Investigation of Psychedelic Effects in Psychoactive Substances

NCT ID: NCT06772753

Last Updated: 2025-02-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-02-05

Study Completion Date

2027-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Psychedelic Effects in Healthy Volunteers

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

inactive substance

Psilocybin

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

Group Type ACTIVE_COMPARATOR

Psilocybin

Intervention Type DRUG

active comparator for psychedelic effects

Other psychoactive drugs

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.

Group Type EXPERIMENTAL

Ketamine

Intervention Type DRUG

psychoactive substance

Dextromethorphan (DXM)

Intervention Type DRUG

psychoactive substance

Dimethyltryptamine (DMT)

Intervention Type DRUG

psychoactive substance

Methylenedioxymethamphetamine (MDMA)

Intervention Type DRUG

psychoactive substance

Tetrahydrocannabinol (THC)

Intervention Type DRUG

psychoactive substance

Interventions

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Placebo

inactive substance

Intervention Type DRUG

Psilocybin

active comparator for psychedelic effects

Intervention Type DRUG

Ketamine

psychoactive substance

Intervention Type DRUG

Dextromethorphan (DXM)

psychoactive substance

Intervention Type DRUG

Dimethyltryptamine (DMT)

psychoactive substance

Intervention Type DRUG

Methylenedioxymethamphetamine (MDMA)

psychoactive substance

Intervention Type DRUG

Tetrahydrocannabinol (THC)

psychoactive substance

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

25 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Johns Hopkins University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Frederick Barrett, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

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Johns Hopkins Center for Psychedelic and Consciousness Research

Baltimore, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Zach Daily

Role: CONTACT

410-550-9777

Facility Contacts

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Zach Daily

Role: primary

410-550-2533

Frederick Barrett, PhD

Role: backup

410-550-9777

References

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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.

Reference Type BACKGROUND
PMID: 8297217 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35923458 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33853422 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 37222753 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 37947321 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33779383 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22526529 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29116367 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26442957 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28401522 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21674151 (View on PubMed)

Other Identifiers

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IRB00376501

Identifier Type: -

Identifier Source: org_study_id

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