Felice Nava, MD, PhDDirettore U.O. Sanità PenitenziariaFelice A. NavaDirettore U.O. Sanità PenitenziariaAzienda ULSS 6 EuganeaIntossicazioni Fatali a Causa di Pericolose Miscele Contenenti Eroina e altri Oppiodi Sintetici Lodi, 23 Novembre 2017Direttore U.O. Sanità PenitenziariaAzienda ULSS 6 Euganea – PadovaDirettore Comitato Scientifico Nazionale FeDerSerDAzienda ULSS 6 EuganeaDirettore Comitato Scientifico Nazionale FeDeSerD

• “…it is likely that the future drugs of abuse will be synthetics rather than plant products. They will be synthesized from readily available chemicals, will be very potent, and often very selective in their action. In addition, they will be marketed very addition, they will be marketed very cleverly.”Gary Henderson, Journal of Forensic Science 1988

NPS: Definition“NPS are compounds designed to mimic exitingestablished recreational drugs such as “ecstasy” (MDMA) and cannabis” Tracy et al., BMJ, 356:i6848, 2017

Club Drugs• Club drugs tend to be used by teenagers and young adults at bars, nightclubs, concerts, and parties Novel Psychoactive Substances• Psychoactive drugs which are not prohibited by the United Nations Drug Conventions but which may pose a public health

NPS vs Club Drugsparties (NIDA)• E.g. Cocaine, MDMA, Ketamine, GHB/GBL, methamphetamine

which may pose a public health threat comparable to that posed by substances listed in these conventions (UK Home Office)• E.g. Cathinones, synthetic cannabinoids, piperazines

NPS in Europe

EMCDDA Report, 2017

NPS: Categories• Stimulant NPS• Cannabinoids NPS• Hallucinogenic NPS• Depressant NPS• Opioid NPSTracy et al., BMJ, 356:i6848, 2017

Tracy et al., BMJ, 356:i6848, 2017

Tracy et al., BMJ, 356:i6848, 2017

EMCDDA Report, 2017

NPS in EuropeEMCDDA Report, 2017

Class of NPS

Opioid NPS: Generality• They are generally sold and consumed in pillor powder form• There are perhaps the least understood of the NPS• This may be because are so similar to establishedrecreational drugs• Fewer NPS opioids have apperead in isolation, butthey may be sold as part of NPS cannabinoid smokingmix (e.g. AH-7921) Tracy et al., BMJ, 356:i6848, 2017

Opioid NPS: Pharmacology (1)• Longer duration of action• They exert their euphoric effects through presynapticmu-opioid receptors• Novel agents such as AH-7921, MT-45, and novel• Novel agents such as AH-7921, MT-45, and novelfentanyls seem to have similar mechanisms of action• Animal data suggest AH-7921 has a higher overdoserisk than morphineKatselou et al., 2005; Forensic Toxicol., 356: 195-201

Opioid NPS: Pharmacology (2)• Both human case series and animal studies haveshown that naloxone can reverse the toxicity seenwith novel opioids (higher doses of naloxone required)• There have been reports of unusual toxicity relatedto the use of MT-45, including short-to-mediumto the use of MT-45, including short-to-mediumterm hearing loss• No long term NPS risk data exist, though animalmodel have shown AH-7921 to be similar to morphine in addictive potential and withdrawal effectsKatselou et al., 2005; Forensic Toxicol., 356: 195-201Helander et al., 2014; Clin Toxicol., 356: 901-904

Opioid NPS: Warming for use• Early onset (<15 years old)• Poly-drug use • Antisocial behaviour• Antisocial behaviour• Being affected by others drug use or domesticviolence, and being a child in need of or on a protection planTracy et al., BMJ, 356:i6814, 2017

Opioid NPS: Detection• There are no well evidenced screening tools for identifying problematic NPS use• Not everyone who uses NPS, or any other• Not everyone who uses NPS, or any otherestablished recreational drug, necessarily needs or wants professional help Tracy et al., BMJ, 356:i6814, 2017

Detection Method: MotivationalInterviewing• Drug class(es): Stimulant, cannabinoid, hallucinogen (dissociatives and psychedelics), depressant (opioids and benzodiazepines)• Method(s) of use: Oral ingestion, nasal insufflation (“snorting”), intravenous injection, rectal insertion• Drug consumption patterns: Quantity, frequency; concomitantconsumption of prescribed or over-the-counter medication or alcohol or other recreational drugs. Use of cigarettes• Acute and chronic harmfull effects: Physical and psychological sequelae, risks from impulsive behaviour, including sexual health. Impact on mentalhealth and social functioning. Identification of individual vulnerabilities, riskof exploitation by others, and potential safeguarding issues towards othersTracy et al., BMJ, 356:i6814, 2017

