Clinical TrialTobacco/Nicotine Use Disorder (TUD)DMTPlaceboCompleted

A study on the safety and effects of the drug DMT in healthy smoking individuals

Randomised, double-blind, placebo-controlled Phase I single ascending dose IV infusion study (n=50) assessing safety, PK/PD and tolerability of target-controlled DMT infusion in healthy smokers.

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Target Enrollment
50 participants
Study Type
Phase I interventional
Design
Randomized, double Blind

Detailed Description

Adaptive, randomized, double-blind, placebo-controlled single ascending dose study evaluating safety, pharmacodynamics and pharmacokinetics of a 90-minute target-controlled intravenous infusion of DMT in healthy regular smokers.

Primary outcomes assess treatment-emergent (S)AEs, vital signs, respiratory rate, ECG, laboratory tests, psychotic symptoms (BPRS), serotonergic toxicity (Hunter criteria) and suicidality (C-SSRS); secondary measures include Neurocart battery, PK sampling, EEG and subjective psychedelic rating scales (HRS, MEQ, 5D-ASC).

Study Protocol

Preparation

sessions

Dosing

1 sessions
90 min each

Integration

sessions

Study Arms & Interventions

DMT infusion

experimental

Single ascending IV infusion of DMT hemifumarate; target-controlled 90-minute infusion.

Interventions

  • DMT0.12 - 2.1 mg/kg
    via IV• single dose• 1 doses total

    Target-controlled 90-minute continuous IV infusion; starting dose 0.12 mg/kg, maximum anticipated 2.1 mg/kg.

Placebo (saline)

inactive

Matching 0.9% saline IV infusion (placebo)

Interventions

  • Placebo
    via IV• single dose• 1 doses total

    0.9% saline, 90-minute continuous IV infusion (placebo).

Participants

Ages
21 – 60
Sexes
Male & Female

Inclusion Criteria

  • 1. Healthy male and female volunteers.
  • 2. Aged 21 - 60 years inclusive.
  • 3. Regular use of nicotine (at least 1 cigarette daily; 5 to 10 cigarettes daily).
  • 4. Self-report of at least one prior hallucinogen drug experience that included a meaningful altered state of consciousness in the past 5 years (psilocybin, LSD, DMT, ayahuasca, mescaline, ibogaine, 2C-drugs, and/or ketamine).
  • 5. BMI between 18.0 and 30.0 kg/m² inclusive.
  • 6. Healthy based on physical exam, medical history, vitals, and 12-lead ECG (minor ECG abnormalities acceptable if judged not clinically significant).
  • 7. Healthy based on clinical laboratory tests at screening (investigator may include minor non-clinically significant abnormalities documented in source).
  • 8. Agree to refrain from psychoactive drugs, including alcohol, within 24 hours of each drug administration.
  • 9. Signed informed consent.
  • 10. Women of childbearing potential agree to effective contraception during participation up to and including the 90-day follow-up after last DMT dose.
  • 11. Agree to refrain from psychoactive drugs from 30 days before dosing until last follow-up and to refrain from alcohol within 24 hours of dosing.

Exclusion Criteria

  • 1. History of or current liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances deemed clinically significant by the investigator.
  • 2. Clinically relevant abnormal history, physical finding, 12-lead ECG (e.g., PQ/PR >210 ms, LBBB, 2nd-degree or higher AV block), permanent pacemaker/ICD, or lab value at screening that could interfere with objectives or safety.
  • 3. History of or current hypertension (systolic >140 mmHg or diastolic >90 mmHg).
  • 4. Presence or history of cardiovascular disease (acute coronary syndrome, angina, ischemic disease, ventricular arrhythmias, cardiac transplantation).
  • 5. History of chronic or frequent migraines.
  • 6. History of hepatitis B surface antigen or hepatitis C antibody positive, or other clinically active liver disease.
  • 7. HIV antibody positive or tests positive for HIV at screening.
  • 8. Ophthalmologic or neurologic condition that would adversely affect eye movement assessments.
  • 9. History of hypersensitivity or allergic reactions to inactive ingredients in active or placebo products, including compounds related to DMT.
  • 10. Females of childbearing potential with positive urine pregnancy at screening or day of first treatment.
  • 11. Drinks on average more than 8 cups of caffeinated beverages per day.
  • 12. Received an investigational intervention or invasive investigational device within 90 days (or 5 half-lives) before planned first dose or currently enrolled in another investigational study.
  • 13. History of drug or alcohol use disorder (DSM-IV/DSM-5) within past five years.
  • 14. Positive test result(s) for alcohol and/or drugs of abuse at screening or admission.
  • 15. Current or history of any clinically relevant psychiatric disorder per DSM-IV/DSM-5 (e.g., psychotic disorder, bipolar I/II, personality disorder, major depressive disorder, OCD, panic disorder, anorexia nervosa, bulimia nervosa, GAD, PTSD, ASD).
  • 16. Family history of a relevant psychiatric disorder in first-degree relatives.
  • 17. Persistent psychological effects following previous use of hallucinogens (e.g., anxiety, depressed mood, paranoid ideation, HPPD, recurrent flashbacks).
  • 18. Risk of suicide, as judged by an Investigator, based on available source information (including the C-SSRS) indicating current suicidal ideation or history of active suicidal ideation or suicide attempts.
  • 19. Donated/received blood or blood loss >500 mL within 3 months before screening.
  • 20. Vulnerable subjects (e.g., persons detained or under guardianship).
  • 21. Subject is an employee of the investigator or study site with direct study involvement, or family members thereof.
  • 22. Unable to read/understand consent forms or complete study procedures.
  • 23. Positive SARS-CoV-2 rapid antigen test prior to first dosing.

Study Protocol, Arms & Participants

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Study Details

Locations

Centre for Human Drug Research — Leiden, Netherlands

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