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

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 20132

THIS LECTURE WILL REVIEW Background on cannabinoids Development of synthetic cannabinoids (SC) Risks associated with use Synthetic cannabinoids versus marijuana © AMSP 20133

NATURAL CANNABINOIDS = MARIJUANA Comes from the plant Cannabis sativa Composed of > 500 compounds 66 compounds are "cannabinoids” © AMSP 20134

CANNABINOIDS Psychoactive Tetrahydrocannabinols (THC) Cannabinol (CBN) Cannabinodiol (CBDL) Non-psychoactive Cannabigerols (CBG) Cannabichromenes (CBC) Cannabidiols (CBD) © AMSP 20135

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 20136

CANNABINOIDS: PSYCHOACTIVE EFFECTS Euphoria Sensation of slowed time Impaired judgment Impaired coordination Social withdrawal Anxiety Psychosis © AMSP 20137

PSYCHOSIS Hallucinations +/- Delusions Without insight Alert/oriented Potential cannabinoid impact THC may ↑ psychosis CBD may ↓ psychosis © AMSP 20138

NON-PSYCHOACTIVE EFFECTS ↓ Nausea ↑ Appetite ↓ Pain © AMSP 20139

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 No legal detox

THIS LECTURE WILL REVIEW Background on cannabinoids Development of synthetic cannabinoids (SC) Risks associated with use SC versus marijuana © AMSP

SC FOR MEDICAL USE Dronabinol (Marinol)Nabilone (Cesamet) © AMSP 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

SPICE MARKETING Sold as herbal incense Labeled “not for human use” © AMSP Spice Red magic K2 Red dragon Diesel Serenity

SPICE PRODUCTION SC sprayed on substance No dose control No regulation of ingredients © AMSP

SPICE USE First seen in Europe 2004 First marketed in U.S  used by 11 % of 12 th graders © AMSP

SPICE: MEDICAL RECOGNITION Calls to US poison control centers 2010: : : ,406 ER visits in 2010 © AMSP

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

WHY IS IT POPULAR? New/novel way to get “high” False belief SC safe because “Herbal” Legal Might ↓ cannabis withdrawal Inexpensive Accessible © AMSP

NOT DETECTED ON DRUG SCREENS Athletes Military personnel Students People on probation Employees with required drug screens Patients in drug tx programs © AMSP

THIS LECTURE WILL REVIEW Background on cannabinoids Development of synthetic cannabinoids (SC) Risks associated with use SC versus marijuana © AMSP

CASE Clinical Course Pt immobile and incommunicative Hospitalized 2 mo with psychosis One year later psychosis free © AMSP

CASE REPORTS: ACUTE TOXICITY PSYCHIATRIC Agitation Anxiety Paranoia Delusions Hallucinations © AMSP Burroughs

ACUTE TOXICITY NEUROLOGIC Dilated pupils Decreased reflexes Jerking movements Seizures © AMSP

ACUTE TOXICITY CARDIOVASCULAR ↑ Heart rate ↑ Blood pressure Chest pain © AMSP

ACUTE TOXICITY GASTROINTESTINAL Nausea Vomiting Diarrhea © AMSP

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

TREATMENT OF ACUTE INTOXICATION NEUROLOGIC Seizure monitoring Evaluate muscle injury Muscle pain/weakness Labs: ↓ kidney function © AMSP

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

TREATMENT OF ACUTE INTOXICATION GASTROINTESTINAL Medication for nausea IV fluids Labs: check for low potassium © AMSP

LASTING CONSEQUENCES Heart attacks 3 healthy adolescents with MI No personal or family history All smoked the SC “K2” © AMSP

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

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

LASTING CONSEQUENCES Self harm/suicide while intoxicated Suicidal thoughts Reports of self-injury © AMSP

THIS LECTURE WILL REVIEW Background on cannabinoids Development of synthetic cannabinoids (SC) Risks associated with use SC versus marijuana © AMSP

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

COMPARING SC TO MARIJUANA (MJ) MJ contains CBD: potential antipsychotic Natural marijuana may ↓ seizures No long-term SC studies © AMSP

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