Neurobiology and Pharmacokinets of Acute MDMA Administration

NCT01148342 | Completed Phase 1

• 2 other identifiers: 99990439404-DA-N394
• Study Type: interventional
• Target: 187
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy, is a synthetic psychoactive drug that has shown a steep increase in recreational use and abuse by young people in recent years. Research studies have reported that chronic MDMA users who also consume other legal and illegal substance show memory deficits; however, because of the combination of drugs often involved, it is difficult to determine MDMA s contribution to these effects.
• Only a few studies have examined the immediate physical and behavioral effects of MDMA given at dose levels commonly used in young adults. Researchers are interested in using functional magnetic resonance imaging (fMRI) to examine changes in brain activity and function in MDMA users compared with users of other drugs and non-drug-using individuals. Objectives: \- To evaluate the effects of MDMA on thinking and brain function. Eligibility: \- Individuals between 18 and 30 years of age who are (1) current users of MDMA (2), current drug users who do not use MDMA, or (3) healthy non-drug-using volunteers. Design:
• Participants will complete one training session and three scanning sessions.
• Before the start of the study, participants will complete questionnaires about medical and psychological history, and provide information about past or current drug use. Researchers will introduce the tasks to be performed during the scanning session(s), and will allow participants to practice the tests.
• Participants will provide urine, saliva, and hair samples for testing before the start of the study, and multiple times during each scanning session.
• Participants who use MDMA and participants who use other drugs will stay overnight at the clinical center prior to each scanning session. Participants who do not use drugs can spend the night prior to scanning or arrive at the clinical center on the morning of the scanning session.
• Participants who use MDMA will receive either MDMA or a placebo during the scanning sessions, and will not be told which one they have received. Because of the nature of MDMA, participants will be required to stay at the clinical center until the effects of the drug have worn off, and will be required to return to the clinical center on the following day for a follow-up examination.
• During the study, participants will be asked to do one or more tasks selected by the researchers. The tasks will be performed on a computer in an MRI machine, and may involve receiving monetary rewards for actions, memory and reaction-time tests, or other tests that involve responding to instructions on the screen.

Conditions

Substance-Related Disorders

Keywords

Ecstacy; fMRI; Alternative Matrices; Cognitive Training; Brain Imaging

Outcome Measures

Primary Outcomes (1)

• MDMA effects on human brain function and relationship between plasma MDMA concentrations and human brain function.

Secondary Outcomes (1)

• MDMA pharmacokinetics in various biological matrices.

Interventions

MDMA DRUG

(+/-)3,4-methylenedioxymethamphetamine Hydrochloride, MDMA HCI Capsules DRUG

0, 1.0 \& 1.6 mg/kg

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Be between the ages of 18 and 40.
• If MDMA group, have consumed at least five tablets of ecstasy in their lifetime with no clinically significant adverse medical or psychiatric reactions from using the drug or other stimulants and must have used at least once within the past 30 days (Drug Use Survey), with no current intention to stop MDMA use. History of ecstasy consumption is supported by a minimum of one positive urine amphetamines or hair MDMA drug test within the past 90 days. Urine drug tests at scanning visits must not be positive for drugs, other than amphetamines and cannabis. Scanning visits can be rescheduled once due to a positive urine test for other drugs.
• If control group, have no history of MDMA use (Drug Use Survey) and have negative urine test for amphetamines. If in the non-drug using group, must have a negative urine test for non-therapeutic psychoactive drugs at screening and scanning visits. Lifetime cannabis use for these participants cannot exceed ten times, with no use in the past two years (Timeline Follow-Back Method (146)). At screening, drug using controls may test positive for other drugs, other than amphetamines. At scanning, drug using controls may be positive for cannabis only. Scanning visits can be rescheduled once due to a positive urine test for other drugs.
• Be without current clinically significant medical problems that would preclude safe study participation.
• If female, must use a reliable method of birth control or abstain from sexual intercourse. Female participants will be counseled that a urine pregnancy test cannot detect pregnancies within 7 to 14 days of conception.
• Have an 8th grade reading and comprehension level.
• Additional requirements for participants undergoing neurocognitive testing:
• Have an IQ ? 85 determined by the Wechsler Abbreviated Scale of Intelligence (WASI) (The Psychological Corporation, 1999).
• Be right handed (Edinburgh Handedness Inventory (147)).
• Speak English as their first language.

You may not qualify if:

• Have known major medical or axis I psychiatric diagnosis other than substance abuse (Structured Clinical Interview (SCID) for the Diagnostic \& Statistical Manual of Mental Disorders IV (DSM-IV) criteria). Participants with a history of psychotropic medicine use will be evaluated by the MRP on a case-by-case basis to uncover the precise diagnosis for the use of the drug. Individuals who have substance dependence other than nicotine or cannabis, based on DSM IV criteria, will be excluded from the study. Prospective participants will be excluded if they smoke more than two packs of cigarettes per day.
• If MDMA user, be currently using (within 30 days of MDMA administration) one of the following inhibitors of CYP2D6 or CYP3A4 or inducers of CYP3A4:
• CYP2D6 inhibiting drugs\<TAB\>\<TAB\>\<TAB\>\<TAB\>
• Antidepressants: paroxetine, fluoxetine, sertraline, fluvoxamine, nefazodone, venlafaxine, clomipramine, amitriptyline, citalopram, bupropion
• Antipsychotics: haloperidol, perphenazine, thioridazine, levomepromazine, pimozide, fluphenazine
• Antiarrythmics: quinidine
• Protease inhibitors: ritonavir
• CYP3A4 inhibiting drugs
• Antidepressants: nefazodone, fluvoxamine, fluoxetine, sertraline, paroxetine, venlafaxine, norfluoxetine
• Azole antifungals: ketoconazole, itraconazole, fluconazole
• Protease inhibitors: ritonavir, nelfinavir, amprenavir
• Nonnucleoside reverse transcriptase inhibitors: efavirenz, delavirdine
• Histamine H2 -receptor antagonists: cimetidine
• Macrolide antibiotics: clarithromycin, erythromycin
• Calcium channel blockers: diltiazem

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): lead

Study Sites (1)

National Institute on Drug Abuse, Biomedical Research Center (BRC)

Baltimore, Maryland, 21224, United States

Location

Related Publications (3)

• Pentney AR. An exploration of the history and controversies surrounding MDMA and MDA. J Psychoactive Drugs. 2001 Jul-Sep;33(3):213-21. doi: 10.1080/02791072.2001.10400568.

  PMID: 11718314 BACKGROUND

• Rosenbaum M. Ecstasy: America's new "reefer madness". J Psychoactive Drugs. 2002 Apr-Jun;34(2):137-42. doi: 10.1080/02791072.2002.10399947.

  PMID: 12691203 BACKGROUND

• Greer GR, Tolbert R. A method of conducting therapeutic sessions with MDMA. J Psychoactive Drugs. 1998 Oct-Dec;30(4):371-9. doi: 10.1080/02791072.1998.10399713.

  PMID: 9924843 BACKGROUND

MeSH Terms

Conditions

Substance-Related Disorders

Interventions

N-Methyl-3,4-methylenedioxyamphetamine

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Marilyn Huestis, Ph.D.

  National Institute on Drug Abuse (NIDA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 19, 2010
• First Posted: June 22, 2010
• Study Start: February 10, 2004
• Study Completion: July 18, 2012
• Last Updated: December 12, 2019

Record last verified: 2012-07-18

Locations

US (1)