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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, Δ9-tetrahydrocannabinol (Δ9-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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R E V I E W A R T I C L E Open Access
Cannabidiol and Sports Performance: a
Narrative Review of Relevant Evidence and
Recommendations for Future Research
Danielle McCartney
, Melissa J. Benson
, Ben Desbrow
, Christopher Irwin
, Anastasia Suraev
Iain S. McGregor
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
-tetrahydrocannabinol (Δ
-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 nutraceuticalproducts. 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-inducingsituations 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.
Keywords: Cannabidiol, CBD, Cannabis, Cannabinoid, Athletic performance, Exercise
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* Correspondence:
The University of Sydney, Faculty of Science, School of Psychology, Sydney,
New South Wales 2050, Australia
The University of Sydney, Lambert Initiative for Cannabinoid Therapeutics,
Sydney, New South Wales, Australia
Full list of author information is available at the end of the article
McCartney et al. Sports Medicine - Open (2020) 6:27
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Key Points
CBD has been reported to exert a number of
physiological, biochemical, and psychological effects
that have the potential to benefit athletes.
The available evidence is preliminary, at times
inconsistent, and largely based on preclinical studies
involving laboratory animals.
Rigorous, controlled investigations clarifying the
utility of CBD in the sporting context are warranted.
Cannabis sativa contains numerous chemical com-
pounds with potential bioactive effects, including at least
144 cannabinoids [56,76]. The most studied of the can-
nabinoids are Δ
-tetrahydrocannabinol (Δ
-THC), re-
nowned for its distinctive intoxicating effects [73,123],
and cannabidiol (CBD)a non-intoxicating cannabinoid
that is particularly enriched in industrial hemp cultivars
grown for seed and fibre [61]. CBD was first isolated in
1940 and initially considered to be biologically inactive,
with no apparent therapeutic or subjectivedrug effects
[1]. However, in 1973, Carlini et al. [27] demonstrated
anticonvulsant effects of CBD in a preclinical model,
which were later mirrored in humans suffering from in-
tractable epilepsy [46]. A subsequent rise in research
into CBD [206] has uncovered interactions with numer-
ous molecular targets [92] and a range of potential
therapeutic applications [138]. Following successful
phase 3 clinical trials [53,54,172], the oral CBD solu-
tion, Epidiolex®, has also recently gained Food and Drug
Administration approval as a regulated prescription
medication to treat certain forms of paediatric epilepsy.
Recently, interest in CBD has intensified among the
general population as evidenced by an exponential rise
in internet searches for CBDin the United States
(USA) [108]. Some professional athletes (e.g. golfers,
rugby players) also appear to be using CBD (e.g. Team
cbdMD, despite there being
no published studies demonstrating beneficial effects on
sport or exercise performance. In many jurisdictions, in-
cluding the USA and Europe, access to regulated, pre-
scription CBD (i.e. Epidiolex®) is limited to patients with
intractable epilepsy. However, a wide range of low dose
(e.g. 550 mg·d
) CBD-containing nutraceuticals(pri-
marily in oil or capsule form) have become readily avail-
able online and over-the-counter (e.g. pharmacies,
health food stores) [20,125]. This includes some var-
ieties that are marketed specifically to recreational and
elite athletes (e.g. cbdMD, fourfivecbd). The use of these
products is likely to become even more widespread if
the World Health Organizations recommendation that
CBD no longer be scheduled in the international drug
control conventions is adopted by the United Nations
member states [201].
Cannabis has been prohibited in all sports during com-
petition since the World Anti-Doping Agency first as-
sumed the responsibility of establishing and maintaining
the list of prohibited substances in sport 15 years ago [89].
In 2018, however, CBD was removed from the Prohibited
List [199], presumably on the basis of mounting scientific
evidence that the cannabinoid is safe and well-tolerated in
humans [16,169], even at very high doses (e.g. 1500
or as an acute dose of 6000 mg) [170]. While
several recent reviews have described the impact of canna-
bis on athlete health and performance [99,176,188], the
influence of CBD alone has yet to be addressed.
The aim of this narrative review was to explore evi-
dence on the physiological, biochemical, and psycho-
logical effects of CBD that may be relevant to sport and/
or exercise performance and to identify relevant areas
for future research. Given the absence of studies directly
investigating CBD and sports performance, this review
draws primarily on preclinical studies involving labora-
tory animals and a limited number of clinical trials in-
volving non-athlete populations.
Cannabidiol (CBD): Molecular Targets,
Pharmacokinetics and Dosing
Molecular Targets
The distinctive intoxicating effects of Δ
-THC (as well as
some of its therapeutic effects) involve the activation of
R (the cannabinoid type 1 receptor) [12]. This ubiqui-
tous receptor is expressed throughout the central nervous
system, the peripheral nervous system, and in the cardio-
vascular system, gastrointestinal (GI) tract, skeletal
musculature, liver, and reproductive organs [205]. Unlike
-THC, CBD is not an agonist of CB
R, although it may
act as a negative allosteric modulator (NAM) at this site
(i.e. decreasing the potency and/or efficacy of other
ligands without activating the receptor itself) [92,106].
-THC also acts as an agonist at CB
type 2 receptor) [12] and there is emerging evidence of
CBD functioning as a partial agonist at this site [171].
R is primarily located on immune system cells but is
also expressed in the cardiovascular system, GI tract,
bone, liver, adipose tissue, and reproductive organs [205].
CBD may also influence the endocannabinoid system in-
directly via the inhibition of fatty acid amide hydrolase
(FAAH), a key enzyme involved in the degradation of the
principle endocannabinoid signalling molecule, ananda-
mide (AEA) [92,110]. The inhibition of FAAH is pre-
dicted to lead to an increase in brain and plasma
concentrations of AEA, which acts as a partial agonist at
R, thereby increasing endocannabinoid tone
[92,110]. Increases in endocannabinoid tone may also
occur as a result of CBD inhibiting AEA transport via
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effects on fatty acid-binding proteins (and this mechanism
may have more relevance than FAAH inhibition in
humans) [57].
CBD also interacts with many other non-endocannabinoid
signalling systems [92]. Briefly, at concentrations 10 μM,
CBD has been reported to interact with the serotonin 1A
] receptor, the orphan G protein-coupled receptor
55, as well as the glycine, opioid, and peroxisome prolifera-
tor-activated receptors, various ion channels (e.g. the transi-
ent potential vanilloid receptor type 1 channel [TRPV1] and
other transient potential vanilloid channels) and various en-
zymes (e.g. cyclooxygenase (COX)1 and COX2, cytochrome
P450 enzymes) [11,92] (see Ibeas et al. [92]forreview).CBD
also possesses antioxidant properties [92].
It is important to recognise that the molecular targets
of CBD are still being established, with many of those
identified in in vitro cellular assays still to be validated
as occurring in vivo. As such, the functional relevance of
many of these interactions remains to be established.
CBD is often consumed orally as oil; however, it can also
be ingested in other forms (e.g. gel capsules, tinctures,
beverages, and confectionery products) and applied topic-
ally [20,125]. High concentration CBD vape oils(i.e. for
use in e-cigarette devices) are also available in some coun-
tries, as are some CBD-dominant forms of cannabis
(sometimes known as light cannabis)thatcanbe
smoked or vaporised [20,125]. Pure, synthetic, crystalline
CBD was also vaporised in a recent laboratory study [160].
Taylor et al. [170] recently conducted a comprehensive
analysis of oral CBD oil pharmacokinetics in healthy partici-
pants. When administered as a single, oral dose (15006000
mg), the time to reach peak plasma concentrations (t
~45 h and the terminal half-life was ~1417 h. Although
did not increase dose-dependently in this investigation
[170], another study [19], involving a much lower oral dose
of CBD (300 mg), did indicate a shorter t
(i.e. ~23h).
Peak plasma concentrations (C
)were~0.92.5 μMin
Taylor et al. [170], but increased ~4.9-fold when CBD was
administered with a high-fat meal (i.e. ~5.3 μM at 1500 mg
dose) [170]. Both studies observed a large amount of inter-
individual variation in pharmacokinetic responses [19,170].
The pharmacokinetics of inhaled CBD are yet to be
well characterised. However, smoked light cannabis
(with a lower Δ
-THC and higher CBD content than
other varieties) has been reported to elicit high serum
CBD concentrations at 30 min post-treatment (that de-
cline over time) [146]. A recent study in which partici-
pants vaporised 100 mg of CBD likewise observed high
blood CBD concentrations 30 min post-treatment [160].
As neither study collected blood samples within < 30
min of CBD administration, t
and C
are unknown
CBD is metabolised by several cytochrome P [CYP]
450 enzymes (e.g. CYP3A4, CYP2C9, CYP2C19) which
convert it to a number of primary and secondary metab-
olites (e.g. 7-OH-CBD, 6-OH-CBD, and 7-COOH-CBD)
[177]. Complex pharmacokinetic interactions may occur
when CBD is co-administered with other drugs (e.g. Δ
THC) and dietary constituents (e.g. caffeine) that also
utilise these enzymes [6,163].
Interspecies Dose Conversions
Given the number of preclinical studies involving animal
models that will be discussed in this review, it is import-
ant to consider interspecies dose equivalence (Table 1).
The USA Food and Drug Administration [30] recom-
mend the following approach to interspecies dose
HED mg kg1
¼DoseAnimal mg kg1
Where HED is the human equivalent dose and Km is
a correction factor estimated by dividing the average
body mass (BM) of the species (60, 0.020 and 0.150 kg
for 11 humans, mice and rats respectively) and by its
surface area (see: Nair, et al. [134] for 12 further details).
Differences between systemic and oral dosing should
also be considered [9]. Intraperitoneal (i.p.) dosing is often
used in animal studies and has been reported to elicit C
values ~7-fold higher than oral dosing in mice [52]. Thus,
an oral equivalent dosecanbeapproximatedbymulti-
plying the i.p. dose by seven [9](Table1). Intravenous
(i.v.) dosing will produce even higher plasma CBD con-
centrations; however, the authors are not aware of any
published data that would facilitate conversion between
i.v. and oral dosing in rodents. Please note that these
values are intended as a guide only and subject to limita-
tions (e.g. interspecies differences in drug potency and re-
ceptor expression/configuration).
Cannabidiol (CBD) in Sport and Exercise
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 Sci-
ence (via Thomas Reuters), and Scopus were searched
between April and October of 2019 using terms such as:
cannabinoid’‘cannabidiol,CBDand cannabis. This
review focuses primarily on effects that have been dem-
onstrated in vivo and generally avoids attempting to pre-
dict functional effects on the basis of target-oriented
in vitro data, given the numerous molecular targets of
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CBD [92] and the fact that exercise itself induces com-
plex 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 (sin-
gle), unless otherwise stated.
