Single and Repeat Doses of DMT in Healthy Subjects

NCT05559931 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: AGN-188-1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to assess the safety and tolerability of single ascending, and fixed repeated doses of N,N-Dimethyltryptamine (DMT) in healthy subjects, when given by intravenous (IV) infusion.

Conditions

Stroke

Outcome Measures

Primary Outcomes (9)

• Safety and Tolerability: Proportion of subjects with abnormal vital signs

  Part A: Up to 10 days post infusion; Part B: Up to 21 days post first infusion

• Safety and Tolerability: Proportion of subjects with abnormal ECG readings

  12-lead ECG

  Part A: Up to 10 days post infusion; Part B: Up to 21 days post first infusion

• Safety and Tolerability: Proportion of subjects with abnormal physical examination findings

  Part A: Up to 10 days post infusion; Part B: Up to 21 days post first infusion

• Safety and Tolerability: percentage of subjects with abnormal haematology, clinical chemistry, coagulation, and urinalysis values

  Part A: Up to 10 days post infusion; Part B: Up to 21 days post first infusion

• Safety and Tolerability: percentage of subjects with local reactions at the injection site

  Part A: Up to 2 days post infusion; Part B: Up to 12 days post first infusion

• Safety and Tolerability: proportion of subjects with abnormal findings on the Columbia-Suicide Severity Ratings Scale (C-SSRS)

  Part A: Up to 2 days post infusion; Part B: Up to 12 days post first infusion

• Safety and Tolerability: proportion of subjects with occurrence of psychotic symptoms (BPRS)

  Part A: Up to 2 days post infusion; Part B: Up to 12 days post first infusion

• Safety and Tolerability: proportion of subjects with occurrence of central 5-HT toxicity

  Hunters criteria + CPK

  Part A: Up to 10 days post infusion; Part B: Up to 21 days post first infusion

• Safety and Tolerability: proportion of subjects with at least one adverse event (AE)

  Part A: Up to 10 days post infusion; Part B: Up to 21 days post first infusion

Secondary Outcomes (8)

• DMT - Maximum Plasma Concentration (Cmax)

  Up to 4 hours post infusion

• DMT - Time to peak drug concentration (tmax)

  Up to 4 hours post infusion

• DMT - Area Under Curve last (AUClast)

  Up to 4 hours post infusion

• DMT - Area Under Curve 0-t (AUC0-t)

  Up to 4 hours post infusion

• DMT - Area Under Curve infinity (AUCinf)

  Up to 4 hours post infusion

Other Outcomes (9)

• Psychedelic effects as measured by 5D-ASC

  Up to 24 hour after start of infusion

• Psychedelic effects as measured by Hallucinogen Rating Scale

  Up to 24 hour after start of infusion

• Neurophysiological and neuropsychological measures (Neurocart test battery)

  Up to 24 hour after start of infusion

Study Arms (4)

Part A: Single Dose Active

EXPERIMENTAL

Subjects will receive a single IV dose of DMT, administered as a bolus loading dose followed by a 6-h infusion. The starting dose will be 1.5 mg bolus, followed by a 0.105 mg/min infusion. Subsequent doses will be based on the safety and tolerability data from previous groups.

Drug: N,N-Dimethyltryptamine

Part A: Single Dose Placebo

PLACEBO COMPARATOR

Subjects will receive a single IV dose of placebo, administered as a bolus loading dose followed by a 6-h infusion.

Drug: Placebo

Part B: Multiple Dose Active

EXPERIMENTAL

Subjects will receive a total of 6 doses of DMT, given as a bolus loading dose, followed by a IV infusion over 6 h, on Days 1, 3, 5, 8, 10, and 12 of a 2-week treatment period. Dose to be determined from single dose phase.

Drug: N,N-Dimethyltryptamine

Part B: Multiple Dose Placebo

PLACEBO COMPARATOR

Subjects will receive a total of 6 doses of placebo, given as a bolus loading dose, followed by IV infusion over 6 h, on Days 1, 3, 5, 8, 10, and 12 of a 2-week treatment period.

