Category Archives: Chronic Inflammatory and Neuropathic Pain

The Therapeutic Potential of Cannabidiol in Revolutionising Opioid Use Disorder Management

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“Opioid use disorder (OUD) is a significant cause of morbidity and mortality worldwide and is linked to a complex interplay of biopsychosocial factors as well as the increasing overprescription and availability of opioid medications. Current OUD management relies on the controlled provision of opioid medications, such as methadone or buprenorphine, known as opioid replacement therapy. There is variable evidence regarding the long-term efficacy of these medications in improving the management of OUD, thereby necessitating an exploration into innovative approaches to complement, or even take the place of, existing treatment paradigms.

Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has garnered attention for its diverse pharmacological properties, including anti-inflammatory, analgesic, and anxiolytic effects. Preliminary studies suggest that CBD may target opioid withdrawal pathways that make CBD a potential therapeutic option for OUD.

This narrative review synthesises current literature surrounding OUD and offers a nuanced review of the current and future role of CBD in managing this condition. In doing so, we highlight the potential avenues to explore with respect to CBD research for the guidance and development of further research opportunities, framework and policy development, and clinical considerations before medicinal CBD can be integrated into evidence-based clinical guidelines.”

https://pubmed.ncbi.nlm.nih.gov/38226097/

https://www.cureus.com/articles/214898-the-therapeutic-potential-of-cannabidiol-in-revolutionising-opioid-use-disorder-management#!/

The impact of cannabis on non-medical opioid use among individuals receiving pharmacotherapies for opioid use disorder: a systematic review and meta-analysis of longitudinal studies

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“Background: The relationship between cannabis use and the risk of returning to using opioids non-medically during treatment for opioid use disorder (OUD) remains unclear.

Objective: We sought to quantify the impact of cannabis use on the risk of non-medical opioid use among people receiving pharmacotherapies for OUD.

Methods: A comprehensive search was performed using multiple databases from March 1 to April 5 of 2023. Eligible studies longitudinally assessed the association between cannabis use and non-medical opioid use among people with OUD receiving treatment with buprenorphine, methadone, or naltrexone. We utilized a random-effects model employing the restricted maximum likelihood method. A sensitivity analysis was conducted to understand potential differences between each OUD treatment modality.

Results: A total of 10 studies were included in the final meta-analysis. There were 8,367 participants (38% female). The average follow-up time across these studies was 9.7 months (SD = 3.77), ranging from 4 to 15 months. The pharmacotherapies involved were methadone (76.3%) buprenorphine (21.3%), and naltrexone (2.4%). The pooled odds ratio did not indicate that cannabis use significantly influenced non-medical opioid use (OR: 1.00, 95% CI: 0.97-1.04, p = .98). There is evidence of moderate heterogeneity and publication bias.

Conclusion: There was no significant association between cannabis use and non-medical opioid use among patients receiving pharmacotherapies for OUD. These findings neither confirm concerns about cannabis increasing non-medical opioid use during MOUD, nor do they endorse its efficacy in decreasing non-medical opioid use with MOUD.

This indicates a need for individualized approaches for cannabis use and challenges the requirement of cannabis abstinence to maintain OUD pharmacotherapies.”

https://pubmed.ncbi.nlm.nih.gov/38225727/

https://www.tandfonline.com/doi/full/10.1080/00952990.2023.2287406

Overview: Chronic Pain and Cannabis-Based Medicines

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“Chronic pain is primarily conceptualized as a disease in its own right when it is associated with emotional distress and functional impairment. Pathophysiologically, dysfunction of the cortico-mesolimbic connectome is of major importance, with overlapping signals in the nociceptive and stress systems.

The endocannabinoid system plays an important role in the central processing of nociceptive signals and regulates the central stress response. Clinically, there is moderate evidence that cannabis-based medicines (CBM) can contribute to a significant reduction in pain, especially the associated pain effect, and improvement in physical function and sleep quality in a proportion of patients with chronic pain.

