II. Pharmacology
- Synthetic Cannabinoids
- Originally produced as research chemicals to study receptor binding in the 1980s
- Synthetic Cannabinoids may have 10-200 times the potency at specific receptor sites
- Produced by spraying dried, shredded herbal plant leaves with cannabinoid receptor agonists
- Synthetic agonists are THC-like agents based on one of four synthetic parent agents
- Synthetic agonists are small, lipid soluble, non-polar molecules (22 to 26 carbons)
- Originally produced as research chemicals to study receptor binding in the 1980s
- Agents act at two cannabinoid receptors (with high affinity to CB1)
- CB1 - CNS receptors (decrease intracellular cAMP and increase MAP kinase)
- Elevates mood and increases feelings of well being
- Affects pain tolerance, time perception, memory
- CB2 - T Cells, B Cells and Macrophages as well as peripheral nerves
- CB1 - CNS receptors (decrease intracellular cAMP and increase MAP kinase)
- Most agents are pure agonists at cannabinoid CB1 cerebral receptor (contrast with THC as a partial agonist)
- Synthetics result in more intense, and unpredictable Intoxication than THC
- Synthetic THC lacks the Cannabidiol (Antipsychotic, anticonvulsant) effects of Cannabis sativa (Marijuana)
- Hence the unpredictable psychotic effects and Seizures with synthetic THC
- In addition, formulations frequently change to overcome detection
- Typically smoked in pipe or Cigarette paper
- Has also been vaporized and inhaled, as well as ingested
III. Preparations
- Sold in 1-3 gram foil pouches of dried Herbals
- Typically labeled as "not for human consumption" or marketed as incense
- More than 50 distinct products have been identified in the U.S.
- Various Herbals and crushed leaves are added for appearance only (drug is dripped onto the leaves)
- Inconsistent effects across products as well as within the same brand (unpredictable)
- Even different effects in the same package shared by different users
- May occur with concentrated portions within the package
- Street Names
- K2
- Kronic
- Spice
- JWH (John W. Huffman)
- Legal Marijuana
- Fake Weed
- Black Mamba
- Mojo
- Scooby Snax
- Death Ride
- Intensely aromatic incense
- Cloud-9 (AB-PINACA)
- Liquid form vaporized and resulted in multiple hospitalizations in 2014
IV. Symptoms: Intoxication
-
Marijuana-like Intoxication (sought effects)
- Euphoria, elevated mood or intense "high"
- Uncontrolled laughter
- Disinhibition
- Other effects
- Hyperadrenergic effects
- Agitated Delirium (with possible Seizures)
- Altered Mental Status with sedation
V. Signs: Intoxication
- Diaphoresis
- Hyperreflexia
- Nystagmus
- Conjunctival injection
VI. Symptoms: Withdrawal
- Headache
- Anxiety
- Depressed Mood
- Irritability
VII. Adverse Effects
- Effects vary due to the ever changing formulations and compositions of Synthetic Cannabinoids and contaminants
- Life threatening bleeding (2018)
- Related to Anticoagulant-laced Synthetic Cannabinoids in 2018
- Cannabinoids were laced with Brodifacoum (rat poison) with effects that last for months
- May require high dose Vitamin K (50 mg PO three times daily) for months (at up to $45,000 per month)
- (2018) Presc Lett 25(6):35 [PubMed]
- Neuropsychiatric effects
- Confusion
- Agitation, irritation or Violent Behavior
- Severe anxiety
- Memory loss
- Loss of consciousness
- Generalized Seizures
- Acute Psychosis ("Spiceophrenia")
- Severe paranoia and Hallucinations (auditory and visual)
- May persist for days to months
- May occur after a single dose
- Gastrointestinal effects
- Cardiovascular effects
- Palpitations and Cardiac Arrhythmia
- Heart Rate changes (Tachycardia or Bradycardia)
- Blood Pressure changes (Hypertension or Hypotension)
- Cardiac ischemia
- Endocrine and renal effects
- Withdrawal symptoms with regular use
VIII. Labs
- Serum Creatinine
- Serum Glucose
- Creatine Kinase (CK)
- Serum Lactic Acid
- Serum Troponin
IX. Diagnostics
X. Management: Acute
- Aggressive supportive care management
- No specific antidotes
- Avoid unnecessary intubation
- Protect patients and staff
- See Agitated Delirium
- Sedation allows for IV Access, patient exposure, labs and diagnostics
- IV crystalloid fluid Resuscitation
- Indicated for dehydration
-
Benzodiazepines
- First-line agent
- Indicated for Agitation
-
Diphenhydramine
- Indicated for Dystonia
- Cooling
- Indicated for hyperthermia
-
Antipsychotics (e.g. Zyprexa, Haloperidol)
- Indicated for acute Psychosis, esp. refractory to Benzodiazepines
- Avoid prophylactically due to theoretical risk of Seizure
XI. Management: Chemical Dependency
- Cognitive Behavioral Therapy
- Motivational Enhancement Therapy with abstinence-based incentives
- No medication is supported with sufficient evidence
XII. Precautions
- Agents are unregulated and unpredictable with variable components, potency and toxicity
- Acute Psychosis lasting months may occur after only a single dose
- Intentionally adulterated products with life threatening effects have been reported
- Life threatening bleeding due to Anticoagulant-laced Synthetic Cannabinoids in 2018
- See Adverse Effects as above
- Associated with 24 deaths in Mississippi in 2015
- Life threatening bleeding due to Anticoagulant-laced Synthetic Cannabinoids in 2018
XIII. Resources
XIV. References
- Tomaszewski (2016) Drugs of Abuse, ACEP PEM Conference, Orlando, attended 3/8/2016
- Fattore (2011) Front Behav Neurosci 5: 60
- Haynes, Meadors and Yuan (2016) Crit Dec Emerg Med 30(2): 3-9
- Rosenbaum (2012) J Med Toxicol 8(1): 15–32
- Swaminathan and LaPoint in Herbert (2019) EM:Rap 19(5): 6-7
- Kemp (2016) Am J Med 129(3):240 [PubMed]
- Khullar (2014) J Gen Intern Med 29(8):1200-4 +PMID:24553958 [PubMed]
- Klega (2018) Am Fam Physician 98(2): 85-92 [PubMed]
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Related Studies
Concepts | Organic Chemical (T109) , Pharmacologic Substance (T121) |
LNC | LP130276-1, MTHU041061 |
English | Cannabinoids.synthetic |