novel psychoactive substances Flashcards
Timeline of drug control
- 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
What was the psychoactive substances act
Novel psychoactive substances (formerly “legal highs”) are compounds designed to mimic existing established recreational drugs
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
The Psychoactive Substances Act 2016 differs from the established approach to drug control under The Misuse of Drugs Act 1971.
It covers substances by virtue of their psychoactive properties, rather than the identity of the drug or its chemical structure.
What are the 4 main types of novel psychoactive substances
Stimulants
depressants- opioids, benzodiazepines
hallucinogens- psychedelics, dissociatives
cannabinoids- synthetic cannabinoid receptor agonists
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’.
For the purposes of the act:
A substance produces a psychoactive effect if ‘by stimulating or depressing the person’s central nervous system, it affects the person’s mental functioning or emotional state’.
How are psychoactive properties of a novel psychoactive substance assessed under The Psychoactive Substances Act 2016?
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)
Published literature
Accounts from a witness of behaviour exhibited by an individual who has taken the substance may also be relevant
Describe receptor binding and functional assays
Receptor binding assay (determine whether the drug binds to a receptor) and a functional assay (to determine whether the drug activates a response following interaction with the receptor).
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)
novel psychoactive substance L binds to GPCR,
triggers intracellular signalling cascade via phospholipase C leading to calcium release
detected using calicum sensing protein
eg Aquorin
relative response of receptor to dose can be measured
by measuring luminsecent signal
the bars on the grid can show detailed dose response against different receptors- generating dose response curve
Describe published literature and witness accounts
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
Witness accounts-Accounts from a witness of behaviour exhibited by an individual who has taken the substance may also be relevant
What changes were made about the legality and illegality of drugs after the Psychoactive substances act 2016
Before, classes A to C and schedules 1-5 were illegal, whilst everything else was legal
after the act, these became legal Alcohol Caffeine Food Nicotine Medicinal products (Controlled substances)
and everything else became illegal
Is the psychoactive substances act working?
(Oct 2015) A total of 113 shops selling novel psychoactive substances on the Internet were found in the English language and shipped to the UK
(after the act 2016)- Only 52% remained open – those that remained were either based overseas (65%), became a ‘headshop’ (19%) or were inactive (16%)
Only 24% of UK-registered websites remained open after the ban
It is 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
Mephedrone is a synthetic cathinone – also known as ‘bath salts’, ‘plant food’ and ‘Meow-Meow’
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 has methylation of amino group and benzene ring in comparison to cathinone
many drugs share structural similarity with mephedrone
eg with amphetamine, methamphetamine and cocaine
important for pharmacolgoical and physiological effects
Mechanism of action of mephedrone
Mephedrone is a non-competitive blocker of the dopamine transporter (DAT), noradrenaline transporter (NET) and serotonin transporter (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
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
What is the 2C series
‘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
For example, additions of methoxy groups at the 2 and 5 positions on the base structure ring or the substitution of iodine or bromine at the 4 position results in increased hallucinogenic effects
2CB vs 2CI- “The two compounds have structures that are truly analogous, in technical terms. In one, there is a strategically located iodine atom, and in the other, an identically placed bromine atom. These are 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 squooshed 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”
2CB was intially intented for psychotherapy but lost fur due to side effects on GI system
impact of Br and I substitution of benzene ring
but this was based on anecodotal experience
pharmacokinetics and dynamics differ
compare 2 CB and 2CI dosage andduration
single substitution can affect hallucinogenic trip
Mechanism of action of 2C series
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
