II. Mechanism

  1. Synthetic designer drug (Illicit Drug)
  2. Methylenedioxypyrovalerone (MDPV) is most common active ingredient in Psychoactive Bath Salts
    1. MDPV is an analog to the naturally occurring psychostimulant, cathinone
    2. Cathinone, a phenylethylamine, is a ß-Ketone analog of Amphetamine, and found in Catha edulis leaves (Khat Plant)
      1. Khat leaves are chewed by users in Middle East, South Asia and East Africa for their stimulant effects
      2. Cathinone is a key psychoactive component in Khat Plant (Catha edulis) extract
  3. MDPV is related to pyrovalerone and alpha-pyrrolidinophenones
    1. MDPV (3,4-Methylenedioxypyrovalerone) has strong adrenergic effects similar to Cocaine (but 10 fold potency)
    2. Inhibits Norepinephrine, Serotonin and Dopamine reuptake, resulting in increased Neurotransmitter levels
      1. Results in Sympathomimetic and Hallucinogenic effects
      2. Earliest agents (Methylone, Mephedrone) were Monoamine Oxidase Inhibitors
    3. CNS stimulant with same active core component (phenethylamine pharmacore) as Amphetamines and MDMA
      1. Synthetic Cathinones contain Ketone moiety (carbonyl group) that differentiates them from Amphetamines
      2. Mescaline (Peyote Cactus extract) is also a Substituted Phenylethylamine
      3. Bupropion is similar in structure as phenylethylamine derivatives and MDPV
        1. Bupropion has been abused via insufflation and injection
        2. Bupropion abuse may result in Seizures, QTc Prolongation, and difficult to treat Arrhythmias
    4. Appear to have worst characteristics of LSD, PCP, MDMA, Cocaine and Methamphetamine
    5. CNS effects are 10 fold greater with MDPV than with Cocaine
    6. Introduced in 2007 (Russia and UK) and appeared in U.S. by 2011
  4. Routes
    1. Intranasal
    2. Orally (salts dissolved in liquid)
  5. Addictive potential
    1. Tolerance, withdrawal and craving with long term use
    2. Mephedrone may have highest risk of dependence (related to Dopaminergic effects)
  6. Marketing claims
    1. Typically labeled as "not for human consumption" as bath salts or plant food
    2. Stimulant (cheap substitute for other stimulants)
    3. Alertness enhancer
    4. Aphrodesiac
  7. Street Names
    1. Ivory Wave
    2. Vanilla Sky
    3. White Lightning
    4. Scarface
    5. Energy-1
    6. Plant Fertilizer or plant food
    7. Legal Cocaine
    8. Jewelry cleaner
    9. Lunar Waves
    10. Bloom
    11. Cloud Nine
    12. Flakka
    13. Meow Meow
  8. Formulations (>30 different chemical compounds, and at least 6 new agents introduced in 2019 alone)
    1. Sold as white or brown powder in pill or capsule at $20-35 per gram
    2. Earliest Synthetic Cathinones (Methylone, Mephedrone and MDPV) are banned in U.S.
    3. Alpha-Pyrrolidinopentiophenone (Alpha-PVP, Flakka, gravel) appeared on market in 2015
    4. Eutylone (bk-EBDB) and N-ethylpentylone, released in 2014 and more commonly found agents in 2021
      1. N-ethylpentylone (MDEVP, bk-EPDP, bk-EBDP) has Cocaine effects (despite marketing as MDMA-like agent)
  9. Delivery
    1. Has been used intranasally, orally, IV/IM and PR, but typically not smoked due to lability
    2. Have been dissolved in beverages or vaporized
    3. Bombing (Swallowing powder wrapped in Cigarette paper)
    4. Keying (nasal insufflation of powder from key surface)

III. Pharmacokinetics

  1. Lowest effective dose: 3-5 mg intranasally, per-Rectum or intravenous
  2. Average dose 5-20 mg
  3. Onset and duration
    1. Insufflation effect onset at 10-20 minutes (duration 1-2 hours)
    2. Oral effect onset at 15-45 minutes (peaks at 1.5 hours, duration 2-4 hours)
    3. Intravenous effect onset at 10-15 minutes (duration 30 minutes)
  4. Course
    1. Agent wears off with "harsh crash"
    2. Entire course from intake may last 8 hours

