1. The Game Changer: the impact of ‘novel highs’
Dr Russell Newcombe
HIT Hot Topics Conference, Liverpool UK
15th November 2013

2. Overview of presentation
1. Definitions: legal highs and NPS
2. Types: by source and effects
3. Legal response
4. Recent research: prevalence, trends
Conclusions

3. Definitions: legal highs
Chemicals which alter the normal functioning of the brain (neurotransmitters and brain-waves), thus producing changes in our experience and behaviour - 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;
(d) 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.

4. 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 literally 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 but it is still referred to as a ‘legal high’ by some sources (notably the mass media). However, it could also be argued that labels like new drugs or novel highs are enough for many purposes.

5. In short:
Legal highs: uncontrolled, but can be new drugs (eg. 6-APB) or older drugs (eg. nitrous oxide) NPS: new, but can be uncontrolled (eg. 6-APB) or controlled (eg. mephedrone)

6. The legal loophole used by NPS
Headshops and online retailers of ‘legal highs’/NPS get round the 1968 UK Medicines Act by stating that their products are not for human consumption, i.e. by definition not a medicine. So: no tests/trials required.
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’.

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

8. http://www.megachems.com November 2013 Research Chemicals
bk-2C-B
Diphenidine Powder
MTTA / MEOP (1:1 Mix)
Ethylphenidate
MPA / NM2AI (combo packs)
5-EAPB powder
NM2AI
3,4 CTMP powder
Methiopropamine
Synthacaine crystal
Nitricaine
MDAI
5-Meo-Dalt freebase
2-AI
Benzodiazepines
Etizolam
Fluromazepam
Diclazepam
Cannabinoids
5fAKB-48
5f-PB22
STS-135
BB-22
2NE1
November 2013
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Diphenidine is a novel chemical which fills that gap perfectly. Its not expensive either and when researched in amounts from mg it produces beautiful results similar to that of the old recently banned products.
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bk-2C-B Powder & Pellets Also Available Now!
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9. 50 of the 73 new NPS in 2012 were synthetic cannab-inoid products

10. Google results (August 2012):
‘buy legal highs’ = 2.74 million
‘buy
research
chemicals’ = 6.91 million

11. Problems with legal high/NPS sales
Headshops/websites cannot give out information about the safer use of the drugs they sell No testing/trials of risks & harms of NPS sold No guarantee that different batches of same product will contain (a) same dose of drug, or (b) even same drug Huge variety of NPS available, with different chemical/ trade/slang names, making drug/health service responses & research work very difficult

12. 2. Types of legal high/NPS
Based on last-year prevalence of use among young adults in 2012/13 in England & Wales (British Crime Survey):
What are the most popular legal highs?
What are the most popular NPS among those
banned since 2005?

13. Most popular legal highs & NPS - last-year use: 16-24s, E&W, 2012/13
Legal highs nitrous oxide 6.1% 2nd poppers 1.2% 7th salvia 1.1% 8th NPS banned mephedrone 1.6% 5th since 2005 ketamine 0.8% 9th magic mushrooms 0.6% 10th Traditional cannabis 1st, cocaine 3rd, ecstasy 4th, Illegal drugs amphets 6th, LSD & tranx 11th/12th
Top 10 drugs: 3 are legal highs, 3 are NPS [steroids 13th; crack & khat 14th/15th; opiates 16th]
Poppers = alkyl nitrites

14. Nitrous oxide used by 350,000 young people in past year Home Office figures show 'hippy crack' is second most popular drug among 16- to 24-year-olds. Guardian, 25 July 2013
“sniffing balloons full
of the gas has become the summer recreational drug of choice, particularly for festival goers”

15. Nitrous oxide: whippets

16. Nitrous oxide (N2O, laughing gas)
Young adults in UK report N2O as most popular legal high in online and media surveys (see later slides on prevalence) year olds: N2O is 2nd most popular of all drugs used in last year in 2012/13 CSEW – reported by about 400,000 (6%) in E&W – only cannabis use is more prevalent Yet: Gets no or very little attention from mass media Coverage by educational publications poor/missed Relatively little research compared to other NPS

