were significantly greater than DXM. Conclusions: This anal. provides new information about domains of psilocybin subjective effects proposed to be related to its reinforcing effects (alternatively described as the "motivation" to use). Obsd. differences on these domains between psilocybin and DXM are consistent with the relative rates of non-medical use of psilocybin and DXM.
- 25Garcia-Romeu, A., Davis, A. K., Erowid, F., Erowid, E., Griffiths, R. R., and Johnson, M. W. (2019) Cessation and reduction in alcohol consumption and misuse after psychedelic use. J. Psychopharmacol. 33 (9), 1088– 1101, DOI: 10.1177/0269881119845793Google Scholar26Cessation and reduction in alcohol consumption and misuse after psychedelic useGarcia-Romeu Albert; Davis Alan K; Griffiths Roland R; Johnson Matthew W; Erowid Fire; Erowid Earth; Griffiths Roland RJournal of psychopharmacology (Oxford, England) (2019), 33 (9), 1088-1101 ISSN:.BACKGROUND: Meta-analysis of randomized studies using lysergic acid diethylamide (LSD) for alcohol use disorder (AUD) showed large, significant effects for LSD efficacy compared to control conditions. Clinical studies suggest potential anti-addiction effects of LSD and mechanistically-related classic psychedelics for alcohol and other substance use disorders. AIMS: To supplement clinical studies, reports of psychedelic use in naturalistic settings can provide further data regarding potential effects of psychedelics on alcohol use. METHODS: An anonymous online survey of individuals with prior AUD reporting cessation or reduction in alcohol use following psychedelic use in non-clinical settings. RESULTS: 343 respondents, mostly White (89%), males (78%), in the USA (60%) completed the survey. Participants reported seven years of problematic alcohol use on average before the psychedelic experience to which they attributed reduced alcohol consumption, with 72% meeting retrospective criteria for severe AUD. Most reported taking a moderate or high dose of LSD (38%) or psilocybin (36%), followed by significant reduction in alcohol consumption. After the psychedelic experience 83% no longer met AUD criteria. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced alcohol misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with a greater reduction in alcohol consumption, controlling for prior alcohol consumption and related distress. CONCLUSIONS: Although results cannot demonstrate causality, they suggest that naturalistic psychedelic use may lead to cessation or reduction in problematic alcohol use, supporting further investigation of psychedelic-assisted treatment for AUD.
- 26Garcia-Romeu, A., Davis, A. K., Erowid, E., Erowid, F., Griffiths, R. R., and Johnson, M. W. (2020) Persisting reductions in cannabis, opioid, and stimulant misuse after naturalistic psychedelic use: An online survey. Front Pharmacol 10, 955, DOI: 10.3389/fpsyt.2019.00955Google ScholarThere is no corresponding record for this reference.
- 27Davis, A. K., Barrett, F. S., and Griffiths, R. R. (2020) Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety. J. Contextual Behav Sci. 15, 39– 45, DOI: 10.1016/j.jcbs.2019.11.004Google Scholar28Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxietyDavis Alan K; Davis Alan K; Barrett Frederick S; Griffiths Roland R; Griffiths Roland RJournal of contextual behavioral science (2020), 15 (), 39-45 ISSN:2212-1447.Prior research has shown that acute subjective psychedelic effects are associated with both spontaneous and intended changes in depression and anxiety. Psychedelics are also theorized to produce increases in psychological flexibility, which could explain decreases in depression and anxiety following a psychedelic experience. Therefore, the present cross-sectional survey study sought to examine whether psychological flexibility mediated the relationship between acute psychedelic experiences and spontaneous or intended changes in depression and anxiety among a large international sample of people who reported having used a psychedelic (n=985; male=71.6%; Caucasian/white=84.1%; Mage=32.2, SD=12.6). A regression analysis showed that acute effects (i.e., mystical and insightful effects) were significantly associated with decreases in depression/anxiety following a psychedelic experience. A path analysis revealed that, while controlling for age and sex, increases in psychological flexibility fully mediated the effect of mystical and insightful experiences on decreases in depression and anxiety following a psychedelic experience. This suggests that psychological flexibility may be an important mediator of the therapeutic effects of psychedelic drugs. Future prospective experimental studies should examine the effect of psychedelic drug administration on psychological flexibility in order to gain a better understanding of the psychological processes that predict therapeutic effects of psychedelics.
- 28Olson, D. The Subjective Effects of Psychedelics May Not Be Necessary for Their Therapeutic Impact. ACS Pharm. Transl. Sci. 2020 DOI: 10.1021/acsptsci.0c00192 .Google ScholarThere is no corresponding record for this reference.