Exercise-Induced Muscle DamageMuscle Function,
Soreness, and Injury
Exercise, particularly when strenuous, unfamiliar, and/or
involving an eccentric component, can cause ultrastruc-
tural damage to skeletal muscle myofibrils and the sur-
rounding extracellular matrix [36,59]. This exercise-
induced muscle damage (EIMD) impairs muscle func-
tion and initiates an inflammatory response [59]. While
inflammation is integral to EIMD repair, regeneration,
and adaptation [59], excessive inflammation may con-
tribute to prolonged muscle soreness and delayed func-
tional recovery [7,158].
CBD modulates inflammatory processes [21]. In pre-
clinical models of acute inflammation, CBD has been re-
ported to attenuate immune cell accumulation (e.g.
neutrophils, lymphocytes macrophages) [102,130,149,
186], stimulate production of anti-inflammatory cyto-
kines (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 oxy-
gen species [62,130,186]. Models demonstrating such
effects have included lung injury induced by chemical
treatment [149] and hypoxicischemia (HI) [10]; liver
injury induced by ischemia-reperfusion [63,130] and al-
cohol feeding [186]; myocardial [55] and renal [62]
ischemia-reperfusion injuries; surgically induced oral le-
sions [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
, i.p.); although, lower doses
(e.g. ~1.5 mg·kg
, i.p.) have indicated efficacy in some
studies [145]. Research investigating the effects of CBD
on inflammation in humans is limited and inconclusive
In terms of muscle-specific inflammation, one preclin-
ical study has investigated the effect of high-dose CBD
(i.e. 60 mg·kg
, 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 degener-
ation, were also reported at this dose. Lower, but still
relatively high, CBD doses (2040 mg·kg
had no functional benefits [91]. Of course, it is im-
portant to recognise that EIMD and muscular dys-
trophy differ in their pathophysiology, and so the
effects observed in MDX mice may involve mecha-
nisms less relevant to EIMD (e.g. skeletal muscle dif-
ferentiation, 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 eluci-
dated, although it may be that the prevention of inflam-
mation inhibits angiogenesis and skeletal muscle
hypertrophy [120]. Human trials also suggest that ibu-
profen may not influence EIMD, inflammation, or sore-
ness [144,175]. Thus, if CBD exerts its effects via similar
mechanisms, it could possibly attenuate the benefits of
training without influencing muscle function or sore-
ness. Future studies investigating this are clearly war-
ranted to clarify such issues and elucidate the potential
benefits of CBD.
Table 1 Oral human equivalent CBD doses from mouse and rat intraperitoneal doses
Mouse to Human CBD Dose Conversion Rat to Human CBD Dose Conversion
Mouse Dose
, i.p.)
(mg, p.o.)
Rat Dose
, i.p.)
(mg, p.o.)
5 170 5 340
10 341 10 681
20 681 20 1362
30 1021 30 2043
60 2043 60 4086
Each HED is based on a body mass of 60 kg and calculated as per the methods described in 2.3 Dose Conversions. The highest documented acute oral CBD dose
in humans is 6000 mg; the highest documented chronic oral CBD dose in humans is 1500 mg [169]. HED: Human Equivalent Dose; i.p.: Intraperitoneal; p.o.: Oral
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NeuroprotectionConcussion and Subconcussion
Recent estimates suggest that 636% of high school and
collegiate athletes in the USA have experienced more
than one concussion [72], potentially predisposing them
to long-term neurodegenerative diseases [72] and an in-
creased risk of suicide [64]. Concussion is a distinct form
of mild traumatic brain injury (TBI) in which a biomech-
anical force temporarily disrupts normal brain function-
ing causing neurologicalcognitivebehavioural signs
and symptoms [97]. Similar injuries that do not produce
overt (acute) signs or symptoms are termed subconcus-
sions[97]. In TBI, the primary injury occurs as a result
of the biomechanical force; secondary injury is then sus-
tained through a complex cascade of events, including
HI, cerebral oedema, increased intracranial pressure, and
hydrocephalus [203]. These processes are, in turn,
related to a number of detrimental neurochemical
changes, including glutamate excitotoxicity, perturbation
of cellular calcium homeostasis, excessive membrane de-
polarisation, mitochondrial dysfunction, inflammation,
increased free radicals and lipid peroxidation, and apop-
tosis [203]. While the primary injury may not be treat-
able, interventions that attenuate secondary sequelae are
likely to be of benefit [203].
Only one study [14] has investigated the biochemical
and neuropsychological effects of CBD in an animal
model of TBI. Here, C57BL/6 mice were given chronic
CBD treatment (3 μg·day
, oral) 114 and 5060 days
post- (weight drop) brain insult. CBD attenuated the be-
havioural (e.g. anxious and aggressive behaviour,
depressive-like behaviour, impaired social interactions,
pain-related behaviours) and some of the cortical bio-
chemical abnormalities were observed. Specifically, CBD
tended to normalise extracellular glutamate, D-aspartate,
and γ-aminobutyric acid concentrations in the medial
prefrontal cortex, suggesting a reduction in excitotoxi-
city. However, neuronal damage was not measured dir-
ectly in this study [14].
Other preclinical studies have investigated the impact
of CBD on different animal models of acute neuronal in-
jury, in particular, acute cerebral HI [4,13,31,68,69,
80,81,83,100,105,127,129,142,143,153]. Studies ad-
ministering a single (acute) dose of CBD shortly post-HI
(e.g. 1 h) have produced inconsistent results. For in-
stance, while Garberg et al. [68,69] found no effect of
CBD (1 or 50 mg·kg
, i.v.) on HI-induced neuronal
damage in piglets, others observed neuroprotection at
similar doses (e.g. 1 mg·kg
, i.v [105,143]., 1 mg·kg
s.c [127,142]., and 5 mg·kg
, i.p [31].) in piglets and
rats. When given chronically, or repeatedly within a
short timeframe proximal to the HI event, however,
CBD appears to be neuroprotective. Effective dosing
strategies have varied and included initiating treatment
several days pre-HI (e.g. 100 or 200 μg·day
intracerebroventricular 5 days; Wistar rats [100]), shortly
pre- and/or post-HI
, and up to 3 days post-HI (e.g. 3
, i.p. 12 days; ddY mice [80]). Thus,
chronic CBD treatment may be more effective than
acute intervention. While pre-incidentdosing might
also be beneficial, it is noted that in practice, this would
require humans at risk of TBI to use CBD chronically as
a prophylactic.
The precise mechanism(s) underpinning the neuropro-
tective effects of CBD are not completely understood
(see Campos et al. [25] for review), but may involve de-
creased inflammation, oxidative stress, and excitotoxicity
[142,143] and increased neurogenesis [129]. Preclinical
studies have also demonstrated beneficial effects of CBD
in other animal models of neurodegeneration (e.g. trans-
genic model of Alzheimers disease [34,35], brain iron-
overload [47,48]). Collectively, these data suggest that
research investigating the utility of CBD in ameliorating
the harmful long-term effects of repeated sports concus-
sions is warranted.
Nociceptive and Neuropathic Pain
Persistent pain is common in athletes [74]. Nociceptive
pain, which includes inflammatory pain, typically occurs
with tissue damage; whereas neuropathic pain typically re-
sults from a lesion or disease in the somatosensory ner-
vous system [74]. Neuropathic pain is common among
para-athletes with spinal cord injuries and can also arise
with surgery (e.g. to treat an existing injury) or if there is
repetitive mechanical and/or inflammatory irritation of
peripheral nerves (e.g. as in endurance sports) [74].
Clinical trials investigating the combined effects of Δ
THC and CBD (e.g. Sativex®) on chronic neuropathic
pain have yielded promising initial results [87,114,151,
156]. However, the therapeutic effects of CBD adminis-
tered alone have received limited clinical attention. Pre-
clinical (in vivo) studies investigating the effects of CBD
on neuropathic and nociceptive pain are summarised in
Table 2. Despite some methodological inconsistencies
(e.g. the pain model, period of treatment, route of deliv-
ery), most preclinical studies appear to have observed a
significant analgesic effect of CBD [29,3941,51,70,75,
78], albeit somewhat less pronounced than the effects of
-THC [29,78] (e.g. Hedgesg= 0.8 vs. 1.8 [78]) or of
gabapentin (e.g. Hedgesg= 2.0 [78]), a commonly used
agent for treating neuropathic pain. Capsazepine co-
treatment has also been reported to attenuate CBD-
induced analgesia, suggesting that the effect may be me-
diated, at least in part, by the TRPV
channel [40,41,
51]. This mechanism is noteworthy as studies have
E.g. 1030 mg·kg
, i.p. 3 days [129,153], 1 mg·kg
, i.v. 3
days [13], 13 mg·kg
, i.p. pre- and 3 h post-HI [81,83] or 0.1
, i.v. 15 and 240 min post-HI [4].
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Table 2 Preclinical studies investigating the effect of CBD on neuropathic and nociceptive pain in vivo
Citation Animal Model Treatment(s) Treatment Effect
Neuropathic Pain
De Gregorio et al., (2019) [51] Wistar rats SNI 5 mg·kg
, s.c. 7 d CBD sig. decreased mechanical allodynia on Tx day 7.
Casey et al., (2017) [29] C57BL/6 mice CCI 30 mg·kg
, s.c. CBD sig. decreased mechanical allodynia 2 h, but not 0.5, 1, 4 or
6 h, post-Tx compared to baseline.
0.01, 0.1, 1, 10 or 100 mg·kg
, s.c. CBD dose-dependently decreased mechanical and cold allodynia.
King et al., (2017) [101] C57BL/6 mice CT (Paclitaxel) 0.62520 mg·kg
, i.p. 15 min prior to CT on days 1, 3, 5 and 7 1 and 20 mg·kg
CBD sig. attenuated the development of
mechanical allodynia measured on Tx days 9 and 14, but not 21.
CT (Oxaliplatin) 1.2510 mg·kg
, i.p. 15 min prior to CT on days 1, 3, 5 and 7 1.2510 mg·kg
CBD sig. attenuated the development of
mechanical allodynia measured on Tx days 2, 4, 7 and 10.
CT (Vincristine) 1.2510 mg·kg
, i.p. 15 min prior to CT on days 1, 3, 5 and 7 CBD did not attenuate the development of CT-induced
mechanical allodynia measured on Tx days 5, 10, 15 and 22.
Harris et al., (2016) [78] C57BL/6 mice CT (Cisplatin) 2 mg·kg
, i.p. CBD sig. decreased tactile allodynia 1 h post-Tx.
0.5, 1 or 2 mg·kg
, i.p. 30 min prior to CT every second day for 12 d CBD did not attenuate the development of CT-induced tactile
allodynia measured on Tx days 6, 10 and 12.
Ward et al., (2014) [187] C57BL/6 mice CT (Paclitaxel) 2.5 or 5 mg·kg
, i.p. 15 min prior to CT on days 1, 3, 5 and 7 2.5 and 5 mg·kg
CBD attenuated the development of
CT-induced mechanical allodynia.
