The rapidly changing nature of novel psycho-

active substance useConference on Legal Highs & Clubbing Drugs: What’s the Story?

Dr Russell Newcombe3D Research, Liverpool

Chelmsford, Essex, January 23rd 2013

director@3Dresearch.org.uk www.3Dresearch.org.uk

The speakerDr 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 disorderCurrently Director of 3D Research, an independent agency

based in Liverpool, Merseyside, UKAreas of expertise: prevalence, consumption and effects of

drugs; harm-reduction services & strategies; evaluation; ‘legal highs’ (use of new/unregulated drugs)

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)?

1. What are ‘legal highs’(1) 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.

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).

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.

The legal loophole used by NPSHeadshops 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’.

Legal Highs: forms & sources FORMS Liquid (solvents, solutions, sprays)

Gas (eg. nitrous oxide)Solid (powder, pills, capsules, organics) *

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SOURCES Herbal (leaf, bud, root, seed, sap, etc.) *Animal (excretions, organs)Technological: Synthetic chemicals *

Electronic devices (eg. brain tuners, binaurals)

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OUTLETS: (1) town/city headshops & (2) online websites

* Most common forms at 2012

Headshops: famous UK chain

Dr Hermans at Bold Street inLiverpool UK

Sell ‘legal highs’ and drug-related paraphernalia and literature

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

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

2. Main types of NPS being sold from headshops & websites to 2012

Main illegal drugs being mimickedPhenethylamines ecstasy (MDMA), amphetaminesTryptamines LSD, psilocin, DMTPiperazerines ecstasy, amphetaminesCathinones amphetamines, cocaineCannabinoids THC (cannabis), hallucinogens, sedativesMiscellaneous stimulant/sedative/hallucinogen/opioid

Source: EMCDDA-Europol Annual Report on the implement-ation of Council Decision 2005/387/JHA [April 2012]

Timeline of legal highs (novel drugs)Decade(s) Initially unregulated drugs becoming popular

1970s-80s solvents (eg. butane, toluene); poppers (alkyl nitrites); magic mushrooms (notably psilocybe)

Nineties ketamine; GHB (gammahydroxybutyrate)(1991-2000) khat

Noughties piperazines (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)

17 new novel drugs, 2011-12The 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-AI2. MDAI (Sparkle) 10. n-ethylbuphedrone3. Etizolam 11. 2-CC-NBoMe4. JWH-250 12. AM-22015. JWH-200 13. Ipracetin6. AM-694 14. Ethacetin7. 4-Me0-PcP 15. 4-HO-MiPT8. 5-Me0-DALT 16. 2-CP

17. 25D-NBOMe

NPS obtained from internet, UK, late 2011A 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).

Supplier Product Compounds detected As described Status

A

Benzofury 1-Benzofuran-6-ylpropan-2-amine (6-APB) Yes LegalJolly Green Granules Benzocaine Contents not specified LegalMDAI 5,6-Methylenedioxy-2-aminoindane Yes Legal

Methoxetamine2-(3-Methoxyphenyl)-2-(ethylamino)cyclohexanone

Yes Legal

MPA N-methyl-1-(thiophen-2-yl)propan-2-amine Yes Legal

NRG-24-Methylethcathinone (4-MEC). Contaminant mephedrone

No Illegal

NRG-3 1-Benzofuran-6-ylpropan-2-amine (6-APB) No Legal5-IAI 5-Iodo-2-aminoindane Yes Legal

BBenzofury 1-Benzofuran-6-ylpropan-2-amine (6-APB) Yes LegalMDAI Benzocaine No Legal5-IAI 5-Iodo-2-aminoindane Yes Legal

CBenzofury 1-Benzofuran-6-ylpropan-2-amine (6-APB) Yes Legal

Methoxetamine2-(3-Methoxyphenyl)-2-(ethylamino)cyclohexanone

Yes Legal

D

Jolly Green Granules Benzocaine Contents not specified LegalMDAI Gold 5,6-Methylenedioxy-2-aminoindane Yes Legal

MPA N-methyl-1-(thiophen-2-yl) propan-2-amine Yes Legal

NRG-24-Methylethcathinone (4-MEC). Contaminant mephedrone

No Illegal

NRG-3 1-Benzofuran-6-ylpropan-2-amine (6-APB) No Legal5-IAI 5-Iodo-2-aminoindane Yes Legal

