The rapidly changing nature of novel psycho-active substance use

1. The rapidly changing nature of novel psycho-active substance use Conference on Legal Highs & Clubbing Drugs: What’s the Story? Dr Russell Newcombe 3D Research, Liverpool Chelmsford, Essex, January 23rd 2013 director@3Dresearch.org.ukwww.3Dresearch.org.uk

2. The speaker Dr Russell Newcombe, BA (Hons) & PhD in Social Psychology Awards: National Rolleston Award for harm-reduction (HRI 2010); Bing Spear Medal for drug policy reform (DPRG 2011); Scientific Committee Award: drugs journal paper (EMCDDA 2011) 30 years as specialist researcher, trainer and lecturer in the field of psychoactive drug use, deviancy and disorder Currently Director of 3D Research, an independent agency based in Liverpool, Merseyside, UK Areas of expertise: prevalence, consumption and effects of drugs; harm-reduction services & strategies; evaluation; ‘legal highs’ (use of new/unregulated drugs)

3. NPS/Legal Highs: key questions 1. What are ‘legal highs’ and/or novel psychoactive drugs (NPS)? 2. What are the main types of NPS currently used, and what are the main trends in the production and sale of NPS? 3. What is the current prevalence of NPS use in the UK? 4. Who are NPS used by, and why are they used? 5. What are the effects of NPS on the body and mind? 6. What are the main risks and potential harms of NPS?  7. How should society respond to users of new psychoactive drugs (policy and services)?

4. 1. What are ‘legal highs’ • Chemicals which alter the normal functioning of the brain – neurotransmitters and brain-waves - thus producing changes in our experience and behaviour [i.e. a ‘high’] (2) Specifically, a ‘legal high’ is a chemical which is: (a) not controlled by the 1971 Misuse of Drugs Act; (b) not licensed for legal use (like alcohol and tobacco); (c) not advertised/sold – and therefore not regulated - as a medicine (Medicines Act 1968) – see next 2 slides; AND: mimics the effects of popular controlled drugs [?] Thus, a legal high is a substance which is not legally regulated – a more accurate term would be ‘legal loophole’ drugs.

5. Novel psychoactive substances (NPS) Over the last few years, the term ‘legal high’ has become replaced by ‘novel psychoactive substance’ (NPS) – because if and when possession and trafficking of a particular new drug is prohibited by the government, it ceases to be a ‘legal high’. For example, use of the term ‘NPS’ allows us to avoid the confusion which currently exists in relation to drugs like mephedrone (meow/m-cat), which was banned by the UK government in April 2010, but is still referred to as a ‘legal high’ by some sources (notably the mass media).

6. What makes a drug a medicine? The classification of drug products as medicines is made on a case-by-case basis by the Medicines and Healthcare products Regulatory Agency (MHRA) under the Medicines Act 1968 and the amended Medicines for Human Use Regulations 1994 (marketing authorisations etc.) . Medicines are also classified into Schedules 1 to 5, which determine the control of prescribing and dispensing, eg. Schedule 1 drugs cannot be prescribed or dispensed (no medical use = totally prohibited, eg. most hallucinogens); Schedule 5 drugs can be dispensed without prescription.

7. The legal loophole used by NPS Headshops and online retailers of ‘legal highs’/NPS get round the UK Medicines Act legislation by stating that their products are not for human consumption, i.e. by definition not a medicine. Instead product packaging typically contains a cross/bones (sign of toxicity), and a warning not to consume the substance – using euphemisms such as bath salts, pond cleaner, room odoriser, incense, cream dispenser refills – and the vaguer product descriptors ‘souvenirs’ and ‘research chemicals’. Packaging also typically states ‘for sale to adults only’.

8. Legal Highs: forms & sources FORMS Liquid (solvents, solutions, sprays) Gas (eg. nitrous oxide) Solid (powder, pills, capsules, organics) * ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- SOURCES Herbal (leaf, bud, root, seed, sap, etc.) * Animal (excretions, organs) Technological: Synthetic chemicals * Electronic devices (eg. brain tuners, binaurals) ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- OUTLETS: (1) town/city headshops & (2) online websites *Most common forms at 2012

9. Headshops: famous UK chain Sell ‘legal highs’ and drug-related paraphernalia and literature Dr Hermans at Bold Street in Liverpool UK

