Barry Logan PhD discusses analysis and effects of synthetic cannabinoids like K2
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The document discusses K2 and synthetic cannabinoids like JWH-018 and JWH-073. It summarizes their origins, effects, and challenges in analyzing them. Studies found synthetic cannabinoids can cause effects like tachycardia, dry mouth, impaired coordination and concentration. They are difficult to detect but studies found metabolites in blood and urine for hours after use, requiring targeted analysis to identify them in overdose or DUI cases.
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Barry Logan PhD discusses analysis and effects of synthetic cannabinoids like K2
- 1. Barry K Logan PhD, DABFT Director of Forensic Services NMS Labs online Seminar September 16, 2010 K2 and the Synthetic Cannabinoids: Pharmacology, Effects, and Chemical Analysis From the Premium Provider of Forensic Services
- 9. Marijuana Most popular recreational drug after alcohol and tobacco. Main psychoactive component THC #1 Drug in the DRE program Some 25 million Americans have smoked marijuana in the past year, and more than 14 million do so regularly. Possession and use illegal under federal law, but states have variable policies on enforcement and prosecution. 6.8% of Friday and Saturday evening drivers test positive for use.
- 10. Synthetic Cannabinoids Synthetic drugs that mimic the effects of cannabis. Investigational use for appetite, blood pressure, nausea, etc First synthesized in the 1980’s Sprayed onto dried plant leaves, flowers and stems, and smoked. Legal or unregulated in most US states.
- 11. K2 Phenomenon Kansas, Georgia, Kentucky, Alabama, Tennessee, Louisiana, Missouri, Hawaii, Arkansas, Illinois Mississippi
- 12. Clemson Series - JWH JWH-018 JWH-073 JWH-250
- 13. Marijuana to Spice THC HU-210 CP 47,497 WIN 55,212
- 14. Cannabinoid Mechanism of Action Cerebral Cortex Higher Cognitive Function Basal Ganglia Cerebellum Movement Hippocampus Learning, Memory, Stress Hypothalamus Appetite Spinal Chord Pain, Peripheral sensation Medulla Nausea, Vomiting
- 15. Herbals - Botanical Substrate Glycyrrhiza glabra (Cultivated Liquorice) Astragalus membranaceus (Milk Vetch) Verbascum thapsus (Common Mullein) (Uchiyama et al, 2010)
- 17. Synthetic Cannabinoids – Drug ID JWH-018 JWH-073 JWH-200 HU-210/11 JWH-019 JWH-200 WIN 55,212 JWH-015 JWH-133 JWH-250 CP55,940 CP 47,497 (n=7) CP 47,497 (n=8)
- 18. K2 Blends - Drug Content (* Uchiyama et al, 2010) JWH-018 (mg/g) JWH-073 (mg/g) CP47,497 (n=8) (mg/g) JWH-250 (mg/g) K2 Blonde 12 13 - - K2 Standard 9 9 - - K2 Citron 10 10 - - K2* (Unknown) - - 6 - K2 Summit 11 9 - - K2 Blue 15 - - - K2 Pink 11 - - - K2 Latte 16 0.28 - 14 K2 Mint 19 0.30 - - K2 Silver 8 - - 16 Spike Gold 20 11 - - Spike Maxx 17 - - 19 Spike Diamond 17 0.07 - - Spike Silver 9 16 - - Space 10 - - - Herbal blends* 2.0 – 35.9 - 1.1 – 16.9 -
- 22. Synthetic Cannabinoid Effects T. Sobolevsky, et al., Detection of JWH-018 metabolites in smoking mixture post-administration urine, Forensic Sci. Int. (2010), doi:10.1016/j.forsciint.2010.04.003
- 25. NMS Labs Special Projects Matrix Analytes Blood Serum Oral Fluid (Refrigerate) Parent Compounds – JWH-018, JWH-073, JWH-200, HU-210, HU-211, JWH-019, JWH-200 WIN 55,212, JWH-015, JWH-133, JWH-250, CP55,940, CP 47,497 (n=7) CP 47,497 (n=8) … Urine (Freeze) Ring monohydroxylated metabolites – glucuronidated Ring dihydroxylated metabolites – glucuronidated Desmethyl ring hydroxylated metabolites - glucuronidated
- 29. K2 use and the DRE Matrix * High doses Drug Symptom Matrix CNS Depressant Inhalants Dissociative Drugs CNS Stimulants Hallucinogens Narcotic analgesics Cannabis K2 Horizontal nystagmus Yes Yes Yes No No No No No Vertical Nystagmus Present * Present* Present No No No No No Lack of Convergence Present Present Present No No No Present Present Pupil Size Normal Normal Normal Dilated Dilated Constricted Dilated* Normal Reaction to Light Slow Slow Normal Slow Normal Little to none Normal Normal Pulse Rate Down Up Up Up Up Down Up Up Blood Pressure Down Up/Down Up Up Up Down Up Up Body Temperature Normal Up/Down/Normal up Up Up Down Normal Normal
- 30. NMS Labs Blood JWH-018 and -073 L/L extraction JWH-073 d-9 Istd Quantitative LOD/LOQ 0.1ng/mL Waters TQD Acquity Gradient 4 minute run Formic acid vs ACN 2 Transitions per analyte
- 31. NMS Labs Blood JWH-018 and -073
- 32. Missouri K2 Administration Study Subject BM Smoked “K2 Citron” 10mg/g JWH-018/073 0.3g in water pipe 3 inhalations over 30 minutes
- 35. NMS Labs Urine JWH-018 and -073 L/L extraction Qualitative JWH-073 d-9 Istd Method 1: hydrolyzed – Waters TQD Mono and Di hydroxy metabolites 2 transitions per analyte Method 2: unhydrolyzed – ABI 5000 Monohydroxy glucuronide – daughter – grandaughter 2 transitions per analyte and precursor
- 36. NMS Labs Urine SC metabolites
- 37. Missouri K2 Administration Study Subject BM - Urine Time JWH-018 Mono-OH Di-OH Tri-OH Glucuronides Pre-dose X X X X X 1:15 +/- √ √ X √ 2:07 X √ √ √ √ 2:40 X √ √ √ √ Time JWH-073 Mono-OH Di-OH Tri-OH Glucuronides Pre-dose X X X X X 1:15 X √ √ X √ 2:07 X √ √ √ √ 2:40 X √ √ √ √
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- more credible reports are now appearing in the medical literature also.
