Investigation of Psychedelic Effects in Psychoactive Substances

NCT06772753 | Recruiting Phase 1 FDA Drug

• 1 other identifier: IRB00376501
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Psychedelic Effects in Healthy Volunteers

Keywords

psychedelic; psychoactive; healthy

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Drug Effects Questionnaire (DEQ)

  Week 2, Week 7

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Participants may receive an inactive placebo during any one of the experimental sessions.

Drug: Placebo

Psilocybin

ACTIVE COMPARATOR

Participants may receive varying oral psychoactive doses of psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine)

Drug: Psilocybin

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.

Drug: Ketamine; Drug: Dextromethorphan (DXM); Drug: Dimethyltryptamine (DMT); Drug: Methylenedioxymethamphetamine (MDMA); Drug: Tetrahydrocannabinol (THC)

Interventions

Placebo DRUG

inactive substance

Placebo

Psilocybin DRUG

active comparator for psychedelic effects

Psilocybin

Ketamine DRUG

psychoactive substance

Other psychoactive drugs

Dextromethorphan (DXM) DRUG

psychoactive substance

Other psychoactive drugs

Dimethyltryptamine (DMT) DRUG

psychoactive substance

Other psychoactive drugs

Methylenedioxymethamphetamine (MDMA) DRUG

psychoactive substance

Other psychoactive drugs

Tetrahydrocannabinol (THC) DRUG

psychoactive substance

Other psychoactive drugs

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Be 25 to 55 years old
• BMI between 18 and 34 kg/m2
• Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the mornings of drug session days. If the subject does not usually consume caffeinated beverages, he or she must agree not to do so on session days
• Agree to refrain from using any psychoactive drugs, including alcoholic beverages, within 24 hours of each drug administration. Exceptions include daily use of caffeine and nicotine.
• Be healthy and psychologically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests
• Agree not to take any PRN prescription medications on the mornings of the sessions unless deemed appropriate by study team.

You may not qualify if:

• Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing; women who are of child-bearing potential and sexually active who are not practicing an effective means of birth control (e.g. oral contraceptives, intrauterine device)
• Cardiovascular conditions-coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g., atrial fibrillation), or transient ischemic attack-that in the clinical opinion of the screening physician or mid-level provider would put the participant at an especially high risk for adverse effects from the study.
• Epilepsy with history of seizures
• Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
• Currently taking on a regular (e.g., daily) basis any medications having a primary centrally acting pharmacological effect on serotonin neurons or medications that are Monoamine oxidase (MAO) inhibitors. For individuals who have intermittent or as needed (PRN) use of such medications, sessions will not be conducted until at least 5 half-lives of the agent have elapsed after the last dose.
• Use of nonprescription medications, nutritional supplements, or herbal supplements except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals
• History of meeting Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for moderate or severe substance use disorder (including alcohol use disorder, but excluding tobacco), requiring that at least one of the endorsed criteria relates to prior loss of control of substance use (e.g. consuming the substance in larger amounts and for a longer amount of time than intended; persistent desire to cut down or regulate use; unsuccessful attempts to stop use; spending a great deal of time obtaining, using, or recovering from the effects of substance use).
• Active suicidal ideation and/or behavior at time of screening.
• Psychiatric disorder that in the clinical opinion of the study team would put the participant at an especially high risk for adverse effects from the study.
• First-degree relative who meets DSM-5 criteria for a Schizophrenia Spectrum or Other Psychotic Disorder (unless disorder is Substance/Medication-Induced Psychotic Disorder or Psychotic Disorder Due to Another Medical Condition), Bipolar I Disorder, or Bipolar II disorder.
• Enrolled in another clinical trial or have received any drug as part of a research study within 30 days prior to dosing.
• Known allergy or prior adverse reaction to any of the study drugs judged by the investigator and/or medical staff to put the study volunteer at greater risk.
• Known allergy or intolerance to nitroglycerin.
• Concomitant use of any CYP2C9 and CYP3A4 inhibitors.

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins Center for Psychedelic and Consciousness Research

Baltimore, Maryland, 21218, United States

RECRUITING

Related Publications (11)

• 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.

  PMID: 8297217 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.

  PMID: 35923458 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.

  PMID: 33853422 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.

  PMID: 37222753 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.

  PMID: 37947321 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.

  PMID: 33779383 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.

  PMID: 22526529 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.

  PMID: 29116367 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.

  PMID: 26442957 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.

  PMID: 28401522 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.

  PMID: 21674151 BACKGROUND

MeSH Terms

Interventions

Psilocybin; Ketamine; Dextromethorphan; N,N-Dimethyltryptamine; N-Methyl-3,4-methylenedioxyamphetamine; Dronabinol

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Biogenic Monoamines; Biogenic Amines; Amines; Amphetamines; Phenethylamines; Ethylamines; Cannabinoids; Terpenes

Study Officials

• Frederick Barrett, Ph.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zach Daily

CONTACT

410-550-9777; zdaily1@jh.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2025
• First Posted: January 14, 2025
• Study Start: February 5, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 23, 2026

Record last verified: 2026-02

Locations

US (1)