10. Online sale of research chemicals For example: BULK RESEARCH CHEMICALS “We are the UK's favourite vendor of research chemicals and run constant quality checks across our whole spectrum of research chemical products. We sell the UK's most popular research chemicals at the best web prices such as Methoxetamine (MXE), MDAI and Methiopropamine (MPA).” • Combo 1 - MPA 1g & MDAI 1g • This pack contains 1g each of MDAI and MPA aka methiopropamine. £24.00 www.bulkresearchchemicals.com

11. Online Legal Highs sites explode Typing “buy legal highs” into Google throws up 2.74 million results, while “buy research chemicals” produces 6.91 million options [August 2012] The Misuse of Drugs Act now covers over 600 substances, but it is 40 years out of date and struggles to keep pace with the sheer amount of new chemical compounds hitting the UK recreational drug scene each year http://m.londonlovesbusiness.com/3267.article

12. 2. Main types of NPS being sold from headshops & websites to 2012 Main illegal drugs being mimicked Phenethylamines ecstasy (MDMA), amphetamines Tryptamines LSD, psilocin, DMT Piperazerines ecstasy, amphetamines Cathinones amphetamines, cocaine Cannabinoids THC (cannabis), hallucinogens, sedatives Miscellaneous stimulant/sedative/hallucinogen/opioid Source: EMCDDA-Europol Annual Report on the implement-ation of Council Decision 2005/387/JHA [April 2012]

13. Timeline of legal highs (novel drugs) Decade(s)Initially unregulated drugs becoming popular 1970s-80ssolvents (eg. butane, toluene); poppers (alkyl nitrites); magic mushrooms (notably psilocybe) Nineties ketamine; GHB (gammahydroxybutyrate) (1991-2000)khat Noughtiespiperazines (notably BZP); cathinones (notably (2001-2010) mephedrone); GBL; N2O (laughing gas) salvia divinorum; kratom 2011-2012 6APB (eg. Benzo Fury), MDAI (eg. Sparkle), methoxetamine (eg. MXE); synthetic cannabinoids (from JWH-018 to AM-2201)

14. 17 new novel drugs, 2011-12 The latest NPS found in Britain by FEWS (Forensic Early Warning System) between January 2011 and March 2012 – reads like a scrabble nightmare: 1. DMMA 9. 2-AI 2. MDAI (Sparkle) 10. n-ethylbuphedrone 3. Etizolam 11. 2-CC-NBoMe 4. JWH-250 12. AM-2201 5. JWH-200 13. Ipracetin 6. AM-694 14. Ethacetin 7. 4-Me0-PcP 15. 4-HO-MiPT 8. 5-Me0-DALT 16. 2-CP 17. 25D-NBOMe

15. NPS obtained from internet, UK, late 2011 A total of 22 ‘legal high’ products were purchased from 5 different internet sites in late 2011 (18 months after the UK ban on substituted cathinones was introduced in April 2010), and each substance was screened to determine its active ingredients. Two products – both labeled NRG2 – contained a banned drug: each had methylethcathinone (4-MEC), as well as a smaller amount of a 2nd banned cathinone: methylmethcathinone (mephedrone). Six products (4 sold as Benzo Fury & 2 as NRG3) contained 6-APB; three contained MDAI; three contained 5-IAI; three contained methoxetamine; three contained benzocaine; & 2 contained MPA. Source: Ayres T & Bond J (2012). A chemical analysis examining the pharmacology of novel psychoactive substances freely available over the internet and their impact on public (ill)health. Legal highs or illegal highs? BMJ Open, July 31, 2012; 2(4).

16. 22 legal highs purchased on internet: compounds detected, accuracy of description & legal status (Ayres & Bond, 2012)

17. Review of NPS websites 2012 A survey of the internet was used to identify websites that were marketing legal highs in the UK. The most fruitful search terms included desoxypipradrol (Ivory Wave/2DPMP), diphenylprolinol (D2PM), methylenedioxy-2-amino-indane (MDAI), methylenedioxy-2-amino-tetralin (MDAT), alpha-methyltryptamine (AMT) & 5-methoxy-N,N-diallyl-tryptamine Conclusions: “Legal highs from the phenylethylamine, cocaine, tryptamine and phencyclidine classes are increasingly being marketed,and, in the majority of cases, little is cited in the literature on their true chemical identity, pharmacology or toxicology”. Source: Gibbons S (20120. 'Legal highs’ - novel and emerging psychoactive drugs: a chemical overview for the toxicologist. Clinical Toxicology (Phila), January 2012; 50(1): 15-24

