Clinical trial NCT04060108: Stanford Regulating Circuits of the Brain Study - MDMA
Official title: Mapping the Influence of Drugs of Abuse on Risk and Reward Circuits - MDMA
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Healthy
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: Lykos Therapeutics
First posted: 2019-08-16
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy participants ages 18-55 years who have had at least two prior exposures to MDMA

Brief summary: This study is a biomarker study designed to characterize how human neural circuits and behaviors are modified during altered states induced by MDMA.

Detailed description: The investigators will assess the effect of acute MDMA modulation on the functioning of human brain circuits. Brain circuits will be assessed using functional magnetic resonance imaging.

Participants will include volunteers who report more than two prior uses of MDMA (also known as Ecstasy), when they were 18 years or older.

The investigators will recruit individuals who have previously tried MDMA rather than those who are MDMA-naïve.

Participants will receive an oral dose of MDMA (80mg and 120mg) and placebo (saline) at 3 separate study sessions. Following established procedures, these three sessions will be randomized in a blinded protocol in order to limit expectancy effects.

Throughout each session, participants will be monitored. Functional imaging will commence after the drug has reached peak levels, following previously established time courses for MDMA administered orally. Participants will also be monitored after the functional imaging session. Secondary effects of MDMA on behavior and self-reported experience will be assessed.

In the assessment of the acute effects of MDMA, the investigators will take into account the cumulative effects of prior drug exposure.

Eligibility criteria: Inclusion Criteria:

1. Ages 18-55
2. Able to swallow capsules
3. All genders and ethno-racial categories
4. Able and willing to enroll and provide written informed consent.
5. Able to comply with study procedures.
6. 2+ prior uses of MDMA when aged 18 years or older and have reported no serious adverse reactions from MDMA or ecstasy.
7. Non-nicotine user, defined as no primary nicotine exposure for last six months.
8. Agree to not use caffeine for 12 hours before and 10 hours after drug administration.
9. Not using any medication or substance that might increase the risk of participation and/or interact with MDMA (i.e., serotonergic agents, antidepressants, opiates, any drugs with known interactions with Monoamine Oxidase Inhibitors).
10. Must agree to inform the investigators within 48 hours of any changes in medical conditions or procedures.
11. If of childbearing potential, must have a negative pregnancy test at study entry and prior to each drug session and must agree to use adequate birth control through 10 days after the last drug session. Adequate birth control methods include intrauterine device (IUD), injected or implanted hormonal methods, abstinence, oral hormones plus a barrier contraception, vasectomized sole partner, or double barrier contraception. Two forms of contraception are required with any barrier method or oral hormones.
12. Able to receive an MRI.

Exclusion Criteria:

