ArticlePDF AvailableLiterature Review

Cannabidiol (CBD) as a treatment of acute and chronic back pain: A case series and literature review



Objective: Two patient case reports are presented describing the use of cannabidiol (CBD) for the symptomatic relief of a lumbar compression fracture and in the mitigation of thoracic discomfort and dysesthesia secondary to a surgically resected meningioma. Discussion: CBD appears to have antisnociceptive and anti-inflammatory effects on opioid-naive patients with neuro-pathic and radicular pain. Of note, the patients in this case series used the same CBD cream: Baskin Essentials Body Wellness Cream (400 mg CBD per two oz.) Conclusion: Hemp-derived CBD in a transdermal cream provided significant symptom and pain relief for the patients described in this case series. Based on these results, we believe further investigation is warranted to see if CBD-containing products should have a more prominent role in the treatment of acute and chronic pain.
Journal of Opioid Management 16:3 n May/June 2020
CliniCal RepoRt
Cannabidiol (CBD) as a treatment of acute and chronic back pain:
A case series and literature review
Jonathan P. Eskander, MD, MBA; Junaid Spall, BS; Awais Spall, BA;
Rinoo V. Shah, MD, MBA; Alan D. Kaye, MD, PhD
Objective: Two patient case reports are presented describing the use of canna-
bidiol (CBD) for the symptomatic relief of a lumbar compression fracture and in
the mitigation of thoracic discomfort and dysesthesia secondary to a surgically
resected meningioma.
Discussion: CBD appears to have antisnociceptive and anti-inflammatory
effects on opioid-naive patients with neuropathic and radicular pain. Of note,
the patients in this case series used the same CBD cream: Baskin Essentials Body
Wellness Cream (400 mg CBD per two oz.)
Conclusion: Hemp-derived CBD in a transdermal cream provided significant
symptom and pain relief for the patients described in this case series. Based on
these results, we believe further investigation is warranted to see if CBD-containing
products should have a more prominent role in the treatment of acute and chronic
Cannabidiol (CBD) is a phytocannabinoid and
one of the most abundant 113 identified cannabi-
noids as well as 432 other chemical compounds
found in the cannabis plant.1,2 Its mechanism
of action has not been determined; however, it
may interact with numerous targets. However,
the Food and Drug Administration (FDA) has
approved the CBD drug Epidiolex® for the treat-
ment of two forms of rare childhood epilepsy
disorders: Dravet syndrome and Lennox-Gastaut
syndrome.3 Based on previous research, cannabi-
noids seem to possess antinociceptive responses
stemming from nociceptive neuron inhibition and
pain processing.2
Cannabinoid (CB) receptors decrease excita-
tory neurotransmission, modulate psychotrophic
effects, as well as ventral tegmental dopamine neu-
ronal activity critically associated with addiction.2
Cannabinoids exert their effects via the activation of
the G-protein coupled receptors, cannabinoid CB1
and CB2. Additionally, it is possible that there are still
more cannabinoid receptors still unknown to us. CB1
receptors are found predominantly along the pain
pathways of the central nervous system4 as well as in
the ocular, cardiovascular, and gastrointestinal sys-
tems.5 The CB2 receptor, which has a significantly
lower affinity for THC compared to CB1,5 is found
primarily in the immune system.6-8 Some authors sug-
gest that CB1 and CB2 agonists might induce antino-
ciception via the release of endogenous opioids and
compression fracture
low back pain
chronic pain
thoracic back pain
© 2020 Journal of Opioid Management,
All Rights Reserved.