18. 3 TYPES OF NPS BASED ON SOURCE Herbal highs: plant/fungi or animal part/product Synthetic highs: substance made by means of chemistry - starting with natural precursors (semi- synthetic) or synthetic chemicals Mixed herbal/synthetic: products with synthetic drugs mixed into natural drugs, eg. Black Mamba: AM2201 chemical saturated into damiana leaves

19. Chewed, smoked or brewed/drank Herbal Highs: KHAT: herbal high (left) – but the most common headshop herbal high is salvia divinorum (below) Contains cathinone - stimulant hallucinogen

20. Kratom Kratom is a tropical tree indigenous to South East Asia including Thailand, Malaysia, & Myanmar. The Kratom tree can reach heights up to 50 feet with a spread of over 15 feet. Normal ingestion methods include drinking it as a tea, smoking it, and chewing the leaves. It is sold from websites as dried leaves, powder and resin pellets. It is stimulant in lower doses, and sedative (opiate-like) in higher doses. Doses range from 2 to 10 grams. Kratom has 25+ alkaloids, the primary psychoactive ingredient being mitragynine (9-methoxy-corynantheidine) Pharmacology studies show mitragynine has opioid-like activity in animals.

21. Synthetic Cannabinoids: history Synthetic cannabinoids are functionally related to THC - Δ9-tetrahydrocannabinol, the key active chemical in cannabis Like THC, they bind to the same cannabinoid receptors in the brain and other organs as the endogenous ligand (brain neurotransmitter) anandamide. Classed as cannabinoid receptor agonists, they were initially developed over past 40 years as therapeutic agents, often for the treatment of pain. However, it is difficult to separate the desired properties from unwanted effects (eg. getting stoned), and so pharma-companies did not market them. But in 21st century, legal-high entrepreneurs began exploring, then marketing, these rejected therapeutic agents as legal cannabis substitutes.

22. Why the rise in interest in synthetic cannabinoid products? • Part of general trend toward using legal highs (2) Cheaper & more reliable product - Police raids on skunk farms (E&W) – premises converted to cannabis cultivation, preventing ‘normal usage’: 2006/7: 800 2009/10: 6,800 2007/8: 3,000 2011/12: 7,900 (3) Series of big rises in price of skunk since 2008 - average price of 1g skunk 2011 (Druglink survey): £10 – though since a gram-bag often weighs nearer 0.75g, the true gram price is probably nearer £13-14 – or £90 to £100 per quarter ounce (4) Skunk problems: dampness, mouldiness, adulteration

23. First group of synthetic cannabinoids banned in UK Spice, K2, Majik – mainly JWH series, but also CP & HU series

24. Black Mamba (AM2201) Legal-high smokables’ are often inert herbal mixtures with synthetic cannabinoids soaked into them (the latter are also sold separately as powders). For instance: Black Mamba (AM2201), Zulu, Doob

25. Herbal products containing synthetic cannabinoids Black Mamba-type products are usually sold as herbal prep- arations containing inert herbal material (leaf etc.) saturated with synthetic cann- abinoids (SCs). The pure SC powder can also be got online.

26. Typical appearance of Black Mamba/Spice-type products Unlike herbal cannabis, there are no seeds; unlike skunk, there are no buds; unlike either, there is no strong smell or sticky texture

27. Sale of Black Mamba in headshops Usually sold as ‘incense’ (herbal mixture) or ‘research chemicals’ (AM2201 powder), and labelled ‘not for human consumption’ & ‘not for sale to under-18s’ £10 for one-gram bag £25 for three-gram bag But just like illicit drugs, the actual weight is usually 5%- 20% less than described ------------------------------------------------------------------------ Black Mamba = three ‘drugs’ in one herbal mixture > damiana > AM2201 (fluoro-pentyl-naphthoyl-indole) > oleamide

28. fluoropentyl-naphthoyl-indole AM-2201synthetic cannabinoid: 1-gram bag of off-white powder Source: Bulk Research Chemicals www.bulkresearchchemicals.com Light dose: 250 mcg Moderate dose: 0.5 - 1 mg Strong dose: 1 – 2 mg NPS like ‘Black Mamba’ contain AM-2201 saturated into damiana leaf to simulate herbal cannabis in both its appearance and effects

29. Synthetic highs: white powders & pills BUBBLE ------------------- UPPERS or TRIPS

30. Conclusions of Lancashire study * “whilst Bubble had been used as a slang term for mephedrone when it emerged in the north west of England in 2009, by late 2010 and after the ban, Bubble was evolving into the slang term for any synthetic legal high or unidentified white powder with stimulant effects which was available from street dealers … our survey respondents were not only unclear about, but also apparently unconcerned about the specific chemical identity of the stimulant white powders they consumed” Measham et al. (2011: 140), op cit. * [based on interviews with people attending nightclubs in North-West England, 2010]

