Transcript New drugs coming our way

New drugs coming our way what are they and how do we detect them?
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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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
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‘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 newlydiscovered
• Before 1997 these substances were often known as
designer drugs – e.g. fentanyl and α-prodine derivatives
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The Early Warning System (EWS)
Three stages:
1. Information collection/dissemination in MS
2. Risk assessment by EMCDDA scientific
committee
3. Control in EU
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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
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The ‘Phenethylamine/tryptamine period’
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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
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Recent developments
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‘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
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Substituted piperazines
CH2
N
N
NH
BZP
Cl
NH
mCPP
• 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
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Substituted cathinones
O
NH2
C
CH2
Cathinone
CH3
• 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
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Misused medicinal products
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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
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Miscellaneous synthetic drugs
CH3
O
CH
Br
CH2
O
NH2
Bromodragonfly
• 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 4Meo-PCP, the pipradrol derivative dipenylpyrrolidinylmethanol
(D2PM), p-fluoroamphetamine, etc.
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Spice Gold smoking mixture
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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
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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
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Synthetic cannabinoid agonists
1. Analogues of Δ9-THC (e.g. HU-210, Nabilone)
2. Cyclohexylphenols (Pfizer CP-compounds)
3. Naphthoylindoles, naphthoylpyrroles (JWH
compounds)
4. Others (fatty acid amides?, etc.)
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Δ9-THC and three synthetic cannabinoids
Δ9-THC
CP 47,497
HU-210
JWH-018
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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:
• drug ‘chat rooms’
• 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
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Summary
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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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