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- Rúna F. E. Walther, Hein T. van Schie. ‘Mind-Revealing’ Psychedelic States: Psychological Processes in Subjective Experiences That Drive Positive Change. Psychoactives 2024, 3
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- Emiliano Loria, Elisabetta Lalumera, Ambra D’Imperio. Psilocybin, moralization and psychotherapy: a scoping review and a case report. Philosophical Psychology 2024, 22 , 1-21. https://doi.org/10.1080/09515089.2024.2389962
- David Wyndham Lawrence, Alex P DiBattista, Christopher Timmermann. N, N-Dimethyltryptamine (DMT)-Occasioned Familiarity and the Sense of Familiarity Questionnaire (SOF-Q). Journal of Psychoactive Drugs 2024, 56
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- Alan K. Davis, Christopher Timmermann, Ana Maria Ortiz Bernal, Rafaelle Lancelotta, Sandeep Nayak, Nathan D. Sepeda, Aki Nikolaidis, Roland R. Griffiths. Translation and Initial Psychometric Evaluation of Spanish Versions of Three Psychedelic Acute Effects Measures: Mystical, Challenging, and Insight Experiences. Journal of Psychoactive Drugs 2024, 56
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Abstract
Figure 1
Figure 1. Left panel shows data from a study (N = 15) of psilocybin on cigarette smoking cessation (replotted from Garcia et al. (22)). Smoking craving data are change scores from pretreatment to the 6-month follow-up. Mystical experience data for each participant are the mean total score on the 43-item version of the Mystical Experience Questionnaire (expressed as a percentage of the maximum possible score) assessed at the end of each of 2 or 3 psilocybin sessions. The middle panel shows data from a study (N = 24) of psilocybin on depression (adapted from Davis et al. (9)). Depression was measured with GRID-Hamilton Depression Rating Scale and expressed as change scores from pretreatment to 4 weeks after the second psilocybin session. Mystical experience data for each participant are the highest of two total scores on the 30-item Mystical Experience Questionnaire (expressed as a percentage of the maximum possible score) assessed at the end of each of two psilocybin sessions. The right panel shows data from a study of (N = 50) of individuals with a life-threatening cancer diagnosis who received either a very low dose or a moderately high dose of psilocybin (Griffiths et al. (5)). Mystical experience data for each participant are the total score on the 30-item Mystical Experience Questionnaire (expressed as a percentage of the maximum possible score) assessed at the end of the first psilocybin session. Anxiety was measured with the Hamilton Anxiety Rating Scale and expressed as a change score from baseline to 5 weeks postsession. More details regarding these images can be found in the citations above describing the original studies.
References
This article references 28 other publications.
- 1Nichols, D. E. (2018) (2016). Psychedelics. Pharmacol. Rev. 68 (2), 264– 355, DOI: 10.1124/pr.115.011478There is no corresponding record for this reference.
- 2Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F., Bäbler, A., Vogel, H., and Hell, D. (1998) Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. NeuroReport 9 (17), 3897– 3902, DOI: 10.1097/00001756-199812010-000243Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2A agonist actionVollenweider, Franz X.; Vollenweider-Scherpenhuyzen, Margreet F. I.; Babler, Andreas; Vogel, Helen; Hell, DanielNeuroReport (1998), 9 (17), 3897-3902CODEN: NERPEZ; ISSN:0959-4965. (Lippincott Williams & Wilkins)Psilocybin, an indoleamine hallucinogen, produces a psychosis-like syndrome in humans that resembles first episodes of schizophrenia. In healthy human volunteers, the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone but were increased by the dopamine antagonist and typical antipsychotic haloperidol. These data are consistent with animal studies and provide the first evidence in humans that psilocybin-induced psychosis is due to serotonin-2A receptor activation, independently of dopamine stimulation. Thus, serotonin-2A overactivity may be involved in the pathophysiol. of schizophrenia and serotonin-2A antagonism may contribute to therapeutic effects of antipsychotics.
