None listed
Conditions
Brief summary
Depressive disorders are the leading cause of “years lived with disability” in New Zealand and there is a clear need for the development of new, alternative antidepressant therapies. In light of problems with the tolerability and efficacy of available treatments, a global trend is emerging for patients to self-treat depression with microdoses of psychedelic drugs such as lysergic acid diethylamide (LSD) and psilocybin. Beyond anecdotal reports from those who self-medicate in this way, there are few clinical trials that have evaluated this practice. In our recent Phase 1 study in healthy volunteers (ACTRN12621000436875) , we determined that LSD microdosing was relatively safe in this cohort and well-tolerated. Further data (ACTRN12623000486628) demonstrated that LSD microdosing is feasible and well tolerated in patients with depression. In this randomised controlled trial with patients with major depressive disorder (MDD) we will test the efficacy of an 8 week regimen of LSD microdosing in this patient group versus an active placebo to treat depressive symptology
Interventions
Sublingually administered Lysergic acid diethylamide (LSD) solution.
Two doses taken every week for eight weeks.
Starting dose is 8 mcg. Range is 2-20 mcg
Adherence will be monitored by participants sending video recordings of each dose administration to the study team
Dose increased decreased by 1 or 2 mcg at each dose if well tolerated at participant discretion.
Sponsors
The University of Auckland
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
21 Years to 65 Years
Healthy volunteers
No
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 the DSM-5 criteria for MDD 5. Have a MADRS score between 18-35 at the time of screening. 6. Ability to take oral medication and be willing to adhere to the study intervention regimen. 7. For persons of child-bearing potential: agree to use an effective or highly effective contraception
Exclusion criteria
1. Current or past history 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 use of alcohol defined as a score on the AUDIT of 16 or greater. 7. Stage II or higher treatment-resistant depression as defined by the Thase and Rush (1997) staging criteria for the current depressive episode. 8. BMI <18 and > 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 (ritalin) or dexamphetamine. 15. Excessive on-going 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. 19. Daily caffeine use > 500 mg per day
Outcome results
None listed