Clinical TrialDepressive DisordersPsilocybinMDMAWithdrawn

Brain Activity Effects of Psychedelic Medicines in Healthy Volunteers

This open-label Phase II trial (n=200) evaluated the safety and efficacy of psilocybin for depression post-traumatic stress disorder.

Target Enrollment
200 participants
Study Type
Phase II interventional
Design
Randomized

Detailed Description

The objective of this project is to investigate changes in neural activity associated with a single session of psychedelic drug exposure, in particular with psilocybin or 3,4- methylenedioxymethamphetamine (MDMA). Specifically, the study aims to use electroencephalography (EEG) to measure neural activity both before and two weeks after psychedelic exposure. EEG activity during a latent inhibition task will be measured, as decreased latent inhibition has been associated with the personality trait of openness to experience, a trait which previous research has shown is increased by exposure to psychedelics. Similarly, EEG activity during an auditory oddball task will be measured, as previous research has shown that exposure to psychedelics reduces neural adaptation to familiar stimuli. Neural activity associated with processing of facial emotions will also be assessed, as this activity has been suggested to be modified by MDMA and could be a potential explanation for therapeutic effects. Additionally, resting EEG measures will be used to test whether psychedelic exposure is associated with changes to the excitation/inhibition balances that underpinning healthy neural activity. We hypothesize that the measures of neural activity listed above will differ from pre to post psychedelic exposure.

Since both psilocybin and MDMA are becoming more commonly used to treat psychiatric illnesses, this study is important to both improve our understanding of the potential mechanisms of action of these drugs. As such, this study will have the potential to be highly beneficial in improving our understanding of these drugs as they transition towards broad scale implementation as therapies for psychiatric conditions.

Study Arms & Interventions

Experimental Arm

experimental

Interventions

  • Psilocybin
  • MDMA

Participants

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.

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 Details

  • Status
    Withdrawn
  • Phase
    Phase II
  • Type
    interventional
  • Design
    Randomized
  • Target Enrollment200 participants
  • Timeline
    Start: 2022-08-22
    End: 2025-08-22
  • Compounds
    PsilocybinMDMA
  • Topic
    Depressive Disorders

Locations

Unknown facility — Australia

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