Today's Designer Drugs - Synthetic Cannabinoids ("K2"/ "Spice") and Synthetic Stimulants ("Bath Salts")

Transcription

1 Today's Designer Drugs - Synthetic Cannabinoids ("K2"/ "Spice") and Synthetic Stimulants ("Bath Salts") R. H. Barry Sample, Ph.D. Director of Science and Technology Employer Solutions Incorporated 9 th Annual FTA Conference April 16 & 17, 2014

2 Questions What are "Synthetic Cannabinoids"? What are Synthetic Stimulants"? What is the legal status of these products? What are the testing considerations? Should employers include tests for these products in their workplace drug testing programs?

3 What is a Controlled Substance? Controlled Substance includes drug, other substance, or immediate precursor included in Schedules I, II, III, IV, V of the Controlled Substance Act (CSA) alcohol and tobacco are explicitly excluded Schedules (classes) Classification based on Potential for abuse Currently accepted medical practice International treaties Changes initiated by DEA or HHS (or public petition/interest) Temporary scheduling bypasses normal review process (e.g. MDMA, K2 ) CSA regulates manufacturing, importation, distribution and possession Analogue Act includes substances with substantially similar chemical structure and pharmacological effects as substances in Schedule I & II

4 CSA Schedules I No currently accepted medical use in treatment in the United States, a lack of accepted safety for use under medical supervision, and a high potential for abuse e.g. LSD, marijuana (cannabis), MDMA II Substances in this schedule have a high potential for abuse with severe psychological or physical dependence e.g. Amphetamine/methamphetamine, cocaine, oxycodone III Substances in this schedule have a potential for abuse less than substances in Schedules I or II e.g. <15 mg Hydrocodone (Vicodin ); benzphetamine, anabolic steroids IV Substances in this schedule have a lower potential for abuse relative to substances in Schedule III e.g. Benzodiazepines, barbiturates V Substances in this schedule have a lower potential for abuse relative to substances listed in Schedule IV and consist primarily of preparations containing limited quantities of certain narcotic and stimulant drugs. These are generally used for antitussive, antidiarrheal and analgesic purposes e.g. Cough preparations with <2 mg/ml codeine

5 Receptors From: NIH Publication No

6 Dopamine Receptor Neuron Methamphetamine Example From: NIH Publication No

7 New Psychoactive Substances (NPS) Synthetic chemicals Intended to produce effects especially, psychotropic, hallucinatory, or stimulant by acting at receptors in a manner similar other drugs or naturally occurring compounds Also referred to as Designer drugs Emerging Psychoactive Substances (outside US) Marketed to youth (& others) as a Legal High Generally, not detected in routine drug screen

8 Synthetic Cannabinoids

9 Cannabinoids Types Phytocannabinoids (natural, herbal, classical) derived from cannabis plant Endocannabinoids naturally produced in body that act at cannabinoid receptor(s) Synthetic May be structurally related to plant derived cannabinoids or endocannabinoids or may have different chemical structure Act at cannabinoid receptor(s) Cannabinoid Receptors (Characterized in late 1980 s) CB 1 Highly expressed in brain Mediates most CNS actions Correlated with physiological, psychomotor, and cognitive effects Also found in liver; muscle; GI-tract; pancreas; and reproductive (prolactin/lh), cardiovascular (HR/BP), and adipose tissues Brain reward systems self-administration of abused substances Food intake, body weight CB 2 Expressed primarily in immune cells

10 How similar are the synthetic cannabinoids to naturally occurring cannabinoids? THC AEA (Endocannabinoid) 2-AG (Endocannabinoid) HU-210 CP 47,497 JWH-018 JWH-073 JWH-200 Permission is granted to copy, distribute and/or modify these images under the terms of the GNU Free Documentation License, Version 1.3 or any later version published by the Free Software Foundation; with no Invariant Sections, no Front-Cover Texts, and no Back-Cover Texts.

