Study of the Effects of MDMA/Ecstasy on Water Regulation, Sleep, and Cognition.
Condition: MDMA Discontinuation Syndrome
Study type: Interventional

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.
    

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.
    

Intervention name(s): 3,4-methylenedioxymethamphetamine or Placebo
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): Ecstasy
Intervention MeSH terms: N-Methyl-3,4-methylenedioxyamphetamine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: MDMA; Ecstasy; MDMA effect on sleep; MDMA effect on water homeostasis; MDMA effect on neurocognitive function; Recreational Drug Use; Drug Abuse