Study of the Effects of MDMA/Ecstasy on Water Regulation, Sleep, and Cognition. (2C)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
John Mendelson, MD, California Pacific Medical Center Research Institute
ClinicalTrials.gov Identifier:
NCT01053403
First received: January 8, 2010
Last updated: May 29, 2013
Last verified: May 2013
  Purpose

The purpose of this study is to measure the effects of MDMA on sleep, mood, thinking, and how your body retains water. The researchers are interested in the effects that occur a few hours after taking MDMA as well as effects occurring over the next two days. We will study these effects in a standardized, controlled setting at the Clinical and Translational Science Institute (CTSI) Clinical Research Center (CRC) located at San Francisco General Hospital.

The primary hypotheses are:

  1. MDMA will induce sleep disruption, as indicated by comprehensive polysomnography, wrist actigraphy, and self-report sleep measures
  2. MDMA will alter sodium and water homeostasis by either increasing or blunting the suppression of arginine vasopressin levels and decreasing free water excretion. Effects will be exacerbated by water loading.

Secondary hypotheses:

  1. Acutely, MDMA will increase both positive and negative arousal, and to increase sociability but not autonomy.
  2. Acutely, MDMA will increase risk-taking and willingness to donate money to others in an economic decision making task.
  3. MDMA will decrease the stressful effects of talking about a negatively-valenced autobiographical but will increase recall for details for these episodes.
  4. MDMA will increase oxidative stress markers and possible ameliorating factors (e.g., ADMA).
  5. The short form of the serotonin transported promoter region will be associated with greater acute and discontinuation effects of MDMA.

Condition Intervention
MDMA Discontinuation Syndrome
Drug: 3,4-methylenedioxymethamphetamine or Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Effects of MDMA on Sleep Architecture, Water Homeostasis and Cognitive Function

Resource links provided by NLM:


Further study details as provided by California Pacific Medical Center Research Institute:

Primary Outcome Measures:
  • Time course, severity, and characteristics of MDMA discontinuation in experienced MDMA users given a known dose of MDMA [ Time Frame: 1 hour post dose through 48 hours post dose ] [ Designated as safety issue: Yes ]
  • Relate observed discontinuation effects to sleep data: polysomnography, wrist actigraphy, and self-report sleep measures. [ Time Frame: 1 hour post dose through 48 hours post dose ] [ Designated as safety issue: No ]
  • Assess the acute effects of MDMA on water and sodium homeostasis [ Time Frame: 1 hour post dose through 48 hours post dose ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Document the acute effects of MDMA on self-reported measures, including positive and negative arousal, autonomy, and sociability. [ Time Frame: 1 hour post dose through 48 hours post dose ] [ Designated as safety issue: No ]
  • Document the acute effects of MDMA on behavioral measures of economic decision making. [ Time Frame: 1 hour post dose through 48 hours post dose ] [ Designated as safety issue: No ]
  • Document the acute effects of MDMA on autobiographical speech and memory [ Time Frame: 1 hour post dose through 48 hours post dose ] [ Designated as safety issue: No ]
  • Measure the effects of MDMA on ADMA [ Time Frame: 1 hour post dose through 48 hours post dose ] [ Designated as safety issue: Yes ]

Enrollment: 12
Study Start Date: April 2010
Study Completion Date: February 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: MDMA Drug: 3,4-methylenedioxymethamphetamine or Placebo
1.5mg/kg MDMA or matched Placebo administered during 2 inpatients stays. There are 2 dosing sessions and all subjects will receive MDMA at least one time.
Other Name: Ecstasy

Detailed Description:

This is a placebo-controlled, double-blind, gender balanced, within-subject study on the acute and 24 to 48 hour post dose effects (discontinuation syndrome) of MDMA on sleep architecture, water homeostasis and neurocognitive function. We will define the signs and symptoms of sleep disruption and time course of alterations in ADH levels and neurocognitive function occurring after administration of a single dose of MDMA in experienced users. The immediate effects of MDMA include euphoria and intoxication; at 24 hours after MDMA these positive effects are replaced by lowered mood and lethargy - we refer to these effects as a discontinuation syndrome. The pleasurable effects of MDMA are thought to be due to elevations of serotonin, norepinephrine and dopamine; the mechanisms of post-MDMA depression are unknown but may be due to relative serotonin depletion. Among its many functions serotonin maintains normal sleep architecture. The effects of MDMA discontinuation on sleep architecture will be assessed using comprehensive polysomnography and wrist actigraphy with measures obtained ~36 hours after a single dose of MDMA. Cognitive measurements will explore the acute effects of MDMA. MDMA can produce hyponatremia. In this study we will evaluate the effects of MDMA on ADH release, urine sodium excretion, and the relationship of gender to these effects.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy men or women aged 18 to 50 years.
  • If female: abstains from heterosexual sex, not of childbearing potential, or reports using an approved contraceptive.
  • Experienced with MDMA
  • Fluent in English.
  • Willing and able to give written consent.
  • Healthy without medical contraindications to MDMA administration determined by the following: medical history, physical examination, 12-lead EKG, hematology, blood chemistry, and urinalysis.
  • Blood liver transaminase elevations up to 3 times the upper limit of normal.
  • If female: negative pregnancy test at screening and at the beginning of each hospital admission.
  • Negative urine drug test at screening and prior to each potential MDMA administration.

Exclusion Criteria:

  • Current enrollment in a MDMA, alcohol, or other drug treatment program or current legal problems relating to MDMA, alcohol, or other drug use, including awaiting trial or supervision by a parole or probation officer.
  • Participants with a past-history of using only low doses of MDMA
  • Currently trying to quit MDMA use.
  • Current dependence on any other psychoactive drug (including nicotine).
  • Significant physical or psychiatric illness that might impair the ability to safely complete the study or that might be complicated by the study drugs, including prior seizures (after age 8) or other active neurological disease or clinically significant abnormalities on physical examination or screening laboratory values.
  • Likelihood of needing medications to treat an illness during the study period.
  • Body Mass Index > 30 or < 18.
  • HIV seropositive by self-report.
  • If female: pregnancy or lactation.
  • History of serious adverse event or hypersensitivity to MDMA.
  • Currently taking any medication other than over-the-counter non-steroidal anti-inflammatories, topical medications, inhaled asthma therapy, and over-the-counter non-sedating antihistamines.
  • Male neck size ≥ 17 inches, female neck size ≥ 16 inches
  • Modified Mallampati class ≥ 3.
  • Recent travel within 3 days to or from a different time zone, other than Mountain Standard Time.
  • Any other medical or psychosocial condition that would preclude useful, safe, or consistent participation.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01053403

Locations
United States, California
CPMC Addiction & Pharmacology Research Laboratory (APRL)
San Francisco, California, United States, 94110
Sponsors and Collaborators
California Pacific Medical Center Research Institute
Investigators
Principal Investigator: John Mendelson, MD CPMC Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: John Mendelson, MD, Senior Scientist, California Pacific Medical Center Research Institute
ClinicalTrials.gov Identifier: NCT01053403     History of Changes
Other Study ID Numbers: IRB# 2009.099-1 (JMen), 5-R01-DA016776 (NIH)
Study First Received: January 8, 2010
Last Updated: May 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by California Pacific Medical Center Research Institute:
MDMA
Ecstasy
MDMA effect on sleep
MDMA effect on water homeostasis
MDMA effect on neurocognitive function
Recreational Drug Use
Drug Abuse

Additional relevant MeSH terms:
N-Methyl-3,4-methylenedioxyamphetamine
Hallucinogens
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Uptake Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014