E

Benzofury 1-Benzofuran-6-ylpropan-2-amine (6-APB) Yes Legal

MDAI Gold 5,6-Methylenedioxy-2-aminoindane Yes Legal

Methoxetamine2-(3-Methoxyphenyl)-2-(ethylamino)cyclohexanone

Yes Legal

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

Review of NPS websites 2012A 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

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

Herbal Highs: KHAT: herbal high (left) – but the most common headshop herbal high is salvia divinorum (below)

Chewed, smoked or brewed/drank

Contains cathinone - stimulant

hallucinogen

KratomKratom is a tropical tree indigenous to South East Asia including Thailand, Malaysia,& Myanmar. The Kratom tree can reach heights up to 50 feet witha spread of over 15 feet. Normal ingestion methods includedrinking 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.

Synthetic Cannabinoids: historySynthetic cannabinoids are functionally related to THC - Δ9-

tetrahydrocannabinol, the key active chemical in cannabisLike 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.

Why the rise in interest in synthetic cannabinoid products?

(1) 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: 6,8002007/8: 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

First group of synthetic cannabinoids banned in UK

Spice, K2, Majik – mainly JWH series, but also CP & HU series

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

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.

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

Sale of Black Mamba in headshopsUsually 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

AM-2201 synthetic cannabinoid: 1-grambag of off-white powder

Source: Bulk Research Chemicals

www.bulkresearchchemicals.com

fluoropentyl-naphthoyl-indole

Light dose: 250 mcgModerate dose: 0.5 - 1 mgStrong 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

Synthetic highs: white powders & pills

BUBBLE-------------------

UPPERS or TRIPS

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]

Some lines of Bubble earlier today

Cocaine – Heroin – Amphetamine – Ecstasy - 2CB – Ketamine – Mephedrone –Naphyrone - Methoxetamine? – or one of dozens of possible legal highs/NPS

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’

Ivory Wave:desoxypipradol (2DPMP)

Ivory Wave & WhackWood & 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.

Ethylphenidate

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

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.

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

Electronic/Technological HighsBrain 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

Trends in NPS availabilityAccording to EMCDDA reports in May 2011 and

November 2012, the number of new NPS marketed in Europe between 2008 & 2012 climbed as follows:

2008 13

2009 24

2010 41

2011 49

2012 57+ – the equivalent of more than one

new NPS every week

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

EMCDDA/Europol Report 2012The number of NPS websites (online headshops) quadrupled in

a two year period between January 2010 and January 2012:

Jan 2010 170Jan 2011 314July 2011 630Jan 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)

3. Estimating levels of NPS use

Problems with estimates of prevalence of NPS useParameters: time-period, place, case, type of estimateInternal validity, eg. dummy drug items (false admissions),

honesty questions (false denials) Specific problem with NPS: large number & multiple namesExternal validity, eg. body fluid tests on a sub-sampleReliability, eg. repeat questions, replicable surveysRepresentativeness, eg. using sampling & statistical methods

which ensure sample is representative of source population, so that findings are generalizable

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

Prevalence of use of legal highsMixmag survey: comparison of 2009 and 2010 findings *

% Lifetime Last-year 2009 2010 2010 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 20112010 sample: 69% male, modal age 20 years (3/4s 18-27), 89% heterosexual

British Crime Survey: 2009/10 - 2011/12Adults in England & Wales reporting last-year use of 5 drugs: ^ 367,000 ~ 220,000

16-59 16-24 .09/10 10/11 11/12 09/10 10/11 11/12

Mephedrone .. 1.4 1.1^ .. 4.4 3.3 ~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)

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

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

Characteristics of mephedrone usersBritish 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%)

Main reasons for taking legal highs

Mixmag survey of readers/clubbers, 2009 (N = 2,220)

1 other illegal drugs not available2 they are not illegal2 able to buy them online2 more reliable product than illegal drugs2 price - cheaper than illegal drugs6 better quality than illegal drugs7 safer than illegal drugs7 a better high & fewer side-effects than illegal drugs

Why have legal highs/NPS become 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

Sources of legal highs in UK

Mixmag survey of readers/clubbers, 2009 (N = 2,220)