IV. Symptoms: Desired Effects

  1. Increased energy
  2. Increased Libido
  3. Euphoria

V. Adverse Effects: Excited Delirium

  1. Sympathetic stimulation
    1. Tachycardia
    2. Hypertension
    3. Hyperthermia
    4. Seizures
    5. Arrhythmias
    6. Vasoconstriction
    7. Mydriasis
    8. Diaphoresis
    9. Palpitations
  2. Neuropsychiatric effects (including Altered Level of Consciousness, Agitated Delirium, acute Psychosis)
    1. Anxiety
    2. Severe Panic Attack
    3. Agitation (66% of patients)
    4. Paranoia
    5. Hallucinations
    6. Acute Psychosis (paranoia, auditory and Visual Hallucinations)
    7. Violent Behavior or aggressive behavior
    8. Self-destructive behavior or self-mutilation
    9. Insomnia
    10. Anorexia
    11. Depressed mood
  3. Miscellaneous effects
    1. Headache
    2. Nausea or Vomiting

VI. Labs

  1. Obtain labs per Unknown Ingestion evaluation
  2. Creatinine Kinase (for Rhabdomyolysis)
  3. No current lab tests detect Psychoactive Bath Salts
  4. Bath salts (as with Ketamine) may cause a False Positive for Phencyclidine (PCP) on Urine Drug Screening

VII. Diagnostics

  1. Electrocardiogram (EKG)
    1. QTc Prolongation may occur (esp. with abused Bupropion)
    2. QRS Widening (suggests mixed ingestion)

VIII. Precautions

  1. Addictive
  2. Deaths have occurred
  3. Polysubstance Overdose with bath salts may occur
    1. Coingestion occurs in 94% of cases (often with Cocaine)
    2. May confuse the presentation
  4. Contaminated products have resulted in severe adverse effects
    1. Methcathinone contamination with manganese (2008, Europe) resulted in refractory Parkinsonism

IX. Management

  1. See Unknown Ingestion
  2. See Agitated Delirium
  3. ICU monitoring
  4. Intravenous Fluids
    1. Prevent Rhabdomyolysis
  5. Evaporative Cooling measures
    1. Indicated for hyperthermia
  6. Physical Restraints may be needed for initial management
    1. However rapidly institute Agitated Delirium management
    2. Avoid prolonged Physical Restraints (see Agitated Delirium) and requires 1:1 observation
  7. Benzodiazepines IV indications
    1. Sedation for Agitation, Psychosis
    2. Seizure managament
    3. Hypertension or Tachycardia
  8. Seizures
    1. First-Line: Benzodiazepines
    2. Avoid Sodium channel blocking agents (e.g. Phenytoin), but other antiepileptic agents may be used
  9. Atypical Antipsychotics
    1. Start with liberal use of Benzodiazepines
    2. Antipsychotics may be used as second line agents, but avoid in QTc Prolongation or QRS Widening
  10. Supportive care
    1. Manage hemodynamic instability
  11. Electrocardiogram abnormalities
    1. QRS Widening
      1. Sodium Bicarbonate ampules until QRS narrows again
    2. QTc Prolongation
      1. Magnesium 2 g IV
  12. Precautions
    1. Avoid Beta Blockers (risk of unopposed Alpha Adrenergic Receptor stimulation)
  13. Disposition
    1. Minor Intoxication without serious findings and Clinical Sobriety may be reasonable for discharge
    2. However, effects vary widely and with potential for serious complications
      1. Consider hospital observation or admission for significant Intoxication

X. Complications

  1. Overdose is a significant risk with packages containing as much as 500 mg
  2. Cerebrovascular Accident
  3. Hyponatremia (and cerebral edema) due to Water Intoxication and Vasopressin release
  4. Respiratory distress
  5. Rhabdomyolysis (higher risk than other stimulants)
  6. Serotonin Syndrome (examine for Clonus)
  7. Acute Psychosis
  8. Acute Kidney Injury
  9. Arrhythmias, Myocardial Infarction or cardiovascular collapse
  10. Hyperthermia (>104.9 F or 40.5 C is associated with 50% mortality)
  11. Deaths have been reported

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