Novel Psychoactive Substances richard.stevenson@nhs.net

NPS Background Confusing terminology “Designer Drugs” “Bath Salts” “Legal Highs” Definition “Psychoactive drugs, newly available in the UK, which are not prohibited by the United Nations Drug Conventions but which may pose a public health threat comparable to that posed by substances listed in these conventions”

History of NPS Drugs often developed decades ago 2008 mephedrone identified as clinical concern Hundreds of drugs identified since Marked geographical variations 98% users have used controlled substance prior

Supply of NPS “Head shops”, Internet, Dealers ,Mates! Branding Various compounds branded under the same name e.g. “burst” “Research chemicals” Marked “not for human consumption” FEWS analysis 61% 2 active drugs 30% 3 active components 88% festival samples contained controlled drugs 2013/2014

Challenges Unknown toxicology Identification of use Mechanism of action Duration of action Metabolism Interactions (including prescription drugs) Short term & long term harms Identification of use Self reporting Post-mortem toxicology Role of urine toxicology screens

Clinical Presentations Concern over health Extended duration of symptoms Abnormal behaviours Mild abnormalities Drug induced psychoses Acute behavioural disturbance Acute drug toxicity Harm associated with intoxication Consequences of method of drug use

Local Demographics Ages from 12 to 50 Equal sex distribution Depends on the substance Polysubstance use is markedly prevalent Alcohol +++ Approx 44 needle exchange service users NPS MSM and “slamming”

Synthetic Cannabinoids Sold openly from head shops Annihilation, Psy-clone, Clockwork Orange, Damnation, Exodus etc Potent endogenous cannabinoid receptor agonists Commonly smoked, ? “vaping” Often present with Nausea +++ Collapse Dissociation, coma Drug induced psychosis

Benzodiazepines Phenzepam, etizolam, diclazepam 1mg = 10mg diazepam May or may not be detected on urine drug screens Increasingly responsible for presumed opiate toxicity Recent study from Abertay Uni & Police Scotland “street blues” found to contain from 8mg to 48mg diazepam Phenazepam & etizolam detected

Ketamine Mimics & Hallucinogens Methoxetamine, 3-MePCP, methoxphenidine Induce dissociation NMDA receptor antagonists Prolonged duration of action Cerebellar signs N-BOMe, DOC Sold on blotters (like LSD) 20 hour duration of action Drug induced psychosis and threat to life behaviours

Cathinones Mephedrone, methedrone, butylone, MDPV Meow Meow, bubbles, M-CAT, Meph (not meth or “ma meff!) Similar mechanism of actions Catecholamine reuptake inhibitors Dopamine releasers (particularly MDPV) Commonly ingested, but insufflated, injected, and “bumping” Predominantly stimulant effects, but some MDMA mimicry

Ethylphenidate Sold as “burst” Ethylphenidate +/- benzocaine Responsible for major outbreak of drug induced psychosis in Lothian Related to methylphenidate but much more potent Addictive Multiple hits per day (some over 6 times) Risky injecting sites Predominantly ex-heroin users who were stable Injecting wounds causing significant concerns

Ecstasy Mimics BZP, PMA/PMMA, Benzo Fury, AMT, MDAI Often sold as Ecstasy, or “legal equivalents” (most now illegal) Mimic the empathogenic effect Potent inducers of serotonin toxicity

Serotonin Toxicity Characterised by Spectrum of toxicity Increased muscle activity Abnormal mental status Autonomic instability Spectrum of toxicity 5-HT2A receptor thought to be responsible Increased level of serotonin at synaptic level Decreased reuptake Serotonin release MAO – inhibition (direct receptor stimulation)

 DEATH  AGITATION MUSCLE ACTIVITY ALTERED MENTAL STATE HYPERTHERMIA DEHYDRATION RHABDOMYOLYSIS ACIDOSIS KIDNEY INJURY HYPERPYREXIA 41+ ↑ K DIC ↓ GLUCOSE ↓ Ca  DEATH 

Acute Behavioural Disturbance Challenging Potentially life threatening to patient Risk to care providers, police, public Extremely difficult to manage May be prolonged (e.g. desoxypipradol) Resistant to conventional interventions Doses of benzodiazepines & antipsychotics much greater Avoid prolonged physical restraint Emergency anaesthesia may be required

NPS & Mental Health NPS responsible for drug induced psychoses Ethylphenidate has 2 “phases” Acute florid episode associated with intoxication Protracted symptomology for weeks following abstinence Changes in neurotransmitters Dopamine reuptake/release/? receptor stimulation Serotonin reuptake/release/receptor stimulation Nor-adrenaline metabolism Poorly responsive to treatment Implications for treatment & continuation of medications

Summary NPS are here to stay Challenging area Limitations with identification of use Toxicology Diagnostic coding Drug induced/related mental illness will rise Don’t forget “classic” drugs of abuse