06-SA-JOM#200008.indd 215 09/05/20 8:13 PM
Journal of Opioid Management 16:3 n May/June 2020
possibly by increasing opioid precursor gene expres-
sion.8 Emerging research suggests that cannabi-
noids may be promising treatments for neuropathic,
inflammatory, and oncologic pain.8
Endocannabinoids, a family of bioactive lipids,
are derived from arachidonic acid metabolism. They
are structurally like arachidonic acid and chemi-
cals that interact with the endocannabinoid system
are believed to diminish inflammation. Arachidonic
acid metabolite regulation is also part of the mech-
anism by which nonsteroidal anti-inflammatory
drugs (NSAIDs) reduce pain and inflammation. This
includes cyclooxygenase-2 (COX-2) inhibition and
fatty acid amide hydrolase (FAAH). Regulation of
these pathways leads to increased endocannabinoids
anandamide (AEA), as well as decreased arachidonic
acid and prostaglandin levels. Endocannabinoid
production is also increased by the conversion of
omega-3 fatty acids which possess anti-inflamma-
tory and vasodilatory properties.9,10 It is believed
that endocannabinoids activate previously described
cannabinoid receptors and modulate neural trans-
mission.8 This suggests that endocannabinoids par-
ticipate in a variety of cerebral and systemic functions
including pain perception, mood-enhancement, anti-
inflammatory effects, and more.11
Encouraging results in the treatment of chronic
pain in animal models have recently been demon-
strated by compounds with multiple mechanisms.12
CBD treatment in diabetic mice showed a reduc-
tion in tactile allodynia, which suggests an effect
on neuropathic pain. Additionally, CBD has shown
antinociceptive and anti-inflammatory properties
without known adverse effects to the central nerv-
ous system.11,13
Regarding neuropathic pain, CB1 agonists work
alongside a set of receptors known as transient
receptor potentials (TRPs). TRPs refers to groups
of ion channels located across plasma membranes
of various organ systems and nerve cells. These ion
channels have nonselective permeability for cati-
ons, the regulation of which, can alter inflammatory
responses.14 As Lowin and Straub note, TRPs induce
the sensation of pain but also support inflamma-
tion via secretion of pro-inflammatory cytokines.14
An important subgroup within this receptor super-
family includes the TRP Vanilloid receptors, which
have been studied to bind to various cannabi-
noids.15 Upon activation, via entrance of calcium
and magnesium, the TRPV1 channel undergoes
desensitization, which has a considerable impact on
nerve-affiliated nociceptive transduction.16 These
hyperalgesic effects of TRPs are critical for under-
standing the physiological dynamics of chronic
nerve injury and pain. Furthermore, nerve injury
also triggers an immunological response initiating
the production of inflammatory macrophages that
retract sympathetic nerve fibers.14 Hypothalamic
norepinephrine thus falls under the threshold for
anti-inflammatory beta-2 receptor activation and this
favors pro-inflammatory effects, via alpha-adrener-
gic signaling.17 Further down in the cascade, this can
lead to an increase of nerve fiber signaling to the
CNS that triggers nociception. In chronic inflamma-
tory conditions, pro-inflammatory cytokines, such
as TNF and IL-10, can over-sensitize TRPV1 recep-
tors.18 Inhibiting TRPV1 function via CB1 activation
and FAAH inhibition reduces intracellular calcium
that can initiate analgesia by reducing the inflamma-
tory cytokine cascade often associated with pain.19
The immunomodulatory component of cannabi-
noids is indirectly accompanied by the antihyper-
algesic effects initiated by the ionotropic regulation
of Ca+.
The route of administration of CBD in the two
patients discussed in this report is transdermal.
Previous studies, using animal models, describe the
steady-state plasma concentrations of transdermal
CBD in guinea pigs did reach potentially therapeu-
tic levels (6.3 ng/mL) which was reached 15 hours
after application. Enhancers did increase absorption
3.7-fold.20 Of note, some CBD creams for sale use
proprietary technology to enhance the absorption
of CBD via the transdermal route. Another study
involved mice and transdermal ethosome CBD.
After application, CBD levels lasted at least 72 hours
and notably there was significant accumulation of
CBD as measured in underlying muscle.21
Some potential side effects of cannabinoids
include increased bleeding risk via suppression of
platelets and anticoagulants.22 In addition, CBD can
interact with warfarin and increase the risk of bleed-
ing complications. Like warfarin, CBD is metabo-
lized through the hepatic P450 enzyme system.
Both share the same isoforms in their metabolism.
CBD acts on CYP1A1, CYP1A2, CYP2C9, CYP2C19,
CYP2D6, CYP3A4, and CYP3A5.
A 40-year-old African American man pre-
sented with 8/10 low back pain secondary to an
06-SA-JOM#200008.indd 216 09/05/20 8:13 PM
Journal of Opioid Management 16:3 n May/June 2020
L3 compression fracture suffered after a fall. His
medical history is significant for an epidural abscess
requiring evacuation and subsequent posterior
instrumentation and fusion of the lumbar spine
10 years ago. He does not take any medications.
After it was determined by his healthcare provid-
ers that he was not a candidate for a kyphoplasty,
he began conservative therapy using a combination
of acetamenophen and NSAIDS; neither of which
provided significant relief. Beginning on week two
status-post L3 vertebral compression fracture, he
began applying CBD cream twice daily to his lower
back. He applied a small amount of cream over the
affected area. He endorsed approximately 10 hours
of pain reduction to a 1/10 or 2/10. Pain from low
back muscle spasms as well as radiating pain to his
sacrum were mitigated. After 4 weeks of treatment,
he stopped using all medications as his low back
pain resolved.
A 61-year-old Caucasian woman presenting with
thoracic sensory disturbance and dysesthesia for
over 2 years following a surgical resection of a spi-
nal meningioma at the T6-7 level involving the lat-
eral intradural extramedullary compartment of the
vertebral canal. Her medical history is significant for
rheumatoid arthritis, cervical degenerative disc dis-
ease with left-sided radiculopathy, and obesity. Her
medications include methotrexate and simvastatin.
