There has been a long history of cannabis used for pain therapy dating back thousands of years. It only made sense that researchers would look into CBD for pain, neuropathy and neuropathic pain relief.
CBD, also known as cannabidiol, is an active compound of cannabis. Unlike its counterpart, THC, cannabidiol has no psychoactive properties – in other words, it won’t make you high.
The studies that follow are most, but certainly not all, of the studies done and published in the U.S. on CBD for pain and neuropathy. The newest studies are listed first and some of these studies deal with new drugs of synthetic cannabinoids like Sativex, a combination of THC and CBD for treatment of diabetic and other neuropathies.
You may notice as you read through the studies that the newer studies expound on older studies and that some older studies may seem more basic in nature as they have been improved upon in newer studies. We are showing all studies to give the reader some idea of the extant of the research done on this subject.
It has been noted in studies (other than on CBD and pain) that the combination of THC with CBD has a synergistic effect, the two combined work better than either by itself. This is not always the case, but for some disorders like pain, this seems to hold true.
By itself or with THC, cannabidiol does have amazing properties for the relief of pain, as you will see from these studies. By the same token, we summarized all studies related to CBD and pain – some of these studies are more neutral in findings or opinion and some point out areas where more research is needed.
Please let us know if you have any opinions or comments about our summaries or if we have made any errors.
Let’s get into the studies and see what CBD can do and how it does it.
neuropathy: disease, damage, or dysfunction of one or more peripheral nerves, typically causing numbness, weakness and pain
The Cannabinoids Δ8THC, CBD, and HU-308 Act via Distinct Receptors to Reduce Corneal Pain and Inflammation
Feb 2018 | Lab study | [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812319/]
Brief summary:
The study focused on pain in cornea and the possible effect of several cannabinoids, including cannabidiol – along with THC, and CBD derivative HU-308.
The study used mice models and used capsaicin induced corneal pain. All 3 of the tested cannabinoids including CBD showed reduced pain and inflammation in the test subjects.
A few cannabinoid receptors were tested as pathways in this study for each cannabinoid.
end study summary
Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis
Sep 2017 | Lab study | [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5690292/]
Brief summary:
The aim of the study was to see if cannabidiol could relieve pain, joint neuropathy and inflammation caused from osteoarthritis. Injections of a compound induced arthritis in rat subjects and pain was measured using various models.
Acute, transient joint inflammation was reduced by local CBD treatment. CBD prevented the development of joint pain at later time points. It was also found to be neuroprotective. Local administration of CBD blocked pain.
CBD treatment prevented the later development of pain and nerve damage in joints. Findings suggested that CBD may be a safe, useful therapeutic for treating osteoarthritic joint neuropathic pain.
end study summary
Mechanical allodynia: is a painful sensation caused by innocuous stimuli like light touch. Unlike inflammatory pain that has a protective role, allodynia has no obvious biological utility.
Cannabidiol Is a Potential Therapeutic for the Affective-Motivational Dimension of Incision Pain in Rats
Jun 2017 | Lab study | [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5690292/]
Brief summary:
The aim of this study was to see how effective CBD would be for blocking or relieving pain caused by incision, as in the pain experienced after a surgical operation.
Rat subjects were used and exposed to an incision pain model – they were subjected to incision and pain was measured. One type of pain they were looking at was mechanincal allodynia (see definition). They also looked at whether CBD had any ability to block any pain caused by incision.
Results showed that injecting CBD in the body cavity did not have an effect on blocking mechanical allodynia, but it was made to be less intense. When CBD was inject directly in to the brain, mechanical allodynia was reduced in a dose dependent manner (the higher the dose, the more effective it was).
The study provides evidence that CBD influences different dimensions of pain response to a surgical incision. Results establish the rACC as a brain area from which CBD evokes pain blocking effects in a manner similar to the systemic administration of CBD.
end study summary
Cannabinoids in Pain Management and Palliative Medicine An Overview of Systematic Reviews and Prospective Observational Studies
Sep 2017 | Review paper | [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645627/]
Brief summary:
Randomized trials and long term studies were reviewed to evaluate the use of cannabinoids and medicinal marijuana for pain management.
