NCCIH Investing in Cannabinoid Research
The cannabis plant contains more than 110 cannabinoids and 120 terpenes, but the only compound that's been studied extensively is THC. All of us know a friend or relative with chronic pain that has benefited from cannabidiol (CBD). Athletes have been particularly vocal promoting the use of CBD for sports-related chronic pain. In 2017, the World Anti-Doping Agency removed CBD from its list of banned substances. And this year, the National Football League Players' Association partnered with the NFL to study marijuana and CBD as alternatives to other pain therapies, namely opioids.
Despite the increasing use of cannabinoids, the mechanism of action and efficacy of these compounds and their receptors are poorly understood. One example of how little we know is found with fish oil. Many of us take fish oil for their anti-inflammatory effects. Few of us realize our bodies convert omega-3 fatty acids Into cannabinoids that exert their effects by binding to cannabinoid receptors. Cannabinoids bind primarily to two types of cannabinoid receptors in the body -- one type found predominantly in the nervous system and one type found in the immune system. Omega-3 derived cannabinoids have a predilection for the immune system cannabinoid receptors.
To expand knowledge of these emerging therapeutic agents, NCCIH funded nine projects to help unravel the efficacy and mechanisms of minor cannabinoids and terpenes. These projects include:
Mechanism and Optimization of CBD-Mediated Analgesic Effects; Boston Children's Hospital, Boston; Zhigang He, Ph.D., B.M., and Kuan Hong Wang, Ph.D. This project will investigate how the pain-relieving effects of cannabidiol (CBD) and other minor cannabinoids may be modulated by the activity of potassium-chloride cotransporter 2 (KCC2), a chloride extruder expressed in most neurons. (Grant1R01AT010779)
Neuroimmune Mechanisms of Minor Cannabinoids in Inflammatory and Neuropathic Pain; University of California, San Francisco; Judith Hellman, M.D., and Mark A. Schumacher, M.D., Ph.D. This project will explore the effects of minor cannabinoids on inflammatory and neuropathic pain in vitro and in vivo, focusing on the interactions of the cannabinoids with the peripheral receptor called TRPV1 and a cannabinoid receptor, CB1R. (Grant1R01AT010757)
Minor Cannabinoids and Terpenes: Preclinical Evaluation as Analgesics; Research Triangle Institute, Research Triangle Park, North Carolina; Jenny L. Wiley, Ph.D. This project will evaluate purified biosynthesized minor cannabinoids and selected terpenes alone and in planned combinations to determine their potential efficacy as pain relievers against acute thermal, inflammatory, neuropathic, and visceral pain. (Grant1R01AT010773)
Identifying the Mechanisms of Action for CBD on Chronic Arthritis Pain; New York University School of Medicine, New York City; Yu-Shin Ding, Ph.D. This project will use neuroimaging studies and behavioral assessments to investigate the mechanisms of action of CBD in the modulation of chronic pain associated with osteoarthritis in a mouse model. (Grant1R21AT010771)
Synthetic Biology for the Chemogenetic Manipulation of Pain Pathways; University of Texas, Austin; Andrew Ellington, Ph.D. This project will use a novel method to evolve individual variants of cannabinoid receptor type 2 (CB2) that interact with high affinity with minor cannabinoids and evaluate the new variants in a mouse model of pain. (Grant1R21AT010777)
Exploring the Mechanisms Underlying the Analgesic Effect of Cannabidiol Using Proton Magnetic Resonance Spectroscopy; University of Utah, Salt Lake City; Deborah A. Yurgelun-Todd, Ph.D. This project will use proton magnetic resonance spectroscopy (1H-MRS) to evaluate changes in brain chemistry in critical pain-processing regions after short-term administration of a cannabis extract enriched in CBD. (Grant1R21AT010736)
Mechanistic Studies of Analgesic Effects of Terpene Enriched Extracts from Hops; Emory University, Atlanta; Cassandra L. Quave, Ph.D. This project will take a multidisciplinary approach to investigate the analgesic effects of terpenes from Humulus lupulus (hops), a plant that is closely related to cannabis and has a very similar terpene profile. (Grant1R21AT010774)
Systematic Investigation of Rare Cannabinoids With Pain Receptors; University of Illinois at Urbana-Champaign; David Sarlah, Ph.D. This project involves synthesizing several classes of rare phytocannabinoids, systematically evaluating their anti-inflammatory potential, and examining the effects of the compounds with the most potent anti-inflammatory potential on the major receptors involved in pain sensation. (Grant1R21AT010761)
Analgesic efficacy of single and combined minor cannabinoids and terpenes; Temple University, Philadelphia; Sara J. Ward, Ph.D. This project will use rodent models of pain to evaluate the effects of four biologically active components of cannabis that may act synergistically to protect against pain development and to assess the interactions of these four substances with morphine. (Grant1R01AT010778)
I look forward to learning more.