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

2. 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 © 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 = 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: o THC may ↑ psychosis o CBD may ↓ psychosis © AMSP 20138

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

10. 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 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. SYNTHETIC CANNABINOIDS (SC) Research compounds None approved for humans Most >potency than THC Full agonists at the CB1 receptor JWH18 © AMSP 201312

13. SPICE: SC COMMERCIAL PRODUCTS Spice K2 Red magic Red dragon Diesel Serenity Blueberry Meditation © AMSP 201313

14. 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” © AMSP 201314

15. SPICE USE First seen in Europe 2004 First marketed in U.S. 2008 2012  used by 11 % of 12 th graders © AMSP 201315

16. SPICE: MEDICAL RECOGNITION Calls to US poison control centers o 2010: 3000 o 2011: 7000 o 2012: 5000 11,406 ER visits in 2010 © AMSP 201316

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 o Head shops o Convenience stores/gas stations o Internet © AMSP 201317

18. 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 © AMSP 201318

19. NOT DETECTED ON DRUG SCREENS Athletes Military personnel Students People on probation Employees with required drug screens Patients in drug tx programs © AMSP 201319

20. THIS LECTURE WILL REVIEW Background on cannabinoids Development of synthetic cannabinoids (SC) Risks associated with use SC versus marijuana © AMSP 201320

21. CASE Clinical Course Pt immobile and incommunicative Hospitalized 2 mo with psychosis One year later psychosis free © AMSP 201321

22. CASE REPORTS: ACUTE TOXICITY Psychiatric Agitation Anxiety Paranoia Delusions Hallucinations © AMSP 201322 William S. Burroughs, 1914-1997, “Self Portrait,” CU Libraries Exhibitions

23. ACUTE TOXICITY Neurologic Seizures Dilated pupils Jerking movements Decreased reflexes © AMSP 201323

24. ACUTE TOXICITY Cardiovascular ↑ Heart rate ↑ Blood pressure Chest pain © AMSP 201324

25. ACUTE TOXICITY Gastrointestinal Nausea Vomiting Diarrhea © AMSP 201325

26. 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 © AMSP 201326

27. TREATMENT OF ACUTE INTOXICATION Neurologic Seizure monitoring Evaluate muscle injury o Muscle pain/weakness o Labs: ↓ kidney function © AMSP 201327

28. 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 © AMSP 201328

29. TREATMENT OF ACUTE INTOXICATION Gastrointestinal Medication for nausea IV fluids Labs: check for low potassium © AMSP 201329

30. LASTING CONSEQUENCES Heart attacks 3 healthy adolescents with MI No personal or family history All smoked the SC “K2” © AMSP 201330

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 201331

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 201332

33. LASTING CONSEQUENCES Self harm/suicide while intoxicated Suicidal thoughts Reports of self-injury © AMSP 201333

34. THIS LECTURE WILL REVIEW Background on cannabinoids Development of synthetic cannabinoids (SC) Risks associated with use SC versus marijuana © AMSP 201334

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 201335

36. COMPARING SC TO MARIJUANA (MJ) MJ contains CBD: potential antipsychotic Natural marijuana may ↓ seizures No long-term SC studies © AMSP 201336

37. CLINICAL CONCLUSIONS Data on optimal Rx not available Need ask patients about SC use Educate patients about SC risks © AMSP 201337

38. 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 © AMSP 201338