31. Some lines of Bubble earlier today Cocaine – Heroin – Amphetamine – Ecstasy - 2CB – Ketamine – Mephedrone –Naphyrone - Methoxetamine? – or one of dozens of possible legal highs/NPS

32. 1-Benzofuran-6-ylpropan-2-amine (6-APB) – aka ‘NRG3’ 6APB – stimulant: note the use of the terms ‘research chemicals’ & ‘pellets’ (not pills), and the warnings ‘harmful’ and ‘not for human consumption’

33. Ivory Wave:desoxypipradol (2DPMP)

34. Ivory Wave & Whack Wood & Dargan used PubMed to search for terms related to D2PM & 2-DPMP (desoxypipradol). 2-DPMP, usually sold as ‘Ivory Wave’, was found to have similar effects on reducing dopamine reuptake to cocaine. D2PM was similar, but was far less biologically effective at boosting dopamine levels. 'Whack‘ was found on analysis to contain 2-DPMP and fluorotropacocaine, so also had similar effects to cocaine. Wood D, Dargan P (2012). Use and acute toxicity associated with the novel psychoactive substances diphenylprolinol (D2PM) and desoxypipradrol (2-DPMP). Clinical Toxicology (Phila), September 2012; 50(8): 727-32.

35. Ethylphenidate Analogue of stimulant drug methylphenidate – better known as Ritalin (for ADHD)

36. Annihilation: ‘herbal incense’ Synthetic cannabinoid in herbal material, possibly AM2201 or one of its chemical relatives. Given a great deal of free publicity by the mass media.

37. Legal high? 50 mg tablets of caffeine (trimethylxanthine) – sold in pharmacies off the shelf to anyone aged 12 years or older. “A stimulant which can help to maintain mental alertness and make you feel less tired”. Max dose in 24 hours: 12 tablets (0.6 gram). LD50 = 10 grams (or 4 packs of 48 tablets) Online price 2012: £4.30

38. Electronic/Technological Highs Brain Tuners: computer programs that, via electrodes attached to skull, produce direct changes in brain-waves - and thus stimulation, sedation or hallucinations Perception Tuners: notably visual, tactile & sound-based (eg. hypnotic images, electro-acupuncture, binaurals) The Chemputer (Cronin): makes molecules from atoms – and psychoactive drugs are typically comprised of two or more of just four atoms: carbon, hydrogen, oxygen and nitrogen http://www.guardian.co.uk/science/2012/jul/21/chemputer-that-prints-out-drugs

39. Trends in NPS availability According to EMCDDA reports in May 2011 and November 2012, the number of new NPS marketed in Europe between 2008 & 2012 climbed as follows: • 13 • 24 • 41 2011 49 2012 57+ –the equivalent of more than one new NPS every week

40. UNODC report, November 2012 Two drug groups - synthetic cannabinoids & cathinones - dominated the world NPS market over 2010 & 2011 Source: ‘Tracking designer drugs, legal highs and bath salts’ – UNODC 1-11-12 http://www.unodc.org/unodc/en/frontpage/2012/November/tracking-designer-drugs-legal-highs-and-bath-salts.html

41. EMCDDA/Europol Report 2012 The number of NPS websites (online headshops) quadrupled in a two year period between January 2010 and January 2012: Jan 2010 170 Jan 2011 314 July 2011 630 Jan 2012 690 In 2010/11, SOCA closed 120 websites for selling 2 newly controlled class B drugs: mephedrone (banned 4/10) and naphyrone (banned 7/10)

42. 3. Estimating levels of NPS use Problems with estimates of prevalence of NPS use Parameters: time-period, place, case, type of estimate Internal validity, eg. dummy drug items (false admissions), honesty questions (false denials) Specific problem with NPS: large number & multiple names External validity, eg. body fluid tests on a sub-sample Reliability, eg. repeat questions, replicable surveys Representativeness, eg. using sampling & statistical methods which ensure sample is representative of source population, so that findings are generalizable

43. EU Survey of legal highs, mid-2011 EU survey in June 2011 found that of the 27 EU countries: • The UK was ranked fourth for legal high use (Ireland was first) • The UK ranked top for the proportion of legal high users who were offered them in clubs & parties