After using CBD cream applied to the affected area
of her thoracic spine, she endorsed approximately
7-8 hours of relief from sensory disturbance and
The CBD has multiple theoretical targets includ-
ing CB2 receptors, alpha-2 adrenergic receptor ago-
nism, indirect stimulation of opioid receptors, and
mediators of the inflammatory processes and noci-
ceptive pathways. Modulation of the noradrenergic
system and indirect stimulation of opioid receptors
via CB2 receptors can be important in the treat-
ment of pain, anxiety, depression, and opioid with-
drawal. This could help explain why CBD appears
to be an effective antinociceptive compound. This
case series suggests that CBD may have antinocicep-
tive and anti-inflammatory effects on opioid-naive
patients with neuropathic and radicular pain. Due
to lack of evidence, it is unknown which products
containing CBD have a similar effect. Since CBD
creams are not regulated by the Food and Drug
Administration (FDA) it is difficult to determine the
efficacy and potency of each product in the market.
Interestingly, both of the aforementioned patients
used the same CBD cream: Baskin Essentials Body
Wellness Cream. Hemp-derived CBD in a topical
cream provided significant symptom and pain relief
for the patients described in this case series. It should
be noted that these products are third-party labora-
tory tested to ensure that the active ingredients are
as stated on the label. Based on these results, we
believe further investigation is warranted to see if
these products have a role in the treatment of acute
and chronic pain. A high-powered study involving
patients afflicted by either chronic and acute pain
conditions is warranted in order to examine to what
extent CBD can mitigate pain.
No funding was received for this manuscript.
1. Boggs DL, Nguyen JD, Morgenson D, et al.: Clinical and pre-
clinical evidence for functional interactions of cannabidiol and
Δ9-tetrahydrocannabinol. Neuropsychopharmacology. 2017;
43(1): 142-154.
2. Vadivelu N, Kai AM, Kodumudi G, et al.: Medical Marijuana:
Current concepts, pharmacological actions of cannabinoid
receptor mediated activation, and societal implications. Curr
Pain Headache Rep. 2018; 22(1): 3.
3. US Food and Drug Administration: FDA approves first drug
comprised of an active ingredient derived from marijuana to
treat rare, severe forms of epilepsy. Silver Spring: US Food and
Drug Administration, 2018.
Jonathan P. Eskander, MD, MBA, Department of
Anesthesiology and Pain Medicine, Portsmouth Anesthesia
Associates, Portsmouth, Virginia.
Junaid Spall, BS, Department of Chemistry, University of
California, San Diego, California.
Awais Spall, BA, Department of Chemistry, University of
California, Berkeley, California.
Rinoo V. Shah, MD, MBA, Department of Anesthesiology,
Louisiana State University Health Sciences Center—
Shreveport, Shreveport, Louisiana.
Alan D. Kaye, MD, PhD, Department of Anesthesiology
and Pharmacology, Louisiana State University School of
Medicine, New Orleans, Louisiana.
06-SA-JOM#200008.indd 217 09/05/20 8:13 PM
Journal of Opioid Management 16:3 n May/June 2020
4. Beaulieu P, Boulanger A, Desroches J, et al.: Medical canna-
bis: Considerations for the anesthesiologist and pain physician.
J Canadien D'anesthesie. 2016; 63(5): 608-624.
5. Schrot RJ, Hubbard JR: Cannabinoids: Medical implications.
Ann Med. 2016; 48(3):128-141.
6. Devane WA, Dysarz FR, Johnson MR, et al.: Determination
and characterization of a cannabinoid receptor in rat brain. Mol
Pharmacol. 1988; 34(5): 605-613.
7. Munro S, Thomas KL, Abu-Shaar M: Molecular characteriza-
tion of a peripheral receptor for cannabinoids. Nature. 1993;
365(6441): 61.
8. Wolf J, Urits I, Orhurhu, V, et al.: The role of the cannabinoid
system in pain control and therapeutic implications for the man-
agement of acute and chronic pain. Curr Pain Headaches (In
9. Eskander JP: A return to homeostasis: The pleiotropic effects
of icosapent ethyl. BMJ case reports (resubmitted).
10. McDougle DR, Watson JE, Abdeen AA, et al.: Anti-
inflammatory ω-3 endocannabinoid epoxides. Proc Natl Acad
Sci USA. 2017; 114(30): E6034-E6043.
11. Manzanares J, Julian MD, Carrascosa A: Role of the can-
nabinoid system in pain control and therapeutic implications
for the management of acute and chronic pain episodes. Curr
Neuropharmacol. 2006; 4(3): 239-257.