Toth et al., (2010) [174] CD1 mice STZ Diabetes 0.1, 1 or 2 mg·kg
, i.n. 3 months 1 and 2 mg·kg
CBD sig. attenuated the development of
thermal and tactile hypersensitivity compared to 0.1 mg·kg
2 mg·kg
, i.n. 1 month CBD did not alleviate developed thermal or tactile hypersensitivity.
1, 10 or 20 mg·kg
, i.p. 3 months 20 mg·kg
CBD sig. attenuated the development of thermal
and tactile hypersensitivity compared to 1 mg·kg
20 mg·kg
, i.p. 1 month CBD did not alleviate developed thermal or tactile
Costa et al., (2007) [41] Wistar rats CCI 2.5, 5, 10 or 20 mg·kg
, oral 7 d 5, 10 and 20 mg·kg
CBD sig. decreased thermal and
mechanical hyperalgesia on Tx day 7.
Nociceptive (Inflammatory) Pain
Genaro et al., (2017) [70] Wistar rats Incision 0.3, 1, 3, 10 or 30 mg·kg
, i.p. 3 mg·kg
CBD sig. decreased mechanical allodynia between 30-
and 150-min post-Tx; 10 mg·kg
CBD sig. decreased mechanical
allodynia 60 min post-Tx, only.
Hammell et al., (2016) [75] Sprague-Dawley rats FCA 0.6, 3.1, 6.2 or 62.3 mg·kg
, t.c. 4 d 6.2 and 62.3 mg·kg
CBD sig. decreased pain-related behaviour
on Tx day 4 and thermal hyperalgesia on Tx days 2, 3 and 4.
Costa et al., (2007) [41] Wistar rats FCA 20 mg·kg
, oral 7 d CBD sig. decreased thermal and mechanical hyperalgesia on
Tx day 7.
Costa et al., (2004) [39] Wistar rats Carrageenan 5, 7.5, 10, 20 and 40 mg·kg
, oral 5, 7.5, 10, 20 and 40 mg·kg
CBD sig. decreased thermal
hyperalgesia 15 h post-Tx.
Costa et al., (2004) [40] Wistar rats Carrageenan 10 mg·kg
, oral CBD sig. decreased thermal hyperalgesia 1 h post-Tx.
The Treatment Effectsdescribed are in comparison to a vehicle condition, unless otherwise stated
CBD Cannabidiol, CCI Chronic Constriction Injury, CT Chemotherapy, FCA Freunds Complete Adjuvant, i.n. Intranasal, i.t. Intrathecal, s.c. Subcutaneous, SNI Spared Nerve Injury, STZ Streptozotocin, t.c. Transcutaneously,
Tx Treatment
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Content courtesy of Springer Nature, terms of use apply. Rights reserved.
implicated the TRPV
in the development of mechanical
hyperalgesia induced by muscle inflammation [66,140].
It is important to recognise that the analgesic effect of
CBD likely depends on several factors, including the
treatment dose and the type of pain involved. Indeed,
low doses of CBD (e.g. 1 mg·kg
, i.p.) do not consist-
ently attenuate pain [29,41,70,75,101]; while higher
doses are sometimes found to be more [29], and other
times, less [70], efficacious than moderate doses in pre-
clinical studies (Table 3). This highlights the importance
of determining a therapeutic dose for CBD in analgesia.
Data from King et al. [101] also demonstrate the select-
ivity of the response, indicating that CBD only effective
in attenuating the development of neuropathic pain in-
duced by certain chemotherapeutic agents (i.e. paclitaxel
and oxaliplatin but not vincristine). Thus, placebo-
controlled trials of CBD in treating pain in clinical popu-
lations and athletes are warranted.
Exercise-Induced Gastrointestinal (GI) Damage
While strenuous exercise increases blood supply to the
active skeletal muscles, cardiopulmonary system and
skinother organs and tissues, including the GI tract,
experience reduced oxygen and nutrient delivery [180].
If exercise is prolonged (e.g. >40 min), this GI ische-
mia, as well as the inflammation and oxidative stress
that accompanies reperfusion, can compromise epithelial
integrity [180]. Such effects may negatively influence ex-
ercise performance and post-exercise recovery due to GI
distress (e.g. nausea, vomiting, abdominal angina, bloody
diarrhoea) and impaired nutritional uptake [180].
CBD has demonstrated some effects that may be rele-
vant to the management of exercise-induced GI damage.
For instance, preclinical studies have shown that CBD
(e.g. 0.0110 mg·kg
, i.v. or 10 mg·kg
, i.p.) can attenu-
ate tissue damage (e.g. reduce necrosis, blood concentra-
tions of tissue damage markers and inflammation)
induced by acute, peripheral ischemia-reperfusion (e.g.
kidney, myocardium, liver) [55,60,62,63,130,185] and
colitis [23,50,154] in vivo; benefits that have generally
been attributed to its reported antioxidant and anti-
inflammatory effects (see also section Exercise-Induced
Muscle DamageMuscle Function, Soreness, and In-
jury)[50,55,60,62,63,130,154,185]. Also, of interest
is that CBD (1100 μM) has been reported to restore in-
testinal permeability in vitro following exposure to Clos-
tridium difficile toxin A, ethylenediaminetetraacetic acid
and pro-inflammatory stimuli (e.g. interferon-gamma,
Of course, it is important to recognise that evidence to
support a therapeutic effect of CBD on GI damage in
humans is currently lacking. In fact, two placebo-
controlled, double-blinded clinical trials, one investigating
the effect of CBD (10 mg·d
; 56 days) on symptom
severity in Crohns disease (n=20)[133] and the other
examining the impact of a CBD-rich botanical extract
(250 mg·day
[4.7% THC]; 56 d) on the likelihood of re-
mission in ulcerative colitis (n=60)[94], have so far been
unable to demonstrate a protective effect of CBD (above
placebo) on disease markers, including C-reactive protein,
faecal calprotectin, and pro-inflammatory cytokines (e.g.
IL-2, IL-6, TNF-α).
While CBD could potentially attenuate exercise-induced
GI damage, it is important to note that other anti-
inflammatory agents, such as the NSAID, ibuprofen, have
been reported to exacerbate exercise-induced GI damage
and impair gut barrier function [181]. The precise mecha-
nism(s) underpinning these effects have not been fully elu-
cidated. However, NSAIDs have been suggested to
augment GI ischemia by inhibiting the COX1 and COX2
enzymes and interfering with nitric oxide production
[180]. Some in vitro research similarly suggests that CBD
partially inhibits COX1 and COX2, although this effect
has only been reported at supraphysiological concentra-
tions (e.g. 50500 μMCBD)[92]. Thus, the effect of CBD
on exercise-induced GI damage warrants clarification.
Bone Health
While the beneficial effects of high-impact exercise on
bone health are well established [38], other factors within
the sporting context (e.g. traumatic injuries, low energy
availability [117]) may cause or contribute to reduced
bone health and the development of fractures in athletes.
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. periodontitis, systemic skeletal degen-
eration due to spinal cord injury) one investigation [103]
did report that CBD improved the healing of femoral
fractures in Sprague-Dawley rats. Specifically, chronic
CBD treatment (i.e. 5 mg·kg
, i.p.) decreased
callus size 4-weeks post-fracture and enhanced the bio-
mechanical properties of the bone at 8-weeks (i.e. max-
imal force, work-to-failure on a 4-point bending test)
[103]. While the mechanism(s) underlying this effect re-
quire clarification, CBD may act to inhibit expression of
RANK and RANK-L (i.e. indicative of an effect to sup-
press osteoclastogenesis, and thus, bone resorption) and
decrease the production of pro-inflammatory cytokines
(e.g. IL-1β, TNF-α) at the site of injury [103,135]. Evi-
dence that activation of CB
R induces bone matrix de-
position has also recently emerged [150] alongside data
suggesting that CBD may have partial agonist effects at
this site [171]. These initial findings suggest that further
research investigating the effect of CBD on acute skeletal
injuries is worthwhile.
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Table 3 Clinical trials investigating the effect of CBD on subjective anxiety
Citation Study design Participants Treatment(s) Context Treatment effect
Healthy participants
Zuardi et al.
(1993) [207]
DB (PC); BSD I: 10; 23 y
C: 10; 23 y
Oral 300 mg Public speaking
(90 min post-tx)
CBD sig. reduced SA post-public speaking. SA prior to, in anticipation of, and during speaking were
Crippa et al.
(2004) [45]
DB (PC); BSD I: 5 M; 30 ± 5 y
C: 5 M; 30 ± 5 y
Oral 400 mg Low stress CBD sig. reduced SA 60 and 75 min post-tx.
et al. (2010) [18]
DB (PC); WSD 15 M; 27 ± 6 y Oral 600 mg Low stress SA was unaffected 1, 2 and 3 h post-tx.
et al. (2012) [123]
DB (PC); WSD 16 M; 26 ± 5 y Oral 600 mg Low stress SA was unaffected 1, 2 and 3 h post-tx.
Hindocha et al.
(2015) [86]
DB (PC); WSD 48; 22 y Vaporised 16
Low stress SA was unaffected 2, 30, 60. 90 and 120 min post-tx.
Zuardi et al.
(2017) [208]
DB (PC); BSD I: 12 (6 M); 23 ± 3 y
I: 11 (5 M); 23 ± 3 y
I: 12 (6 M); 23 ± 3 y
C: 12 (6 M); 22 ± 2 y
I: Oral 100 mg
I: Oral 300 mg
I: Oral 900 mg
Public speaking
(150 min post-tx)
300 mg CBD sig. reduced SA compared to 900 mg CBD (but not placebo) during public speaking. SA
prior to, in anticipation of, and post-speaking were not affected by any treatment.
Linares et al.
(2019) [116]
DB (PC); BSD I: 15 M; 24 ± 3 y
I: 15 M; 25 ± 3 y
I: 12 M; 23 ± 3 y
C: 15 M; 25 ± 4 y
I: Oral 150 mg
I: Oral 300 mg
I: Oral 600 mg
Public speaking
(90 min post-tx)
300 mg CBD (but not 150 or 600 mg) sig. reduced SA during public speaking. SA prior to, in
anticipation of, and post-speaking were not affected by any treatment.
Clinical populations
Crippa et al.
(2011) [44]
SAD Participants
10 M; 24 ± 4 y Oral 400 mg Low stress CBD sig. reduced SA 60, 75 and 140 min post-Tx.
et al. (2011) [15]
SAD Participants
I: 12 (6 M); 23 ± 2 y
C: 12 (6 M); 23 ± 2 y
Oral 600 mg Public speaking
(90 min Post-Tx)
CBD sig. reduced SA during public speaking. SA prior to, in anticipation of, and post-speaking were
not affected.