11 How many synthetic cannabinoids are there? HU (Hebrew University) series CP (Pfizer) series JWH (researcher s initials, CU) series - >400 WIN (Sterling Winthrop) series AM (researcher s initials, NEU) series - >30 Many halogenated version of JWH-series RCS (Research Chemical Supply) series and 3 rd generation compounds

12 Herbal Incense Products First Generation: K2, Spice, Genie, Sky, Yucatan Fire and many others

13 Herbal Incense What is it? Dried, treated plant materials Plant materials may include - Baybean, Lion s Tail, Indian Warrior, Machona Brava, Marshmallow, Siberian Motherwort, Turnera Diffusa (Damiana) May be flavored: vanilla, honey, strawberry, cherry, blueberry Available over the internet and over the counter at some retail stores tobacco/smoke shops, gas stations, convenience stores, drug paraphernalia shops How is it used? Smoking like a cigarette Inhaling smoke from open container or pipe Ingestion WARNING: All Herbal Incense and Aromatic Potpourri products sold on this site are not for human consumption. Contents are non-toxic and are NOT approved by the FDA for HUMAN CONSUMPTION

14 Active Ingredients in Herbal Incense One or more chemicals applied to dried, plant material Cannabinoid receptor agonists Caffeine Menthol Vitamin E Chromium Not all ingredients listed on package label Amount applied (i.e. dose) not consistent Ingredients may vary, lot-lot-lot and between manufacturers Bottom Line: K2, Spice and other Herbal Incense products are essentially trade names with varying substances/doses

15 Product Information $30-40 per 3g packet All are laced with a synthetic cannabinoid JWH compound AM compound RCS compound WIN compound 3 rd Gen compounds (e.g. UR-144) High variability between products, even the same label: Constituents and components change within product label and batch to batch May also contain Nicotine, THC, Cannabidiol Also sold as Fake Weed / Fake Pot

16 Are synthetic cannabinoids dangerous? Action at cannabinoid receptor may produce marijuana-like effects As research chemicals design for in-vitro use, little is known about in-vivo effects, metabolism (or what metabolites are found in a urine sample) and toxicity in humans. Some have 50-fold or greater potency than THC (the principle component of marijuana) Some compounds have a shorter duration of action, others longer Adverse effects include: agitation, anxiety, nausea, vomiting, tachycardia (fast, racing heartbeat), elevated blood pressure, tremor, seizures, hallucinations, paranoid behavior, and non-responsiveness. Case reports describe: intense hallucinations, psychotic episodes, withdrawal, dependence, feelings of impaired motor skills, and acute kidney injury. First responders report that individuals using these substances have suffered from intense hallucinations.

17 Data from Poison Control Centers In Mar. 2010, 112 calls from 15 states related to synthetic cannabinoids to US poison control centers since Nine months later it was 2700 calls from 49 states and DC. In 2010 there were a total of 2900 calls, nearly 7000 calls in 2011, and 5200 calls in Doesn t mean use is going down!

18 Synthetic Cannabinoid Seizures (as percentage of all hallucinogen seizure reports in the United States, 2012) Hallucinogen Reports Percent AM , % XLR11 8, % UR 144 5, % JWH 122 2, % JWH 210 1, % MAM , % JWH 018 (AM 678) % Others 29, % Source: NFLIS Annual Report 2012

19 What is the legal status of Synthetic Cannabinoids at the Federal level? CSA - Schedule I HU-210 Eff. 3/1/2011 JWH-018, JWH-073, JWH-200, CP 47,497 & C8 homolog of CP 47,497 Emergency/temporary scheduling [76FR11075] for 1 year to complete studies 2/29/ month extension July 2012 Synthetic Drug Abuse Prevention Act of structural classes and their analogs (15 named examples) May 2013 (Temporary Scheduling) 3 more compounds, UR-144, XLR-11 (Fluorinated UR-144), AKB-48 (APINACA) February 2014 (Temporary Scheduling) 4 more PB-22, 5-F-PB-22, AB-FUBINACA, ADB-PINACA Analogue Act provisions of CSA may also impact legality of these substances This information is being provided for informational purposes only. It is not intended to be, and does not constitute, legal advice or opinion. If you have questions regarding the information provided, please consult your attorney.

20 What is the legal status of Synthetic Cannabinoids at the State level? State Laws ( By the end of 2012, at least 41 states & PR had laws impacting herbal incense / synthetic marijuana products In 2011 & 2012 many states crafted broadly worded statutes banning classes of compounds This information is being provided for informational purposes only. It is not intended to be, and does not constitute, legal advice or opinion. If you have questions regarding the information provided, please consult your attorney.

