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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
1,2,3*
, Melissa J. Benson
1,2,3
, Ben Desbrow
4
, Christopher Irwin
4,5
, Anastasia Suraev
1,2,3
and
Iain S. McGregor
1,2,3
Abstract
Cannabidiol (CBD) is a non-intoxicating cannabinoid derived from Cannabis sativa. CBD initially drew scientific
interest due to its anticonvulsant properties but increasing evidence of other therapeutic effects has attracted
the attention of additional clinical and non-clinical populations, including athletes. Unlike the intoxicating
cannabinoid, Δ
9
-tetrahydrocannabinol (Δ
9
-THC), CBD is no longer prohibited by the World Anti-Doping
Agency and appears to be safe and well-tolerated in humans. It has also become readily available in many
countries with the introduction of over-the-counter “nutraceutical”products. The aim of this narrative review
was to explore various physiological and psychological effects of CBD that may be relevant to the sport and/
or exercise context and to identify key areas for future research. As direct studies of CBD and sports
performance are is currently lacking, evidence for this narrative review was sourced from preclinical studies
and a limited number of clinical trials in non-athlete populations. Preclinical studies have observed robust
anti-inflammatory, neuroprotective and analgesic effects of CBD in animal models. Preliminary preclinical
evidence also suggests that CBD may protect against gastrointestinal damage associated with inflammation
and promote healing of traumatic skeletal injuries. However, further research is required to confirm these
observations. Early stage clinical studies suggest that CBD may be anxiolytic in “stress-inducing”situations and
in individuals with anxiety disorders. While some case reports indicate that CBD improves sleep, robust
evidence is currently lacking. Cognitive function and thermoregulation appear to be unaffected by CBD while
effects on food intake, metabolic function, cardiovascular function, and infection require further study. CBD
may exert a number of physiological, biochemical, and psychological effects with the potential to benefit
athletes. However, well controlled, studies in athlete populations are required before definitive conclusions
can be reached regarding the utility of CBD in supporting athletic performance.
Keywords: Cannabidiol, CBD, Cannabis, Cannabinoid, Athletic performance, Exercise
© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,
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* Correspondence: danielle.mccartney@sydney.edu.au
1
The University of Sydney, Faculty of Science, School of Psychology, Sydney,
New South Wales 2050, Australia
2
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
https://doi.org/10.1186/s40798-020-00251-0
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
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.
Introduction
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
9
-tetrahydrocannabinol (Δ
9
-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 “subjective”drug 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 ‘CBD’in the United States
(USA) [108]. Some professional athletes (e.g. golfers,
rugby players) also appear to be using CBD (e.g. ‘Team
cbdMD’https://www.cbdmd.com/), 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. 5–50 mg·d
−1
) 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 Organization’s 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
mg·day
−1
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
9
-THC (as well as
some of its therapeutic effects) involve the activation of
CB
1
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
Δ
9
-THC, CBD is not an agonist of CB
1
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].
Δ
9
-THC also acts as an agonist at CB
2
R(thecannabinoid
type 2 receptor) [12] and there is emerging evidence of
CBD functioning as a partial agonist at this site [171].
CB
2
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
CB
1
RandCB
2
R, thereby increasing endocannabinoid tone
[92,110]. Increases in endocannabinoid tone may also
occur as a result of CBD inhibiting AEA transport via
McCartney et al. Sports Medicine - Open (2020) 6:27 Page 2 of 18
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
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
[5-HT
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.
Pharmacokinetics
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 (1500–6000
mg), the time to reach peak plasma concentrations (t
max
)was
~4–5 h and the terminal half-life was ~14–17 h. Although
t
max
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
max
(i.e. ~2–3h).
Peak plasma concentrations (C
max
)were~0.9–2.5 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
9
-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
max
and C
max
are unknown
[146,160].
