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Oral human equivalent CBD doses from mouse and rat intraperitoneal doses
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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...
Contexts in source publication
Context 1
... the number of preclinical studies involving animal models that will be discussed in this review, it is important to consider interspecies dose equivalence (Table 1). The USA Food and Drug Administration [30] recommend the following approach to interspecies dose conversion: ...Context 2
... (i.p.) dosing is often used in animal studies and has been reported to elicit C max values ~7-fold higher than oral dosing in mice [52]. Thus, an "oral equivalent dose" can be approximated by multiplying the i.p. dose by seven [9] (Table 1). Intravenous (i.v.) dosing will produce even higher plasma CBD concentrations; however, the authors are not aware of any published data that would facilitate conversion between i.v. and oral dosing in rodents. ...Similar publications
Phytocannabinoids are psychotropic substances ofcannabis with the ability to bind endocannabinoid (eCB) receptors that regulate synaptic activity in the central nervous system (CNS). Synthetic cannabinoids (SCs) are synthetic analogs of Δ9-tetrahydrocannabinol (Δ9-THC), the psychotropic compound of cannabis, acting as agonists of eCB receptor CB1....
Citations
... It is becoming more prevalent in various sports and competition levels [3]. Unlike THC, CBD is no longer prohibited by the World Anti-Doping Agency (WADA) and is generally considered safe and well-tolerated in humans [4]. In contrast to recreational use, medical cannabis therapy aims to enhance or modulate the body's extensive endocannabinoid system (ECS)-a complex, interactive, and crucial regulatory network responsible for maintaining homeostasis. ...
Introduction and Objective. Cannabis, particularly its active compounds THC (tetrahydrocannabinol) and CBD (cannabidiol), has gained attention in the sports community for its potential therapeutic benefits. Researchers are exploring its use in managing pain, reducing inflammation, enhancing recovery, and alleviating anxiety, making it appealing for treating both acute injuries and chronic conditions in athletes. While CBD is considered safe, THC can impair cognitive functions, potentially affecting performance and increasing the risk of injury. Unlike THC, CBD is not prohibited by the World Anti-Doping Agency (WADA) and is well-tolerated in humans. Methods. A literature review was conducted using PubMed and Google Scholar, searching terms like "CBD", "THC", "cannabinoids", "physical activity", and "medical marihuana". Articles from the last five years were prioritized. Brief description of the State of Knowledge. Cannabinoids interact with the body's endocannabinoid system (ECS) and are classified into phytocannabinoids (from cannabis), endocannabinoids (produced by the body), and synthetic cannabinoids (man-made). The two most studied phytocannabinoids are THC, which is psychoactive, and CBD, known for therapeutic benefits like anxiety reduction without intoxication. THC activates both CB1 receptors (in the brain) and CB2 receptors (in immune cells), while CBD modulates these receptors indirectly. Cannabinoids show potential in managing chronic pain, inflammation, and neurological conditions, with some studies suggesting they could replace opioids for pain relief. They may help in injury recovery among athletes. Conclusions. The consumption of CBD and THC offer both benefits and risks. However, there is insufficient evidence on the direct impact of cannabis use on athletes beyond its role in pain management and recovery. Further research is needed to provide stronger evidence on their effects in sports.
... Apesar de não haver numerosos estudos específicos que analisem os canabinóides como auxiliares de recuperação no exercício, muitos marcadores inflamatórios têm sido associados à dor muscular de início tardio, fadiga muscular e inflamação. O CBD, por sua vez, tem sido associado à produção de citocinas anti-inflamatórias, por exemplo, interleucina IL-4, IL-10, e à inibição da produção de citocinas pró-inflamatórias -IL-1β, IL-6, IL-8, o que pode estar relacionado à recuperação muscular acentuada (Mccartney et al, 2020). Além disso, a recuperação e desempenho esportivo para muitos atletas, estão associados com a qualidade do sono, que também, em doses altas, é influenciada pela interação do CBD com o sistema endocanabinóide. ...
... Os ensaios com foco na dor crônica incluíram um amplo espectro de condições, incluindo neuropática, inflamatória, central, musculoesquelética e reumatológica. Ensaios clínicos que investigam os efeitos combinados de THC e CBD na dor neuropática crônica produziram resultados iniciais promissores de alívio da dor (Mccartney et al, 2020) (Maurer et al, 2020). ...
