EU Action on new drugs New synthetic drugs and the challenge of monitoring new psychoactive substances
Dr. R. Sedefov, M.D.M.A. Project, Milan, 10 October 2006
Outline of talk
• EMCDDA • Brief overview of synthetic drugs situation in EU • The Joint Action on new synthetic drugs • The Council Decision on new psychoactive substances • Piperazines • Hallucinogenic mushrooms • Anticipation of new synthetic drugs
EMCDDA the EU drugs agency: data coverage
EMCDDA – European Monitoring Center for Drugs and Drug Addiction, Lisbon (Portugal) OHIM – Office for Harmonization in the Internal market (Trade Marks and Designs), Alicante (Spain) EU-OSHA – European Agency for Safety and Health at Work, Bilbao (Spain) CPVO – Community Plant Variety Office, Angers (France) ETF – European Training Foundation, Turin (Italy) CEDEFOP – European Centre for the Development of Vocational Training, Thessalonica (Greece) EMEA – European Medicines Agency, London (United Kingdom) EUROFUND – European Foundation for the Improvement of Living and Working Conditions, Dublin (Ireland) EEA – European Environment Agency, Copenhagen (Denmark) CDT – Translation Centre for the Bodies of the European Union, Luxembourg (Luxembourg) EUMC – European Monitoring Centre on Racism and Xenophobia, Vienna (Austria) EAR – European Agency for Reconstruction, Thessalonica (Greece) EFSA – European Food Safety Authority, Parma (Italy) EMSA – European Maritime Safety Agency, Lisbon (Portugal) EASA – European Aviation Safety Agency, Köln (Germany) ENISA – European Network and Information Security Agency, Brussels (Belgium) ECDC – European Centre for Disease Prevention and Control, Solna (Sweden)
FI NO SE EE LV DK LT
IR UK NL BE DE CZ SK AT FR HU RO IT PT ES GR EL PL
BG
TR
MT CY
Monitoring fields and tools
• 5 key epidemiological indicators • Prevalence & patterns of drug use in the general population • Prevalence & patterns of problem drug use • Drug-related infectious diseases (HIV, HCV, HBV) • Drug-related deaths and mortality of drug users • Demand for drug treatment • Core data situation • Crime and market/supply/availability • Youth and school surveys (incl. ESPAD) • Action on new drugs (EWS, EDND) • Core data responses • Prevention (EDDRA), treatment, rehabilitation, harm reduction • National and Community strategies • National and Community legislation (ELDD)
Synthetic drugs: amphetamines and ecstasy
EU is concerned because: • Synthetic drugs are widely consumed in Europe: upward trend in amphetamine and ecstasy use in most EU countries (young adults) • Europe still major centre for ecstasy production but manufacture spreads to other parts of world • Global amphetamine production and seizures still concentrated in Europe • Growing problems with methamphetamine use in Africa, Asia, Australia, New Zealand and US, significant use in EU only in the Czech Republic
Trends in recent use (last year) of amphetamines among young adults (aged 15 to 24) by national surveys
http://stats05.emcdda.eu.int/en/elements/gpsfig17-en.html
Trends in recent (last year) amphetamine + ecstasy use in young adults (15–34 years)
Changes 1995-2003 in lifetime prevalence (percentage) of ecstasy use among 15 to 16 year old school students
http://stats05.emcdda.eu.int/en/elements/eyefig02a-en.html
Drug use among UK clubbers
High – cannabis, ecstasy, and cocaine (powder) LTP range 84% - 93% LMP range 48% - 60% Medium – amphetamine, amyl nitrate, magic mushrooms, ketamine LTP range 43% - 78% LMP range 18% - 30% Low – salvia, GHB, crack, heroin, methamphetamine, and new synthetics LTP range 1% - 18% LMP range 1% - 8%
Self-reports of drug use (Mixmag UK 2004 survey N = 1131)
Percentage of Mixmag readers who regularly use drugs
80% 70% 60% 50% 40% 30% 20% 10% 0% ECSTASY 75% COCAINE 57% KETAMINE 17% LSD 7% VIAGRA 5% CANNABIS 65% SPEED 27% MUSHROOMS 13% BENZODIAZEPINES 6% GHB 3%
Results are based on drugs taken in an average month. Mixmag drugs survey ’04-’05
1997 EU Joint action on new synthetic drugs
A former EU legal instrument implemented by the Member States, EMCDDA, Europol, the Commission and the Council. Concerned synthetic drugs: • which are not listed in any of the Schedules of 1971 UN Convention; • which pose a serious threat to public health comparable to the substances listed in Schedules I or II thereto; • which have a limited therapeutic value. Provided for: • early-warning system to identify new drugs as soon as they appear on the European drug scene; • scientific risk assessment of health and social risks of new drugs; • mechanism through which such drugs may be subjected to control measures at EU level.