In this review, one long term study involving a combination THC/CBD spray was looked at.
Overall, their opinion was that there was inadequate evidence to support benefits of madicinal marijuana for disease treatment.
However, for neuropathic pain, their opinion was…
“By contrast, sufficient evidence is available for neuropathic pain. A meta-analysis based on individual patient data on the use of medical marijuana to treat neuropathic pain found an NNTB of 6 for pain relief of at least 30%. This finding meets the criteria for a clinically relevant benefit” – direct quote.
end study summary
Sativex® is an oromucosal spray of a formulated extract of the cannabis sativa plant that contains the principal cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a 1:1 ratio (US approved name: nabiximols) as well as specific minor cannabinoids and other non-cannabinoid components.
Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies
May 2017 | Clinical trial | [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5521351/]
Brief summary:
Two different clinical trials in phase 3 were examined where Sativex was used for pain relief in advanced cancer patients where opiate pain relief was not working. These were patients on high doses of opioids to where more would not relieve pain.
Sativex doseage was Δ9-tetrahydrocannabinol (27 mg): cannabidiol (25 mg).
In Study-1, patients were randomized to Sativex or placebo, and then self-titrated (patient chooses the number of doses) study medications over a 2-week period to gauge effect and tolerability, followed by a 3-week treatment period.
In Study-2, all patients self-titrated Sativex over a 2-week period. Patients with a ≥15% improvement from baseline in pain scores were then equally split into randomized Sativex or placebo, followed by 5-week treatment period.
Overall, Sativex did not statistically demonstrate superiority to placebo in reducing self-reported pain in advanced cancer patients with chronic pain unalleviated by opioid therapy.
However, one group did demonstrate statistically favorable treatment effect for Sativex, in US patients less than 65 years of age.
In addition, treatment effect in favour of Sativex was observed on quality-of-life questionnaires.
end study summary
Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis
Oct 2015 | Lab study | [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851925/]
Brief summary:
This study examined the effectiveness of cannabidiol used transdermally (absorption through the skin) on inflammation and pain on arthritis.
It was noted before the study that CBD has been shown to reduce inflammation and pain without side-effects, but CBD does not mix well with water and has poor oral bioavailability.
Can it be used effectively as a topical agent?
Using rat subjects and knee joint arthritis models, cannabidiol was used topically as a gel.
Result showed that CBD concentrations in the blood and other plasma were in direct proportion to dosages given. Transdermal CBD gel significantly reduced joint swelling, limb posture scores as a rating of spontaneous pain, immune cell infiltration – all in a dose dependent manner, meaning the higher the dose, the greater the effectiveness.
Pro-inflammatory biomarkers were reduced in the spinal cord and dorsal root ganglia.
The gel used contained from 1% to 10% CBD. Results showed from 6.2 mg/day to 62 mg/day were effective doses based on the rat subjects.
419
end study summary
Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT1A receptors without diminishing nervous system function or chemotherapy efficacy
Jan 2014 | Lab study | [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969077/]
Brief summary:
Paclitaxel is associated with chemotherapy-induced neuropathic pain.
Using mice subjects, this study wished to examine the ability of intense cannabidiol pretreatment to prevent paclitaxel-induced pain sensitivity was assessed. The effect of CBD on stimulus conditioning and on an learning and memory tasks was also assessed.
In addition, the potential interaction of CBD and paclitaxel on breast cancer cell viability was determined using human cell cultures in a lab dish.
The results showed paclitaxel-induced pain sensitivity was prevented by administration of cannabidiol and that it is protective against induced neurotoxicity. The pathway receptor that was demonstrated in this case was the 5-HT1A receptor.
CBD did not demonstrate any cognitive impairment. It did not interfere with conditioned rewarding effects and did not affect conditioned learning and memory.
