A Field-Wide Review and Analysis of Study Materials Used in Psilocybin Trials: Assessment of Two Decades of Research

Madsen MK , Fisher PM , Burmester D , et al. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology, 2019; 44(7):1328–1334; doi: py10.1038/s41386-019-0324-9

Nichols DE . Psychedelics. Pharmacol Rev, 2016; 68(2):264–355; doi: 10.1124/pr.115.011478

Nichols DE , Nichols CD , Hendricks PS . Proposed consensus statement on defining psychedelic drugs. Psychedelic Med, 2023; 1(1):12–13; doi: 10.1089/psymed.2022.0008

Nutt D , King LA , Saulsbury W , et al. Development of a rational scale to assess the harm of drugs of potential misuse. Lancet, 2007; 369(9566):1047–1053; doi: 10.1016/S0140-6736(07)60464-4

Johnson MW , Hendricks PS , Barrett FS , et al. Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacol Ther, 2019; 197:83–102; doi: 10.1016/j.pharmthera.2018.11.010

Johnson MW , Sewell RA , Griffiths RR . Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers. Drug Alcohol Depend, 2012; 123(1–3):132–140; doi: 10.1016/j.drugalcdep.2011.10.029

Barrett FS , Johnson MW , Griffiths RR . Validation of the revised mystical experience questionnaire in experimental sessions with psilocybin. J Psychopharmacol, 2015; 29(11):1182–1190; doi: 10.1177/0269881115609019

Holze F , Ley L , Müller F , et al. Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects. Neuropsychopharmacology, 2022; 47(6):1180–1187; doi: 10.1038/s41386-022-01297-2

Vollenweider FX , Preller KH . Psychedelic drugs: Neurobiology and potential for treatment of psychiatric disorders. Nat Rev Neurosci, 2020; 21(11):611–624; doi: 10.1038/s41583-020-0367-2

Yaden DB , Griffiths RR . The subjective effects of psychedelics are necessary for their enduring therapeutic effects. ACS Pharmacol Transl Sci, 2021; 4(2):568–572; doi: 10.1021/acsptsci.0c00194

Schultes RE . Hallucinogens of plant origin. Science, 1969; 163(3864):245–254; doi: 10.1126/science.163.3864.245

Roberts CA , Osborne-Miller I , Cole J , et al. Perceived harm, motivations for use and subjective experiences of recreational psychedelic “magic” mushroom use. J Psychopharmacol, 2020; 34(9):999–1007; doi: 10.1177/0269881120936508

Simonsson O , Sexton JD , Hendricks PS . Associations between lifetime classic psychedelic use and markers of physical health. J Psychopharmacol, 2021; 35(4):447–452; doi: 10.1177/0269881121996863

Hendricks PS , Thorne CB , Clark CB , et al. Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. J Psychopharmacol, 2015; 29(3):280–288; doi: 10.1177/0269881114565653

Carbonaro TM , Bradstreet MP , Barrett FS , et al. Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. J Psychopharmacol, 2016; 30(12):1268–1278; doi: 10.1177/0269881116662634

Carhart-Harris R , Nutt D . User perceptions of the benefits and harms of hallucinogenic drug use: A web-based questionnaire study. J Subst Use, 2010; 15(4):283–300; doi: 10.3109/14659890903271624

Pilecki B , Luoma JB , Bathje GJ , et al. Ethical and legal issues in psychedelic harm reduction and integration therapy. Harm Reduct J, 2021; 18(1):40; doi: 10.1186/s12954-021-00489-1

Brennan W , Jackson MA , MacLean K , et al. A qualitative exploration of relational ethical challenges and practices in psychedelic healing. J Humanist Psychol, 2021; 2216782110452; doi: 10.1177/00221678211045265

Carhart-Harris RL , Roseman L , Haijen E , et al. Psychedelics and the essential importance of context. J Psychopharmacol, 2018; 32(7):725–731; doi: 10.1177/0269881118754710

Leary T , Metzner R , Dass R . The Psychedelic Experience: A Manual Based on the Tibetan Book of the Dead. Citadel Press; 1995.