... Consequently, CBD has the potential to limit blood brain barrier permeability, improve cerebral functional connectivity, and the heart-brain axis interactions following mTBI [4,24]. To date, no research has examined CBDmediated neuroprotection in elite contact sport athletes, but such effects have been inferred [3,4,27]. Furthermore, specific dosage, pharmacokinetic, and pharmacodynamic data are lacking, or are difficult to compare between studies that use different sources of CBD [28]. ...
Background
Cannabinoids such as cannabidiol (CBD) exhibit anti-inflammatory properties and have the potential to act as a therapeutic following mild traumatic brain injury. There is limited evidence available on the pharmacological, physiological and psychological effects of escalating CBD dosages in a healthy, male, university athlete population. Furthermore, no dosing regimen for CBD is available with implications of improving physiological function. This study will develop an optimal CBD dose based on the pharmacokinetic data in contact-sport athletes. The physiological and psychological data will be correlated to the pharmacokinetic data to understand the mechanism(s) associated with an escalating CBD dose.
Methods/design
Forty participants will receive escalating doses of CBD ranging from 5 mg CBD/kg/day to 30 mg CBD/kg/day. The CBD dose is escalated every two weeks in increments of 5 mg CBD/kg/day. Participants will provide blood for pharmacological assessments at each of the 10 visits. Participants will complete a physiological assessment at each of the visits, including assessments of cerebral hemodynamics, blood pressure, electrocardiogram, seismocardiogram, transcranial magnetic stimulation, and salivary analysis for genomic sequencing. Finally, participants will complete a psychological assessment consisting of sleep, anxiety, and pain-related questionnaires.
Discussion
This study will develop of an optimal CBD dose based on pharmacological, physiological, and psychological properties for future use during contact sport seasons to understand if CBD can help to reduce the frequency of mild traumatic injuries and enhance recovery.
Trial registration
Clinicaltrials.gov: NCT06204003.
... Recently, attention has been focused on cannabidiol (CBD), a cannabinoid in the marijuana plant, that lacks psychoactive properties thus having promising results for the treatment of pain in several disease conditions [15,16], for physical health and fitness, and for possible use in athletes, due to a number of physiological, biochemical, and psychological effects potentially useful in improving performance, cell damage, and fatigue recovery, related to physical and cognitive exertion in sports, see [17][18][19] for recent review. ...
... The opioid and cannabinoid systems also influence other aspects of health and fitness with possible use in athletes due to physiological, biochemical, and psychological effects potentially capable of ameliorating several aspects related to physical and cognitive exertion in sports (see [17][18][19], for recent review). Table 2 summarizes the main features of opioids' and cannabinoids' effects, risks, and uses in sport. ...
Pain is an unpleasant sensory and emotional experience. Adequate pain control is often challenging, particularly in patients with chronic pain. Despite advances in pain management, drug addiction, overtreatment, or substance use disorders are not rare. Hence the need for further studies in the field. The substantial progress made over the last decade has revealed genes, signalling pathways, molecules, and neuronal networks in pain control thus opening new clinical perspectives in pain management. In this respect, data on the epigenetic modulation of opioid and cannabinoid receptors, key actors in the modulation of pain, offered new perspectives to preserve the activity of opioid and endocannabinoid systems to increase the analgesic efficacy of opioid- and cannabinoid-based drugs. Similarly, upcoming data on cannabidiol (CBD), a non-psychoactive cannabinoid in the marijuana plant Cannabis sativa, suggests analgesic, anti-inflammatory, antioxidant, anticonvulsivant and ansiolitic effects and supports its potential application in clinical contexts such as cancer, neurodegeneration, and autoimmune diseases but also in health and fitness with potential use in athletes. Hence, in this review article, we summarize the emerging epigenetic modifications of opioid and cannabinoid receptors and focus on CBD as an emerging non-psychoactive cannabinoid in pain management in clinical practice, health, and fitness.
... Interaction with the 5-HT1A receptors is also associated with anxiolytic effects [34]. The potential mechanisms of action of the CBD are described in more detail in the following works [35,36]. ...
