Cannabidiol (CBD) in Sport and Exercise Performance
Literature Search Methodology
The clinical and preclinical literature was reviewed to identify studies investigating the effects of CBD that might be relevant within a sport and/or exercise context. The online databases PubMed (MEDLINE), Web of Science (via Thomas Reuters), and Scopus were searched between April and October of 2019 using terms such as: ‘cannabinoid’ ‘cannabidiol’, ‘CBD’ and ‘cannabis’. This review focuses primarily on effects that have been demonstrated in vivo and generally avoids attempting to predict functional effects on the basis of target-oriented in vitro data, given the numerous molecular targets of CBD [92] and the fact that exercise itself induces complex biochemical changes. Nonetheless, some potential interactions are noted. As our intent was to summarise evidence on a range of potentially relevant topics, rather than provide a detailed assessment of the literature, the reader will be directed to more focused reviews, where appropriate. All doses described are oral and acute (single), unless otherwise stated.
Exercise-Induced Muscle Damage—Muscle Function, Soreness, and Injury
Exercise, particularly when strenuous, unfamiliar, and/or involving an eccentric component, can cause ultrastructural damage to skeletal muscle myofibrils and the surrounding extracellular matrix [36, 59]. This exercise-induced muscle damage (EIMD) impairs muscle function and initiates an inflammatory response [59]. While inflammation is integral to EIMD repair, regeneration, and adaptation [59], excessive inflammation may contribute to prolonged muscle soreness and delayed functional recovery [7, 158].
CBD modulates inflammatory processes [21]. In preclinical models of acute inflammation, CBD has been reported to attenuate immune cell accumulation (e.g. neutrophils, lymphocytes macrophages) [102, 130, 149, 186], stimulate production of anti-inflammatory cytokines (e.g. interleukin (IL)-4, IL-10) [190, 191, 23] and inhibit production of pro-inflammatory cytokines (e.g. IL-1β, IL-6, IL-8, tumour necrosis factor (TNF)-α) [10, 50, 55, 62, 63, 113, 130, 149, 154, 186] and reactive oxygen species [62, 130, 186]. Models demonstrating such effects have included lung injury induced by chemical treatment [149] and hypoxic–ischemia (HI) [10]; liver injury induced by ischemia-reperfusion [63, 130] and alcohol feeding [186]; myocardial [55] and renal [62] ischemia-reperfusion injuries; surgically induced oral lesions [102]; chemically induced osteoarthritis [145]; spinal cord contusion injury [113], and colitis [23, 50, 154] (see Burstein [24] for review). Anti-inflammatory effects are generally observed at higher CBD doses in vivo (e.g. ≥ 10 mg·kg−1, i.p.); although, lower doses (e.g. ~1.5 mg·kg−1, i.p.) have indicated efficacy in some studies [145]. Research investigating the effects of CBD on inflammation in humans is limited and inconclusive [94, 133].
In terms of muscle-specific inflammation, one preclinical study has investigated the effect of high-dose CBD (i.e. 60 mg·kg−1·d−1, i.p.) on transcription and synthesis of pro-inflammatory markers (i.e. IL-6 receptors, TNF-α, TNF-β1, and inducible nitric oxide synthase) in the gastrocnemius and diaphragm of dystrophic MDX mice (a mouse model of Duchenne muscular dystrophy) [91]. In this investigation, CBD attenuated mRNA expression of each marker and reduced plasma concentrations of IL-6 and TNFα. Improvements in muscle strength and coordination, as well as reductions in tissue degeneration, were also reported at this dose. Lower, but still relatively high, CBD doses (20–40 mg·kg−1·day−1, i.p.) had no functional benefits [91]. Of course, it is important to recognise that EIMD and muscular dystrophy differ in their pathophysiology, and so the effects observed in MDX mice may involve mechanisms less relevant to EIMD (e.g. skeletal muscle differentiation, autophagy) [91].
While CBD could potentially aid in muscle recovery, other anti-inflammatory agents, such as ibuprofen (a non-steroidal anti-inflammatory drug [NSAID]) have been reported to attenuate exercise-induced skeletal muscle adaptation [120]. The precise mechanism(s) underpinning these effects have not been fully elucidated, although it may be that the prevention of inflammation inhibits angiogenesis and skeletal muscle hypertrophy [120]. Human trials also suggest that ibuprofen may not influence EIMD, inflammation, or soreness [144, 175]. Thus, if CBD exerts its effects via similar mechanisms, it could possibly attenuate the benefits of training without influencing muscle function or soreness. Future studies investigating this are clearly warranted to clarify such issues and elucidate the potential benefits of CBD.