12. Glaser ST, Kaczocha M: Cyclooxygenase-2 mediates anan-
damide metabolism in the mouse brain. J Pharmacol Exp Ther.
2010; 335(2): 380-388.
13. Toth CC, Jedrzejewski NM, Ellis CL, et al.: Cannabinoid-
mediated modulation of neuropathic pain and microglial accu-
mulation in a model of murine type I diabetic peripheral neuro-
pathic pain. Mol Pain. 2010; 6: 1744-8069.
14. Lowin T, Straub R: Cannabinoid-based drugs targeting CB1
and TRPV1, the sympathetic nervous system, and arthritis.
Arthritis Res Therapy. 2015; 17(1): 226.
15. Pellati F, Borgonetti V, Brighenti V, et al.: Cannabis sativa
L. and nonpsychoactive cannabinoids: Their chemistry and role
against oxidative stress, inflammation, and cancer. BioMed Res
Int. 2018: 2018; pp. 1-15.
16. Vennekens R, Owsianik G, Nilius B: Vanilloid transient
receptor potential cation channels: An overview. Curr Pharm
Des. 2008; 14(1): 18–31.
17. Tan KS, Nackley AG, Satterfield K, et al.: Beta2 adrenergic
receptor activation stimulates pro-inflammatory cytokine pro-
duction in macrophages via PKA- and NF-kappaB-independent
mechanisms. Cell Signal. 2007; 19(2): 251-260.
18. Russell FA, Fernandes ES, Courade JP, et al.: Tumour necro-
sis factor alpha mediates transient receptor potential vanilloid
1-dependent bilateral thermal hyperalgesia with distinct periph-
eral roles of interleukin-1beta, protein kinase C and cyclooxyge-
nase-2 signalling. Pain. 2009; 142: 264-274.
19. Boillat A, Alijevic O, Kellenberger S: Calcium entry via
TRPV1 but not ASICs induces neuropeptide release from sen-
sory neurons. Mol Cell Neurosci. 2014; 61: 13
20. Paudel KS, Hammell DC, Agu RU, et al.: Cannabidiol bioa-
vailability after nasal and transdermal application: Effect of per-
meation enhancers. Drug Dev Ind Pharm. 2010; 36: 1088-1097.
21. Lodzki M, Godin B, Rakou L, et al.: Cannabidiol-transdermal
delivery and anti-inflammatory effect in a murine model.
J Control Release. 2003; 93: 377-387.
22. Coetzee C, Levendal RA, van de Venter M, et al.:
Anticoagulant effects of a Cannabis extract in an obese rat
model. Phytomedicine. 2007; 14(5): 333-337.
06-SA-JOM#200008.indd 218 09/05/20 8:13 PM
... They were, however, limited in size and quality. The six human studies were comprised of four case reports, [43][44][45][46] one case series, 47 and one voluntary RCT. 32 As such, the case reports and case series were classified as high risk of bias, while the RoB 2 tool was used to characterize the voluntary RCT as some concerns (online supplemental figure 1). ...
... The four case studies all reported a reduction in pain ratings after using topical cannabinoids. [43][44][45][46] Case studies reported reductions in pain ratings in three cases of epidermolysis bullosa, 44 two cases of low back pain, 45 three cases of pyoderma gangrenosum, 43 and two cases of non-puremic calciphylaxis ulcers. 46 The non-randomized and non-controlled methodologies of case reports were subject to high risk of bias. ...
... The four case studies all reported a reduction in pain ratings after using topical cannabinoids. [43][44][45][46] Case studies reported reductions in pain ratings in three cases of epidermolysis bullosa, 44 two cases of low back pain, 45 three cases of pyoderma gangrenosum, 43 and two cases of non-puremic calciphylaxis ulcers. 46 The non-randomized and non-controlled methodologies of case reports were subject to high risk of bias. ...
Background/importance Cannabinoids are emerging as an alternative pain management option, preliminarily supported by preclinical and clinical studies. Unwanted side effects from oral or inhaled cannabinoids remain, however, a major barrier to widespread use. Peripherally acting cannabinoids (eg, topically applied) may circumvent these side effects while providing localized pain management. Objective Our purpose was to systematically review the literature on the effectiveness of peripherally acting cannabinoids for pain management. Evidence review We searched MEDLINE, EMBASE, CENTRAL, CINAHL, and PubMed databases. Included studies examined the effect of topical/peripherally administered cannabinoids on pain ratings in humans, as well as pain-related outcomes in animals (eg, paw withdrawal). Due to a lack of trials, human studies were summarized in a narrative synthesis. Separate meta-analyses were performed for animal studies using radiant tail flick or paw withdrawal outcomes. Findings Our search yielded 1182 studies following removal of duplicates, with 46 studies (6 human, 40 animal) included. Human studies (one randomized controlled trial and five case studies/series) reported no adverse events to topical cannabinoids and preliminary evidence of decreased pain ratings. Animal studies reporting tail flick (5) (2.81, 95% CI 1.93 to 3.69, p<0.001) and mechanical withdrawal (11) (2.74, 95% CI 1.82 to 3.67, p<0.001) reported prolonged responses (analgesia) in peripheral cannabinoid groups compared with controls. Conclusions Preclinical animal studies provided low-quality evidence for peripherally administered cannabinoids to provide regional, antinociceptive effects. The scarcity of high-quality human studies underscores the need to translate preclinical evidence into well-controlled human trials.