% Friends 95 nearly all Websites 92 9 in 10 Headshops 78 8 in 10 Festival stalls 67 7 in 10 Drug dealers 51 half

5. The effects of NPSCategories of effects of drugs

Stages: Short-term: onset > main > residual Medium-term: after-effects, eg. come-down

Long-term: health/social, eg. dependence--------------------------------------------------------------------------Mental: thought emotion perception motivation

Physical: muscular respiratory circulatory sensorydigestive hormonal sexual facial

Snorting & Smoking: fastest hits

…excluding injecting Swallowing delays effects by 30 to 90 minutes

The facial effects of stimulant / empathogen drugs:

* bin-lids - dilated pupils of eyes

* wide-open eyelids, jerky eyes

* Flushed/hot-looking skin

* Clenched jaw, teeth-grinding

* Muscle-rippling, lip-chewing

The facial effects of depressant drugs (esp. opiate-type):

* pinned (constricted) pupils

* sagging/droopy eyelids

* paler complexion

* relaxed facial muscles

* nodding head (gouching)

Psychoactive drugs: 2-dimensional model of their general effects

Hallucinogen (trip)

|Stimulant ▬▬ ▬▬ Depressant (upper) | (downer)

Anti-psychotic (normalizer)

Drugs classified by effects model Hallucinogen (trip)

LSD

MDMA | ketamine

|Stimulant amphet. ▬▬ ▬▬ heroin

Depressant (upper) | (downer)

nicotine | cannabidiol (CBD)

quetiapine (Seroquel)

Anti-psychotic (normalizer)

mephedrone methoxetamine

Hallucinations: Machine-Elf (DMT)

Mephedrone Hallucinations“I was staring at the pattern on the carpet in the centre of

the room, and first some black smoke came up out of it, then I saw Michael Jackson float out of the smoke. I said ‘that can’t be Michael Jackson, he’s dead’, and anyway I don’t even like Michael Jackson – then I thought ‘it’s OK, I’m in District-9’ – then I came right out of it, and felt shocked, real terrified ... I hope I see Elvis next time”.

R. Newcombe (2009). Mephedrone: the use of m-cat (Meow) in Middlesbrough. Manchester: Lifeline Publications.

http://www.lifeline.org.uk/wp-content/_old-site-docs/M-cat%20report%20small.pdf

6. Risks & Harms from use of NPS

RISKS HARMS .

Behaviours involved in Consequences of using consumption of drugs drugs in specific ways

7 types of risk/safety 9 types of harm/benefit

eg. Injecting with used needles Infections (eg. HIV, HCV)

Taking too-high doses Overdose

Toxicity of substance Bodily damage etc.

Risks of using NPS/legal highsThe Risk CAMP-MAP identifies the 7 core areas of the riskiness/

safety of drug consumption (drug-taking behaviour):

1 What drugs are they taking (at same time)? Mixture

2 How are they getting hold of it (who/where)? Access

3 What are the contents of products being used? Product

4 What setting do they use it in (place, time)? Context

5 How much are they using (per dose, per period)? Amount

6 How are they consuming it (prep. & admin.)? Method

7 How frequently & regularly are they using it? Pattern

Source: Newcombe R (2010). A multi-disciplinary theory of drug-related harm reduction. http://www.3dresearch.org.uk/?p=info

Model of drug-related harms L e v e l T y p e o f H a r m .o f H a r m Health Social Economic

Individual

Community

Societal

Main harms of NPS/legal highsHealth Problems Mental disorder: anxiety, psychosis, mood Dependence: craving, tolerance, withdrawals Physical health: ‘route’ damage, diseases Poisoning: acute intoxication, overdose Death: fatal ODs, accidents, suicideSocial Problems: crime & CJS, relationships,

children, social exclusion, discrimination etc.Economic Problems: personal debts, policy costs etc.

Extent of these problems: mostly unknown

Economic costs of drug prohibition

THE UK spends more than any other country in Europe on its drugs policy – 0.48 per cent of GDP according to EMCDDA (European Monitoring Centre for Drugs and Drug Addiction) – City AM 15/1/13

Image of left upper limb of Patient 3 (mephedrone injector) post debridement.

Dorairaj J, Healy C, McMenamin M, Eadie P (2012). Journal of Plastic, Reconstructive & Aesthetic Surgery, 65, 37-41.

