Understanding the ‘Spice’ phenomenon Perspectives from the EU Early warning system

Rita Jorge

Riga, 27 January 2016

1. Who we are, what we do

2. How we do it

3. What we know

4. Synthetic cannabinoids

5. What we need to find out

2

1. Who we are, what we do

2. How we do it

3. What we know

4. Synthetic cannabinoids

5. What we need to find out

3

The EU EWS: who we are

4

The EU EWS: what we do

5

• Changes in purity of established (controlled) drugs

• Established (controlled) drugs adulterated with unusual and/or harmful cutting agents

• Substances sold as others e.g. heroin sold as cocaine

• New patterns (forms) of use e.g. injection of cathinones

• Fatal and non-fatal intoxications

• Large seizures, seizures that show evidence of international trafficking and/or involvement of

organised crime

‘New narcotic or psychotropic drug, in pure form or in preparation, that is not controlled by the 1961 or

the 1971 UN Conventions, but which may pose a public health threat comparable to that posed by

substances listed in Schedule I or II or IV of the former and in Schedule I or II or III or IV of the latter

convention’ (CD 2005/387/JHA)

Scope of the EU-EWS:

New psychoactive substances i.e. ‘New’ to the drug market or newly misused

1. Who we are, what we do

2. How we do it

3. What we know

4. Synthetic cannabinoids

5. What we need to find out

6

The EU EWS: how we do it

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General population surveys (GPS)

High-risk drug use (HRDU)

Treatment demand indicator (TDI)

Drug-related deaths and mortality (DRD)

Drug-related infectious diseases (DRID)

Structured information

Markets, crime and supply

Event based surveillance

Long term / structural response

Drug seizures (police, customs, etc)

Serious Adverse Events (e.g. hospitals)

Calls to Poison Information Centres

Collected samples (various sources)

Open source information (media, etc.)

Rapid / Immediate response

Other ad-hoc reporting, Targeted research

“when in doubt, report”

8

EMCDDA

individual national focal points

Reporting forms

Notifications

Progress and Final Reports

Notifications

Joint Reports

Alerts Risk Assessments

Signal detection

Challenges of monitoring NPS

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• The market is driven by supply, not only demand

• Users do not know what they are using

• Dealers/vendors do not know what they are

selling

• Emergency services do not know which

substance was taken

• Reporting authorities do not necessarily have the

tools to analytically identify substances

• If you don’t know it’s there, you don’t look for it

• NPS issues may be “hidden” in the midst of

issues related to “traditional”/classical drugs

Our data is likely to be an underestimation of

the ‘real’ situation

Are you sure?

“We have no problem with NPS

in our region/country”…

1. Who we are, what we do

2. How we do it

3. What we know

4. Synthetic cannabinoids

5. What we need to find out

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From synthesis to consumer

12

NPS in Europe: Reported for the 1st time

13

Total: 567 substances under monitoring; 63% of which since 2012

0

20

40

60

80

100

120

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

Other substances

Opioids

Benzodiazepines

Arylalkylamines

Piperidines & pyrrolidines

Plants & extracts

Aminoindanes

Arylcyclohexylamines

Synthetic cannabinoids

Cathinones

Piperazines

Tryptamines

Phenethylamines

NPS ‘phenomenon’ is not slowing down

14 Source: European Drug Report 2014 (2013 data)

1. Who we are, what we do

2. How we do it

3. What we know

4. Synthetic cannabinoids

5. What we need to find out

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Brain, meet drugs

16 Source: http://slideplayer.com/slide/7239779/

Endocannabinoids

(endogenous)

e.g. Anandamide

Phytocannabinoids

(plant derived)

e.g. THC, CBD,…

Endocannabinoid

receptors

(CB1, CB2)

Synthetic cannabinoids

(man made)

Cannabinoid receptors are important…

17

From a medical perspective:

• Cannabinoid receptors (CB1 and CB2) are involved in regulating a variety of

physiological processes, including appetite, pain and pleasure sensation, immune

system, mood and memory

• Important pharmacological targets

• Stimulated research into the structure-activity relationships between a number of

molecules and their ability to bind to CB1 (and CB2)

From a drugs perspective:

• Δ9-THC is one of the many cannabinoids present in cannabis that binds to

Cannabinoid receptors (CB1 and CB2)

• Cannabis is the most used drug in Europe. Almost ¼ of the adult population of the

EU has used cannabis at least once (EDR 2014). 20 million have used the drug in

the last year. 11 million have used cannabis in the last month.

