Effects of Dimethyltryptamine in Healthy Subjects

NCT ID: NCT04353024

Last Updated: 2022-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-18
• Study Completion Date: 2022-09-22

Brief Summary

N,N-dimethyltryptamine (DMT) is a naturally-occurring psychedelic substance widely used in recreational and spiritual settings. DMT can be used as a tool to induce an altered state of consciousness of interest in psychological and psychiatric research. DMT is rapidly metabolized by monoamine oxidase (MAO) A. Therefore, it is inactive when administered orally and has a very short duration of action when administered parenterally (<20 min).Therefore, an intravenous administration regime including a bolus and maintenance perfusion has been proposed to induce a stable and prolonged DMT experience allowing to study the psychological and autonomic acute effects of DMT. This administration allows to induce and end an altered state safely and quickly. The goal of the present study is to experimentally test different intravenous DMT administration schedules to investigate the subjective and autonomic effects of DMT in healthy subjects.

Detailed Description

N,N-dimethyltryptamine (DMT) is a naturally-occurring psychedelic substance widely used in recreational and spiritual settings in the form of Ayahuasca. Similar to lysergic acid diethylamide (LSD) or psilocybin, DMT is considered a tool to induce an altered state of consciousness of interest in psychological and psychiatric research. Pharmacologically, DMT interacts with the serotonin 5-HT2A receptor similar to other classic hallucinogens including LSD and psilocybin. The main difference of DMT in comparison with LSD or psilocybin is inactivity when administered orally without monoamine oxidase (MAO) A inhibition and its short action when administered intravenously or by inhalation. In Ayahuasca, DMT is consumed iin combination with harmala alkaloids that inhibit MAO to increase the oral bioavailability of DMT and to prolong its action after oral use. Alternatively, an intravenous administration regime including a bolus and a one hour maintenance perfusion has been proposed to induce a stable and prolonged DMT experience, allowing to study the psychological and autonomic acute effects of DMT. Also, the maintenance perfusion administration allows to end an altered state of consciousness quickly. In the present study this model will be tested using four modified administration schemes. The goal of this study is to experimentally test different intravenous DMT administration schedules to investigate the subjective and autonomic effects of DMT in healthy subjects. The study is expected to inform researchers on dosing regimes of intravenous DMT as a tool to examine alterations of the mind and is of interest for psychology and psychiatry. This study does not intend to provide any therapeutic benefit for the participants. Currently, no study has validly determined the elimination half-life of DMT and other pharmacokinetic parameters. The key aim is to test the dose-response of DMT as well as the difference between the loading dose bolus and no-bolus perfusion conditions regarding pharmacokinetic, subjective, and autonomic effects including psychological and physical tolerability.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Bolus of 0 mg DMT + perfusion of 0 mg/min DMT over 60 min, resulting in a total dose of 0 mg DMT.

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

Intravenous saline bolus and/or saline maintenance perfusion over 90 min

Low dose

Intravenous bolus of 0 mg DMT + perfusion of 0.6 mg/min DMT over 90 min, resulting in a total dose of 54 mg DMT.

Group Type: EXPERIMENTAL

Dimethyltryptamine (DMT)

Intervention Type: DRUG

Intravenous DMT bolus and/or DMT maintenance perfusion over 90 min

Saline

Intervention Type: DRUG

Intravenous saline bolus and/or saline maintenance perfusion over 90 min

Low dose with bolus

Intravenous bolus of 15 mg DMT + perfusion of 0.6 mg/min DMT over 90 min, resulting in a total dose of 69 mg DMT.

Group Type: EXPERIMENTAL

Dimethyltryptamine (DMT)

Intervention Type: DRUG

Intravenous DMT bolus and/or DMT maintenance perfusion over 90 min

High dose

Intravenous bolus of 0 mg DMT + perfusion of 1 mg/min DMT over 90 min, resulting in a total dose of 90 mg DMT.

Group Type: EXPERIMENTAL

Dimethyltryptamine (DMT)

Intervention Type: DRUG

Intravenous DMT bolus and/or DMT maintenance perfusion over 90 min

Saline

Intervention Type: DRUG

Intravenous saline bolus and/or saline maintenance perfusion over 90 min

High dose with bolus

Intravenous bolus of 25 mg DMT + perfusion of 1 mg/min DMT over 90 min, resulting in a total dose of 115 mg DMT.

Group Type: EXPERIMENTAL

Dimethyltryptamine (DMT)

Intervention Type: DRUG

Intravenous DMT bolus and/or DMT maintenance perfusion over 90 min

Interventions

Dimethyltryptamine (DMT)

Intravenous DMT bolus and/or DMT maintenance perfusion over 90 min

Intervention Type: DRUG

Saline

Intravenous saline bolus and/or saline maintenance perfusion over 90 min

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age between 25 and 65 years old
• Sufficient understanding of the German language
• Understanding of procedures and risks associated with the study
• Willing to adhere to the protocol and signing of the consent form
• Willing to refrain from the consumption of illicit psychoactive substances during the study
• Abstaining from xanthine-based liquids from the evenings prior to the study sessions and during the sessions
• Willing not to operate heavy machinery within 6 h of DMT administration
• Willing to use double-barrier birth control throughout study participation
• Body mass index between 18-29 kg/m2

Exclusion Criteria

• Chronic or acute medical condition
• Current or previous major psychiatric disorder
• Psychotic disorder or bipolar disorder in first-degree relatives
• Hypertension (SBP>140/90 mmHg) or hypotension (SBP<85 mmHg)
• Hallucinogenic substance use (not including cannabis) more than 20 times or any time within the previous two months
• Pregnancy or current breastfeeding
• Participation in another clinical trial (currently or within the last 30 days)
• Use of medication that may interfere with the effects of the study medication
• Tobacco smoking (>10 cigarettes/day)
• Consumption of alcoholic beverages (>20 drinks/week)

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthias E Liechti, Prof. Dr. MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

University Hospital Basel

Basel, Basel-Stadt BS, Switzerland

Countries

Switzerland

References

Vogt SB, Ley L, Erne L, Straumann I, Becker AM, Klaiber A, Holze F, Vandersmissen A, Mueller L, Duthaler U, Rudin D, Luethi D, Varghese N, Eckert A, Liechti ME. Acute effects of intravenous DMT in a randomized placebo-controlled study in healthy participants. Transl Psychiatry. 2023 May 23;13(1):172. doi: 10.1038/s41398-023-02477-4.

Reference Type: DERIVED

PMID: 37221177 (View on PubMed)

Other Identifiers

BASEC 2020-00376

Identifier Type: -

Identifier Source: org_study_id