... Three articles studied the use of cannabinoid derivatives by routes other than oral and inhalation in neuropathic pain, but its design gave us serious concerns (Table 2). Participants had spinal cord injuries [44], facial posherpetic neuralgia [45] and back pain [46]. ...
... Finally, Eskander et al. reported two patients that used topical CBD cream (400 mg CBD per two oz; Baskin Essentials Body Wellness Cream ® ) for the symptomatic relief of pain secondary to a lumbar compression fracture and in the mitigation of chest discomfort and dysesthesia secondary to a surgically resected meningioma, reporting significant symptom and pain relief [46]. This did not meet the inclusion criteria because it was a case report. ...
Full-text available
The use of cannabis and cannabinoid products for the treatment of neuropathic pain is a growing area of research. This type of pain has a high prevalence, limited response to available therapies and high social and economic costs. Systemic cannabinoid-based therapies have shown some unwanted side effects. Alternative routes of administration in the treatment of neuropathic pain may provide better acceptance for the treatment of multiple pathologies associated with neuropathic pain. To examine the efficacy, tolerability, and safety of cannabinoids (individualized formulations, phytocannabinoids, and synthetics) administered by routes other than oral or inhalation compared to placebo and/or conventional medications in the management of neuropathic pain. This systematic review of the literature reveals a lack of clinical research investigating cannabis by routes other than oral and inhalation as a potential treatment for neuropathic pain and highlights the need for further investigation with well-designed clinical trials. There is a significant lack of evidence indicating that cannabinoids administered by routes other than oral or inhaled may be an effective alternative, with better tolerance and safety in the treatment of neuropathic pain. Higher quality, long-term, randomized controlled trials are needed to examine whether cannabinoids administered by routes other than inhalation and oral routes may have a role in the treatment of neuropathic pain.
... Currently, the Food and Drug Administration (FDA) does not regulate CBD products; therefore, the safety and efficacy of these products are not clearly established [22]. Two recent case reports describe the use of topical CBD creams for the symptomatic relief of chronic and acute back pain [18]. Both reports noted patient-reported relief of back pain from CBD transdermal creams. ...
... (2020) [18] Case report Two patient case reports Patients reported relief of chronic back pain when using CBD transdermal creams Xantus et al (2021) [19] Perspective article N/A CBD may have benefits in pain and fear reduction, which are important components in managing cLBP Allan et al. ...
Full-text available
Purpose of Review Cannabis is among the most used illicit substances globally, with medical applications, increased legalization, and shifting social attitudes leading to increased use in recent years. Cannabinoids are a group of psychoactive substances found within the cannabis plant, with the most common being Δ⁹-tetrahydrocannabinol and cannabidiol. Due to the high prevalence of use, it is increasingly important to evaluate the effects of cannabis and cannabinoids on spine patients, in both operative and nonoperative settings. Recent Findings Cannabis and cannabinoids may be effective in treating patients with chronic conditions such as back pain and spinal cord injuries. Longitudinal effects and implications on surgical outcomes and complications are poorly understood. High-quality, outcomes-focused research can inform approaches for clinicians to approach cannabis and cannabinoid use. Studies to elucidate the standardization of cannabis regimens can help develop guidelines for potential therapeutic applications. Cannabis and cannabinoids may be useful alternatives or additions for many spine patients, but future research is needed for recommendations to be determined. Summary Our manuscript reviews the available literature regarding cannabis use and various spinal conditions, organizing our findings into the following narrative themes: (1) the management of chronic lower back pain, (2) perioperative outcomes, (3) cannabis use in general orthopaedic procedures, and (4) spinal cord injuries.
... The natural terpenophenolic compound cannabidiol from Cannabis sativa is endowed with a plethora of pharmacological activities, including analgesic, antidepressant, antiepileptic, anti-inflammatory, antioxidant, cytotoxic, and antineoplastic, among others [1][2][3][4][5][6][7][8][9]. It has been the subject of numerous experimental and clinical studies and has been granted orphan drug designation for the treatment of rare pediatric forms of epilepsy [1,[6][7][8]. ...
