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SYNTHETIC CANNABINOIDS
Shelley A. Holmer MDDuke University School of Medicine
©AMSP 2013
© AMSP 2013 1
CASE
• 27 yo woman who presented with
• Trembling
• Confusion
• Voices
• Fears people want to harm her
• No family history of psychosis
• Medical work-up → no major medical dx
• Recent use of the synthetic cannabinoids
© AMSP 2013 2
THIS LECTURE WILL REVIEW
• Background on cannabinoids
• Development of synthetic cannabinoids (SC)
• Risks associated with use
• Synthetic cannabinoids versus marijuana
© AMSP 2013 3
NATURAL CANNABINOIDS = MARIJUANA
•Comes from the plant Cannabis sativa
•Composed of > 500 compounds
•66 compounds are "cannabinoids”
© AMSP 2013 4
CANNABINOIDSPsychoactive
• Tetrahydrocannabinols (THC)
• Cannabinol (CBN)
• Cannabinodiol (CBDL)
Non-psychoactive
• Cannabigerols (CBG)
• Cannabichromenes (CBC)
• Cannabidiols (CBD)© AMSP 2013 5
CANNABINOID RECEPTORS
CB1 receptor• Psychoactive effects• In brain and spinal cord (CNS)• THC = partial agonist (positive effect)• CBD = antagonist (blocker of CB1)
CB2 receptors• Immune cells outside CNS• Immune function and inflammation
© AMSP 2013 6
CANNABINOIDS: PSYCHOACTIVE EFFECTS
• Euphoria
• Sensation of slowed time
• Impaired judgment
• Impaired coordination
• Social withdrawal
• Anxiety
• Psychosis
© AMSP 2013 7
PSYCHOSIS• Hallucinations +/-
• Delusions
• Without insight
• Alert/oriented
• Potential cannabinoid impact• THC may ↑ psychosis• CBD may ↓ psychosis
© AMSP 2013 8
CHRONIC USE LEADS TO• Tolerance
• Withdrawal symptoms when stopped• Irritability/anger/aggression• Anxiety• Sleep difficulty• ↓ Appetite• Restlessness• Depressed mood• Physical Symptoms
• Peak ~3-4 days, resolves after ~7 days© AMSP 2013 10
No legal detox
THIS LECTURE WILL REVIEW
• Background on cannabinoids
• Development of synthetic cannabinoids (SC)
• Risks associated with use
• SC versus marijuana
© AMSP 2013 11
SC FOR MEDICAL USE
Dronabinol (Marinol)Nabilone (Cesamet)
© AMSP 2013 12
• Nausea/vomiting with cancer chemotherapy
• AIDS associated anorexia and weight loss
SC FOR RECREATIONAL USE
• Research compounds
• None approved for humans
• Most >potency than THC
• Full agonists at the CB1 receptor
JWH18
© AMSP 2013 13
SPICE MARKETING
Sold as herbal incense
Labeled “not for human use”© AMSP 2013 14
Spice Red magic
K2 Red dragon
Diesel Serenity
SPICE PRODUCTION
• SC sprayed on substance
• No dose control
• No regulation of ingredients
© AMSP 2013 15
SPICE USE
• First seen in Europe 2004
• First marketed in U.S. 2008
• 2012 used by 11 % of 12th graders
© AMSP 2013 16
SPICE: MEDICAL RECOGNITION
• Calls to US poison control centers
• 2010: 3000
• 2011: 7000
• 2012: 5000
• 11,406 ER visits in 2010
© AMSP 2013 17
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• Head shops• Convenience stores/gas stations• Internet
© AMSP 2013 18
WHY IS IT POPULAR?
• New/novel way to get “high”
• False belief SC safe because
• “Herbal”
• Legal
• Might ↓ cannabis withdrawal
• Inexpensive
• Accessible© AMSP 2013 19
NOT DETECTED ON DRUG SCREENS
• Athletes
• Military personnel
• Students
• People on probation
• Employees with required drug screens
• Patients in drug tx programs© AMSP 2013 20
THIS LECTURE WILL REVIEW
• Background on cannabinoids
• Development of synthetic cannabinoids (SC)
• Risks associated with use
• SC versus marijuana
© AMSP 2013 21
CASE
Clinical Course
• Pt immobile and incommunicative
• Hospitalized 2 mo with psychosis
• One year later psychosis free
© AMSP 2013 22
CASE REPORTS: ACUTE TOXICITY
PSYCHIATRIC
• Agitation
• Anxiety
• Paranoia
• Delusions
• Hallucinations© AMSP 2013 23
Burroughs
ACUTE TOXICITY
NEUROLOGIC
• Dilated pupils
• Decreased reflexes
• Jerking movements
• Seizures© AMSP 2013 24
TREATMENT OF ACUTE INTOXICATION
PSYCHIATRIC (anxiety/psychosis)
• Verbal reassurance “talk down”
• Medication for agitation (lorazepam)
• Seclusion/restraint only if serious danger
• Evaluate need for ongoing psychiatric care
© AMSP 2013 27
TREATMENT OF ACUTE INTOXICATION
NEUROLOGIC
• Seizure monitoring
• Evaluate muscle injury
• Muscle pain/weakness
• Labs: ↓ kidney function
© AMSP 2013 28
TREATMENT OF ACUTE INTOXICATION
CARDIOVASCULAR
• Monitor • Blood pressure
• Heart rate
• Check EKG
• Labs: heart damage enzymes • Troponin > 0.2 ng/ml
• CKMB > 3 ng/ml
© AMSP 2013 29
TREATMENT OF ACUTE INTOXICATION
GASTROINTESTINAL
• Medication for nausea
• IV fluids
• Labs: check for low potassium
© AMSP 2013 30
LASTING CONSEQUENCES
Heart attacks
• 3 healthy adolescents with MI
• No personal or family history
• All smoked the SC “K2”
© AMSP 2013 31
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© AMSP 2013 32
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
© AMSP 2013 33
LASTING CONSEQUENCES
Self harm/suicide while intoxicated
• Suicidal thoughts
• Reports of self-injury
© AMSP 2013 34
THIS LECTURE WILL REVIEW
• Background on cannabinoids
• Development of synthetic cannabinoids (SC)
• Risks associated with use
• SC versus marijuana
© AMSP 2013 35
Marijuana vs Synthetic Cannabinoids
• Nature controls dose• Low-medium potency• Partial CB1 agonist • Contains CBD
• No dose control• High potency• Full CB1 agonist• No CBD
© AMSP 2013 36
COMPARING SC TO MARIJUANA (MJ)
• MJ contains CBD: potential antipsychotic
• Natural marijuana may ↓ seizures
• No long-term SC studies
© AMSP 2013 37