The analgesic effect appears to be largely independent of the cause of pain. In this context, CBM preferentially regulates stress-associated pain processing.”

https://pubmed.ncbi.nlm.nih.gov/38198809/

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-2231-6630

A preliminary study evaluating self-reported effects of cannabis and cannabinoids on neuropathic pain and pain medication use in people with spinal cord injury

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“Approximately 60% of individuals with a spinal cord injury (SCI) experience neuropathic pain, which often persists despite the use of various pharmacological treatments. Increasingly, the potential analgesic effects of cannabis and cannabinoid products have been studied; however, little research has been conducted among those with SCI-related neuropathic pain. Therefore, the primary objective of the study was to investigate the perceived effects of cannabis and cannabinoid use on neuropathic pain among those who were currently or had previously used these approaches. Additionally, the study aimed to determine if common pain medications are being substituted by cannabis and cannabinoids. Participants (N = 342) were recruited from existing opt-in listserv sources within the United States. Of those, 227 met the inclusion criteria and were enrolled in the study. The participants took part in an anonymous online survey regarding past and current use of cannabis and their perceived effects on neuropathic pain, including the use of pain medication. Those in the sample reported average neuropathic pain intensity scores over the past week of 6.8 ± 2.1 (0 to 10 scale), reflecting a high moderate to severe level of pain. Additionally, 87.9% noted that cannabis reduced their neuropathic pain intensity by more than 30%, and 92.3% reported that cannabis helped them to better deal with their neuropathic pain symptoms. Most participants (83.3%) also reported substituting their pain medications with cannabis, with the most substituted medication categories being opioids (47.0%), gabapentinoids (42.8%) and over-the-counter pain medications (42.2%). These preliminary results suggest that cannabis and cannabinoids may be effective in reducing neuropathic pain among those with SCI and may help to limit the need for certain pain medications.”

https://pubmed.ncbi.nlm.nih.gov/38188193/

https://www.frontiersin.org/articles/10.3389/fpain.2023.1297223/full

Phytocannabinoids for the Treatment of Neuropathic Pain: A Scoping Review of Randomised Controlled Trials Published Between 2012 and 2023

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“Purpose of review: Neuropathic pain (NP) remains a challenge to treat, with 50% of patients experiencing limited efficacy from current treatments. Medicinal cannabis, which contains tetrahydrocannabinol (THC), cannabidiol (CBD) and other minor cannabinoids, is garnering attention as an alternative treatment for NP. This paper reviews the clinical evidence for phytocannabinoid treatment of NP.

Recent findings: Seventeen randomised controlled trials (RCT) were identified for inclusion in this review. Of these, ten studies using phytocannabinoid preparations containing THC alone had the most evidence for pain relief. Four studies investigating THC/CBD combinations showed some reductions in pain scores, although not all findings were statistically significant, whereas studies investigating CBD (two studies) or cannabidivarin (one study) showed no analgesic effect over placebo. However, CBD studies were of small sample size when compared to other studies in the review and short duration. Results for treatment of diabetic peripheral neuropathy patients with THC showed better improvements over those for NP induced by chemotherapy and multiple sclerosis, with these trials using vaporised whole plant cannabis. This formulation may have trace amounts of other minor cannabinoids, compared with synthetic cannabinoids such as dronabinol or nabilone that were investigated in other studies. This review provides an overview of RCTs that have investigated phytocannabinoid use for the treatment of NP. There appears to be evidence to necessitate further high quality RCTs into novel formulations of phytocannabinoids for the treatment of NP.”

https://pubmed.ncbi.nlm.nih.gov/38095748/

https://link.springer.com/article/10.1007/s11916-023-01196-1

Medical Cannabis: A Review from the American Society of Pain and Neuroscience

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“Cannabinoids have recently gained a renewed interest due to their potential applicability to various medical conditions, specifically the management of chronic pain conditions.

Unlike many other medications, medical cannabis is not associated with serious adverse events, and no overdose deaths have been reported.