Athlete performance and post-load recovery can be considered one of the most important and actively discussed topics in professional sport. One substance aimed at improving performance is cannabidiol (CBD), which has been actively gaining popularity with several studies published in recent years. The PubMed, Scopus, and Cochrane Library databases were searched from inception to April 2024 according to PRISMA recommendations to identify studies on the effects of CBD on exercise capacity and post-load recovery. An initial search identified 901 publications, of which seven fully met the inclusion criteria. Current evidence supports a limited beneficial effect of CBD on a number of physiological parameters, such as VO2, mean power, and relative mean power. At the same time, there were limited data on the beneficial effects of CBD on strength parameters (including vertical jump, counter movement jump, one repetition max bench press, and barbell back squat) and post-load recovery. Notably, most of the studies included in the analysis were conducted between 2021 and 2024, indicating a growing interest among researchers in the use of CBD in healthy, physically active individuals. Further studies are needed to assess the safety of different CBD administration protocols in professional athletes.
... Cannabis is capable of inducing psychological effects on mood, perception, and cognition, as well as somatic effects to the cardiovascular, respiratory, digestive, immune, neurologic, and endocrine systems [11,12]. Like the general population, the majority of athletes report using cannabis for social reasons [13]; however, a significant percentage of athletes used it to improve sports performance via its perceived benefits on pain management, recovery, sleep promotion and reducing anxiety, among other things [14][15][16][17]. While the ergolytic versus ergogenic benefits have been hotly debated over the years [18,19], cannabis has been on the World Anti-Doping Agency (WADA) prohibited list since 2004 due to it fulfilling the latter two of the three criteria: potential to enhance sport performance, actual or potential health risk to the athlete, and violating spirit of the sport [20,21]. ...
... Studies for cannabis use in chronic pain are more robust and have shown moderate pain reduction and opioid-sparing effects in several different patient populations including those with cancer and non-cancer related pain, as well as neuropathic pain [41][42][43]. CBD use has been linked to decreased inflammatory marker IL-6 and improvement in sleep at higher doses [17], which hypothetically may help athletes recover from training [16,44,45]. While it has not been directly studied in the setting of sports related anxiety, CBD has been shown to have anxiolytic effects under 'stress inducing' conditions in both healthy participants and those with social anxiety disorder [17]. ...
... CBD use has been linked to decreased inflammatory marker IL-6 and improvement in sleep at higher doses [17], which hypothetically may help athletes recover from training [16,44,45]. While it has not been directly studied in the setting of sports related anxiety, CBD has been shown to have anxiolytic effects under 'stress inducing' conditions in both healthy participants and those with social anxiety disorder [17]. Some studies have even postulated that cannabis my play a role in recovery from concussion given the ECS role in traumatic brain injury [16,17,46]. ...
Abstract and ARP Position Statement
Based on the available body of scientific evidence and with the goals of promoting safety of combat sports athletes and striving for the advancement of clean sport, the Association of Ringside Physicians recommends the following regarding cannabis:
●Use of marijuana or synthetic cannabinoids by combat sports athletes is discouraged due to unproven benefits and many known adverse effects. Acute use can impair cognition and complex motor function, which likely leads to reduced performance in combat sports. Chronic use can increase risk for heart and lung disease, several cancers, schizophrenia, and can reduce testosterone in men and impair fertility. Benefits from cannabis in most contexts, including athletic performance, have not been proven.
●Use of topical purified CBD is neither encouraged nor discouraged.
●Since acute cannabis intoxication can impair complex cognitive and motor function, any athlete suspected of acute intoxication at the time of competition – based on clinical judgment – should be banned from that competition.
●Wide-scale regulation of cannabis based on quantitative testing has limited usefulness in combat sports, for the following reasons:
○Cannabis is not ergogenic and is likely ergolytic.
○Concentrations in body fluids correlate poorly with clinical effects and timing of use.
○Access to testing resources varies widely across sporting organizations.
... [30] With the recent legal opening for the medicinal prescription of cannabinoids, as well as an allocation for recreational use with greater popular acceptance, studies have begun to emerge. Although the publication rate on CBD worldwide is relatively low due to some administrative processes regarding the local pharmaceutical institution [31], scientists' interest has increased significantly, implying the need to direct efforts based on the evidence gathered to date. 3 In sports, recently published narrative reviews on the effect of cannabidiol and its relationship with performance [32] and recovery [33] suggest that CBD possesses anti-inflammatory, neuroprotective, and analgesic effects, and also promotes the healing of traumatic skeletal injuries. Additionally, early-stage clinical studies suggest that CBD may have anxiolytic effects, and some evidence points to an improvement in sleep. ...
