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Trial registered on ANZCTR


Registration number
ACTRN12622000883718p
Ethics application status
Submitted, not yet approved
Date submitted
15/06/2022
Date registered
22/06/2022
Date last updated
22/12/2022
Date data sharing statement initially provided
22/06/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Brain Activity Effects of Psychedelic Medicines
Scientific title
Brain Activity Effects of Psychedelic Medicines in Healthy Volunteers
Secondary ID [1] 307357 0
None
Universal Trial Number (UTN)
Trial acronym
BAE-PM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 326657 0
Post-traumatic stress disorder 326658 0
Condition category
Condition code
Mental Health 323897 323897 0 0
Studies of normal psychology, cognitive function and behaviour
Mental Health 323898 323898 0 0
Depression
Mental Health 323929 323929 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will undergo a single drug exposure session with either psilocybin or Methylenedioxymethamphetamine (MDMA). This may occur individually or in small groups of 2-6 individuals depending on participant availability, but regardless of circumstances they will be supported all times by two therapists (one male and one female) for the duration of the experience, in comfortable surroundings.

Some participants may return for a second series of sessions, where they will receive the drug they did not receive in the first session. For example, if they were administered MDMA initially, the second session will involve psilocybin. The selection of these participants will be based on participant choice and study staff and resource availability. This second session will take place at least 3 months following the first session.

For the psilocybin arm of the study, a single dose of 25 mg of psilocybin will be provided for a person weighing under 90 kg. A single dose of 30 mg of psilocybin will be provided for a person weighing between 90 kg and 115 kg. A single dose of 35 mg of psilocybin will be provided for a person weighing over 115 kg.

For the MDMA arm of the study, a single dose of 80 mg of MDMA will be provided, followed by an optional half-dose of 40 mg.

Both the MDMA and psilocybin will be orally administered in capsule form under the supervision of study personnel.
Intervention code [1] 323786 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 331712 0
The first primary outcome will be the electroencephalographic (EEG) measure known as the N100 (a negative voltage deflection occurring 100ms after stimulus presentation) in a latent inhibition task.
Timepoint [1] 331712 0
The primary timepoints will be a single baseline assessment within 16 days prior to the psychedelic exposure session, and a single post-psychedelic exposure assessment, within 16 days after the psychedelic exposure session.
Primary outcome [2] 331713 0
The second primary outcome will be the EEG N100 measure obtained during an auditory oddball task.
Timepoint [2] 331713 0
The primary timepoints will be a single baseline assessment within 16 days prior to the psychedelic exposure session, and a single post-psychedelic exposure assessment, within 16 days after the psychedelic exposure session.
Primary outcome [3] 331714 0
The third primary outcome will be the EEG N170 measure obtained during an emotional Stroop task.
Timepoint [3] 331714 0
The primary timepoints will be a single baseline assessment within 16 days prior to the psychedelic exposure session, and a single post-psychedelic exposure assessment, within 16 days after the psychedelic exposure session.
Secondary outcome [1] 410845 0
The power-frequency slope of non-oscillatory EEG activity during resting EEG recordings
Timepoint [1] 410845 0
The timepoints will be a single baseline assessment within 16 days prior to the psychedelic exposure session, and a single post-psychedelic exposure assessment, within 16 days after the psychedelic exposure session.
Secondary outcome [2] 410846 0
Self-report measures of personality using the IPIP-NEO-60 (Maples-Keller et al., 2019).
Timepoint [2] 410846 0
The timepoints will be a single baseline assessment within 16 days prior to the psychedelic exposure session, and another single post-psychedelic exposure assessment within 16 days after the psychedelic exposure session.
Secondary outcome [3] 410847 0
Side effect reports via a study-specific self-report questionnaire.

Examples of side effects are: a dry mouth, difficulty concentrating, sweating, jaw clenching, headache, dizziness, nausea, anxiety, irritability, and confusion.
Timepoint [3] 410847 0
Side effects will be measured within 3 days and also again within 2 weeks of the psychedelic dosing session.
Secondary outcome [4] 410898 0
Trust using the The General Trust Scale (Horii & Tsuchiya, 1995).
Timepoint [4] 410898 0
The timepoints will be a single baseline assessment within 16 days prior to the psychedelic exposure session, and another single post-psychedelic exposure assessment within 16 days after the psychedelic exposure session.
Secondary outcome [5] 410899 0
Mindfulness using the Mindful Attention Awareness Scale (MAAS; Brown & Ryan, 2003)
Timepoint [5] 410899 0
The timepoints will be a single baseline assessment within 16 days prior to the psychedelic exposure session, and another single post-psychedelic exposure assessment within 16 days after the psychedelic exposure session.
Secondary outcome [6] 410900 0
Metaphysical Beliefs Questionnaire to assess whether their metaphysical beliefs become less materialist after exposure to the psychedelic substance, as has been found in previous research (Timmermann et al., 2021).
Timepoint [6] 410900 0
The timepoints will be a single baseline assessment within 16 days prior to the psychedelic exposure session, and another single post-psychedelic exposure assessment within 16 days after the psychedelic exposure session.

