Transcript NPS demand reduction, Mr Gilberto Gerra, UNODC

New psychoactive substances:
exploring new frontiers
of health protection
Gilberto Gerra
Chief
Drug Prevention and Health Branch
Dark clouds at the horizon
World Drug Report 2016
database (UNODC): lifetime
• Ketamine:
15-64 years old: 0.02% - 4.0%
Youth
: 0.19% - 4.7%
• Synthetic cannabinoids
15-64 years old: 0.3% - 2.5%
Youth
: 1.10% - 13.2%
• Misc. NPS (Salvia Divinorum, Mephedrone,
MDVP, Piperazines, BZP)
15-64 years old: 0.1% - 13.5%
Youth
: 1.7% - 19.9%
NPS use prevalence: uncertain figures
Eurobarometer/ EMCDDA
NPS 8% lifetime
NPS 3% last year
0.0% lifetime to 9.7% lifetime in Europe
Mephedrone 1.9% last year in UK
Synthetic cathinones 0.2% Finland
1.2% of individuals in the US, age 13–34,
use of novel psychoactive substance lifetime
- tryptamines
- psychedelic phenethylamines
- synthetic cannabinoids
Palamar et al., 2015
.
aged 14 and over / lifetime
1.3% of Australians
synthetic cannabinoids
0.4% of Australians
new psychoactive substances
7.0% of Australians
methamphetamines lifetime
2.1% of Australians
methamphetamines
previous 12 months
Australian Institute
of Health and Welfare, 2014
Mephedrone-associated fatalities 90 cases;
Schifano et al., 2012
Fatalities involving mephedrone (National Programme
on Substance Abuse Deaths database): 30 cases
Loi et al., 2015
Deaths involving heroin
and morphine in England
and Wales have increased
by 64%, from 579 deaths
in 2012 to 952 in 2014
Wise, 2015
Office for National Statistics
Do not forget old drugs
Changes in patterns of injecting drug use in Hungary:
a shift to synthetic cathinones.
heroin
mephedrone
decreasing heroin use and the appearance of mephedrone injecting
Péterfi et al., 2014
NPS: "Internet drugs/designer drugs/legal highs"
in Sweden
Among 189 cases
of drug intoxications
at emergency departments
and intensive care units
50 substances identified:
- synthetic cannabinoid receptor agonists ("Spice")
- piperazines
- substituted phenethylamines
- synthetic cathinones
- hallucinogenic tryptamines
- piperidines
Helander et al., 2014
New psychoactive substances as adulterants of controlled drugs.
A worrying phenomenon?
173 samples believed to be MDMA, amphetamine, ketamine, cocaine,
mescaline, or methamphetamine.
The NPS adulterant most frequently observed
2-(4-bromo-2,5-dimethoxyphenyl)ethanamine
(2C-B)
- 69 different combinations of substances were detected:
- 20 involving a controlled drug combined with an NPS
- 49 involving one or more NPS that substituted the controlled drug
Giné et al., 2014
Tryptamines: monoamine alkaloid found in plants, fungi and animals
Binding serotonin receptors – hallucinogenic effects
Psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine)
α-methyltryptamine
N,N-diisopropyltryptamine
4-hydroxy-N-methyl-N-ethyltryptamine
Mephedrone, 4-methylmethcathinone(4-MMC)
or 4-methylephedrone:
Releasing dopamine/norepinephrine
Dopamine transporter inhibitor
Stimulant effects
Teeth grinding, cardiovascular problems, behavioural undercontrol
Bath salts containing substituted cathinones
White crystals often resemble legal bathing products
cathinone
mephedrone
Dizziness
Double vision
Euphoria
Blurred vision
Finding it hard to express emotions
Feeling sick and vomiting
Nightmares
Illusions
Hallucinations
Changed body image
Impaired memory and attention
Ketamine is a NMDA antagonist
Dissociative anaesthetic
Useful drugs in shock/surgery patients
because of blood pressure maintained
Phenethylamine, β-phenethylamine, or phenylethylamine
a natural monoamine alkaloid
amine in the brain
Monoamines uptake inhibitors. Stimulant effects
Phenethylamine
Piperazine
organic compound
GABA (γ-aminobutyric acid) receptor agonist
Serotonin agonist
Piperazines
Clozapine
Olanzapine
4-Bromo-2,5-dimethoxy-1- benzylpiperazine(2C-B-BZP)
1-Benzylpiperazine (BZP)
2,3-Dichlorophenylpiperazine (DCPP)
4-Chlorophenylpiperazine(pCPP)
Sold as ecstasy
Stimulant / hallucinogenic effects
Adv Pharmacol.