- 3Johnson, M. W., Hendricks, P. S., Barrett, F. S., and Griffiths, R. R. (2019) Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacol. Ther. 197, 83– 102, DOI: 10.1016/j.pharmthera.2018.11.0104Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network functionJohnson, Matthew W.; Hendricks, Peter S.; Barrett, Frederick S.; Griffiths, Roland R.Pharmacology & Therapeutics (2019), 197 (), 83-102CODEN: PHTHDT; ISSN:0163-7258. (Elsevier)The purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are serotonin 2A receptor (5-HT2AR) agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been administered as sacraments since ancient times. They were of prominent interest within psychiatry and neuroscience in the 1950s to 1960s, and during this time contributed to the emergence of the field of mol. neuroscience. Promising results were reported for treatment of both end-of-life psychol. distress and addiction, and classic psychedelics served as tools for studying the neurobiol. bases of psychol. disorders. Moreover, classic psychedelics were shown to occasion mystical experiences, which are subjective experiences reported throughout different cultures and religions involving a strong sense of unity, among other characteristics. However, the recreational use of classic psychedelics and their assocn. with the counterculture prompted an end to human research with classic psychedelics in the early 1970s. We provide the most comprehensive review of epidemiol. studies of classic psychedelics to date. Notable among these are a no. of studies that have suggested the possibility that nonmedical naturalistic (non-lab.) use of classic psychedelics is assocd. with pos. mental health and prosocial outcomes, although it is clear that some individuals are harmed by classic psychedelics in non-supervised settings. We then review recent therapeutic studies suggesting efficacy in treating psychol. distress assocd. with life-threatening diseases, treating depression, and treating nicotine and alc. addictions. We also describe the construct of mystical experience, and provide a comprehensive review of modern studies investigating classic psychedelic-occasioned mystical experiences and their consequences. These studies have shown classic psychedelics to fairly reliably occasion mystical experiences. Moreover, classic-psychedelic-occasioned mystical experiences are assocd. with improved psychol. outcomes in both healthy volunteer and patient populations. Finally, we review neuroimaging studies that suggest neurobiol. mechanisms of classic psychedelics. These studies have also broadened our understanding of the brain, the serotonin system, and the neurobiol. basis of consciousness. Overall, these various lines of research suggest that classic psychedelics might hold strong potential as therapeutics, and as tools for exptl. investigating mystical experiences and behavioral-brain function more generally.
- 4Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A., Wilcox, C. E., Barbosa, P. C. R., and Strassman, R. J. (2015) Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J. Psychopharmacol. 29 (3), 289– 299, DOI: 10.1177/02698811145651445Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept studyBogenschutz, Michael P.; Forcehimes, Alyssa A.; Pommy, Jessica A.; Wilcox, Claire E.; Barbosa, P. C. R.; Strassman, Rick J.Journal of Psychopharmacology (London, United Kingdom) (2015), 29 (3), 289-299CODEN: JOPSEQ; ISSN:0269-8811. (Sage Publications Ltd.)Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clin. relevant effects in alc. and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alc. dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alc.-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alc. dependence received orally administered psilocybin in one or two supervised sessions in addn. to Motivational Enhancement Therapy and therapy sessions devoted to prepn. for and debriefing from the psilocybin sessions. Participants' responses to psilocybin were qual. similar to those described in other populations. Abstinence did not increase significantly in the first 4 wk of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 wk. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5-8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms.
- 5Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., Cosimano, M. P., and Klinedinst, M. A. (2016) Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J. Psychopharmacol. 30 (12), 1181– 1197, DOI: 10.1177/02698811166755136Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trialGriffiths, Roland R.; Johnson, Matthew W.; Carducci, Michael A.; Umbricht, Annie; Richards, William A.; Richards, Brian D.; Cosimano, Mary P.; Klinedinst, Margaret A.Journal of Psychopharmacology (London, United Kingdom) (2016), 30 (12), 1181-1197CODEN: JOPSEQ; ISSN:0269-8811. (Sage Publications Ltd.)Cancer patients often develop chronic, clin. significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 wk between sessions and a 6-mo follow-up. Instructions to participants and staff minimized expectancy effects. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-mo follow-up, these changes were sustained, with about 80% of participants continuing to show clin. significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.
- 6Ross, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., Mennenga, S. E, Belser, A., Kalliontzi, K., Babb, J., Su, Z., Corby, P., and Schmidt, B. L (2016) Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J. Psychopharmacol. 30 (12), 1165– 1180, DOI: 10.1177/02698811166755127Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trialRoss, Stephen; Bossis, Anthony; Guss, Jeffrey; Agin-Liebes, Gabrielle; Malone, Tara; Cohen, Barry; Mennenga, Sarah E.; Belser, Alexander; Kalliontzi, Krystallia; Babb, James; Su, Zhe; Corby, Patricia; Schmidt, Brian L.Journal of Psychopharmacology (London, United Kingdom) (2016), 30 (12), 1165-1180CODEN: JOPSEQ; ISSN:0269-8811. (Sage Publications Ltd.)Background: Clin. significant anxiety and depression are common in patients with cancer, and are assocd. with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. Methods: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 wk. Results: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-mo follow-up, psilocybin was assocd. with enduring anxiolytic and anti-depressant effects (approx. 60-80% of participants continued with clin. significant redns. in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. Conclusions: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychol. distress.
