Allosteric Modulation: The Versatility of Cannabinoid Receptors

These are exciting times for a cannabinoid researcher; new information must constantly be integrated with the growing body of knowledge surrounding the endocannabinoid system. At times, that new information can even flip our understanding of the system on its head. One great example of that is embodied in the research surrounding allosteric modulation. In our traditional understanding of the endocannabinoid system, there are two types of receptors: CB1 receptors, which are located primarily in the brain, and CB2 receptors, which are located throughout the central nervous system and immune system. CB1 receptors are known to be the primary cause of psychedelic effects from cannabis, so readers should not be surprised that THC bonds to those. In this model, receptors can either be activated or de-activated at varying degrees. For instance, a cannabinoid that barely activates a CB1 receptor would be a “weak/partial CB1 agonist”, while one that deactivates all CB2 receptors would be a “strong CB2 antagonist”. The first cannabinoids that were studied, such as THC, could adequately be described in such terms. However, as time went on, researchers began to suspect that cannabinoids could bond to our cannabinoid receptors at alternate sites, based on the knowledge that similar properties have been observed in other types of receptors. What’s the difference? Everything. Consider the process of inhibition: normal (orthosteric) inhibitors can either trap the agonist to keep it from activating the receptor or can compete with the agonist for a bonding site (effectively reducing the number of receptors that can…

Seeing is Believing: ICRS

Greetings readers, we’ve just returned from the 2015 International Cannabinoid Research Society (ICRS) conference. ICRS describes itself as “a non-political, non-religious organization dedicated to scientific research in all fields of the cannabinoids, ranging from biochemical, chemical, and physiological studies of the endogenous cannabinoid system to studies of the abuse potential of recreational Cannabis.” Many one-off or repeating conferences regarding cannabis and cannabinoid science have been held since the 70’s, after Raphael Mechoulam’s structural identification and synthesis of THC. However, ICRS represents one of the first and longest-running to focus on research stemming from Mechoulam’s later discovery of the endocannabinoid system, the system of receptors, enzymes, and neuromodulatory lipids that plays a role in a host of physiological and neurological activities. After attending almost every talk, we have a fresh stockpile of new information to report to you, straight from the frontlines of research. We will begin to unfold this information in the next few articles, but some of the most exciting new pieces involve new types of cannabinoid receptors and ways that cannabinoids can signal biological changes without receptors at all. Other new innovations in the field were highlighted by a terrific closing speech by Mechoulam, who spoke of endocannabinoid signaling that might occur through sources as unexpected as bacterial films, as well as the need for more testing to determine the actual harm cannabis might have on children. One perhaps unavoidable theme of the conference was the harmony and clash between research focusing on phytocannabinoids and synthetic cannabinoids. Although…