Medical Marijuana: Evidence for Medical Use

Medical Marijuana: Evidence for Medical Use

Cannabis has been used as a medical product for many centuries. In recent decades it has been discovered that the human brain and other organs contain naturally occurring cannabinoid receptors as well chemicals that bind to those receptors. This is called the endocannabinoid system. 

It is known that the endocannabinoid system has a range of important natural functions, including modulation of pain, control of movement, protection of nerve cells and a role in natural brain adaptability (plasticity), as well as a role in various metabolic, immune and inflammatory processes and a possible role in the control of tumour growth.

Plant cannabis probably works in the human body by “mimicking” the effects of the human endocannabinoid system. The main plant cannabinoids (phytocannabinoids) studied, and thought to be the most important in terms of efficacy, are tetrahydrocannabinol (THC) and cannabidiol (CBD), although many others exist and a role for them may become clearer in due course.

Whilst the medical benefits of cannabis have been known for many centuries, it is only in very recent years that a scientific rationale for the effects of cannabis on human bodily systems has been developed. In 1990 Matsuda and colleagues first described a cannabinoid receptor in several species, including man (Matsuda et al, 1990). Eventually, this receptor was called the CB1 receptor and a few years later another receptor, called CB2, was also identified (Munro et al 1993). CB1 receptors are present throughout the central nervous system and in some peripheral tissues, including the immune system, reproductive and gastrointestinal systems and are also found in the heart, lung and bladder. The CB2 receptors are mainly expressed by immune cells. 

The discovery of these cannabinoid receptors led to significant further studies on what is now termed the endocannabinoid system (ECS). The endocannabinoid system is characterised by the two primary receptors, CB1 and CB2, and the chemicals (called lipid ligands) that bind to those receptors and the mechanism of their synthesis and metabolism. The key ligands are Anandamide and 2-Arachidonoylglycerol (2-AG), although others are known. It is thought that the phytocannabinoids found in the natural cannabis plant (see Section 5) mimic the effects of the human cannabinoid receptor ligands, particularly Anandamide. The endocannabinoid system has now been identified in many bodily regions, not only the brain but also in the digestive tract and bladder (Izzo, et al 2015) and is now known to be involved in a number of metabolic (Gatta-Cherifi and Cota 2015) and endocrine (Hillard 2015) and immune (Cabral et al 2015) disorders. The ECS also seems to have a role in the
regulation of tumour growth (Velasco et al 2015).

In summary, the medical effects of herbal cannabis in man are very likely to be modulated by the phytocannabinoids found in the cannabis plant which mimic the actions of the naturally occurring cannabinoid receptor ligands. There is, of course, much more to be learnt about the effects of the endocannabinoid system. It is likely that as our knowledge of the human endocannabinoid system develops then we will be in a better position to develop strategies for improving the efficacy of cannabinoids. It may, for example, be possible to target specific cannabinoid receptors located outside the brain or receptors only expressed by a particular tissue. This may allow for better targeting of effects and limitation of side effects.