Bath salts, mephedrone, and methylenedioxypyrovalerone as emerging illicit drugs
that will need targeted therapeutic intervention.
Glennon, 2014
The actions of these agents resemble those of central stimulants:
- dopamine, norepinephrine, and/or serotonin reuptake inhibitors
- dopamine, norepinephrine release
Effects of neurological and/or cardiovascular nature
a broad class of agents/variety of actions
to be evaluated on a case-by-case basis
Treatment of synthetic cathinone intoxication requires
more "basic science" research
At this time, treatment is mostly palliative
J Neurochem.
3,4-Methylenedioxypyrovalerone prevents while methylone
enhances methamphetamine-induced damage to dopamine
nerve endings: β-ketoamphetamine modulation of neurotoxicity
by the dopamine transporter.
Anneken et al., 2015
Bath salts that are substrates for the DAT
and release DA (METHY, MEPH)
accentuate METH neurotoxicity
Bath salts that are non-substrate
of the DAT (MDPV) are neuroprotective,
but do cause hyperthermia
Am J Drug Alcohol Abuse.
"Bath salt" ingestion leading to severe intoxication delirium:
two cases and a brief review of the emergence of mephedrone use.
Kasick, 2012
J Emerg Med.
Bath salts intoxication: a case series.
Imam et al., 2013
intense mephedroneinduced psychosis
- Antipsychotics
- Benzodiazepines
- mechanical ventilation
- intravenous hydration
- hospitalizations and
intensive care
Addict Sci Clin Pract.
Designer drugs 2015: assessment and management.
Weaver et al., 2015
constellation of psychiatric and medical effects
- anxiety
- agitation
- psychosis
- tachycardia
- deaths
evaluating substance use in young adults or in anyone presenting
with acute neuropsychiatric complaints
- Treatment of acute intoxication:
care targeting signs and symptoms
- Long-term treatment
lack of evidence to guide treatment
Br J Pharmacol.
Differential effects of cathinone compounds and MDMA
on body temperature in the rat, and pharmacological
characterization of mephedrone-induced hypothermia.
Shortall et al., 2013
MDMA decreased 5-HT
and/or 5-hydroxyindoleacetic acid (5-HIAA)
MDMA reduced striatal homovanillic acid (HVA) levels
cathinone and meth-cathinone increased striatal HVA and 5-HIAA
Different effects on body temperature.
Clin Toxicol.
Treatment of cocaine cardiovascular toxicity: a systematic review.
Richards et al., 2016
Benzodiazepines
GABA-active agents
Calcium channel blockers
Nitric oxide-mediated vasodilators
Alpha-adrenoceptor blocking drugs
Alpha-1 blockers
Alpha-2-adrenoceptor agonists (dexmedetomidine).
Beta-blockers
β/α-blockers (labetalol and carvedilol)
Crit Rev Toxicol.
Pharmacokinetics and pharmacodynamics of
3,4-methylenedioxymethamphetamine (MDMA): inter-individual differences
due to polymorphisms and drug-drug interactions.
Rietjens et al., 2012
Carvedilol
Ketanserin
Haloperidol
Benzodiazepines
Intravenous hydration
Aggressive cooling
Correction of electrolytes
Dtsch Med Wochenschr.
Fatal brain edema after ingestion of ecstasy
and benzylpiperazine.
Balmelli et al., 2001
Excessive rehydration
The patient had severe hypervolaemic
hypotonic hyponatraemia
Measurement of serum sodium and
brain CT scan is recommended in all patients
with altered mental status after MDMA consumption
J Psychoactive Drug
Psychological Burden and Gender Differences
in Methamphetamine-Dependent Individuals in Treatment.
Simpson et al., 2016
Women reported experiencing problems
because of METH use at a younger age
Women were also more likely to have
injected METH in the past year
they reported greater severity
of drug problems compared to men
METH-dependent women had greater psychological burden,
reported more use of an emotional-coping strategy
CNS Drugs.
Methamphetamine psychosis: epidemiology
and management.
Glasner-Edwards and Mooney, 2014
The pharmacological treatment
of acute methamphetamine-induced
psychosis may include the use of
antipsychotic medications
as well as benzodiazepines
Treating anxiety
Behavioral therapy
J Addict Med.
Utilizing a Two-stage Design to Investigate the Safety and Potential Efficacy
of Monthly Naltrexone Plus Once-daily Bupropion as a Treatment for
Methamphetamine Use Disorder.
Mooney et al., 2016
Long term treatment
naltrexone (slow release/Vivitrol)
plus extended-release oral bupropion
(Wellbutrin)
smartphone-assisted
medication adherence platform
Drug Alcohol Rev.
