Ecstasy

• ecstasy - name given by its users to 3,4-methylene-dioxymethamphetamine (MDMA)
  • second most commonly used controlled drug (after cannabis) in Europe
  • MDMA is a ring-substituted amphetamine derivative
  • related to the hallucinogenic compound mescaline
    • does not produce the profound sensory disruptions or hallucinations associated with classical hallucinogens such as lysergic acid diethylamine (LSD)e
    • increases emotional sensitivity and empathy
      • also MDMA use associated with a loss of inhibitions; reduced anxiety; increased sense of closeness with other people
• pharmacology
  • action in the central nervous system is complex
    • major effects on serotonin (5-hydroxytryptamine [5-HT]) pathways - however also affects two other major transmitter systems in the brain: dopamine (DA) and noradrenaline
    • use of MDMA causes an acute and rapid increase in extracellular 5-HT
      • causes a marked depletion of 5-HT from brain tissue in the first few hours following drug administration
    • in rat models 5-HT levels recover within 24 h after a single dose of MDMA; however higher doses of MDMA can result in sustained depletion of 5-HT that can last for up to 12 months
      • MDMA also blocks the activity of tryptophan hydroxylase (rate-limiting enzyme in the biosynthesis of 5-HT)
        • this effect occurs within 15 min following administration - can last for up to two weeks
• acute toxic effects
  • malignant hyperthermia - this syndrome of persistent hyperthermia which leads to the rhabdomyolysis with subsequent renal and other organ failure
    • mechanism for this is unknown - there may be a possible role for uncoupling protein-3, a mitochondrial protein known to play a role in thermogenesis
• neuropsychological effects of depletion of brain levels of 5-HT
  • following MDMA use
    • subjective effects reported are euphoria, changes in perception (sound and light), a reduction in defensiveness (negative affect), emotional openness, empathy and a reduction of inhibitions
      • effects are likely to be mediated via the 5-HT-system
      • the use of ectasy does not leave the user with a "neutral" mood
        • following ecstasy use there is an ‘offset’ period - during this period there is a worsening of mood - this low mood persists for several days (known as the ‘midweek blues’)
        • it has been suggested that there may be an increase in aggression/anger/anxiety occurs after taking ecstasy - tends to peak four days after taking the drug
        • effects of ecstasy on mood appear to be reversible
        • there is study evidence that indicate that depression, impulsivity, and sensation seeking do not predict first time ecstasy use in a population of young adults with the intention to start using ecstasy (2)
• there is evidence from studies of long term MDMA use of long-term (weeks to months) impairments in memory and learning; in particular, working memory, planning ability, executive control and cognitive impulsivity

The effects of ecstasy on the cardiovascular system are described in the linked item.

Notes:

• a study investigating the safety of single or low dose of ecstasy has been undertaken (3):
  • the study showed no differences in metabolites concentrations before and after ecstasy use and found no indications for major neuronal damage after a single or low dose of ecstasy use in first time ecstasy users. Howeve the authors stated that, because there might be various factors that play a role in individual vulnerability for acute and long-term effects of ecstasy, it is not possible to state that the use of a single or low dose of ecstasy is totally safe

Reference:

1. Curr Opin Pharmacol. 2005 Feb;5(1):79-86
2. J Psychopharmacol. 2006 Mar;20(2):226-35.
3. Europ Neuropsychopharm 2006; 16(1): S79-S80.