Hundal et al.
(2017) [90]
High Trait Paranoia
I: 16 (8 M); 26 ± 9 y
C: 18 (8 M); 25 ± 8 y
Oral 600 mg Virtual reality
(130 min Post-Tx)
SA was unaffected.
Masataka (2019)
SAD Participants
I: 17 (8 M); 1819 y
C: 20 (8 M); 1819 y
Oral 300
Low stress CBD sig. reduced SA 4-weeks post-tx.
BSD between-subject design, Ccontrol group, CBD cannabidiol, DB double-blind, Iintervention group, Mmale subjects, PC placebo-controlled, SAD social anxiety disorder, SA subjective anxiety, SB single-blind, Tx
treatment, WSD within-subject design
The Treatment effectsdescribed are in comparison to a placebo condition, unless otherwise stated
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Cardiovascular (CV) and Metabolic Functions
A number of studies have measured CV responses to
CBD (1001200 mg) in humans and, overall, it appears
that resting HR is unaffected (see Sultan et al. [165] for
review). However, some evidence does suggest that CBD
(600 mg) reduces resting systolic BP (e.g. 6 mmHg) [95,
164]. Preclinical studies have likewise shown that CBD
influences vascular function [139,161,162,193,194].
Briefly, in vitro CBD treatment (i.e. 2 h exposure to 1
10 μM) has been reported to induce vasorelaxation [139]
and potentiate vasorelaxation to acetylcholine [162,193]
in isolated (pre-constricted) arteries of rats [139,162,
193]. A recent study [161] also found that in vitro CBD
treatment (i.e. 2 h exposure to 10 μM) induced ~40%
vasorelaxation in isolated (pre-constricted) mesenteric
arteries of humans with various clinical conditions (e.g.
cancer, inflammatory bowel disease, type Z diabetes mel-
litus [T2DM]).
In addition to restingCV parameters, a recent meta-
analysis (of largely preclinical studies) found that CBD
attenuated stress-induced(e.g. via fear-conditioning or
physical-restraint) increases in HR and BP (BP 3.5
mmHg; 95% CI 5.2, 1.9; I
= 73%; HR 16 mmHg;
95% CI 26, 6; I
= 92%) [165], that said, most studies
measuring CV responses to CBD (150600 mg) under
stress-inducingconditions in humans (e.g. public
speaking) find no effect on HR or BP [15,116,207]. One
placebo-controlled, double-blinded (single-dose) cross-
over trial of healthy males (n=9)[95] did report that
CBD (600 mg) increased HR in the presence of certain
stressors (i.e. a mental arithmetic test, an isometric con-
traction on a hand-grip dynamometer, and cold expos-
ure); and, at times, reduced systolic and diastolic BP.
However, these differences were apparent at baseline
(pre-stress) and the data were not standardised to ac-
count for this, making interpretation difficult.
Taken together, these findings suggest that CBD has
the potential to influence CV function. However, the im-
plications of these effects in regard to exercise perform-
ance are unclear. Studies investigating the effect of CBD
on exercise-induced CV responses are therefore required
to clarify its utility within the sport and exercise context.
One final observation to note is that some initial data
suggest CBD might influence mitochondrial function.
Indeed, in vivo CBD treatment has been reported to in-
crease the activity of mitochondrial complexes [48,77,
130,178] (3060 mg·kg
, i.p. acute or chronic 14 days
Wistar rats; 3 and 10 mg·kg
, i.v. C57BL/6 J mice; 10
, i.p. 5 days C57BL/6 J mice; and 10
, i.p. 14 days Wistar rats) in various tissues
and models (i.e. healthy brain, myocardium following
doxorubicin treatment, brain following neonatal iron-
overload, hepatic ischemia-reperfusion injury) and in-
crease mitochondrial biogenesis [77] (10 mg·kg
i.p. 5 days C57BL/6 J mice; myocardium following doxo-
rubicin treatment). Such effects could have implications
for energy metabolism during exercise.
Heat loss mechanisms play a pivotal role in the mainten-
ance of homeostasis during exercise; any treatment or
condition that alters core body temperature (T
), there-
fore has the potential to impact exercise performance
[192]. The effect of CBD on T
has been investigated in
rodents [65,82,83,85,96,118,166,182]. The most re-
cently published study found that CBD (100 mg·mL
30 min vaporised; Wistar rats) reduced T
(1.0 °C) 60
and 90 min following inhalation in resting animals [96].
In contrast, Long et al. [118] reported a hyperthermic ef-
fect (+2.0 °C) 30 min post-treatment (1 and 10 mg·kg
i.p.; C57BL/6JArc mice) during a chronic-dosing experi-
ment, although, this response was only observed inter-
mittently during a 21-day protocol (e.g. ~8% of total
measurements). The fact that CBD affected T
in these
experiments is difficult to explain, since although other
cannabinoids (e.g. Δ
-THC, AEA) have demonstrated a
capacity to moderate T
when administered exogenously
(e.g. low doses of Δ
-THC may sometimes induce hyper-
thermia [168] and high doses cause hypothermia [65,82,
83,85,96,118,166,182]), these effects occur via a
R-mediated mechanism [42,166,196]. In addition to
this, no other studies appear to have detected changes in
with CBD administration [65,82,83,85,166,182].
Overall, despite some inconsistencies, the available
data suggest that CBD is unlikely to have a major influ-
ence on T
or thermoregulatory processes. In any case,
it seems that with the exception of self-reported feelings
of coldness[33,88], exogenous cannabinoids do not
typically induce the same overt, significant effects on T
in humans [104,183] as are seen in rodents. Still, it
should be acknowledged that the thermoregulatory re-
sponse to heat stress (i.e. passive or metabolic), specific-
ally, has not been studied.
Dietary Intake and Feeding
An adequate intake of energy and nutrients is essential
to support optimal athletic training, recovery, and per-
formance [173]. Various preclinical studies have investi-
gated the effect of CBD on feeding behaviour in rodents
[58,93,155,159,195], with results suggesting that
higher doses may influence food intake several hours
post-treatment. Indeed, while CBD, at doses of 3100
, i.p. (IRC mice) [195] and 120 mg·kg
, i.p.
(Wistar rats) [155], failed to influence food intake during
a 1 h ad libitum feeding period, moderate to high doses
of CBD (4.4 mg·kg
, i.p. [58]. and 50 mg·kg
, i.p. [159])
suppressed food intake (in rats) during longer ad libitum
feeding periods (i.e. 46 h). In line with these results,
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Ignatowska-Jankowska et al. [93] found that chronic
CBD treatment (2.5 and 5 mg·kg
, i.p. 14 days) at-
tenuated BM gains in growing Wistar rats. A recent sys-
tematic review of human trials also reported that
individuals with epilepsy receiving CBD (520
) were more likely to experience decreased
appetite than those receiving placebo (i.e. ~20 vs. 5% of
patients) [107].
That said, a mechanistic understanding of these effects
of CBD on feeding behaviour remains to be established.
Other cannabinoids with CB
R agonist effects (e.g. Δ
THC, AEA, cannabinol) reliably induce hyperphagia
when administered exogenously [58,197,198]; but CBD
lacks such an effect. Ignatowska-Jankowska et al. [93]
did report that the selective CB
R antagonist, AM630,
prevented CBD-induced BM changes; however, CB
has not generally been linked to feeding behaviour, and
if CBD is indirectly increasing endocannabinoid tone
(i.e. via AEA) [92], this might be expected to promote
feeding behaviour (via indirect CB
R agonist effects)
[197]. A role for GI side effects in affecting appetite
therefore cannot be ruled out [107]. Further preclinical
research appears to be required to clarify the mecha-
nisms underlying these functional effects on feeding.
Controlled trials are also needed to determine whether
CBD influences appetite and dietary behaviour in
humans, particularly during the pre- and post-exercise
period, where nutrient provision is critical.
Illness and Infection
Some research suggests that athletes experience a de-
crease in immunity and are at increased risk of develop-
ing acute illnesses (particularly upper respiratory tract
infections) during periods of heavy training and compe-
tition [184]. This phenomenon has been attributed to
various factors such as increased psychological stress,
poor sleep, long-haul travel, exposure to extreme envi-
ronments (e.g. altitude), and low energy availability
[184]. A recent review of online content identified a
number of webpages claiming benefits of using CBD for
the treatment of viral illnesses, including cold and flu
[167]. However, research supporting such protective ef-
fectsof CBD is extremely limited. In fact, the authors
identified only two (in vitro) studies reporting anti-
microbial effects [5,179] and two (in vitro) studies
reporting anti-viral effects [119,122] (see Tagne et al.
[167] and Nichols et al. [136] for reviews). In the former,
CBD demonstrated anti-microbial activity against vari-
ous strains of Staphylococcus aureus [5,179], as well as
Staphylococcus pyogenes,Staphylococcus milleri, and
Staphylococcus faecalis [179] at minimum concentra-
tions of ~3.215.9 μM; however, one study also found
that these effects were virtually abolished when the ori-
ginal media (a nutrient broth agar) was replaced with
one containing 5% blood (increasing the minimum con-
centration to ~160 μM CBD) [179]. In the latter, CBD
indicated anti-viral activity against the hepatitis C virus
= 3.2 μM) and the Kaposis sarcoma-associated
herpesvirus (EC
= 2.1 μM), but not the hepatitis B
virus [119,122]. While these findings hint at some
promise, others caution that CBD could potentially
weaken host defence against invading pathogens because
of its tendency to modify the function of various im-
mune cells (see also section Exercise-Induced Muscle
DamageMuscle Function, Soreness, and Injury)[136,
147]. Importantly, a systematic review of studies investi-
gating the safety of CBD in individuals with intractable
epilepsy found that upper respiratory tract infections
were similarly infrequent in participants who received
the active treatment (520 mg·kg
) and placebo
(approx. 10% of individuals) [107]. Further research to
develop a better understanding of ifand howCBD
influences the development and progression of illness
and infection in both athlete and non-athlete popula-
tions would be useful.
Sports Performance Anxiety (SPA)
High levels of pre-competition stress, or sports perform-
ance anxiety (SPA) [141], can be detrimental to athletic
performance [43]. This impairment has been attributed
to both the direct (i.e. anxiogenic) and indirect (e.g. de-
creased nutritional intake, increased energy expenditure,
loss of sleep) effects of SPA [28]. While behaviour ther-
apies (e.g. cognitive behavioural therapy) are the pre-
ferred treatment, a combination of pharmaceutical and
psychological interventions may be indicated in some
cases [141].