44. Prevalence of use of legal highs Mixmag survey: comparison of 2009 and 2010 findings * % LifetimeLast-year 200920102010 poppers 69 56 20 nitrous oxide 59 57 38 (4 in 10) mephedrone 42 61 51 (5 in 10) salvia 29 .. .. BZP 26 17 5 Spice/Magic 13 10 2 methylone 11 14 9 GBL 6 6 2 _________________________________________________________________________________________________ * 2009 findings reported in February 2010; 2010 findings given in March 2011 2010 sample: 69% male, modal age 20 years (3/4s 18-27), 89% heterosexual

45. British Crime Survey: 2009/10 - 2011/12 Adults in England & Wales reporting last-year use of 5 drugs: ^ 367,000~ 220,000 16-59 16-24 . 09/1010/1111/1209/1010/1111/12 Mephedrone .. 1.4 1.1^ .. 4.43.3 ~ Spice * 0.4 0.2 0.1 1.2 0.4 .. BZP 0.5 0.1 0.1 1.4 0.2 .. Khat 0.2 0.2 0.2 0.5 0.3 .. GBL/GHB 0.1 0.0 0.1 0.5 0.1 .. _____________________________________________________________________ All five drugs were ‘legal highs’ until controlled by the UK Misuse of Drugs Act in 2010 – the exceptions being GHB (banned in 2005) & khat (still uncontrolled) * and other synthetic cannabinoids .. not reported E&W = England & Wales ~ 95% CI: 173,000-267,000 last-year mephedrone users in E&W: 16-24s, 2011/12 (7th) ^ 95% CI: 317,000-416,000 last-year mephedrone users in E&W: 16-59s, 2011/12 (4th)

46. Global Drug Survey: use of NPS UK 2010/11 % Last 12 months Last month Nitrous oxide 27.2 .. Mephedrone 19.5 7.2 Isopropyl nitrate (poppers) 13.1 5.2 Methoxetamine 4.2 2.4 Synthetic cannabis (some legal) 3.3 1.5 Benzo Fury (6APB) 2.4 0.8 MDAI (Sparkle) 2.2 0.5 Methylone 1.4 0.4 GBL (gammabutyrolactone) 1.6 0.5 MDPV (methylenedioxypyrovalerone) 0.5 0.0 AMT (alphamethyltryptamine) 0.4 0.2 Kratom 1.1 0.2 Solvents 0.4 0.2

47. 4. Who uses NPS, & why? 3 main groups: Clubbers/partiers (mainly young adults & students) Psychonauts (all ages - main interest is hallucinogens) Poly-drug users (esp. prior cocaine/speed/heroin-users) Demographics About 2:1 male-female ratio for regular users Main age-range of 16-45 – peak age-range 20-29 yrs Gay men use (& initiate use) more than heterosexuals Use found among all races & social groups, esp. Whites/Mixed

48. Characteristics of mephedrone users British Crime Survey 2011/12: levels of last-year use in E&W Age: 16-19 (2.9%) & 20-24 (3.6%) vs 25-59 (0.5%) Sex: men 1.5% vs women 0.7% Ethnic group: white (1.2%) & mixed (1.9%) vs other races (0.3%) Marital status: single (2.7%) vs others (0 to 1%) Occupational status: students (2.7%) & unemployed (2.2%) vs others (0-1.3%) Area: city-dweller (2.8%) vs others (0.5%-1.4%) Past-month nightclub attendance: 9+ (9.7%) vs none (0.5%) Past-month pub/bar attendance: 9+ (4.7%) vs none (0.3%)

49. Main reasons for taking legal highs Mixmag survey of readers/clubbers, 2009 (N = 2,220) 1 other illegal drugs not available 2 they are not illegal 2 able to buy them online 2 more reliable product than illegal drugs 2 price - cheaper than illegal drugs 6 better quality than illegal drugs 7 safer than illegal drugs 7 a better high & fewer side-effects than illegal drugs

50. Why have legal highs/NPSbecome so popular over the last 5 years? Not just because of price – many illegal drugs are cheaper than they were 20 years ago, and NPS can cost more. Main reasons seem to be: (1) the drop in the purity of several popular drugs (next slide) (2) the drop in availability of some popular drugs (eg. skunk) (3) the advent of the Internet and headshops as new ways of buying psychoactive drugs (4) Entrepreneurs prepared to research, produce and market many new legal substances for getting ‘high’ (notably China) (5) Modern society: consumer-oriented, pleasure-oriented