Cannabis has been at the center of one of the most exciting—and underreported—developments in modern science. Marijuana plants have been used since antiquity for both herbal medication and intoxication. The current debate over the medical use of marijuana is essentially a debate over the value of its medicinal properties relative to the risk posed by its use.
Marijuana’s use as an herbal remedy before the 20th century is well documented. However, modern medicine adheres to different standards from those used in the past. The question is not whether marijuana can be used as an herbal remedy but rather how well this remedy meets today’s standards of efficacy and safety.
Thanks to the research on marijuana’s effects, there has been a discovery of, until now, unknown biochemical communication system within the human body, the Endocannabinoid System, which plays a crucial role in regulating our physiology and mood.
Research on marijuana’s effects brought the discovery of the Endocannabinoid System, which plays a crucial role in regulating our physiology, mood, and state of mind. It’s a neurotransmission system found in different zones and tissues of our body that helps regulate various metabolic processes.
Cannabinoid receptors (CB) along with endocannabinoids constitute the endocannabinoid system and these are essential for the body to function normally.
The two major cannabinoid receptors are CB1 and CB2. These are not the only cannabinoid receptors, but they were the first discovered and remain the most studied.
CB1 receptors are one of the most abundant receptor types in the brain. These receptors are the ones that interact with THC and lead to the “known” high.
CB2 receptors are more abundant outside of the nervous system, in places like the immune system. However, both receptors can be found throughout the body.
Endocannabinoids are molecules produced by our bodies, acting as messengers through cannabinoid receptors. The human body produces naturally within its cells these compounds. The two main endocannabinoids are anandamide and 2-AG.
Anandamide is an endocannabinoid that belongs within the class of fatty acid amides and is produced naturally by our body. Anandamide interacts with CB1 receptors in the nervous system and CB2 receptors in the peripheral nervous system. It usually improves mood when it reaches the neurotransmitters. Similarities can be observed in the structure of anandamide compared to that of THC, as this cannabinoid (THC) in the same way activates the CB1 receptor.
During the past decade, several studies have well established the role of 2-AG in mediating endocannabinoid synaptic signalling. Indeed, at excitatory synapses, all key components of 2-AG-mediated are ideally localized to facilitate retrograde control of neurotransmitter release.
The plant Cannabis contains about 500 different types of chemical compounds, of which about 5% make part of the phytocannabinoids family. The cannabinoids that have been studied until now are mostly for a therapeutic end, and they are: delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD). Researchers have also started to widen their studies onto cannabinoids such as Cannabinol (CBN), Tetrahydrocannabivarin (THCV) and Cannabigerol (CBG), as they show potential medical characteristics for different pre-clinical studies.
Tetrahydrocannabinol or THC as it is more commonly known as one of the main psychoactive elements in cannabis. For the first time in 1964, Dr. Raphael Mechoulam isolated THC and since then he has investigated its therapeutic potentials. Currently, there are more than 8000 articles on international medical research portals that analyse the therapeutic uses of tetrahydrocannabinol.
THC is mostly a psychoactive element and is considered an illegal substance in many countries. The legal dosage of THC in cannabinoid-based products, that are sold commercially, is <0.2.
The main therapeutic effects of THC are as follows:
For the first time around 1930 and 1940, researchers isolated CBD from the cannabis plant, . Though, only until the 1960s, Professor Rafael Mechoulam was able to describe the structure and chemical composition of the molecule. From this date, only until 2013, PubMed, a medical research database, has recorded more than 1,500 studies focusing on cannabidiol. Due to this, many scientists consider CBD as one of the most important cannabinoids that have ever been discovered.
Although all the benefits of cannabidiol are not fully known, there are many studies showing its benefits from a clinical point of view.
Its most important therapeutic effects are given by its properties:
So it is possible to administer equal amounts of CBD and THC (or higher THC) without the strong side effects that are cause by the high amounts of THC (which are psychoactive effects, tachycardia and anxiety attacks).
Up to this day there are still studies and debates surrounding the “Entourage” effect, as the theory shows that high quantity of different compounds presence can result in pharmacological interactions either synergistically or antagonistically. These interactions are in fact more effective when the treatments are based on the whole plant compounds and not simply isolated cannabinoids, such as Raphael Mechoulam first described in 1998 (Ben-Shabbat, 1998; Russo and Taming, 2011). Even though there are few studies on the entourage effect, it is thought that its effect is also due to the interaction between cannabinoids and non-cannabinoid components of the plant, like the terpenes and flavonoids.