Hartogsohn I . Set and setting, psychedelics and the placebo response: An extra-pharmacological perspective on psychopharmacology. J Psychopharmacol, 2016; 30(12):1259–1267; doi: 10.1177/0269881116677852

Golden TL , Magsamen S , Sandu CC , et al. Effects of setting on psychedelic experiences, therapies, and outcomes: A rapid scoping review of the literature. Curr Top Behav Neurosci, 2022; 56:35–70; doi: 10.1007/7854_2021_298

Johnson M , Richards W , Griffiths R . Human hallucinogen research: Guidelines for safety. J Psychopharmacol, 2008; 22(6):603–620; doi: 10.1177/0269881108093587

Carhart-Harris RL , Bolstridge M , Rucker J , et al. Psilocybin with psychological support for treatment-resistant depression: An open-label feasibility study. Lancet Psychiatry, 2016; 3(7):619–627; doi: 10.1016/S2215-0366(16)30065-7

Carhart-Harris R , Giribaldi B , Watts R , et al. Trial of psilocybin versus escitalopram for depression. N Engl J Med, 2021; 384(15):1402–1411; doi: 10.1056/NEJMoa2032994

Davis AK , Barrett FS , May DG , et al. Effects of psilocybin-assisted therapy on major depressive disorder: A randomized clinical trial. JAMA Psychiatry, 2021; 78(5):481–489; doi: 10.1001/jamapsychiatry.2020.3285

Goodwin GM , Aaronson ST , Alvarez O , et al. Single-dose psilocybin for a treatment-resistant episode of major depression. N Engl J Med, 2022; 387(18):1637–1648; doi: 10.1056/NEJMoa2206443

Griffiths RR , Johnson MW , Carducci MA , et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol, 2016; 30(12):1181–1197; doi: 10.1177/0269881116675513

Grob CS , Danforth AL , Chopra GS , et al. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry, 2011; 68(1):71–78; doi: 10.1001/archgenpsychiatry.2010.116

Raison CL , Sanacora G , Woolley J , et al. Single-dose psilocybin treatment for major depressive disorder: A randomized clinical trial. JAMA, 2023; 330(9):843–853; doi: 10.1001/jama.2023.14530

Ross S , Bossis A , Guss J , et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: A randomized controlled trial. J Psychopharmacol, 2016; 30(12):1165–1180; doi: 10.1177/0269881116675512

Sloshower J , Skosnik PD , Safi-Aghdam H , et al. Psilocybin-assisted therapy for major depressive disorder: An exploratory placebo-controlled, fixed-order trial. J Psychopharmacol, 2023; 37(7):698–706; doi: 10.1177/02698811231154852

Von Rotz R , Schindowski EM , Jungwirth J , et al. Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. eClinicalMedicine, 2023; 56:101809; doi: 10.1016/j.eclinm.2022.101809

Bogenschutz MP , Forcehimes AA , Pommy JA , et al. Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study. J Psychopharmacol, 2015; 29(3):289–299; doi: 10.1177/0269881114565144

Bogenschutz MP , Ross S , Bhatt S , et al. Percentage of heavy drinking days following psilocybin-assisted psychotherapy vs placebo in the treatment of adult patients with alcohol use disorder: A randomized clinical trial. JAMA Psychiatry, 2022; 79(10):953–962; doi: 10.1001/jamapsychiatry.2022.2096

Johnson MW , Garcia-Romeu A , Cosimano MP , et al. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol, 2014; 28(11):983–992; doi: 10.1177/0269881114548296

Barrett FS , Doss MK , Sepeda ND , et al. Emotions and brain function are altered up to one month after a single high dose of psilocybin. Sci Rep, 2020; 10(1):2214; doi: 10.1038/s41598-020-59282-y

Griffiths R , Richards W , Johnson M , et al. Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J Psychopharmacol, 2008; 22(6):621–632; doi: 10.1177/0269881108094300

Griffiths RR , Richards WA , McCann U , et al. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology (Berl), 2006; 187(3):268–283; doi: 10.1007/s00213-006-0457-5

Griffiths RR , Johnson MW , Richards WA , et al. Psilocybin occasioned mystical-type experiences: Immediate and persisting dose-related effects. Psychopharmacology (Berl), 2011; 218(4):649–665; doi: 10.1007/s00213-011-2358-5