However, both safety and efficacy data for medical cannabis treatment of chronic, nonmalignant pain conditions are lacking. Therefore, representatives from the American Society of Pain and Neuroscience summarize the evidence, according to level and grade, for medical cannabis treatment of several different pain conditions. Treatment of cancer-related pain has prospective evidentiary support for the use of medical cannabis. Although 3 large and well-designed randomized controlled trials investigated cannabis treatment of cancer-related pain, the evidence yielded only a grade D recommendation. Neuropathic pain has been investigated in prospective studies, but a lack of high-quality evidence renders cannabis treatment for this indication a grade C recommendation. Both safety and efficacy data are lacking for use of medical cannabis to treat chronic nonmalignant pain conditions.”

https://pubmed.ncbi.nlm.nih.gov/38094100/

https://www.dovepress.com/medical-cannabis-a-review-from-the-american-society-of-pain-and-neuros-peer-reviewed-fulltext-article-JPR

Relief of nocturnal neuropathic pain with the use of cannabis in a patient with Fabry disease

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“Neuropathic pain is one of the most invalidating symptoms in patients with Fabry disease (FD), affecting their quality of life, it is linked to small fiber neuropathy and it may not respond to available disease specific treatments. We report the case of a 32 years old man with classic FD and severe neuropathic pain who, after the failure of several standard pharmaceutical approaches, was treated with medical cannabis with relief of nocturnal pain and sleep improvement.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694749/

“In conclusion: although more evidence is needed, this case report suggests that the use of medical cannabis could be considered as a pain treatment option for patient with FD, in particular for nocturnal pain relief, when other pharmacological approaches have failed.”

https://www.sciencedirect.com/science/article/pii/S2214426923000563?via%3Dihub


Terpenes in Cannabis sativa Inhibit Capsaicin Responses in Rat DRG Neurons via Na+/K+ ATPase Activation

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“Terpenes in Cannabis sativa exert analgesic effects, but the mechanisms are uncertain. We examined the effects of 10 terpenes on capsaicin responses in an established model of neuronal hypersensitivity. Adult rat DRG neurons cultured with neurotrophic factors NGF and GDNF were loaded with Fura2AM for calcium imaging, and treated with individual terpenes or vehicle for 5 min, followed by 1 µMol capsaicin. In vehicle treated control experiments, capsaicin elicited immediate and sustained calcium influx. Most neurons treated with terpenes responded to capsaicin after 6-8 min. Few neurons showed immediate capsaicin responses that were transient or normal. The delayed responses were found to be due to calcium released from the endoplasmic reticulum, as they were maintained in calcium/magnesium free media, but not after thapsigargin pre-treatment. Terpene inhibition of calcium influx was reversed after washout of medium, in the absence of terpenes, and in the presence of the Na+/K+ ATPase inhibitor ouabain, but not CB1 or CB2 receptor antagonists. Thus, terpenes inhibit capsaicin evoked calcium influx by Na+/K+ ATPase activation. Immunofluorescence showed TRPV1 co-expression with α1β1 Na+/K+ ATPase in most neurons while others were either TRPV1 or α1β1 Na+/K+ ATPase positive.”

https://pubmed.ncbi.nlm.nih.gov/38003528/

“The neuromodulatory effects of cannabinoids have been recognized for millenia in traditional medicine, including for pain relief. Following the opioid crisis, attention has been focussed on developing alternatives including cannabinoid-based pain therapies, as chronic pain remains an unmet need. The best known of the phytocannabinoids is Δ9tetrahydrocannabinol (THC), the only known psychoactive component, along with many other cannabinoids with potential therapeutic benefits, such as cannabidiol (CBD), and cannabigerol (CBG) [2]. Amongst the several hundred components in Cannabis sativa are terpenes, which are produced in small and varying amounts in different cultivars of C. sativa, leading to potential variation in their effects [3]. Some of these, including limonene, phytol, borneol, terpineol, and caryophyllene, provide pain relief via calcium channel inhibition [4]. Similarly, antinociceptive and anti-tumour effects of α-phellandrene were reported, although the mechanisms were unknown. Terpenes as a class of compounds are generally described as safe by the FDA, with low toxicity that extends their efficacy to a variety of indications including chronic pain and anxiety.”

