The Basics: What Are Synthetic Cannabinoids (SCBs)? Synthetic cannabinoids are a class of man-made molecules that bind to the same receptors in our bodies (CB1 and CB2 receptors) as natural cannabinoids. Synthetic cannabinoids are commonly referred to as SCBs. Many SCBs were made with the intention of replicating the chemical structure and effects of THC and CBD. In general, we here at Leafwell would advise everyone to avoid synthetic cannabinoids (SCBs) outside of clinical settings. This is because: Synthetic cannabinoids are not usually as well-tolerated by the human body as naturally-derived plant cannabinoids. In fact, synthetic cannabinoids can be rather dangerous. Synthetic cannabinoids are often not tested for their safety. Little is known about how synthetic cannabinoids interact with the endocannabinoid system (ECS). We do not know enough about the ECS and the cannabis-derived ones, let alone synthetic cannabinoids. Get Your Medical Card Sign up to get your medical card Sign up to get your medical card What Makes Synthetic Cannabinoids Dangerous? We’ve already mentioned the three main reasons above, but to explain further, the danger comes from thinking synthetic cannabinoids are the same as, and work the same as, naturally occurring cannabinoids. SCBs should be seen as completely different from the natural versions. They may have been made with the idea of mimicking THC and CBD in mind, but the results are often far more potent and dangerous. Products like K2 and Spice, which have now been made illegal, are examples of products containing synthetic cannabinoids. They can be highly addictive and it is possible to have a deadly overdose on them. As the ECS is involved in the functioning of some extremely important bodily functions (e.g. appetite, sleep cycle regulation, metabolism, immune function), using synthetic cannabinoids can shut one of them off and have deadly consequences. Spice – inert plant material containing synthetic cannabinoids, and now illegal in the US and elesewhere in the world. Picture from https://commons.wikimedia.org/wiki/File:USMC-100201-M-3762C-001.jpg The cannabis plant naturally develops a variety of cannabinoids that are kept in balance with one another. Cannabinoids like THC are broken down rapidly by the ECS, meaning that overdose on cannabis alone is more of a theoretical than practical concern. No one has ever overdosed from cannabis alone. Synthetic cannabinoids, on the other hand, have none of these checks and balances, and the differences in their chemical structure means that they are not broken down as quickly by the human body. Where THC is a partial agonist of the CB1 receptor, a synthetic cannabinoid can be fully agonistic, and thus have more potent effects. Combined with dangerous interaction between SCBs and other receptors such as serotonin, dopamine and NMDA glutamate, and you have a substance far more dangerous than natural cannabis. Sometimes, it is not the SCB itself, but the metabolites they are broken down into by the body. These metabolites can be extremely toxic, even at low levels. Get Your Medical Card Sign up to get your medical card Sign up to get your medical card What Are Some of the Dangers of Synthetic Cannabinoid Use? SCB use can have far more deadly consequences compared to their natural counterparts. Other than an exacerbation of the negatives usually associated with overconsumption of naturally-derived cannabinoids (e.g. dry mouth, anxiety, paranoia, palpitations), SCB use has been associated with effects not at all seen with THC and CBD, including: Acute kidney injury Significantly depressed breathing Seizures Stroke Tremor Cardiac toxicity Dangerously low levels of potassium in blood serum (hypokalemia) Rapid breakdown of skeletal muscle (rhabdomyolysis) What Sorts of Products Contain Synthetic Cannabinoids? Products like K2 and Spice are usually sold as incenses or herbal mixtures for the purposes of smoking. These are now illegal, but there are still some things that reach the grey or “legal high” market. Unfortunately, SCBs can sometimes be found in tinctures and vape juices as well. There May Be Some Benefits to Using Synthetic Cannabinoids Whilst we would suggest to give SCBs a wide berth, they may have some uses in a clinical environment, under medical supervision. Synthetic cannabinoids can be made to target receptors in a very specific way and to a greater degree of precision than naturally-derived cannabinoids. The cannabis plant also contains hundreds of pharmacologically active compounds all working together. This can be an advantage with regards to safety where the negative effects of one cannabinoid are mitigated by another, but also a disadvantage in that