A number of (small) clinical trials have investigated
the effect of CBD on subjective anxiety in healthy indi-
viduals [18,45,86,116,123,207,208] and in individuals
with social anxiety disorder (SAD) [15,44,124] and high
trait paranoia [90] under both standard (i.e. low stress)
[18,44,45,86,123,124]andstress-inducing(e.g. sim-
ulated public speaking) [15,90,116,207,208] conditions
(Table 3). Overall, results suggest that CBD has little in-
fluence on anxiety under low stressconditions in
healthy participants [18,86,123]. However, several stud-
ies have demonstrated anxiolytic effects of CBD (300
600 mg) under stress-inducingconditions in both
healthy participants and those with SAD [15,44,116,
124,207]. In fact, CBD (300 mg) had comparable efficacy
to the anxiolytic 5-HT
agonist drug, ipsapirone (5 mg),
during a simulated public speaking test in one study
[207]. On the other hand, some other clinical investiga-
tions (involving similar stress-inducingstimuli) have
found no effect of CBD [90,208] and Hundal et al. [90]
observed a non-significant trend (p< 0.10) towards an
anxiogenic effect with 600 mg CBD in a high trait
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paranoid group (n= 32). Inconsistencies could be due to
inter-individual differences in baseline anxiety levels and
the magnitude of the stress-response to the stressor im-
posed, small sample sizes, and differences in the dose
and formulation of CBD provided. Indeed, Linares et al.
[116] observed an inverted U-shaped dose-response rela-
tionship between acute CBD treatment and subjective
anxiety, indicating that 300 mg (Hedgesg= 1.0) had a
stronger anxiolytic effect than 150 mg (Hedgesg= 0.7)
or 600 mg (Hedgesg= 0.6).
Taken together, it appears that moderate doses of
CBD may be anxiolytic in stressful situations and in in-
dividuals with SAD. Thus, studies investigating the effect
of CBD (in conjunction with behaviour therapies) on
pre-competition anxiety, as well as nutritional intake, en-
ergy expenditure, symptom perception during exercise
(e.g. ratings of perceived exertion), and sleep in athletes
who are negatively impacted by SPA are warranted.
The importance of adequate sleep in facilitating optimal
athletic performance and recovery is increasingly recog-
nised [121]. Yet, athletes often sleep less (e.g. ~6.56.7
) and experience poorer quality sleep than non-
athletes [79,109,152]. Factors that contribute to poor
sleep among athletes include evening competitions and
training sessions, pre-competition anxiety, use of caffeine,
and long-haul travel (e.g. jet lag, travel fatigue) [121].
Several studies have investigated the effect of CBD on
sleep in humans [26,32,115,157]. The first placebo-
controlled, double-blinded (single-dose) crossover trial
[26] found that 160 mg CBD (but not 40 or 80 mg) in-
creased self-reported sleep duration in individuals with
insomnia (n= 15); although time to sleep onset, number
of sleep interruptions, and likelihood of experiencing
good sleepwere unchanged. Two case studies also in-
dicated the benefits of CBD [32,157]. Specifically, Cha-
gas et al. [32] observed a reduction in symptoms of rapid
eye movement sleep-behaviour disorder in four individ-
uals with Parkinsons disease (75300 mg·day
; 42 day)
and Shannon et al. [157] found that CBD (~25 mg·day
improved subjective sleep quality in a young girl with
post-traumatic stress disorder (PTSD). Of course, these
studies [26,32,157] are limited in that they rely on sub-
jective measures of sleep and involve small sample sizes;
the improvements observed could also be due to CBD
attenuating other sleep-impairing comorbid conditions
(e.g. anxiety, PTSD). Indeed, a recent placebo-controlled,
double-blinded (single-dose) crossover trial [115] found
no effect of CBD (300 mg) on sleep architecture mea-
sured via polysomnography in healthy adults (n=27).
While CBD seems unlikely to directly influence sleep
in healthy humans [115] (and may be sleep-promoting
in those with certain comorbid conditions) [26,32,157],
a small number of rodent studies suggest that the canna-
binoid could actually be wake-inducing[128,132,204].
One placebo-controlled, double-blinded (single-dose)
crossover trial of healthy individuals (n=8)[137] also
found that low-dose CBD (15 mg) counteracted some of
the sedative effects of co-administered Δ
-THC (15 mg),
i.e. increasing overnight wakefulness; although, this ef-
fect could be due to CBD acting as a NAM of CB
thereby attenuating Δ
-THCs effects on that receptor
[92]. Differences in the doses of CBD administered
might partly explain this inconsistency. Indeed, Monti
[128] observed a biphasic effect of CBD on sleep in Wis-
tar rats, such that a lower dose decreased, and a higher
dose increased (20 vs. 40 mg·kg
, i.p.), slow-wave sleep
latency. However, inter-species differences are also a
consideration as nocturnal animals appear to exhibit dif-
ferent circadian patterns of endocannabinoid signaling
compared to humans [84,131]. Collectively, the current
evidence on CBD and sleep endorses the need for fur-
ther research in clinical populations and athletes.
Cognitive and Psychomotor Function
A small number of clinical trials have investigated the ef-
fects of CBD on cognitive and psychomotor function in
healthy individuals (Table 4). Overall, results suggest a
minimal influence of CBD on cognitive or psychomotor
function. While one early investigation [98]reportedthat
CBD (15 or 60 mg) caused participants to under-/over-es-
timate the duration of a 60-s interval on several occasions
throughout a repetitive testing protocol (i.e. as is indicative
of impaired concentration), the magnitude of error was
small (e.g. <5 s; particularly, in comparison to that ob-
served with Δ
-THC, e.g. ~1025 s [98]) and the effect
was inconsistent, suggesting it may be an artefact of the
between-subject design and small sample size. A more re-
cent investigation [86] observed an improvement in emo-
tion recognition with CBD (16 mg vaporised); however,
this abilitymay have limited relevance to the sporting
context. More applicable, perhaps, is Dalton et al. [49]
finding no effect of CBD (150 μg·kg
vaporised) on bal-
ance or coordination (a product of both cognitive and
motor function). A more recent investigation likewise
found no effect of oral or vaporised CBD (100 mg) on cog-
nitive performance between 30 min and 8 h post-
treatment [160](Table4). Thus, while only a narrow
range of doses and relatively few discrete cognitive func-
tions have been studied, the available data suggest that
CBD is unlikely to impact cognitive or psychomotor func-
tion on healthy individuals.
Other Considerations
CBD NutraceuticalProducts
Over-the-counter CBD-containing nutraceuticalsare
now readily available in many countries and of increasing
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Table 4 Clinical trials investigating the effect of CBD on cognitive and psychomotor function in healthy individuals
Citation Study design Participants Treatment(s) Cognitive tasks Treatment effect
Karniol et al.
(1974) [98]
DB (PC); BSD I: 5 M; 2134 y
I: 5 M; 2134 y
I: 5 M; 2134 y
C: 5 M; 2134 y
I: Oral 15 mg
I: Oral 30 mg
I: Oral 60 mg
Time estimation task
15 mg CBD sig. altered the ETI (without FB) at 45 and 95 min. 60 mg CBD sig. altered the ETI
(without FB) at 95 and 180 min. No other sig. differences were observed.
Dalton et al.
(1975) [49]
DB; WSD 15 M; 2124 y Vaporised
150 μg·kg
Wobble board
Pursuit meter
Delayed auditory feedback
Standing steadiness, hand-eye coordination, cognition and manual coordination were un-
changed from baseline 585 min post-tx
Leweke et al.
(2000) [111]
SB; WSD 9 M; 2635 y Oral 200 mg Binocular depth inversion Depth inversion scores were unchanged from baseline 1, 2, 3, 4, 5, 6 and 24 h post-tx.
Bogwardt et al.
(2008) [22]
DB (PC); WSD 15 M; 27 ± 6 y Oral 600 mg Go/No-Go Task Reaction time and accuracy were unaffected between ~1 and 2h post-tx.
et al. (2009)
DB (PC); WSD 15 M; 27 ± 6 y Oral 600 mg Verbal memory task Word recall was unaffected ~12 h post-tx.
Palo Fusar-Poli
et al. (2009)
DB (PC); WSD 15 M; 27 ± 6 y Oral 600 mg Facial emotion recognition Reaction time and accuracy were unaffected ~12 h post-tx.
Hindocha et al.
(2015) [86]
DB (PC); WSD 48 (34 M); ~22 y Vaporised 16 mg Facial emotion recognition CBD sig. improved emotion recognition at 60% intensity 10 min post-tx. Recognition at 20, 40,
80 and 100% intensity were unaffected.
Hundal et al.
(2017) [90]
DB (PC); BSD I: 16 (8 M); 26 ± 9 y
C: 18 (8 M); 25 ± 8 y
Oral 600 mg Symbol coding
Digit span (forward and
Verbal learning task
Digit-symbol recoding, forward digit span, reverse digit span, immediate recall and delayed
recall were unaffected 135 min post-tx.
Arndt & de Wit
(2017) [8]
DB (PC); WSD 38 (19 M); 24 ± 4 y Oral 300, 600
and 900 mg
Emotional stroop
Facial emotion recognition
Attentional bias task
Reaction time, emotion recognition and attentional bias were unaffected 34 h post-tx.
Birnbaum et al.
(In Press) [19]
No blind; WSD 8 (6 M); 49 y Oral 300 mg Phonemic and semantic
Digit span
Trail making test (A & B)
Symboldigit modality task
Test scores were unchanged from baseline 2.5 h post-tx (test outcomes not specified)
Spindle et al.
(In Press) [160]
DB (PC); WSD 18 (9 M); 31 ± 6 y Oral 100 mg and
Vaporised 100
Digit symbol substitution
Divided attention task
Paced serial addition task
Speed and accuracy of digit symbol substitution and paced serial addition, as well as speed,
accuracy and tracking on the divided attention task were unaffected between 0.5 and 8 h post-
BSD between-subject design, Ccontrol group, CBD cannabidiol, DB double-blind, ETI estimated time interval, FB feedback, Iintervention group, Mmale subjects, PC placebo-controlled, SB single-blind, Tx treatment,
WSD within-subject design
The Treatment effectsdescribed are in comparison to a placebo condition, unless otherwise stated
Time estimation task: participants were asked to produce a 60 s interval 10 times. The first 5 estimations were without feedback and the remaining 5 were with feedback. This task was repeated 45, 95. and
180 min post-treatment
McCartney et al. Sports Medicine - Open (2020) 6:27 Page 12 of 18
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
interest to the community [108]. However, it is important
to be aware that these products are often limited in that
they typically contain low levels of CBD (e.g. ~10-50
), [20] making it difficult to achieve the higher
doses often used in the studies described in this review.
Additionally, over-the-counter CBD nutraceuticals are
not always manufactured to the same pharmaceutical
standards as regulated, prescription CBD products (e.g.