- Including acute intoxications, with anxiety, paranoia, gross impairment, and marked tachycardia.
- Marijuana, the most popular recreational drug in the United states after alcohol is enjoying growing popularity and seeing increasing efforts for its legalization. Californians will decide on November second whether to pass a ballot initiative, proposition 19, to legalize MJ under CA but not federal law, and regulate and tax its trade and distribution. Meanwhile, MJ is the number 1 drug in the DRE program, some 25 million Americans have smoked it in the past year, and a recent national roadside drug test survey showed that 6.8% of Friday and Saturday evening drivers tested positive for its use.
- Synthetic drugs that mimic the effects of cannabis through binding at the same receptors, principally the CB1 receptor, more of which about momentarily. The drugs were developed in the 1980’s and 1990’s as potential cannabinoid agonists that might possess some of the advantageous effects of cannabis, appetite stimulation, and anti- nausea properties, blood pressure, and much flaunted as adjuncts in cancer pain therapy, without the euphoric intoxicating effects for which the drug was popular recreationally. Now the drugs are sold widely on the internet and convenience stores and gas stations, smoke shops and head shops.
- Other C1 agonists with very diverse structures have also been identified in these illicit materials, including HU-210, a true THC analog, first synthesized at Hebrew University if Jerusalem, where the structure of THC was first elucidated, and partial analogs the synthetic compounds CP47,497 (C7 and C8 homologs), first manufactured by Pfizer, and WIN 55,212 developed by Sterling Winthrop. Their diversity makes the outlawing of these compounds as analogs, very difficult. The comparative receptor binding strengths of these compounds have been evaluated but how this relates to their potency in-vivo is unknown. HU-210 for example has a binding potency several hundred times that of THC. This potency can clearly lead to challenges in detecting pharmacologically significant amounts. There are literally dozens of these compounds whose synthesis has been described, and clearly many other analogs that could be synthesized with minor modification to circumvent scheduling or other regulation. This presents a greater challenge for the future not just dealing with those drugs already on the market, but those in the wings as the regulated landscape changes.
- Cannabinoids and their synthetic analogs can function as either agonists or antagonists at the CB1 and 2 receptors in the brain. The latter are mainly found in the immune system and in nerve terminals where their function is not well understood, but the major effects are in the CB1 receptor sites whose distribution in the brain correlates with areas involved in physiological, psychomotor and cognitive effects. Principally in the areas associated with cognitive function, movement, learning, memory and stress, appetite, pain perception, and nausea and vomiting. All factors that we associate with and are familiar with from the effects of THC. We will see later how the initial reports of the observed effects of these synthetics correlate with these expectations.
- Teske and coworkers conducted self administration of a product containing JWH-018. They reported sickness, sedation and dry mouth, hot flushes, burning eyes, and thought disruption. No change in pupil size. But pulse and blood pressure were noticeably elevated.
- They reported quantitative concentrations in in serum, with peak concentrations occurring in the range of 8-10 ng/mL within a few minutes of smoking, and concentrations falling below 1ng/mL within 3 hours. Trace concentrations were reported at 24 hours (<0.1ng/mL)
- Our findings show that there are major mono di and tri hydroxymetabolites present in the first urine samples collected within a hour of administration. The isomer shown are commercially available in the last two weeks, however none of the indole hydroxylated metabolites are major, the side chain OH is minor, and the major monohydroxy metabolite is hydroxylated in a position other than shown in the Sobolevsky paper. This is under investigation, and will be reported at the workshop at AAFS in Chicago in February at the K2 workshop. Dr John Huffman will be a guest speaker and it promises to be a lively presentation.
- Because of the complex metabolic profile, the urine method has taken a lot longer to develop and validate than the blood method. The method has been validated however through the use of authenticated positive and negative urine samples. Two independent complementary methods have been developed to provide further certainty of identification – critical for forensic casework in the absence of authentic reference standards. We believe this level of detail distinguishes our assay from that of our competitors. Other aspects of the validation procedure, sensitivity, selectivity, PPV and NPV apply to the methods also. Stability at room temp, refrigerated and frozen have been assessed, as well as in the autosampler, and appears to be relatively stable, but as noted does stick to plastic, requiring very careful handing of controls and SRMs. Authentic pedigreed samples diluted to the detection threshold are used as controls, and the method requires the presence of the major mono and di hydroxymetabolites, with transition ratios in range and retention time matching in order to report positives. All screened positives are confirmed.
- Here is an example of the LCMSMS data from method 1. Describe