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
9
-
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
conversion:
HED mg kg‐1
¼DoseAnimal mg kg‐1
KmAnimal
KmHuman
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
max
values ~7-fold higher than oral dosing in mice [52]. Thus,
an “oral equivalent dose”canbeapproximatedbymulti-
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
Performance
Literature Search Methodology
The clinical and preclinical literature was reviewed to
identify studies investigating the effects of CBD that
might be relevant within a sport and/or exercise context.
The online databases PubMed (MEDLINE), Web of Sci-
ence (via Thomas Reuters), and Scopus were searched
between April and October of 2019 using terms such as:
‘cannabinoid’‘cannabidiol’,‘CBD’and ‘cannabis’. This
review focuses primarily on effects that have been 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
McCartney et al. Sports Medicine - Open (2020) 6:27 Page 3 of 18
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
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 Damage—Muscle 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 hypoxic–ischemia (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
−1
, i.p.); although, lower doses
(e.g. ~1.5 mg·kg
−1
, i.p.) have indicated efficacy in some
studies [145]. Research investigating the effects of CBD
on inflammation in humans is limited and inconclusive
[94,133].
In terms of muscle-specific inflammation, one preclin-
ical study has investigated the effect of high-dose CBD
(i.e. 60 mg·kg
−1
·d
−1
, i.p.) on transcription and synthesis
of pro-inflammatory markers (i.e. IL-6 receptors, TNF-α,
TNF-β1, and inducible nitric oxide synthase) in the
gastrocnemius and diaphragm of dystrophic MDX mice
(a mouse model of Duchenne muscular dystrophy) [91].
In this investigation, CBD attenuated mRNA expression
of each marker and reduced plasma concentrations of
IL-6 and TNFα. Improvements in muscle strength and
coordination, as well as reductions in tissue degener-
ation, were also reported at this dose. Lower, but still
relatively high, CBD doses (20–40 mg·kg
−1
·day
−1
,i.p.)
had no functional benefits [91]. Of course, it is 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
(mg·kg
-1
, i.p.)
HED
(mg, p.o.)
Rat Dose
(mg·kg
-1
, i.p.)
HED
(mg, p.o.)
134168
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
McCartney et al. Sports Medicine - Open (2020) 6:27 Page 4 of 18
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Neuroprotection—Concussion and Subconcussion
Recent estimates suggest that 6–36% 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 neurological–cognitive–behavioural 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
−1
, oral) 1–14 and 50–60 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
−1
, i.v.) on HI-induced neuronal
damage in piglets, others observed neuroprotection at
similar doses (e.g. 1 mg·kg
−1
, i.v [105,143]., 1 mg·kg
−1
,
s.c [127,142]., and 5 mg·kg
−1
, 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
−1
,
intracerebroventricular 5 days; Wistar rats [100]), shortly
pre- and/or post-HI
1
, and up to 3 days post-HI (e.g. 3
mg·kg
−1
·day
−1
, i.p. 12 days; ddY mice [80]). Thus,
chronic CBD treatment may be more effective than
acute intervention. While “pre-incident”dosing 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 Alzheimer’s 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
9
-
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 [29,39–41,51,70,75,
78], albeit somewhat less pronounced than the effects of
Δ
9
-THC [29,78] (e.g. Hedges’g= 0.8 vs. 1.8 [78]) or of
gabapentin (e.g. Hedges’g= 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
1
channel [40,41,
51]. This mechanism is noteworthy as studies have
1
E.g. 10–30 mg·kg
−1
·day
−1
, i.p. 3 days [129,153], 1 mg·kg
−1
·day
−1
, i.v. 3
days [13], 1–3 mg·kg
−1
, i.p. pre- and 3 h post-HI [81,83] or 0.1
mg·kg
−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
-1
·d
-1
, 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
-1
, 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
-1
, s.c. CBD dose-dependently decreased mechanical and cold allodynia.
King et al., (2017) [101] C57BL/6 mice CT (Paclitaxel) 0.625–20 mg·kg
-1
, i.p. 15 min prior to CT on days 1, 3, 5 and 7 1 and 20 mg·kg
-1
CBD sig. attenuated the development of
mechanical allodynia measured on Tx days 9 and 14, but not 21.