Eligibility
Key inclusion criteria
Participants can be included if they are between the ages of 21 and 70, and voluntarily consent to participate after demonstrating competence to consent following discussion with one of the study researchers. Additional inclusion criteria will be:
- Participants must be able to swallow capsules.
- If of childbearing potential, agree to practice an effective means of birth control throughout the duration of the study.
- Participants must have an identified support person and agree to be accompanied home by that person following dosing be in the presence of that person until the next day.
- Agree to not operate a vehicle for at least 48 hours after initial drug administration. Participants must have transportation available after the Experimental Session and through the following day. Participants will also be warned that the substances will be potentially detectable in roadside drug tests for a number of days after ingestion.
- Must provide a contact (relative, spouse, close friend, or other caregiver) who is willing and able to be reached by the investigator in the event of an emergency or if the participant is unreachable.
- Must agree to inform the investigator within 48 hours if any medical conditions occur or medical procedures are planned.
- Are proficient in speaking and reading English.
- Have completed a Certificate in Psychedelic-Assisted Therapies course.
Minimum age
21 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Participants who are not able to give adequate informed consent.
- Participants will be excluded if they are pregnant or lactating, have a history of neurological or mental illness or substance abuse or dependence. Participants will also be excluded if taking medication or drugs known to alter brain activity or have a history of seizures.
- Have any of the following cardiovascular conditions: uncontrolled hypertension, coronary artery disease, congenital long QT syndrome, cardiac hypertrophy, cardiac ischemia, congestive heart failure, myocardial infarction, tachycardia, artificial heart valve, a clinically significant screening ECG abnormality, or any other significant cardiovascular condition.
- Participants who are older than 40 years with a positive family history (in a first degree relative) of coronary heart disease and/or presenting substantive risk factors for cardiovascular disease as determined judged by a study doctor.
- Have a history of ventricular arrhythmia at any time, other than occasional premature ventricular contractions (PVCs) in the absence of ischemic heart disease.
- Have Wolff-Parkinson-White syndrome or any other accessory pathway that has not been successfully eliminated by ablation.
- Moderate to severe previous or current head injury/Traumatic Brain Injury (TBI).
- Have a history of stroke or Transient Ischemic Attack (TIA).
- Have moderate to severe hepatic impairment.
- Have epilepsy.
- Have insulin-dependent diabetes.
- Nicotine dependence that would disallow an individual to be nicotine free for the 7-10 hours during the dosing period.
- Current or previous diagnosis of schizophrenia spectrum or other psychotic disorders, including major depressive disorder with psychotic features, or Bipolar I or Bipolar II Disorder.
- Or an immediate family member with a diagnosed psychotic disorder or meeting the DSM-5 criteria for any of these disorders.
- Current or previous diagnosis of alcohol or drug use disorder, or meeting the DSM-5 criteria for either of these disorders.
- History of serious suicide attempts requiring hospitalisation, or any participant presenting current serious suicide risk, as determined through meeting criteria on the Columbia Suicide Severity Rating Scale (C-SSRS) (participants will be excluded if they meet criteria on this scale).
- Significant history of mania.
- Any other psychiatric condition judged to be incompatible with safe exposure to psilocybin, e.g. borderline personality disorder.
- Positive pregnancy test at screening or during the study, women who are planning a pregnancy and/or women who are nursing/breastfeeding. Any person with female reproductive organs and of childbearing potential will undertake a pregnancy test as part of the study prior to any dosing of MDMA or psilocybin.
- Participants who do not agree to use an acceptable contraceptive method throughout their participation in study.
- Use of contraindicated medication (outlined further below).
- Previous experience with MDMA or psilocybin in the past three months.
- Current or previous diagnosis of antisocial personality disorder, or meeting the DSM-5 criteria for this disorder, or any other significant personality disorder as determined by the Standardized Assessment of Personality: Abbreviated Scale (SAPAS; Moran et al., 2003).
- Participants who weigh less than 48kg.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Participants will either receive MDMA or psilocybin, however, these two conditions will not be compared against each other. Instead, the study will compare outcomes from participants from each condition between baseline data (obtained prior to the psychedelic exposure) and a post-psychedelic exposure timepoint.
Phase
Phase 2 / Phase 3
Type of endpoint/s
Pharmacodynamics
Statistical methods / analysis
While there is no directly comparable research available from which to extrapolate potential effect sizes, effect sizes in previous research that has examined the effects of acute exposure to psychedelics across a range of neural activity measures reported large effect sizes (Cohen’s d > 0.70) in measures obtained using the oddball task and other EEG measures (Duerler et al., 2021; Muthukumaraswamy et al., 2013; Timmermann et al., 2018). However, the effects of some clinical disorders on facial emotion processing (one of the tasks used in the current study) are small (d = 0.35) (Schneider et al., 2018). Additionally, effect sizes in cross-sectional studies comparing heavy MDMA users to healthy controls in EEG measures of the oddball task produce only medium effect sizes (d ~=0.6) (Croft, Klugman, Baldeweg, & Gruzelier, 2001; Tuchtenhagen et al., 2000). As such, we expect that non-acute effects of a single session psychedelic exposure are likely be similarly small for facial emotion processing, the oddball task, and our other measures also. As such, we will take a conservative approach and power our core study to detect small effect sizes (d = 0.3). Comparisons will be performed using paired samples t-test designs with two tailed statistical testing, comparing pre- to post MDMA exposure in a separate analysis to the pre- and post psilocybin exposure . With this study design, recruiting 100 participants and accounting for 10% attrition or technical issues in data collection (N = 90) provides sufficient statistical power to detect an effect size d = 0.3 with a power value of 0.80 at an alpha of 0.05.

