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

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)?
NORTH WEST: Cumbria, Lancashire, Cheshire, Merseyside & Greater Manchester

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

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

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-80s solvents (eg. butane, toluene); poppers (alkyl
nitrites); magic mushrooms (notably psilocybe)
Nineties ketamine; GHB (gammahydroxybutyrate)
( ) khat
Noughties piperazines (notably BZP); cathinones (notably
( ) mephedrone); GBL; N2O (laughing gas)
salvia divinorum; kratom
APB (eg. Benzo Fury), MDAI (eg. Sparkle),
methoxetamine (eg. MXE); synthetic
cannabinoids (from JWH-018 to AM-2201)
Drugs in table: past-year use in surveys is typically higher than 1% (when adjusted for under-
estimation, i.e. low validity & reliability)
Red = synthetic (or semi-synthetic)
Green = natural (typically herbal)

14. 17 new novel drugs,
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 CC-NBoMe 4. JWH AM JWH Ipracetin 6. AM Ethacetin 7. 4-Me0-PcP HO-MiPT 8. 5-Me0-DALT CP D-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)
Supplier
Product
Compounds detected
As described
Status A
Benzofury
1-Benzofuran-6-ylpropan-2-amine (6-APB)
Yes
Legal
Jolly Green Granules
Benzocaine
Contents not specified
MDAI
5,6-Methylenedioxy-2-aminoindane
Methoxetamine
2-(3-Methoxyphenyl)-2-(ethylamino)cyclohexanone
MPA
N-methyl-1-(thiophen-2-yl)propan-2-amine
NRG-2
4-Methylethcathinone (4-MEC). Contaminant mephedrone No
Illegal
NRG-3
5-IAI
5-Iodo-2-aminoindane B C D
MDAI Gold
N-methyl-1-(thiophen-2-yl) propan-2-amine E
BMJ Open (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 ( '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. Herbal Highs: Chewed, smoked or brewed/drank
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: /10: 6,800
2007/8: 3, /12: 7,900
(3) Series of big rises in price of skunk since 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. bag of off-white powder
fluoropentyl-naphthoyl-indole
AM synthetic cannabinoid: 1-gram
bag of off-white powder
Source: Bulk Research
Chemicals
Light dose: 250 mcg
Moderate dose: 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):

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)
In short, the cost of death by caffeine is about £17. Caffeine half-life is about 4 hours. Also: LD50 for paracetamol is just 12 grams (24 tablets)
One can of Relentless energy drink (500ml) contains 160 mg caffeine (its targeted at young people)
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

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
– 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

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
Jan
July
Jan
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 *
% Lifetime Last-year
poppers
nitrous oxide (4 in 10)
mephedrone (5 in 10)
salvia
BZP
Spice/Magic
methylone
GBL
_________________________________________________________________________________________________
* 2009 findings reported in February 2010; findings given in March 2011
2010 sample: 69% male, modal age 20 years (3/4s 18-27), 89% heterosexual
3 legal highs had similar LT and LY use-rates: nitrous oxide, mephedrone & methylone

45. British Crime Survey: 2009/10 - 2011/12
Adults in England & Wales reporting last-year use of 5 drugs:
  ^ 367, ~ 220,000
09/ / / / / /12
Mephedrone ^ ~
Spice *
BZP
Khat
GBL/GHB
_____________________________________________________________________
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 last-year mephedrone users in E&W: 16-24s, 2011/12 (7th)
^ 95% CI: 317, ,000 last-year mephedrone users in E&W: 16-59s, 2011/12 (4th)
Note: the BCS does not include poppers or solvents in its definition of ‘legal highs’ or ‘recently controlled drugs’

46. Global Drug Survey: use of NPS UK 2010/11
% Last 12 months Last month
Nitrous oxide
Mephedrone
Isopropyl nitrate (poppers)
Methoxetamine
Synthetic cannabis (some legal)
Benzo Fury (6APB)
MDAI (Sparkle)
Methylone
GBL (gammabutyrolactone)
MDPV (methylenedioxypyrovalerone)
AMT (alphamethyltryptamine)
Kratom
Solvents
For 2011/12 GDS, only findings for energy drinks and nitrous oxide are presently available. Blue = previous legal highs, now banned
Also, Ivory Wave (2DPMP) not listed. AMT= alphamethyltryptamine

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 – peak age-range 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: (2.9%) & (3.6%) vs (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/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