Griffiths RR , Johnson MW , Richards WA , et al. 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, 2018; 32(1):49–69; doi: 10.1177/0269881117731279

van Elk M , Yaden DB . Pharmacological, neural, and psychological mechanisms underlying psychedelics: A critical review. Neurosci Biobehav Rev, 2022; 140:104793; doi: 10.1016/j.neubiorev.2022.104793

Yaden DB , Potash JB , Griffiths RR . Preparing for the bursting of the psychedelic hype bubble. JAMA Psychiatry, 2022; 79(10):943–944; doi: 10.1001/jamapsychiatry.2022.2546

Yaden DB , Yaden ME , Griffiths RR . Psychedelics in psychiatry-keeping the renaissance from going off the rails. JAMA Psychiatry, 2021; 78(5):469–470; doi: 10.1001/jamapsychiatry.2020.3672

Agin-Liebes G , Ekman E , Anderson B , et al. Participant reports of mindfulness, posttraumatic growth, and social connectedness in psilocybin-assisted group therapy: An interpretive phenomenological analysis. J Humanist Psychol, 2024; 64(4):564–591; doi: 10.1177/00221678211022949

Studerus E , Kometer M , Hasler F , et al. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: A pooled analysis of experimental studies. J Psychopharmacol, 2011; 25(11):1434–1452; doi: 10.1177/0269881110382466

Hinkle JT , Graziosi M , Nayak SM , et al. Adverse events in studies of classic psychedelics: A systematic review and meta-analysis. JAMA Psychiatry, 2024; 81(12):1225–1235.

Holze F , Gasser P , Müller F , et al. Lysergic acid diethylamide–assisted therapy in patients with anxiety with and without a life-threatening illness: A randomized, double-blind, placebo-controlled phase II study. Biol Psychiatry, 2023; 93(3):215–223.

Garcia-Romeu A , Richards WA . Current perspectives on psychedelic therapy: Use of serotonergic hallucinogens in clinical interventions. Int Rev Psychiatry, 2018; 30(4):291–316; doi: 10.1080/09540261.2018.1486289

Yaden DB , Earp D , Graziosi M , et al. Psychedelics and psychotherapy: Cognitive-behavioral approaches as default. Front Psychol, 2022; 13:873279; doi: 10.3389/fpsyg.2022.873279

Szigeti B , Heifets B . Expectancy effects in psychedelic trials. Biol Psychiatry Cogn Neurosci Neuroimaging, 2024; 9(5):512–521; doi: 10.1016/j.bpsc.2024.02.004

Aday JS , Heifets BD , Pratscher SD , et al. Great Expectations: Recommendations for improving the methodological rigor of psychedelic clinical trials. Psychopharmacology (Berl), 2022; 239(6):1989–2010; doi: 10.1007/s00213-022-06123-7

Muthukumaraswamy SD , Forsyth A , Lumley T . Blinding and expectancy confounds in psychedelic randomized controlled trials. Expert Rev Clin Pharmacol, 2021; 14(9):1133–1152; doi: 10.1080/17512433.2021.1933434

van Elk M , Fried EI . History repeating: Guidelines to address common problems in psychedelic science. Ther Adv Psychopharmacol, 2023; 13:20451253231198466; doi: 10.1177/20451253231198466

Szigeti B , Weiss B , Rosas FE , et al. Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression. Psychol Med, 2024; 54(8):1717–1724; doi: 10.1017/S0033291723003653

Braun V , Clarke V . Using thematic analysis in psychology. Qual Res Psychol, 2006; 3(2):77–101; doi: 10.1191/1478088706qp063oa

Terry G , Hayfield N , Clarke V , et al. Thematic Analysis. In: The SAGE Handbook of Qualitative Research in Psychology. ( Carly Willig , Wendy Stainton Rogers eds) SAGE Publications Ltd: 55 City Road; 2017, pp. 17–36; doi: 10.4135/9781526405555

Frost NA . Qualitative Research Methods in Psychology: Combining Core Approaches. 2nd ed. McGraw Hill; 2011.

QSR International Pty Ltd. NVivo. 2020.