A potential role for N-acetylcysteine in the management of methamphetamine dependence.
McKetin et al., 2016
Long term treatment
to restore homeostasis
to brain glutamate system
reducing craving
has also antioxidant properties
that protect against
methamphetamine-induced toxicity
Int J Neuropsychopharmacol.
Subjective and Cardiovascular Effects of Intravenous Methamphetamine during
Perindopril Maintenance: A Randomized, Double-Blind, Placebo-Controlled
Human Laboratory Study.
Verrico et al., 2016
Long term treatment
Angiotensin II is known to facilitate
the effects of norepinephrine
which contributes to methamphetamine's
subjective effects
angiotensin-converting enzyme (ACE) inhibitor
perindopril reduces methamphetamine's effects
Addict Biol.
A partial trace amine-associated
receptor 1 agonist exhibits properties consistent
with a methamphetamine substitution treatment.
Pei et al., 2016
Tyramine, β-phenylethylamine,
tryptamine, octopamine
are biogenic amines
present in trace levels in mammalian
nervous systems.
Curr Psychiatry Rep.
Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal.
Cooper, 2016
unpredictable and severe nature of acute intoxication
effects of long-term chronic use
symptoms relief with:
- benzodiazepines
- atypical antipsychotics
- quetiapine
Int J Cardiol.
Can your heart handle the spice:
A case of acute myocardial infarction and left
ventricular apical thrombus.
Shah et al., 2016
Case Rep Crit Care.
The Wide and Unpredictable Scope of Synthetic Cannabinoids Toxicity.
Orsini et al., 2015
- acute hypoxemic/hypercapnic respiratory failure
- acute congestive heart failure
- myocardial stunning
- non-ST-segment elevation myocardial infarction
Brain Res Bull.
brainresbull.2015.10.013. [Epub ahead of print]
The behavioral profile of spice and synthetic cannabinoids in humans.
Müller et al., 2015
Most of the observed effects
are related to sympathomimetic-cardiac
effects and neuropsychiatric manifestations
Clinical treatment is primarily based on
- intensive therapy
- supportive therapy
Clin Toxicol (Phila). A systematic review of adverse events arising
from the use of synthetic cannabinoids and their associated treatment.
Tait et al., Caldicott, 2016
Major complications:
myocardial infarction
ischemic stroke and emboli
acute kidney injury
generalized tonic-clonic seizures
psychiatric presentations
first episode psychosis
paranoia
self-harm/suicide ideation
hyperemesis
Most frequently result in tachycardia, agitation and nausea
symptomatic care
- intravenous fluids
- benzodiazepines
- anti-emetics
J Emerg Med.
Repeated Thrombosis After Synthetic Cannabinoid Use.
Raheemullah and Laurence, 2016
Thrombo-embolic events after smoking
synthetic cannabinoids:
- kidney infarcts
- pulmonary emboli
- ischemic stroke
- both venous and arterial thrombosis,
activation of coagulation or inflammatory
pathways
WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?
Australas Psychiatry.
Signs and symptoms associated with synthetic cannabinoid toxicity: systematic review.
Courts et al., 2016
tachycardia, hypertension,
nausea/vomiting
agitation, irritability, paranoia
drowsiness, aggression
hallucinations
clinicians in emergency services
should consider
synthetic cannabinoid toxicity
when evaluating young adult male patients
presenting with unexplained agitation
or cardiovascular symptoms.
Focusing on:
Intoxication emergency treatment
Chronic/long term treatment
Prevention programs / reliable information
- Disco club personnel /owners
- Rave party organizers
- Web interactions
- Low threshold interventions
Peer programs
Hydratation
Drug testing
Control mechanism
CND / MS request for WHO investigation/evaluation
CND approval after WHO report
International control
National control
16 substances under control in 58th and 59th CND Sessions
Under control at the international level:
58th session CND, 2015
AH-7921
25B-NBOMe (2C-B-NBOMe)
25C-NBOMe (2C-C-NBOMe)
25I-NBOMe (2C-I-NBOMe)
4-methylmethcathinone)
N-benzylpiperazine (BZP)
JWH-018, AM-2201
3,4-methylenedioxypyrovalerone (MDPV)
methylone (beta-keto-MDMA).
59th session CND, 2016
acetylfentanyl
MT-45
para-methoxymethylamphetamine (PMMA)
α-pyrrolidinovalerophenone (α-PVP)
para-methyl-4-methylaminorex (4,4’-DMAR)
methoxetamine (MXE)
phenazepam