- 7Carhart-Harris, R. L, Bolstridge, M., Rucker, J., Day, C. M J, Erritzoe, D., Kaelen, M., Bloomfield, M., Rickard, J. A, Forbes, B., Feilding, A., Taylor, D., Pilling, S., Curran, V. H, and Nutt, D. J (2016) Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry 3 (7), 619– 627, DOI: 10.1016/S2215-0366(16)30065-78Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility studyCarhart-Harris Robin L; Bolstridge Mark; Day Camilla M J; Erritzoe David; Kaelen Mendel; Nutt David J; Rucker James; Bloomfield Michael; Rickard James A; Forbes Ben; Feilding Amanda; Taylor David; Pilling Steve; Curran Valerie HThe lancet. Psychiatry (2016), 3 (7), 619-27 ISSN:.BACKGROUND: Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. METHODS: In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797. FINDINGS: Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference -11·8, 95% CI -9·15 to -14·35, p=0·002, Hedges' g=3·1) and 3 months (-9·2, 95% CI -5·69 to -12·71, p=0·003, Hedges' g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted. INTERPRETATION: This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach. FUNDING: Medical Research Council.
- 8Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P., and Griffiths, R. R. (2014) Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J. Psychopharmacol. 28 (11), 983– 992, DOI: 10.1177/02698811145482969Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addictionJohnson, Matthew W.; Garcia-Romeu, Albert; Cosimano, Mary P.; Griffiths, Roland R.Journal of Psychopharmacology (London, United Kingdom) (2014), 28 (11), 983-992, 10 pp.CODEN: JOPSEQ; ISSN:0269-8811. (Sage Publications Ltd.)Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To det. the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-wk smoking cessation treatment protocol. Participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. Biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-mo follow-up. The obsd. smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacol. therapies (typically <35%). Although the open-label design does not allow for definitive conclusions regarding the efficacy of psilocybin, these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models. The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction.
- 9Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., and Griffiths, R. R. Effects of psilocybin-assisted therapy for major depressive disorder: A randomized clinical trial. JAMA Psychiatry , 2020, online. DOI: 10.1001/jamapsychiatry.2020.3285There is no corresponding record for this reference.
- 10Hibicke, M., Landry, A. N., Kramer, H. M., Talman, Z. K., and Nichols, C. D. (2020) Psychedelics, but not ketamine, produce persistent antidepressant-like effects in a rodent experimental system for the study of depression. ACS Chem. Neurosci. 11 (6), 864– 871, DOI: 10.1021/acschemneuro.9b0049311Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of DepressionHibicke, Meghan; Landry, Alexus N.; Kramer, Hannah M.; Talman, Zoe K.; Nichols, Charles D.ACS Chemical Neuroscience (2020), 11 (6), 864-871CODEN: ACNCDM; ISSN:1948-7193. (American Chemical Society)Psilocybin shows efficacy to alleviate depression in human clin. trials for six or more months after only one or two treatments. Another hallucinogenic drug, esketamine, has recently been U.S. Food and Drug Administration (FDA)-approved as a rapid-acting antidepressant. The mechanistic basis for the antidepressant effects of psilocybin and ketamine appear to be conserved. The efficacy of these two medications has not, however, been directly compared either clin. or preclinically. Further, whether or not a profound subjective existential experience is necessary for psilocybin to have antidepressant effects is unknown. To address these questions, we tested psilocybin, lysergic acid diethylamide (LSD), and ketamine in a rat model for depression. As in humans, a single administration of psilocybin or LSD produced persistent antidepressant-like effects in our model. In contrast, ketamine produced only a transient antidepressant-like effect. Our results indicate that classic psychedelics may have therapeutic efficacy that is more persistent than that of ketamine, and also suggest that a subjective existential experience may not be necessary for therapeutic effects.
- 11Ly, C., Greb, A. C., Cameron, L. P., Wong, J. M., Barragan, E. V., Wilson, P. C., Burbach, K. F., Soltanzadeh Zarandi, S., Sood, A., Paddy, M. R., Duim, W. C., Dennis, M. Y., McAllister, A. K., Ori-McKenney, K. M., Gray, J. A., and Olson, D. E. (2018) Psychedelics promote structural and functional neural plasticity. Cell Rep. 23 (11), 3170– 3182, DOI: 10.1016/j.celrep.2018.05.02212Psychedelics Promote Structural and Functional Neural PlasticityLy, Calvin; Greb, Alexandra C.; Cameron, Lindsay P.; Wong, Jonathan M.; Barragan, Eden V.; Wilson, Paige C.; Burbach, Kyle F.; Soltanzadeh Zarandi, Sina; Sood, Alexander; Paddy, Michael R.; Duim, Whitney C.; Dennis, Megan Y.; McAllister, A. Kimberley; Ori-McKenney, Kassandra M.; Gray, John A.; Olson, David E.Cell Reports (2018), 23 (11), 3170-3182CODEN: CREED8; ISSN:2211-1247. (Cell Press)Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiol. of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse no. and function, as measured by fluorescence microscopy and electrophysiol. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clin. effectiveness of these compds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chem. efforts focused on developing plasticity-promoting compds. as safe, effective, and fast-acting treatments for depression and related disorders.