Also, CBD + paclitaxel combinations did produce synergistic inhibition of breast cancer cell viability.
end study summary
Phytocannabinoids: cannabinoids that occur naturally in the cannabis plant.
The Endocannabinoid System, Cannabinoids, and Pain
Oct 2013 | Review paper | [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820295/]
Brief summary:
This review presents cannabinoids, and specifically cannbidiol, as possible therapeutic agents for pain and chronic pain, including neuropathic pain.
It looks at research history and more current studies u to the date of this review.
“The phytocannabinoids have efficacy in the treatment of various chronic pain conditions with greatest promise as a therapeutic adjunct in treating peripheral and central neuropathic pain and inflammation-mediated chronic pain.” – direct quote.
end study summary
Cannabidiol in Humans—The Quest for Therapeutic Targets
May 2012 | Review paper | [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763649/]
Brief summary:
This review searched for studies involving human trials, both healthy and disease related.
It found some conflicting data on whether CBD inhibits or enhances the effects of THC when both are administered – for those trials addressing that aspect.
“Finally, preliminary clinical trials suggest that high-dose oral CBD (150–600 mg/d) may exert a therapeutic effect for social anxiety disorder, insomnia and epilepsy, but also that it may cause mental sedation.” – direct quote.
end study summary
Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors
Jun 2012 | Lab Study | [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371734/]
Brief summary:
CBD was directly involved with this study. The study wanted to report on what mechanisms (how it works) are used when cannabidiol is administered.
They did by subjecting two mice subject groups to chronic pain induced by chemicals. One group was normal, the other was genetically modified to not have the α3 glycine receptors. This was to see if this receptor was the influential receptor for pain.
They also tested both CBD and DH-CBD (dehydroxylcannabidiol), another form of cannabidiol.
They showed that CBD and DH-CBD significantly suppress chronic inflammatory and neuropathic pain without causing apparent analgesic tolerance in rodents. No cause of analgesic tolerance meant that they did not build up a tolerance which would create a need for more CBD to have the same effect.
This was the case for the normal mice subjects with the α3 glycine receptors – the modified mice (without α3 glycine receptors) were not affected by either CBD or DH-CBD – demonstrating that the α3 glycine receptor was indeed involved in pain and neuropathic pain relief and suppression.
end study summary
neuropathy: disease or dysfunction of one or more peripheral nerves
Cannabidiol may help relieve chemotherapy related neuropathy pain.
Oct 2011 | Lab Study | [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249239/]
Brief summary:
CBD may be a treatment to reduce pain in those getting the chemotherapy drug paclitaxel. Results of this study showed cannabidiol has pain- and inflammation-reducing effects, while avoiding the psychoactive side effects.
In female mice, cannabidiol reduces paclitaxel-induced neuropathy, which is a potentially serious complication.
Paclitaxel, commonly used in the treatment of advanced breast or ovarian cancer, can cause neuropathy, or nerve damage, leading to symptoms like pain, numbness, or tingling. This type of pain can prevent patients from getting their full course of chemotherapy.
end study summary
Allodynia: refers to central pain sensitization (increased response of neurons) following normally non-painful, often repetitive, stimulation – triggering of a pain response from stimuli which do not normally provoke pain.
Cannabidiol Prevents the Development of Cold and Mechanical Allodynia in Paclitaxel-Treated Female C57Bl6 Mice
Jul 2011 | Lab study | [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249239/]
Brief summary:
The aim of this study was to examine whether cannbidiol had any effect on pain and neuropathic pain in female rat subjects. Femail rats were chosen specifically because there were stuides with male rats but not enough with female rats.
By inducing allodynia pain with a chemotherapy drug known to cause pain (paclitaxel) and testing CBD effectiveness, they were able to show that CBD prevented the pain in female rat subjects.
end study summary
Microglia: are a type of neuron cell of the central nervous system located throughout the brain and spinal cord. Microglia account for 10–15% of all cells found within the brain.
Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain
Mar 2010 | Lab study | [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845559/]
Brief summary:
The role microglial cells in diabetic neuropathic pain was a focus of this study and how these cells might be influenced by cannabinoid receptors and cannbinoids.
Using mice subjects and a diabetic pain model, the study performed tests on various cannabinoids. One of these was cannabidiol.
When initiated together with diabetes, moderate-high doses of cannabidiol attenuated the development of a neuropathic pain state, even after their discontinuation and without reducing the induced diabetic state.
CBD was also associated with restriction in elevation of microglial density in the dorsal spinal cord.
end study summary
Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain.
Feb 2010 | Clinical Trial | [https://www.ncbi.nlm.nih.gov/pubmed/19896326]
Brief summary:
This trial involved 177 total patients with severe pain from advanced cancer who also had chronic opioid use, but not getting pain relief from opioids. Two extracts and a placebo were administered. One extract was a combination of THC:CBD; another was a THC extract.
Using a numerical rating scale for pain, the results heavily favored the THC:CBD extract (and improvement of -1.37 vs. -0.69). “Twice as many patients taking THC:CBD showed a reduction of more than 30% from baseline pain NRS score when compared with placebo” – direct quote.
There were no significant issues found with THC:CBD vs THC or placebo when it came to sleep quality or nausea scores. “This study shows that THC:CBD extract is effective for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids.” – direct quote.
end study summary
Pharmacodynamics is the study of how a drug affects an organism, whereas pharmacokinetics is the study of how the organism affects the drug. Both together influence dosing, benefit, and adverse effects.
Plasma Cannabinoid Pharmacokinetics following Controlled Oral Δ9-Tetrahydrocannabinol and Oromucosal Cannabis Extract Administration
Nov 2010 | Clinical trial | [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717338/]
Brief summary:
At the time of this trial, Sativex (a new drug under development containing THC and CBD) was undergoing trials to see if it might be effective for cancer pain.
This trial examines the pharmacodynamics and pharmacokinetics of Sativex by analyzing blood plasma.
A randomized, controlled and double blind trial was conducted on cannabis users.
Relative bioavailability was calculated to determine the relative rate and extent of THC absorption; 5 and 15 mg oral THC bioavailability was 92.6% (13.1%) and 98.8% (11.0%) of low- and high-dose Sativex, respectively.
Data suggested that CBD modulation of THC’s effects is not due to a pharmacokinetic interaction at these therapeutic doses.
end study summary
Standardized natural product cannabis in pain management and observations at a Canadian compassion society: a case report
May 2009 | Case study | [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2740265/]
Brief summary:
This was a case study of one male individual and the effects of cannabis use for their pain.
Cannabis use and cannabinoid levels were measured as well as the subjects pain levels.
The subject, as with other subjects at this clinic, achieved “a significant degree of pain management using standardized natural product cannabis. Often a better quality of life is attained with cannabis use only, or in conjunction with reduced opiate consumption.” – direct quote.
end study summary
Vanilloid TRPV1 receptor mediates the anti-hyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation.
Sep 2004 | Lab Study | [https://www.ncbi.nlm.nih.gov/pubmed/15313881]
Brief summary:
An examination was conducted to discover whether a proven CBD anti-hyperalgesic (pain sensitivity reduction) could be controlled by receptor type (CB1, CB2, TRPV1)
After rat subjects were injected with a chemical to induce pain sensitivity, they were given CBD and selected antagonists to see which, if any, could reverse the CBD effects. This could show which receptor CBD targets for the anti-pain effect.
“Here, we report for the first time that the antihyperalgesic effect of CBD is mediated by TRPV1 receptors and does not involve the cannabinoid receptor subtypes CB1 and CB2. These findings highlight TRPV1 as a molecular target for CBD” – direct quote.
end study summary
As you can see from these studies, the overwhelming evidence points to some amazing benefits of using CBD for pain. And in addition to that, there are benefits shown for using CBD for neuropathy and neuropathic pain.
If you appreciated the summaries on these studies on CBD for pain and neuropathy, you may like this article on CBD and inflammation.
