Category Archives: Chronic Pain

Tetrahydrocannabinol and Cannabidiol for Pain Treatment-An Update on the Evidence

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“In light of the current International Association for the Study of Pain (IASP) clinical practice guidelines (CPGs) and the European Society for Medical Oncology (ESMO) guidelines, the topic of cannabinoids in relation to pain remains controversial, with insufficient research presently available.

Cannabinoids are an attractive pain management option due to their synergistic effects when administered with opioids, thereby also limiting the extent of respiratory depression.

On their own, however, cannabinoids have been shown to have the potential to relieve specific subtypes of chronic pain in adults, although controversies remain. Among these subtypes are neuropathic, musculoskeletal, cancer, and geriatric pain.

Another interesting feature is their effectiveness in chemotherapy-induced peripheral neuropathy (CIPN). Analgesic benefits are hypothesized to extend to HIV-associated neuropathic pain, as well as to lower back pain in the elderly.

The aim of this article is to provide an up-to-date review of the existing preclinical as well as clinical studies, along with relevant systematic reviews addressing the roles of various types of cannabinoids in neuropathic pain settings. The impact of cannabinoids in chronic cancer pain and in non-cancer conditions, such as multiple sclerosis and headaches, are all discussed, as well as novel techniques of administration and relevant mechanisms of action.”

https://pubmed.ncbi.nlm.nih.gov/38397910/

https://www.mdpi.com/2227-9059/12/2/307

Perceptions of Orthopaedic Sports Medicine Surgeons About Medical Cannabidiol Use: A Survey Study

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“Introduction: Multiple studies exist identifying cannabidiol (CBD) as an effective part of an orthopaedic patient’s pain regimen; however, there is a paucity of studies elucidating orthopaedic surgeons’ perception of the use and prescription of CBD in the medical setting. This study surveys orthopaedic sports medicine surgeons about their previous education on and current perceptions and usage of CBD in their medical practice.

Methods: Between April 2023 and July 2023, orthopaedic sports medicine surgeons from across the country were surveyed. This survey was designed in hopes of identifying physician perceptions and current use of CBD as well as their previous education and training on its use.

Results: Overall, 75 orthopaedic surgeons responded. More than three-fourths of responders had not received formal education on medical CBD use, nor did they have partners or colleagues who used CBD in their practice. More than half of all surgeons believed that there is a stigma associated with CBD use. A higher proportion of surgeons from CBD legal states recommended CBD to help patients control their pain (53.7% vs. 37.5%). Less than 15% of responders believed that CBD can adversely affect surgical outcomes. Finally, four-fifths of all responders believed that CBD is easy to legally access and affordable to buy by patients who desire it.

Discussion: The relative novelty of CBD inclusion in medicine has led to a lack of early education and overall experience with its use among orthopaedic sports medicine surgeons. Still, surgeons believe that CBD is a safe and effective option to control pain. As surgeons continue to gain more familiarity and trust with CBD’s medical uses over time, it has the potential to be a mainstay in orthopaedic multimodal pain regimens.”

https://pubmed.ncbi.nlm.nih.gov/38318555/

https://www.cureus.com/articles/205336-perceptions-of-orthopaedic-sports-medicine-surgeons-about-medical-cannabidiol-use-a-survey-study#!/

Cannabinoids in anesthesia and chronic pain: Where do we stand?

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“Cannabis derivatives have been conventionally employed globally for their curative and restorative properties for various ailments. However, its recreational use and consequent legal restrictions have substantially cramped its scientific research.

An emerging interest regarding the profound therapeutic potential of cannabinoids has been observed among clinicians. Despite a rich cultural background, high-quality research on cannabinoids is lacking in the Indian scenario. This review readdresses the challenges on this front and brings an insight into the current status of cannabinoids and their utility in scientific exploration.

Cannabinoids have a significant medicinal value in various clinical disorders. Its use so far has been based on scarce resources and corroborations, as evidence-based substantiation is limited.

Through this review article, we emphasize the remarkable role enacted by cannabinoids in the treatment of various clinical disorders and an utterly significant need to formulate stringent research methodologies to promote its systematic investigation.”

https://pubmed.ncbi.nlm.nih.gov/38313715/

https://journals.lww.com/sjan/fulltext/2024/18010/cannabinoids_in_anesthesia_and_chronic_pain__where.16.aspx

Perceptions in orthopedic surgery on the use of cannabis in treating pain: a survey of patients with spine pain (POSIT Spine)

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“Background: Back pain is the leading cause of disability worldwide. Despite guidelines discouraging opioids as first-line treatment, opioids remain the most prescribed drugs for back pain. There is renewed interest in exploring the potential medical applications of cannabis, and with the recent changes in national legislation there is a unique opportunity to investigate the analgesic properties of cannabis.

