New & Emerging Psychoactive Substances

Robert Ali

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Emerging Psychoactive Substances

Most NPS have little or no history of medical use

Few comprehensive studies on toxicitymost studies based on animals work , fatal

poisonings in humans or clinical observations in intoxicated patients

Toxicity, abuse liability and risks associated with long-term use unknown

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“Legal Highs”

Piperazines2000’s

BZPTFMPPMCPP

Phenylethylamines2005

2C-B derivatives Cathinones

MephedroneMPDV

Synthetic Cannabinoids

2008

SpiceKronic

Piperazines

described as ‘failed pharmaceuticals’ no current human or veterinary pharmaceutical use Have manufacturing applications Synthetically manufactured stimulants which gained popularity in early 2000’s as

legal alternative to methamphetamine and MDMA Now often sold as counterfeit MDMA Consumed by swallowing

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Piperazines

Stimulate release and prevent reuptake of DA, 5HT and NA Mimics effects of ecstasy (MDMA) Metabolized in the liver and COMT Adverse events included hypertension, reduced

consciousness, psychotic episode, hallucinations, tachycardia, hyperthermia, coma

dangerous with seizure disorders, psychiatric illness, or coronary disease

Could be toxic if combined with MDMA or amphetamines

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Phenylethylamines

Cathinones EMCCDA cites 44 substances

HallucinogensEMCCDA cites 58 substances

2C-xD series PMA

Synthetic Cathinones“Bath Salts”

Includes MDPV, 4-MMC, mephedrone, or methylone

Sold on-line with little info on ingredients, dosage, etc.

Advertised as ‘research chemicals’, ‘plant food’, ‘bath salts’ or ‘glass cleaner’

Taken orally or by inhaling, sometimes injecteddesired effects are increase in energy, empathy,

openness, and libidoLittle known of detailed pharmacology

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Mephedrone

4-methylmethcathinone (Miaow) effect profile similar to MDMAEffects short lived and dose dependentRepeated administration common

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Mephedrone

Severe adverse effects appear dose related but are rare at typical levels of use

Interactions with other substances may be significant in risk profile

student survey of mephedrone users, more than half reported adverse effects

first fatality Sweden 2008 Most fatalities associated with the use of other

substances

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Mephedrone-related

Clinical Symptoms of Synthetic Cathinones

Agitation 82%

Combative/Violent behavior 57%

Tachycardia 56%

Hallucinations 40%

Paranoia 36%

Confusion 34%

Myoclonus/Movement disorders 19%

Hypertension 17%

Chest pain 17%

CPK elevations 9%

SOURCE: Spiller et al. (2011). Clinical Toxicology, 49, 499-505.

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2C-x

Includes 2C-B and 2C-I Synthesized Alexander Shulgin variations on the mescaline molecule Ingestion most common route of administration Can be snorted or dissolved into a liquid and placed on

blotter paper under the tongue effects usually occurs within two hours, typically last 4 to

12 hours psychoactive effects dose dependent

stimulant effect at lower doses hallucinogenic and empathogenic effects at higher doses

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25B-NBOMe

Derivative of 2C-B (N-methoxybenzyl) effects lasts about 12-16 hours Potent 5HT2A receptor agonist Google Trends shows interest in NBOMe by Australians

began in April 2012 and continues to increase in 2013 high potency increases the likelihood of individuals

overdosing responsible for the deaths

bizarre and irrational behaviour, paranoia, fear and confusion

Synthetic Cannabinoids

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Synthetic Cannabinoids

functionally similar to Δ 9-tetrahydrocannabinol (THC)

But chemically unrelated structures bind to the cannabinoid receptors initially developed over past 40 years as

therapeutic agentsoften for treatment of pain

Little known about metabolism and toxicology

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Synthetic Cannabinoids

between 100 to 800 times more potent than THC

usually available in powder form Typically 3 g of dried vegetable matter to which one

or more cannabinoids addedusually smokedoral use also reportedoften contain several chemicals in different

concentrations 17

Timeline of Synthetic Cannabinoids and Spice Products

SOURCE: Fattore & Fratta. (2011). Frontiers in Behavioral Neuroscience, 5(60), 1-12.