Synthetic drugs
Physiologically-active substances True poisons
Foods Natural products Medicines
Drugs Synthetic drugs
Semi-synthetic drugs ‘Illicit’ drugs
Substances in UN 1961/1971 (‘old’ synthetic drugs)
New synthetic drugs (NSD) (designer drugs)
Principles for risk assessment of NSD
• Consider scientific evidence in relation to better-known drugs • Consider a dual definition of risk as probability and degree of seriousness (hazard) • Consider weighting separately the issues of reliability (quality) of information and relevance (specific risk issues involved such as health and social issues, and consequences of prohibition) • Risk is considered independently of legal status • Consider a wide range of control options • Proportionality and precaution
EMCDDA risk assessment on new synthetic drugs
MBDB 4-MTA ketamine GHB PMMA 2C-I 2C-T-2 2C-T-7 TMA-2 N-methyl-1-(1,3-benzo-dioxol-5-yl)-2-butanamine (1998) 4-methylthioamphetamine (1999) 2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone (2000) γ-hydroxybutyrate (2000/2001) para-methoxymethamphetamine (2001) 2,5-dimethoxy-4-iodophenethylamine (2003) 2,5-dimethoxy-4ethylthiophenethylamine (2003) 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2003) 2,4,5-trimethoxyamphetamine (2003)
Council Decision 2005/387/JHA of 10 May 2005
• Replaces the Joint action while keeping the notion of EWS - risk assessment - control measures • Extends the scope to all new psychoactive substances i.e. includes new psychotropic and new narcotic drugs alike, i.e. similar to those listed 1961 & 1971 UN Conventions • Stimulates exchange of information on abused and misused psychoactive medicines in cooperation with EMEA (in addition to the pharmacovigilance system) • Stimulates exchange of information on emerging trends in new uses of existing substances and on possible public health related measures
Synthetic drugs
Physiologically-active substances True poisons
Foods Natural products Medicines
Drugs Synthetic drugs
Semi-synthetic drugs ‘Illicit’ drugs
Substances in UN 1961/1971 (‘old’ synthetic drugs)
New synthetic drugs (NSD) (designer drugs)
Council Decision 2005/387/JHA: a three-step process
Information exchange/Early-warning
A new psychoactive substance is detected in the EU Member States and described in a reporting form
Reitox focal points
EMCDDA
The European Commission
(Official Journal/ L 117, 20.05.2005) Europol national units Europol European Medicines Agency (EMEA)
Risk assessment
The Council of the EU may request a risk assessment, based on a EMCDDA– Europol Joint report
EMCDDA extended Scientific Committee
Risk assessment report
Decision-making
At the initiative of the European Commission or a Member State based on the Risk assessment report
Council of the EU decides whether or not to submit the new psychoactive substance to control measures
Council Decision on control measures
Control measures and criminal penalties in the EU Member States
Main sources of EWS-related information
At national level: • heath and care system: specialised and non-specialised treatment centres, hospitals’ emergency rooms, poisoning centres, psychiatric departments, low threshold, outreach and street-work agencies, drug prevention centres, drug help lines, GPs, etc.; law enforcement agencies: prosecution authority, police, specialised drug units, customs, border guards, etc.; laboratory networks: forensic analysis of seized drugs, toxicological analyses of specimens from deceased or living individuals, etc.; key informants: users, pill-testing sites, organisers of youth events (festivals, concerts, raves, etc.), owners and staff of clubs, etc.; media: in general, internet (incl. discussion groups and forums), etc. research establishments: published and grey literature
• • • • •
Early-warning system sources and response
Indicator-based Event-based Reitox EWS Europol
KE Indicators Core data Early-warning
Limited warning
Public health early-warning
Adapted from R. Kaiser at al., 2005
Council Decision: what triggers the system?
It is upon the discretion of EMCDDA and Europol to decide whether there is sufficient evidence, which merits further collection of information and, consequently, drafting a joint report. The decision is based on joint assessment of the: • • • • • • amount of the seized material; evidence of organised crime involvement; evidence of international trafficking; analogy to better-studied compounds; evidence about the potential for further (rapid) spread; and evidence about serious intoxications or death cases.
In 2005/2006 the EWS monitors
• Phenethylamines: 2C-I, 2C-T-2, 2C-T-7, 2C-D, 2C-H, 2C-E, 2C-P, (2C-B), 2C-T-4, 4-MTA, TMA-2, PMMA (PMA), MBDB, (DOB, DOM), MDHOET, DPIA and MDMCAT (methylone) Tryptamines: DMT, AMT, DPT, DIPT, 5-MeO-DMT, 5-MeOAMT, 5-MeO-DIPT, 5-MeO-T, 5-MeO-MIPT, 5MeO-DET,4-AcO-DET, 4-HO-DIPT, 4-HO-DET, MIPT and 4-AcO-DIPT BZP, TFMPP, CPP (mCPP & pCPP), MeOPP MOPPP, MDPPP, MPPP, MPHP ketamine, GHB
•
• • •
Piperazines: Cathinones: Others:
Challenges in 2006 and beyond
• • • • •
Reference materials (seized substances or reference substances) New unanticipated chemicals A new risk assessment procedure guidelines (f. e. plants) Internet sales New trends identification and monitoring
Piperazine
HN NH
• • • •
A synthetic substance Anthelminthic drug (treatment of intestinal roundworms) No activity on CNS Parent of numerous N-arylpiperazines
N-Arylpiperazines: Structures
Ar N NH
CH2
N
NH
Benzylpiperazine (BZP)
N Cl
NH
m-Chlorophenylpiperazine (CPP) p-Methoxyphenylpiperazine (MeOPP)
H3C
O
N
NH
All reported in EU as NSD/NPAS
N-Arylpiperazines: Structures - contd.
Ar N NH
F
N
NH
p-Fluorophenylpiperazine (FPP) m-Trifluorophenylpiperazine (TFMPP)
N C F F
NH
F
CH2
N
N
CH3
1-Benzyl-4-methylpiperazine
All reported in EU as NSD/NPAS
N-Arylpiperazines: Properties
Ar N NH
• • • • • • •
Originally developed as anthelminthic drugs (but not licensed in EU) Some are used to manufacture antidepressant drugs (e.g. mCPP trazodone Molipaxin®) Some are metabolites of those antidepressant drugs (e.g. trazodone mCPP + other metabolites) All synthetic substances: note confusion in literature with piperine ex. pepper plant {Piper nigrum} Some behave as weak stimulants (especially BZP) Some may have weak MDMA-like effects (mCPP)
N-Arylpiperazines: Problems of Analysis
Ar N NH
• • • • • • •
Low prevalence Colour tests usually fail Do not cross-react with urine immunoassays Reference standards often unavailable Some reference data lacking Some are metabolites of medicinal products Some consumed with other drugs (e.g. MDMA)
N-Arylpiperazines: Misuse/Control
Ar N NH
• • • • • •
First appeared in USA in mid-1990’s (BZP now a scheduled drug) Widespread in New Zealand (“party-pills”) Six N-arylpiperazines reported in Europe in past two years None listed in UN Conventions – some scheduled by MS CPP has become the most widespread NSD/NPAS in the EU since 1997 No EU risk assessment on CPP – excluded by Art. 7.3 of the Council Decision (2005)
m-Chlorophenylpiperazine (mCPP)
N Cl NH
• • • • • • • • • • • • • •
Reported in most Member States since 2004 Usually as tablets (8 - 80mg mCPP), some powders Sometimes mixed with MDMA in dosage units Largest seizure in Ireland, December 2005 (123,000 tablets) A mixed agonist and antagonist at 5HT receptors Little reaction with dopaminergic system Widely used in experimental human pharmacology Intoxications resemble the ‘serotonin syndrome’ Not neurotoxic No major impairment of cognitive functions Little potential for dependence No fatal poisonings reported Commercially available Ortho- and para-CPP isomers also occur
m-Chlorophenylpiperazine (mCPP): dosage units
Tablets known in different European countries as: X4’ (Netherlands, Sweden), ‘duhovka’ (Hungary, Czech Republic), ‘regenboogies’, ‘arc-en-ciel’ (Belgium), ‘arlequin’ (France), ‘rainbow’ (Slovenia), Rolls Royce’, ‘smarties’ (Switzerland)
Benzylpiperazine (BZP/A2)
.