1. Have current serious suicide risk, as determined through psychiatric interview, responses to C-SSRS, and clinical judgment of the investigator.
2. Current psychiatric, mood, anxiety, eating or psychotic disorder assessed at screening with the MINI and medical history.
3. Current use of any psychotropic medication (a wash-out period of 5 half-lives will be required prior to drug visits followed by a 1-week stabilization period, if the participant reports recently discontinuing a psychotropic medication).
4. Have used Ecstasy (material represented as containing MDMA) within 6 months of the first study dose; or have previously participated in a MAPS-sponsored MDMA clinical trial.
5. Positive for drug, or alcohol abuse disorders as assessed through DAST, CUDIT-R, Fagerstrom and AUDIT measures.
6. Positive test on urine drug screen for illicit and/or drugs of abuse at screening and prior to study drug administration.
7. Concurrent use of any medication or substance that might increase the risk of participation and/or interact with MDMA (i.e., serotonergic agents, antidepressants, opiates, any drugs with known interactions with Monoamine Oxidase Inhibitors).
8. Unable or unwilling to agree to refrain from using any psychoactive substances (i.e., cannabis), supplements (i.e., St. John's Wort, SAMe, 5HTP) and nonprescription medications (i.e., dextromethorphan) starting 1-week prior to study start and for duration of study.
9. Current use of any opioids, including codeine, hydrocodone, and morphine.
10. Have an exclusionary metal device (e.g., presence of metallic device or dental braces, which are contraindications for MRI) as determined by the discretion of the Clinical Investigator.
11. BMI outside of healthy range (18-30)
12. Inability to speak, read or understand English at a 5th grade level or severe hearing impairment.
13. Plan to move out of the area during the study period (given repeated testing sessions)
14. Individuals who are pregnant or nursing.
15. Schizophrenia in a first degree relative.
16. Direct physical access to or routinely handling of addicting drugs in the regular course of work duties.
17. Allergy or hypersensitivity to MDMA
18. Renal/hepatic impairment (assessed via laboratory tests during initial screening appointment)
19. Hypertension (Hypertension, Stage 1 as defined by a systolic blood pressure \>140 mmHg or diastolic blood pressure \> 90 mmHg on two of three measurements at least 15 minutes apart at initial screening appointment; systolic blood pressure \>155 mmHg or diastolic blood pressure \>99 mmHg on two of three measurements at least 15 minutes apart during drug administration visits)
20. Heart rate \<50bpm or \>150bpm assessed at initial screening visit (PI discretion for bradycardia)
21. Chronic congestive heart failure, tachyarrhythmias, myocardial ischemia (assessed via EKG at initial screening appointment)
22. Have a marked Baseline prolongation of QT/QTc interval e.g., repeated demonstration of a QTc interval \>450 milliseconds (ms) in males and \>460 ms in females. For transgender or non-binary participants, QTc interval will be evaluated based on sex assigned at birth, unless the participant has been on hormonal treatment for 5 or more years.
23. Have evidence or history of significant (controlled or uncontrolled) hematological, endocrine, cerebrovascular, cardiovascular, coronary, pulmonary, renal, gastrointestinal, immunocompromising, or neurological disease, including seizure disorder, or any other medical disorder judged by the investigator to significantly increase the risk of MDMA administration (participants with hypothyroidism who are on adequate and stable thyroid replacement will not be excluded). Note: if participants present with a history of glaucoma, enrollment would be allowed only with the approval of their ophthalmologist.
24. Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
25. Have history of hyponatremia or hyperthermia

Primary outcomes:
measure: Facial Expressions of Emotion Task (FEET, nonconscious and conscious) evoked functional activity and connectivity
timeFrame: up to 2 hours after the administration of MDMA or Placebo
Secondary outcomes:
measure: Resting-state functional activity and connectivity
timeFrame: up to 2 hours after the administration of MDMA or Placebo
measure: MID evoked functional activity and connectivity
timeFrame: up to 2 hours after the administration of MDMA or Placebo
measure: Go-No-Go evoked functional activity and connectivity
timeFrame: up to 2 hours after the administration of MDMA or Placebo
measure: Behavioral responses on the WebNeuro computerized test battery assessing cognitive capacity
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Self-reported responses as assessed by the 21-item Depression, Anxiety and Stress Scale (DASS)
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Self-reported responses as assessed by the 29-item Rotter's Locus of Control (RLoC)
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Self-reported responses as assessed by the 15-item Mini Brief Risk-Resilience Index for Screening (BRISC)
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Self-reported responses as assessed by the 14-item Snaith-Hamilton Please Scale (SHAPS)
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Self-reported responses as assessed by the 24-item Dimensional Apathy Scale (DAS)
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Self-reported responses as assessed by the 18-item Motivation and Pleasure Scale Self-Report (MAP-SR)
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Self-reported responses as assessed by the 17-item Dimensional Anhedonia Rating Scale (DARS)
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Self-reported responses as assessed by the 94-item 5-Dimensional Altered States of Consciousness Rating Scale (DASC)
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Self-reported responses as assessed by the 23-item Social Reward Questionnaire (SRQ)
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Self-administered computerized task assessed by Multifaceted Empathy Test (MET)
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Level of subjectively experienced mood and feelings as assessed by rating scale
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Self-reported responses as assessed by the 23-item Clinician Administered Dissociative States Scale (CADSS)
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Self-reported responses as assessed by a clinician on the 18-item Brief Psychiatric Rating Scale (BPRS)
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Self-reported responses as assessed by the Acceptance/Avoidance-Promoting Experiences Questionnaire (APEQ)
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Self-reported responses as assessed by the MID Cue Rating
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Self-reported responses as assessed by the Face Likability Rating
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Steroid hormone assay via saliva collection
timeFrame: up to 5 hours after the administration of MDMA or Placebo
measure: Qualitative free responses
timeFrame: up to 5 hours after the administration of MDMA or Placebo
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Psychiatry and Behavioral Sciences Department
state: California
Study officials:
affiliation: Stanford PI
name: Leanne M Williams, PhD
role: PRINCIPAL_INVESTIGATOR
References: