Clinical TrialMajor Depressive Disorder (MDD)LSDRecruiting

Assessing the effects of Lysergic acid diethylamide (LSD) microdosing in people experiencing depression (LSDDEP1)

This open-label pilot trial (n=20) aims to evaluate the tolerability and feasibility of LSD microdosing in patients with major depressive disorder (MDD).

Target Enrollment
20 participants
Study Type
Phase II interventional
Design
Non-randomized

Detailed Description

Open-label, single-group Phase II pilot (n=20) testing sublingual LSD solution microdosing twice weekly for 8 weeks with a predefined titration (start 8 µg, +1 µg per dose, limits 5–15 µg; reduce by 3 µg if not tolerated). Adherence monitored via video-recorded dosing.

Primary outcomes: percentage of participants completing the dosing regimen (audit of case report files) and total MADRS score at 8 weeks. Assessments at baseline, 2, 4, 6 and 8 weeks.

Study Protocol

Preparation

sessions

Dosing

16 sessions

Integration

sessions

Study Arms & Interventions

LSD microdose

experimental

Sublingual LSD solution, titrated microdoses twice weekly for 8 weeks.

Interventions

  • LSD8 µg
    via Sublingual• twice weekly• 16 doses total

    Start 8 µg; titrate +1 µg each dose; reduce by 3 µg if not tolerated; titration limits 5–15 µg; adherence monitored by video of each dose.

Participants

Ages
21 – 65
Sexes
Male & Female

Inclusion Criteria

  • 1. Provision of signed and dated informed consent form.
  • 2. Stated willingness to comply with all study procedures and availability for the duration of the study.
  • 3. Any gender identity aged 21-65 years.
  • 4. Diagnosis of Major Depressive Disorder (MDD) as per DSM-5 criteria.
  • 5. MADRS score between 18 and 35 at screening.
  • 6. Ability to take oral medication and willing to adhere to study intervention regimen.
  • 7. For persons of child-bearing potential: agree to use effective or highly effective contraception.

Exclusion Criteria

  • 1. Current or past history of schizophrenia or other psychotic disorders, or bipolar I or II disorder.
  • 2. Diagnosis of PTSD as assessed by clinical interview.
  • 3. Diagnosis of an eating disorder as assessed by clinical interview.
  • 4. Risk of suicide as determined by The Columbia-Suicide Severity Rating Scale (C-SSRS).
  • 5. Substance dependence in the previous 6 months.
  • 6. Problematic alcohol use (AUDIT score ≥16).
  • 7. Stage II or higher treatment-resistant depression (Thase and Rush 1997 staging) for the current episode.
  • 8. BMI <18 or >35.
  • 9. Planned or current pregnancy or lactation.
  • 10. Cardiovascular conditions including abnormal heart rate or blood pressure.
  • 11. Significant renal or hepatic impairment.
  • 12. Abnormal 12-lead ECG as judged by a study physician.
  • 13. Abnormal laboratory test findings as judged by a study physician.
  • 14. Use of monoamine oxidase inhibitors, methylphenidate or dexamphetamine.
  • 15. Excessive ongoing medication burden as determined by a study physician.
  • 16. Any lifetime history of psychedelic microdosing.
  • 17. Use of serotonergic psychedelic drugs in the last year.
  • 18. Lifetime history of self-medicating with psychedelics to treat their depression.

Primary Results(3 publications)

Participants

N = 17Mean age: 39.67 across armsC. et al. 2025 →
N = 19Mean age: 41.52 across armsD. et al. 2026 →
N = 19Mean age: 41.52 across armsD. et al. 2026 →

Adverse Events (from all publications)

Arm / GroupnAny TEAESevereSeriousDiscont.
LSD microdoseexperimental17————
LSD microdoseexperimental198(42.1%)0(0.0%)0(0.0%)1(5.3%)
LSD microdoseexperimental19————

* The paper is a qualitative thematic analysis. While it mentions 'negative effects' including sleep disruptions, anxiety, dizziness, and light-headedness, it does not provide summary-level counts for TEAEs. The nAtRisk is the 17 participants who completed the regimen.

* nAtRisk is the number of participants who received the intervention. One participant withdrew due to anxiety. No serious or severe adverse events were reported. Total TEAEs (8 participants) includes headache, anxiety, abnormal dreams, upset ruminations, and upset stomach.

* The paper states that a titration protocol reduced the occurrence of adverse events leading to withdrawal, but does not provide specific summary counts for TEAEs in this study. Safety and outcomes are noted to be presented in Daldegan-Bueno et al., 2025.

Study Details

  • Status
    Recruiting
  • Phase
    Phase II
  • Type
    interventional
  • Design
    Non-randomized
  • Target Enrollment20 participants
  • Timeline
    Start: 2023-08-14
    End: 2024-08-08
  • Compound
    LSD
  • Topic
    Major Depressive Disorder (MDD)

Locations

Unknown facility — Australia

Related Publications

What is it like to microdose LSD for depression? a thematic analysis of participant interviews from an open-label trial

Published
Authors
Joy Donegan, C., Daldegan-Bueno, D., Sumner, R. L., Forsyth, A., Evans, W., Hoeh, N. R., Sundram, F., Menkes, D., Muthukumaraswamy, S., Reynolds, L.

LSD microdosing in major depressive disorder: results from an open-label trial

Published
Authors
Daldegan-Bueno, D., Donegan, C. J., Sumner, R. L., Forsyth, A., Evans, W. J., Alshakhouri, M., Reynolds, L. M, Roop, P., Ponton, R., Smith, T., Hoeh, N. R., Allen, N., Sundram, F., Menkes, D. B., Muthukumaraswamy, S.

LSD microdosing for major depressive disorder: Mood and pharmacokinetic outcomes from a Phase 2a trial

Published
Authors
Daldegan-Bueno, D., Donegan, C. J., Sumner, R., Forsyth, A., Jeong, S. H., Evans, W., Alshakhouri, M., Murphy, R. J., Reynolds, L., Hoeh, N., Allen, N., Sundram, F., Menkes, D. B., Muthukumaraswamy, S.

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