CT (Oxaliplatin) 1.25–10 mg·kg
-1
, i.p. 15 min prior to CT on days 1, 3, 5 and 7 1.25–10 mg·kg
-1
CBD sig. attenuated the development of
mechanical allodynia measured on Tx days 2, 4, 7 and 10.
CT (Vincristine) 1.25–10 mg·kg
-1
, 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
-1
, i.p. CBD sig. decreased tactile allodynia 1 h post-Tx.
0.5, 1 or 2 mg·kg
-1
, 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
-1
·d
-1
, i.p. 15 min prior to CT on days 1, 3, 5 and 7 2.5 and 5 mg·kg
-1
·d
-1
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
-1
·d
-1
, i.n. 3 months 1 and 2 mg·kg
-1
·d
-1
CBD sig. attenuated the development of
thermal and tactile hypersensitivity compared to 0.1 mg·kg
-1
·d
-1
CBD.
2 mg·kg
-1
·d
-1
, i.n. 1 month CBD did not alleviate developed thermal or tactile hypersensitivity.
1, 10 or 20 mg·kg
-1
·d
-1
, i.p. 3 months 20 mg·kg
-1
·d
-1
CBD sig. attenuated the development of thermal
and tactile hypersensitivity compared to 1 mg·kg
-1
·d
-1
CBD.
20 mg·kg
-1
·d
-1
, i.p. 1 month CBD did not alleviate developed thermal or tactile
hypersensitivity.
Costa et al., (2007) [41] Wistar rats CCI 2.5, 5, 10 or 20 mg·kg
-1
·d
-1
, oral 7 d 5, 10 and 20 mg·kg
-1
·d
-1
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
-1
, i.p. 3 mg·kg
-1
CBD sig. decreased mechanical allodynia between 30-
and 150-min post-Tx; 10 mg·kg
-1
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
-1
·d
-1
, t.c. 4 d 6.2 and 62.3 mg·kg
-1
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
-1
·d
-1
, 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
-1
, oral 5, 7.5, 10, 20 and 40 mg·kg
-1
·d
-1
CBD sig. decreased thermal
hyperalgesia 1–5 h post-Tx.
Costa et al., (2004) [40] Wistar rats Carrageenan 10 mg·kg
-1
, oral CBD sig. decreased thermal hyperalgesia 1 h post-Tx.
The ‘Treatment Effects’described are in comparison to a vehicle condition, unless otherwise stated
CBD Cannabidiol, CCI Chronic Constriction Injury, CT Chemotherapy, FCA Freund’s Complete Adjuvant, i.n. Intranasal, i.t. Intrathecal, s.c. Subcutaneous, SNI Spared Nerve Injury, STZ Streptozotocin, t.c. Transcutaneously,
Tx Treatment
McCartney et al. Sports Medicine - Open (2020) 6:27 Page 6 of 18
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
implicated the TRPV
1
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
−1
, 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
skin—other 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. 0.01–10 mg·kg
−1
, i.v. or 10 mg·kg
−1
, 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 Damage—Muscle Function, Soreness, and In-
jury”)[50,55,60,62,63,130,154,185]. Also, of interest
is that CBD (1–100 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,
TNF-α)[2,3,71].
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
−1
; 56 days) on symptom
severity in Crohn’s disease (n=20)[133] and the other
examining the impact of a “CBD-rich botanical extract”
(250 mg·day
−1
[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. 50–500 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
–1
·day
–1
, 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
2
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
unaffected.
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.
Bhattacharyya
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.