BODILY DAMAGE CAUSED BY MEPHEDRONE INJECTING

Causes: toxicity? adulterants? dose? injecting frequency?

The Sun Newspaper,Thursday 3rd May 2012: article about death from use of “legal highs”, when the drug involved was GBL – which was banned in UK in December 2009

DEATHS

Trends in deaths from ‘legal highs’ Mephedrone BZP/TFMPP GBH/GBL

2001 0 0 12002 0 0 52003 0 0 62004 0 0 12005 0 0 42006 0 0 72007 0 0 92008 0 0 202009 0 9 162010 6 5 122011 6 2 20

Source: Office of National Statistics (England & Wales); 2012

Deaths related to legal inhalants nitrous oxide poppers solvents helium2006 4 3 37 22007 3 2 39 22008 2 3 46 122009 .. .. 31 212010 .. .. .. 332011 .. .. .. 40

Sources: Office for National Statistics. Deaths related to drug poisoning in England & Wales 2010 (August 2011) .. Not available

Trends in Death Associated With Abuse of Volatile Substances 1971-2009. St. Georges Hospital, University of London (2010).

Note: helium deaths are mainly suicides Poppers = alkyl nitritesInhalant: drug ingested by inhaling a gas or the fumes of room-temp. solvent

7. UK Responses to use of NPSLegal bans & controlsPolice & CJS responsesEducational responses (schools, mass mediaHospital responses (A&E, psychiatric, etc.)Treatment responsesHarm ReductionLegal Regulation & Users’ Rights

MODA amendments: TCDOs 2011

2011 Temporary Class Drug Orders - Police Reform & (Nov) Social Responsibility Act 2011, Sec. 151 & Sch. 17

Home Office can place a drug in a TC if the ACMD advise that (a) it is or is likely to be misused, and (b) it has or could have harmful effects – and that a fast response is required to protect public. Covers all MoDA offences for 12 months – except possession, though police can still confiscate TCDs.

Penalties as for class B/C (max. 14 years custody)In first 6 months, just one new drug has been placed under a

TCDO: methoxetamine (MXE)

Import bans, 2010 to 2012

2010 Import ban on desoxypipradol (2DPMP) [stimulant](Nov) {Ivory Wave}

2011 Import ban on phenazepam [benzo] (June)

2011 Import bans on pipradol analogues of 2DPMP) (Nov)

2012 First TCDO under MoDA: methoxetamine(April) Also: 2DPMP (Ivory Wave) & phenazepam (Bonsai)

[draft Misuse of Drugs Act 1971 (Amendment) Order 2012]

Banning of synthetic cannabinoids

Under the 2009 Amendment Order to MoDA 1971, four types of synthetic cannabinoid were added to class B, schedule 1 of Misuse of Drugs Act [see Appendix]

Further Consideration of Synthetic Cannabinoids (Oct 2012)“The ACMD recommend that the substances detailed in

Annex A have potential harms commensurate with those of cannabis and should, therefore, be classified and controlled under the Misuse of Drugs Act (1971) as Class B [and Schedule 1] under an extended generic definition”.

BUT many groups of synthetic cannabinoids remain legal…

Banning of arylcyclohexylamines“the harms of methoxetamine are commensurate with Class B,

of the Misuse of Drugs Act (1971); and it should be scheduled under Schedule I of the Misuse of Drugs Regulations (2001) (having no known recognised medicinal use). The ACMD also recommend that a number of closely related analogues of ketamine and phencyclidine, some of which have already appeared on sale as “legal high alternatives”, be controlled by means of a generic chemical description detailed in Annex 3.”

Advisory Council on the Misuse of Drugs, Methoxetamine Report, October 2012

But many groups of arylcyclohexylamines remain legal…

Prohibition of khat?In January 2013, the UK government will make

a decision about whether or not to control khat under the 1971 Misuse of Drugs Act

ACPO position on TCDOsSubmission from Association of Chief Police Officers to Home

Affairs Select Committee on drugs policy, 2nd April 2012

“the solution to the particular challenge of legal highs does not lie in adding inexorably to the list of illicit substances.

A key question for the Government to determine is the extent to which legislation can realistically be used to address active choices being made by people and to tackle the undoubted harms caused by the misuse of substances taken essentially for pleasure.

