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Leslie A King
UK Focal Point on Drugs
EMCDDA Conference: Identifying Europe’s information needs for effective drug policy, Lisbon,
6-8 May 2009
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UK Focal Point on Drugs
EMCDDA Conference: Identifying Europe’s information needs for effective drug policy, Lisbon,
6-8 May 2009
The political-legal background of EU initiatives
* ‘Joint Action’ on New Synthetic Drugs (1997)
* The Early Warning System (EWS)
* Council Decision 2005/387/JHA on the information exchange, risk assessment and control of new psychoactive substances
* The ‘Phenethylamine/tryptamine period’
* Recent developments
3
‘Joint Action’ on New Synthetic Drugs (1997-2005)
* Focus on substances (NSD) not already listed in UN1971 Convention, but with similar potential for harm as psychotropic drugs already in Schedules I or II
* New means newly-abused – not necessarily newly-discovered
* Before 1997 these substances were often known as designer drugs – e.g. fentanyl and α-prodine derivatives
4
The Early Warning System (EWS)
Three stages:
* Information collection/dissemination in MS
* Risk assessment by EMCDDA scientific committee
* Control in EU
5
The 2005 Council Decision:
New Psychoactive Substances (NPAS)
* Extends scope to include both psychotropics (i.e. UN1971 candidates) and narcotics (i.e. UN1961 candidates)
* Not restricted to synthetic materials – plant products also covered (e.g. Salvia divinorum)
* Allows information collection (but not risk assessment) on misuse of medicinal products and their precursors
6
The ‘Phenethylamine/tryptamine period’
* PIHKAL and TIHKAL
* Search for the ‘new ecstasy’
* Tablets > powders > capsules
* Risk assessments (1999 – 2004):
MBDB, 4-MTA, PMMA, TMA-2, 2C-T-2, 2C-T-7, 2C-I
* By 2004 over 20 illicit phenethylamine derivatives discovered in EU
* Tryptamines less common – all hallucinogens
7
Recent developments
* ‘Designer drugs’ now often called ‘legal highs’
* Phenethylamines/tryptamines increasingly uncommon
* Wide diversity of new substances
* Substituted piperazines
* Substituted cathinones
* Misused medicinal products
* Plant products
* Miscellaneous synthetic drugs
* Spice
8
Substituted piperazines
* By 2006, 1(3-chlorophenyl)piperazine (mCPP) found in 10% of ‘ecstasy’ tablets in EU. More seizures, larger quantities than any other substance since 1997
* 2007: EMCDDA risk assessment on 1-benzylpiperazine (BZP) leads to expected EU-wide control in 2009
* Others include TFMPP, DBZP, FPP
* Critical review of six piperazine derivatives by ECDD/WHO in 2009
BZP
mCPP
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Substituted cathinones
* Over 20 illicit substances derived from cathinone (e.g. mephedrone, methylone, MDPV)
* Available from websites and shops
* They are β-keto analogues of phenethylamines
* Mostly CNS stimulants
Cathinone
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Misused medicinal products
* Dextromethorphan (DMX)
* Glaucine
* Benzydamine
* Phenazepam
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Plant products
* Salvia divinorum (Mexican Sage) - salvinorin A
* Mitragyna speciosa (Kratom) - mitragynine
* Piper methysticum (Kava) - kavalactones
* Argyreia nervosa (Hawaiian Baby Woodrose) - lysergamide
12
Miscellaneous synthetic drugs
* Indans, tetralines etc. - aryl-variants on the phenethylamine theme
* Difuranyl-phenethylamines (2CB-Fly and Bromodragonfly)
* Fluorotropacocaine – the first designer drug based on cocaine
* Many other synthetic psychoactive substances are being sold via websites, but misuse remains low, e.g. the phencyclidine derivative 4-Meo-PCP, the pipradrol derivative dipenylpyrrolidinylmethanol (D2PM), p-fluoroamphetamine, etc.
Bromodragonfly
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Spice Gold smoking mixture
* Marketed since ~ 2006; imported from China
* Contains unidentified herbal matter
* The claimed plant constituents are innocuous
* About €20 for 3g
* Produces a ‘cannabis-like’ effect
* Related products: Yucatan Fire, Spice Diamond etc.
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‘Spice’ – recent developments
* December 2008: Analysis by THC Pharma, Germany showed Spice contains JWH-018 and other synthetic cannabinoid receptor agonists
* January 2009: Germany controls JWH-018 and several CP compounds under narcotic laws. Similar action by Austria using medicines legislation
* February 2009: France controls 5 synthetic cannabinoids under narcotic laws
* May 2009: Controls planned in further MS
15
Synthetic cannabinoid agonists
* Analogues of Δ9-THC (e.g. HU-210, Nabilone)
* Cyclohexylphenols (Pfizer CP-compounds)
* Naphthoylindoles, naphthoylpyrroles (JWH compounds)
* Others (fatty acid amides?, etc.)
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Δ9-THC
HU-210
CP 47,497
JWH-018
Δ9-THC and three synthetic cannabinoids
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Detecting new psychoactive substances
Problem areas:
* Pure reference materials and analytical data are often not available in the early stages
* Not all forensic/toxicological laboratories in the EU have the means to identify new substances - the EWS often relies on those with NMR spectroscopy
* Examining non-scheduled drugs is not a priority for forensic science organisations in some countries
* Some substances may be active at doses below 1mg; detection in body fluids if not in dosage units may be challenging
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Can new substances be anticipated?
* The Early Warning System is reactive
* But almost all new psychoactive substances were previously described in the scientific literature
* The Internet may provide information on new substances:
o drug ‘chat rooms’
o purchases from websites selling ‘legal highs’
* We could use this knowledge and devise a set of rules based on previous experience
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A rule-based system for prediction?
* Synthetic drugs will continue to dominate – herbal products will remain uncommon
* Precursor chemicals or essential reagents should be commercially available or readily synthesised and not controlled
* The method of synthesis should be straightforward
* The end-product should be either a stimulant or have MDMA-like properties, but not be a synthetic hallucinogen
* The end-product should be active orally and the required dose should be no more than 100mg
* Further PIHKAL substances are unlikely to appear
* More synthetic cannabinoids can be expected
20
Summary
* A formal mechanism to monitor, assess and control new drugs has been in operation within the EU since 1997
* In that time over 90 new psychoactive substances have been reported
* Most are synthetic compounds; plant/herbal products remain uncommon
* Most have not been widespread and most did not survive for long on the illicit market
* Risk assessments were carried out on 10 substances, of which 7 were recommended for control
* Nearly all presented analytical challenges when first encountered
* For many, little was and still is known about their pharmacology/toxicology
* Nearly all substances had been described in the scientific literature, often many years ago; they are effectively ‘failed’ pharmaceutical agents
* In the early years, most substances were either phenethylamine or tryptamine derivatives
* In the past 5 years there has been a great diversity of chemical structures, although most are stimulants, or are ‘MDMA-like’ or, less-commonly, hallucinogens
* Rather than be reactive, it should be possible to anticipate new substances given a knowledge of the literature and the use of rules
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