17. 3 TYPES OF NPS BASED ON SOURCE
Herbal highs: plant/fungi or animal part/product
Synthetic highs: substance made by means of chemistry
(semi-synthetic if started with natural precursors)
Mixed herbal/synthetic: synthetic drugs mixed into natural drugs, esp. herbal material + cannabinoids
Electronic highs: perceptual, electrical (eg. brain tuners)

18. Herbal Highs: Chewed, smoked or brewed/drank Salvia divinorum
Khat: cathinone (stimulant)
Salvia divinorum
salvinorin A
(hallucinogen)
Kratom: mitragynine (stimulant/ opioid-like)

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

20. Some common NPS/legal highs
Accessed: 5th March 2013

21. Mephedrone: methylmethcathinone
4MMC
m-cat
meph
drone
fert

22. Mephedrone injecting problems
Photograph of left upper limb of Patient 3 post debridement
Dorairaj J, Healy C, McMenamin M, Eadie P (2012). The untold truth about “bath salt” highs: A case series demonstrating local tissue injury. Journal of Plastic, Recon-structive & Aesthetic Surgery, 65,

23. Synthetic opioids: bromadol
Bromophenyldimethylaminophenylethylcyclohexanol
500 times stronger than morphine:
20 mg morphine / 10 mg heroin = 0.04 mg bromadol [40 mcg]
Short-term effects include analgesia, sedation, euphoria, constipation, itching & respiratory depression
Longer-term effects include tolerance and dependence
VX-Chem
Bromadol: C22H28BrNO  Purity: 99%
Minimum Order Quantity: 500 grams
Price: $3,440 for 500 grams ($6.88 a gram)

24. Herbal products containing synthetic cannabinoids
Usually sold as herbal preparations containing inert herbal material (leaf etc.) saturated with synthetic cannabin- oids (SCs) & other drugs. The pure SC powder can also be obtained online.

25. New legal synthetic cannabinoids
Latest batch of legal synthetic cannabinoids sold online include: 5F-PB22, AKB-48F, STS-135 & BB-22: from £15 a gram to £3,000 a kg – e.g.

26. “Acute Kidney Injury Associated with Synthetic Cannabinoid (SC) Use”
In 2012, Wyoming Department of Health investigated 16 cases
of Acute Kidney Injury (AKI) following SC use, across 6 states.
5 of the 16 patients had used a new SC called XLR-11
Also: SCs are 2 to 3 times more likely than cannabis to produce
sympathomimetic effects (tachycardia, hypertension), and 5
times more likely to produce hallucinations – with an
increased risk of seizures.
“No antidote exists”
Morbidity & Mortality Weekly Report, Vol. 62 (6), 93-8 (February 15, 2013)

27. Types of novel psychoactive drugs
Main illegal drugs being mimicked Phenethylamines ecstasy (MDMA), amphetamines Piperazerines ecstasy, amphetamines Cathinones ecstasy, amphetamines, cocaine Tryptamines LSD, psilocin, DMT Cannabinoids THC, hallucinogens, sedatives Miscellaneous stimulant/sedative/hallucinogen/opioid Source: EMCDDA-Europol Annual Report on the implement-ation of Council Decision 2005/387/JHA [April 2012]

28. Recent guide to NPS, Nov 2013

29. 3. Legal responses to NPS
Misuse of Drugs Act amendments (see Appendices) Temporary Class Drug Orders - ban trafficking for 1 year while ACMD review (max 14 years prison) > methoxetamine (made class B, 2013) > June 2013: 5APB & 6APB (Benzo Fury) & NBOMe Importation bans: 2DPMP, phenazepam (class C, 2012) Intoxicating Substances Supply Act 1985 ( : 0) Trade/consumer legislation Anti-social Behaviour, Crime & Policing Bill 2013

30. Response of NPS marketers to NPS bans
Continuing to sell banned NPS in countries which have not yet banned them ‘Tweaking’ banned chemical to produce new legal version with similar effects Producing new NPS in unbanned groups Banned NPS move into illicit drug market, usually with rise in price & adulterants and fall in purity, eg. mephedrone banned in 2010 but still 5th most popular last-year drug for 16-24s in 2012/13 BCS (after cannabis, nitrous oxide, cocaine and ecstasy)