Drug: Placebo

Interventions

N,N-Dimethyltryptamine DRUG

IV infusion over 6 hours

Also known as: DMT

Part A: Single Dose Active; Part B: Multiple Dose Active

Placebo DRUG

Placebo infusion over 6 hours

Part A: Single Dose Placebo; Part B: Multiple Dose Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female volunteer. Subject must be healthy based on physical examination, medical history, vital signs, and 12-lead ECG. Minor abnormalities in ECG, which are not considered to be of clinical significance by the investigator, are acceptable.
• Subjects must be healthy based on clinical laboratory tests performed at screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities to be not clinically significant. This determination must be recorded in the subject's source documents and initialled by the sub investigator.
• Aged 18-60 years inclusive.
• A body mass index (BMI; Quetelet index) in the range 18.5-30.0 kg/m2.
• Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial.
• Willingness to give written consent to participate after reading the information and consent form, and after having the opportunity to discuss the trial with the investigator or their delegate.
• Agree to follow the contraception requirements of the trial.
• Agree not to donate blood or blood products during the study and for up to 3 months after the administration of the trial medication.
• Agree to refrain from using any psychoactive drugs from 30 days before dosing and until the last follow up visit, to refrain from using cannabis from 14 days before dosing and until the last follow up visit and to refrain from using alcoholic beverages within 24 hours of each drug administration.

You may not qualify if:

• Clinically relevant abnormal history, physical findings, ECG (e.g. PQ/PR interval \> 210ms, presence of Left Bundle Branch Block, AV Block (second degree or higher), or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the volunteer.
• Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease or any of the following cardiovascular conditions: arrhythmia, family history of long QT syndrome or sudden death, artificial heart valve, current or any history of hypertension, or any other significant current or history of cardiovascular condition,
• History of chronic or frequent migraines.
• Blood pressure and heart rate in supine position at the screening examination outside the ranges: blood pressure 90-140 mm Hg systolic, 40-90 mm Hg diastolic; heart rate 40-100 beats/min.
• Repeat measurements are permitted if values are borderline (ie values that are within 5 mm Hg for blood pressure or 5 beats/min for heart rate) or if requested by the investigator. Subjects can be included if the repeat value is within range or still borderline, but deemed not clinically significant by the investigator.
• Presence or history of a medically diagnosed clinically significant seizure disorder.
• Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer's participation in the trial or make it unnecessarily hazardous.
• Woman who is pregnant or lactating, or pre-menopausal woman who is sexually active and not using a reliable method of contraception (see section 11).
• Any current or previously diagnosed clinically significant mental health disorder as classified according to DSM-IV or DSM 5.
• Presence or history of drug or alcohol abuse within 1 year before Screening, or intake of more than 14 units of alcohol weekly.
• Regular use of nicotine (\>5 cigarettes daily). Significant suicide risk as defined by (1) suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within the past year; (2) suicidal behaviours within the past year; or (3) clinical assessment of significant suicidal risk during participant interview.
• Persistent psychological effects following the previous use of psilocybin, LSD, DMT, ayahuasca, mescaline, ibogaine, 2C-drugs (such as 2CB, 2CI and 2CE) and/or ketamine. Such effects might include but are not limited to anxiety, depressed mood, paranoid ideation and/or hallucinations (including hallucinogen persisting perception disorder - HPPD) or recurrent flash-backs related to use.
• First or second-degree relative with schizophrenia spectrum or other psychotic disorders, or bipolar and related disorders as classified according to DSM-IV or DSM 5.
• Habitual users of psychedelic drugs (regular use (≥every 2 weeks) over the last 12 months). Psychedelic drugs include, but are not limited to: DMT, ayahausca, LSD, mescaline, peyote, ibogaine and psilocybin (including mushroom species containing psilocybin).
• Disposition judged by the investigator (or delegate) to be incompatible with establishment of rapport with therapy team and/or safe exposure to DMT.

Sponsors & Collaborators

• Algernon Pharmaceuticals: lead
• Centre for Human Drug Research, Netherlands: collaborator

Study Sites (1)

Centre for Human Drug Research

Leiden, Netherlands

Location

Related Publications (1)

• van der Heijden KV, Zuiker RGJA, Otto ME, Bryan CS, Stewart N, Stillwell C, De Kam ML, van Leuken MB, van Gerven JMA, Jacobs GE. Safety, Pharmacokinetics, and Pharmacodynamics of a 6-h N,N-Dimethyltryptamine (DMT) Infusion in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial. Clin Transl Sci. 2025 May;18(5):e70234. doi: 10.1111/cts.70234.

  PMID: 40356576 DERIVED

MeSH Terms

Conditions

Stroke

Interventions

N,N-Dimethyltryptamine

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tryptamines; Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Gabriel Jacobs, MD, PhD

  Centre for Human Drugs Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: September 29, 2022
• Study Start: January 13, 2023
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: January 28, 2025

Record last verified: 2025-01

Locations

NL (1)