The police will continue to focus their energies on serious criminality and take a less robust enforcement approach on matters relating to personal possession”

ACPO also warned the Government that the banning of ‘legal high’ drugs will fail, and forces will treat anyone found with them leniently – cautioning instead of prosecuting them.

Other recent major reports re NPSUK Drug Policy Commission: A Fresh Approach to Drugs (10/2012)

Recommended depenalization and harm reduction approach

Advisory Council on the Misuse of Drugs (October 2012) Recommended decriminalizing the possession of drugs

Home Affairs Committee, House of Commons (December 2012) 9th Report: Drugs – Breaking the Cycle Recommended decriminalization & harm reduction approach

All-Party Parliamentary Group for Drug Policy Reform, Jan 2013

Towards a Safer Drug Policy: Challenges & Opportunities arising from ‘legal highs’ – Inquiry into New Psychoactive Substances

Recommended decriminalization and harm reduction policy Proposed that the “less harmful” NPS be regulated and sold

from retail pharmacies

UK PM David Cameron: rejected all of the recent calls for drug policy reform – including a Royal Commission on drug policy - yet in 2002 stated that the War on Drugs “does not work”

Attitudes of politicians & top officials

Government’s leading adviser, Prof Les Iversen (head of ACMD) said in October 2012 that young people caught in possession of banned substances such as cannabis should be spared criminal prosecution to prevent their futures being blighted

Ken Clarke, Justice Minister, also claimed in 2012 there was no evidence that the ‘war on drugs’ had had any effect over the past 30 years

Tom Hollis, drugs spokesman for the Association of Chief Police Officers stated in January 2013 that responsibility for drug policy should be moved from the Home Office to Dept of Health: “the police are ‘flat-footed’ trying to keep up with the pace of change” (eg. training sniffer dogs, etc.)

How many new drugs (NPS/legal highs) are possible?

“Each new substance that emerges from the laboratory is a tabula rasa: its effects on human consciousness cannot be predicted simply from its chemical structure … The permutations may be, to all practical purposes, infinite” (p105-6).

_____________________________________________Mike Jay (2010). High Society: Mind Altering Drugs in

History and Culture. London: Thames & Hudson

Legal regulation of psychoactive drugs

Ultimately, legal regulation – as with alcohol and tobacco - may be the only viable solution to the exponential increase in ways of getting high which have emerged in the 21st century – from tweakable legal highs to electronic highs. If banning an NPS only leads to increased use and/or problems, the outcome is harm maximization not harm minimization.

The optimal solution would be to make available for adults’ private use the least toxic versions of each of the main kinds of psychoactive drug: notably stimulant, depressant, hallucinogenic and anti-psychotic drugs.

Transform’s report shows how legal regulation would work: ‘After the War on Drugs: Blueprint for Regulation’ (2009)

Responses to NPS/legal high use

Early-warning monitoring systems (eg. Drugwatch)Multi-agency approaches – local & nationalIn-service staff training – to stay up to date –

especially drugs workers & paramedicsConsultation with/representation of LH usersExploration of prescribing/treatment optionsRisk-reduction information – esp. online & appsWorking with headshops & ‘legal high’ websitesResearch – evidence-based services/strategies

Monitoring systems

European Monitoring Centre on Drugs & Drug Addiction: EMCDDA Early Warning System - for new synthetic drugs

European Medicines Agency Pharmacovigilance System - to monitor abuse of medicines

UK National Poisons Information Service – annual reports

FEWS – UK Home Office Forensic Early Warning System

Drugwatch

Substitute prescribingStimulant substitutes for mephedrone class/schedule

dexamfetamine (Dexedrine): max dose 60 mg/day B2 methylphenidate (Ritalin, etc.) B2 . modafinil (Provigil): average 100-200 mg per day POM-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Forms: tablets or syrup.

