What are synthetic cannabinoids and why are they dangerous?
What is a synthetic cannabinoid?
Synthetic cannabinoids are compounds that have similar properties to plant-derived cannabinoids but are man-made. They do not include naturally occurring isomers of THC such as delta 7 THC, delta 8 THC or delta 10 THC. Most synthetic cannabinoids are agonists endocannabinoid system. They are designed to mimic THC and produce similar effects on the user as smoking marijuana. There are hundreds of individual compounds classified as synthetic THC or synthetic CBD - the vast majority of which have never been evaluated for safety. There are reports of people experiencing severe and unpredictable physical or psychological side effects after using synthetic cannabis products such as K2 or Spice. Naturally occurring forms of THC are very unlikely to lead to addiction or overdose and there is much scientific research to support this.
However, this cannot be said of synthetic cannabinoids. All of them activate the ECS in some way, but many also affect other types of receptors, such as NMDA, GABA, dopamine, serotonin or opiate receptors. When substances target several separate receptors, they are referred to as 'dirty drugs'. The result can be a myriad of unwanted or unexpected side effects.
Are synthetic cannabinoids legal?
Today, synthetic cannabinoids are illegal in most parts of the world, including the USA, Canada, the UK and Australia. But it wasn't always so. Synthetic cannabinoids have been legal in many countries. They were sold as "smoke/smoke" or legal highs in places where marijuana products were illegal. These compounds are sold under many different names, but the most widely used is K2 or Spice, which were previously available in brick-and-mortar and online stores. They often boasted brightly coloured, eye-catching packaging and had all sorts of catchy names, such as Joker, Black Mamba, Kush or Kronic.
After many reports of people suffering permanent physical or psychological side-effects after taking synthetic cannabinoids, governments began to ban them. But the problem is that once the government banned a particular molecule, manufacturers invented and marketed others that were not affected by the new regulation. It was an endless cat and mouse game between regulators and synthetic cannabis labs until finally the US federal government introduced a new law outlawing any new psychoactive substances (NPS).
This decision basically makes all substances that have a psychoactive effect illegal. Only after careful analysis can a newly created psychoactive substance become legal, not the other way around. Several prescription drugs classified as synthetic cannabinoids have gone through this process. These include Nabilone, Marinol (Dronabinol) and Dexanabinol Cannabinor and CT-3.
Spice on the black market
Banning the use of Spice didn't solve the problem - in fact it was much worse. As with other illegal drugs, manufacturers have been encouraged to produce new versions that are stronger than before. The market has moved from public trade operating in a grey area on the edge of legality to the black market. Spice, which started appearing on the streets about a year after it was banned, was from a different barrel altogether. It was far more addictive, far more potent and far more dangerous. Now millions of people are addicted to the substance. Some of them have even switched from using Spice to highly addictive drugs like heroin.
What could be behind this?
What's K2 or Spice?
Synthetic cannabis-mimicking products (such as Spice or K2) are made by spraying any amount of synthetic cannabinoids or other chemicals onto dried plant material (usually rosehip, nettle, alfalfa and other leaves). People then smoke the leaves in the same way as for cannabis products.
It was rarely known what these products contained. Most of them were a combination of a few ingredients that had not been tested at all. Harmful chemicals have even been found in some US samples, including pharmaceutical drugs such as benzodiazepines or opiates. Before the NPS ban, Spice was made entirely from synthetic cannabinoids. Now it can contain virtually anything.
Are synthetic cannabinoids dangerous?
Yes, there have been deaths related to the use of synthetic cannabinoids in the past. Apart from approved pharmaceutical products, there is no official research on synthetic cannabinoids. They are considered laboratory chemicals because little is known about their effects or safety profile. There have also been countless reports of users developing both behavioural and physical dependence on these various synthetic cannabinoids, sometimes after several weeks of use.
Not all synthetic cannabinoids are inherently dangerous or addictive, but without proper testing it is almost impossible to know which products will cause serious side effects, addiction or even death. To make matters worse, most synthetic products contain a number of these compounds, none of which are publicly known in the product. The addition of other additives such as benzoates, opiates or other drugs also pose a major risk when using these products.
Side effects observed in people who have used synthetic cannabinoids include:
- High blood pressure
- Rapid heart rate
- Altered perception
- Suicidal thoughts
- Vomiting
- Violent behaviour
- Psychosis or delirium
- Cardiac arrhythmias
- Kidney damage
- Seizures
Deaths have also been reported following the use of synthetic cannabis
Some synthetic cannabinoids are up to 100 times more potent than naturally occurring cannabinoids. It is common for people to take too much of these substances, leading to overdose. Most overdose deaths from the use of these products have been caused by dangerous foreign substances such as opiates or benzodiazepines.
A common phenomenon in cases of overdose with Spice is that they appear in waves. This suggests that there are certain batches that have a particularly high hazard. For example, in May 2018, nearly 100 people died and hundreds more suffered serious side effects after smoking Spice. Later that year, 56 people overdosed in Brooklyn, New York, and another 40 in Dallas, Texas
Types of synthetic cannabinoids
There are three main types of synthetic cannabinoids (plus hybrid cannabinoids). Some have exactly the same structure as THC or other cannabinoids produced by the cannabis plant (classic cannabinoids). Others mimic the shape and structure of endocannabinoid produced in our bodies (eicosanoids). The last group has nothing to do with any class but binds to the same receptors (non-classical cannabinoids).
