II. Pathophysiology

  1. Background
    1. Illicit Drug used at raves and clubs
    2. Street drug names include Lover's speed, molly, X, ecstacy
    3. Typically available in pill form (but may also be snorted, or drank as a liquid)
  2. MDMA is commonly mixed with other unlisted substances
    1. May contain Caffeine, Pseudoephedrine or Methamphetamine
    2. May contain Hallucinogens (e.g. LSD, MDA, MDEA, 2-CB)
  3. Variants: Mandy or Molly (crystalline powder form or MDMA)
    1. Promoted as "pure" MDMA (erroneously since powder form is more easily modified)
    2. Commonly adulterated (cut or replaced with cheaper, often more dangerous products)
      1. May contain Amphetamines or stimulants
      2. Contaminants include PMA ("chicken" or "death"), Methylone, bath salts

III. Mechanism

  1. Type of Amphetamine, with chemical structure similar to Serotonin
  2. Stimulant effects and psychedelic effects
  3. Results in increased energy and pleasure (esp. with tactile stimulation)
  4. Stimulates Serotonin, Dopamine, and Norepinephrine release
    1. Serotonin release effects are 10 fold greater than with Methamphetamine
    2. Results in intense mood effects and negative withdrawal effects after brain Serotonin depletion
  5. Also stimulates release of cortisol, Oxytocin, antidiuretic hormone
  6. Inhibits monoamine oxidase
    1. Limits breakdown of neurotransmitters

IV. Pharmacokinetics

  1. Onset: 30-60 minutes after oral intake
  2. Duration: 3-8 hours
    1. Doses are often repeated to sustain effects

V. Symptoms

  1. Initial
    1. Agitated
    2. Time sense is altered
    3. Decreased hunger and thirst
  2. Later
    1. Euphoria
    2. Sense of intimacy with others
    3. Sense of well-being

VI. Adverse Effects

  1. See Sympathomimetic Toxicity
  2. Trismus or Bruxism
    1. Users reduce this by sucking on Pacifier or lollipop
  3. Sympathetic overdrive
    1. Agitated or violent
    2. Tachycardia
    3. Mydriasis
    4. Diaphoresis (severe)
    5. Urinary Retention
    6. Hypertension
  4. Serotonin Syndrome
  5. Hyperthermia
    1. Secondary to CNS Stimulation
  6. Hyponatremia
    1. Secondary to SIADH (renal free water reabsorption) and increased fluid intake (water Intoxication)
  7. NMDA withdrawal related depression
    1. Associated with Serotonin depletion
  8. Longstanding effects
    1. Serotonin containing Neurons may be chronically damaged despite cessation

VII. Drug Interactions

  1. Ritonavir (Norvir)
    1. Potentiates MDMA
    2. Cardiac Arrest and deaths have occurred

VIII. Labs

  1. Urine toxicology is unreliable
    1. Ingested MDMA may be too low dose to detect (despite causing significant toxicity)
    2. Contaminants are not typically detected such as cathinone (bath salts) or piperazines

IX. Precautions

  1. MDMA (Molly, Ecstasy) is unsafe at any dose (hyperthermia may occur at low dose)
  2. Associated with numerous deaths and ED visits since introduced in 2004
    1. Deaths have occurred regardless of MDMA form, whether "pure" or contaminated (e.g. bath salts)

X. Management: Toxicity

  1. See Sympathomimetic Toxicity
  2. Treat hyperthermia aggressively
    1. Cooling and Benzodiazepines are typically used
    2. Rapid Sequence Induction and paralysis may be required

XI. Management

  1. Cognitive Behavioral Therapy
  2. Recovery support group
  3. No specific management protocols or medications have been identified

XII. Complications: Class effect of stimulant Drugs of Abuse

XIII. References

  1. Nordt and Swadron in Herbert (2014) EM:Rap 14(5): 9
  2. (2013) Presc Lett 20(12): 72
  3. Gahlinger (2004) Am Fam Physician 69:2619-27 [PubMed]
  4. Klega (2018) Am Fam Physician 98(2): 85-92 [PubMed]

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Ontology: Ecstasy - drug (C0115471)