- 12Carhart-Harris, R. L. (2018) The entropic brain-revisited. Neuropharmacology 142, 167– 178, DOI: 10.1016/j.neuropharm.2018.03.01013The entropic brain - revisitedCarhart-Harris, Robin L.Neuropharmacology (2018), 142 (), 167-178CODEN: NEPHBW; ISSN:0028-3908. (Elsevier B.V.)The entropic brain hypothesis proposes that within upper and lower limits, after which consciousness may be lost, the entropy of spontaneous brain activity indexes the informational richness of conscious states. Here the hypothesis is revisited four years on from its original publication. It is shown that the principle that the entropy of brain activity is elevated in the psychedelic state is increasingly well supported by sep. and independent studies and analyses, and evidence for greater brain criticality under psychedelics is also highlighted. It is argued that heightened brain criticality enables the brain to be more sensitive to intrinsic and extrinsic perturbations which may translate as a heightened susceptibility to "set" and "setting". This updated version of the original entropic brain hypothesis now offers more concrete information on specific measures of brain entropy and suggests new studies to scrutinise it further, as well as examine its utility for describing and informing the treatment of psychiatric and neurol. conditions such as depression and disorders of consciousness.
- 13Schultes, R. E. (1969) Hallucinogens of plant origin. Science 163, 245, DOI: 10.1126/science.163.3864.24514Hallucinogens of plant originSchultes R EScience (New York, N.Y.) (1969), 163 (3864), 245-54 ISSN:0036-8075.There is no expanded citation for this reference.
- 14Belser, A. B., Agin-Liebes, G., Swift, T. C., Terrana, S., Devenot, N., Friedman, H. L., Guss, J., Bossis, A., and Ross, S. (2017) Patient experiences of psilocybin-assisted psychotherapy: an interpretative phenomenological analysis. J. Humanist Psychol 57 (4), 354– 388, DOI: 10.1177/0022167817706884There is no corresponding record for this reference.
- 15Noorani, T., Garcia-Romeu, A., Swift, T. C., Griffiths, R. R., and Johnson, M. W. (2018) Psychedelic therapy for smoking cessation: qualitative analysis of participant accounts. J. Psychopharmacol. 32 (7), 756– 769, DOI: 10.1177/026988111878061216Psychedelic therapy for smoking cessation: Qualitative analysis of participant accountsNoorani Tehseen; Noorani Tehseen; Garcia-Romeu Albert; Swift Thomas C; Griffiths Roland R; Johnson Matthew W; Swift Thomas C; Swift Thomas C; Griffiths Roland RJournal of psychopharmacology (Oxford, England) (2018), 32 (7), 756-769 ISSN:.BACKGROUND: Recent pilot trials suggest feasibility and potential efficacy of psychedelic-facilitated addiction treatment interventions. Fifteen participants completed a psilocybin-facilitated smoking cessation pilot study between 2009 and 2015. AIMS: The aims of this study were as follows: (1) to identify perceived mechanisms of change leading to smoking cessation in the pilot study; (2) to identify key themes in participant experiences and long-term outcomes to better understand the therapeutic process. METHODS: Participants were invited to a retrospective follow-up interview an average of 30 months after initial psilocybin sessions. Semi-structured interviews were conducted with 12 of the 15 participants. Data were analysed using thematic analysis. RESULTS: Participants reported gaining vivid insights into self-identity and reasons for smoking from their psilocybin sessions. Experiences of interconnectedness, awe, and curiosity persisted beyond the duration of acute drug effects. Participants emphasised that the content of psilocybin experiences overshadowed any short-term withdrawal symptoms. Preparatory counselling, strong rapport with the study team, and a sense of momentum once engaged in the study treatment were perceived as vital additional factors in achieving abstinence. In addition, participants reported a range of persisting positive changes beyond smoking cessation, including increased aesthetic appreciation, altruism, and pro-social behaviour. CONCLUSIONS: The findings highlight the value of qualitative research in the psychopharmacological investigation of psychedelics. They describe perceived connections between drug- and non-drug factors, and provide suggestions for future research trial design and clinical applications.
- 16Griffiths, R. R., Richards, W. A., McCann, U., and Jesse, R. (2006) Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology 187 (3), 268– 283, DOI: 10.1007/s00213-006-0457-517Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significanceGriffiths, R. R.; Richards, W. A.; McCann, U.; Jesse, R.Psychopharmacology (Berlin, Germany) (2006), 187 (3), 268-283CODEN: PSCHDL; ISSN:0033-3158. (Springer GmbH)Rationale Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects. Objectives This double-blind study evaluated the acute and longer-term psychol. effects of a high dose of psilocybin relative to a comparison compd. administered under comfortable, supportive conditions. Materials and methods The participants were hallucinogen-naive adults reporting regular participation in religious or spiritual activities. Two or three sessions were conducted at 2-mo intervals. Thirty volunteers received orally administered psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) in counterbalanced order. To obscure the study design, six addnl. volunteers received methylphenidate in the first two sessions and unblinded psilocybin in a third session. The 8-h sessions were conducted individually. Volunteers were encouraged to close their eyes and direct their attention inward. Study monitors rated volunteers' behavior during sessions. Volunteers completed questionnaires assessing drug effects and mystical experience immediately after and 2 mo after sessions. Community observers rated changes in the volunteer's attitudes and behavior. Results Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 mo, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained pos. changes in attitudes and behavior consistent with changes rated by community observers. Conclusions When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences. The ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.