•Appear in the dance scene as ‘uncontrolled alternative’ to MDMA in Switzerland and in the U.S. since late 1990‘s/early 2000‘s • Use promoted in the dance scene in New Zealand - approximately 8 million tablets have been sold since 2001
In 2006 further vigilance of EWS: Methylone (MDMCAT)
• The benzylic ketone derivate of MDMA – can be described as ringsubstituted cathinone. • Appeared in the end of 2004 in NL (DIMS), sold in liquid form via the internet and under the name ‘Explosion’ as an ‘air freshener’ (room odoriser in plastic tubes with vanilla oil) in ‘smartshops’; in Sweden as tablets sold on the internet. • Behaviourally and pharmacologically the substance resembles MDMA, but the observed subjective effects are not completely identical.
In 2006 further vigilance of EWS: liquids, mixtures
Right: 125 mg MDMA base per bottle (0,5%), Dec. 2005, NL Left: mixture of cocaine, amphetamine & Viagra, July 2005, Northern Germany Below: 5 ml, 170 mg MDMA base per vials (3,5%), launched under the names of : Ambient Pear, Caribbean Cocoas, Fruitage Ananas, Red Passion, Dec. 2005, NL
Magic mushrooms: objectives of this presentation
• Background of the E-POD Project • Reasons for selecting magic mushrooms as an emerging trend case study • Methodology • Results & Conclusions • Limitations and way forward
Magic mushrooms - summary
• Smart shops appear to be a key factor with their use of English, French & German for promoting and selling Rapid development of Internet helped sales and to disseminate information Natural substances in general had entered into vogue A trend for developing for adventuresome lifestyles/holidays and mind experiences Lack of mechanisms to control supply
•
• •
•
Background of the E-POD Project can we monitor trends at the EU level?
EUROTREND Project The EU Drugs Action Plan (2005-2008) - “develop clear information on emerging trends and patterns of drug use and drug markets” Eearly Warning System, EMCDDA European-Perspectives-on-Drugs (E-POD)
Internal selection of topics prompted by
Associated risks • Risk assessment on hallucinogenic mushrooms in the Netherlands (2000) • Report on the risk assessment of GHB in the framework of the joint action on new synthetic drugs (2002) • Media reports (2005) • Both drugs not well covered by the key indicators but some survey data available showing prevalence estimates above 1%
E-POD objectives
• To collect and analyse information on hallucinogenic mushrooms in the EU within a limited timeframe (between July 2005 and October 2005). • To take into account lifestyle trends among potential users and economic interests of suppliers. • To publish findings electronically. • To inform the way forward for other EU work in the field of emerging trends.