Definition (NCI) A ring-substituted amphetamine derivative, structurally related to the hallucinogen mescaline, with entactogenic, neurotoxic, and motor-stimulatory activities. 3,4-methylenedioxymethamphetamine (MDMA) produces an acute, rapid enhancement in both the release of serotonin from and the inhibition of serotonin reuptake by serotonergic nerve endings in the brain. Once within the cell, MDMA depletes stores of tryptophan hydroxylase (TPH) via acute oxidative inactivation; in turn, depleted stores of TPH leave cell terminals open to damage from oxidative stress, possibly a source of MDMA neurotoxicity. This agent also induces norepinephrine, dopamine, and acetylcholine release and can act directly on a number of receptors, including alpha 2-adrenergic and 5-hydroxytryptamine (5-HT) 2A receptors. MDMA may suppress the dyskinesia associated with long-term use of L-dopamine (L-DOPA) without affecting the efficacy of L-DOPA treatment.
Definition (MSH) An N-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as MDMA or ecstasy.
Definition (CSP) synthetic adrenergic agonist resembling both amphetamine (a stimulant) and mescaline (a hallucinogen); "designer drug" once touted as potentially psychotherapeutic, but now a controlled substance considered a drug of abuse.
Definition (PDQ) A ring-substituted amphetamine derivative, structurally related to the hallucinogen mescaline, with entactogenic (openess- and empathy-generating), neurotoxic, and motor-stimulatory activities. Although the mechanism by which it causes its unusual entactogenic effects is largely unknown, 3,4-methylenedioxymethamphetamine (MDMA) produces an acute, rapid enhancement in both the release of serotonin from and the inhibition of serotonin reuptake by serotonergic nerve endings in the brain. Once within the cell, MDMA depletes stores of tryptophan hydroxylase (TPH) via acute oxidative inactivation; in turn, depleted stores of TPH leave cell terminals open to damage from oxidative stress, possibly a source of MDMA neurotoxicity. This agent also induces norepinephrine, dopamine, and acetylcholine release and can act directly on a number of receptors, including alpha 2-adrenergic and 5-hydroxytryptamine (5-HT) 2A receptors. MDMA may suppress the dyskinesia associated with long-term use of L-dopamine (L-DOPA) without affecting the efficacy of L-DOPA treatment, perhaps via indirect stimulation of 5-HT 1A receptors. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=475676&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=475676&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C61081" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Hazardous or Poisonous Substance (T131) , Organic Chemical (T109)
MSH D018817
SnomedCT 288459003, 229010005, 79838002, 386996008, 115539008
LNC LP18612-9, MTHU004797
English MDMA, Ecstasy (Drug), Methylenedioxymethamphetamine, N Methyl 3,4 methylenedioxyamphetamine, N-Methyl-3,4-methylenedioxyamphetamine, 1,3-Benzodioxole-5-ethanamine, N,alpha-dimethyl-, 3,4 methylenedioxymethamphetamine, MMDA, 3-Methoxy-4,5- methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, METHYLMETHYLENEDIOXYAMPHETAMINE N 03 04, Ecstasy - drug, E - Ecstasy, Ecstasy, 3,4-Methylenedioxymethamphetamine, MDMA - Methylenedioxymethamphe, ecstasy (drug), Ecstasy - agent, N-Methyl-3,4-methylenedioxyamphetamine [Chemical/Ingredient], mdma, ecstasy, ecstasy drug, mdm, methylene dioxymethamphetamine, methylenedioxymethamphetamine, XTC, n-Methyl-3, 4-methylenedioxyamphetamine (substance), n-Methyl-3, 4-methylenedioxyamphetamine, Ecstasy - agent (substance), Methylene-dioxymethamphetamine (substance), MDM, MDMA - Methylenedioxymethamphetamine, Methylene-dioxymethamphetamine (product), Methylene-dioxymethamphetamine, Methylenedioxymethamphetamine (substance), Ecstasy - drug (substance), Methylenedioxymethamfetamine
Swedish N-metyl-3,4-metylendioxyamfetamin
Spanish 3-metoxi-4,5-metilendioxianfetamina, MMDA, Methylenedioxymethamphetamine, MDMA - Methylenedioxymethamphetamine, Methylenedioxymethamphetamine (substance), metilen-dioximetanfetamina (sustancia), éxtasis - agente (sustancia), n-metil-3,4-metilenedioxianfetamina, n-metil-3,4-metilenedioxianfetamina (sustancia), metilen-dioximetanfetamina, éxtasis - agente, metilendioximetanfetamina (producto), metilendioximetanfetamina, metilendioximetanfetamina (sustancia), MDMA, Metilenodioximetanfetamina, N-Metil-3,4-metilenodioxianfetamina
Czech extáze, MDMA, N-methyl-3,4-methylendioxyamfetamin
Finnish N-metyyli-3,4-metyleenidioksiamfetamiini
Russian N-METIL-3,4-METILENDIOKSIAMFETAMIN, METILENDIOKSIAMFETAMIN, METILENDIOKSIMETAMFETAMIN, MDMA, N-МЕТИЛ-3,4-МЕТИЛЕНДИОКСИАМФЕТАМИН, МЕТИЛЕНДИОКСИАМФЕТАМИН, МЕТИЛЕНДИОКСИМЕТАМФЕТАМИН
Japanese N-メチル-3,4-メチレンジオキシアンフェタミン, メチレンジオキシメタンフェタミン
German METHYLMETHYLENDIOXYAMPHETAMIN N 03 04, MDMA, Methylendioxymethamphetamin, N-Methyl-3,4-Methylendioxyamphetamin, Ecstasy
French N-Méthyl-3,4-méthylènedioxy-amphétamine, N-Méthyl-3,4-méthylènedioxyamphétamine, Ecstasy, MDMA, Méthylènedioxymethamphétamine
Polish MEDMA, Metylenedioksymetamfetamina, N-metylo-3,4-metylenodioksyamfetamina
Portuguese N-Metil-3,4-Metilenodioxianfetamina, MDMA, Metilenodioximetanfetamina
Italian n-Metil-3,4-metilenediossiamfetamina