Cannabidiol (CBD) in Sport and Exercise Performance
Literature Search Methodology
The clinical and preclinical literature was reviewed to identify studies investigating the effects of CBD that might be relevant within a sport and/or exercise context. The online databases PubMed (MEDLINE), Web of Science (via Thomas Reuters), and Scopus were searched between April and October of 2019 using terms such as: ‘cannabinoid’ ‘cannabidiol’, ‘CBD’ and ‘cannabis’. This review focuses primarily on effects that have been demonstrated in vivo and generally avoids attempting to predict functional effects on the basis of target-oriented in vitro data, given the numerous molecular targets of CBD [92] and the fact that exercise itself induces complex biochemical changes. Nonetheless, some potential interactions are noted. As our intent was to summarise evidence on a range of potentially relevant topics, rather than provide a detailed assessment of the literature, the reader will be directed to more focused reviews, where appropriate. All doses described are oral and acute (single), unless otherwise stated.
Exercise-Induced Muscle Damage—Muscle Function, Soreness, and Injury
Exercise, particularly when strenuous, unfamiliar, and/or involving an eccentric component, can cause ultrastructural damage to skeletal muscle myofibrils and the surrounding extracellular matrix [36, 59]. This exercise-induced muscle damage (EIMD) impairs muscle function and initiates an inflammatory response [59]. While inflammation is integral to EIMD repair, regeneration, and adaptation [59], excessive inflammation may contribute to prolonged muscle soreness and delayed functional recovery [7, 158].
CBD modulates inflammatory processes [21]. In preclinical models of acute inflammation, CBD has been reported to attenuate immune cell accumulation (e.g. neutrophils, lymphocytes macrophages) [102, 130, 149, 186], stimulate production of anti-inflammatory cytokines (e.g. interleukin (IL)-4, IL-10) [190, 191, 23] and inhibit production of pro-inflammatory cytokines (e.g. IL-1β, IL-6, IL-8, tumour necrosis factor (TNF)-α) [10, 50, 55, 62, 63, 113, 130, 149, 154, 186] and reactive oxygen species [62, 130, 186]. Models demonstrating such effects have included lung injury induced by chemical treatment [149] and hypoxic–ischemia (HI) [10]; liver injury induced by ischemia-reperfusion [63, 130] and alcohol feeding [186]; myocardial [55] and renal [62] ischemia-reperfusion injuries; surgically induced oral lesions [102]; chemically induced osteoarthritis [145]; spinal cord contusion injury [113], and colitis [23, 50, 154] (see Burstein [24] for review). Anti-inflammatory effects are generally observed at higher CBD doses in vivo (e.g. ≥ 10 mg·kg−1, i.p.); although, lower doses (e.g. ~1.5 mg·kg−1, i.p.) have indicated efficacy in some studies [145]. Research investigating the effects of CBD on inflammation in humans is limited and inconclusive [94, 133].
In terms of muscle-specific inflammation, one preclinical study has investigated the effect of high-dose CBD (i.e. 60 mg·kg−1·d−1, i.p.) on transcription and synthesis of pro-inflammatory markers (i.e. IL-6 receptors, TNF-α, TNF-β1, and inducible nitric oxide synthase) in the gastrocnemius and diaphragm of dystrophic MDX mice (a mouse model of Duchenne muscular dystrophy) [91]. In this investigation, CBD attenuated mRNA expression of each marker and reduced plasma concentrations of IL-6 and TNFα. Improvements in muscle strength and coordination, as well as reductions in tissue degeneration, were also reported at this dose. Lower, but still relatively high, CBD doses (20–40 mg·kg−1·day−1, i.p.) had no functional benefits [91]. Of course, it is important to recognise that EIMD and muscular dystrophy differ in their pathophysiology, and so the effects observed in MDX mice may involve mechanisms less relevant to EIMD (e.g. skeletal muscle differentiation, autophagy) [91].
While CBD could potentially aid in muscle recovery, other anti-inflammatory agents, such as ibuprofen (a non-steroidal anti-inflammatory drug [NSAID]) have been reported to attenuate exercise-induced skeletal muscle adaptation [120]. The precise mechanism(s) underpinning these effects have not been fully elucidated, although it may be that the prevention of inflammation inhibits angiogenesis and skeletal muscle hypertrophy [120]. Human trials also suggest that ibuprofen may not influence EIMD, inflammation, or soreness [144, 175]. Thus, if CBD exerts its effects via similar mechanisms, it could possibly attenuate the benefits of training without influencing muscle function or soreness. Future studies investigating this are clearly warranted to clarify such issues and elucidate the potential benefits of CBD.