Medication for stabilizing & treating mephedrone users anti-depressants (for mood disorders) hypnosedatives (for sleep disturbances & anxiety) vitamins/nutrients (for malnourishment)______________________________________________________________________POM = prescription only medicine (Medicines Act 1968)

Lifeline leaflet/card

on safer use of mephedrone

Guide to safer use of hallucinogenic drugs(Lifeline Publications, Manchester 2005)www.lifelinepublications.org

Apps for smartphones etc. are now one of the best mass media for providing information about safer use of legal and illegal drugs

Agency Interventions with NPS users: needsconsultation with and representation of clients/users on policy-making groups and service providers

Appendices

ABSTRACT: The rapidly changing nature of novel psychoactive substance use Issue. Although use of many illegal drugs has stabilized or declined over the 21st century, this has been accompanied by a significant rise in the use of 'legal highs' - unregulated novel psychoactive substances (NPS) designed to mimic the effects of banned drugs like cocaine, amphetamines, MDMA, cannabis and ketamine. Also, some NPS have fairly unique effects, and these include laughing gas (nitrous oxide), salvia and kratom. These NPS are sold online and from street headshops as 'not for human consumption' in order to sidestep medicine laws. First, ketamine, GBH and magic mushrooms became popular from the 1990s, followed by party pills (notably BZP), GBL and laughing gas during the early 'noughties'. But, following the government’s banning of most of these NPS, by 2008 the market for new synthetic drugs was showing a notable surge. In particular, sensationalist media coverage helped to make mephedrone (meow/m-cat/drone) and other cathinones (eg. methylone/bk-MDMA) the most popular NPS ever. Indeed, by 2010, the British Crime Survey reported that mephedrone had become the 4 th most popular drug, resulting in the government banning it along with a dozen other cathinones. Predictably, by 2009, online and urban headshops responded to the cathinone ban by marketing a wide range of new NPS with a much wider variety of chemical structures, including Benzo Fury, Ivory Wave, Annihilation, Black Mamba and methoxetamine.Key arguments. Indeed, according to a 2011 EMCDDA report, the number of NPS marketed in Europe climbed from 13 in 2008, to 24 in 2009, 41 in 2010, 49 in 2011, and over 57 in 2012 – the equivalent of more than one new NPS every week. The most popular new types of synthetic NPS include cannabinoids (eg. AM2201) and cathinones (eg. MDPV, NRG1), while the most popular natural NPS include salvia, khat and kratom. A further concern for the drugs field is the advent of electronic highs, which work through the brain’s perceptual and electrical systems rather than directly on its neurotransmitters - such as binaurals (mind-altering sounds), dream machines (mind-altering visual displays), and brain tuners (brain-wave modifiers).Despite the vast numbers of NPS available, in October 2012 the UK government announced it would be banning just two main groups: synthetic cannabinoids such as Black Mamba and methoxetamine-type drugs (which had already been made the sole target of the new TCDO ‘holding class’). This clearly shows that the legal machinery available for controlling drugs is hopelessly out of date, and just as it failed to prevent the use of traditional drugs like cannabis and cocaine, UK drug laws are now patently failing to control use of NPS. Attempts at legal prohibition have been an outright failure - as demonstrated by the increase in mephedrone use and harm after it was banned - and interest in NPS continues to rise across many groups. For instance, an EC survey published in mid-2011 reported that one in 20 young adults (15-24s) across the EU's 27 countries had tried NPS - with the top four countries including Britain (one in 12) and Ireland (one in six). Conclusion. This paper concludes by arguing that current British policies toward NPS are ineffective and counterproductive, and that interventions are urgently needed to minimize harm from NPS use – including advice and education on safer use, outreach work in clubs, relevant treatment responses (eg. substitute drug prescribing), and legal regulation which prioritizes harm reduction and respect for human rights over the criminalization of people who take drugs (a victimless crime).

1. What are legal highs/NPS?

Natural product ‘legal highs’“Natural product legal highs are by their very nature highly

chemically complex, and in the clear majority of cases, chemical studies were conducted some considerable time ago. Their pharmacology and toxicology generally focuses on the major active principles with few studies detailing the potentially highly complicated and multiple effects of their extracts. This complexity, coupled with the inherent natural product variability of plant and fungal species, adds a further dimension to the potential harms associated with natural product legal high use”.

Source: Arunotayanun W, Gibbons S. (2012). Natural product 'legal highs'. Natural Product Reports, November 2012; 29(11): 1304-16.

Police definition of ‘head shop’A commercial retail outlet (including online businesses)

specialising in the sale or supply of equipment, paraphernalia or literature related to the growing, production or consumption of cannabis, or other drugs, and includes the sale or supply of ‘New Age’ herbs, exotic plant materials or other ‘New Psychoactive Substances’ (aka ‘Legal or Herbal Highs’)

Their primary function is to promote, facilitate and glamorise the cultivation, production, preparation and consumption of drugs.