Full-text available
Cannabidiol (CBD) has attracted increasing interest due to its therapeutic potential for treating numerous diseases. However, CBD is very lipophilic and has very unfavorable pharmacokinetics and low bioavailability. Efforts are focused on developing drug delivery systems for enhanced solubilization and therapeutic activity of CBD. Here, we report the preparation of original super-macroporous cryogels from 2-hydroxyethyl cellulose (HEC) and β-cyclodextrin (β-CD) designed for the topical delivery of CBD. The cryogels were synthesized by photochemical crosslinking in a frozen aqueous system, purified, and then loaded with CBD. The effect of HEC/β-CD mass ratio (100:0; 50:50; 40:60 and 20:80) in the reaction mixture on the reaction efficiency, physico-mechanical properties of cryogels, drug release profile, and antineoplastic potential were evaluated in detail. The cryogels showed a bi-phasic release behavior: initial burst release in the first 3 hours followed by slower drug release which can be beneficial in the treatment of cutaneous neoplastic diseases.
Full-text available
In the last decades, a lot of attention has been paid to the compounds present in medicinal Cannabis sativa L., such as Δ ⁹ -tetrahydrocannabinol (Δ ⁹ -THC) and cannabidiol (CBD), and their effects on inflammation and cancer-related pain. The National Cancer Institute (NCI) currently recognizes medicinal C. sativa as an effective treatment for providing relief in a number of symptoms associated with cancer, including pain, loss of appetite, nausea and vomiting, and anxiety. Several studies have described CBD as a multitarget molecule, acting as an adaptogen, and as a modulator, in different ways, depending on the type and location of disequilibrium both in the brain and in the body, mainly interacting with specific receptor proteins CB 1 and CB 2 . CBD is present in both medicinal and fibre-type C. sativa plants, but, unlike Δ ⁹ -THC, it is completely nonpsychoactive. Fibre-type C. sativa (hemp) differs from medicinal C. sativa , since it contains only few levels of Δ ⁹ -THC and high levels of CBD and related nonpsychoactive compounds. In recent years, a number of preclinical researches have been focused on the role of CBD as an anticancer molecule, suggesting CBD (and CBD-like molecules present in the hemp extract) as a possible candidate for future clinical trials. CBD has been found to possess antioxidant activity in many studies, thus suggesting a possible role in the prevention of both neurodegenerative and cardiovascular diseases. In animal models, CBD has been shown to inhibit the progression of several cancer types. Moreover, it has been found that coadministration of CBD and Δ ⁹ -THC, followed by radiation therapy, causes an increase of autophagy and apoptosis in cancer cells. In addition, CBD is able to inhibit cell proliferation and to increase apoptosis in different types of cancer models. These activities seem to involve also alternative pathways, such as the interactions with TRPV and GRP55 receptor complexes. Moreover, the finding that the acidic precursor of CBD (cannabidiolic acid, CBDA) is able to inhibit the migration of breast cancer cells and to downregulate the proto-oncogene c-fos and the cyclooxygenase-2 (COX-2) highlights the possibility that CBDA might act on a common pathway of inflammation and cancer mechanisms, which might be responsible for its anticancer activity. In the light of all these findings, in this review we explore the effects and the molecular mechanisms of CBD on inflammation and cancer processes, highlighting also the role of minor cannabinoids and noncannabinoids constituents of Δ ⁹ -THC deprived hemp.
Full-text available
Purpose of review: The purpose of the following review is to summarize the history and current policies related to marijuana use and prevalence, basic and clinical science pharmacological literature regarding efficacy, subpopulations of concern, and varying policies regarding its use at present. Recent findings: With the increasingly widespread utilization of marijuana, there is also a growing complexity of public health policy, regulation, and necessity to further assess the medical indications and adverse long-term effects of marijuana use. Health care providers as well as the general public must be prepared to become familiar and up-to-date with medical literature, legislation, and educational material regarding medical marijuana.
