Clinical Experience of Novel Psychoactive Substances

Dr Richard Stevenson

BackgroundLegal Highs -> Novel Psychoactive

Substances41 new substances in 2010 aloneDiverse collection of compounds

PiperazinesCathinonesSynthetic cannabinoidsIsolated compounds

Recreational problem identified in 2008/2009Varying legal status

GRI Emergency Dept Experience12 AMT22 synthetic cannabinoids3 cathinone2 methoxetamine1 salvia

9 life threatening toxicities

Why are people taking them?Legal statusPerception of safetyDifficult to detect

Point of care urine testingOdourless

AvailabilityInternet“Head shops”

Sold as other drugs

AMT

5-IT

Common ProblemsLack of reliable data“Not what is says on the tin”DosageInter-individual variabilityTime of onset to effectPolysubstance misuseInteractions ?

Challenges in Clinical CareAcute

Identification of xenobioticLack of toxicological data

Mechanism of action Duration Clinical effects

Appropriate treatmentChronic

Long term psychological effectsLong term physical effects

CathinonesSynthetic variations of natural cathinones in KhatMephedrone, methedrone, naphyroneIvory wave, meow-meow, bubbles, ocean snow,

NRGSympathetic Toxidrome

↑HR, RR, BP, tempTremor, agitation, paranoia, hallucinations, seizures***duration 24 – 48 hours***

TreatmentsBenzodiazepines +/- haloperidol

PiperazinesDeveloped in 1950s – anti-helminthic agentsBZP “Benzo Fury”

Neurotransmitter release/reuptake inhibitionPhenylpiperazines

Direct serotonin receptor activationReversal of serotonin uptake

ClinicallySympathetic toxidromeSerotonin toxicity?

Synthetic CannabinoidsAnnihilation, Black Mamba, Spice, K2Structurally dissimilar to THCHerbal material sprayed with chemicalsClinical effects

Nausea +++CollapseSome psychotropic effects

MethoextamineStructurally similar to ketamineNMDA receptor agonistClinically (dose related)

Excitation, tachycardia, euphoriaHallucinationsDissociationProlonged neurological effects - ataxia

Supportive management

AMT/5-ITAMT – Alphamethyltryptamine5-IT – 5-aminopropylindoleAMT researched as antidepressant in 1960’sNon-specific MAOI

Hallucinations +++Psychomotor agitation +++Serotonin toxicity

High risk of toxicity

Serotonin ToxicityExposure to a

serotonergic drugClinical features

ConfusionAutonomic

instabilityHyperkinetic

musculoskeletal system

Treatment of Serotonin ToxcityMorbidity & Mortality related to

hyperthermiaTemp ≥40 oCDuration

ConsequencesRhabdomyolysisAcute kidney injuryAcidosisCerebral damage

Treatment of Serotonin ToxicityAggressive coolingAntipyretics do not work!Control muscular activity

High dose benzodiazepinesHaloperidol for severe non-responders

Appropriate fluid controlBP control agentsAnaesthesia with muscle paralysis

The Future?Market flooded with NPSDifficult to legislate/controlLong term effects?