- 17Griffiths, R. R., Richards, W. A., Johnson, M. W., McCann, U. D., and Jesse, R. (2008) Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J. Psychopharmacol. 22 (6), 621– 632, DOI: 10.1177/026988110809430018Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months laterGriffiths, R. R.; Richards, W. A.; Johnson, M. W.; McCann, U. D.Journal of Psychopharmacology (London, United Kingdom) (2008), 22 (6), 621-632CODEN: JOPSEQ; ISSN:0269-8811. (Sage Publications Ltd.)Psilocybin has been used for centuries for religious purposes; however, little is known scientifically about its long-term effects. We previously reported the effects of a double-blind study evaluating the psychol. effects of a high psilocybin dose. This report presents the 14-mo follow-up and examines the relationship of the follow-up results to data obtained at screening and on drug session days. Participants were 36 hallucinogen-naive adults reporting regular participation in religious/spiritual activities. Oral psilocybin (30 mg/70 kg) was administered on one of two or three sessions, with methylphenidate (40 mg/70 kg) administered on the other session(s). During sessions, volunteers were encouraged to close their eyes and direct their attention inward. At the 14-mo follow-up, 58% and 67%, resp., of volunteers rated the psilocybin-occasioned experience as being among the five most personally meaningful and among the five most spiritually significant experiences of their lives; 64% indicated that the experience increased well-being or life satisfaction; 58% met criteria for having had a "complete" mystical experience. Correlation and regression analyses indicated a central role of the mystical experience assessed on the session day in the high ratings of personal meaning and spiritual significance at follow-up. Of the measures of personality, affect, quality of life and spirituality assessed across the study, only a scale measuring mystical experience showed a difference from screening. When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences that, at 14-mo follow-up, were considered by volunteers to be among the most personally meaningful and spiritually significant of their lives.
- 18Griffiths, R. R., Johnson, M. W., Richards, W. A., Richards, B. D., McCann, U., and Jesse, R. (2011) Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology 218 (4), 649– 665, DOI: 10.1007/s00213-011-2358-519Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effectsGriffiths, Roland R.; Johnson, Matthew W.; Richards, William A.; Richards, Brian D.; McCann, Una; Jesse, RobertPsychopharmacology (Heidelberg, Germany) (2011), 218 (4), 649-665CODEN: PSCHDL; ISSN:0033-3158. (Springer)Rationale: This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting pos. effects on attitudes, mood, and behavior. Objectives: This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions. Methods: Participants were 18 adults (17 hallucinogen-naive). Five 8-h sessions were conducted individually for each participant at 1-mo intervals. Participants were randomized to receive the four active doses in either ascending or descending order (nine participants each). Placebo was scheduled quasi-randomly. During sessions, volunteers used eyeshades and were instructed to direct their attention inward. Volunteers completed questionnaires assessing effects immediately after and 1 mo after each session, and at 14 mo follow-up. Results: Psilocybin produced acute perceptual and subjective effects including, at 20 and/or 30 mg/70 kg, extreme anxiety/fear (39% of volunteers) and/or mystical-type experience (72% of volunteers). One month after sessions at the two highest doses, volunteers rated the psilocybin experience as having substantial personal and spiritual significance, and attributed to the experience sustained pos. changes in attitudes, mood, and behavior, with the ascending dose sequence showing greater pos. effects. At 14 mo, ratings were undiminished and were consistent with changes rated by community observers. Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose, with the lowest dose showing significant effects. Conclusions: Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting pos. effects on attitudes, mood, and behavior. Implications for therapeutic trials are discussed.
