II. Pharmacology

  1. Synthetic Cannabinoids
    1. Originally produced as research chemicals to study receptor binding in the 1980s
      1. Synthetic Cannabinoids may have 10-200 times the potency at specific receptor sites
    2. Produced by spraying dried, shredded herbal plant leaves with cannabinoid receptor agonists
    3. Synthetic agonists are THC-like agents based on one of four synthetic parent agents
    4. Synthetic agonists are small, lipid soluble, non-polar molecules (22 to 26 carbons)
  2. Agents act at two cannabinoid receptors (with high affinity to CB1)
    1. CB1 - CNS receptors (decrease intracellular cAMP and increase MAP kinase)
      1. Elevates mood and increases feelings of well being
      2. Affects pain tolerance, time perception, memory
    2. CB2 - T Cells, B Cells and Macrophages as well as peripheral nerves
  3. Most agents are pure agonists at cannabinoid CB1 cerebral receptor (contrast with THC as a partial agonist)
    1. Synthetics result in more intense, and unpredictable Intoxication than THC
    2. Synthetic THC lacks the Cannabidiol (Antipsychotic, anticonvulsant) effects of Cannabis sativa (Marijuana)
      1. Hence the unpredictable psychotic effects and Seizures with synthetic THC
      2. In addition, formulations frequently change to overcome detection
  4. Typically smoked in pipe or Cigarette paper
    1. Has also been vaporized and inhaled, as well as ingested

III. Preparations

  1. Sold in 1-3 gram foil pouches of dried Herbals
    1. Typically labeled as "not for human consumption" or marketed as incense
    2. More than 50 distinct products have been identified in the U.S.
    3. Various Herbals and crushed leaves are added for appearance only (drug is dripped onto the leaves)
    4. Inconsistent effects across products as well as within the same brand (unpredictable)
      1. Even different effects in the same package shared by different users
      2. May occur with concentrated portions within the package
  2. Street Names
    1. K2
    2. Kronic
    3. Spice
    4. JWH (John W. Huffman)
    5. Legal Marijuana
    6. Fake Weed
    7. Black Mamba
    8. Mojo
    9. Scooby Snax
    10. Death Ride
    11. Intensely aromatic incense
    12. Cloud-9 (AB-PINACA)
      1. Liquid form vaporized and resulted in multiple hospitalizations in 2014

IV. Symptoms: Intoxication

  1. Marijuana-like Intoxication (sought effects)
    1. Euphoria, elevated mood or intense "high"
    2. Uncontrolled laughter
    3. Disinhibition
  2. Other effects
    1. Hyperadrenergic effects
    2. Agitated Delirium (with possible Seizures)
    3. Altered Mental Status with sedation

V. Signs: Intoxication

  1. Diaphoresis
  2. Hyperreflexia
  3. Nystagmus
  4. Conjunctival injection

VI. Symptoms: Withdrawal

  1. Headache
  2. Anxiety
  3. Depressed Mood
  4. Irritability

VII. Adverse Effects

  1. Effects vary due to the ever changing formulations and compositions of Synthetic Cannabinoids and contaminants
  2. Life threatening bleeding (2018)
    1. Related to Anticoagulant-laced Synthetic Cannabinoids in 2018
    2. Cannabinoids were laced with Brodifacoum (rat poison) with effects that last for months
    3. May require high dose Vitamin K (50 mg PO three times daily) for months (at up to $45,000 per month)
    4. (2018) Presc Lett 25(6):35 [PubMed]
  3. Neuropsychiatric effects
    1. Confusion
    2. Agitation, irritation or Violent Behavior
    3. Severe anxiety
    4. Memory loss
    5. Loss of consciousness
    6. Generalized Seizures
  4. Acute Psychosis ("Spiceophrenia")
    1. Severe paranoia and Hallucinations (auditory and visual)
    2. May persist for days to months
    3. May occur after a single dose
  5. Gastrointestinal effects
    1. Nausea or Vomiting
    2. Diarrhea
  6. Cardiovascular effects
    1. Palpitations and Cardiac Arrhythmia
    2. Heart Rate changes (Tachycardia or Bradycardia)
    3. Blood Pressure changes (Hypertension or Hypotension)
    4. Cardiac ischemia
  7. Endocrine and renal effects
    1. Hypokalemia
    2. Metabolic Acidosis
    3. Hyperglycemia
    4. Acute Kidney Injury
    5. Rhabdomyolysis
  8. Withdrawal symptoms with regular use
    1. Anxiety, irritability, Insomnia
    2. Chills
    3. Profuse diaphoresis
    4. Tremors
    5. Myalgias
    6. Headaches
    7. Anorexia, Nausea, Vomiting

IX. Diagnostics

X. Management: Acute

  1. Aggressive supportive care management
    1. No specific antidotes
    2. Avoid unnecessary intubation
    3. Protect patients and staff
      1. See Agitated Delirium
      2. Sedation allows for IV Access, patient exposure, labs and diagnostics
  2. IV crystalloid fluid Resuscitation
    1. Indicated for dehydration
  3. Benzodiazepines
    1. First-line agent
    2. Indicated for Agitation
  4. Diphenhydramine
    1. Indicated for Dystonia
  5. Cooling
    1. Indicated for hyperthermia
  6. Antipsychotics (e.g. Zyprexa, Haloperidol)
    1. Indicated for acute Psychosis, esp. refractory to Benzodiazepines
    2. Avoid prophylactically due to theoretical risk of Seizure

XI. Management: Chemical Dependency

  1. Cognitive Behavioral Therapy
  2. Motivational Enhancement Therapy with abstinence-based incentives
  3. No medication is supported with sufficient evidence

XII. Precautions

  1. Agents are unregulated and unpredictable with variable components, potency and toxicity
  2. Acute Psychosis lasting months may occur after only a single dose
  3. Intentionally adulterated products with life threatening effects have been reported
    1. Life threatening bleeding due to Anticoagulant-laced Synthetic Cannabinoids in 2018
      1. See Adverse Effects as above
    2. Associated with 24 deaths in Mississippi in 2015

XIV. References

  1. Tomaszewski (2016) Drugs of Abuse, ACEP PEM Conference, Orlando, attended 3/8/2016
  2. Fattore (2011) Front Behav Neurosci 5: 60
    1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3187647/
  3. Haynes, Meadors and Yuan (2016) Crit Dec Emerg Med 30(2): 3-9
  4. Rosenbaum (2012) J Med Toxicol 8(1): 15–32
    1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3550220/
  5. Swaminathan and LaPoint in Herbert (2019) EM:Rap 19(5): 6-7
  6. Kemp (2016) Am J Med 129(3):240 [PubMed]
  7. Khullar (2014) J Gen Intern Med 29(8):1200-4 +PMID:24553958 [PubMed]
  8. Klega (2018) Am Fam Physician 98(2): 85-92 [PubMed]

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Ontology: Cannabinoids.synthetic (C3260252)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
LNC LP130276-1, MTHU041061
English Cannabinoids.synthetic