• IMPORTANT TARGETS DUE TO POTENTIAL FOR PSYCHOACTIVITY

Where did they come from?

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Hebrew University

HU series

THC analogues

~10 compounds

John W. Huffman

JWH series

Aminoalylindoles

~470 compounds

Pfizer pharmaceuticals

e.g. CP series

Cyclohexylphenyls

~ 700 compounds

Alexandros

Makriyannis

AM series

Indoles

~ 45 compounds

e.g. JWH-018 e.g. HU-210 e.g. CP-55,940 e.g. AM-2201

…but others soon followed

‘Playing’ with Lego®

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• Synthetic cannabinoids are structurally very diverse

• Some maintain names from original patents

• Unequivocal naming is vital for good monitoring

Linked Group-Tail-Core-Linker

• Linked Group: methyl amino butanone (AB)

• Tail – Fluoro benzyl (FUB)

• Core – Indazole (INA)

• Linker – carboxamide (CA)

Further info:

emcdda.europa.eu/topics/pods/synthetic-

cannabinoids

Cannabinoids in Europe: Reported for the 1st time

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Total: 160 substances under monitoring; 73% of which since 2012 (100% since 2007)

0

5

10

15

20

25

30

35

40

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

Synthetic cannabinoids in Europe

21 Source: European Drug Report 2014 (2013 data)

Quickly replaced in the NPS market

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Substance JWH-018 JWH-018 adamantyl

derivative

JWH 018 adamantyl

carboxamide

AKB48

(Apinaca) 5F-AKB48

Year of first detection 2008 2011 2012 2012 2012

Number of seizures in

2013 162 8 98 404 3362

Harms: Alerts issued in 2015

Deaths in UK and SE associated with Superman 'ecstasy' tablets containing PMMA

Superman logo ecstasy tablets containing a high concentration of PMMA in Spain

1 death associated with PMMA in Belgium

Fatal intoxication associated with PMMA in Norway

Outbreak of soft tissue infections in people who inject drugs, particularly those using new

psychoactive substances in Scotland, United Kingdom

Death in Belgium associated with ocfentanil

2 deaths and 3 non-fatal intoxications in Germany associated with MDMB-CHMICA

Multiple outbreaks of intoxications, including deaths, associated with synthetic cannabinoid

products in the United States

15 non-fatal intoxications associated with tablets containing ADB-FUBINACA in Hungary

2 deaths associated with acetylfentanyl in the United Kingdom

Outbreak of serious intoxications in Poland associated with a ‘legal high’ called ‘Mocarz'

Harms

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Pharmacology?

• Act on CB1 receptor…but what about other targets?

• THC partial agonist, many SCRA’s are full agonists

Manufacturing?

• Low solubility of cannabinoids (and poor practices) might lead to “hot pockets”

• “small lumps (usually 4-6 mg, but up to 120 mg) of almost pure substance”

New concerns: MDMB-CHMICA

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• Synthetic cannabinoid — not found in the literature

• Analogue of AB-CHMINACA (CB1 agonist Ki : 0.78 nM (16x

Δ9-THC))

• Internet snapshot: commonly (wrongly) called MMB-

CHMINACA by EU web vendors

• Internet snapshot: availability at EU level

Detected in 20 EU countries

Luxembourg: China en-route to

Spain = 40kg

Harms: new concerns

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Anecdotal evidence

- users report injecting cannabinoids at needle

exchange points

- JWH-250 in syringe next to dead body

- 2 confirmed cases (SCRA unknown)

1. Who we are, what we do

2. How we do it

3. What we know

4. Synthetic cannabinoids

5. What we need to find out

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What we need to find out

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• Changing patterns of drug use

• Misleading/mislabelled substances

• Polydrug use – combined use of synthetic cannabinoids with alcohol, with

other controlled drugs and with other NPS

• Limited knowledge on pharmacology, toxicology, safety profile (research

needed)

• Limited data on acute and chronic toxicity

• Insufficient information to correlate blood SCRA concentration to effect

• Limited/no experience in how to manage clinically acute/chronic presentations

Strong national and regional early warning systems play a key role

EWS central to public health responses in the EU

Paldies!

http://www.emcdda.europa.eu/activities/action-on-new-drugs

@toxicovigilance