Cannabis Complex

The cannabis plant contains hundreds of different compounds – and most are difficult to formulate – but if overcoming the complexities means new medicines for unmet needs, it’s worth it.

By George E. Anastassov

June 2017

The term “medicinal marijuana” is becoming increasingly used by patients and members of the public, but it is also a misconception – medical cannabis has not been registered as a medicine in any country and, to date, only a small number of cannabinoid medicines (mostly based on synthetic cannabinoids) have reached the market. Legality, of course, is one challenge for the field, as are the negative perceptions stemming from the use of cannabis as a recreational drug, but there are also significant scientific hurdles – the cannabis plant is extremely complex, with over 100 cannabinoids and over 700 other compounds, such as flavonoids and terpenes.

Some researchers take the viewpoint that cannabis should be used in its whole form because the mixture of different compounds are what give the plant its intriguing medical properties. However, the scientific community still does not understand what every substance in the plant does, which will make it very difficult to turn the plant into a regulated medical product. The active pharmaceutical ingredient in most medicines is a single molecule that can easily be characterized. If a medicine contains two or more active molecules then development is more difficult because you must investigate the interactions between the molecules – and if you have 700 different compounds then thorough investigation becomes virtually impossible. The consequences of getting it wrong are severe. In 2016, there was a disastrous clinical trial in France involving the testing of a fatty acid amide hydrolase (FAAH) inhibitor, which resulted in a patient death. FAAH inhibitors aren’t based on cannabinoids, but FAAH is part of the pathway that cannabinoids target. Such disasters highlight the challenge of synthesizing safe compounds when you do not fully understand the biochemistry and pharmacology involved.