Q: How does cannabis work to treat pain?
A: This is a good question because chronic pain tops the list of reasons that people seek out medical cannabis for relief. According to a recent study, 62% of people using medical cannabis do so for pain relief. Additionally, a CDC report indicated it is estimated that 1 in 5 US adults has chronic pain, with about 8% stating that it limits their life or work activities on most days during the past 6 months.
Pain is a complex neurological “protective” response involving the brain and spinal cord (the central nervous system) and nerves coming in and out of the spinal cord running throughout the body (the peripheral nervous system) with cannabinoid receptors distributed all along these three levels of the ascending and descending pain pathways. There are both CB1 and/or CB2 receptors all along these areas and they are what cannabinoids interact with to create the physiological effects. It is proposed that both CB1 and CB2 agonists, molecules that bind and activate these receptors, are distributed in these regions of the brain and spinal cord and can affect pain transmission, perception and cause modulation to decrease pain.
In the periphery of our body, CB1 receptors are present in sensory nerves that bring sensation signals including pain, back to the spinal cord. CB1 and CB2 receptors are present in areas along the spinal cord called the dorsal root ganglia which is a cluster of nerves running in all along the levels of the spinal cord, bringing sensory signals in from the body. In the spinal cord, CB1 receptors are near the central canal in the dorsal lateral funiculus (the most lateral bundle of nerves) and the superficial dorsal horn, where nerves come in from the skin and muscles and internal organs to transmit and modulate pain. In the supraspinal region, CB1 receptors are found in different areas of the brain that are involved in pain processing and perception, called the thalamus, amygdala, periaqueductal gray matter, and the rostroventral medulla. Additionally, some are present in other areas of the brain called the caudate nucleus, basal ganglia, hypothalamus, and cerebellum. There are also some CB2 receptors in the cortex and cerebellum expressed on neurons and glial cells, which are the cells that support and protect nerves in the central nervous system.
There are different types of pain. Inflammatory pain comes from tissue injury and neuropathic pain from nerve injury. Chronic pain continues even though the initial injury that caused the pain is no longer present. And this making this condition is especially difficult to treat . Some studies, mostly in animals, have shown that endocannabinoids, in general, have demonstrated comparable analgesic (painkilling) properties to opioids and cyclooxygenase inhibitors which are anti-inflammatory medication, like aspirin, ibuprofen, or naproxen.
THC has been found to have anti-inflammatory and analgesic properties, in animal studies, it has been shown to suppress the physiological response to painful stimuli in spinal neurons and can be blocked by a compound called Rimonabant, a CB1 receptor antagonist (blocker). It is alternatively proposed that pain relief of THC is also mediated by other receptors outside the endocannabinoid system and can also act via opioid receptors in both acute and chronic pain; because there is evidence that its effects can be blocked by an opioid antagonist given in overdoses called Naloxone. As far as THC and its CB2 receptor, there have been many animal studies that show decreasing pain in inflammatory diseases such as, Multiple sclerosis (MS) and inflammatory bowel disease (IBS) such as Crohn’s disease and Ulcerative colitis.
CBD has low affinity for the CB1 and CB2 receptors, meaning it does not bind well to these receptors. However, it does modulate several non-endocannabinoid receptors. CBD may block mediators of inflammation to help regulate inflammatory pain and neuropathic pain. CBD is also a negative allosteric modulator, meaning it binds to other areas on the cannabinoid receptors as opposed to the main binding site. It thereby weakens the binding of THC at the main site and thus decreases its psychoactive effects. Additionally, it also decreases the associated tachycardia (high heart rate) and potential anxiety sometimes seen with THC use. The amount it will decrease these effects depending on the concentration and ratio of THC to CBD.
There is so much redundancy in our endocannabinoid system. Some may argue that THC may be best for central and neuropathic pain while CBD may be best for inflammatory pain. When comparing one to the other with respect to pain relief, in my practice I have not found that one is particularly better than the other. But in fact, I agree with some researchers who argue to use them both together in a full spectrum form with their added terpenes and flavonoids in the hopes of producing the best therapeutic effects due to synergism and the entourage effect.
Dr. Leigh Vinocur is a board-certified emergency physician who also has a cannabis consulting practice for patients and industry. She is a member of the Society of Cannabis Clinicians and a graduate of the inaugural class, with the first Master of Science in the country in Medical Cannabis Science and Therapeutics from the University of Maryland School of Pharmacy.
Originally published on greenstate.com, September 28, 2021.