which produce a “burning” sensation, such as capsaicin, NCPA CBD the active compound in hot peppers. They are also SOURCE sensitive to temperatures over 109 degrees. CBD acts as a partial agonist at these receptors, unlike capsaicin or heat, which are full agonists. This means CBD doesn’t produce a pain effect like that of heat or hot peppers, but it does still lead to down regulation of the receptors. Do you understand CBD’s ADENOSINE RECEPTORS Adenosine receptors are involved in a wide number of mechanisms of action? processes across the body. They are also the target of caffeine, which acts as an antagonist. CBD has an affinity for these receptors, but it exhibits both agonistic by Harry Lattanzio, RPh; Tim Gregorius, RPh; and antagonistic activities depending on several factors. More research into the exact effects of this activity is in and Evan Gregorius progress. GLYCINE RECEPTORS CBD has a similar dual action at glycine receptors. In CBD’s diverse range of effects spans many different the spinal cord, CBD typically behaves as an agonist protein targets, including receptors, enzymes, ion at these receptors which act as “pressure valves” channels, and transcription factors. CBD is an agonist, modulating the strength of pain signals. However, in the antagonist, or modulator of at least six different g brain, CBD has the opposite action, and is an antagonist protein-coupled receptors (GPCRs), the main type of at the glycine receptors. membrane receptor in plants and animals. (This gets a little technical, so it may take an extra read or two, but ORPHAN RECEPTORS hang in there!) These receptors are listed as follows. Orphan receptors are receptors which we have known about for years that don’t fit into to any of the well-clas- THE TWO CANNABINOID RECEPTORS, sified receptor systems. It has recently been discovered CB1 AND CB2 that CBD is active at these sites, but until their entire CBD is a negative allosteric modulator at the two pri- function is elucidated, they are referred to simply as mary cannabinoid receptors. This means it reduces the GPR3, GPR6, GPR12, GPR18, GPR55, and GPR92. affinity of other ligands (such as anandamide or THC) for these receptors. Ultimately, this reduced activation leads Along with the effects at various protein targets other to an increase in receptor expression, and therefore than receptors, CBD’s two free hydroxyl groups give it increased overall cellular activity. potent antioxidant activity. This contributes to many of the observed effects of CBD which cannot be attributed 5-HT1A SEROTONIN RECEPTORS to any specific biological target. Because CBD is such CBD acts as a full — yet weak an active drug throughout the entire body, it should be — agonist at 5-HT1a serotonin used cautiously due to this wide array of actions. receptors, which are the target of most SSRI medications. This article is a brief overview of a much more extensive Similar to the net effect piece that is available to our premium members at the of CBD on cannabinoid NCPA CBD Source, powered by PRS. Become a premium receptors, and SSRIs at member to learn everything you need to know about how serotonin receptors, this and why CBD works, and what that means for your cus- ultimately produces an tomer and your pharmacy. Please call us at 800-338-3688, increase in serotonin or visit us at NCPACBDSource.com to learn more. ■ signaling. Harry Lattanzio, RPh, is PRS president, and Tim Gregorius, RPh, TRPV1 RECEPTORS is PRS vice president of operations. Evan Gregorius is PRS CBD TRPV1 receptors are the scientific and industry adviser. target for compounds 22 America’s PHARMACIST | September 2020.