21 Use by High School Seniors

22 Trends in Synthetic Cannabinoid Positives Source: NMS Labs Designer Drug Trends Report. February 2014

23 Is it possible to test for the use of Synthetic Cannabinoids? Yes..and, No. From limited studies with several of the synthetic cannabinoids in humans, it appears that there is extensive metabolism. Consequently, laboratories cannot simply test for parent substances. Still a limited number of laboratories offer testing Older, basic panels test for metabolites of JWH-018 and JWH-073. More comprehensive panels test for metabolites of 1 st & 2 nd generation compounds e.g. JWH- 018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-250, JWH-398, AM-2201, RCS-4 (depending on lab) Current comprehensive panels also include 3 rd generation compounds e.g. UR-144, XLR-11, MAM-2201, AKB-48, PB-22 (depending on lab) As the metabolites cannot be detected by routine immunoassay screening techniques for cannabinoids, more sophisticated (and costly) analytical techniques such as LC/MS(/MS) or GC/MS(/MS) are required not only for confirmation, but also for screening. (Note: Some labs are now offering an ELISA screen) Given the evolution of the herbal incense products; the change in, and variety (>400) of, chemicals that may be used to treat the plant material; and the need for metabolism studies, it is neither practical nor cost-effective to routinely screen (e.g. preemployment) workplace specimens for the use of these compounds

24 Synthetic Cannabinoid Testing Evolution (Not all Labs Test for All Compounds) 1 st Generation Testing JWH-018 JWH-073 JWH-200 CP-47,497 Cannabicyclohexanol (CP-47,497-C8) 3 rd Generation Testing JWH-015 SR-18 (RCS-8) JWH-019 WIN JWH-081 WIN-48,098 JWH-122 AKB-48 JWH-203 MAM-2201 JWH-210 UR-144 JWH-250 XLR-11 JWH-251 BB-22 JWH-398 PB-22 AM-694 STS-135 AM-1221 AB-PINACA AM-2201 ADB-PINACA SR-19 (RCS-4) ADBICA

25 What can an employer do? Policy Development Employers could include a provision prohibiting the use and/or possession of synthetic cannabinoids or herbal incense while on company property Even existing, broadly worded policies may not address the use of these substances especially for the chemicals that are not Schedule I or covered by state law Before implementing any testing, Consider the employee/applicant demographics. While older workers may use these products, they are predominantly used by younger individuals Consider what substances are likely to be used With the recent Federal regulatory and state legislative efforts, the substances that were most common in 2010 & 2011 & 2012 are much less likely to be found in 2013 (and beyond) The aforementioned is not legal advice and employers wishing to develop such a policy should consult an attorney licensed to practice law in their state.

26 Synthetic Stimulants

27 Synthetic Stimulants Sold over the internet as Bath Salts, Plant Food, Vacuum Fresheners, Pond Cleaner Also available at over the counter at some retail stores tobacco/smoke shops, gas stations, convenience stores, drug paraphernalia shops not for human consumption

28 Product Information $20-50 per packet (250 mg, 500 mg, 1 gm) High variability between products, even the same label Constituents and components change within product label and batch to batch Brand Names include: Ivory Wave, Purple Wave, Vanilla Sky, White Rush, White Girl, White China, Dynamite, Bliss, Energy-1 (NRG-1), Ocean Snow, Hurricane Charlie, White Lightening, Red Dove, Cloud-9, & White Dove

29 Synthetic Stimulants How are they used? Orally/ingestion (powders, crystals, liquids, capsules, tablets) Inhalation Injection Snorting What are they? Amphetamine-like stimulants drugs (typically, cathinone family) Also referred to as legal cocaine, legal ecstasy What drugs are found? MDPV Mephedrone Methedrone Methylone and other cathinones

30 Drug Similarity Methamphetamine MDMA Cathinone MDPV Mephedrone

31 Synthetic Cathinones

32 Are Synthetic Stimulants dangerous? Mechanism of action similar to amphetamines at the dopamine receptor Max. effects in 5-45 min., depending on drug and route of administration Effects last 2-7 hrs, depending on drug and route of administration Adverse effects include: chest pains, increased blood pressure, increased heart rate, agitation, hallucinations, extreme paranoia and delusions.

