Fixed Order, Open-Label, Dose-Escalation Study of DMT in Humans

The goal of this fixed order, open-label, dose-escalation study is to investigate the safety and efficacy of specific doses of dimethyltryptamine (DMT) in humans.

Study Overview

• Status: Active, not recruiting
• Conditions: Depression; Major Depressive Disorder
• Intervention / Treatment: Drug: 0.1 mg/kg Dimethyltryptamine (DMT); Drug: 0.3 mg/kg Dimethyltryptamine (DMT)

Detailed Description

The results of this study will inform the doses to be used in a larger, double-blind, randomized, placebo-controlled, crossover study. Since the goal of the open label study is to inform the double-blind, randomized, placebo-controlled study, the investigators are citing the hypothesis of the latter solely for providing context. The investigators hypothesize that the administration of DMT will result in neuroplastic changes in healthy and depressed subjects. These changes in neuroplasticity will be indexed using electroencephalographic (EEG) measures and tasks. These neuronal changes may in parallel cause changes in mood measured both in healthy and depressed subjects, which will be captured using appropriate psychometric measures of mood.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Biological Studies Unit at the VA Connecticut Healthcare System, Yale School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Healthy controls inclusion criteria:

• Medically healthy
• Psychiatrically healthy

Healthy controls exclusion criteria:

• Unstable medical conditions
• Psychiatric illness

Depression inclusion criteria:

• Medically healthy
• Diagnosis of major depressive disorder

Depression exclusion criteria:

-Unstable medical conditions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 0.1 mg/kg DMT; 0.1 mg/kg DMT administered intravenously	Drug: 0.1 mg/kg Dimethyltryptamine (DMT); 0.1 mg/kg DMT; Other Names: Low Dose DMT
Active Comparator: 0.3 mg/kg DMT; 0.3 mg/kg DMT administered intravenously	Drug: 0.3 mg/kg Dimethyltryptamine (DMT); 0.3 mg/kg DMT; Other Names: Moderate Dose DMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Blood Pressure	Systolic and diastolic blood pressure will be measured before and several times after the administration of DMT on each test day.	-60 and -30 minutes before DMT administration; 0, +5, +10, +15, +20, +30, +45, +60, and +120 minutes after DMT administration
Change in Heart Rate	Heart rate will be measured before and several times after the administration of DMT on each test day.	-60 and -30 minutes before DMT administration; 0, +5, +10, +15, +20, +30, +45, +60, and +120 minutes after DMT administration
Change in Psychedelic Effects	The modified Altered States of Consciousness Rating Scale (ASC) will be used to assess drug-induced altered states of consciousness before and several times after drug administration. This is a 23-item subjective rating scale that will be completed using a visual analog scale format. Questions are scored 0 to 100 each; higher numbers indicate greater psychedelic effects.	-60 minutes before DMT administration; 0, +30, and +60 minutes after DMT administration
Change in Anxiety	Anxiety will be assessed using a visual analog scale that subjects will be asked to score from 0 (not at all) to 100 (worst ever) to capture the net anxiety produced by DMT. This will be collected before and several times after DMT administration.	-60 minutes before DMT administration; 0, +30, and +60 minutes after DMT administration
Drug Reinforcing Effects	Subjects will be asked to answer questions such as (1) How likely are you to use this drug? and (2) How much are you willing to pay for this experience? using a visual analog scale.	+120 minutes after DMT administration
Overall Tolerability assessed by the VAS	Overall tolerability will be assessed using a visual analog scale that subjects will be asked to score from 0 (well tolerated) to 100 (intolerable) to capture the net tolerability of DMT.	+120 minutes after DMT administration

Collaborators and Investigators

• Sponsor: Yale University

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2021
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 12, 2021
• First Submitted That Met QC Criteria: January 12, 2021
• First Posted (Actual): January 15, 2021

Study Record Updates

• Last Update Posted (Actual): August 3, 2025
• Last Update Submitted That Met QC Criteria: July 31, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Psychotropic Drugs; Serotonin Antagonists; Serotonin Agents; Hallucinogens; Serotonin Receptor Agonists; N,N-Dimethyltryptamine
• Other Study ID Numbers: 2000027720

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No