Category Archives: Pain

Recreational and Medical Cannabis Legalization and Opioid Prescriptions and Mortality

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“Importance: While some have argued that cannabis legalization has helped to reduce opioid-related morbidity and mortality in the US, evidence has been mixed. Moreover, existing studies did not account for biases that could arise when policy effects vary over time or across states or when multiple policies are assessed at the same time, as in the case of recreational and medical cannabis legalization.

Objective: To quantify changes in opioid prescriptions and opioid overdose deaths associated with recreational and medical cannabis legalization in the US.

Design, setting, and participants: This quasiexperimental, generalized difference-in-differences analysis used annual state-level data between January 2006 and December 2020 to compare states that legalized recreational or medical cannabis vs those that did not.

Intervention: Recreational and medical cannabis law implementation (proxied by recreational and medical cannabis dispensary openings) between 2006 and 2020 across US states.

Main outcomes and measures: Opioid prescription rates per 100 persons and opioid overdose deaths per 100 000 population based on data from the US Centers for Disease Control and Prevention.

Results: Between 2006 and 2020, 13 states legalized recreational cannabis and 23 states legalized medical cannabis. There was no statistically significant association of recreational or medical cannabis laws with opioid prescriptions or overall opioid overdose mortality across the 15-year study period, although the results also suggested a potential reduction in synthetic opioid deaths associated with recreational cannabis laws (4.9 fewer deaths per 100 000 population; 95% CI, -9.49 to -0.30; P = .04). Sensitivity analyses excluding state economic indicators, accounting for additional opioid laws and using alternative ways to code treatment dates yielded substantively similar results, suggesting the absence of statistically significant associations between cannabis laws and the outcomes of interest during the full study period.

Conclusions and relevance: The results of this study suggest that, after accounting for biases due to possible heterogeneous effects and simultaneous assessment of recreational and medical cannabis legalization, the implementation of recreational or medical cannabis laws was not associated with opioid prescriptions or opioid mortality, with the exception of a possible reduction in synthetic opioid deaths associated with recreational cannabis law implementation.”

https://pubmed.ncbi.nlm.nih.gov/38241056/

https://jamanetwork.com/journals/jama-health-forum/fullarticle/2813866

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

Cannabis for medical use versus opioids for chronic non-cancer pain: a systematic review and network meta-analysis of randomised clinical trials

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“Objective: The objective of this study is to evaluate the comparative benefits and harms of opioids and cannabis for medical use for chronic non-cancer pain.

Design: Systematic review and network meta-analysis.

Data sources: EMBASE, MEDLINE, CINAHL, AMED, PsycINFO, PubMed, Web of Science, Cannabis-Med, Epistemonikos and the Cochrane Library (CENTRAL) from inception to March 2021.

Study selection: Randomised trials comparing any type of cannabis for medical use or opioids, against each other or placebo, with patient follow-up ≥4 weeks.

Data extraction and synthesis: Paired reviewers independently extracted data. We used Bayesian random-effects network meta-analyses to summarise the evidence and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to evaluate the certainty of evidence and communicate our findings.

Results: Ninety trials involving 22 028 patients were eligible for review, among which the length of follow-up ranged from 28 to 180 days. Moderate certainty evidence showed that opioids provide small improvements in pain, physical functioning and sleep quality versus placebo; low to moderate certainty evidence supported similar effects for cannabis versus placebo. Neither was more effective than placebo for role, social or emotional functioning (all high to moderate certainty evidence). Moderate certainty evidence showed there is probably little to no difference between cannabis for medical use and opioids for physical functioning (weighted mean difference (WMD) 0.47 on the 100-point 36-item Short Form Survey physical component summary score, 95% credible interval (CrI) -1.97 to 2.99), and cannabis resulted in fewer discontinuations due to adverse events versus opioids (OR 0.55, 95% CrI 0.36 to 0.83). Low certainty evidence suggested little to no difference between cannabis and opioids for pain relief (WMD 0.23 cm on a 10 cm Visual Analogue Scale (VAS), 95% CrI -0.06 to 0.53) or sleep quality (WMD 0.49 mm on a 100 mm VAS, 95% CrI -4.72 to 5.59).

Conclusions: Cannabis for medical use may be similarly effective and result in fewer discontinuations than opioids for chronic non-cancer pain.”

https://pubmed.ncbi.nlm.nih.gov/38171632/

Cannabidiol and Tetrahydrocannabinol Antinociceptive Activity is Mediated by Distinct Receptors in Caenorhabditis elegans

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“Cannabis has gained popularity in recent years as a substitute treatment for pain following the risks of typical treatments uncovered by the opioid crisis. The active ingredients frequently associated with pain-relieving effects are the phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), but their effectiveness and mechanisms of action are still under research. In this study, we used Caenorhabditis elegans, an ideal model organism for the study of nociception that expresses mammal ortholog cannabinoid (NPR-19 and NPR-32) and vanilloid (OSM-9 and OCR-2) receptors. Here, we evaluated the antinociceptive activity of THC and CBD, identifying receptor targets and several metabolic pathways activated following exposure to these molecules. The thermal avoidance index was used to phenotype each tested C. elegans experimental group. The data revealed for the first time that THC and CBD decreases the nocifensive response of C. elegans to noxious heat (32-35 °C). The effect was reversed 6 h post- CBD exposure but not for THC. Further investigations using specific mutants revealed CBD and THC are targeting different systems, namely the vanilloid and cannabinoid systems, respectively. Proteomic analysis revealed differences following Reactome pathways and gene ontology biological process database enrichment analyses between CBD or THC-treated nematodes and provided insights into potential targets for future drug development.”

https://pubmed.ncbi.nlm.nih.gov/38141130/

https://link.springer.com/article/10.1007/s11064-023-04069-6

The Basic Science of Cannabinoids

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“The cannabis plant has been used for centuries to manage the symptoms of various ailments including pain.

Hundreds of chemical compounds have been identified and isolated from the plant and elicit a variety of physiological responses by binding to specific receptors and interacting with numerous other proteins.

In addition, the body makes its own cannabinoid-like compounds that are integrally involved in modulating normal and pathophysiological processes.

As the legal cannabis landscape continues to evolve within the United States and throughout the world, it is important to understand the rich science behind the effects of the plant and the implications for providers and patients.

This narrative review aims to provide an overview of the basic science of the cannabinoids by describing the discovery and function of the endocannabinoid system, pharmacology of cannabinoids, and areas for future research and therapeutic development as they relate to perioperative and chronic pain medicine.”

https://pubmed.ncbi.nlm.nih.gov/38100799/

https://journals.lww.com/anesthesia-analgesia/fulltext/2024/01000/the_basic_science_of_cannabinoids.6.aspx

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