33 Data from Poison Control Centers In 2010, 304 calls related to bath salts to US poison control centers. In 2011, there were more than 6100 calls, more than 2600 calls in 2012, and more than 690 in first 8 months of Doesn t mean use is going down! Michigan emergency department reports (11/10 3/11), 35 patients: agitation (66%), tachycardia (63%), delusions/hallucinations (40%) hospitalized, 1 DOA

34 Stimulant Seizures (as percentage of all stimulant (& selected hallucinogen) seizure reports in the United States, 2012) Source: NFLIS Annual Report 2012 Stimulants Reports Percent Methamphetamine 162, % Amphetamine 8, % MDMA % 1 Benzylpiperazine (BZP) 4, % Methylone 3, % MDPV 3, % alpha PVP 2, % Methylphenidate 2, % 4 MEC % Pentedrone % Cathinone % Butylone % Others 8, %

35 What is the legal status of Synthetic Stimulants at the Federal level? CSA - Schedule I Eff. 10/21/2011 MDPV, methylone, mephedrone Emergency/temporary scheduling [76FR65371] for 1 year to complete studies July 2012 Synthetic Drug Abuse Prevention Act of 2012 Added MDPV, mephedrone and 9 other compounds April 2013 Methylone added March 2014 (Temporary Scheduling) 10 more compounds, 4-MEC, 4-MePPP, alpha-pvp, butylone, pentedrone, pentylone, 4-FMC, 3-FMC, naphyrone, alpha-pbp Analogue Act provisions of CSA may also impact legality of these substances This information is being provided for informational purposes only. It is not intended to be, and does not constitute, legal advice or opinion. If you have questions regarding the information provided, please consult your attorney.

36 What is the legal status of Synthetic Stimulants at the State level? State Laws ( By the end of 2012, at least 43 states & PR had laws impacting synthetic stimulant products In 2011 & 2012 many states crafted broadly worded statutes banning classes of compounds This information is being provided for informational purposes only. It is not intended to be, and does not constitute, legal advice or opinion. If you have questions regarding the information provided, please consult your attorney.

37 Synthetic Stimulant Positives Source: NMS Labs Designer Drug Trends Report. February 2014

38 Is it possible to test for the use of bath salts? Yes..and, No. From limited studies with substances in bath salts, it appears that there is significant metabolism similar to amphetamines. Consequently, laboratories may not be able to simply test for parent substances. Still a limited number of laboratories offer testing Basic panels test for metabolites of MDPV, methylone, and mephedrone. More comprehensive panels test for metabolites up to 21 different compounds, As these drugs and their metabolites have limited detection by routine immunoassay screening techniques for amphetamines, more sophisticated (and costly) analytical techniques such as LC/MS(/MS) or GC/MS(/MS) are required not only for confirmation, but also for screening. Given the wide variety of potential cathinone/amphetamine-like drugs that could be used in bath salts and the need for metabolism studies, it is neither practical nor costeffective to routinely screen workplace specimens for the use of these compounds

39 What can an employer do? Policy Development Employers could include a provision prohibiting the use and/or possession of synthetic cannabinoids or herbal incense while on company property Even existing, broadly worded policies may not address the use of these substances especially for the chemicals that are not Schedule I or covered by state law Before implementing any testing, Consider the employee/applicant demographics. While older workers may use these products, they are predominantly used by younger individuals Consider what substances are likely to be used With the recent Federal regulatory and state legislative efforts, the substances that were most common in 2010 & 2011 & 2012 are much less likely to be found in 2013 The aforementioned is not legal advice and employers wishing to develop such a policy should consult an attorney licensed to practice law in their state.

40 What are the issues in testing for use of Synthetic Cannabinoids and Synthetic Stimulants products? Number of potential substances Literally, hundreds of compounds Specific substances used is a moving target Legal status Only a limited number of substances are listed on CSA Analogue Act provisions may impact some substances Differences in state laws Impacts multi-state employers (with more recent legislation, less of an issue) Impacts how policies are written

41 What are some of the technical issues in testing for products marketed as legal highs? Test for metabolites, not parent compound Need documented, peer-reviewed studies for maximum legal defensibility Limited or no effective rapid screening tests POCT device for synthetic cannabinoids Not FDA-cleared Tests for parent and not metabolite(s) Generally, requires slower throughput, more expensive instrumentation (e.g. LC/MS/MS) for screen and confirmation Recent ELISA at one lab provider for screening synthetic cannabinoids

42 Questions