Cannabis is the most commonly used recreational drug in the world – as it has been for generations. Furthermore, this ancient crop is increasingly being utilised for its impressive potential in a number of medical applications. However, it is not only naturally occurring derivatives of the cannabis plant that have been gaining popularity in recent years. Both medical and recreational ‘cannabis’ sectors are beginning to see the adoption of synthetic forms of the compounds found within the plant – cannabinoids.
Cannabinoids are the most studied and perhaps therapeutically useful category of compounds found within the cannabis plants; however, there is more than one kind of cannabinoid. For example, the cannabinoids that are produced by cannabis plants are known as phytocannabinoids, while cannabinoids produced by our bodies are referred to as endo- (endogenous) cannabinoids. The third type of cannabinoids is synthetic, or man-made, cannabinoids.
What are Synthetic Cannabinoids?
Synthetic cannabinoids are compounds that have been specifically designed to mimic the effects of cannabinoids. Like natural endo- and phytocannabinoids, synthetic cannabinoids target cannabinoid receptors in the body to induce various physiological and cognitive reactions. While synthetic cannabinoids have similar structures and induce similar effects to their naturally-occurring counterparts, they are usually more potent.
One of the most commonly synthesised cannabinoids is an analogue of Δ-9 tetrahydrocannabinol (THC) – the main psychoactive compound found in cannabis plants. Synthetic cannabinoids such as these may be utilised for either medicinal and therapeutic purposes, or recreational uses.
The Medicinal Use of Synthetic Cannabinoids
Synthetic cannabinoid APIs (active pharmaceutical ingredients) has been developed at an increasing rate in recent years as evidence suggests they may be useful in the treatment of a number of different human pathologic conditions. Furthermore, various promising synthetic cannabinoid formulations are currently under clinical evaluation to determine their potential in medical treatments.
The manufacture of synthetic cannabinoid pharmaceuticals has been an important focus of research since scientists first isolated and identified the structure of THC in 1964. The aim of this research is to be able to access the therapeutic potential of these compounds in a more sustainable and cost-effective way. Examples of synthetic cannabinoids that have been approved for medicinal use include Dronabinol, Nabilone, and Rimonabant.
There are three main categories of pharmaceutical synthetic cannabinoids: Those that are identical in structure to naturally-occurring cannabinoids; those that are structurally related and developed to mimic the effects of naturally occurring cannabinoids; and those that are not structurally related to natural cannabinoids but which bind to cannabinoid receptors in the body.
Dronabinol is a synthetic form of THC – the most common cannabinoid produced by the cannabis plant. As a pharmaceutical product, Dronabinol has been approved for use in several countries for the treatment of nausea and vomiting associated with chemotherapy. It may also be considered to treat loss of appetite and weight loss in people with immunodeficiency syndrome (AIDS). Dronabinol is an example of a synthetic cannabinoid that is identical in structure to a naturally occurring cannabinoid – in this case, THC.
Nabilone, which is sold under the brand name Cesamet among others, is a pharmaceutical product constituting a synthetic cannabinoid designed to mimic THC. It has been approved for use in several countries, including the UK and the US and is considered useful for the management of vomiting and nausea. Some evidence suggests that Nabilone may also be useful in the treatment of chronic pain, pain-associated insomnia, PTSD-induced nightmares, dyskinesia and chronic anxiety. Nabilone is an example of a synthetic cannabinoid that is structurally related and developed to mimic the effects of THC.
Rimonabant is an anorectic drug that was approved for use in Europe in 2006 to treat obesity. The formulation was able to induce weight loss, increase high-density lipoprotein, and reduce triglycerides, abdominal fat, fasting glucose, and fasting insulin in patients with metabolic syndrome. However, Rimonabant was later withdrawn in 2008 due to associated side effects, including increased incidence of depression and anxiety.
Other promising synthetic cannabinoid products have been developed for the treatment of obesity, including CP-945598 (otenabant). Otenabant was developed by Pfizer with the intended purpose of treating obesity; however, clinical trials found that it may also be useful for patients with nonalcoholic steatohepatitis – a form of advanced non-alcohol liver disease. Furthermore, Surinabant, developed by Sanofi-Aventis, has been found to have promising potential in the treatment of nicotine dependence, and Drinabant – also developed by Sanofi-Aventis – may be beneficial for the treatment of cognitive impairment in patients with schizophrenia and mild Alzheimer’s disease. While these additional formulations may have promising potential, Dronabinol and Nabilone remain the only synthetic cannabinoid products to be approved for use in the UK.
Synthetic Cannabinoids as Active Pharmaceutical Ingredients
As laid out above, the synthetic formulation of products, both identical and similar to naturally-occurring cannabinoids, has been explored by the pharmaceutical industry for decades. As a result, there are now several synthetic cannabinoid active pharmaceutical ingredients (API) being clinically tested for the treatment of a wide range of conditions – and, in some cases, being actively prescribed for these purposes. However, evidence has shown that some synthetic cannabinoid formulations may also carry significant adverse effects, including anxiety, depression, and even potential for addiction. As a result, the number of synthetically produced cannabinoid APIs remains relatively low.
It is also important to note that the production of synthetic cannabinoids has also been utilised by the illegal drug market. Synthetic ‘cannabis’ products such as ‘Spice’ and ‘K2’ have increasingly been found on illicit recreational drug markets around the world. These drugs are part of a group of drugs known as ‘new psychoactive substances’ (NPS) that are intended to produce the same, or similar, effects as illegal drugs. Unfortunately, synthetic cannabis products such as these can carry significant risks and side effects, including a higher risk of developing addiction and other severe illnesses, including psychosis. Therefore, it is crucial to be aware of the differences between these illegally available synthetic cannabinoid products and APIs that have been clinically tested and approved for medicinal use.
In conclusion, approved formulations have demonstrated that synthetic cannabinoid APIs could offer safe and effective alternatives to current treatment options for a number of conditions. The synthetic cannabinoid sector of the pharmaceutical industry will likely continue to develop as patients and clinicians continue to show an interest in such alternative therapies.