52. 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

53. 5. The effects of NPS
Categories 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 sensory digestive hormonal sexual facial

54. Snorting & Smoking: fastest hits
…excluding injecting Swallowing delays effects by 30 to 90 minutes

55. 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

56. The facial effects of depressant drugs (esp. opiate-type):
* pinned (constricted) pupils
* sagging/droopy eyelids
* paler complexion
* relaxed facial muscles
* nodding head (gouching)

57. Psychoactive drugs: 2-dimensional model of their general effects
Hallucinogen
(trip) |
Stimulant ▬▬ ▬▬ Depressant
(upper) | (downer)
Anti-psychotic
(normalizer)

58. 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
CBD = cannabidiol – the 2nd most psychoactive agent (cannabinoid) in cannabis after THC (tetrahydrocannabinol)

59. Hallucinations: Machine-Elf (DMT)

60. 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.

61. 6. Risks & Harms from use of NPS
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.

62. Risks of using NPS/legal highs
The 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.
Prep = preparation Admin = administration (route of use)

63. 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

64. Main harms of NPS/legal highs
Health Problems
Mental disorder: anxiety, psychosis, mood
Dependence: craving, tolerance, withdrawals
Physical health: ‘route’ damage, diseases
Poisoning: acute intoxication, overdose
Death: fatal ODs, accidents, suicide
Social Problems: crime & CJS, relationships,
children, social exclusion, discrimination etc.
Economic Problems: personal debts, policy costs etc.
Extent of these problems: mostly unknown

65. 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

66. BODILY DAMAGE CAUSED BY MEPHEDRONE INJECTING
Image of left upper limb of Patient 3 (mephedrone injector) post debridement.
Causes: toxicity? adulterants? dose? injecting frequency?
Dorairaj J, Healy C, McMenamin M, Eadie P (2012). Journal of Plastic, Reconstructive & Aesthetic Surgery, 65,

67. DEATHS 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

68. Trends in deaths from ‘legal highs’
Mephedrone BZP/TFMPP GBH/GBL
Source: Office of National Statistics (England & Wales); 2012
Mephedrone: 2010: Scotland 3, N. Ireland 1; 2011: Scotland ?, N. Ireland 2

69. Deaths related to legal inhalants
nitrous oxide poppers solvents helium
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 St. Georges Hospital, University of London (2010).
Note: helium deaths are mainly suicides Poppers = alkyl nitrites
Inhalant: drug ingested by inhaling a gas or the fumes of room-temp. solvent
The rise in helium deaths is the largest percentage increase in deaths mentioning a specific substance between 2006 and there seems to be a reluctance to ban any drug which is an inhalant (gas or solvent)

70. 7. UK Responses to use of NPS
Legal bans & controls Police & CJS responses Educational responses (schools, mass media Hospital responses (A&E, psychiatric, etc.) Treatment responses Harm Reduction Legal Regulation & Users’ Rights

71. MODA amendments: TCDOs 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)

72. Import bans, 2010 to 2012
Import ban on desoxypipradol (2DPMP) [stimulant]
(Nov) {Ivory Wave}
Import ban on phenazepam [benzo]
(June)
Import bans on pipradol analogues of 2DPMP)
(Nov)
First TCDO under MoDA: methoxetamine
(April) Also: 2DPMP (Ivory Wave) & phenazepam (Bonsai)
[draft Misuse of Drugs Act 1971 (Amendment) Order 2012]
ALSO: In September 2011, the ACMD recommended that DPMP (Ivory Wave) be made class C drug under MoDA

73. 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…

74. 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…

75. 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

76. ACPO position on TCDOs
Submission 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.

77. Other recent major reports re NPS
UK 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

78. 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”

79. 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.)

80. 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

81. 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)

82. Responses to NPS/legal high use
Early-warning monitoring systems (eg. Drugwatch) Multi-agency approaches – local & national In-service staff training – to stay up to date – especially drugs workers & paramedics Consultation with/representation of LH users Exploration of prescribing/treatment options Risk-reduction information – esp. online & apps Working with headshops & ‘legal high’ websites Research – evidence-based services/strategies

83. 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

84. Substitute prescribing
Stimulant substitutes for mephedrone class/schedule
dexamfetamine (Dexedrine): max dose 60 mg/day B2
methylphenidate (Ritalin, etc.) B2 .
modafinil (Provigil): average 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)
Like methamphetamine, cocaine (A2) is also unlikely to be considered as an acceptable substitute drug for the treatment of mephedrone dependence

85. Lifeline leaflet/card on safer use of mephedrone

86. Guide to safer use of hallucinogenic drugs
(Lifeline Publications, Manchester 2005)
Apps for smartphones etc. are now one of the best mass media for providing information about safer use of legal and illegal drugs

87. Agency Interventions with NPS users: needs
consultation with and representation of clients/users on policy-making groups and service providers

88. Appendices

89. 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 4th 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).

