Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts

Kogan, Natalya M.; Melamed, Eitan; Wasserman, Elad; Raphael, Bitya; Breuer, Aviva; Stok, Kathryn S.; Sondergaard, Rachel; Escudero, Ana V. Villarreal; Baraghithy, Saja; Attar-Namdar, Malka; Friedlander-Barenboim, Silvina; Mathavan, Neashan; Isaksson, Hanna; Mechoulam, Raphael; Müller, Ralph; Bajayo, Alon; Gabet, Yankel; Bab, Itai

doi:10.1002/jbmr.2513

Cited by 82 publications

(56 citation statements)

References 49 publications

(81 reference statements)

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“…CBD exerts beneficial effects on bone formation and fracture healing (443) and reduces bone resorption in vivo in mice. Antagonism of GPR55, which suppresses osteoclast formation but stimulates osteoclast function, seems to underlie CBD negative effects on osteoclast function (914).…”

Section: Bone Formation and Fracture Healingmentioning

confidence: 99%

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Ligresti¹,

Petrocellis²,

Marzo³

2016

Physiological Reviews

363

337

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Apart from having been used and misused for at least four millennia for, among others, recreational and medicinal purposes, the cannabis plant and its most peculiar chemical components, the plant cannabinoids (phytocannabinoids), have the merit to have led humanity to discover one of the most intriguing and pleiotropic endogenous signaling systems, the endocannabinoid system (ECS). This review article aims to describe and critically discuss, in the most comprehensive possible manner, the multifaceted aspects of 1) the pharmacology and potential impact on mammalian physiology of all major phytocannabinoids, and not only of the most famous one ⌬ 9 -tetrahydrocannabinol, and 2) the adaptive prohomeostatic physiological, or maladaptive pathological, roles of the ECS in mammalian cells, tissues, and organs. In doing so, we have respected the chronological order of the milestones of the millennial route from medicinal/recreational cannabis to the ECS and beyond, as it is now clear that some of the early steps in this long path, which were originally neglected, are becoming important again. The emerging picture is rather complex, but still supports the belief that more important discoveries on human physiology, and new therapies, might come in the future from new knowledge in this field.

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Section: Bone Formation and Fracture Healingmentioning

confidence: 99%

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Ligresti¹,

Petrocellis²,

Marzo³

2016

Physiological Reviews

363

337

View full text Add to dashboard Cite

show abstract

“…Thus, in another investigation inhibition of the CB 1 receptor was found to be associated with resistance to ovariectomy-induced bone loss via inhibition osteoclast differentiation [ 8 ]. Finally, other studies reported enhanced bone loss in wild-type compared with CB 2 knockout mice [ 53 ] and found CBD to gain fracture healing [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Decisive role of P42/44 mitogen-activated protein kinase in Δ9-tetrahydrocannabinol-induced migration of human mesenchymal stem cells

et al. 2017

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In past years, medical interest in Δ9-tetrahydrocannabinol (THC), the major psychoactive ingredient of the Cannabis plant, has been renewed due to the elucidation of the endocannabinoid system and diverse other receptor targets involved in biological cannabinoid effects. The present study therefore investigates the impact of THC on the migration of mesenchymal stem cells (MSCs) which are known to be involved in various regenerative processes such as bone healing. Using Boyden chamber assays, THC was found to increase the migration of adipose-derived MSCs. Migration by THC was almost completely suppressed by the CB1 receptor antagonist AM-251 and to a lesser extent by the CB2 receptor antagonist AM-630. By contrast, the TRPV1 antagonist capsazepine as well as the G protein-coupled receptor 55 (GRP55) agonist O-1602 did not significantly interfere with the promigratory effect of THC. Furthermore, increased migration by THC was fully suppressed by PD98059, an inhibitor of p42/44 mitogen-activated protein kinase (MAPK) activation, and was accompanied by a time-dependent activation of this pathway accordingly. In line with the migration data, additional inhibitor experiments pointed towards a decisive role of the CB1 receptor in conferring THC-induced activation of p42/44 MAPK. Collectively, this study demonstrates THC to exert a promigratory effect on MSCs via a CB1 receptor-dependent activation of p42/44 MAPK phosphorylation. This pathway may be involved in regenerative effects of THC and could be a target of pharmacological intervention.

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“…A small number of preclinical studies have investigated the effects of CBD on bone structure and function [103,112,135]. While most have used animal models that are limited in their direct relevance to sport and/or exercise performance (e.g.…”

Section: Bone Healthmentioning

confidence: 99%

Cannabidiol and Sports Performance: a Narrative Review of Relevant Evidence and Recommendations for Future Research

et al. 2020

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Cannabidiol (CBD) is a non-intoxicating cannabinoid derived from Cannabis sativa. CBD initially drew scientific interest due to its anticonvulsant properties but increasing evidence of other therapeutic effects has attracted the attention of additional clinical and non-clinical populations, including athletes. Unlike the intoxicating cannabinoid, Δ 9-tetrahydrocannabinol (Δ 9-THC), CBD is no longer prohibited by the World Anti-Doping Agency and appears to be safe and well-tolerated in humans. It has also become readily available in many countries with the introduction of over-the-counter "nutraceutical" products. The aim of this narrative review was to explore various physiological and psychological effects of CBD that may be relevant to the sport and/ or exercise context and to identify key areas for future research. As direct studies of CBD and sports performance are is currently lacking, evidence for this narrative review was sourced from preclinical studies and a limited number of clinical trials in non-athlete populations. Preclinical studies have observed robust anti-inflammatory, neuroprotective and analgesic effects of CBD in animal models. Preliminary preclinical evidence also suggests that CBD may protect against gastrointestinal damage associated with inflammation and promote healing of traumatic skeletal injuries. However, further research is required to confirm these observations. Early stage clinical studies suggest that CBD may be anxiolytic in "stress-inducing" situations and in individuals with anxiety disorders. While some case reports indicate that CBD improves sleep, robust evidence is currently lacking. Cognitive function and thermoregulation appear to be unaffected by CBD while effects on food intake, metabolic function, cardiovascular function, and infection require further study. CBD may exert a number of physiological, biochemical, and psychological effects with the potential to benefit athletes. However, well controlled, studies in athlete populations are required before definitive conclusions can be reached regarding the utility of CBD in supporting athletic performance.

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Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts

Cited by 82 publications

References 49 publications

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Decisive role of P42/44 mitogen-activated protein kinase in Δ9-tetrahydrocannabinol-induced migration of human mesenchymal stem cells

Cannabidiol and Sports Performance: a Narrative Review of Relevant Evidence and Recommendations for Future Research

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