Sumner RL , Chacko E , McMillan R , et al. A qualitative and quantitative account of patient’s experiences of ketamine and its antidepressant properties. J Psychopharmacol, 2021; 35(8):946–961; doi: 10.1177/0269881121998321

Thal S , Engel LB , Bright SJ . Presence, trust, and empathy: Preferred characteristics of psychedelic carers. J Humanist Psychol, 2022; 221678221081380; doi: 10.1177/00221678221081380

Pahnke WN . The psychedelic mystical experience in the human encounter with death. H Theolo Review, 1969; 62(1):1–21; doi: 10.1017/S0017816000027577

Hayes SC , Strosahl KD , Wilson KG . Acceptance and Commitment Therapy, Second Edition: The Process and Practice of Mindful Change. Guilford Press; 2011.

Hartogsohn I . The meaning-enhancing properties of psychedelics and their mediator role in psychedelic therapy, spirituality, and creativity. Front Neurosci, 2018; 12:129; doi: 10.3389/fnins.2018.00129

Carhart-Harris RL , Kaelen M , Whalley MG , et al. LSD enhances suggestibility in healthy volunteers. Psychopharmacology (Berl), 2015; 232(4):785–794; doi: 10.1007/s00213-014-3714-z

Gukasyan N , Nayak SM . Psychedelics, placebo effects, and set and setting: Insights from common factors theory of psychotherapy. Transcult Psychiatry, 2022; 59(5):652–664; doi: 10.1177/1363461520983684

Dyck E . Psychedelic Psychiatry: LSD from Clinic to Campus. Psychedelic Psychiatry: LSD from Clinic to Campus. Johns Hopkins University Press: Baltimore, MD, US; 2008.

Haijen ECHM , Kaelen M , Roseman L , et al. Predicting responses to psychedelics: A prospective study. Front Pharmacol, 2018; 9:897; doi: 10.3389/fphar.2018.00897

Studerus E , Gamma A , Kometer M , et al. Prediction of psilocybin response in healthy volunteers. PLoS One, 2012; 7(2):e30800; doi: 10.1371/journal.pone.0030800

Gandy M . Urban political ecology: A critical reconfiguration. Prog Hum Geogr, 2022; 46(1):21–43; doi: 10.1177/03091325211040553

Barrett FS , Preller KH , Kaelen M . Psychedelics and music: Neuroscience and therapeutic implications. Int Rev Psychiatry, 2018; 30(4):350–362; doi: 10.1080/09540261.2018.1484342

Kaelen M , Giribaldi B , Raine J , et al. The hidden therapist: Evidence for a central role of music inpsychedelic therapy. Psychopharmacology (Berl), 2018; 235(2):505–519; doi: 10.1007/s00213-017-4820-5

Barrett FS , Robbins H , Smooke D , et al. Qualitative and quantitative features of music reported to support peak mystical experiences during psychedelic therapy sessions. Front Psychol, 2017; 8:1238; doi: 10.3389/fpsyg.2017.01238

Strickland JC , Garcia-Romeu A , Johnson MW . Set and setting: A randomized study of different musical genres in supporting psychedelic therapy. ACS Pharmacol Transl Sci, 2021; 4(2):472–478; doi: 10.1021/acsptsci.0c00187

Kaelen M , Barrett FS , Roseman L , et al. LSD enhances the emotional response to music. Psychopharmacology (Berl), 2015; 232(19):3607–3614; doi: 10.1007/s00213-015-4014-y

Labate BC , Pacheco G . Opening the Portals of Heaven: Brazilian Ayahuasca Music. LIT Verlag Münster; 2010.

Williams MT , Davis AK , Xin Y , et al. People of color in North America report improvements in racial trauma and mental health symptoms following psychedelic experiences. Drugs (Abingdon Engl), 2021; 28(3):215–226; doi: 10.1080/09687637.2020.1854688

Richards W . Sacred Knowledge: Psychedelics and Religious Experiences. Columbia University Press; 2015; doi: 10.7312/columbia/9780231174060.001.0001

McCartney AM , McGovern HT , De Foe A . Predictors of psychedelic experience: A thematic analysis. J Psychoactive Drugs, 2023; 55(4):411–419; doi: 10.1080/02791072.2022.2129885

Johnson MW . Consciousness, religion, and gurus: Pitfalls of psychedelic medicine. ACS Pharmacol Transl Sci, 2021; 4(2):578–581; doi: 10.1021/acsptsci.0c00198

Nayak S , Singh M , Yaden D , et al. Belief changes associated with psychedelic use. 2022. J Psychopharmacol, 2023; 37(1):80–92; doi: 10.1177/02698811221131989

Timmermann C , Kettner H , Letheby C , et al. Psychedelics alter metaphysical beliefs. Sci Rep, 2021; 11(1):22166; doi: 10.1038/s41598-021-01209-2

Jacobs E . What if a pill can change your politics or religious beliefs? 2021. Available from: https://www.scientificamerican.com/article/what-if-a-pill-can-change-your-politics-or-religious-beliefs/ [Last accessed: March 21, 2024].

