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SYNTHETIC CANNABINOIDS
Shelley A. Holmer MD
Duke University School of Medicine
©AMSP 2013
© AMSP 2013
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CASE
• 27 yo woman who presented with
o Trembling
o Confusion
o Voices
o Fears people want to harm her
• No family history of psychosis
• Medical work-up → no major medical dx
• Recent use of the synthetic cannabinoids
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THIS LECTURE WILL REVIEW
• Background on cannabinoids
• Development of synthetic cannabinoids (SC)
• Risks associated with use
• Synthetic cannabinoids versus marijuana
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NATURAL CANNABINOIDS = MARIJUANA
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• Comes from the plant Cannabis sativa
• Composed of > 500 compounds
• 66 compounds are "cannabinoids”
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CANNABINOIDS
Psychoactive
• Tetrahydrocannabinols (THC)
• Cannabinol (CBN)
• Cannabinodiol (CBDL)
Non-psychoactive
• Cannabigerols (CBG)
• Cannabichromenes (CBC)
• Cannabidiols (CBD)
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CANNABINOID RECEPTORS
CB1 receptor
• Psychoactive effects
• In brain and spinal cord (CNS)
• THC = partial agonist (positive effect)
• CBD = blocker of CB1
CB2 receptors
• Immune cells outside CNS
• Immune function and inflammation
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CANNABINOIDS:
PSYCHOACTIVE EFFECTS
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Euphoria
Sensation of slowed time
Impaired judgment
Impaired coordination
Social withdrawal
Anxiety
Psychosis
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PSYCHOSIS
• Hallucinations +/• Delusions
• Without insight
• Alert/oriented
• Potential cannabinoid impact:
o THC may ↑ psychosis
o CBD may ↓ psychosis
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NON-PSYCHOACTIVE EFFECTS
• ↓ Nausea
• ↑ Appetite
• ↓ Pain
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CHRONIC USE LEADS TO
• Tolerance
o Increased amount required for same effect
o Diminished effect with use of same amount
• Withdrawal symptoms when stopped
o Irritability
o Anxiety
o ↓ Appetite
o Sleep problems
No legal detox
• Peak ~3-4 days, resolves after ~7 days
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THIS LECTURE WILL REVIEW
• Background on cannabinoids
• Development of synthetic cannabinoids (SC)
• Risks associated with use
• SC versus marijuana
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SYNTHETIC CANNABINOIDS (SC)
• Research compounds
• None approved for humans
• Most >potency than THC
JWH18
• Full agonists at the CB1 receptor
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SPICE: SC COMMERCIAL PRODUCTS
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Spice
K2
Red magic
Red dragon
Diesel
Serenity
Blueberry Meditation
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SPICE
• SC sprayed on substance
• No dose control
• No regulation of ingredients
• Similar psychoactive effects to THC
• Marketed as herbal incense
“not for human use”
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SPICE USE
• First seen in Europe 2004
• First marketed in U.S. 2008
• 2012  used by 11 % of 12th graders
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SPICE: MEDICAL RECOGNITION
• Calls to US poison control centers
o2010: 3000
o2011: 7000
o2012: 5000
• 11,406 ER visits in 2010
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LEGAL STATUS OF SPICE
• 2008 Europe banned for health concerns
• 2011 US federal law deemed “no medical use”
• Possession illegal in 41 states
• Remains available
o Head shops
o Convenience stores/gas stations
o Internet
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WHY IS IT POPULAR?
• New/novel way to get “high”
• False belief SC safe because
o “Herbal”
o Legal
• Cannabis substitute
• Might ↓ cannabis withdrawal
• Inexpensive
• Accessible
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NOT DETECTED ON DRUG SCREENS
• Athletes
• Military personnel
• Students
• People on probation
• Employees with required drug screens
• Patients in drug tx programs
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THIS LECTURE WILL REVIEW
• Background on cannabinoids
• Development of synthetic cannabinoids (SC)
• Risks associated with use
• SC versus marijuana
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CASE
Clinical Course
• Pt immobile and incommunicative
• Hospitalized 2 mo with psychosis
• One year later psychosis free
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CASE REPORTS: ACUTE TOXICITY
Psychiatric
• Agitation
• Anxiety
• Paranoia
• Delusions
William S. Burroughs, 1914-1997, “Self Portrait,”
CU Libraries Exhibitions
• Hallucinations
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ACUTE TOXICITY
Neurologic
• Seizures
• Dilated pupils
• Jerking movements
• Decreased reflexes
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ACUTE TOXICITY
Cardiovascular
• ↑ Heart rate
• ↑ Blood pressure
• Chest pain
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ACUTE TOXICITY
Gastrointestinal
• Nausea
• Vomiting
• Diarrhea
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TREATMENT OF ACUTE INTOXICATION
Psychiatric: anxiety and psychosis
• Verbal reassurance “talk down”
• Medication for agitation (lorazepam)
• Seclusion/restraint only if serious danger
• Evaluate need for ongoing psychiatric care
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TREATMENT OF ACUTE INTOXICATION
Neurologic
• Seizure monitoring
• Evaluate muscle injury
o Muscle pain/weakness
o Labs: ↓ kidney function
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TREATMENT OF ACUTE INTOXICATION
Cardiac
• Monitor
o Blood pressure
o Heart rate
• Check EKG
• Labs: heart damage enzymes
o Troponin > 0.2 ng/ml
o CKMB > 3 ng/ml
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TREATMENT OF ACUTE INTOXICATION
Gastrointestinal
• Medication for nausea
• IV fluids
• Labs: check for low potassium
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LASTING CONSEQUENCES
Heart attacks
• 3 healthy adolescents with MI
• No personal or family history
• All smoked the SC “K2”
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LASTING CONSEQUENCES
May trigger psychosis if prior history
• 15 forensic inpts with psychotic illness
• All actively taking antipsychotics
• 5 with relapse of psychotic symptoms
• 24 hours after smoking JWH-018
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LASTING CONSEQUENCES
May cause first episode psychosis
• 10 men admitted for psychosis
• 9 had no FH of psychosis
• 7 needed meds
• 3 still psychotic 5 mo later
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LASTING CONSEQUENCES
Self harm/suicide while intoxicated
• Suicidal thoughts
• Reports of self-injury
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THIS LECTURE WILL REVIEW
• Background on cannabinoids
• Development of synthetic cannabinoids (SC)
• Risks associated with use
• SC versus marijuana
© AMSP 2013
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Marijuana vs Synthetic Cannabinoids
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Nature controls dose
Low-medium potency
Partial CB1 agonist
Contains CBD
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No dose control
High potency
Full CB1 agonist
No CBD
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COMPARING SC TO MARIJUANA (MJ)
• MJ contains CBD: potential antipsychotic
• Natural marijuana may ↓ seizures
• No long-term SC studies
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CLINICAL CONCLUSIONS
• Data on optimal Rx not available
• Need ask patients about SC use
• Educate patients about SC risks
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OVERALL CONCLUSIONS
• Not a safe marijuana alternative
• Easy to obtain despite ban
• Inquire about use
• Risks not commonly known by public
• Not detected on urine tests
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