Spice, K2 and Other Synthetic Cannabinoids

1. Spice, K2 and Other Synthetic Cannabinoids

2. Herbal Incense Sold in head shops or online as an incense product Herbs and botanicals treated with synthetic cannabinoid chemicals Many varieties/scents Labeled �Not for Human Consumption�

3. Herbal Incense Variety of Products Available Spice, K2, Smoke, Yucatan Fire, Hush, Genie

4. Single Use or Bulk Product Sold Loose or in joint form $10-15 gram $10-15 gram

5. Aromatic Herbs Canavalia maritima, Nymphaea caerulea, Scutellaria nana, Pedicularis densiflora, Leonotis leonurus, Zornia latifolia, Nelumbo nucifera , Leonurus sibiricus� many more. Bay Bean, Blue Egyptian Water Lily, Dwarf Skullcap, Indian Warrior, Lions Tail, Indian Lotus, Honeyweed or Motherwort, Marshmallow, Rosehip Bay Bean, Blue Egyptian Water Lily, Dwarf Skullcap, Indian Warrior, Lions Tail, Indian Lotus, Honeyweed or Motherwort, Marshmallow, Rosehip

6. Herbal Effects Most of the herbal components have very little psychoactive effects, although some traditional herbalists may disagree. At most, they: Add color and flavor May have mild relaxing properties Decrease blood pressure Reduce inflammation Induce mild euphoria Marketed the herbal components as the cause of psychoactive properties. They do not mention the REAL cause�Marketed the herbal components as the cause of psychoactive properties. They do not mention the REAL cause�

7. Drug Discovery Intense psychoactive properties were being reported, but with little verification. In late 2008, forensic analyses conducted in Europe identified JWH-018 as a psychoactive ingredient in many of these products. JWH-018: synthetic cannabinoid synthesized in 1995 for experimental purposes. Austria / Germany forensic labs (e.g. THCPharm) conducted Forensic testsAustria / Germany forensic labs (e.g. THCPharm) conducted Forensic tests

8. Laced product Spice-like herbal incense products are laced with potent, potentially life-threatening Synthetic Cannabinoids. User provided with no real knowledge as to what is in the product he/she is smoking. Synthetic ingredients are ever-changing to stay one step ahead of the law. Austria / Germany forensic labs (e.g. THCPharm) conducted Forensic testsAustria / Germany forensic labs (e.g. THCPharm) conducted Forensic tests

9. Prevalence Very popular amongst individuals who are in substance abuse program that requires drug testing 40-60% positive rate in both adult and juvenile populations. As high as >90% in juvenile drug court populations oberved. Target individuals who are reported to exhibit marijuana-like symptoms and behavior, but who fail to test positive for THC. Austria / Germany forensic labs (e.g. THCPharm) conducted Forensic testsAustria / Germany forensic labs (e.g. THCPharm) conducted Forensic tests

10. Cannabis Overview Used for more than 4000 years for euphoric and therapeutic effects Most commonly abused drug in the world. Roughly 4% of the world's adult population (162�million people) use cannabis annually, and about 0.6% (22.5�million) use it on a daily basis THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Weight Reduction, Smoking Cessation, Analgesics Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Weight Reduction, Smoking Cessation, Analgesics Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer

11. Cannabis Contains: >450 chemicals >60-90 different cannabinoids D9-Tetrathydrocannabinol (THC) Main psychoactive ingredient of marijuana THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Weight Reduction, Smoking Cessation, Analgesics Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Weight Reduction, Smoking Cessation, Analgesics Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer

12. Cannabis THC content in marijuana varies � typically 2-5% in cannabis, but much higher has been found Marijuana users may experience stimulant, depressant, and/or hallucinogenic properties Most commonly used for hallucinogenic effects Most individuals self-titrate their THC intake THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Weight Reduction, Smoking Cessation, Analgesics Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Weight Reduction, Smoking Cessation, Analgesics Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer

13. Cannabis Most common Medicinal Uses: Relief from nausea and vomiting Stimulation of hunger  General analgesic effects (pain reliever) Lowered intraocular eye pressure THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Weight Reduction, Smoking Cessation, Analgesics Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Weight Reduction, Smoking Cessation, Analgesics Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer

14. What are Cannabinoids? Class of chemicals that have similar structure and/or activity that mimic: Phytocannabinoids (found in cannabis plants) Natural, herbal, classical Endocannabinoids (found in CNS and immune systems of animals)  THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer

15. Cannabinoid Functions What are the Endocannabinoid functions? Signaling molecules (Lipid messengers) that are released from cells to bind to nearby cell receptors. Signaling is retrograde (reverse direction postsynatic to presynaptic neurons) THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Weight Reduction, Smoking Cessation, Analgesics Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Weight Reduction, Smoking Cessation, Analgesics Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer

16. Cannabinoid Receptors At least two subtypes of Cannabinoid Receptors: CB1 Receptor Found throughout the peripheral and CNS systems CB2 Receptor Found throughout the peripheral nervous system and associated with the immune system  THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Weight Reduction, Smoking Cessation, Analgesics Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Weight Reduction, Smoking Cessation, Analgesics Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer

17. At least two subtypes of Cannabinoid Receptors: THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Weight Reduction, Smoking Cessation, Analgesics Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Weight Reduction, Smoking Cessation, Analgesics Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer

19. Synthetic Cannabinoids Four Groups of Synthetic Cannabinoids: THC Analogue (classical) Non-classical � Cyclohexylphenyl (CP) series Aminoalkylindoles � (JWH compounds) Other � Fatty Acid Amides All four types found in Spice products Fat-souble, non-polar, small molecules Volatile (smokable) Many times more potent than THC Dose may be less than 1 mgAll four types found in Spice products Fat-souble, non-polar, small molecules Volatile (smokable) Many times more potent than THC Dose may be less than 1 mg

20. Synthetic Cannabinoid Agonists Most are full CB1 & CB2 receptor agonists Originally investigated for medicinal purposes: Analgesics Weight management Control of Nausea Smoking cessation THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Weight Reduction, Smoking Cessation, Analgesics Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer THC is a partial dopamine, serotonin, GABA agonist (CB1) EX: GABA gamma-aminobutyric acid induces relaxation and sleep, inhibits over-excitation and anxiety, epilepsy. Contributes to motor control and vision, memory, mood, sleep Weight Reduction, Smoking Cessation, Analgesics Full agonists (not Partial) � far more intense. Anxiety, agitation, seizures, convulsions (panic attacks) May be involved in the development of Osteoporosis, Liver Disease, Cancer

21. Cannabinoid Agonists THC AnaloguesHU-210, HU-211, HU-243, HU-308, HU-320, HU-331, HU-336, HU-345 Raphael Mechoulam  Hebrew University HU � Professor Raphael Mechoulam at the Hebrew University of Jerusalem � Famous for d9-THC isolation and synthesis Some compounds are 100-800x more potent than THC, longer duration -HU � Professor Raphael Mechoulam at the Hebrew University of Jerusalem � Famous for d9-THC isolation and synthesis Some compounds are 100-800x more potent than THC, longer duration -

22. Cannabinoid Agonists Cyclohexylphenyl (CP) SeriesPfizer Pharmaceutical  CP 47,497, CP 55,940, CP 47,497 � (C8), CP 50,556-1, CP 55,244  CP � Cyclohexylphenols - Pfizer � analgesic - 5-45x more potent than THC CP � Cyclohexylphenols - Pfizer � analgesic - 5-45x more potent than THC

23. Cannabinoid Agonists AminoalylindolesOver 470 analogues JWH-015, JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-133, JWH-147, JWH-171, JWH-210, JWH-250, JWH-398 John W.Huffman  Clemson University JWH � John W. Huffman (Clemson University) � NIDA research of more than 470 analoguesJWH � John W. Huffman (Clemson University) � NIDA research of more than 470 analogues

26. Inhibition of GABA neurotransmitter � probable cause of convulsions and seizuresInhibition of GABA neurotransmitter � probable cause of convulsions and seizures

28. JWH-018 � Full CB1 Agonist - 3X affinity for CB2 than THC JWH-073 � Full CB1 Agonist - 5X affinity for CB2 than THC JWH-200 � 3X affinity for CB1 than THC (less sedative) - Analgesic JWH-018 � Full CB1 Agonist - 3X affinity for CB2 than THC JWH-073 � Full CB1 Agonist - 5X affinity for CB2 than THC JWH-200 � 3X affinity for CB1 than THC (less sedative) - Analgesic

29. Detection Synthetic cannabinoids are not detected by traditional drug screening tests Detection period roughly 24-72 hours in urine Only metabolites are detected in urine Typically JWH metabolites analyzed due to availability of standards Approximately 12-48 hours in blood and oral fluid Parent drug detected Advanced testing methodology utilized Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS)

