Clinical TrialHealthy VolunteersDMTDMTCompleted

Safety, blood levels and effects of N,N-dimethyltryptamine [DMT (SPL026)] in healthy participants that have taken psychedelic substances before (Part A) and in healthy participants with little to no psychedelic experience (Part B)

Open-label, crossover Phase I study (target n=30, actual enrolment 14) assessing safety, blood levels and effects of SPL026 (DMT fumarate) given IM and IV in healthy psychedelic-experienced (Part A) and little/no-experience (Part B) participants.

Target Enrollment
14 participants
Study Type
Phase I interventional
Design
Non-randomized

Detailed Description

This open-label crossover Phase I trial assessed single IM and IV doses of SPL026 (DMT fumarate) in healthy volunteers; Part A (psychedelic‑experienced) received IM 20 mg then IV 27.5 mg in a crossover, and Part B (little/no experience) received doses/routes informed by Part A.

Primary outcomes were safety and tolerability (AEs, labs, vitals) with PK sampling (IV PK to 2 h, IM PK to 4 h) and multiple PD measures including WEMWBS, STAI, MEQ, EDI, EBI and CEQ; follow-up assessments occurred up to 15 days post-second dosing session.

Study Protocol

Preparation

sessions

Dosing

2 sessions
240 min each

Integration

sessions

Study Arms & Interventions

SPL026 (DMT)

experimental

Open-label, crossover IM and IV single-dose SPL026 (DMT fumarate) administration across Part A (experienced) and Part B (little/no experience); dosing route and dose for Part B informed by Part A.

Interventions

  • DMT20 mg
    via IM• single dose• 1 doses total

    Planned Part A IM single dose 20 mg; Part B may receive IM doses based on Part A.

  • DMT27.5 mg
    via IV• single dose• 1 doses total

    Planned Part A IV single dose 27.5 mg (crossover with IM dose 2-3 weeks apart).

Participants

Ages
25 – 65
Sexes
Male & Female

Inclusion Criteria

  • Part A only:
  • 1. Healthy psychedelic-experienced female or male participants (defined as at least two previous experiences, with breakthrough, of serotonergic psychedelic drugs).
  • 2. No psychedelic drug use within 6 weeks prior to dosing.
  • Part B only:
  • 3. Healthy female or male participants with little to no psychedelic experience (never taken serotonergic psychedelics, or only sub-breakthrough doses, <5 times).
  • 4. No psychedelic drug use within 6 months prior to dosing.
  • Parts A and B:
  • 5. Aged 25-65 years.
  • 6. BMI 18.0-33.9 kg/m2.
  • 7. Sufficient intelligence and communication to consent and comply.
  • 8. Willing to give written consent and follow contraception requirements.
  • 9. Agree not to donate blood during study and for 3 months after last administration.
  • 10. Willing to refrain from psychedelic drug use (excluding study drug) during trial and until follow-up.
  • 11. Willing to have data entered into TOPS and be contacted by email/video call.
  • 12. Has veins suitable for cannulation (IV/blood sampling).

Exclusion Criteria

  • 1. Current or previously diagnosed mental health disorder per DSM‑V.
  • 2. First degree relative with schizophrenia spectrum or other psychotic disorders, or bipolar and related disorders.
  • 3. Disposition judged incompatible with safe exposure to DMT.
  • 4. Pregnant or lactating women, or sexually active pre‑menopausal women not using reliable contraception.
  • 5. Clinically relevant abnormal history, exam, ECG, or labs interfering with objectives or safety.
  • 6. Acute or chronic illness (including seizure disorder) rendering participation hazardous.
  • 7. Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease or specified cardiovascular conditions (arrhythmia, significant ECG abnormality, family history of long QT or sudden death, artificial heart valve, current/history of hypertension) or other significant cardiovascular disease per investigator.
  • 8. History of serious suicide attempts (requiring hospitalisation); as assessed by the BSS.
  • 9. History of severe adverse reaction to any drug or sensitivity to serotonergic psychedelics.
  • 10. Use of prescription medicines (except oral contraceptives/hormone therapy), certain herbal supplements (eg St John's Wort) or OTC medicines within 28 days before first dose (paracetamol/NSAIDs permitted up to 4 h prior).
  • 11. Receipt of an investigational product within 3 months before first admission or being in another trial follow-up at screening.
  • 12. History of drug or alcohol abuse, or >14 units alcohol weekly.
  • 13. Daily cannabis use or dependence; use of cannabis within 24 h before each visit.
  • 14. Evidence of drug abuse on urine testing (except cannabis).
  • 15. Unable to be nicotine-free for 24 h before and until morning after dosing.
  • 16. Screening BP or pulse outside allowed ranges (BP 80-150/30-100 mmHg; pulse 40-100 bpm) after repeat testing rules.
  • 17. QTcF at screening >450 ms (men) or >470 ms (women) on 12-lead ECG (triplicate mean). Repeat allowed once.
  • 18. Inability to cooperate with protocol requirements.
  • 19. Positive test for hepatitis B, hepatitis C or HIV.
  • 20. Loss of >400 mL blood in prior 3 months.
  • 21. Phobia of needles or blood.
  • 22. Objection by GP to participation.

Study Details

  • Status
    Completed
  • Phase
    Phase I
  • Type
    interventional
  • Design
    Non-randomized
  • Target Enrollment14 participants
  • Timeline
    Start: 2022-05-22
    End: 2023-04-05
  • Compounds
    DMTDMT
  • Topic
    Healthy Volunteers

Locations

Hammersmith Medicines Research Limited — London, United Kingdom

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