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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01053403
Recruitment Status : Completed
First Posted : January 21, 2010
Last Update Posted : May 31, 2013
Information provided by (Responsible Party):
John Mendelson, MD, California Pacific Medical Center Research Institute

Brief Summary:

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 or disease Intervention/treatment Phase
MDMA Discontinuation Syndrome Drug: 3,4-methylenedioxymethamphetamine or Placebo Not Applicable

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Effects of MDMA on Sleep Architecture, Water Homeostasis and Cognitive Function
Study Start Date : April 2010
Actual Primary Completion Date : December 2010
Actual Study Completion Date : February 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. Assess the acute effects of MDMA on water and sodium homeostasis [ Time Frame: 1 hour post dose through 48 hours post dose ]

Secondary Outcome Measures :
  1. 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 ]
  2. Document the acute effects of MDMA on behavioral measures of economic decision making. [ Time Frame: 1 hour post dose through 48 hours post dose ]
  3. Document the acute effects of MDMA on autobiographical speech and memory [ Time Frame: 1 hour post dose through 48 hours post dose ]
  4. Measure the effects of MDMA on ADMA [ Time Frame: 1 hour post dose through 48 hours post dose ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01053403

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

Responsible Party: John Mendelson, MD, Senior Scientist, California Pacific Medical Center Research Institute Identifier: NCT01053403     History of Changes
Other Study ID Numbers: IRB# 2009.099-1 (JMen)
5-R01-DA016776 (NIH)
First Posted: January 21, 2010    Key Record Dates
Last Update Posted: May 31, 2013
Last Verified: May 2013

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

Additional relevant MeSH terms:
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Adrenergic Agents