The FRAMES motivational interviewing model for encouraging engagement and self responsibility with drug useFeedback - Discuss the potential adverse outcomes and drug use, individualised to the person’s pattern of use, and listen their responsesResponsibility – Emphasise that it is up to the individual to decide if they wishto change their behaviorAdvice – Straighforward advice on how dru use can be chngedMenu – Provide the individual with their therapeutic options, and facilitate theirdecision makingEmpathy – Have a non-judgmental and warm clinical approachSelf-efficacy – Project optimism that they have the ability to positively changetheir life if they so wishHester RK, Miller WR. Handbook of alcoholism treatment approaches. 2° ed. Allyn and Bacon, 1995

‘Traditional’ drug users • Heroin users moving to mephedrone injecting?• Some evidence from EMCDDA• Other anecdotal• Other anecdotal• But, evidence of injecting of NPS and club drugs

Clinical Scenario 1: Emergency Presentation• Clinical and behaviour presentation• Assessment and management of toxicityTracy et al., BMJ, 356:i6814, 2017

Clinical Scenario 1: Emergency PresentationA 29 year old man is bought into emercency department by ambulanceafter acting erratically with staff at a nightclub. On arrival, he is pacing,agitated, and midly aggressive. On examination, his heart rate is 130 bpm,blood pressure 160/95 mm Hg, temperature 38.5°C, and he has dilatedpupils, increased tone and hyperreflexia in his lower limbs, and 5-6 beats of pupils, increased tone and hyperreflexia in his lower limbs, and 5-6 beats of inducible ankle clonus. His friends told paramedics he hadtaken a “whitepowder” which he bought as a legal high on the internet.

Clinical Scenario 1: Emergency Presentation• Clinical and behaviour presentationSerotoninergic syndromeTracy et al., BMJ, 356:i6814, 2017

Clinical Scenario 1: Emergency Presentation• Assessment and management of toxicityBenzodiazepines (reduces agitation, hypertension, tachycardia, ect.)Tracy et al., BMJ, 356:i6814, 2017

Cyproheptadine – oral 5-HT2A antagonist (reducesthe excess serotonin concentrations)Cold intravenous fluids (reduces hyperpyrexia)

Clinical Scenario 2: Chronic Use• Exploring harmful use and dependency

Tracy et al., BMJ, 356:i6814, 2017

Clinical Scenario 2: Chronic UseA 24 year old woman presents to her GP with low mood and feeling “up and down”. She admits she is concerned about her use of “spice”, whichshe has been smoking regularly for several years, but she is not sure shewants professional help with this at the moment. She says that most of her friends use similar drugs, and she does not think she woulddiscontinue use completely

Tracy et al., BMJ, 356:i6814, 2017

Clinical Scenario 2: Chronic Use• Exploring harmful use and dependencyDetox (OST for Opioid NPS)RehabRehabHarm minimizationTracy et al., BMJ, 356:i6814, 2017

Challenge for specialist drug services• Clinical staff have poor knowledge of changing patterns of drug use• ‘technical’ knowledge (what are the drugs, how do they work)they work)• ‘cultural’ knowledge (who is using, how are they using)• ‘clinical’ knowledge (how to clinical manage acute/chronic presentation)• ‘service’ knowledge (when and where to refer)

How and where treat<

Take Home Messages• Most standard urinary drug test have limited sensitivityand specificity to NPS• Discuss risks and encorouge reduction in the frequency and quantity of harmful NPS use (cautionwith BDZs or Opioids can lead to physical withdrawal)with BDZs or Opioids can lead to physical withdrawal)• In case of Opioid NPS evaluate the need of OST• Offer referral to drug and alcohol treatment services or other professionals, (e.g. psychiatry, sexual health or social service when appropriate

Felice Nava, MD, PhDDirettore U.O. Sanità PentienziariaAzienda ULSS 16 PadovaTel. 049-8214904Fax 049-8214908felicealfonso.nava@aulss6.veneto.itfelicealfonso.nava@aulss6.veneto.itDirettore Comitato Scientifico Nazionale FeDerSerDwww.federserd.ithttp://www.felice-nava.itfelnava@tin.it