Cannabis vs. Cannabinoids: Effects Seen in Clinical Cases

• Most symptoms similar to cannabis intoxication:– Tachycardia– Reddened eyes– Mild sedation– Anxiousness– Memory deficits– Hallucinations– Acute psychosis

• Symptoms not typically seen after cannabis intoxication:– Nausea/vomiting– Agitation– Violent behavior– Hypertension– Seizures– Hypokalemia– Coma

SOURCES: Hermanns-Clausen et al. (In Press), Addiction; Rosenbaum et al. (2012). Journal of Medical Toxicology; Forrester et al. (2011). Journal of Addictive Disease; Schneir et al. (2011). Journal of Emergency Medicine.

Rare Events

reports of suicides associated with preceding use

seizures tachyarrhythmiasmay be carcinogenic

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Summary

• Rapid explosion in manufacture and availabilty• High interest due to their properties and their

legal status• Rapid evolving chemicals made by producers• Ingredients often not representative of claim• Fatalities haven’t really dented demand

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Why do these drugs represent challenges for policy?

Why do these drugs represent challenges for policy?

Ethical issues

Technical issues

Legislative issues

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Ethical IssuesHarm relative to other drugs

Greater levels of harm from tobacco, alcohol and illicit drugs

A demand market may become established without action

Unknown harms – is a preventive approach needed?

Potential interest to organised crime

Unintended consequencesLegitimate uses

Effects on drug markets 24

Technical Issues

Identification, analysis and harms assessments - increased resources

Displacement of law enforcement resources

Treatment capabilities

Risks from non-substance-specific impairments Driving

High risk workplaces 25

Legislative Issues

Speed of legislative response

Using other legislative models? therapeutic goods, food safety and

environmental protection legislative approaches

Upstream implications – precursor chemicals

Alternate sentencing

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Types of control

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Controls using existing consumer safety or medicines legislation

Extending, modifying or adapting existing laws and processes

Devising new legislation to tackle new substances

New Models: Ireland’s approach

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Irish legislation makes it an offence to sell, import, export or advertise “psychoactive substances”

Psychoactive substances are defined broadly

exceptions for medicines, tobacco, alcoholic beverages, approved food, controlled drugs or other substances specified by Ministerial order

New Models: Ireland’s approach

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Focus on community safety and seizure of suspicious substances

Has no possession offences

For community safety, some ability to seize small amounts may be required

Ireland’s approach

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Able to distinguish products such as petrol, which may have psychoactive property if inhaled but is sold/supplied for other purposes from products which are sold/supplied for their psychoactive properties

has reduced shopfront sales and led to closure of ‘head shops’

online sales with postal distribution remain a problem

New Models: New Zealand’s approach

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Similar to Irish scheme Adds new permit scheme to regulate

manufacture and sale of ‘low-risk’ psychoactive substances

Sponsor pays for a harm assessment for new psychoactive substance and attempts to prove the product is safe

If substance assessed as low risk of harm it will be granted a permit for sale, subject to conditions

New Zealand’s approach

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Scheme modelled on existing schemes applied to therapeutic goods

may result in substances being approved for sale for no other purpose than recreational psychoactive use

may reduce the introduction of more harmful drugs onto an uncontrolled black market, and allow point of sale and other controls to be placed on relatively safe substances

Reverse Onus of Proof Principle

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Putting the burden of proof for safety on the seller, rather than on government

Making unknown psychoactive substances prohibited unless the seller can prove that they are in fact a substance which is permitted under a law, or is otherwise subject to an exception (eg. it is safe)

Issues for Australia

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Commonwealth can only legislate to ban importation

Complementary legislation to ban sale, manufacture or advertising of new psychoactive substances needs cooperation of Commonwealth, State and Territory Governments

Administration of the scheme requires cooperation of both law enforcement and health agencies in every jurisdiction, as well as support of industry

The details…

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Should possession offences be included in diversion programs?

Precautionary seizures for possession amounts?

How to frame legislation so the state is not left with an onus to prove psychoactivity?

The details…

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Public awareness and education about the nature and risks of new psychoactive substances?

Better coordination between jurisdictions to address inconsistencies between the controls in different countries

Next steps?

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Continue extending existing drug legislation?

Introducing “Reverse onus of proof” system?

Basic safety net approach (Ireland)? New approval scheme for psychoactive

substances (New Zealand)?

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Summary

Variety of synthetic drugs and research chemicals

Many have stimulant and hallucinogenic properties

Long term harms not clearMany showing evidence of dependence

forming potential Best legislative framework still evolving