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…
