and the Therapeutic Potential of Cannabis in Medicine
// Cannabis as a medicine is not a new concept to the world. As we learned in the previous chapter the use of this plant dates back centuries in use as a therapeutic agent. However on the grand scale of things, we have only just recently begun to scratch the surface of how cannabinoids actually interact with our bodies.
In the late 1980’s researchers were able to demonstrate that cannabinoids inhibit adenosine cyclase (a building block of the messenger system that regulates a range of functions such as metabolism, olfaction, cell growth and differentiation.) via G-Proteins, which implied for scientists that cellular signaling was present. In 1990, molecular biologist Lisa Matsuda mapped the Cannabinoid-1 (CB-1) receptor, showing it’s affinity for THC molecules. Generally speaking CB-1 receptors are found more predominately expressed in the brain, precisely occupying synaptic terminals. CB-1 receptors are consider the most abundant G-Protein Coupled Receptors (GPCR) in the central nervous system.
It wasn’t until the 1992 discovery of anandamide; the first discovered endocannabinoid in the body that derives it’s name from the Sanskrit word ananda meaning “joy, bliss or delight”. “Endo” means coming from within, or in this sense a cannabinoid that is naturally produced by the body. This cannabinoid was recorded as binding to the CB-1 receptor similar to THC.
The second receptor, Cannabinoid-2 (CB-2) was not mapped until 1993. The CB-2 receptor is unique in comparison to the CB-1 in that concentrates on immune cells. CB-2 receptors generally reduce immune activity and down regulate inflammation. CB-2 receptors also show a lower affinity for THC and a higher affinity for CBD.
Together these from The Endocannabinoid System or The ECS. At it’s core this system is essentially a series of checks and balances for the body to maintain homeostasis and to maintain itself at the healthiest means possible. While we have this baseline understanding of the system, we have yet to fully grasp it’s full physiological potential. However we do know that is does encompass functions such as the immune system, pain, hunger urges, neurological protection and finally the bodies reward system. However, The ECS is not exclusive in the molecules that it interacts with. While previously believed to be limited to the two different cannabinoid receptors mentioned, scientists have found there is more appropriately four cannabinoid receptors and are interacting with molecules such as capsaicin (found in chili peppers) to trigger responses in what is known as the “vanilla” receptors known as (TRPV-1) to signal the “pain” information for the body to receive. Where cannabis enters the pictures is that is was believed that capsaicin was one of the few molecules that could active the TRPV-1 receptors, however to the surprise of science, these receptor sites also were found to be targets of not just anandamide but also of CBD. This could help open the doorway to explain how CBD’s role in combating pain. Even more interesting scientists have found that capsaicin will synergies with anandamide to help reduce Type 1 diabetes and combat gut inflammation.
The final receptor that has been discovered as part of a whole of the The ECS is a small entity known as the GPR-55 receptor. While as of now scientists don’t know the exact function of the GPR-55 receptor, it has been shown to be activated by not only anandamide, but 2-AG and also THC. This receptor is known to transmit and process stimuli related to pain and inflammation throughout the body and shares a scant resemblance to both the CB-1 and CB-2 receptors, some scientists have suggested recategorized as an addition to cannabinoid-receptor family and hence renamed as CB-3.
Even before the knowledge of the endocannabinoid system, physicians and patients have recognized the benefits of cannabis sativa L for thousands of years. This is due to the interaction of phytocannabinoids such as THC or CBD. As we learned earlier with endocannabinoids being an internally produced molecule, phytocannabinoids would be the inverse; as they are derived from plants.
THC is a high affinity partial agonist of the CB-1 receptor. This generates psychotropic effects when consumed in significant quantities, including but not limited to: relaxation, euphoria and perceptive time dilation. However, an end user can also experience negative effects such as anxiety, paranoia and dysphoria. As a partial agnostic activity on the CB-2 receptor augments the analgesic properties of THC.
CBD however is not considered a psychotropic agent and does not demonstrate significant affinity to either CB-receptor, yet acts as a low affinity negative allosteric modulator when attached to a CB-1 receptor. In a layman’s terms when CBD attached to the certain binding sites on the CB-1 receptor it subtly changes the shape of said receptor, making it harder for THC to bind. Essentially CBD is a molecular dimmer switch at CB-1 receptors.
In the grand scheme of things, what does this all mean? Unfortunately, for now we don’t have enough information to truly answer that question. The discovery of the endocannbinoid system is still so new in the historical context of cannabis based medicine. The current status of cannabis as a schedule 1 narcotic has made it difficult to fully research the plant to reach FDA standards for use. Despite this, the state-side regulation of cannabis has opened the doors for universities and labs to explore more of this system’s potential and how it interacts with various cannabinoids and terpenes by creating regulatory frameworks for use and production of cannabis. In Washington State for example, a portion of the tax revenue that is generated via recreational cannabis sales is directly earmarked for medical research at both the University of Washington and Washington State University.
The research industry that has been sparked in states such as Washington, Colorado and California has provided such a more comprehensive approach to the science and medicine of cannabis. While cannabis remains a Schedule I narcotic, the only federal source of research would be at the University of Mississippi, which very undoubtably has access to not only the quality of cannabis found in the aforementioned states, but may be limited in the variety of strains available to study. Unfortunately, the bureaucratic hurdles for researchers as a whole currently is very cumbersome and has stifled the growth in this sector as a whole.
Time will tell if the legislative actions in states that have legalized cannabis in some capacity have any effect on the future outlook, legally speaking- of the field. Both on a medical and recreational level. But as more time passes and more research is openly conducted, one would be inclined to believe that Congress and the Federal Government would be more open to the rescheduling of cannabis; considering it’s basis in selective information. The more we learn about the molecular composition of the endocannabinoid system, the more we understand both the role it and cannabis can play in day to day health.
