Although several clinical studies on medical Cannabis and chronic pain show very promising results, many physicians still do not feel confident in recommending the use of cannabinoid derivatives such as cannabidiol and tetrahydrocannabinol for the management of neuropathic pain.
In this content, we will talk about the tolerance profile of the substances and what we already know scientifically about the mechanisms of action of cannabinoids in neuropathic pain conditions. Read on and understand the role of medical Cannabis in this context.
Mechanisms of action of Cannabis for neuropathic pain
Neuropathic pain is estimated to affect a significant portion of the world’s population, and in some cases, it can become a severe and disabling condition. This type of chronic pain is due to lesions in the sensory nerves of the central and/or peripheral nervous system, which can cause different perceptions of pain intensity and frequency.
The use of medical Cannabis to treat neuropathic pain emerges as an important pharmacological tool in the therapeutic arsenal of these patients, given the greater refractoriness and incidence of adverse effects associated with polypharmacy, which are common in the approach to these cases. However, many physicians still feel insecure about cannabinoid therapy, despite several studies demonstrating the safety and efficacy of these substances in this context.
An example is this systematic review which analyzed 374 studies covering 171 interventions for antinociceptive efficacy in preclinical pain models. The results showed that selective type 1 cannabinoids, type 2 cannabinoids, non-selective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol) and peroxisome proliferator-activated receptor agonists (PPARs) significantly attenuated behaviors associated with neuropathic and inflammatory pain. CBD, fatty acid amide hydrolase inhibitors, and monoacylglycerol lipase inhibitor significantly attenuated pain-associated behaviors in neuropathic pain models, but produced mixed results in inflammatory pain models.
>> You can read the full review here: Systematic review and meta-analysis of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain..
CBD and THC for neuropathic pain
The Cannabidiol is the main cannabinoid that has been most often addressed in scientific research, but there is already a lot of evidence regarding the therapeutic properties of other cannabinoid derivatives to fight neuropathic pain, such as tetra-hydrocannabinol (THC) and cannabidiol (CBDV).
An example is this preclinical experiment which evaluated the use of the phytocannabinoids THC and CBD, as well as morphine in mice over a period of three weeks. The results showed that all substances brought positive effects in fighting chronic pain resulting from sciatic nerve damage. However, it was shown that the cannabinoids THC and CBD, in contrast to morphine, produce lasting relief from neuropathic pain in this model of sciatic nerve injury. CBD, specifically, may represent a remarkably interesting therapeutic option due to its low psychoactive profile and low association with potential adverse effects.
>> You can read the full experiment here: Orally consumed cannabinoids provide long-lasting relief of allodynia in a mouse model of chronic neuropathic pain..
This other study carried out with 15 patients with chronic neuropathic radicular pain showed that THC could significantly reduce pain in these patients compared to placebo. The investigators related the analgesia induced by THC to a reduction in functional connectivity, as assessed by functional magnetic resonance imaging, between the anterior cingulate cortex (ACC) and the sensory-motor cortex, two regions characteristically involved in pain processing.
>> You can read the full study here: Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity.
Another example of the therapeutic potential of CBD and THC in neuropathic pain is this meta-analysis which evaluated the use of THC:CBD, THC, CBD, and CBDV in the treatment of neuropathic pain. The review covered 379 studies,involving 861 patients with this type of pain.
Compared to placebo, the results showed that patients taking THC:CBD were 1,756 times more likely to achieve a 30% reduction in pain and 1,422 times more likely to achieve a 50% reduction in pain..
However, the investigators pointed out that the use of CBDV did not show significant differences, and further research is therefore needed to investigate the benefits of this cannabinoid in the management of neuropathic pain.
>> You can read the full review here: Efficacy of cannabis-based medications compared to placebo for the treatment of chronic neuropathic pain: a systematic review with meta-analysis..
The Nabiximolwhich combines similar proportions of CBD and THC, has also been evaluated in a systematic review with meta-analysis of randomized controlled trials in the treatment of neuropathic pain. The study encompassed 9 randomized clinical trials – involving a total of 1,289 participants – and showed that the use of nabiximol brought superior results to placebo in the treatment of neuropathic pain in patients with inadequate pain relief. The pooled analysis indicated a small but statistically significant effect size in reducing pain.
>> You can read the full review here: Nabiximols in Chronic Neuropathic Pain: A Meta-Analysis of Randomized Placebo-Controlled Trials.
Efficacy, tolerability and safety of medical Cannabis in the treatment of neuropathic pain
The studies discussed throughout this content suggest the efficacy of medical Cannabis in the context of neuropathic pain, especially regarding the use of cannabidiol and tetra-hydrocannabinol. Although the results are promising, the investigators warn for the need for further research on the subject, especially in relation to other phytocannabinoids and chemical elements of the plant, aiming for more robust evidence.
This bibliographical review carried out by a global task force of the International Association for the Study of Pain evaluated the medical use of Cannabis in neuropathic pain under three main aspects: 1) the use of cannabinoids in preclinical pain models, 2) the pain-related efficacy and possible adverse effects involved, and 3) the perspectives and directions for future research.
The preclinical (rodent) models in this review assist in understanding the mechanisms of action of cannabinoid derivatives and the Endocannabinoid System in suppressing nociceptive signaling and behaviors. The authors concluded that there is substantial evidence in animal models that supports cannabinoid derivatives as very promising agents for analgesic drug development, although the challenge of translating this knowledge into clinically useful drugs should not be underestimated.
>> You can read the full review here: Cannabinoids, the endocannabinoid system, and pain: a review of preclinical studies..
Another literature systematic reviewwith a clinical trial comprised 15 double-blind, randomized studies (1619 participants) comparing the use of phytocannabinoids or synthetic cannabinoids with placebo in the treatment of chronic neuropathic pain. The duration of treatment ranged from 2 and 15 weeks.
Regarding efficacy, the clinical outcomes of these studies showed a 30% to 50% reduction in pain episodes and pain intensity, as well as a general improvement in the quality of life of the evaluated patients.
>> You can read the full review here: Efficacy, tolerability and safety of cannabinoids for chronic neuropathic pain: A systematic review of randomized controlled studies.
Although the studies addressed herein suggest a good safety profile of Cannabis for neuropathic pain, we reinforce the importance of thoroughly understanding the mechanisms of action of the main phytocannabinoids to make safe and effective prescriptions. For this reason, specialized training in the field is essential for physicians who wish to incorporate medical Cannabis into their therapeutic arsenal.
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