Neurobiology and Pharmacokinets of Acute MDMA Administration
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|ClinicalTrials.gov Identifier: NCT01148342|
Recruitment Status : Completed
First Posted : June 22, 2010
Last Update Posted : December 12, 2019
|First Submitted Date ICMJE||June 19, 2010|
|First Posted Date ICMJE||June 22, 2010|
|Last Update Posted Date||December 12, 2019|
|Study Start Date ICMJE||February 10, 2004|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||MDMA effects on human brain function and relationship between plasma MDMA concentrations and human brain function.|
|Original Primary Outcome Measures ICMJE
||MDMA effects on human brain function and relationship between plasma MDMA concentrations and human brain function. [ Time Frame: Pharmacodynamic and pharmacokinetic measures are assessed 60 minutes prior to MD ]|
|Current Secondary Outcome Measures ICMJE
||MDMA pharmacokinetics in various biological matrices.|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Neurobiology and Pharmacokinets of Acute MDMA Administration|
|Official Title ICMJE||Neurobiology and Pharmacokinetics of Acute MDMA Administration|
- To evaluate the effects of MDMA on thinking and brain function.
- 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.
Background: 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy, is a synthetic compound that has shown a steep increase in abuse by young people in recent years. In animals, when high and multiple doses of MDMA were given, serotonergic toxicity was observed. Clinically, the number of severe ecstasy related acute toxicities is low in relation to the extent of recreational use. Data from some retrospective studies report memory deficits in abstinent chronic users who often abuse MDMA with other illicit and licit substances; therefore, it is difficult to determine MDMA s contribution to observed cognitive deficits. There are few prospective controlled MDMA human administration studies that describe its acute physiological and behavioral effects following doses commonly used in young adults. We propose a functional magnetic resonance imaging (fMRI) study to examine specific changes in brain activity and cognitive performance and to correlate these changes with plasma MDMA concentrations.
Goals: The primary goals are identification of MDMA effects on human brain function and elucidation of the relationship of effects to plasma MDMA concentrations. We propose a within-subject design of changes in memory, attention, affect, semantic processing and decision-making performance following placebo and two recreational MDMA doses with simultaneous fMRI monitoring and plasma collections. Secondly, pharmacokinetic data will be collected on the disposition of MDMA and metabolites in plasma, urine, oral fluid, sweat, breath, and hair. These data are needed to accurately interpret drug concentrations in alternative biological matrices in order for drug tests to function as a deterrent to drug use in drug abuse treatment, law enforcement, military, and workplace drug testing programs. Pharmacokinetic data will also enable drug tests to serve as valid diagnostic tools in emergency medicine and public safety settings, as well as useful objective outcome measures in treatment research.
Subject Population: Eighteen current MDMA users will complete the neurocognitive and pharmacokinetics group. Thirty-six MDMA non-using controls will include 18 non-drug using participants and 18 drug using (primarily cannabis) participants. Controls in each group will be matched to MDMA users in the neurocognitive and pharmacokinetics group. All participants must be between the ages of 18 and 40. The estimated target enrollment, based on ecstasy use by race/ethnic group and Baltimore demographics, will be 41% female and 59% male, 83% Caucasian, 14% African American, 3% Asian, and 2% Hispanic.
Experimental Design and Methods: A randomized, balanced, double blind, within-subject drug administration study with placebo, low (1.0 mg/kg, approximately 70 mg) and high (1.6 mg/kg, approximately 112 mg) doses of MDMA is proposed. The non-drug using and drug using control groups will be matched to MDMA users in the neurocognitive and pharmacokinetics group for sex, age, IQ, education level and intersession interval. The drug using control group will control for cannabis and other drug usage in the MDMA group. The drug using control group is necessary because many MDMA users also use other drugs, primarily cannabis. Control groups allow for a between-subjects analysis for trait differences between the population groups, as well as provide normative data for the cognitive tasks. Drug using control group participants will stay on the clinical research unit overnight prior to each of the three sessions; non-drug using control group participants will arrive the morning of each session. Participants from the MDMA group will complete three separate stays, each lasting approximately 26 hours, within one year. While under the influence of MDMA, qualified participants will perform memory, attention, semantic processing, affect and decision-making tasks before, during, and after fMRI scanning. Physiological, behavioral and biochemical measures of all MDMA users will be monitored throughout the study to determine onset, magnitude and duration of pharmacodynamic effects. Blood, urine, oral fluid, sweat, breath, and hair specimens will be collected from MDMA users for analysis of MDMA and metabolite concentrations by GC/MS and/or LC/MS/MS to determine the disposition and pharmacokinetics of MDMA.
Risks and Benefits: A main potential risk of this study is associated with acute cardiovascular responses to MDMA administration; however, these doses have proven safe and well tolerated in previous human studies conducted within the US and abroad. In addition, impaired cognitive function has been reported following long-term MDMA use in some but not all studies. A potential benefit of the proposed study is to understand how MDMA affects human brain function at doses employed by recreational users. Additionally, advances will be made in understanding MDMA pharmacokinetics.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 1|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Crossover Assignment
Primary Purpose: Other
|Condition ICMJE||Substance-Related Disorders|
|Study Arms ICMJE||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Actual Study Completion Date ICMJE||July 18, 2012|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
EXCLUSION CRITERIA: Participants must NOT:
|Ages ICMJE||18 Years to 40 Years (Adult)|
|Accepts Healthy Volunteers ICMJE||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01148342|
|Other Study ID Numbers ICMJE||999904394
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute on Drug Abuse (NIDA)|
|Collaborators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||July 18, 2012|
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