Research Studies Relating to CANNABIDIOL USE FOR PAIN

Research Summaries by Dr. Karen Hufnagl


PAIN

Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain. 

https://www.ncbi.nlm.nih.gov/pubmed/17257464   

This meta-analysis reviewed 7 randomized, double-blinded, placebo-controlled trials, which evaluated the use of several cannabis-based medicines for the treatment of pain associated with multiple sclerosis or comparable neuropathic pain in adults.  The cannabis-based medicines were compared with placebo and included:

·      Cannabidiol in conjunction with a delta-9-tetrahydrocannabinol (THC) buccal spray

·      Cannabidiol only

·      Dronabinol only

The studies assessed pain using the BS-11 scale, VAS scale, a 100-mm VAS scale, or an 11-point ordinal scale. Scores on an 11-point scale ranged from 0 (no pain) to 10 (worst pain imaginable).

Five of the studies measured the effect of cannabidiol alone and demonstrated a significant reduction in pain comparable to the other cannabis-based medicines.  The difference in pain reduction from baseline was 1.7 for the CBD/THC spray, 1.5 for the CBD, and 1.5 for the dronabinol.

The authors of this review state that “Cannabis preparations were more effective in reducing pain scores than placebo for the treatment of MS-related or neuropathic pain...” and concluded that “Cannabinoids are associated with a clinically relevant and statistically significant lowering of pain scores.”


Chronic Pain Treatment With Cannabidiol in Kidney Transplant Patients in Uruguay. 

https://www.ncbi.nlm.nih.gov/pubmed/29579828  

Just published in March of 2018, this clinical trial evaluated the use of CBD for chronic pain in kidney transplant patients.   There were 7 patients enrolled in the study, and oral doses of CBD were titrated up starting at 50 mg twice a day and increasing to 150 mg twice a day over the period of 3 weeks.

The results showed that 28% of patients had total pain improvement, 57% had a partial reduction in pain over the first 15 days, and 14% (1 patient) had no improvement.

While this is a small sample size and the authors encourage additional follow up studies, it does support the use of CBD for pain relief and the authors conclude that “CBD was well-tolerated, and there were no severe adverse effects.”


The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. National Academies of Sciences and Medicine. 2017, Washington, D.C.: The National Academies Press. 

http://nationalacademies.org/hmd/reports/2017/health-effects-of-cannabis-and-cannabinoids.aspx  

In this January 2017 report released US National Academy of Sciences, an expert committee presented nearly 100 conclusions on the health effects of cannabis and cannabinoid use (including CBD) based on the medical literature up to that date.

The report found that “…In adults with chronic pain, patients who were treated with cannabis or cannabinoids are more likely to experience a clinically significant reduction in pain symptoms.”   


A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms.

https://www.ncbi.nlm.nih.gov/pubmed/12617376  

This paper reports the results of a consecutive series of double-blind, randomized, placebo-controlled single-patient cross-over trials with two-week treatment periods.  There were 24 patients enrolled in the study; all had neurogenic symptoms unresponsive to standard treatment.   Their symptoms were the result of multiple sclerosis, spinal cord injury, brachial plexus damage, or limb amputation due to neurofibromatosis.

The study evaluated three different whole-plant cannabis extracts and compared them to placebo:

·      Delta-9-tetrahydrocannabinol (THC)

·      Cannabidiol (CBD)

·      1:1 CBD:THC

All of these extracts were administered via sublingual spray.  Patients were instructed to use the spray by titrating the dose upwards based on their individual need for symptom relief.  They were required to stay within a dosage range of 2.5 – 120 mg per 24 hour period.

The results showed that “Pain relief associated with both THC and CBD was significantly superior to placebo.”  To be clear, this is to say that the THC provided significantly superior pain relief and the CBD also separately provided significantly superior pain relief.

The researchers concluded that “Cannabis medicinal extracts can improve neurogenic symptoms unresponsive to standard treatments.”


Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It's Been. 

https://www.ncbi.nlm.nih.gov/pubmed/26015168   

This review paper discusses the pharmacology and physiology of the endocannabinoid system and cannabis-derived cannabinoids, and provides a comprehensive literature review of the clinical uses of medicinal cannabis and cannabinoids with a focus on migraine and other headache disorders.  It also lays out general guidelines for clinical practice.

In discussing the various routes of administration, types and pharmacokinetics of medicinal cannabis, the author states that “CBD…typically provides much of the analgesic effects of cannabis.”


Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5690292/

Published in 2017, this pre-clinical (animal model) study of osteoarthritis set out to determine whether CBD could relieve the pain of this condition, as well as whether inhibition of inflammation by CBD could prevent the development of pain in the first place.  Researchers also looked at whether CBD could prevent the development of joint neuropathy.

The results showed that “Acute, transient joint inflammation was reduced by local administration of CBD” and “…local administration of CBD blocked [osteoarthritis] pain.”

The study also demonstrated that “Prophylactic CBD treatment prevented the later development of pain and nerve damage in these [osteoarthritic] joints.”  In discussing their results, the researchers note that their “study shows for the first time that CBD is an effective anti-nociceptive and anti-inflammatory agent when administered locally around the joint.  Successful relief of [osteoarthritis] symptoms by peripherally administered CBD suggests a therapeutic option that has a low chance of adverse effects, which is more desirable for patients.”  

These findings led the researchers to conclude that “CBD may be a safe therapeutic to treat [osteoarthritis] pain locally as well as block the acute inflammatory flares that drive disease progression and joint neuropathy.”


Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851925/     

Other pre-clinical (animal model) data also provides evidence for the ability of topical CBD to reduce inflammation and pain in arthritis.

This particular study examined the efficacy of a transdermal CBD gel in reducing pain and inflammation in arthritis.  Four different doses of gel were evaluated (0.6, 3.1, 6.2, and 62.3 mg/day) and plasma levels of CBD were measured with each.  “The three lower doses displayed excellent linear pharmacokinetic correlation.”

The results showed that “Transdermal CBD gel significantly reduced joint swelling, limb posture scores as a rating of spontaneous pain, immune cell infiltration and thickening of the synovial membrane in a dose-dependent manner.”

Consistent with other research showing that CBD has no psychoactive effects, this paper also demonstrated that higher brain function was not altered by CBD.

The researchers concluded that “topical CBD application has therapeutic potential for relief of arthritis pain-related behaviours and inflammation without evident side-effects.”


Overcoming the Bell‐Shaped Dose‐Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol    

http://dx.doi.org/10.4236/pp.2015.62010

In 2015, researchers published a study directly evaluating the anti-inflammatory and pain-relieving effects of a specific standardized whole plant cannabis extract (clone 202) containing high amounts of CBD with the anti-inflammatory and pain-relieving effects of CBD isolate. 

Not only did the results of this animal study show benefit of CBD for pain and inflammation, it also clearly revealed that the whole plant extract was significantly more efficient for relieving pain than the CBD isolate.  The whole plant extract also demonstrated a correlative dose-response on inflammation, with higher doses resulting in a greater anti-inflammatory effect.  In contrast, higher doses of CBD isolate had less effect on inflammation (the so-called “biphasic dose response curve” widely documented in studies using CBD isolate).

As compared to CBD isolate, the authors report that “the higher efficiency of plant extract might be explained by additive or synergistic interactions between CBD and minor phytocannabinoids or non-cannabinoids presented in the extracts.” 

This paper also documents three other studies showing that “CBD in a standardized Cannabis sativa extract is more potent or efficacious than pure CBD.”  For reference, these include:

·      http://dx.doi.org/10.1016/j.phymed.2013.11.006  (Romano  et al., 2014)

·      http://dx.doi.org/10.1016/j.urology.2010.12.006  (Capasso  et al., 2011)

·      http://dx.doi.org/10.1111/j.1476-5381.2012.02027.x (De Petrocellis  et al., 2013)