https://www.mdpi.com/1422-0067/24/22/16340

The holistic effects of medical cannabis compared to opioids on pain experience in Finnish patients with chronic pain

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“Background: Medical cannabis (MC) is increasingly used for chronic pain, but it is unclear how it aids in pain management. Previous literature suggests that MC could holistically alter the pain experience instead of only targeting pain intensity. However, this hypothesis has not been previously systematically tested.

Method: A retrospective internet survey was used in a sample of Finnish chronic pain patients (40 MC users and 161 opioid users). The patients evaluated statements describing positive and negative phenomenological effects of the medicine. The two groups were propensity score matched to control for possible confounding factors.

Results: Exploratory factor analysis revealed three experience factors: Negative Side Effects, Positive Holistic Effects, and Positive Emotional Effects. The MC group (matched n = 39) received higher scores than the opioid group (matched n = 39) in Positive Emotional Effects with large effect size (Rank-Biserial Correlation RBC = .71, p < .001), and in Holistic Positive Effects with medium effect size (RBC = .47, p < .001), with no difference in Negative Side Effects (p = .13). MC and opioids were perceived as equally efficacious in reducing pain intensity. Ratings of individual statements were exploratively examined in a post hoc analysis.

Conclusion: MC and opioids were perceived to be equally efficacious in reducing pain intensity, but MC additionally positively affected broader pain-related factors such as emotion, functionality, and overall sense of wellbeing. This supports the hypothesis that MC alleviates pain through holistically altering the pain experience.”

https://pubmed.ncbi.nlm.nih.gov/37941019/

“The results of the present study support the hypothesis that the effects of MC on pain experience are more holistic than those of opioids. MC may alleviate pain through affecting a broad range of pain-related experience experiental factors such as relaxation, improved sleep and mood, being able not to react to the pain, as well as a sense of control. These holistic effects of MC could explain the inconsistencies in clinical trials, where focus has mainly been on pain intensity instead of broader pain phenomenology. The results highlight the importance of taking these holistic effects into account in treating patients with MC, considering them as part of the therapeutic process.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-023-00207-7

Complex Regional Pain Syndrome Type I: Evidence for the CB1 and CB2 Receptors Immunocontent and Beneficial Effect of Local Administration of Cannabidiol in Mice

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“Introduction: Complex regional pain syndrome type I (CRPS-I) is a debilitating neuropathic painful condition associated with allodynia, hyperalgesia, sudomotor and/or vasomotor dysfunctions, turning investigation of its pathophysiology and new therapeutic strategies into an essential topic. We aim to investigate the impact of ischemia/reperfusion injury on the immunocontent of CB1 and CB2 cannabinoid receptor isoforms in the paws of mice submitted to a chronic postischemia pain (CPIP) model and the effects of local administration of cannabidiol (CBD) on mechanical hyperalgesia. 

Methods: Female Swiss mice, 30-35 g, were submitted to the CPIP model on the right hind paw. Skin and muscle samples were removed at different periods for western blot analysis. 

Results: No changes in the immunocontent of CB1 and CB2 receptors in paw muscle tissues after ischemia-reperfusion were observed. CBD promoted an antihyperalgesic effect in both phases. AM281 reversed the effect of CBD, whereas ruthenium red abolished the late phase. 

Conclusion: Our results point to the possible beneficial effects of local administration of CBD in modulating CRPS-I in humans. As possible targets for CBD antihyperalgesia in this model, the contribution of cannabinoid receptor CB1, in addition to TRPM8 is suggested.”

https://pubmed.ncbi.nlm.nih.gov/37903029/

https://www.liebertpub.com/doi/10.1089/can.2023.0093