Full-text available
Clinical studies suggest that diets rich in ω-3 polyunsaturated fatty acids (PUFAs) provide beneficial anti-inflammatory effects, in part through their conversion to bioactive metabolites. Here we report on the endogenous production of a previously unknown class of ω-3 PUFA-derived lipid metabolites that originate from the crosstalk between endocannabinoid and cytochrome P450 (CYP) epoxygenase metabolic pathways. The ω-3 endocannabinoid epoxides are derived from docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to form epoxyeicosatetraenoic acid-ethanolamide (EEQ-EA) and epoxydocosapentaenoic acid-ethanolamide (EDP-EA), respectively. Both EEQ-EAs and EDP-EAs are endogenously present in rat brain and peripheral organs as determined via targeted lipidomics methods. These metabolites were directly produced by direct epoxygenation of the ω-3 endocannabinoids, docosahexanoyl ethanolamide (DHEA) and eicosapentaenoyl ethanolamide (EPEA) by activated BV-2 microglial cells, and by human CYP2J2. Neuroinflammation studies revealed that the terminal epoxides 17,18-EEQ-EA and 19,20-EDP-EA dose-dependently abated proinflammatory IL-6 cytokines while increasing anti-inflammatory IL-10 cytokines, in part through cannabinoid receptor-2 activation. Furthermore the ω-3 endocannabinoid epoxides 17,18-EEQ-EA and 19,20-EDP-EA exerted antiangiogenic effects in human microvascular endothelial cells (HMVEC) and vasodilatory actions on bovine coronary arteries and reciprocally regulated platelet aggregation in washed human platelets. Taken together, the ω-3 endocannabinoid epoxides' physiological effects are mediated through both endocannabinoid and epoxyeicosanoid signaling pathways. In summary, the ω-3 endocannabinoid epoxides are found at concentrations comparable to those of other endocannabinoids and are expected to play critical roles during inflammation in vivo; thus their identification may aid in the development of therapeutics for neuroinflammatory and cerebrovascular diseases.
Full-text available
Chronic inflammation in rheumatoid arthritis (RA) is accompanied by activation of the sympathetic nervous system, which can support the immune system to perpetuate inflammation. Several animal models of arthritis already demonstrated a profound influence of adrenergic signaling on the course of RA. Peripheral norepinephrine release from sympathetic terminals is controlled by cannabinoid receptor type 1 (CB1), which is activated by two major endocannabinoids (ECs), arachidonylethanolamine (anandamide) and 2-arachidonylglycerol. These ECs also modulate function of transient receptor potential channels (TRPs) located on sensory nerve fibers, which are abundant in arthritic synovial tissue. TRPs not only induce the sensation of pain but also support inflammation via secretion of pro-inflammatory neuropeptides. In addition, many cell types in synovial tissue express CB1 and TRPs. In this review, we focus on CB1 and transient receptor potential vanilloid 1 (TRPV1)-mediated effects on RA since most anti-inflammatory mechanisms induced by cannabinoids are attributed to cannabinoid receptor type 2 (CB2) activation. We demonstrate how CB1 agonism or antagonism can modulate arthritic disease. The concept of functional antagonism with continuous CB1 activation is discussed. Since fatty acid amide hydrolase (FAAH) is a major EC-degrading enzyme, the therapeutic possibility of FAAH inhibition is studied. Finally, the therapeutic potential of ECs is examined since they interact with cannabinoid receptors and TRPs but do not produce central side effects.
The plant Cannabis sativa, commonly called cannabis or marijuana, has been used for its psychotropic and mind-altering side effects for millennia. There has been growing attention in recent years on its potential therapeutic efficacy as municipalities and legislative bodies in the United States, Canada, and other countries grapple with enacting policy to facilitate the use of cannabis or its constituents for medical purposes. There are over 550 chemical compounds and over 100 phytocannabinoids isolated from cannabis, including Δ(9)-tetrahydrocannabinol (THC) and Cannabidiol (CBD). THC is thought to produce the main psychoactive effects of cannabis, while CBD does not appear to have similar effects. Studies conflict as to whether CBD attenuates or exacerbates the behavioral and cognitive effects of THC. This includes effects of CBD on THC induced anxiety, psychosis and cognitive deficits. In this article, we review the available evidence on the pharmacology and behavioral interactions of THC and CBD from pre-clinical and human studies particularly with reference to anxiety and psychosis like symptoms. Both THC and CBD, as well as other cannabinoid molecules, are currently being evaluated for medicinal purposes, separately and in combination. Future cannabis-related policy decisions should include consideration of scientific findings including the individual and interactive effects of CBD and THC.Neuropsychopharmacology accepted article preview online, 06 September 2017. doi:10.1038/npp.2017.209.
Herbal cannabis has been used for thousands of years for medical purposes. With elucidation of the chemical structures of tetrahydrocannabinol (THC) and cannabidiol (CBD) and with discovery of the human endocannabinoid system, the medical usefulness of cannabinoids has been more intensively explored. While more randomized clinical trials are needed for some medical conditions, other medical disorders, like chronic cancer and neuropathic pain and certain symptoms of multiple sclerosis, have substantial evidence supporting cannabinoid efficacy. While herbal cannabis has not met rigorous FDA standards for medical approval, specific well-characterized cannabinoids have met those standards. Where medical cannabis is legal, patients typically see a physician who "certifies" that a benefit may result. Physicians must consider important patient selection criteria such as failure of standard medical treatment for a debilitating medical disorder. Medical cannabis patients must be informed about potential adverse effects, such as acute impairment of memory, coordination and judgment, and possible chronic effects, such as cannabis use disorder, cognitive impairment, and chronic bronchitis. In addition, social dysfunction may result at work/school, and there is increased possibility of motor vehicle accidents. Novel ways to manipulate the endocannbinoid system are being explored to maximize benefits of cannabinoid therapy and lessen possible harmful effects.
