SYNTHETIC CANNABINOIDS Shelley A. Holmer MD Duke University School of Medicine ©AMSP 2013 © AMSP 20131

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

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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

•Comes from the plant Cannabis sativa

•Composed of > 500 compounds

•66 compounds are "cannabinoids”

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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

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CANNABINOIDS: PSYCHOACTIVE EFFECTS

• 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• THC may ↑ psychosis• CBD may ↓ psychosis

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NON-PSYCHOACTIVE EFFECTS

• ↓ Nausea

• ↑ Appetite

• ↓ Pain

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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





• SC versus marijuana

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SC FOR MEDICAL USE

Dronabinol (Marinol)Nabilone (Cesamet)

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• 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

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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

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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

• 2010: 3000

• 2011: 7000

• 2012: 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• Head shops• Convenience stores/gas stations• Internet

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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






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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

• Hallucinations© AMSP 2013 23

Burroughs

https://exhibitions.cul.columbia.edu/archive/files/090069052_6e6cc5cd77.jpg

ACUTE TOXICITY

NEUROLOGIC

• Dilated pupils

• Decreased reflexes

• Jerking movements

• Seizures© AMSP 2013 24

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/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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NEUROLOGIC

• Seizure monitoring

• Evaluate muscle injury

• Muscle pain/weakness

• Labs: ↓ kidney function

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CARDIOVASCULAR

• Monitor • Blood pressure

• Heart rate

• Check EKG

• Labs: heart damage enzymes • Troponin > 0.2 ng/ml

• CKMB > 3 ng/ml

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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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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


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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Self harm/suicide while intoxicated

• Suicidal thoughts

• Reports of self-injury

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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

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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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CONCLUSIONS

• SC are commonly used• Easy to obtain despite ban• Not detected on urine tests• Risks not commonly known

• Ask about use

• Tell patients about risks © AMSP 2013 38

Documents

SYNTHETIC CANNABINOIDS Shelley A. Holmer MD Duke University School of Medicine ©AMSP 2013 © AMSP 20131