Martin-Santos
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
mg
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]
DB (PC); WSD
SAD Participants
10 M; 24 ± 4 y Oral 400 mg Low stress CBD sig. reduced SA 60, 75 and 140 min post-Tx.
Bergamaschi
et al. (2011) [15]
DB (PC); BSD
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]
DB (PC); BSD
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)
[124]
DB (PC); BSD
SAD Participants
I: 17 (8 M); 18–19 y
C: 20 (8 M); 18–19 y
Oral 300
mg·d
-1
(28-
days)
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 effects”described are in comparison to a placebo condition, unless otherwise stated
McCartney et al. Sports Medicine - Open (2020) 6:27 Page 8 of 18
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Cardiovascular (CV) and Metabolic Functions
A number of studies have measured CV responses to
CBD (100–1200 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 “resting”CV 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
2
= 73%; HR −16 mmHg;
95% CI −26, −6; I
2
= 92%) [165], that said, most studies
measuring CV responses to CBD (150–600 mg) under
“stress-inducing”conditions 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] (30–60 mg·kg−
1
, i.p. acute or chronic 14 days
Wistar rats; 3 and 10 mg·kg
−1
, i.v. C57BL/6 J mice; 10
mg·kg
−1
·day
−1
, i.p. 5 days C57BL/6 J mice; and 10
mg·kg
−1
·day
−1
, 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
−1
·day
−1
,
i.p. 5 days C57BL/6 J mice; myocardium following doxo-
rubicin treatment). Such effects could have implications
for energy metabolism during exercise.
Thermoregulation
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
C
), there-
fore has the potential to impact exercise performance
[192]. The effect of CBD on T
C
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
−1
,
30 min vaporised; Wistar rats) reduced T
C
(−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
−1
,
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
C
in these
experiments is difficult to explain, since although other
cannabinoids (e.g. Δ
9
-THC, AEA) have demonstrated a
capacity to moderate T
C
when administered exogenously
(e.g. low doses of Δ
9
-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
CB
1
R-mediated mechanism [42,166,196]. In addition to
this, no other studies appear to have detected changes in
T
C
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
C
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
C
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 3–100
mg·kg
−1
, i.p. (IRC mice) [195] and 1–20 mg·kg
−1
, 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
−1
, i.p. [58]. and 50 mg·kg
−1
, i.p. [159])
suppressed food intake (in rats) during longer ad libitum
feeding periods (i.e. 4–6 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
−1
·day
−1
, 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 (5–20
mg·kg
−1
·day
−1
) 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
1
R agonist effects (e.g. Δ
9
-
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
2
R antagonist, AM630,
prevented CBD-induced BM changes; however, CB
2
R
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
1
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-
fects”of 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 ~3.2–15.9 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
(EC
50
= 3.2 μM) and the Kaposi’s sarcoma-associated
herpesvirus (EC
50
= 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
Damage—Muscle 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 (5–20 mg·kg
−1
·day
−1
) and placebo
(approx. 10% of individuals) [107]. Further research to
develop a better understanding of “if”and “how”CBD
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]and“stress-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 stress”conditions in
healthy participants [18,86,123]. However, several stud-
ies have demonstrated anxiolytic effects of CBD (300–
600 mg) under “stress-inducing”conditions 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
1A
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-inducing”stimuli) 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 (Hedges’g= 1.0) had a
stronger anxiolytic effect than 150 mg (Hedges’g= 0.7)
or 600 mg (Hedges’g= 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.
Sleep
The importance of adequate sleep in facilitating optimal
athletic performance and recovery is increasingly recog-
nised [121]. Yet, athletes often sleep less (e.g. ~6.5–6.7
h·night
−1
) 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 sleep”were 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 Parkinson’s disease (75–300 mg·day
−1
; 42 day)
and Shannon et al. [157] found that CBD (~25 mg·day
−1
)
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
9
-THC (15 mg),
i.e. increasing overnight wakefulness; although, this ef-
fect could be due to CBD acting as a NAM of CB
1
R,
thereby attenuating Δ
9
-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
−1
, 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
9
-THC, e.g. ~10–25 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 “ability”may have limited relevance to the sporting
context. More applicable, perhaps, is Dalton et al. [49]
finding no effect of CBD (150 μg·kg
−1
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 “Nutraceutical”Products
Over-the-counter CBD-containing “nutraceuticals”are
now readily available in many countries and of increasing
McCartney et al. Sports Medicine - Open (2020) 6:27 Page 11 of 18
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
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; 21–34 y
I: 5 M; 21–34 y
I: 5 M; 21–34 y
C: 5 M; 21–34 y
I: Oral 15 mg
I: Oral 30 mg
I: Oral 60 mg
Time estimation task
a
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; 21–24 y Vaporised
150 μg·kg
-1
Wobble board
Pursuit meter
Delayed auditory feedback
“Pegs”
Standing steadiness, hand-eye coordination, cognition and manual coordination were un-
changed from baseline 5–85 min post-tx
Leweke et al.