Epidiolex®). Indeed, a recent study [20]reportedthatonly
~31% of CBD extracts sold online (n= 84) were labelled
accurately(i.e. a measured CBD content within 10% of
the labelled value); nearly half underestimated, and a quar-
ter overestimated, their CBD contentapproximately
one-fifth of samples also contained detectable levels of Δ
THC. A similar investigation [148]ofnineCBDe-liq-
uids(used for vaporising) found that two contained Δ
THC, four contained 5-fluoro MDMB-PINACA (a potent
synthetic cannabinoid receptor agonist with powerful psy-
choactive effects), and one contained dextromethorphan.
Thus, individuals using these products are at risk of over-/
under-dosing, adverse health effects and/or possibly, re-
cording a positive drug test result. This suggests that until
such time as better manufacturing standards are imposed,
athletes in competition might wish to avoid using non-
regulated CBD-containing nutraceuticals, or, at least care-
fully investigating their quality control and provenance be-
fore using them.
Conversion of CBD to Δ
In vitro studies have shown that CBD can undergo con-
version to Δ
-THC with prolonged exposure to simulated
gastric fluid [126,189]. However, this effect has not been
observed in vivo. When investigating the phenomenon in
minipigs (30 mg CBD·kg
, oral 5 days), which, like
humans, have omnivorous diets and other GI similarities
(e.g. pH, transit time, drug absorption), Wray et al. [202]
found no detectable (i.e. <0.5 ng·mL
-THC or 11-
OH-THC in any plasma or GI tract samples collected.
Consroe et al. [37] also found no detectable Δ
-THC (i.e.
<0.5 ng·mL
) in human plasma following chronic high-
dose CBD treatment (700 mg·day
; 30 days). These data
suggest that pure CBD is unlikely to produce a positive
drug test result (i.e. indicated by a urinary THCCOOH
level > 150 ng·mL
[200]) or any intoxicating (ergolytic)
effects due to conversion to Δ
-THC. To date, however,
no studies have directly investigated whether CBD can
elicit a positive drug test result in athletes.
CBD has been reported to exert a number of physio-
logical, biochemical, and psychological effects, that have
the potential to benefit athletes. For instance, there is
preliminary supportive evidence for anti-inflammatory,
neuroprotective, analgesic, and anxiolytic actions of
CBD and the possibility it may protect against GI dam-
age associated with inflammation and promote the heal-
ing of traumatic skeletal injuries. However, it is
important to recognise that these findings are very pre-
liminary, at times inconsistent, and largely derived from
preclinical studies. Such studies are limited in their gen-
eralisability to athletes (and humans in general), and
often administer high doses of CBD that may be difficult
to replicate in humans. The central observation is that
studies directly investigating CBD and sports perform-
ance are lacking, and until these are conducted, we can
only speculate in regard to its effects. Nonetheless, this
review suggests that rigorous, controlled investigations
clarifying the utility of CBD in the sporting context are
clearly warranted.
-tetrahydrocannabinol; 5-HT
: Serotonin 1A receptor;
AEA: Anandamide; CV: Cardiovascular; CBD: Cannabidiol; CB
R: Cannabinoid
receptor; CB
R: Cannabinoid CB
receptor; C
: Maximum plasma
concentrations; COX: Cyclooxygenase; CYP: Cytochrome P; EIMD: Exercise-
induced muscle damage; HI: Hypoxic ischemia; FAAH: Fatty acid amide
hydrolase; GI: Gastrointestinal; GPR: G protein-coupled receptor;
IL: Interleukin; i.p.: Intraperitoneal; i.v.: Intravenous; NAM: Negative allosteric
modulator; NSAID: Non-steroidal anti-inflammatory drug; p.o.: Oral;
SPA: Sports performance anxiety; SAD: Social anxiety disorder; TBI: Traumatic
brain injury; T
: Core body temperature; t
: Time to reach maximum
plasma concentrations; TRVP
: Transient potential vanilloid receptor type 1
channel; TNF: Tumour necrosis factor; USA: United States of America
Not applicable.
All authors were involved in the conception and design of this review. DM
was responsible for collating the relevant manuscripts and data. All authors
contributed to the drafting and revising of the article, and the final approval
of the published version of the manuscript.
Not applicable.
Danielle McCartney, Melissa J Benson, Anastasia S Suraev, and Iain S
McGregor receive salary support from the Lambert Initiative for Cannabinoid
Therapeutics, a philanthropically funded centre for medicinal cannabis
research at the University of Sydney. No other sources of funding were used
to assist in the preparation of this article.
Availability of Data and Materials
Not applicable.
Ethics Approval and Consent to Participate
Not applicable.
Consent for Publication
Not applicable.
Competing Interests
Danielle McCartney, Melissa J Benson, Ben Desbrow, Christopher Irwin, and
Anastasia S Suraev have no potential conflicts of interest with the content of
this article. Iain S McGregor currently acts as a consultant to Kinoxis
Therapeutics and is named as an inventor on several patents relating to
novel cannabinoid therapeutics, none of which relate to sports physiology or
McCartney et al. Sports Medicine - Open (2020) 6:27 Page 13 of 18
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Author details
The University of Sydney, Faculty of Science, School of Psychology, Sydney,
New South Wales 2050, Australia.
The University of Sydney, Lambert
Initiative for Cannabinoid Therapeutics, Sydney, New South Wales, Australia.
The University of Sydney, Brain and Mind Centre, Sydney, New South Wales,
School of Allied Health Sciences, Griffith University, Gold Coast,
Queensland, Australia.
Menzies Health Institute Queensland, Gold Coast,
Queensland, Australia.
Received: 5 February 2020 Accepted: 17 May 2020
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... Cannabidiol (CBD) is considered as a non-intoxicating product of Cannabis sativa, a plant that contains several organic compounds with various physiological effects. 1 Although this plant contains at least 144 cannabinoids (CBs), the well-studied compounds are Δ 9 -tetrahydrocannabinol (Δ9-THC), which is notorious for its intoxicating and psychoactive effects, and CBD, for its beneficial effects in biological systems. 2,3 CBD was first isolated many decades ago and was initially considered to be biologically inactive since it seemed to impart no considerable effects. 1 It was not until the early 1970s that researchers documented one of the first significant effects of this CB in convulsive crises in mice. ...
... 2,3 CBD was first isolated many decades ago and was initially considered to be biologically inactive since it seemed to impart no considerable effects. 1 It was not until the early 1970s that researchers documented one of the first significant effects of this CB in convulsive crises in mice. 4 With considerable optimism, this was later replicated in a preclinical trial involving epileptic patients in 1980, 5 and since then, continuous research expanding into other fields of medicine has been on the rise. ...
... 115 Unlike the intoxicating Δ9-THC molecule, CBD is no longer banned by WADA and also shown to be safe and well tolerated in humans. 1 Over the years, the prejudice associating CBD with recreational drugs has slowly faded away. Some countries are beginning to review legislation regarding the use of CBD for medicinal purposes with the liberation of without a prescription "nutraceutical" products. ...
Chronic musculoskeletal (MSK) pain is one of the most prevalent causes, which lead patients to a physician's office. The most common disorders affecting MSK structures are osteoarthritis, rheumatoid arthritis, back pain, and myofascial pain syndrome, which are all responsible for major pain and physical disability. Although there are many known management strategies currently in practice, phytotherapeutic compounds have recently begun to rise in the medical community, especially cannabidiol (CBD). This natural, non-intoxicating molecule derived from the cannabis plant has shown interesting results in many preclinical studies and some clinical settings. CBD plays vital roles in human health that go well beyond the classic immunomodulatory, anti-inflammatory, and antinociceptive properties. Recent studies demonstrated that CBD also improves cell proliferation and migration, especially in mesenchymal stem cells (MSCs). The foremost objective of this review article is to discuss the therapeutic potential of CBD in the context of MSK regenerative medicine. Numerous studies listed in the literature indicate that CBD possesses a significant capacity to modulate mammalian tissue to attenuate and reverse the notorious hallmarks of chronic musculoskeletal disorders (MSDs). The most of the research included in this review report common findings like immunomodulation and stimulation of cell activity associated with tissue regeneration, especially in human MSCs. CBD is considered safe and well tolerated as no serious adverse effects were reported. CBD promotes many positive effects which can manage detrimental alterations brought on by chronic MSDs. Since the application of CBD for MSK health is still undergoing expansion, additional randomized clinical trials are warranted to further clarify its efficacy and to understand its cellular mechanisms.
... Essa mediação se dá devido à interação entre os canabinóides CBD CB1 e CB2 e receptores de adenosina, resultando em níveis reduzidos de citocinas e uma regulamentação negativa das células imunes hiperreativas 16 . Ademais, ingestão de CBD parece ter efeitos positivos nos processos relacionados à proteção contra danos gastrointestinais causados pela inflamação, bem como na cicatrização de lesões esqueléticas 22 . ...
... Além disso, o CBD pode induzir alterações nos glicocorticóides cortisol em humanos, contribuindo para a regulação da resposta inflamatória à lesão. Além disso, uma revisão recente no esporte sugere que este composto também pode ter efeitos anti-inflamatórios em seres humanos, melhorando o desempenho dos atletas 22 . Tal afirmação é baseada na sugestão de que o CBD consegue interagir com receptores envolvidos no controle da inflamação, tais como os canabinóides CB1 e CB2, a adenosina A2A, além de reduzir os níveis das citocinasIL-1 (interleucina-1) e TNFα (fator de necrose tumoral alpha). ...
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Objective: To discuss the effects of CBD and THC on the athlete and their influences on the sport. Method: A literature review was carried out on Google Scholar, ScienceDirect, PubMed, and on the ResearchGate research network, as well as searches on the reference lists of pre-selected works on the subject, using as descriptors: cannabidiol, THC, athletes and sports to check state of the art. Publications in English were used. Research was carried out between April and November 2022. Results: CBD is used as an adjuvant for the treatment of disorders, providing antioxidant, analgesic, anti-inflammatory and neuroprotective properties in sports and clinical environments. Such benefits are observed both in the specific use of CBD, as well as in combination with THC. Conclusion: CBD and THC can exert physiological, biochemical and psychological effects that benefit athletes, however, studies with sportsmen are needed before definitive conclusions can be reached about the usefulness of CBD and THC effects to athletic performance. DESCRIPTORS: Cannabidiol; THC; Athletes; Sports.
... Although their best-known positive effects are related to NCDs, the different kind of compounds that are studied within the scope of physical exercise involve sport performance [26][27][28], fatigue [29,30], muscle recovery [31][32][33], and immunomodulatory antioxidant [5,6,34], and anti-inflammatory actions [32,34]. The results of studie associating polyphenol (mainly flavonoid) supplementation with exercise, especially those involving outcomes related to the immune system, are still controversial. ...
... Although their best-known positive effects are related to NCDs, the different kinds of compounds that are studied within the scope of physical exercise involve sports performance [26][27][28], fatigue [29,30], muscle recovery [31][32][33], and immunomodulatory, antioxidant [5,6,34], and anti-inflammatory actions [32,34]. The results of studies associating polyphenol (mainly flavonoid) supplementation with exercise, especially those involving outcomes related to the immune system, are still controversial. ...