31. 4. Recent research and notable studies
New Musical Express Drugs Survey – October 2013
Sample: 5,295 respondents: 63% male, 56% in FT education, 55% years (20% U-18)
Lifetime drug use: 78% in 10 had tried legal highs
Last-year drug use: 74%: legal highs 2.6%, mephedrone 1.1 %
First drug used: legal highs 1.6%, mephedrone 1.2%
Attitudes: 54% believed legal highs should not be banned

32. Global Drug Survey 2013
Online survey advertised in Mixmag, Guardian & Gay Times 2012, n = 22,000 (80% aged 18-30) NPS/Legal Highs – 12% had ever used Unknown drugs – 14% had used a drug at a party/club without knowing what it was Bought drugs online: 22% Past-month use in UK (n = 7,000+) Nitrous oxide 26.9% Mephedrone 13.8% Poppers 13.6%

33. NPS obtained from internet, UK, late 2011
A total of 22 ‘legal high’ products were purchased from 5 different internet sites in late 2011, and each substance was screened to determine its active ingredients.
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; two (labelled NRG2) contained cathinones, including the banned mephedrone; and two contained MPA.
Overall, 23% did not contain the listed active ingredients
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).

34. Emergence of multi-drug NPS products, e.g. 11 drugs in E tablet
Analysis of RockStar ecstasy tablet in 2013 found ELEVEN different drugs present, including MDMA, amphetamine, cathinones, BZPs & methoxetamine
Scottish Police Authority, reported by Crew2000 pic.twitter.com/6MPb2DfoZR

35. The NPS are mutating…
Many new NPS identified in Japan in 2012, including a product containing both URB-754* (inhibitor of an endo-cannabinoid deactivating enzyme) & 4-Me-MABP (cathinone derivative)
Also, a 3rd unknown compound - N,5-dimethyl-N-(1-oxo-1-(p-tolyl)butan-2-yl)-2-(N′-(p-tolyl)ureido)benzamide) – was also found in the product, and deduced to be an unexpected reaction between URB-754 and 4-Me-MABP.
* 6-methyl-2-[(4-methylphenyl)amino]-1-benzoxazin-4-one
~ 4-methylbuphedrone
Uchiyama N et al. (2012). URB-754: A new class of designer drug and 12 synthetic cannabinoids detected in illegal products. Forensic Science International, October 2012.

36. Deaths related to NPS, England & Wales
mephedrone/cathinones
BZP/TFMPP
GHB/GBL
novel psycho. substances
NPS includes current legal highs and former legal highs like mephedrone
Office of National Statistics (2013). Deaths related to drug poisoning in England & Wales, 2012
Deaths related to NPS, Scotland
novel psycho. substances
NPS: substances which were legally available at the time of the death
National Records of Scotland (2013). Drug-related deaths in Scotland, 2012.

37. Deaths from legal highs in 2012
An average of:
one death per week in England & Wales
One death every 3 days in Scotland
Given differences in population size, this means that the annual mortality rate for legal highs is three times higher in Scotland (about 1 in 300,000) compared with England & Wales (about 1 in a million)

38. 5. Conclusions NPS are a ‘game-changer’ - they have:
> hugely expanded the number of psychoactive drugs
> sidestepped drug-related laws (legal loophole), and banned NPS are rapidly replaced by more legal NPS
> introduced new drug-related risks and harms;
> caught many drug services unprepared/untrained
> AND they require a harm-reduction approach more than a recovery approach – but the UK drug strategy’s primary aim is recovery

39. Legal high users = guinea pigs
Source: Lifeline (2013). “Big Blue Book of Drugs”.
[Available
from:
Exchange
Supplies]

40. What should we do next?
Take an evidence-based approach Take a principled approach: theory & models – not common-sense or counter-productive bans Cross-national/regional comparisons: especially New Zealand – Psychoactive Substances Act 2013 Take a harm-reduction approach based on categories of NPS - stimulant, sedative, hallucinogen etc. – as well as the effects/harms of specific substances Involve NPS users: representation, participation

41. NPS/legal high use interventions: need
consultation with and representation of NPS users on policy-making and drug service groups

42. Dr Russell Newcombe www.3Dresearch.org.uk director@3Dresearch.org.uk
Research, Training & Consultancy
on Drugs, Disorder & Deviancy