90. 1. What are legal highs/NPS?

91. 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):

92. 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)

93. 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..

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

95. 7 major structural groups of synthetic cannabinoids
Naphthoylindoles
Naphthylmethylindoles
Naphthoylpyrroles
Naphthylmethylindenes
Phenylacetylindoles
Cyclohexylphenols
Benzoylindoles

96. The history of headshops
1990s mainly inert/mild herbal substances
(khat tincture banned as class C drug prepar.)
fresh psilocbye mushrooms/kits (banned 2005)
2006 party pills: ‘ecstasy-like’ drugs (some banned 2009)
mephedrone & cathinones get popular
(13 & relatives banned in 2010); salvia div.
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

97. 3. Estimating levels of NPS use

98. The Sun: Thursday 5th May 2012
Legal 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.

99. 4. Who uses NPS, & why?

100. Main reasons for drug use
Initiation – 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 Market
Family & childhood factors Availability
Income & social exclusion Price
Peer influence/friend-groups Quality/purity
Genes: personality, attitudes, etc.

101. 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 powder
Inhale fumes: moth-balls, petrol, cleaning fluids
Taste/swallow: toilet paper, cushion-foam, A-B wipes
Eat: cat-food/hair/plaster/tape/glass/soap/dirt/laxatives/ash
Drink: urine, nail polish, detergents, petrol, hand sanitizer
Skin habits: cutting, picking scabs, pulling hair out, nail-biting
Excess grooming: tanning/bleaching, make-up, plastic surgery
Excess exercising – body-building, cycling & risky sports
Excess computer/phone/technological habits – esp. gaming,
social networking, texting
Common habits. Following pleasure, many then felt shame/guilt/negative. Most had emotional problems as kids, esp years (eg. divorce, abuse)

102. 5. The effects of NPS

103. Venn Diagram Model of Psycho- Active Drugs (by effects)

104. 6. Risks & Harms from use of NPS

105. Drug-Harm Ranking 2012
The 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 2012

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

107. Trends in deaths from stimulants, E&W
mephedrone * ecstasy amphetamines cocaine
England & Wales figures come under heading of ‘mephedrone/cathinones’
2010: Scotland 4, N. Ireland 1 [UK: 11] : 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.

108. 7. UK Responses to use of NPS

109. MODA amendments, from 2001 to 2010
phenethylamines [hallucinogens] A1
GHB (gammahydroxybutyrate) C4
psilocin-based mushrooms (live/fresh) A1
ketamine C4
GBL (gammabutyrolactone), 14BD (butanediol) C
(Dec.) BZP (benzylpiperazine) & other piperazines C1
Synthetic cannabinoid receptor agonists * B1
mephedrone & substituted cathinones B1
(April) [10+ stimulants + 2 entactogens]
Naphyrone B1
(June)
Red letter = MODA class (A-C) Red number = MODA schedule (1-5)
2001: one of 35 phenethylamines was a stimulant, placed in Class B: hydroxyamphetamine
* Synthetic cannabinoids, eg. JWH-018 (Spice) – but excludes nabilone (Cesamet)
~ full list of banned cathinones in Cathinone/Mephedrone powerpoint file

112. Banning of synthetic cannabinoids
Under 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…

113. Drugwatch
Lifeline 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’

114. UK Forensic Early Warning System
FEWS 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 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.
6 specific new drugs were: 5-IAI, methoxyphenamine, ethylphenidate, camfetamine, JWH-022 and etizolam.
Source: ANNUAL REPORT ON THE HOME OFFICE FORENSIC EARLY WARNING SYSTEM (FEWS). A SYSTEM TO IDENTIFY NEW PSYCHOACTIVE SUBSTANCESIN THE UK (May 2012, Home Office)

115. CLUB DRUG USE IN ENGLAND: LITTLE IMPACT ON NUMBERS ENTERING TREATMENT
“Data collected since 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.