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Food bioactive compounds (FBC) comprise a vast class of substances, including polyphenols, with different chemical structures, and they exert physiological effects on individuals who consume them, such as antioxidant and anti-inflammatory action. The primary food sources of the compounds are fruits, vegetables, wines, teas, seasonings, and spices, and there are still no daily recommendations for their intake. Depending on the intensity and volume, physical exercise can stimulate oxidative stress and muscle inflammation to generate muscle recovery. However, little is known about the role that polyphenols may have in the process of injury, inflammation, and muscle regeneration. This review aimed to relate the effects of supplementation with mentation with some polyphenols in oxidative stress and post-exercise inflammatory markers. The consulted papers suggest that supplementation with 74 to 900 mg of cocoa, 250 to 1000 mg of green tea extract for around 4 weeks, and 90 mg for up to 5 days of curcumin can attenuate cell damage and inflammation of stress markers of oxidative stress during and after exercise. However, regarding anthocyanins, quercetins, and resveratrol, the results are conflicting. Based on these findings, the new reflection that was made is the possible impact of supplementation associating several FBCs simultaneously. Finally, the benefits discussed here do not consider the existing divergences in the literature. Some contradictions are inherent in the few studies carried out so far. Methodological limitations, such as supplementation time, doses used, forms of supplementation, different exercise protocols, and collection times, create barriers to knowledge consolidation and must be overcome.
... CBD can exert a range of physiological, biochemical, and psychological effects with the potential to benefit athletes. However, studies in athletic Vol 16 Iss 2 Year 2023 International Journal of Nutrology populations are needed to better define the usefulness of CBD in supporting athletic performance [41]. ...
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Introduction: The correct interaction between elements of the endocannabinoid system plays an important role in the development of the central nervous system. Clinical and preclinical studies suggest that cannabidiol (CBD) may be useful for athletes due to its anti-inflammatory, analgesic, anxiolytic, and neuroprotective properties and its influence on the sleep-wake cycle. In addition, a series of implications for epigenetic processes have also been proven, through changes in the expression of microRNAs responsible for modulating the immune and inflammatory systems. Objective: It was to develop a systematic review study to highlight the main aspects of cannabidiol in the interaction with microRNAs and exosomes in the modulation of inflammatory and immunological processes in athletes. Methods: The systematic review rules of the PRISMA Platform were followed. The research was carried out from February to April 2023 in Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 228 articles were found, and 84 articles were evaluated in full and 60 were included and developed in this systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 20 studies with a high risk of bias and 90 studies that did not meet GRADE. CBD has been reported to exert a range of physiological, biochemical, and psychological effects with the potential to benefit human health. For example, there is preliminary supporting evidence for the anti-inflammatory, neuroprotective, analgesic, and anxiolytic actions of CBD and the possibility that it may protect against gastrointestinal damage associated with inflammation and promote the healing of traumatic skeletal injuries. The combination of Δ9-THC and CBD can alter the activity of microRNAs responsible for increasing the biosynthesis of inflammatory mediators, leading to a reduction in the inflammatory profile. However, it is important to recognize that these findings are very preliminary, sometimes inconsistent, and largely derived from preclinical studies. These studies are limited in their generalizability to athletes and often administer high doses of CBD. The central observation is that there is a lack of studies that directly investigate CBD and sports performance.
... The terminal half-life of cannabidiols is approximately nine hours and they are primarily excreted through urine in free or in glucuronide form. Existing research showed that cannabidiol manifests anti-inflammatory, immune-modulatory, anxiolytic, antidepressant, and neuro-protective effects due to which it might be useful for athletes (McCartney, Benson, Desbrow, Irwin, Suraev, & McGregor, 2020). Unlike tetrahydrocannabinol, the use of cannabidiol does not cause euphoria or tachycardia (Naik & Trojian, 2021). ...
... These considerations are based on the idea that inflammation, exercise-related damage proliferation, and cell differentiation are closely related to ROS, which gives rise to another hypothesis, that the reduction in oxidative stress can have an important role in sports [249]. On the same note, CBD, by regulating cortisol release via CB1, CB2, and A 2 receptors, decreases the level of immune cells and cytokines (IL-1, TNF-α), and in addition, favors the release of arachidonic acid with the stimulation of healing capacity, promoted by growth and anti-inflammatory signals (lipoxin A4, 15d-PGJ2) [250,251]. ...
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The literature provides scientific evidence for the beneficial effects of cannabidiol (CBD), and these effects extend beyond epilepsy treatment (e.g., Lennox–Gastaut and Dravet syndromes), notably the influence on oxidative status, neurodegeneration, cellular protection, cognitive function, and physical performance. However, products containing CBD are not allowed to be marketed everywhere in the world, which may ultimately have a negative effect on health as a result of the uncontrolled CBD market. After the isolation of CBD follows the discovery of CB1 and CB2 receptors and the main enzymatic components (diacylglycerol lipase (DAG lipase), monoacyl glycerol lipase (MAGL), fatty acid amino hydrolase (FAAH)). At the same time, the antioxidant potential of CBD is due not only to the molecular structure but also to the fact that this compound increases the expression of the main endogenous antioxidant systems, superoxide dismutase (SOD), and glutathione peroxidase (GPx), through the nuclear complex erythroid 2-related factor (Nrf2)/Keep1. Regarding the role in the control of inflammation, this function is exercised by inhibiting (nuclear factor kappa B) NF-κB, and also the genes that encode the expression of molecules with a pro-inflammatory role (cytokines and metalloproteinases). The other effects of CBD on cognitive function and physical performance should not be excluded. In conclusion, the CBD market needs to be regulated more thoroughly, given the previously listed properties, with the mention that the safety profile is a very good one.
Doping, the use of a banned performance-enhancing substance or masking agent, is as old as sports itself. The goal of doping control programs is to promote athlete safety, ensure fair competition, and maintain the integrity of sports. Though doping techniques have become increasingly sophisticated, the overwhelming majority of athletes are against doping. Therefore, the future of anti-doping must be a collaborative effort between players, support personnel, governing bodies, and the public to both improve detection and reduce desire and culture to use in the first place. This chapter is a comprehensive resource for athletes, coaches, and non-professionals.
Cannabidiol (CBD) is a non-psychoactive cannabinoid purported to reduce symptoms of discomfort. Individuals are now using CBD to treat symptoms of multiple sclerosis, seizures, and chronic pain. Animal models indicate that CBD may be effective at reducing inflammation post fatiguing exercise. However, little evidence is available to evaluate these findings in humans. Therefore, the purpose of this investigation was to evaluate the impact of two doses of CBD oil on inflammation (IL-6), performance, and pain after an eccentric loading protocol. Participants (n = 4) participated in three conditions (placebo, low dose, and high dose), in this randomized, counterbalanced design. Each condition took 72 hours to complete, with a 1-week washout period between conditions. At the beginning of each week, participants were subjected to a loading protocol of six sets of ten eccentric only repetitions in the single-arm bicep curl. Participants consumed capsules of either a placebo, low dose (2mg/kg) or high dose (10mg/kg) of CBD oil immediately following the session and continued every twelve hours for 48 hours. Venipunctures were taken before exercise and repeated at 24, 48, and 72 hours post exercise. Blood samples were centrifuged for 15 minutes in gel and lithium heparin vacutainers. Plasma was separated from cells and stored at -80° until analysis. Samples were analyzed using an immunometric assay for IL-6 (ELISA). Data were analyzed using a three (condition) by four (time) repeated measure ANOVA. There were no differences in inflammation between conditions (F(2,6) = 0.726, p = 0.522, np 2 = 0.195) or across time (F(3,9) = 0.752, p = 0.548, np 2 = 0.200), handgrip strength between conditions (F(2,6) = 0.542, p = 0.607, np 2 = .153) or across time (F(3,9) = 2.235, p = .153, np 2 = .427), or bicep curl strength between conditions (F(2,6) = 0.675, p = 0.554, np 2 = .184) or across time (F(3,9) = 3.513, p = .150, np 2 = .539). There were no differences in pain between conditions (F(2,6) = 0.495, p = 0.633, np 2 = .142), but there was a difference across time (F(3,9) = 7.028, p = .010, np 2 = .701). There were no significant interactions to note. Although there was no statistical significance between conditions (likely due to the low sample size), there was a visible increase in IL-6 48 (4.88 ± 6.53) and 72 hours (3.12 ± 4.26) post exercise in the placebo condition which was not observed in the low (48: 0.35 ± 2.22; 72: 1.34 ± 5.6) and high dose condition (48: 1.34 ± 1.34; 72: -0.79 ± 5.34). Future investigations should consider implementing eccentric resistance training across a larger portion of the body to improve ecological validity of the exercise. A larger sample would reduce risk of researchers committing a type II statistical error and give strength to detecting differences between conditions.
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Background Recent legislative change has allowed increased access to cannabis products in many jurisdictions. In some locations, this includes over-the-counter (OTC) and/or online access to products containing cannabidiol (CBD), a non-intoxicating cannabinoid with therapeutic properties. Here we compared the availability of CBD products and the associated legislative and regulatory background in nine selected countries. Methods Accessibility of CBD products was examined in the USA, Canada, Germany, Ireland, United Kingdom, Switzerland, Japan, Australia, and New Zealand as of May 2020. Regulatory and other relevant documents were obtained from government agency websites and related sources. Relevant commercial websites and some physical retailers were visited to verify access to CBD-containing products and the nature of the products available. Results A range of CBD products appeared to be accessible without prescription in seven out of nine countries reviewed. Australia and New Zealand were the exceptions where clinician prescription was required to access any CBD-containing product. CBD products commonly available without prescription included oils, gel capsules, purified crystal and topical products. The daily recommended doses with orally administered non-prescription products were typically well below 150 mg and substantially lower than the doses reported to have therapeutic effects in published clinical trials (e.g., 300-1500 mg). The legal foundations enabling access in several countries were often unclear, with marketed products sometimes failing to meet legal requirements for sale. There was an obvious disparity between federal directives and available products in both the USA and European countries examined. Conclusions There are a variety of approaches in how countries manage access to CBD products. Many countries appear to permit OTC and online availability of CBD products but often without legislative clarity. As consumer demand for CBD escalates, improved legislation, guidelines and quality control of CBD products would seem prudent together with clinical trials exploring the therapeutic benefits of lower-dose CBD formulations.