- 19Griffiths, R. R., Johnson, M. W., Richards, W. A., Richards, B. D., Jesse, R., MacLean, K. A., Barrett, F. S., Cosimano, M. P., and Klinedinst, M. A. (2018) Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors. J. Psychopharmacol. 32 (1), 49– 69, DOI: 10.1177/026988111773127920Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviorsGriffiths, Roland R.; Johnson, Matthew W.; Richards, William A.; Richards, Brian D.; Jesse, Robert; MacLean, Katherine A.; Barrett, Frederick S.; Cosimano, Mary P.; Klinedinst, Maggie A.Journal of Psychopharmacology (London, United Kingdom) (2018), 32 (1), 49-69CODEN: JOPSEQ; ISSN:0269-8811. (Sage Publications Ltd.)Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examd. enduring changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were randomized to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2) with moderate-level ("std.") support for spiritual-practice (LD-SS); (2) high-dose (20 and 30 mg/70 kg on sessions 1 and 2, resp.) with std. support (HD-SS); and (3) high-dose (20 and 30 mg/70kg on sessions 1 and 2, resp.) with high support for spiritual practice (HD-HS). Psilocybin was administered double-blind and instructions to participants/staff minimized expectancy confounds. Psilocybin was administered 1 and 2 mo after spiritual-practice initiation. Outcomes at 6 mo included rates of spiritual practice and persisting effects of psilocybin. Compared with low-dose, high-dose psilocybin produced greater acute and persisting effects. At 6 mo, compared with LD-SS, both high-dose groups showed large significant pos. changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings. Determinants of enduring effects were psilocybin-occasioned mystical-type experience and rates of meditation/spiritual practices. Psilocybin can occasion enduring trait-level increases in prosocial attitudes/behaviors and in healthy psychol. functioning. Trial Registration ClinicalTrials.gov Identifier NCT00802282.
- 20Yaden, D. B., Haidt, J., Hood, R. W., Jr, Vago, D. R., and Newberg, A. B. (2017) The varieties of self-transcendent experience. Rev. Gen Psychol 21 (2), 143– 160, DOI: 10.1037/gpr0000102There is no corresponding record for this reference.
- 21Barrett, F. S., Johnson, M. W., and Griffiths, R. R. (2015) Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin. J. Psychopharmacol. 29 (11), 1182– 1190, DOI: 10.1177/026988111560901922Validation of the revised mystical experience questionnaire in experimental sessions with psilocybinBarrett, Frederick S.; Johnson, Matthew W.; Griffiths, Roland R.Journal of Psychopharmacology (London, United Kingdom) (2015), 29 (11), 1182-1190CODEN: JOPSEQ; ISSN:0269-8811. (Sage Publications Ltd.)The 30-item revised Mystical Experience Questionnaire (MEQ30) was previously developed within an online survey of mystical-type experiences occasioned by psilocybin-contg. mushrooms. The rated experiences occurred on av. eight years before completion of the questionnaire. The current paper validates the MEQ30 using data from exptl. studies with controlled doses of psilocybin. Data were pooled and analyzed from five lab. expts. in which participants (n = 184) received a moderate to high oral dose of psilocybin (at least 20 mg/70 kg). Results of confirmatory factor anal. demonstrate the reliability and internal validity of the MEQ30. Structural equation models demonstrate the external and convergent validity of the MEQ30 by showing that latent variable scores on the MEQ30 pos. predict persisting change in attitudes, behavior, and well-being attributed to experiences with psilocybin while controlling for the contribution of the participant-rated intensity of drug effects. These findings support the use of the MEQ30 as an efficient measure of individual mystical experiences. A method to score a "complete mystical experience" that was used in previous versions of the mystical experience questionnaire is validated in the MEQ30, and a stand-alone version of the MEQ30 is provided for use in future research.
- 22Garcia-Romeu, A., Griffiths, R., and Johnson, M. (2015) Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Curr. Drug Abuse Rev. 7 (3), 157– 164, DOI: 10.2174/1874473708666150107121331There is no corresponding record for this reference.
- 23Roseman, L., Nutt, D. J., and Carhart-Harris, R. L. (2018) Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression. Front. Pharmacol. 8, 974, DOI: 10.3389/fphar.2017.00974There is no corresponding record for this reference.
- 24Carbonaro, T. M., Johnson, M. W., and Griffiths, R. R. (2020) Subjective features of the psilocybin experience that may account for its self-administration by humans: A double-blind comparison of psilocybin and dextromethorphan. Psychopharmacology 237, 2293– 2304, DOI: 10.1007/s00213-020-05533-925Subjective features of the psilocybin experience that may account for its self-administration by humans: a double-blind comparison of psilocybin and dextromethorphanCarbonaro, Theresa M.; Johnson, Matthew W.; Griffiths, Roland R.Psychopharmacology (Heidelberg, Germany) (2020), 237 (8), 2293-2304CODEN: PSCHDL; ISSN:0033-3158. (Springer)Objective: New data are presented from a study of psilocybin and DXM relevant to understanding the features of psilocybin subjective effects that may account for its higher rates of non-medical use. Methods: Single, acute oral doses of psilocybin (10, 20, 30 mg/70 kg), DXM (400 mg/70 kg), and placebo were administered under double-blind conditions to 20 healthy participants with histories of hallucinogen use. Results: High doses of both drugs produced similar time courses and increases in participant ratings of peak overall drug effect strength. Nine subjective effect domains are proposed to be related to the reinforcing effects of psilocybin: liking, visual effects, pos. mood, insight, pos. social effects, increased awareness of beauty (both visual and music), awe/amazement, meaningfulness, and mystical experience. For most ratings, (1) psilocybin and DXM both produced effects significantly greater than placebo; (2) psilocybin showed dose-related increases; 3, DXM was never significantly higher than psilocybin; (4) the two highest psilocybin doses were significantly greater than DXM. Conclusions: This anal. provides new information about domains of psilocybin subjective effects proposed to be related to its reinforcing effects (alternatively described as the "motivation" to use). Obsd. differences on these domains between psilocybin and DXM are consistent with the relative rates of non-medical use of psilocybin and DXM.