it makes it difficult to get a specific effect. Some cannabinoids, in particular acidic ones like CBDA and THCA, are notoriously unstable and quickly turn into CBD or THC when exposed to sunlight and oxygen. Synthetic versions of these acidic cannabinoids can be made with greater chemical stability in mind. It is also possible to make semi-synthetic cannabinoids, where the natural cannabinoid can be altered to increase stability. Examples of Synthetic Cannabinoids There are hundreds of synthetic cannabinoids out there, so we cannot conceivably list all of them. We can, however, list some of the most popular ones. Dronabinol (Marinol, Syndros) Dronabinol is a synthetic form of THC that was made available in the 1980s for AIDS/HIV and cancer patients. Dronabinol is often prescribed for treating chemotherapy-induced nausea and vomiting, and as an appetite stimulant and analgesic. Dronabinol is generally well-tolerated, but many have reported it being overwhelming in its effects compared to natural THC. This could be because there aren’t other cannabinoids and terpenes counterbalancing the THC. Dronabinol is a schedule III substance, unlike THC, which is schedule I. A petitioner by the name of Jon Gettman took note of this in 2002, stating, “Cannabis is a natural source of dronabinol (THC), the ingredient of Marinol, a Schedule III drug. There are no grounds to schedule cannabis in a more restrictive schedule than Marinol.” Tetrahydrocannabinol (THC), which marinol/dronabinol mimics (but is far stronger). Author: Yikrazuul. From https://commons.wikimedia.org/wiki/File:Tetrahydrocannabinol.svg HU-210 HU-210 was first synthesized in 1988 by a group led by Professor Raphael Mechoulam at the Hebrew University. HU-210 is between 100 and 800 times more powerful than natural THC. HU-210 can potentially help prevent the inflammation caused by amyloid beta proteins involved in Alzheimer’s disease. HU-210 is also a potent analgesic. However, compared to natural THC, HU-210 is not anywhere near as tolerable, and repeated exposure may prove to be dangerous and could potentially lead to psychosis. CP 47, 497 CP 47, 497 is a very potent CB1 receptor agonist with significant analgesic effects. CP 47, 497 was developed by Pfizer in the 1980s, and is even more potent than HU-210. CP 47,497 is the main active ingredient in the herbal “incense” product Spice. Rimonabant Rimonabant is an inverse agonist of the CB1 receptor, meaning it binds to the CB1 receptor in a similar way to THC, but has the opposite effects. Rimonabant was approved in Europe as an antiobesity drug in 2006, but was withdrawn in 2008 due to the adverse effects. Data from clinical trials submitted to regulatory authorities showed that rimonabant caused depressive disorders or mood alterations in up to 10% of subjects and suicidal ideation in around 1%. Some have compared Rimonabant to tetrahydrocannabivarin (THCV), as it has similar appetite-curbing effects at low doses. Rimonobant metabolization. Yid at en.wikipedia. CC BY-SA 3.0. JWH-018 JWH-018 was synthesized by John W. Huffman at Clemson University, South Carolina. JWH-018 is a full agonist of both the CB1 and CB2 receptors, and is classed as an analgesic medication. JWH-018 has been shown to cause profound changes in CB1 receptor density following administration, causing desensitization to its effects more rapidly than related cannabinoids. JWH-018 is considered to be addictive, and has been noted to cause extreme anxiety, agitation, seizures, convulsions and even organ failure. JWH-250 JWH-250 is also a full agonist of the CB1 and CB2 receptors, and was also discovered by John W. Huffman (hence the JWH). JWH-250 is also a powerful analgesic. Like many synthetic cannabinoids, JWH-250 is not very well tolerated by humans. Synthetic cannabinoids tend to fall into one of the following seven structural groups: Naphthoylindoles (e.g. JWH-018, JWH-073 and JWH-398). Naphthylmethylindoles. Naphthoylpyrroles. Naphthylmethylindenes. Phenylacetylindoles (i.e. benzoylindoles, e.g. JWH-250). Cyclohexylphenols (e.g. CP 47,497 and homologues of CP 47,497). Classical cannabinoids (e.g. HU-210). Synthetic Cannabinoids: Overall Synthetic cannabinoids can certainly be useful in the right context. However, in a non-medical environment, they can be extremely dangerous. It is also apparent that many of these cannabinoids have entered the market because the natural ones were made illegal, which has inadvertently led to a much worse health problem reaching the public. Whilst legalizing cannabis may not have necessarily taken these products off the market completely, they probably would not have been as desirable had the natural versions been more readily available.