Cannabis over Synthetic Cannabinoids, The Difference is Fatal

Expert in synthetic cannabinoids, Dr Caitlyn Norman, explains the crucial difference between these highly-potent compounds and cannabis.

Synthetic cannabinoids are not the same as cannabis. 

The former is up to 500 times more potent, is highly addictive and can cause extremely dangerous side effects or even death.

However, the difference between the two substances is hard to spot, especially as both can be presented as cannabis products, making purchases from unknown sources particularly risky.

This was made starkly clear earlier this week when a young woman accidentally ingested a lethal dose of synthetic cannabinoids after buying what she thought were cannabis sweets.

Sky News reported that the 23-year-old from Ilford purchased the ‘gummies’ for herself and a friend, using a phone messaging app and they were delivered to her home.

 The women, who both fell ill after consuming the sweets were taken to hospital for treatment but the older of the two sadly died on Saturday 2 April.

The news came following a virtual conference in March, held by Drug Science, which covered the different scientific, medical, technological and recreational perspectives on cannabis.

Dr Caitlyn Norman gave a particularly timely talk on the pharmacology and effects of synthetic cannabinoid receptor agonists (SCRAs).

The post-doctoral researcher at the Leverhulme Research Centre for Forensic Science, University of Dundee, explained in depth how the substances differ from cannabis.

What are cannabinoids?

There are three main categories of cannabinoids.

Endogenous cannabinoids, also known as endocannabinoids, are developed by the body, phytocannabinoids occur naturally in the cannabis plant, and synthetic cannabinoids are man made or synthesised.

“Synthetic cannabinoids are not synthetic cannabis,” she stressed. “SCRAs are full agonists of the cannabinoid receptors whereas THC is only a partial agonist.

“In addition, SCRAs have been found to be up to 500 times more potent than THC, and they can have different and more severe effects.”

The synthetic chemicals have been found to have up to 30 times higher risk of adverse effects requiring emergency treatment than cannabis.

These effects are often more typical of psychostimulants such as methamphetamine, Dr Norman said.

They can include cardiovascular effects, seizures, acute kidney injury, suppression of breathing, aggression, acute and chronic psychosis, self-harm and suicide, addiction and death.

SCRAs are also highly addictive and produce persistent cravings and strong compulsions to re-dose. 

Severe withdrawal symptoms occur soon after use and last about a week.

How they are made

SCRAs were originally synthesised for research purposes from as early as the 1940s, following the reported positive effects of cannabis.

Research papers and patents documenting cannabinoid synthesis and the effects were then published.

The first SCRAs for recreational use were identified in Germany in 2008 and the compounds were created from information in the academic literature.

Since then, the number of new SCRAs detected around the world has significantly increased.

There are 209 synthetic chemicals being monitored by the EU early warning system, and over 300 have been reported worldwide to the UN Office on Drugs and Crime.

Naming SCRAs

The early research SCRAs were named after the person or organisation that originally synthesised it. For example, JWH for John W Huffman or HU for Hebrew University.

When later openly sold in UK head shops – shops that specialise in tobacco and cannabis and related paraphernalia – a variety of names were adopted.

These included Spice, K2, Black Mamba, Banana Cream Nuke, Krypton and Lava Red.

Producers continued to create slightly new versions of the compound before legislators could outlaw them, allowing them to exist as a “legal high”.

But sale in head shops stopped in 2016 with the enactment of the Psychoactive Substances Act, a blanket ban which intended to restrict production, sale and supply.

The science bit

Binding affinity is how strongly a ligand binds to a receptor – in this case the ligand is the SCRAs or THC and the receptors are cannabinoid receptors CB1 and CB2.

It is measured as Ki. The lower the Ki value, the stronger the binding to the receptor.

THC has a far larger Ki value than synthetic cannabinoids.

Potency is the amount of drug necessary to produce an effect. Again, a lower value indicates greater potency.

“THC is not very potent, whereas SCRAs have drastically different potencies and can be up to 500 times more potent than THC,” Dr Norman said.

She added: “We now have a pretty good understanding of the parts of the cannabinoid structure that can actually impact binding and potency.”

There is also some evidence that SCRAs and their metabolites may be distributed into deeper compartments and released up to a year later for heavy users resulting in prolonged effects.

Vulnerable communities

SCRAs have rapid in vitro clearance rates and are quickly metabolised, which makes them much more difficult to detect than cannabis.

This is why they are popular among communities that are being monitored for drug use, such as prisons or probation, Dr Norman told Cannabis Health after the conference.

They are also popular among the rough sleeping community as they can be purchased at a much lower price than natural cannabis products.

In the general population intentional use of synthetic cannabinoids will be much lower and may only be seen among “psychonauts” – recreational drug users looking for a new experience.

Unintentional use of the dangerous chemical substances and adverse effects from ingestion, is usually down to suppliers infusing products with SCRAs and selling them as cannabis, which can sell at a higher price, Dr Norman said.

But they are unlikely to know the effects of the specific SCRA compound, so proper dosing is “almost impossible, thereby leading to adverse effects”.

She explained that while she does not support legalisation of cannabis, she is a proponent of the decriminalisation of the use of the drug.

“Within the prisons, there has been speculation that if they were allowed to use cannabis, then you’d see a decrease in the use of synthetic cannabinoids.

“I do think that that is the case but that still doesn’t necessarily mean you provide a legal market – maybe we just don’t test for it with mandatory drug testing.”

She added that there is no easy solution to preventing deaths from synthetic cannabinoids.

“People are going to use drugs, and it’s just figuring out how they can use drugs in the safest way possible. It’s all about harm reduction.”




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