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

2. 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

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

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

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

6. 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

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

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

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

10. 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 201310 No legal detox

11. THIS LECTURE WILL REVIEW Background on cannabinoids Development of synthetic cannabinoids (SC) Risks associated with use SC versus marijuana © AMSP 201311

12. SC FOR MEDICAL USE Dronabinol (Marinol)Nabilone (Cesamet) © AMSP 201312 Nausea/vomiting with cancer chemotherapy AIDS associated anorexia and weight loss

13. SC FOR RECREATIONAL USE Research compounds None approved for humans Most >potency than THC Full agonists at the CB1 receptor JWH18 © AMSP 201313

14. SPICE MARKETING Sold as herbal incense Labeled “not for human use” © AMSP 201314 Spice Red magic K2 Red dragon Diesel Serenity

15. SPICE PRODUCTION SC sprayed on substance No dose control No regulation of ingredients © AMSP 201315

16. SPICE USE First seen in Europe 2004 First marketed in U.S. 2008 2012  used by 11 % of 12 th graders © AMSP 201316

17. SPICE: MEDICAL RECOGNITION Calls to US poison control centers 2010: 3000 2011: 7000 2012: 5000 11,406 ER visits in 2010 © AMSP 201317

18. 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 201318

19. WHY IS IT POPULAR? New/novel way to get “high” False belief SC safe because “Herbal” Legal Might ↓ cannabis withdrawal Inexpensive Accessible © AMSP 201319

20. NOT DETECTED ON DRUG SCREENS Athletes Military personnel Students People on probation Employees with required drug screens Patients in drug tx programs © AMSP 201320

21. THIS LECTURE WILL REVIEW Background on cannabinoids Development of synthetic cannabinoids (SC) Risks associated with use SC versus marijuana © AMSP 201321

22. CASE Clinical Course Pt immobile and incommunicative Hospitalized 2 mo with psychosis One year later psychosis free © AMSP 201322

23. CASE REPORTS: ACUTE TOXICITY PSYCHIATRIC Agitation Anxiety Paranoia Delusions Hallucinations © AMSP 201323 Burroughs

24. ACUTE TOXICITY NEUROLOGIC Dilated pupils Decreased reflexes Jerking movements Seizures © AMSP 201324

25. ACUTE TOXICITY CARDIOVASCULAR ↑ Heart rate ↑ Blood pressure Chest pain © AMSP 201325

26. ACUTE TOXICITY GASTROINTESTINAL Nausea Vomiting Diarrhea © AMSP 201326

27. 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 201327

28. TREATMENT OF ACUTE INTOXICATION NEUROLOGIC Seizure monitoring Evaluate muscle injury Muscle pain/weakness Labs: ↓ kidney function © AMSP 201328

29. 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 201329

30. TREATMENT OF ACUTE INTOXICATION GASTROINTESTINAL Medication for nausea IV fluids Labs: check for low potassium © AMSP 201330

31. LASTING CONSEQUENCES Heart attacks 3 healthy adolescents with MI No personal or family history All smoked the SC “K2” © AMSP 201331

32. 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 201332

33. 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 201333

34. LASTING CONSEQUENCES Self harm/suicide while intoxicated Suicidal thoughts Reports of self-injury © AMSP 201334

35. THIS LECTURE WILL REVIEW Background on cannabinoids Development of synthetic cannabinoids (SC) Risks associated with use SC versus marijuana © AMSP 201335

36. 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 201336

37. COMPARING SC TO MARIJUANA (MJ) MJ contains CBD: potential antipsychotic Natural marijuana may ↓ seizures No long-term SC studies © AMSP 201337

38. 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 201338