30. Analysis by LC/MS/MS

32. HU-210 � 8X THC � potent analgesic JWH-133 selective for CB2 receptor � 200X THC � devoid of psychoactive properties. All three prevents inflammation caused by amyloid proteins (plaques that build up in brain of Alzheimers patients) Rimonabant Rimonabant (SR141716) antiobesity drug � antagonist of CB1 receptor Selectivity of CB1 provided tool for examining endocannabinoid system and behavioral and physiological effects of THC. Possible use to mediate CB1 cannabinoidpharmacodynamics by blockade of cannabinoid agonists Decrease in heart rate (BPM)reduced cannabis effects of 40-75% in single dose or multiple small dosingNo significant cannabis withdrawlNo clinical adverse effectsNIDA interested in pharacotherapy usage Assisted in smoking cessation therepyAddiction reduced cocaine-seeking responses by 2 of 3 most common triggers in relapse (priming and cues)Possible reduction of ethanol and opiate-seeking behaviorHypothetically could improve short-term memory (demonstrated in rats)Blocks psychoactive and cardiovascular effects of D9-Tetrathydrocannabinol (THC) without affecting the pharmocokinetics HU-210 � 8X THC � potent analgesic JWH-133 selective for CB2 receptor � 200X THC � devoid of psychoactive properties. All three prevents inflammation caused by amyloid proteins (plaques that build up in brain of Alzheimers patients) Rimonabant Rimonabant (SR141716) antiobesity drug � antagonist of CB1 receptor Selectivity of CB1 provided tool for examining endocannabinoid system and behavioral and physiological effects of THC. Possible use to mediate CB1 cannabinoidpharmacodynamics by blockade of cannabinoid agonists Decrease in heart rate (BPM)reduced cannabis effects of 40-75% in single dose or multiple small dosingNo significant cannabis withdrawlNo clinical adverse effectsNIDA interested in pharacotherapy usage Assisted in smoking cessation therepyAddiction reduced cocaine-seeking responses by 2 of 3 most common triggers in relapse (priming and cues)Possible reduction of ethanol and opiate-seeking behaviorHypothetically could improve short-term memory (demonstrated in rats)Blocks psychoactive and cardiovascular effects of D9-Tetrathydrocannabinol (THC) without affecting the pharmocokinetics

35. Bath Salts and Other Stimulants

36. Bath Salts Sold in head shops, gas stations and online Psychoactive / Dissociative Illegal in many states Highly addictive and dangerous Snorted, but can be smoked, taken orally or injected

37. Bath Salts 4MMC, Meow-meow, MC, MTV, M-CAT, Bounce, Plant Food $30-90 / gram - talc-like Usually made in China / Asia Pixie Dust, Ivory Wave, Ocean, Charge Plus, White Lightning, White Girl, Scarface, Hurricane Charlie, Vanilla Sky, Bonzai, Grow, Blue Silk, Lovey Dovey

38. Bath Salt Effects Effects last 2 - 4 hours  Feelings of euphoria - Increased alertness Dilated pupils Slurred speech, Inability to stop talking Increased heart rate Both decreased and/or increased sexual function/desire

39. Negative Effects Physical: CNS stimulant Increase BP and heart rate Chest pain, heart attack, stroke Infertility Psychological: Delusions, paranoia, psychosis Personality disorders Depression when not using � as long as several weeks After effects such as tachycardia, hypertension, and mild stimulation lasting from 6 - 8 hours

40. Chemical Composition Mephedrone - 4-methylmethcathinone (4-MMC) AKA: Meph, drone, MCAT Originally developed in 1929 - recently �rediscovered�  Analogue to other controlled substances Sold as plant food or bath salts � not for human consumption

41. Chemical Composition MDPV (3,4-methylenedioxypyrovalerone) AKA: MDPK, Magic, Super Coke, MTV and PV Originally developed in the 60�s for chronic fatigue and appetite suppression.  Abuse and dependence a problem with a compulsive desire to continuously re-dose Similar in structure to MDMA, but more of a stimulant  Only has mild empathogenic or entactogenic properties Standard, Premium, Ultra, Summit, Blueberry, Citron, Strawberry, Apple Baked, Pineapple (Express), Kush, Blonde, Sex, Honey, Thai Dream, Orisha, Blue, Pink Standard, Premium, Ultra, Summit, Blueberry, Citron, Strawberry, Apple Baked, Pineapple (Express), Kush, Blonde, Sex, Honey, Thai Dream, Orisha, Blue, Pink

42. High Addiction Potential Abuse and dependence a problem with a compulsive desire to continuously re-dose Some are constantly chase that first high Mephedrone reduces to 4-methylephedrine - a known Cardiotoxic compound Crushing chest pain � common redosing the cause?