- 25Garcia-Romeu, A., Davis, A. K., Erowid, F., Erowid, E., Griffiths, R. R., and Johnson, M. W. (2019) Cessation and reduction in alcohol consumption and misuse after psychedelic use. J. Psychopharmacol. 33 (9), 1088– 1101, DOI: 10.1177/026988111984579326Cessation and reduction in alcohol consumption and misuse after psychedelic useGarcia-Romeu Albert; Davis Alan K; Griffiths Roland R; Johnson Matthew W; Erowid Fire; Erowid Earth; Griffiths Roland RJournal of psychopharmacology (Oxford, England) (2019), 33 (9), 1088-1101 ISSN:.BACKGROUND: Meta-analysis of randomized studies using lysergic acid diethylamide (LSD) for alcohol use disorder (AUD) showed large, significant effects for LSD efficacy compared to control conditions. Clinical studies suggest potential anti-addiction effects of LSD and mechanistically-related classic psychedelics for alcohol and other substance use disorders. AIMS: To supplement clinical studies, reports of psychedelic use in naturalistic settings can provide further data regarding potential effects of psychedelics on alcohol use. METHODS: An anonymous online survey of individuals with prior AUD reporting cessation or reduction in alcohol use following psychedelic use in non-clinical settings. RESULTS: 343 respondents, mostly White (89%), males (78%), in the USA (60%) completed the survey. Participants reported seven years of problematic alcohol use on average before the psychedelic experience to which they attributed reduced alcohol consumption, with 72% meeting retrospective criteria for severe AUD. Most reported taking a moderate or high dose of LSD (38%) or psilocybin (36%), followed by significant reduction in alcohol consumption. After the psychedelic experience 83% no longer met AUD criteria. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced alcohol misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with a greater reduction in alcohol consumption, controlling for prior alcohol consumption and related distress. CONCLUSIONS: Although results cannot demonstrate causality, they suggest that naturalistic psychedelic use may lead to cessation or reduction in problematic alcohol use, supporting further investigation of psychedelic-assisted treatment for AUD.
- 26Garcia-Romeu, A., Davis, A. K., Erowid, E., Erowid, F., Griffiths, R. R., and Johnson, M. W. (2020) Persisting reductions in cannabis, opioid, and stimulant misuse after naturalistic psychedelic use: An online survey. Front Pharmacol 10, 955, DOI: 10.3389/fpsyt.2019.00955There is no corresponding record for this reference.
- 27Davis, A. K., Barrett, F. S., and Griffiths, R. R. (2020) Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety. J. Contextual Behav Sci. 15, 39– 45, DOI: 10.1016/j.jcbs.2019.11.00428Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxietyDavis Alan K; Davis Alan K; Barrett Frederick S; Griffiths Roland R; Griffiths Roland RJournal of contextual behavioral science (2020), 15 (), 39-45 ISSN:2212-1447.Prior research has shown that acute subjective psychedelic effects are associated with both spontaneous and intended changes in depression and anxiety. Psychedelics are also theorized to produce increases in psychological flexibility, which could explain decreases in depression and anxiety following a psychedelic experience. Therefore, the present cross-sectional survey study sought to examine whether psychological flexibility mediated the relationship between acute psychedelic experiences and spontaneous or intended changes in depression and anxiety among a large international sample of people who reported having used a psychedelic (n=985; male=71.6%; Caucasian/white=84.1%; Mage=32.2, SD=12.6). A regression analysis showed that acute effects (i.e., mystical and insightful effects) were significantly associated with decreases in depression/anxiety following a psychedelic experience. A path analysis revealed that, while controlling for age and sex, increases in psychological flexibility fully mediated the effect of mystical and insightful experiences on decreases in depression and anxiety following a psychedelic experience. This suggests that psychological flexibility may be an important mediator of the therapeutic effects of psychedelic drugs. Future prospective experimental studies should examine the effect of psychedelic drug administration on psychological flexibility in order to gain a better understanding of the psychological processes that predict therapeutic effects of psychedelics.
- 28Olson, D. The Subjective Effects of Psychedelics May Not Be Necessary for Their Therapeutic Impact. ACS Pharm. Transl. Sci. 2020 DOI: 10.1021/acsptsci.0c00192 .There is no corresponding record for this reference.