It’s commonly known that THC is the cannabinoid in cannabis that will get you high. It does this by binding to the CB1 receptors in your brain, causing feelings of bliss and euphoria. But what does CBD do and how does it work? CBD is a little more complicated that its intoxicating cousin because it doesn’t simply bind to one receptor and cause one main effect. It indirectly affects many receptors and helps your body to produce or inhibit its own endocannabinoids and neurotransmitters.
The Endocannabinoid System
The endocannabinoid system, or ECS, is a biological system in animals that is comprised of endocannabinoids and endocannabinoid receptors. Endocannabinoids are neurotransmitters produced within the body that bind to the CB1 and CB2 endocannabinoid receptors. Examples of the endocannabinoids naturally produced in our bodies include anandamide and 2-arachidonoylglycerol (2-AG).
The endocannabinoid system is a regulatory system that helps to maintain the balance of the other various physiological system in our bodies, including our central nervous systems, immune systems, reproductive systems, and digestive systems. Endocannabinoid levels can affect mood, pain sensation, appetite, sleep, memory, and a wide variety of other bodily functions.
Phytocannabinoids, such as CBD and THC, can directly and indirectly interact with our endocannabinoid receptors, as well as other receptors in our bodies. This allows these compounds to interact with our bodies in various ways and provide their medicinal and therapeutic effects.
CBD’s Effects on the Endocannabinoid System
Although it was previously believed that CBD binds with the CB2 receptors in your endocannabinoid system it now appears that CBD doesn’t have much binding affinity for either of the endocannabinoid receptors. Instead, CBD can stimulate, inhibit, block, and modulate these and other non-cannabinoid receptors throughout your body. It can indirectly cause your body to use more of it’s own natural endocannabinoids rather than binding directly to the endocannabinoid receptors as THC does.
GPR55, or G-protein coupled receptor 55, has recently been referred to as a third, or atypical, endocannabinoid receptor. It hasn’t officially been given this designation because it’s quite different from the CB1 and CB2 receptors. It appears that the phytocannabinoid THC and the endocannabinoids anandamide and 2-AG have some binding affinity for this receptor but CBD seems to block or deactivate it.
Many studies involving GPR55 are still in the early stages but this study shows evidence of seizure reduction in relation to the blocking of GPR55 receptors by CBD.
GPR55 also appears to promote cancer growth and bone resorption. Because this receptor can be blocked by CBD, it may be a possible therapeutic target in the treatment and prevention of various forms of cancer and osteoporosis. This abstract discusses GPR55’s role in cancer and osteoporosis and mentions that GPR55 antagonists could be valuable in the treatment of these diseases.
Fatty acid-binding proteins (FABPs) are proteins that transport anandamide to fatty acid amide hydrolase (FAAH), which is an enzyme that breaks down the anandamide. Anandamide is an endocannabinoid that, when present, can help to improve mood, combat anxiety, and help with depression. CBD is able to bind to the FABPs which then creates some competition for the anandamide molecules. Blocking the transportation of anandamide to the catabolizing FAAH proteins prevents the reuptake of anandamide, resulting in higher levels of this natural endocannabinoid in your system.
Peroxisome proliferator activated receptors (PPARs) are a class of nuclear hormone receptors. Activation of these receptors can produce analgesic, neuroprotective, and anti-tumor effects. CBD has the ability to activate these receptors, which partially contributes to the way CBD can help treat cancer and Alzheimer’s disease.
TRPV1 Receptor Activation
TRPV1, or transient receptor potential vanilloid 1, detects and regulates body temperature and also controls sensations of heat and pain. TRPV1 is also referred to as the vanilloid receptor or the capsaicin receptor due to its binding affinity for these compounds. When CBD binds with the TRPV1 receptors, pain perception can be regulated and body temperature controlled. Anandamide and various other phytocannabinoids also act as TRPV1 agonists.
5-HT1a Receptor Activation
The 5-hydroxytryptamine (5-HT1a) receptor is a serotonin receptor that helps to regulate anxiety, appetite, depression, pain, nausea, and sleep. In high amounts, CBD activates these receptors and can provide relief for issues related to these physiological processes. CBDA, the raw acidic form of CBD before it undergoes decarboxylation, has an even higher binding affinity for there receptors.
CBD can also modulate the shape of the CB1 cannabinoid receptor. This is the receptor that binds with THC and produces the intoxicating effects that often occur with marijuana use. By changing the shape of the CB1 receptors, THC can no longer bind to them and cannot cause its psychoactive effects. This is the reason that cannabis products with higher levels of CBD than THC are generally non-intoxicating.
This study talks about CBD’s negative allosteric modulation of the CB1 receptors and the effects that has on THC’s efficacy. It mentions that this may explain CBD’s antipsychotic, antiepileptic and antidepressant effects.
There is a lot of talk about the benefits of CBD and all the fantastic things it can do but not many people seem to know the “how” of it. Understanding what CBD is actually doing within your body can give people a better sense of CBD’s full potential and why it’s able to help with such a wide range of different ailments. CBD is kind of like a jack of all trades when it comes to all the different receptors it can affect and physiological processes it can influence.