... Additionally, early-stage clinical studies suggest that CBD may have anxiolytic effects, and some evidence points to an improvement in sleep. [32,33] Based on this evidence, and understanding the need to orient future research on CBD and sports recovery, this systematic review aims to: a) systematize the first and second-level scientific evidence related to the study of CBD, b) associate the biomedical properties attributed to CBD with those required for optimal fatigue recovery, and c) recommend a future research agenda related to the role of CBD in recovery. ...
... [30,109] A single 300mg CBD dose alters human glucocorticoid levels including the key inflammatory regulator cortisol [70], that is considered as one of the main homeostatic regulators of the inflammatory response to injury. [110] A recent narrative review proposed CBD's anti-inflammatory effects in humans could benefit athletic performance [32], potentially by interacting with inflammation-modulating receptors (e.g., CB1, CB2, A2A) and attenuating pro-inflammatory cytokines including IL-1, TNFα, thus suppressing hyperactive immune responses and associated tissue damage. [30,92,93] There is also evidence suggesting the potential of CBD to promote the release of arachidonic acid, leading to greater healing capacity as a result of central regulation of growth signals mediated by pro-resolving substances such as lipoxin A4 and 15d-PGJ2. ...
Recovery between physical efforts is essential for optimal performance in sports. Dietary supplements like cannabidiol (CBD) have been proposed to facilitate recovery and performance optimization. This systematic review aimed to: a) systematize the scientific evidence on CBD for recovery, b) associate CBD's biomedical properties with those required for optimal fatigue recovery, and c) recommend a future research agenda. Searches across databases identified 70 relevant studies from 1990-2022, including 38.6% preclinical, 31.4% clinical trials, and 30.0% reviews/meta-analyses across various populations like mice, rats, epileptics, and athletes. CBD demonstrated potentially beneficial properties for athlete recovery such as anti-inflammatory, neuroprotective, anxiolytic, and analgesic effects with doses ranging from 5-600mg administered orally, intravenously, and via other routes. However, rigorous confirmatory research specifically in athlete populations is lacking. While CBD appears promising for facilitating recovery and performance optimization, further randomized placebo-controlled trials are needed to test the acute and chronic effects of different CBD dosing regimens in athletes. Future research should focus on elucidating CBD's physiological mechanisms of action as they relate to post-exercise recovery, as well as its comparative effectiveness versus conventional medications and therapies. Advancing our understanding of CBD's role in athlete recovery could provide new therapeutic strategies to optimize recovery and performance.
... Within the last 10 years, there have been noteworthy increases within the scientific literature on cannabidiol (CBD) research, as it has been suggested to have potential therapeutic properties aiding in inflammation, anxiety, sleep, well-being, musculoskeletal conditions, and vascular function [1,5,18,28,47]. The inflammatory potential of CBD has recently taken the spotlight within the context of exercising populations, with past and current active adults and athletes alike claiming advocacy for CBD usage without evidence-based support to encourage its efficacy [5,[27][28]. Thus, the rapid influx of CBD curiosity and usage in exercising populations has exposed an immense gap in the scientific literature concerning the potentially harmful or beneficial effects of various cannabis constituents on exercising individuals' vascular health. ...
... Within the last 10 years, there have been noteworthy increases within the scientific literature on cannabidiol (CBD) research, as it has been suggested to have potential therapeutic properties aiding in inflammation, anxiety, sleep, well-being, musculoskeletal conditions, and vascular function [1,5,18,28,47]. The inflammatory potential of CBD has recently taken the spotlight within the context of exercising populations, with past and current active adults and athletes alike claiming advocacy for CBD usage without evidence-based support to encourage its efficacy [5,[27][28]. Thus, the rapid influx of CBD curiosity and usage in exercising populations has exposed an immense gap in the scientific literature concerning the potentially harmful or beneficial effects of various cannabis constituents on exercising individuals' vascular health. ...
... Thus, the rapid influx of CBD curiosity and usage in exercising populations has exposed an immense gap in the scientific literature concerning the potentially harmful or beneficial effects of various cannabis constituents on exercising individuals' vascular health. As evidence of potential positive and negative influence grows, the safety profile of CBD continues to be provoked [18][19]28]. ...
