The new psychoactive substances:Toxicity and management

Bruno Mégarbane, MD, PhD

Department of Medical and Toxicological Critical Care

INSERM UMRS 1144 - Paris-Diderot University

Lariboisière Hospital, Paris, France

bruno.megarbane@lrb.aphp.fr

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gTop 20 most commonly reported drugs in the ED in Europe

(n=8709 in 5529 presentations)

EuroDEN, Clin Tox 2015

Classification of NPS stimulants according to DAT/SERT ratio

5-HTDominant

DADominant

Toxicity of synthetic cathinones

N= 236

Adrenergic signs

Encephalopathy signs

Serotoninergic signs

Spiller HA. Clin Tox 2011

Organ dysfunction

1

Intoxications involving MDPV - the Swedish STRIDA project -

Beck O. ClinTox 2015

Corkery JM. Hum. Psychopharmacol Clin Exp 2013

Expected effects:

mild euphoria, empathy, increased mental clarity, sexual arousal,

intensification of sensory experience, music appreciation, visual

distortions, mood enhancement, sociability and loquacity

Adverse effects:

insomnia, nausea/vomiting, confusion and fatigue

Serotonin syndrome = possible factor in fatalities

- Structural similarities with MDMA and MDA

- A serotonin-releasing agent producing empathogenic effects

and acting as sedative, rather than generating stimulant action

Toxicity of aminoindanes, piperazines, and pipradrol derivatives

Conditioned place preference

The animal preferring to spend more time in the environment associated with the drug

Karlsson L. BCPT 2014

MEPH/methylone/MDPV produce more CPP than amphetamine

MEPH-induced environmental CPP persists for at least 3 weeks

Cathinone-induced dependence liability

Self-administration paradigms

Evaluation of drug reinforcing potential as predictor of addictive properties

Acquisition with greater potency with MDPV than amphetamineEscalation of intake at higher rather than lower MDPV doses

Watterson LR. Addict Biol 2012

Toxicity of

synthetic cannabinoids

Hermanns-Clausen M. Addiction 2012

First generation:

Nausea/vomiting,

Occasional seizures

More recent generation:

Seizures,

Cardiotoxicity,

Sympathomimetic syndrome

Serotoninergic syndrome

Cardiovascular events

Stroke

2

Ischemic stroke associated with the use of a synthetic cannabinoid (ADB-FUBINACA)

Moeller S. Asian J Psychiatry 2016

Rose DZ. Neurology 2015

Hemorrhagic stroke following synthetic cannabinoid use

Raheemullah A. J Emerg Med 2016

Repeated thrombosis after synthetic cannabinoid use

Age: 15 – 27 yrs

- Intense nausea and flank or abdominal pain

- Median peak creatinine: 6.6 mg/dL; proteinuria (N=8), casts (N=5),

RBC in urine (N=8); increased cortical echogenicity (N=9/12)

Biopsy (N=8): tubular injury (N=6); interstitial nephritis (N=3)

Detection of fluorinated SCB (XLR-11) (N=4/6)

All patients were hospitalized; one required dialysis; none died

Cannabinoids-induced AKI (N=16)

Tait RJ. Clin Tox 2016

Cannabinoid hyperemesis acute renal failure

Habboushe J. Am J Emerg Med 2014

Risk factors: male, intractable vomiting, constant hot showers

AK-47 24 Karat Gold Foil Wrapper containing herbal products, recoveredfrom a patient involved in the outbreak(12 Jul 2016, Brooklyn, New York)

Auto-mutilationsType de spice

(AM2201) Patton AL. J Forensic Sci 2013

Fatalities attributed to synthetic cannabinoids

Psychedelic hallucinogen drug belonging to the phenylethylamine family

300 time more powerful than mescaline and 1/5 time than LSD

Powerful 5-HT2A, agonist with -agonist effects

Toxicity of the psychedelic hallucinogens

N-Bome (Bromo-dragonfly)

Wood DM. JMT 2009

3

Toxicity of methoxetamine

Hill SL. Emerg Med J 2014

N=47

(High-affinity selective NMDA-R antagonist)

The first count of fentanyl deaths in 2016: Up 540% in three years

Drug overdoses killed ~ 64,000 people

Fentanyl

Heroin

Prescription analgesics

Cocaine

Methamph

Methadone

New York Times 2017

4

Intoxications involving acrylfentanyl– the Swedish STRIDA project -

Helander A. Clin Tox 2017

Efficiency of naloxone when used

Widespread folliculitis and dermatitis

Helander A. Br J Dermatol 2016

Acute skin and hair symptoms followed by severe, delayed eye

complications in subjects using the

synthetic opioid MT-45

Management of NPS-poisoned patients

Mainly in EMD > ICU

Supportive care- Fluids- Sedation (BZD) if agitation, anticonvulsive if seizures - Oxygenation if respiratory failure- Catecholamines if circulatory failure- Intubation + MV if coma or life-threatening presentation

- ECTR (hemodialysis): for electrolytic equilibrationNo role to enhance elimination

Cyproheptadine (5HTR-2A et 5HTR-2C antagonist) to treat NPS-related serotonin syndrome + external cooling, muscle paralyzing agents. Dantrolene controversial

Naloxone to reverse opioid NPS-related neuro-respiratory depression (Possible higher doses to avoid intubation)

Take home message

AgitationConfusionSeizures

Adrenergic SdSerotoninergic Sd

Organ failure

1- NPS toxicity as mainly amphetamine-like

2- Possible life-threatening presentation and organ failure

3- Importance of analytical identification

4- Supportive care

Recreational context

Negativity of the usual tox screening (opiates, cocaine,

amphetamine, THC)

- Suspect NPS intoxication

- Call the Poison Center

- Send a blood sample to a specialized Tox lab