Source: ACPO Guidance on Policing New Psychoactive Substances Including Temporary Class Drugs (Nov. 2011)

Is your legal high really legal?Answer depends not only on which drug it is, but: * when (the year) * where (the country)and * who you are (eg. adult, doctor etc.)

Also: if not legal, how illegal is it? MoD Act 1971 UK -class A, class B, class C or TCDO (supply only) – or Medicines Act 1968 etc..

2. Main types of NPS being sold from headshops & websites to 2012

7 major structural groups of synthetic cannabinoids

1. Naphthoylindoles2. Naphthylmethylindoles3. Naphthoylpyrroles4. Naphthylmethylindenes5. Phenylacetylindoles6. Cyclohexylphenols7. Benzoylindoles

The history of headshops1990s mainly inert/mild herbal substances

(khat tincture banned as class C drug prepar.)--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

2000- fresh psilocbye mushrooms/kits (banned 2005) 2006 party pills: ‘ecstasy-like’ drugs (some banned 2009)--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

2007- mephedrone & cathinones get popular

2010 (13 & relatives banned in 2010); salvia div.--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

2010- synthetic cannabinoids (eg. Black Mamba) now laughing gas (nitrous oxide) – refill capsules etc

various new stimulants & hallucinogens--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Next: Deep Web (eg. Silk Road); electronic highs

3. Estimating levels of NPS use

The Sun: Thursday 5th May 2012Legal Highs still for sale: Replacements for banned drugs

MARY JOY (£10 a gram): Similar to cannabis, users report hallucinations and insomnia after taking it. HE-MAN (£63 for 2 half-gram sachets): Reported to be the new “Mexxy”, its named after the cartoon character as it makes users feel like Masters Of The Universe. Side-effects include loss of balance and hallucinations. MPA (£15 a gram): Sold as bath salts and said to emulate “Mexxy”. Causes palpitations and temperature spikes. DOVES (£10 for 2 pills): Name linked to Love Doves, a type of ecstasy. Users can overheat and suffer a racing heartbeat. KARMA (£6 a gram): Leaves users dozy and confused.

4. Who uses NPS, & why?

Main reasons for drug useInitiation – Continuation – Cessation

Intoxication (high, buzz, pleasure)Stimulation (energy, excitement; working, dancing, sex)

Relaxation (sedation, trance-state, reducing anxiety)Psychonautics (exploring mind, tripping, hallucinations)

Socio-economic causes Drug MarketFamily & childhood factors AvailabilityIncome & social exclusion PricePeer influence/friend-groups Quality/purity

Genes: personality, attitudes, etc.

My Strange Addiction (US TV)29 episodes about 50+ ‘addictions’ (2010 to 2012): done first

for pleasure – typically a distortion of natural drives:Snorting baby powderInhale fumes: moth-balls, petrol, cleaning fluidsTaste/swallow: toilet paper, cushion-foam, A-B wipesEat: cat-food/hair/plaster/tape/glass/soap/dirt/laxatives/ashDrink: urine, nail polish, detergents, petrol, hand sanitizerSkin habits: cutting, picking scabs, pulling hair out, nail-bitingExcess grooming: tanning/bleaching, make-up, plastic surgeryExcess exercising – body-building, cycling & risky sportsExcess computer/phone/technological habits – esp. gaming, social networking, texting

5. The effects of NPS

VennDiagramModel ofPsycho-ActiveDrugs (by

effects)

6. Risks & Harms from use of NPS

Drug-Harm Ranking 2012The ranking of combined self and social scores for harm:

Taylor M et al. (2012). Quantifying the RR of harm to self and others from substance misuse: results from a survey of clinical experts across Scotland. BMJ Open 2012http://bmjopen.bmj.com/content/2/4/e000774.long

Research has only started recently, but a review paper on the effects of synthetic cannabinoidsand wider implications is now available

Trends in deaths from stimulants, E&W mephedrone * ecstasy amphetamines cocaine

2001 0 55 24 972002 0 56 38 1282003 0 50 31 1292004 0 43 37 1542005 0 58 45 1762006 0 48 44 1902007 0 47 50 1962008 0 44 45 2352009 0 27 49 2022010 6 8 48 1442011 6 13 49 112

England & Wales figures come under heading of ‘mephedrone/cathinones’ .2010: Scotland 4, N. Ireland 1 [UK: 11] 2011: Scotland 1, N.Ireland 2 [UK: 9] 3 other cathinone deaths in Scotland 2011: 4MEC, cathinone & MDPV (one each)Thus UK had a total of 12 cathinone deaths in 2011.