(2000) [111]
SB; WSD 9 M; 26–35 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.
Bhattacharyya
et al. (2009)
[17]
DB (PC); WSD 15 M; 27 ± 6 y Oral 600 mg Verbal memory task Word recall was unaffected ~1–2 h post-tx.
Palo Fusar-Poli
et al. (2009)
[67]
DB (PC); WSD 15 M; 27 ± 6 y Oral 600 mg Facial emotion recognition Reaction time and accuracy were unaffected ~1–2 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
reverse)
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 3–4 h post-tx.
Birnbaum et al.
(In Press) [19]
No blind; WSD 8 (6 M); 49 y Oral 300 mg Phonemic and semantic
fluency
Digit span
Trail making test (A & B)
Symbol–digit 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
mg
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-
tx.
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 effects”described are in comparison to a placebo condition, unless otherwise stated
a
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
mg·mL
−1
), [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 content—approximately
one-fifth of samples also contained detectable levels of Δ
9
-
THC. A similar investigation [148]ofnineCBD“e-liq-
uids”(used for vaporising) found that two contained Δ
9
-
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
9
-THC
In vitro studies have shown that CBD can undergo con-
version to Δ
9
-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
−1
·day
−1
, 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
−1
)Δ
9
-THC or 11-
OH-THC in any plasma or GI tract samples collected.
Consroe et al. [37] also found no detectable Δ
9
-THC (i.e.
<0.5 ng·mL
−1
) in human plasma following chronic high-
dose CBD treatment (700 mg·day
−1
; 30 days). These data
suggest that pure CBD is unlikely to produce a positive
drug test result (i.e. indicated by a urinary THC–COOH
level > 150 ng·mL
−1
[200]) or any intoxicating (ergolytic)
effects due to conversion to Δ
9
-THC. To date, however,
no studies have directly investigated whether CBD can
elicit a positive drug test result in athletes.
Conclusions
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.
Abbreviations
Δ
9
-THC: Δ
9
-tetrahydrocannabinol; 5-HT
1A
: Serotonin 1A receptor;
AEA: Anandamide; CV: Cardiovascular; CBD: Cannabidiol; CB
1
R: Cannabinoid
CB
1
receptor; CB
2
R: Cannabinoid CB
2
receptor; C
max
: 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
C
: Core body temperature; t
max
: Time to reach maximum
plasma concentrations; TRVP
1
: Transient potential vanilloid receptor type 1
channel; TNF: Tumour necrosis factor; USA: United States of America
Acknowledgements
Not applicable.
Authors’Contributions
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.
Authors’information
Not applicable.
Funding
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
medicine.
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
1
The University of Sydney, Faculty of Science, School of Psychology, Sydney,
New South Wales 2050, Australia.
2
The University of Sydney, Lambert
Initiative for Cannabinoid Therapeutics, Sydney, New South Wales, Australia.
3
The University of Sydney, Brain and Mind Centre, Sydney, New South Wales,
Australia.
4
School of Allied Health Sciences, Griffith University, Gold Coast,
Queensland, Australia.
5
Menzies Health Institute Queensland, Gold Coast,
Queensland, Australia.
Received: 5 February 2020 Accepted: 17 May 2020
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