Synthetic cannabinoid agonists (SCRAs) Harry Shapiro DrugScope

What are they? Smoking mixtures – (usually) inert herbs plus chemicals. Look like natural cannabis, but high potency varieties can be dyed in bright colours Spice (original generic name) – latterly Annihilation, Happy Joker. Exodus Damnation; Kronic; Black Mamba, Psyclone, Blue Cheese

Prescient? Gary Henderson: J Forensic Science 1988: “In the view of this author, it is likely that the future drugs of abuse will be synthetics rather than plant products. They will be synthesized from readily available chemicals, may be derivatives of pharmaceuticals, will be very potent, and often very selective in their action. In addition, they will be marketed very cleverly”.

Chemistry EMCDDA identified seven main structural groups including : AMxxx; HUxxx; JWHxxx; HUxxx, CPxxx 5F compounds (e.g Psyclone) could be classified within any of the major structural groups Most of these compounds discovered by underground chemists in the published scientific literature JWH = John William Huffman doing research into making a drug that would target the brain’s natural cannabinoid receptors to aid research into HIV/AIDS, chemotherapy and MS. Leaked out in Germany as K2 and Spice around 2008 where the first street use of SCRAs was identified. But some compounds identified more recently not in the literature at all – suggests chemists are examining legislation and working round it.

Action on brain THC is a partial agonist – doesn’t fully engage with the brain receptors CB1 and CB2 (because of the presence of CBD?) Some SRCAs shown to be full agonists which makes them potentially more potent than THC. Huffman aslo investigated retail SCRAs and discovered that JWH-018 binds to the CB1 receptor four times tighter than THC and ten times tighter to CB2 We had no idea that anybody would be stupid enough to use it”

Patterns and prevalence of use Virtually no official data Some data from 10/11 and 11/12 CSEW (0.2% and 0.1% lifetime use) More data from 2015 from CSEW and ‘Smoking, drinking drugs among school students’ survey 2014 Global Drug Survey, SCRAs not listed in top 20 drugs used in the last year. But UK second only to USA in last year use, although generally not popular among regular club drug/festival drug users Much more problematic use among vulnerable young people, young and adult offenders, street homeless, existing service users – often in areas of higher economic and social deprivation where selling not restricted to head shops – whole range of outlets plus street To what extent will official data improve the picture?

Health impacts Impossible to gauge what brand will have what effect – not least because any individual packet could be a SCRA blend or ‘single estate’! Anything from dreamy euphoria to something akin to psychedelics Dosage – not the same as cannabis! More potent varieties carry most risk: anxiety, panic, disorientation, confusion, severely impaired short-term memory; cardio-vascular and respiratory problems, aggression, seizures, collapse. Many reported incidents of A&E admissions – “Mambulance” Dependency (receptor binding)

Control 1 Two rounds of MDA generic legislation (2009 and 2012) proposed by ACMD to mop up “first and second” generation SCRAs “Third generation” advice to Home Office in November 2014 – modifications of one JWH compound (4 sub-structures,16 compounds??)

Control 2 How sustainable is this approach? Where does it all end?

Control 3 Neurological approach to SCRAs Blanket ban on high street sales Local authority action – cases brought under GPSL; bans of use in public spaces Internet

Neurological approach? Control on any drug acting on the CB1 or CB2 receptors US law from 2012 – CB1. Success? What about licensed medicines that might also act in this way? At what level of activity does law kick in? Expense of testing a wide range of drugs to ascertain activity level?

Guidance and further information PHE Guidance to commissioners LGA Guidance to local authorities Clinical Guidance on club and other drugs due from Project Neptune (Dr Owen- Bowden Jones) Harry Shapiro