1. New & Emerging Psychoactive
Substances
Robert Ali

2. Emerging Psychoactive Substances
Most NPS have little or no history of medical
use
Few comprehensive studies on toxicity
most 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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3. 3

4. 4
“Legal
Highs”
Piperazines
2000’s
BZP
TFMPP
MCPP
Phenylethylamines
2005
2C-B
derivatives
Cathinones
Mephedrone
MPDV
Synthetic
Cannabinoids
2008
Spice
Kronic

5. 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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6. 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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7. Phenylethylamines
Cathinones
 EMCCDA cites 44 substances
Hallucinogens
EMCCDA cites 58 substances
2C-x
D series
PMA
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8. 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 injected
desired effects are increase in energy, empathy,
openness, and libido
Little known of detailed pharmacology
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9. Mephedrone
4-methylmethcathinone (Miaow)
effect profile similar to MDMA
Effects short lived and dose dependent
Repeated administration common
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10. 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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11. Mephedrone-related
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12. 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.

13. 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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14. 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
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15. Synthetic Cannabinoids
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16. 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 agents
often for treatment of pain
Little known about metabolism and toxicology
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17. 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 added
usually smoked
oral use also reported
often contain several chemicals in different
concentrations
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18. Timeline of Synthetic
Cannabinoids and Spice Products
SOURCE: Fattore & Fratta. (2011). Frontiers in Behavioral Neuroscience, 5(60), 1-12.

19. 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.

20. Rare Events
reports of suicides associated with preceding
use
seizures
tachyarrhythmias
may be carcinogenic
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21. 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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22. Why do these drugs represent
challenges for policy?
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23. Why do these drugs represent
challenges for policy?
 Ethical issues
 Technical issues
 Legislative issues
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24. Ethical Issues
Harm 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 consequences
Legitimate uses
Effects on drug markets
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25. 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
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26. 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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27. 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

28. 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

29. 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

30. 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

31. 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

32. 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

33. 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)

34. 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

35. 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?

36. 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

37. 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)?

38. Summary
Variety of synthetic drugs and research
chemicals
Many have stimulant and hallucinogenic
properties
Long term harms not clear
Many showing evidence of dependence
forming potential
Best legislative framework still evolving
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