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Background: The possibility of cannabidiol (CBD) to be used as an antiviral or to treat viral diseases has received limited attention so far, despite the growing number of claims that CBD could be used for the treatment of viral infection-related conditions. Aim and Methods: Therefore, we systematically retrieved and critically evaluated the scientific literature available on PubMed and the claims on the Internet, to assess the current state of knowledge on the use of CBD in viral diseases, and to provide suggestions for future research directions. Results: PubMed search referenced two original articles supporting the use of CBD for the treatment of hepatitis C and Kaposi sarcoma and one article reporting the ability of CBD to reduce neuroinflammation in a virus-induced animal model of multiple sclerosis. Internet search found 25 websites claiming more indications for CBD. Remarkably, those claims were provided mostly by commercial websites and were not supported by appropriate scientific references. Conclusion: Although preclinical studies suggest the potential effectiveness of CBD in viral diseases such as hepatitis C and Kaposi sarcoma, clinical evidence is still lacking. Anecdotal experiences of CBD use retrieved on the Internet, on the other side, lack any support from sound scientific evidence, although they might in some cases provide suggestions for conditions associated with viral infections that may deserve proper assessment in well-designed clinical trials.
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Accumulated evidence indicates that cannabidiol (CBD), a nonpsychotomimetic and nonaddictive main component of the Cannabis sativa plant, reverses anxiety-like behavior. The purpose of the present study was to assess the efficacy of CBD treatment for Japanese late teenagers with social anxiety disorder (SAD). Thirty-seven 18–19-year-old Japanese teenagers with SAD and avoidant personality disorder received, in a double-blind study, cannabis oil (n = 17) containing 300 mg CBD or placebo (n = 20) daily for 4 weeks. SAD symptoms were measured at the beginning and end of the treatment period using the Fear of Negative Evaluation Questionnaire and the Liebowitz Social Anxiety Scale. CBD significantly decreased anxiety measured by both scales. The results indicate that CBD could be a useful option to treat social anxiety.
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This cross-sectional study examines Google searches for cannabidiol (CBD) in the United States to gauge public interest in the use of CBD.
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Introduction: Cannabidiol (CBD) as Epidiolex® (GW Pharmaceuticals) was recently approved by the U.S. Food and Drug Administration (FDA) to treat rare forms of epilepsy in patients 2 years of age and older. Together with the increased societal acceptance of recreational cannabis and CBD oil for putative medical use in many states, the exposure to CBD is increasing, even though all of its biological effects are not understood. Once such example is the ability of CBD to be anti-inflammatory and immune suppressive, so the purpose of this review is to summarize effects and mechanisms of CBD in the immune system. It includes a consideration of reports identifying receptors through which CBD acts, since the “CBD receptor,” if a single one exists, has not been definitively identified for the myriad immune system effects. The review then provides a summary of in vivo and in vitro effects in the immune system, in autoimmune models, with a focus on experimental autoimmune encephalomyelitis, and ends with identification of knowledge gaps. Conclusion: Overall, the data overwhelmingly support the notion that CBD is immune suppressive and that the mechanisms involve direct suppression of activation of various immune cell types, induction of apoptosis, and promotion of regulatory cells, which, in turn, control other immune cell targets.
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Background The main psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC), can impair driving performance. Cannabidiol (CBD), a non-intoxicating cannabis component, is thought to mitigate certain adverse effects of THC. It is possible then that cannabis containing equivalent CBD and THC will differentially affect driving and cognition relative to THC-dominant cannabis. Aims The present study investigated and compared the effects of THC-dominant and THC/CBD equivalent cannabis on simulated driving and cognitive performance. Methods In a randomized, double-blind, within-subjects crossover design, healthy volunteers (n = 14) with a history of light cannabis use attended three outpatient experimental test sessions in which simulated driving and cognitive performance were assessed at two timepoints (20–60 min and 200–240 min) following vaporization of 125 mg THC-dominant (11% THC; < 1% CBD), THC/CBD equivalent (11% THC, 11% CBD), or placebo (< 1% THC/CBD) cannabis. Results/outcomes Both active cannabis types increased lane weaving during a car-following task but had little effect on other driving performance measures. Active cannabis types impaired performance on the Digit Symbol Substitution Task (DSST), Divided Attention Task (DAT) and Paced Auditory Serial Addition Task (PASAT) with impairment on the latter two tasks worse with THC/CBD equivalent cannabis. Subjective drug effects (e.g., “stoned”) and confidence in driving ability did not vary with CBD content. Peak plasma THC concentrations were higher following THC/CBD equivalent cannabis relative to THC-dominant cannabis, suggesting a possible pharmacokinetic interaction. Conclusions/interpretation Cannabis containing equivalent concentrations of CBD and THC appears no less impairing than THC-dominant cannabis, and in some circumstances, CBD may actually exacerbate THC-induced impairment.
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Bone is a dynamic tissue, whose homeostasis is maintained by a fine balance between osteoclast (OC) and osteoblast (OB) activity. The endocannabinoid/endovanilloid (EC/EV) system’s receptors are the cannabinoid receptor type 1 (CB1), the cannabinoid receptor type 2 (CB2), and the transient receptor potential cation channel subfamily V member 1 (TRPV1). Their stimulation modulates bone formation and bone resorption. Bone diseases are very common worldwide. Osteoporosis is the principal cause of bone loss and it can be caused by several factors such as postmenopausal estrogen decrease, glucocorticoid (GC) treatments, iron overload, and chemotherapies. Studies have demonstrated that CB1 and TRPV1 stimulation exerts osteoclastogenic effects, whereas CB2 stimulation has an anti-osteoclastogenic role. Moreover, the EC/EV system has been demonstrated to have a role in cancer, favoring apoptosis and inhibiting cell proliferation. In particular, in bone cancer, the modulation of the EC/EV system not only reduces cell growth and enhances apoptosis but it also reduces cell invasion and bone pain in mouse models. Therefore, EC/EV receptors may be a useful pharmacological target in the prevention and treatment of bone diseases. More studies to better investigate the biochemical mechanisms underlining the EC/EV system effects in bone are needed, but the synthesis of hybrid molecules, targeting these receptors and capable of oppositely regulating bone homeostasis, seems to be a promising and encouraging prospective in bone disease management.
Introduction The use and availability of oral and inhalable products containing cannabidiol (CBD) as the principal constituent has increased with expanded cannabis/hemp legalization. However, few controlled clinical laboratory studies have evaluated the pharmacodynamic effects of oral or vaporized CBD or CBD-dominant cannabis. Methods Eighteen healthy adults (9 men; 9 women) completed four, double-blind, double-dummy, drug administration sessions. Sessions were separated by ≥1 week and included self-administration of 100 mg oral CBD, 100 mg vaporized CBD, vaporized CBD-dominant cannabis (100 mg CBD; 3.7 mg THC), and placebo. Study outcomes included: subjective drug effects, vital signs, cognitive/psychomotor performance, and whole blood THC and CBD concentrations. Results Vaporized CBD and CBD-dominant cannabis increased ratings on several subjective items (e.g., Like Drug Effect) relative to placebo. Subjective effects did not differ between oral CBD and placebo and were generally higher for CBD-dominant cannabis compared to vaporized CBD. CBD did not increase ratings for several items typically associated with acute cannabis/THC exposure (e.g., Paranoid). Women reported qualitatively higher ratings for Pleasant Drug Effect than men after vaporized CBD and CBD-dominant cannabis use. CBD-dominant cannabis increased heart rate compared to placebo. Cognitive/psychomotor impairment was not observed in any drug condition. Conclusions Vaporized CBD and CBD-dominant cannabis produced discriminable subjective drug effects, which were sometimes stronger in women, but did not produce cognitive/psychomotor impairment. Subjective effects of oral CBD did not differ from placebo. Future research should further elucidate the subjective effects of various types of CBD products (e.g., inhaled, oral, topical), which appear to be distinct from THC-dominant products.
Background: Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) time courses in serum, and physiological and behavioral effects associated with smoking 1 or 4 "light cannabis" cigarettes were studied. Biomarkers to differentiate light cannabis vs. illegal and medical cannabis use were also investigated. Methods: Sera were obtained at different times from 6 healthy light cannabis consumers and 6 individuals who smoked 1 and 4 cigarettes, within 4 h via a liquid-liquid method and analyzed by liquid chromatography-tandem mass spectrometry. Results: In serum, minimal THC concentration was observed after a single cigarette smoke, while repeated smoking increased it by one order of magnitude. CBD concentrations were higher, but did not increase linearly, probably because it does not preferentially volatilize compared to THC. The highest THC and CBD concentrations were observed 0.5 h after the start of the smoking of 1 cigarette. Serum THC ranged from 2.7 to 5.9 ng/mL, while serum CBD varied from 5.7 to 48.2 ng/mL. Similarly, the highest THC and CBD concentrations were observed 0.5 h after the smoking of 4 cigarettes. Specifically, the ranges were THC: 11.0-21.8 ng/mL, and CBD: 19.4-35.3 ng/mL. In both cases and the mean THC/CBD concentration ratio ranged from 0.2 to 0.9. There were no significant changes in blood pressure, heart rate, and body temperature, but participants who smoked 4 cigarettes experienced severe drowsiness. Conclusions: THC and CBD time courses in the sera of light cannabis smokers were similar to those previously observed in oral fluid and blood. Serum THC/CBD concentration ratio not higher than the mean value of 0.9 might be a useful biomarker to identify use of light cannabis vs. that of illegal THC cannabis (where THC/CBD concentration ratios are generally greater than 10) or vs. that of medical cannabis (where ratios are greater than 1). Consumers should be advised of possible drowsiness after he repeated smoking of light cannabis cigarettes.
Objective: To evaluate the pharmacokinetics of a purified oral cannabidiol (CBD) capsule administered with and without food in adults with refractory epilepsy. Methods: Adult patients who were prescribed CBD for seizures, had localization-related intractable epilepsy with ≥4 seizures per month, and qualified for Minnesota cannabis were enrolled. A single dose of 99% pure CBD capsules was taken under both fasting (no breakfast) and fed (high fat 840-860 calorie) conditions. Blood sampling for CBD plasma concentrations was performed under each condition between 0 and 72 hours post-dose and measured by a validated liquid chormatography-mass spectometry assay. CBD pharmacokinetic profiles including maximum concentration (Cmax ), area-under-the-curve from zero to infinity (AUC0-∞ ), and time-to-maximum concentration (Tmax ) were calculated. The confidence intervals (CIs) for log-transformed Cmax and AUC0-∞ ratios between fed and fasting states were calculated. Seizure and adverse events information was collected. Results: Eight patients completed the study. On average Cmax was 14 times and AUC0-∞ 4 times higher in the fed state. The 90% CI for the ratio of fed versus fast conditions for Cmax and AUC0-∞ were 7.47-31.86 and 3.42-7.82, respectively. No sequence or period effect for Cmax and AUC0-∞ was observed. No adverse events were reported. Significance: Administering CBD as a capsule rather than a liquid allows for more precise determination of pharmacokinetics parameters and is more representative of CBD swallowed products. The fat content of a meal can lead to significant increases in Cmax and AUC0-∞ and can account for variability in bioavailability and overall drug exposure within patients with oral products.