EEG analyses will be performed automatically on the processed EEG data, time-locked to the stimuli presentation from each task, including all electrodes and time windows (without any specific electrode or time window selection that excludes any of the data), using randomisation statistics provided by the randomisation graphical user interface (RAGU) software (Habermann, Weusmann, Stein, & Koenig, 2018). This analysis approach applies randomisation statistics to robustly test for differences in the neural response strength using the global field potential, and for differences in the distribution of neural activity using global dissimilarity maps. This approach uses all electrodes and timepoints in its analysis, so prevents any potential experimenter bias from selection of electrodes or timepoints for analysis, while still robustly controlling for multiple comparisons using variations on traditional randomisation statistical approaches (the global duration statistic and global count statistic).

Lastly, the self-report measures will be analysed as exploratory comparisons using robust repeated measures ANOVAs with the WRS2 package in R, which are as sensitive as traditional parametric t-tests, but robust against violations of the assumptions of traditional statistical methods (such as normality) (Mair & Wilcox, 2020) .

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
22/08/2022
Actual
Date of last participant enrolment
Anticipated
22/08/2025
Actual
Date of last data collection
Anticipated
18/11/2025
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 37805 0
3127 - Surrey Hills

Funding & Sponsors
Funding source category [1] 311641 0
Commercial sector/Industry
Name [1] 311641 0
Transcranial Magnetic Stimulation Clinics Australia
Country [1] 311641 0
Australia
Funding source category [2] 311643 0
Commercial sector/Industry
Name [2] 311643 0
Mind Medicine Australia
Country [2] 311643 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Transcranial Magnetic Stimulation Clinics Australia
Address
Suite 701, Level 7, 225 Clarence Street, Sydney 2000
Country
Australia
Secondary sponsor category [1] 313084 0
None
Name [1] 313084 0
Address [1] 313084 0
Country [1] 313084 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 311097 0
Bellberry Limited
Ethics committee address [1] 311097 0
Ethics committee country [1] 311097 0
Australia
Date submitted for ethics approval [1] 311097 0
03/09/2021
Approval date [1] 311097 0
Ethics approval number [1] 311097 0
2021-08-877

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 119934 0
Dr Neil Bailey
Address 119934 0
TMS Clinics Australia, Shop 2, 629 Canterbury Road, Surrey Hills Vic 3127.
Country 119934 0
Australia
Phone 119934 0
+61 1300 867 888
Fax 119934 0
Email 119934 0
nbailey@tmsaustralia.com.au
Contact person for public queries
Name 119935 0
Samantha Webb
Address 119935 0
TMS Clinics Australia, Shop 2, 629 Canterbury Road, Surrey Hills Vic 3127.
Country 119935 0
Australia
Phone 119935 0
+61 1300 867 888
Fax 119935 0
Email 119935 0
MonarchResearchInstitute@mmhg.com.au
Contact person for scientific queries
Name 119936 0
Neil Bailey
Address 119936 0
TMS Clinics Australia, Shop 2, 629 Canterbury Road, Surrey Hills Vic 3127.
Country 119936 0
Australia
Phone 119936 0
+61 1300 867 888
Fax 119936 0
Email 119936 0
nbailey@tmsaustralia.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Both the EEG data and the self-report data, with all data de-identified prior to sharing.
When will data be available (start and end dates)?
Beginning 3 months following main results publication, with no end date determined.
Available to whom?
Anyone who wishes to access it.
Available for what types of analyses?
Any purpose.
How or where can data be obtained?
Unrestricted access via web address yet to be determined.


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.