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The aim of this double-blind, placebo-controlled, within-subjects study is to determine whether other psychoactive substances can produce experiences akin to those seen with classic psychedelics. Screening involves a medical and psychiatric examination, including blood draw, history and physical, interviews, and questionnaires. Eligible participants will then be asked to complete up to 6 experimental drug administration session during which the participants will potentially receive and report on the subjective effects of 6 different psychoactive substances or inactive placebo. Drug assignment for some sessions will be randomized (like flipping a count or rolling a pair of dice), and both participants and study staff will be blind to the drug condition on any given day. Participants will also complete 2 preparation sessions (4 hours total) before the first experimental session, and follow-up visits after each session to discuss and debrief on the participants subjective experience.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants may receive an inactive placebo during any one of the experimental sessions. |
|
| Psilocybin | Active Comparator | Participants may receive varying oral psychoactive doses of psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) |
|
| Other psychoactive drugs | Experimental | Participants may receive varying oral psychoactive doses of ketamine, dextromethorphan (DXM), N,N-dimethyltryptamine (DMT), 3,4-methylenedioxymethamphetamine (MDMA), or delta-9-tetrahydrocannabinol (THC). All dose levels will be limited to doses that have been safely administered within a single day in a laboratory context in the past. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | inactive substance |
| |
| Psilocybin |
| Measure | Description | Time Frame |
|---|---|---|
| Mystical Experience Questionnaire (MEQ-30) | The MEQ is a 30-item self-report instrument intended to assess psychedelic-specific acute subjective effects of psychoactive drugs. At the end of each experimental session, participants will be instructed to rate each of the items of the MEQ relative to the experiences that the participant encountered during the course of the drug administration session. The total score on all items is then calculated as the primary outcome measure for each experimental session. Scores range from 0 to 150 on this measure with higher scores reflecting more mystical experience | Week 2, Week 7 |
| Measure | Description | Time Frame |
|---|---|---|
| Drug Effects Questionnaire (DEQ) | The DEQ is a self-report instrument intended to assess a range of psychoactive drug effects. Individual items include ratings of abuse-related drug effects (e.g. drug effect, good effect, bad effect, liking) and behavioral/mood states often associated with drug intoxication. The DEQ will be rated at baseline prior to the first session, and then at the end of each experimental session. The the primary outcomes for each session will be DEQ score change from baseline. Scores range from 0 to 200 on this measure where 0 is the least impactful effect. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zach Daily | Contact | 410-550-9777 | zdaily1@jh.edu |
| Name | Affiliation | Role |
|---|---|---|
| Frederick Barrett, Ph.D. | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Center for Psychedelic and Consciousness Research | Recruiting | Baltimore | Maryland | 21218 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8297217 | Background | Strassman RJ, Qualls CR, Uhlenhuth EH, Kellner R. Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale. Arch Gen Psychiatry. 1994 Feb;51(2):98-108. doi: 10.1001/archpsyc.1994.03950020022002. | |
| 35923458 | Background | Ko K, Knight G, Rucker JJ, Cleare AJ. Psychedelics, Mystical Experience, and Therapeutic Efficacy: A Systematic Review. Front Psychiatry. 2022 Jul 12;13:917199. doi: 10.3389/fpsyt.2022.917199. eCollection 2022. |
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| ID | Term |
|---|---|
| D011562 | Psilocybin |
| D007649 | Ketamine |
| D003915 | Dextromethorphan |
| D004130 | N,N-Dimethyltryptamine |
| D018817 | N-Methyl-3,4-methylenedioxyamphetamine |
| D013759 | Dronabinol |
| ID | Term |
|---|---|
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
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| Drug |
active comparator for psychedelic effects |
|
| Ketamine | Drug | psychoactive substance |
|
| Dextromethorphan (DXM) | Drug | psychoactive substance |
|
| Dimethyltryptamine (DMT) | Drug | psychoactive substance |
|
| Methylenedioxymethamphetamine (MDMA) | Drug | psychoactive substance |
|
| Tetrahydrocannabinol (THC) | Drug | psychoactive substance |
|
| Week 2, Week 7 |
| 33853422 | Background | Schmid Y, Gasser P, Oehen P, Liechti ME. Acute subjective effects in LSD- and MDMA-assisted psychotherapy. J Psychopharmacol. 2021 Apr;35(4):362-374. doi: 10.1177/0269881120959604. Epub 2020 Oct 8. |
| 37222753 | Background | Breeksema JJ, Niemeijer A, Kuin B, Veraart J, Vermetten E, Kamphuis J, van den Brink W, Schoevers R. Phenomenology and therapeutic potential of patient experiences during oral esketamine treatment for treatment-resistant depression: an interpretative phenomenological study. Psychopharmacology (Berl). 2023 Jul;240(7):1547-1560. doi: 10.1007/s00213-023-06388-6. Epub 2023 May 24. |
| 37947321 | Background | Wolinsky D, Barrett FS, Vandrey R. The psychedelic effects of cannabis: A review of the literature. J Psychopharmacol. 2024 Jan;38(1):49-55. doi: 10.1177/02698811231209194. Epub 2023 Nov 10. |
| 33779383 | Background | Earleywine M, Ueno LF, Mian MN, Altman BR. Cannabis-induced oceanic boundlessness. J Psychopharmacol. 2021 Jul;35(7):841-847. doi: 10.1177/0269881121997099. Epub 2021 Mar 28. |
| 22526529 | Background | Reissig CJ, Carter LP, Johnson MW, Mintzer MZ, Klinedinst MA, Griffiths RR. High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens. Psychopharmacology (Berl). 2012 Sep;223(1):1-15. doi: 10.1007/s00213-012-2680-6. Epub 2012 Apr 13. |
| 29116367 | Background | Carbonaro TM, Johnson MW, Hurwitz E, Griffiths RR. Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences. Psychopharmacology (Berl). 2018 Feb;235(2):521-534. doi: 10.1007/s00213-017-4769-4. Epub 2017 Nov 7. |
| 26442957 | Background | Barrett FS, Johnson MW, Griffiths RR. Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin. J Psychopharmacol. 2015 Nov;29(11):1182-90. doi: 10.1177/0269881115609019. Epub 2015 Oct 6. |
| 28401522 | Background | Barrett FS, Griffiths RR. Classic Hallucinogens and Mystical Experiences: Phenomenology and Neural Correlates. Curr Top Behav Neurosci. 2018;36:393-430. doi: 10.1007/7854_2017_474. |
| 21674151 | Background | Griffiths RR, Johnson MW, Richards WA, Richards BD, McCann U, Jesse R. Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology (Berl). 2011 Dec;218(4):649-65. doi: 10.1007/s00213-011-2358-5. Epub 2011 Jun 15. |
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D014363 | Tryptamines |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D015306 | Biogenic Monoamines |
| D001679 | Biogenic Amines |
| D000588 | Amines |
| D000662 | Amphetamines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D002186 | Cannabinoids |
| D013729 | Terpenes |