Methods: This was a multi-center survey-based study examining patient perceptions regarding cannabis for spine pain. We included patients presenting with back or neck pain to one of three Orthopedic clinics in Ontario. Our primary outcome was perceived effect of cannabis on back pain, while secondary outcomes were perceptions regarding potential applications and barriers to cannabis use.

Results: 259 patients participated in this study, 35.3% (90/255) stating they used cannabis medically. Average pain severity was 6.5/10 ± 0.3 (95% CI 6.2-6.8). Nearly three-quarters were prescribed opioids (73.6%, 148/201), with oxycodone/oxycontin (45.9% 68/148) being the most common, and almost half of (49.3%, 73/148) had used an opioid in the last week. Patients estimated cannabis could treat 54.3% ± 4.0 (95% CI 50.3-58.3%) of their spine pain and replace 46.2% ± 6. 6 (95% CI 39.6-52.8%) of their current analgesics. Age (β = – 0.3, CI – 0.6-0.0), higher pain severity (β = 0.4, CI 0.1-0.6) and previous cannabis use (β = 14.7, CI 5.1-24.4) were associated with a higher perceived effect of cannabis. Patients thought cannabis would be beneficial to treat pain (129/146, 88.4%), and reduce (116/146, 79.5%) or eliminate opioids (102/146, 69.9%). Not considering using cannabis for medical purposes (65/150, 43.3%) was the number one reported barrier.

Conclusions: Patients estimated medical cannabis could treat more than half of their spine pain, with one in three patients already using medical cannabis. 79% of patients also believe cannabis could reduce opioid usage. This data will help support more research into cannabis for musculoskeletal pain.”

https://pubmed.ncbi.nlm.nih.gov/38291451/

https://josr-online.biomedcentral.com/articles/10.1186/s13018-024-04558-6

Suppression of neuropathic pain in the circadian clock-deficient Per2m/m mice involves up-regulation of endocannabinoid system

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“Neuropathic pain often results from injuries and diseases that affect the somatosensory system. Disruption of the circadian clock has been implicated in the exacerbation of the neuropathic pain state. However, in this study, we report that mice deficient in a core clock component Period2 (Per2m/m mice) fail to develop tactile pain hypersensitivity even following peripheral nerve injury. Similar to male wild-type mice, partial sciatic nerve ligation (PSL)-Per2m/m male mice showed activation of glial cells in the dorsal horn of the spinal cord and increased expression of pain-related genes. Interestingly, α1D-adrenergic receptor (α1D-AR) expression was up-regulated in the spinal cord of Per2m/m mice, leading to increased production of 2-arachidonoylglycerol (2-AG), an endocannabinoid receptor ligand. This increase in 2-AG suppressed the PSL-induced tactile pain hypersensitivity. Furthermore, intraspinal dorsal horn injection of adeno-associated viral vectors expressing α1D-AR also attenuated pain hypersensitivity in PSL-wild-type male mice by increasing 2-AG production.

Our findings reveal an uncovered role of the circadian clock in neuropathic pain disorders and suggest a link between α1D-AR signaling and the endocannabinoid system.”

https://pubmed.ncbi.nlm.nih.gov/38239754/

https://academic.oup.com/pnasnexus/article/3/1/pgad482/7564865?login=false

Antinociceptive Effects of Cannabichromene (CBC) in Mice: Insights from von Frey, Tail-Flick, Formalin, and Acetone Tests

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“Cannabis sativa contains minor cannabinoids that have potential therapeutic value in pain management. However, detailed experimental evidence for the antinociceptive effects of many of these minor cannabinoids remains lacking. Here, we employed artificial intelligence (AI) to perform compound-protein interaction estimates with cannabichromene (CBC) and receptors involved in nociceptive signaling.

Based on our findings, we investigated the antinociceptive properties of CBC in naïve or neuropathic C57BL/6 male and female mice using von Frey (mechanical allodynia), tail-flick (noxious radiant heat), formalin (acute and persistent inflammatory pain), and acetone (cold thermal) tests. For von Frey assessments, CBC dose (0-20 mg/kg, i.p.) and time (0-6 h) responses were measured in male and female neuropathic mice. For tail-flick, formalin, and acetone assays, CBC (20 mg/kg, i.p.) was administered to naïve male and female mice 1 h prior to testing.

The results show that CBC (10 and 20 mg/kg, i.p.) significantly reduced mechanical allodynia in neuropathic male and female mice 1-2 h after treatment. Additionally, CBC treatment caused significant reductions in nociceptive behaviors in the tail-flick assay and in both phase 1 and phase 2 of the formalin test. Finally, we found a significant interaction in neuropathic male mice in the acetone test.

In conclusion, our results suggest that CBC targets receptors involved in nociceptive signaling and imparts antinociceptive properties that may benefit males and females afflicted with diverse forms of acute or chronic/persistent pain.”

https://pubmed.ncbi.nlm.nih.gov/38255191/

https://www.mdpi.com/2227-9059/12/1/83

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