The Cannabinoids Effect on Bone Formation and Bone Healing
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BONE AND JOINT PAIN (P MANTYH AND T SCHNITZER, SECTION EDITORS)
The Cannabinoids Effect on Bone Formation and Bone Healing Bitya Raphael-Mizrahi 1
&
Yankel Gabet 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review Here, we overview the latest findings from studies investigating the skeletal endocannabinoid (EC) system and its involvement in bone formation and resorption. Recent Findings The endocannabinoid system consists of endogenous ligands, receptors, and enzymes. The main cannabinoids found in the cannabis plant are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabinoid receptors CB1 and CB2 are expressed in bone and regulate bone homeostasis in rodents and humans. CBD treatment was shown to enhance fracture healing in rats. Recent studies in mice indicate that strain, age, and sex differences dictate the skeletal outcome of the EC activation. Summary CBD treatment was shown to enhance bone healing, but needs validation in clinical trials. While research shows that EC activity protects against bone loss, studies on CB1 and CB2 agonists in bone regeneration models are lacking. Whether modulating the EC system would affect bone repair remains therefore an open question worth investigating. Keywords Skeleton . Bone . Osteoporosis . Fracture . Cannabis . Cannabinoid . Endocannabinoid . CBD . CB1 receptor . CB2 receptor
Introduction A variety of therapies including opioids are frequently used to manage severe pain in both cancer and non-cancer patients. Opioids were recently found to inhibit healthy bone remodeling and promote bone loss and fractures [1, 2]. While opioid therapy maybe the most potent analgesic option for cancer patients, it is widely known that patients may develop a lifelong dependence for this narcotic substance. Thus, it is important to replace opioid treatment with an alternative pain reliving remedy with no deleterious effects and perhaps even with beneficial actions on bone homeostasis and healing. The identification of the psychoactive ingredient of cannabis/ marijuana, Δ9-tetrahydrocannabinol, THC [3], leads to the discovery of the endocannabinoid (EC) system. The EC system is a complicated endocrine system consists of ligands, receptors, and biosynthesizing and biodegrading enzymes [4]. The This article is part of the Topical Collection on Bone and Joint Pain * Bitya Raphael-Mizrahi [email protected] 1
Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 69978 Tel Aviv, Israel
endocannabinoid main endogenous ligands are Narachidonoylethanolamine (anandamide, AEA) and 2arachidonoylglycerol (2-AG) [5, 6] that are hydrolyzed by fatty acid amid hydrolase (FAAH) and monoacylglycerol lipase (MAGL) respectfully [7]. The main cannabinoid receptors are CB1 and CB2; both are G protein–coupled receptor (GPCR) class A, seven transmembrane domain [8]. While these receptors are expressed in low levels in a wide range of tissues, high levels of CB1 expression are found in the central and periph
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