Purpose: New regulations are in place at the federal and provincial levels in Canada regarding the way medical cannabis is to be controlled. We present them together with guidance for the safe use of medical cannabis and recent clinical trials on cannabis and pain. Source: The new Canadian regulations on the use of medical cannabis, the provincial regulations, and the various cannabis products available from the Canadian Licensed Producers were reviewed from Health Canada, provincial licensing authorities, and the licensed producers website, respectively. Recent clinical trials on cannabis and pain were reviewed from the existing literature. Principal findings: Health Canada has approved a new regulation on medical marijuana/cannabis, the Marihuana for Medical Purposes Regulations: The production of medical cannabis by individuals is illegal. Health Canada, however, has licensed authorized producers across the country, limiting the production to specific licenses of certain cannabis products. There are currently 26 authorized licensed producers from seven Canadian provinces offering more than 200 strains of marijuana. We provide guidance for the safe use of medical cannabis. The recent literature indicates that currently available cannabinoids are modestly effective analgesics that provide a safe, reasonable therapeutic option for managing chronic non-cancer-related pain. Conclusion: The science of medical cannabis and the need for education of healthcare professionals and patients require continued effort. Although cannabinoids work to decrease pain, there is still a need to confirm these beneficial effects clinically and to exploit them with acceptable benefit-to-risk ratios.
Cyclooxygenase-2 (COX-2) mediates inflammation and contributes to neurodegeneration. Best known for its pathological up-regulation, COX-2 is also constitutively expressed within the brain and mediates synaptic transmission through prostaglandin synthesis. Along with arachidonic acid, COX-2 oxygenates the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol in vitro. Inhibition of COX-2 enhances retrograde signaling in the hippocampus, suggesting COX-2 mediates endocannabinoid tone in healthy brain. The degree to which COX-2 may regulate endocannabinoid metabolism in vivo is currently unclear. Therefore, we explored the effect of COX-2 inhibition on [(3)H]AEA metabolism in mouse brain. Although AEA is hydrolyzed primarily by fatty acid amide hydrolase (FAAH), ex vivo autoradiography revealed that COX-2 inhibition by nimesulide redirected [(3)H]AEA substrate from COX-2 to FAAH in the cortex, hippocampus, thalamus, and periaqueductal gray. These data indicate that COX-2 possesses the capacity to metabolize AEA in vivo and can compete with FAAH for AEA in several brain regions. Temporal fluctuations in COX-2 expression were observed in the brain, with an increase in COX-2 protein and mRNA in the hippocampus at midnight compared with noon. COX-2 immunolocalization was robust in the hippocampus and several cortical regions. Although most regions exhibited no temporal changes in COX-2 immunolocalization, increased numbers of immunoreactive cells were detected at midnight in layers II and III of the somatosensory and visual cortices. These temporal variations in COX-2 distribution reduced the enzyme's contribution toward [(3)H]AEA metabolism in the somatosensory cortex at midnight. Taken together, our findings establish COX-2 as a mediator of regional AEA metabolism in mouse brain.
The nonpsychoactive cannabinoid, cannabidiol (CBD), has great potential for the treatment of chronic and 'breakthrough' pain that may occur in certain conditions like cancer. To fulfill this goal, suitable noninvasive drug delivery systems need to be developed for CBD. Chronic pain relief can be best achieved through the transdermal route, whereas 'breakthrough' pain can be best alleviated with intranasal (IN) delivery. Combining IN and transdermal delivery for CBD may serve to provide patient needs-driven treatment in the form of a nonaddictive nonopioid therapy. Herein we have evaluated the IN and transdermal delivery of CBD with and without permeation enhancers. In vivo studies in rats and guinea pigs were carried out to assess nasal and transdermal permeation, respectively. CBD was absorbed intranasally within 10 minutes with a bioavailability of 34-46%, except with 100% polyethylene glycol formulation in rats. Bioavailability did not improve with enhancers. The steady-state plasma concentration of CBD in guinea pigs after transdermal gel application was 6.3 +/- 2.1 ng/mL, which was attained at 15.5 +/- 11.7 hours. The achievement of a significant steady-state plasma concentration indicates that CBD is useful for chronic pain treatment through this route of administration. The steady-state concentration increased by 3.7-fold in the presence of enhancer. A good in vitro and in vivo correlation existed for transdermal studies. The results of this study indicated that CBD could be successfully delivered through the IN and transdermal routes.