Cannabis and its compound constituents are being used globally for medicinal and recreational purposes. There has been a growing interest in the use of cannabis, specifically cannabidiol (CBD), and its potential effects on vascular health measures. However, no study has investigated the use of CBD vascular health measures via flow-mediated dilation (FMD) ultrasound assessment. This review aims to critically evaluate emerging evidence of the influence of CBD on vascular health via FMD ultrasound assessment in exercising populations. Examining associations among CBD use, vascular health, and exercise may enhance understanding of how cannabis constituents affect cardiovascular response during exercise. Illuminating the cardiovascular effects of CBD on exercising populations is vital for researchers and sports practitioners, given the global use of this cannabinoid and its potential to interact with exercisers' vascular health and exercise performance. While few examinations of CBD and FMD have shown effects on performance and vascular health, studies of adequate rigor to demonstrate cannabinoid effects on FMD require future research.
... CBD increases 5-HT levels in the mouse brain and modulates 5-HT 1A mediated responses in vivo [17]. Studies have shown that the antidepressant, anxiolytic, and anticonvulsant activities of CBD are related to the modulation of the 5-HT system [18,19]. Fogaça et al. showed that CBD regulation of 5-HT 1Amediated neurotransmission in the prelimbic medial prefrontal cortex influences anxiety [20]. ...
Cannabis sativa has been used for improving sleep for long history. Cannabidiol (CBD) has drown much attention as a non-addictive psychoactive component in Cannabis sativa extract. However, the effects of CBD on sleep architecture and it’s acting mechanism remains unclear. In the present study, we evaluated the sedative-hypnotic effect of cannabidiol (CBD), assessed the effects of CBD on sleep using a wireless physiological telemetry system. We further explored the therapeutic effects of CBD using 4-chloro-dl-phenylalanine (PCPA) induced insomnia model and changes in sleep latency, sleep duration and intestinal flora were evaluated. CBD shortened sleep latency and increases sleep duration in both normal and insomnia mice, and those effects were blocked by 5-HT1A receptor antagonist WAY100635. We determined that CBD increases 5-HT1A receptors expression and 5-HT content in the hypothalamus of PCPA-pretreated mice and affects tryptophan metabolism in the intestinal flora. These results showed that activation of 5-HT1A receptors is one of the potential mechanisms underlying the sedative-hypnotic effect of CBD. This study validated the effects of CBD on sleep and evaluated its potential therapeutic effects on insomnia.
... In addition, there is emerging evidence about the potential applications of cannabinoids within sports medicine, especially CBD. Unlike tetrahydrocannabinol (THC), CBD lacks side efects and is safe and well-tolerated in human studies [4,[6][7][8]. ...
... Following the shift from being a prohibited to an allowed substance, CBD has quickly become a booming multibilliondollar industry in sports. Several professional athletes have new lines of CBD products marketed for various claims, including pain relief, improvements in sports performance anxiety, and postexercise recovery [6,20]. Leas et al. revealed that in April 2019, Google searches for CBD surpassed acupuncture by a factor of 7.49, meditation by 3.38, exercise by 1.59, and marijuana by 1.13 with 6.4 million searches [2]. ...
Objectives. There is growing evidence regarding cannabinoid use in sports medicine and performance, especially cannabidiol (CBD). This study aims to determine if sports medicine physicians are recommending cannabinoids for therapeutic purposes, as well as analyze perceptions of cannabinoids within sports medicine and performance. Methods. Physician members of the American Medical Society for Sports Medicine (AMSSM) completed an anonymous survey on demographics, CBD and Cannabis recommendations, as well as attitudes toward cannabinoid products within sports medicine. Factors associated with CBD and cannabis recommendations as well as perceptual differences were found using multivariate regression modelling. Results. Responses from 333 physicians were recorded. The following groups were less likely to agree with allowing cannabis for recreational purposes: female gender (coeff. = 0.79 (0.33–1.25), p = 0.001 ), increasing age (coeff. = 0.04 (0.02, 0.07), p < 0.001 ), and rural respondents (compared to baseline urban, coeff. = 1.16 (0.36, 1.95), p = 0.004 ). Similarly, these three factors were associated with a higher likelihood of disagreeing with WADA removing cannabis from the prohibited substance list and with the NCAA allowing CBD use by collegiate athletes ( p ≤ 0.045 ). CBD was less likely to be recommended by pediatricians, rural physicians, and academic physicians ( p ≤ 0.030 ). Male physicians and younger physicians were less likely to identify cannabis as performance-enhancing ( p ≤ 0.042 ). Conclusions. Sports medicine physicians have varying views on cannabinoids. While sports medicine physicians generally have favorable attitudes toward CBD and cannabis, these perceptions appear to be significantly affected by age, practice type, and gender.
