The therapeutic potential of cannabinoids to manage several clinical conditions, including pain, inflammation, sleep disorders, and epilepsy, is finding support through a growing body of evidence.1 With changes in legislation and attitudes toward the medical use of cannabis, more pharmaceutical companies are exploring the therapeutic use of cannabinoids while prioritizing alternate routes of delivery.
Two cannabinoids under scrutiny are tetrahydrocannabinol (THC) and cannabidiol (CBD), which use the endocannabinoid system to regulate a range of physiologic, endocrine, and immune functions. Although THC has been shown to provide therapeutic benefits, its psychoactive effects are generally unwanted. The ability to isolate CBD to target endocannabinoid receptors is paving a promising road for the development of cannabis-based pharmaceuticals.
This article takes a closer look at the mechanism underlying the clinical efficacy of cannabinoids, and reviews a selection of currently available cannabis-derived therapeutics, which may benefit patients with otherwise difficult-to-treat conditions or who are resistant to traditional pharmacotherapy.
Elucidating the therapeutic mechanism of cannabinoids
Understanding the activity of endocannabinoid receptors located throughout the body has helped researchers elucidate the mechanism of action of THC, CBD, and other cannabis-derived therapeutics. This has allowed us to target specific receptors that are involved in controlling pain and mediating the inflammatory pathway.
Cannabinoids interact with the endocannabinoid receptor isoforms CB1 and CB2. CB1 receptors are located throughout the central nervous system, whereas CB2 receptors are found in tissues of the peripheral nervous system, the digestive system, and specialized immune cells.1
The psychotropic effects of THC occur via agonism of CB1 receptors in the brain, but THC also binds CB2 receptors to modulate pain, enhance appetite, promote digestion, and stimulate emotional processes.2 CBD counters the psychoactive effects of THC through antagonism of CB1 receptors and weak inverse agonism of CB2 receptors.
However, CBD has lower affinity for CB1 and CB2 receptors compared with serotonin, adenosine, and other receptors involved in a range of inflammatory pathways. Specifically, CBD acts as an antagonist in pathways responsible for neurogenic inflammation, and mediates the nociceptive response, contributing to analgesic, anti-inflammatory, antiepileptic, and antiemetic effects.