Source: Office of National Statistics (England & Wales), 2012; etc.

7. UK Responses to use of NPS

MODA amendments, from 2001 to 20102001 35 phenethylamines [hallucinogens] A1

2003 GHB (gammahydroxybutyrate) C4

2005 psilocin-based mushrooms (live/fresh) A1

2005 ketamine C4

2009 GBL (gammabutyrolactone), 14BD (butanediol) C(Dec.) BZP (benzylpiperazine) & other piperazines C1

Synthetic cannabinoid receptor agonists * B1

2010 mephedrone & substituted cathinones B1(April) [10+ stimulants + 2 entactogens]

2010 Naphyrone B1(June)--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Red letter = MODA class (A-C) Red number = MODA schedule (1-5)

Banning of synthetic cannabinoidsUnder the 2009 Amendment Order to MoDA 1971, four types

of synthetic cannabinoid were added to class B, schedule 1:

[2,3–Dihydro–5–methyl–3–(4–morpholinylmethyl)pyrrolo[1, 2, 3–de]–1,4–benzoxazin–6–yl]–1–naphthalenylmethanone.

3–Dimethylheptyl–11–hydroxyhexahydrocannabinol.[9–Hydroxy–6–methyl–3–[5–phenylpentan–2–yl] oxy–5, 6, 6a,

7, 8, 9, 10, 10a–octahydrophenanthridin–1–yl] acetate.9-(Hydroxymethyl)–6, 6–dimethyl–3–(2–methyloctan–2–yl)–6a,

7, 10, 10a–tetrahydrobenzo[c]chromen–1–ol.NABILONE was excluded by adding many statements such as: “Any compound structurally derived from 3–(1–naphthoyl)indole or 1H–indol–3–yl–

(1–naphthyl)methane by substitution at the nitrogen atom of the indole ring by alkyl, alkenyl, cycloalkylmethyl, cycloalkylethyl or 2–(4–morpholinyl)ethyl, whether or not further substituted in the indole ring to any extent and whether or not substituted in the naphthyl ring to any extent …” and so forth and so on…

DrugwatchLifeline originally developed RADAR: Rapid Assessment of Drug

Activities & Risks, designed to provide information about drug use far more quickly than other systems (eg. NDTMS).

Applied for Lottery Funding, but were unsuccessful. DrugWatch is currently an informal association of agencies

including DrugScope, Lifeline and Release, who share an interest in establishing a robust early warning system in the UK for all types of drugs.

When appropriate, DrugWatch’s early warning system will communicate information to the drugs sector on new and emerging compounds, including controlled drugs & ‘legal highs’

UK Forensic Early Warning SystemFEWS was set up to identity New Psychoactive Substances (NPS)

more promptly to enable Government “to take action before a harmful substance takes a foothold in the UK”, and to feed into the UK-wide Drugs Early Warning System (DEWS).

Latest report is an annex to Drug Strategy Annual Review, May 2012. Aims are (1) to reduce the demand for NPS, (2) ensuring statutory services can provide effective treatment/recovery from NPS, (3) encouraging individuals to take personal responsibility, & (4) promoting the choice not to take unknown potentially harmful psychoactive drugs.

Analysis of 1,300 samples tested during January 2011 to March 2012 found 17 NPS (9 already banned in UK): 5 synthetic cannabinoids, 4 tryptamines, 2 phenethylamines, 1 cathinone & 5 other NPS.

CLUB DRUG USE IN ENGLAND: LITTLE IMPACT ON NUMBERS ENTERING TREATMENT

“Data collected since 2005-06 now tells us enough to form an idea of the scale and nature of the problems associated with the more established club drugs – ecstasy, ketamine, methamphetamine, GHB/GBL, and mephedrone. What is becoming clear is that despite the widespread use of club drugs, they are currently causing a treatment problem for relatively few people”.

National Treatment Agency (2012). “Club Drugs: Emerging Trends And Risks”. December 2012.