Novel Psychoactive Substances Flashcards
A timeline of drug control
1868: post isolation of morphine + coke Pharmacy Act: Opium sold only by pharm (kept records)
1908: Post heroin synthesis: pharm act: Morphine and Cocaine (and derivatives with more than 1%) sold only by pharmacist
1916: post MDMA synth + beg WW1: Defence of the Realm act- Offence for non-pharmacists or doctors to be in possession of cocaine – first time Home Office
becomes involved
1928: Dangerous Drugs act: Criminalising possession of cannabis –
responsibility moved to
Home from Health
ministry
1964: Post synth of Mephedrone + LSD - Drug Prevention of Misuse Act:
Amphetamines
criminalised – amended to include LSD in 1966
1977: MDMA illegal
2003: Meph. re-synth
2016: Psychoactive Substances Act
What was happening in history? (3)
- Chemists would synthesise a new drug – it would be unscheduled and therefore legal.
- Drug sold legally until the government managed to get it into the controlled drugs
category - it would then
become illegal - A new drug would be
synthesised and the cycle continues
The Psychoactive Substances Act 2016
- Legislation varies internationally – in the
UK it is now illegal to distribute or sell
novel psychoactive substances, but
possession is not a criminal offence - The Psychoactive Substances Act 2016
criminalises any substance intended for
human consumption that has a psychoactive effect…
It covers substances by virtue of their psychoactive properties, rather than the identity
of the drug or its chemical structure
Novel psychoactive substances =
compounds (former legal highs) designed to mimic existing established recreational drugs
Novel psychoactive substances can be grouped into four main categories… (4)
Stimulants (cathinone - methadone) -ST+LT
Depressants (opioids and benzo’s) - LT
Hallucinogens (psychedelics (2C family) + dissociative (-KET/PCP)
Cannabinoids (cannabis)
What is classified as a psychoactive substance?
A psychoactive substance is any substance which is: ‘capable of producing a
psychoactive effect in a person who consumes it’.
- talks about property and not the specific drug name
What did the act try to do? (4)
make it an offence to: produce, supply, possess with intent to supply, import or export
psychoactive substances
How are psychoactive properties of a novel psychoactive substance assessed under The Psychoactive Substances Act 2016? (4)
Receptor binding assay
(to determine whether the drug binds to a receptor)
Functional assay
(to determine whether the drug activates a response following
interaction with the receptor)
OR
Published literature
Accounts from a witness of behaviour exhibited by an individual who has
taken the substance may also be relevant
Receptor binding and functional assays drug e.g.’s (7)
Immobilising cells that express specific receptors, exposing them to a drug and measuring the response:
- CB1 (cannabis and synthetic cannabinoids)
- GABAA (benzodiazepines)
- 5-HT2A (e.g., psychedelics)
- NMDA (dissociative/hallucinogenic drugs e.g., ketamine)
- μ-opioid (opioid drugs e.g., heroin)
- Monoamine transporters (psychostimulants e.g., MDMA, cocaine)
Published literature and witness accounts (3)
In vitro tests are not suited to all types of substance (e.g., nitrous oxide and solvents) – alternative sources of evidence are therefore required.
Published literature: Wealth of evidence available on both in
vitro and in vivo studies by academic
researchers which can be referenced by
expert witnesses
FINAL:=
Accounts from a witness of behaviour exhibited by an individual who has taken the substance may also be relevant
What was legal? pre 2016 (3)
everything except:
Classes A-C
Schedules 1-5
What is legal? post 2016 (6)
everything is illegal except:
Alcohol
Caffeine
Food
Nicotine
Medicinal products
(controlled substances)
Is The Psychoactive Substances Act 2016 working? (4)
Before act: Total of 113 shops selling psycho. substance on internet in English + shipped to UK
After act: Only 52% remained open – those that remained were either based overseas
(65%), became a ‘headshop’ (19%) or were
inactive (16%)
Only 24% of UK-reg websters remained open after
unknown whether the UK retailers have ceased
selling or have been displaced to underground
markets (street level dealing or the hidden web
introduction to mephedrone (4)
Mephedrone is a synthetic cathinone – also known as ‘bath salts’, ‘plant food’ and ‘Meow-Meow’ (related to khat)
- Abused due to their psychostimulant and
hallucinogenic effects – similar to cocaine, MDMA, amphetamines and methamphetamines - Serious side effects including increased heart rate, chest pain, change in body temperature (sweating chills), insomnia, amnesia and seizures
- Target of intense media interest – classified as a Class B substance under The Misuse of Drugs Act 1971 in April 2010
Mephedrone MoA: (3)
- Mephedrone is a non-competitive blocker
of the DAT + (NET) and (SERT) - This means less DA, NA and 5-HT are taken up into the pre-synaptic
terminal - This leads to an increase in DA, NA
and 5-HT in the synaptic cleft, leading to increased DA, NA and 5-
HT post-synaptic receptor activation
Relative 5-HT/DA activity (determined by the DAT:SERT ratio) can be helpful in predicting
psychoactive effects, toxic effects and potential for addiction (4)
Low DAT/SERT inhibition ratio (<0.1) indicates tenfold greater relative 5-HT vs DA activity similar to MDMA
High DAT/SERT inhibition ratio (>10) indicates greater relative DA vs 5-HT activity similar to
methamphetamine
Mephedrone falls between MDMA
and methamphetamine ratios
This corresponds with the psychoactive effects of mephedrone
Mephedrone Phys effects (3)
inc seizures
dec body temp - sweats
inc BP = tachycardia
Mephedrone behavioural effects (3)
social : elated mood + impulsivity
cognitive: impairment of function (upon chronic use)
binging
Alexander Shulgin
- In 1991, Alexander Shulgin, along with his wife Ann, published PIHKAL, A Chemical Love Story (acronym representing ‘Phenethylamines I Have Known And
Loved’) - Book detailed synthesis instructions for over 200
psychedelic compounds including bioassays, dosages+ other commentaries - ‘Shulgin rating scale’ was used to report the
subjective effect of psychoactive substances at a given dosage:
-, +,++,+++,++++ - Included the ‘2C’ series…
2C series (3)
- ‘2C’ is in reference to an acronym invented
by Shulgin to describe the two carbons
between the amino group and the
benzene ring in the chemical structure - Designer substitution to the 2C structure
can result in increased hallucinogenic
activity
e.g. additions of methoxy groups at the 2 and 5 positions on the base structure ring or the substitution of iodine (6-10hrs) or bromine (4-8hrs) at the 4 position results in increased hallucinogenic effects
2C-B and 2C-I (4)
two compounds have structures that are truly analogous.
strategically located iodine atom and an identically placed
bromine atom in other
directly above and below one-another in the periodic table. And what is particularly maddening to the synthetic diddler, is that they cannot be lengthened, or shortened, or squashed around in any way.
You can’t make a longer and narrower version of a bromine atom, as you can do with, say, a butyl group. You’ve got what you’ve got, like it or not
‘2C’ series MoA (3)
- A clear mechanism of action for the ‘2C’ series yet to be established
- However, ‘2C’ compounds are partial
agonists for different subtypes of 5-HT
receptors – specifically 5-HT2A , 5-HT2B
and 5-HT2C receptors - ‘2C’ compounds have also been shown to
inhibit SERT, and to a lesser extent, NET and DAT – however, very low potency
