Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000128594
Ethics application status
Approved
Date submitted
26/12/2023
Date registered
13/02/2024
Date last updated
29/02/2024
Date data sharing statement initially provided
13/02/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessing the effects of Lysergic acid diethylamide (LSD) microdosing in people experiencing depression (LSDDEP2)
Scientific title
A randomised, double-dummy, triple-blind, active placebo-controlled, parallel groups, trial of LSD microdosing in patients with major depressive disorder (LSDDEP2).
Secondary ID [1] 311244 0
Nil known
Universal Trial Number (UTN)
Trial acronym
LSDDEP2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder (MDD) 332466 0
Condition category
Condition code
Mental Health 329160 329160 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 327702 0
Treatment: Drugs
Comparator / control treatment
Orally administered caffeine or ritalin pills (randomly allocated)
Two doses taken every week for eight weeks.
Starting dose is 100 mg caffeine or 20 mg Ritalin.
Range (caffeine) is 50-300 mg
Range (ritalin) is 10 - 60 mg
Adherence will be monitored by participants sending video recordings of each dose administration to the study team
Doses increased/decreased by 50 mg (caffeine) or 5 mg (ritalin) if well tolerated at participant discretion
Control group
Active

Outcomes
Primary outcome [1] 336989 0
Total score of the Montomery-Asberg Depressive Rating Scale (MADRS)
Timepoint [1] 336989 0
8 weeks post-commencement of the intervention. Additional assessments are made at baseline (pre-commencement), 2 weeks, 4 weeks and 6 weeks post-commencement of intervention
Secondary outcome [1] 430326 0
Total score of the Hamilton Anxiety (HAM-A) Scale
Timepoint [1] 430326 0
8 weeks post-commencement of the intervention with additional assessment made at baseline (pre-commencement)
Secondary outcome [2] 430327 0
Depression sub scale of the Depression Anxiety and Stress Scale (DASS-21)
Timepoint [2] 430327 0
8 weeks post-commencement of the intervention with an additional assessment made at baseline (pre-commencement)
Secondary outcome [3] 430328 0
Anxiety sub scale of the Depression Anxiety and Stress Scale (DASS-21)
Timepoint [3] 430328 0
8 weeks post-commencement of the intervention with an additional assessment made at baseline (pre-commencement)
Secondary outcome [4] 430329 0
Stress sub scale of the Depression Anxiety and Stress Scale (DASS-21)
Timepoint [4] 430329 0
8 weeks post-commencement of the intervention with an additional assessment made at baseline (pre-commencement)
Secondary outcome [5] 430330 0
Total score of the Dimensional Anhedonia Rating Scale (DARS)
Timepoint [5] 430330 0
8 weeks post-commencement of the intervention with an additional assessment made at baseline (pre-commencement)
Secondary outcome [6] 430331 0
Total score of the Ruminative Response Scale (RRS)
Timepoint [6] 430331 0
8 weeks post-commencement of the intervention with an additional assessment made at baseline (pre-commencement)
Secondary outcome [7] 430332 0
Total score of the World Health Organisation Quality of Life Scale (WHOQOL-BREF)
Timepoint [7] 430332 0
8 weeks post-commencement of the intervention with an additional assessment made at baseline (pre-commencement)

Eligibility
Key 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
Minimum age
21 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation with block size of varying sizes (eight, ten and twelve)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
11/03/2024
Actual
Date of last participant enrolment
Anticipated
1/10/2025
Actual
Date of last data collection
Anticipated
26/11/2025
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment outside Australia
Country [1] 26056 0
New Zealand
State/province [1] 26056 0

Funding & Sponsors
Funding source category [1] 315500 0
Government body
Name [1] 315500 0
Health Reseach Council of New Zealand
Country [1] 315500 0
New Zealand
Funding source category [2] 315501 0
Commercial sector/Industry
Name [2] 315501 0
MindBio Therapeutics Ltd
Country [2] 315501 0
Australia
Primary sponsor type
University
Name
The University of Auckland
Address
University of Auckland Private Bag 92019 Auckland 1142 New Zealand
Country
New Zealand
Secondary sponsor category [1] 317578 0
None
Name [1] 317578 0
Address [1] 317578 0
Country [1] 317578 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314404 0
Southern HDEC
Ethics committee address [1] 314404 0
Health and Disability Ethics Committees Ministry of Health 133 Molesworth Street PO Box 5013 Wellington 6011
Ethics committee country [1] 314404 0
New Zealand
Date submitted for ethics approval [1] 314404 0
Approval date [1] 314404 0
14/12/2022
Ethics approval number [1] 314404 0

Summary
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
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 131462 0
A/Prof Suresh Muthukumaraswamy
Address 131462 0
School of Pharmacy The University of Auckland Private Bag 92019 Auckland 1142
Country 131462 0
New Zealand
Phone 131462 0
+64 093737599
Fax 131462 0
Email 131462 0
sd.muthu@auckland.ac.nz
Contact person for public queries
Name 131463 0
A/Prof Suresh Muthukumaraswamy
Address 131463 0
School of Pharmacy The University of Auckland Private Bag 92019 Auckland 1142
Country 131463 0
New Zealand
Phone 131463 0
+64 093737599
Fax 131463 0
Email 131463 0
sd.muthu@auckland.ac.nz
Contact person for scientific queries
Name 131464 0
A/Prof Suresh Muthukumaraswamy
Address 131464 0
School of Pharmacy The University of Auckland Private Bag 92019 Auckland 1142
Country 131464 0
New Zealand
Phone 131464 0
+64 093737599
Fax 131464 0
Email 131464 0
sd.muthu@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.