43. Other Stimulants Cathinone Found in the shrub Catha edulis (Khat)  Part of the Middle East culture Stimulant typically extracted from chewing fresh leaves  Standard, Premium, Ultra, Summit, Blueberry, Citron, Strawberry, Apple Baked, Pineapple (Express), Kush, Blonde, Sex, Honey, Thai Dream, Orisha, Blue, Pink Standard, Premium, Ultra, Summit, Blueberry, Citron, Strawberry, Apple Baked, Pineapple (Express), Kush, Blonde, Sex, Honey, Thai Dream, Orisha, Blue, Pink

44. Other Stimulants Methcathinone First synthesized in 1928 It was used in the Soviet Union during the 1930s and 1940s as an anti-depressant.  Since the 1960s, methcathinone has been used as a recreational drug in the (former) Soviet Union. Standard, Premium, Ultra, Summit, Blueberry, Citron, Strawberry, Apple Baked, Pineapple (Express), Kush, Blonde, Sex, Honey, Thai Dream, Orisha, Blue, Pink Standard, Premium, Ultra, Summit, Blueberry, Citron, Strawberry, Apple Baked, Pineapple (Express), Kush, Blonde, Sex, Honey, Thai Dream, Orisha, Blue, Pink

46. Detection Most compounds are not detected by drug screening tests Detection period roughly 24-72 hours in urine Analyte-specific methodologies are used Gas Chromatography/Mass Spectrometry (GCMS) Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) Specialized Stimulants Panel should include: Amphetamine / Methamphetamine MDA / MDMA Cathinone / Methcathinone Mephedrone / MDPV Standard, Premium, Ultra, Summit, Blueberry, Citron, Strawberry, Apple Baked, Pineapple (Express), Kush, Blonde, Sex, Honey, Thai Dream, Orisha, Blue, Pink Standard, Premium, Ultra, Summit, Blueberry, Citron, Strawberry, Apple Baked, Pineapple (Express), Kush, Blonde, Sex, Honey, Thai Dream, Orisha, Blue, Pink

47. Kratom Mitragynine Krypton Sold for $5/gram � in bulk Powder, dry leaf, and resin forms �Bomb� ingestion � Consume powder wrapped in tissue Dose 0.5-1.5 grams  Standard, Premium, Ultra, Summit, Blueberry, Citron, Strawberry, Apple Baked, Pineapple (Express), Kush, Blonde, Sex, Honey, Thai Dream, Orisha, Blue, Pink Standard, Premium, Ultra, Summit, Blueberry, Citron, Strawberry, Apple Baked, Pineapple (Express), Kush, Blonde, Sex, Honey, Thai Dream, Orisha, Blue, Pink

48. Kratom Mitragynine Leaves of Kratom (mitragyna speciosa) � medicinal plant from Southwest Asia, a mu-receptor agonist Binds to mu-opiate receptors responsible for the enjoyable effects of the opiates, analgesia, and physical dependence. Low dose � stimulant effect; High dose � opioid-like sedative effect 2-3 hours � numbing effects / 6-8 hours � stimulant effect as the experience wears off Standard, Premium, Ultra, Summit, Blueberry, Citron, Strawberry, Apple Baked, Pineapple (Express), Kush, Blonde, Sex, Honey, Thai Dream, Orisha, Blue, Pink Standard, Premium, Ultra, Summit, Blueberry, Citron, Strawberry, Apple Baked, Pineapple (Express), Kush, Blonde, Sex, Honey, Thai Dream, Orisha, Blue, Pink

49. Kratom Mitragynine Risks High risk for accidental overdose Brain and lung edema, congestion of inner organs In reported deaths, other psychotropic drugs were found (Benzodiazepines, Effexor, Prozac) Standard, Premium, Ultra, Summit, Blueberry, Citron, Strawberry, Apple Baked, Pineapple (Express), Kush, Blonde, Sex, Honey, Thai Dream, Orisha, Blue, Pink Standard, Premium, Ultra, Summit, Blueberry, Citron, Strawberry, Apple Baked, Pineapple (Express), Kush, Blonde, Sex, Honey, Thai Dream, Orisha, Blue, Pink