1. Classical cannabinoids
Classical cannabinoids refer to compounds naturally produced by the plant or synthetic isomers of these molecules. They have the same general shape and structure as phytocannabinoids such as THC or CBD. The technical definition of a classical cannabinoid is any natural or synthetic ABC-tricyclic compound containing a benzopyran moiety. They consist of two parts - aromatic and alicyclic.
Synthetic classical cannabinoids include:
- HU-210
- 9-ketocannabinoid (nabilone)
- AM-2389
- AM-993
- AM-994
- AM-7499
- THC-O-Acetate
2. Synthetic eicosanoids
The human body produces its own cannabinoids to interact with endocannabinoid system. These compounds are classified as eicosanoids. An eicosanoid is a large group of signaling molecules similar to hormones or neurotransmitters that are formed from arachidonic acid. Several synthetic can interact with endocannabinoid system including synthetic versions of naturally occurring endocannabinoids.
Eicosanoids include:
- N-arachidonoylethanolamine - anandamide (AEA)
- 2-arachidonoylglycerol (2-AG)
- N-arachidonoyl dopamine (NADA)
- O-arachidonoyl ethanolamine (Virodhamin)
3. Non-classical cannabinoids
Once we enter the realm of non-classical cannabinoids, the possibilities are virtually endless. Non-classical cannabinoids are the most common street versions of synthetic cannabinoids. This class refers to any compounds that interact with endocannabinoid system that lacks the benzopyran ring of classical cannabinoids. They have many of the same properties as cannabinoids such as THC, but have a completely different chemical structure. Pfizer developed the first synthetic non-classical cannabinoids in the 1970s. They developed a number of AC-bicyclic and ACD-tricyclic cannabinoids such as CP-47,497. CBD is technically a non-classical cannabinoid because it lacks the benzopyran ring in its chemical structure.
There are several classes of non-classical cannabinoids:
- Naphthalicylinders - JWH-007, JWH-018, JWH-073, JWH-200, JWH-398, AM-1221, AM-2201, AM-694, WIN-55,212-2
- Phenylacetylindoles - JWH-250, RCS-8
- Cyclohexylphenols - CP-47,947, CP-55,940
- Benzoylindoles - AM-2233
- Tetramethylcyclopropyl cylinders - UR-144, XLR-11
- Adamantoylindols - 5F-AKB-48, APICA, STS-135
- Indazole carboxamides - AB-PINACA, AB-FUBINACA
- Quinolinyl ester - PB-22, 5F-PB-22
4. Hybrid cannabinoids
Hybrid cannabinoids are derived from classical and non-classical cannabinoids. The first hybrid cannabinoid was identified in 1994 by Makriyannis and Tius. Since then, pharmaceutical companies including Sanofi a Sterling-Winthrop other hybrids - some of which are currently being investigated for their medicinal value.
Hybrid cannabinoids include:
- Diarylpyrazoles - SR-141716A, SR-144528
- Aminoalkylindoles - WIN-55,212-2
- Derivatives HU-210 - AM-4030
Synthetic cannabinoids by prescription only
Most of the pharmaceutical cannabinoid drugs on the market today are synthetic. The only pharmaceutical product approved for medical use that comes directly from the marijuana plant is Sativex®.
- Cesamet® (Nabilone) - classic cannabinoid
- Epidiolex® (Cannabidiol) - a non-classical cannabinoid
- Dexanabinol® (HU-211) - hybrid cannabinoid
- Dronabinol® (trans-?9-tetrahydrocannabinol) - a classic cannabinoid
- Cannabinor® (PRS-211 375) - a non-classical cannabinoid
- CT-3 (ajulemic acid) - a classical cannabinoid
- Taranabant (MK-0364) - non-classical cannabinoid
Is Delta 8 THC a synthetic cannabinoid?
The short answer is no. Delta 8 THC is not a synthetic cannabinoid because it occurs naturally in the cannabis plant. However, products with delta 8 THC are not made by direct extraction from the cannabis plant because it is not present in high enough concentrations to be useful. You would have to process an entire field of cannabis to get even one dose of delta 8 THC. Instead, companies are converting more common cannabinoids, such as CBD, into the delta 8 THC isomer.
While the process itself is "synthetic" and requires laboratory equipment, it is a far cry from what we are talking about here in terms of synthetic cannabinoids. This process is classified as 'naturally derived'. It involves the conversion of one naturally occurring substance (CBD) into another naturally occurring substance (delta 8 THC). Unsurprisingly, delta 8 THC has never been associated with any of the harmful effects associated with true synthetic cannabinoids.
Summary: What are synthetic cannabinoids?
Synthetic cannabinoids are any man-made substances that look or act like naturally occurring cannabinoids. There are four main classes of synthetic cannabinoids - classical cannabinoids, non-classical cannabinoids, hybrid cannabinoids and eicosanoids. Naturally occurring cannabinoids such as THC or CBD are not considered 'synthetic cannabinoids'. This term specifically refers to cannabinoids that are not found in nature. This class of cannabinoids is very large and diverse and very little is known about the medicinal value, effect profile or safety of most synthetic cannabinoids. As a result of many problems with side effects and even death, all synthetic cannabinoids are considered illegal unless proven safe.
For safety reasons, we recommend sticking to natural things. Natural phytocannabinoids already have proven safety and have a long history of use.
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