Johnson MW , Yaden DB . There’s no good evidence that psychedelics can change your politics or religion. 2020. Available from: https://www.scientificamerican.com/article/theres-no-good-evidence-that-psychedelics-can-change-your-politics-or-religion/ [Last accessed: December 23, 2023].

Devenot N , Seale-Feldman A , Smith E , et al. Psychedelic identity shift: A critical approach to set and setting. Kennedy Inst Ethics J, 2022; 32(4):359–399; doi: 10.1353/ken.2022.0022

Weiss B , Nygart V , Pommerencke LM , et al. Examining psychedelic-induced changes in social functioning and connectedness in a naturalistic online sample using the five-factor model of personality. Front Psychol, 2021; 12:749788.

Colloca L , Barsky AJ . Placebo and nocebo effects. N Engl J Med, 2020; 382(6):554–561; doi: 10.1056/NEJMra1907805

Enck P , Bingel U , Schedlowski M , et al. The placebo response in medicine: Minimize, maximize or personalize? Nat Rev Drug Discov, 2013; 12(3):191–204; doi: 10.1038/nrd3923

Flowers EP , Freeman P , Gladwell VF . Enhancing the acute psychological benefits of green exercise: An investigation of expectancy effects. Psychol Sport Exerc, 2018; 39:213–221; doi: 10.1016/j.psychsport.2018.08.014

Kaptchuk TJ , Hemond CC , Miller FG . Placebos in chronic pain: Evidence, theory, ethics, and use in clinical practice. Bmj, 2020; 370:m1668; doi: 10.1136/bmj.m1668

Butler M , Jelen L , Rucker J . Expectancy in placebo-controlled trials of psychedelics: If so, so what? Psychopharmacology (Berl), 2022; 239(10):3047–3055; doi: 10.1007/s00213-022-06221-6

Aday JS , Skiles Z , Eaton N , et al. Personal psychedelic use is common among a sample of psychedelic therapists: Implications for research and practice. Psychedelic Med, 2023 Mar;1(1):27–37.

Barnett BS , Arakelian M , Beebe D , et al. American psychiatrists’ opinions about classic hallucinogens and their potential therapeutic applications: A 7-year follow-Up survey. Psychedelic Med, 2024 Mar;2(1):1–9.

Davis AK , Agin-Liebes G , España M , et al. Attitudes and beliefs about the therapeutic use of psychedelic drugs among psychologists in the United States. J Psychoactive Drugs, 2022; 54(4):309–318.

Barnett BS , Siu WO , Pope HG . A survey of American psychiatrists’ attitudes toward classic hallucinogens. J Nerv Ment Dis, 2018; 206(6):476–480.

Bogenschutz MP , Forcehimes AA . Development of a psychotherapeutic model for psilocybin-assisted treatment of alcoholism. J Humanist Psychol, 2017; 57(4):389–414; doi: 10.1177/0022167816673493

Sloshower J , Guss J , Krause R , et al. Psilocybin-assisted therapy of major depressive disorder using acceptance and commitment therapy as a therapeutic frame. J Context Behav Sci, 2020; 15:12–19; doi: 10.1016/j.jcbs.2019.11.002

Michaels TI , Purdon J , Collins A , et al. Inclusion of people of color in psychedelic-assisted psychotherapy: A review of the literature. BMC Psychiatry, 2018; 18(1):245; doi: 10.1186/s12888-018-1824-6

Ortiz CE , Dourron HM , Sweat NW , et al. Special considerations for evaluating psilocybin-facilitated psychotherapy in vulnerable populations. Neuropharmacology, 2022; 214:109127; doi: 10.1016/j.neuropharm.2022.1091