Information fields
• Description • Prevalence and patterns • Trends • Markets and availability • Dose and effects
• Consequences • Responses – legal, prevention • Contributing factors • Barriers to diffusion
Main data sources
• EMCDDA reporting form (received from 13 countries) • Early Warning System standard reports/Reitox national reports • ESPAD (14 countries/STs) • Scientific articles published in peer reviewed journals • Forensic science bulletins • Grey literature • Newspaper and magazine media articles • Internet websites and discussion groups • Personal communication
Naturally occurring hallucinogens
• Mushrooms: psilocybin and psilocin containing fungi and other fungi not containing psilocybin and psilocin e.g. Amanita muscaria (Fly agaric)
• More than 100 different types
• Grow wild in central and northern Europe but also other part of the world: Mexico, Central America
Front cover of Life Magazine in 1957
Markets: mushroom hunting
Evidence from the Czech Republic, UK, Ireland, Poland, Slovakia, Bulgaria Location news (UK) at:
http://members.lycos.co.uk/shroommap/map.htm
Markets: retail outlets
• 120-150 smart shops (estimation) in the Netherlands. Magic mushrooms make up 50% of their turnover (estimation from 2000) • About 300 shops and market stalls across the UK sold hallucinogenic mushrooms until the change in legal status in July 2005 prohibited sales • UK Treasury sales tax on hallucinogenic mushrooms: 255,000 Euro per year on a turnover of approx. 1.46 million Euro per annum (estimations) • Little is know from other Member States. Some evidence from the Czech Republic
Markets – online internet shops
Snapshot via Google and Alta Vista using four different key words and examining first 300 sites. Results: • The internet provides retailers with opportunities to develop international markets for hallucinogenic mushrooms: 39 online shops selling magic mushroom products – 82% based in the Netherlands but also Austria, Germany, UK • Different language versions (mainly English, French and German) to attract foreign customers • The quality and amount of information about associated risks of use provided by retailers on the internet varies • UK retailers interest for legal types of hallucinogenic mushroom such as Amanita muscaria (Fly agaric), Purple ohms capsules
UK online Shop linked to Wrongshop in the Netherlands
Risk groups I
Comparison of lifetime use of hallucinogenic mushrooms by current drug users, clubbers and 16-19 year olds, in 2000 (Source: UK Home Office) 50 45 40 35 30 25 20 15 10 5 0 44
%
24 11
Current drug users in club sample
Clubbers
General population 16-19 year olds (British Crime Survey)
Risk groups II
Comparison of male and female lifetime prevalence (average % ) of hallucinogenic mushroom use by different user groups in 13 European countries (Source: ESPAD experts)
%
50 40 30 20 10 0
er er er er er s er er er us us us us us us us s t y e s e o l* is s u c a in l an t as et t ab oh in e ho n a r s c n o a n ge al lc ec co in h ta m ci g ca in o ea he g p uc b in am a ll h er th do User groups an D LS s lu er
female male
Mental health risks
• Bad trips • Underlying psychotic or personality disorder • Extreme cases reported by the media
Death leap man 'ate magic mushrooms' Neal Keeling Robert McCracken A MAN jumped to his death from the 23rd floor of a Salford tower block after eating mind-altering magic mushrooms. ….
Legal response
• Psilocin and psilocybin are controlled under 1971 UN Convention on Psychotropic Substances and listed in Schedule I under the name psilocybine and psilocine (or psilotsin) respectively. • All EU Member States control them accordingly • Six EU countries have tightened their legislation on mushrooms since 2001, to coincide with recent increases in prevalence. (DN, NL,DE, EE, UK IE) • Austria to follow? • Legal loopholes
Information for risks reduction
• Information included in many prevention programmes
• Examples with specific focus on hallucinogenic mushrooms
• Information exchange among users
• Warnings and information on safe use practices from retailers
Examples from Dutch smart shop
Conclusions
Contributing factors • Mega consumer trends • Recreational drug settings • Ease of access • Legal loopholes
Barriers to diffusion • Legal control • Cost/benefits of use
Methodological reflections and limitations
Use of different sources
Top-Down
Routine monitoring data Scientific literature (25%)
Thematic paper
Internet, newspaper/media survey data (75%)
Bottom-Up
Triangulation
• Combination of quantitative and qualitative data to broaden the understanding of emerging trend. • Limited quantitative data and time series highlights importance of “softer” data. • Need to triangulate a wide range of different sources to assess the veracity of the accumulated information. • Networks used for data collection are at an early stage when it comes to the collection of data on emerging trends. • Thus the collected data obviously lack completeness.
Limitations
• More information available that we did not take into account. • Publication itself let to more information – first case study=first stage that can lead to further stages • Emphasis on English language (search and literature) • Limitations of snapshot exercise • Unsystematic searches • Timing • A perennial problem in the dissemination of information about emerging trends is the danger of promoting: “the oxygen of publicity”.
Front Page Azarius 29.June 2006
Next steps
• Online publication of GHB case study – December 2006
• Development of a methodology/criteria to select topics (what is a new trend?)
• Advance our methodology for internet searches
Contacts & acknowledgements
Roumen.Sedefov@emcdda.eu.int Anabela.Almeida@emcdda.eu.int http://www.emcdda.eu.int/ Thanks to J. Hillebrand & D. Olszewski (Hallucinogenic mushrooms) L.A. King (piperazines)