Category Archives: Pain

The Efficacy and Safety of Use of Cannabis and Cannabinoid Products for Pain Relief in Orthopaedic Conditions and Trauma

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“This systematic review examines the efficacy of medical cannabis in pain management within orthopaedic domains, including arthritis pain, postsurgical pain, back pain, and post-trauma pain. Given the challenges and risks associated with traditional pain medications, particularly opioids, this review aims to assess the efficacy and safety of medical cannabis for orthopaedic pain management.

A literature search was conducted on databases such as PubMed and Cochrane to find primary research papers on the efficacy and safety of cannabis. A comprehensive analysis was conducted on available literature, focusing on studies that evaluated the efficacy and safety profile of medical cannabis in various orthopaedic pain conditions. Only randomised controlled trials (RCTs) were included to keep the evidence of high quality. The quality of the studies was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool, and the risk of bias was assessed using the Cochrane Risk of Bias tool. The review particularly assessed the effectiveness of medical cannabis compared to no treatment, placebo, and active comparators. Additionally, the review examined the optimal dosing, methods of administration, and the safety profile of medical cannabis.

The review reveals minimal high-quality evidence supporting the efficacy of medical cannabis in the targeted orthopaedic areas. Most evidence suggests effectiveness only when compared with no treatment or placebo, with limited data against active comparators. The review also highlights the need for more research to determine optimal dosing and administration methods. The safety profile of medical cannabis, characterised by generally mild to moderate adverse effects, suggests its potential as a safer alternative or adjunct to opioid pain management.

The findings indicate that while medical cannabis may hold promise as an alternative or adjunct therapy in orthopaedic pain management, there is a need for more robust and methodologically sound research. Future studies should focus on long-term efficacy and safety, standardisation of dosing and administration, and comprehensive reporting of adverse effects. This is essential for developing effective treatment protocols that balance pain relief with safety and understanding the role of medical cannabis in orthopaedic pain management.”

https://pubmed.ncbi.nlm.nih.gov/40755585/

https://www.cureus.com/articles/354641-the-efficacy-and-safety-of-use-of-cannabis-and-cannabinoid-products-for-pain-relief-in-orthopaedic-conditions-and-trauma#!/

Expanding the Therapeutic Profile of Topical Cannabidiol in Temporomandibular Disorders: Effects on Sleep Quality and Migraine Disability in Patients with Bruxism-Associated Muscle Pain

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“Background: Cannabidiol (CBD) has demonstrated potential as a therapeutic agent for muscle tension, pain, and sleep bruxism, yet its broader impact on comorbid conditions such as sleep disturbance and migraine disability remains underexplored. This study aimed to assess the effects of topical CBD on sleep quality and migraine-related disability in patients with bruxism-associated muscular pain. 

Methods: In a randomized, double-blind clinical trial, 60 participants with bruxism were allocated equally into three groups: control (placebo gel), 5% CBD gel, and 10% CBD gel. Participants applied the gel intraorally to the masseter muscles nightly for 30 days. Sleep quality and migraine-related disability were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Migraine Disability Assessment Scale (MIDAS), respectively. Surface electromyography (sEMG) and the Bruxoff® device were used for objective evaluation of muscle tension and bruxism intensity. 

Results: Both CBD treatment groups demonstrated statistically significant improvements in PSQI and MIDAS scores compared to the control group (p < 0.001). No significant differences were observed between the 5% and 10% CBD groups, suggesting comparable efficacy. The sEMG findings corroborated a reduction in muscle tension. Improvements in sleep and migraine outcomes were positively correlated with reductions in muscle activity and pain. 

Conclusions: Topical CBD gel significantly improved sleep quality and reduced migraine-related disability in patients with bruxism-associated muscular pain, supporting its role as a multifaceted therapeutic option in the management of TMD and related comorbidities. Further research is needed to confirm long-term benefits and determine optimal dosing strategies.”

https://pubmed.ncbi.nlm.nih.gov/40732351/

“This study demonstrates that topical application of cannabidiol (CBD) gel, at both 5% and 10% concentrations, significantly improves sleep quality and reduces migraine-related disability in patients with bruxism-associated muscular pain. These effects were observed alongside reductions in muscle tension and pain, suggesting a broader therapeutic impact of CBD beyond localized symptom relief. Notably, no substantial differences were found between the two concentrations, indicating that lower doses may achieve comparable clinical outcomes.

The findings support the use of topical CBD as a well-tolerated, non-invasive adjunct in the multimodal management of temporomandibular disorders (TMD), especially in patients experiencing comorbid sleep and headache disturbances. Future research should explore long-term efficacy, optimal dosing, and underlying mechanisms through objective neurophysiological and sleep assessments”

https://www.mdpi.com/1424-8247/18/7/1064

Cannabis Use for Chronic Pain in Sickle Cell Disease: A Scoping Review

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“Purpose: The purposes of this scoping review were to: (1) systematically evaluate the literature on the types and effectiveness of cannabis and cannabinoids for pain management in adults with sickle cell disease (SCD), (2) assess the effect of cannabis and cannabinoids on pain outcomes, and (3) identify research gaps.

Design: Systematic scoping review.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines, relevant studies were identified across PubMed, CINAHL, and Cannakeys databases. Inclusion criteria were studies involving medical and recreational cannabis use in adult SCD patients addressing pain management. Exclusion criteria included studies on pediatric populations, non-English publications, or case reports.

Results: Of 369 articles, 12 met inclusion criteria (one clinical trial, two reviews, seven observational, one mixed-methods, and one qualitative study), revealing mixed but generally positive evidence on cannabinoid effectiveness. While some studies indicated reduced pain scores with inhaled cannabis, results varied for other pain outcomes, such as hospitalizations for vaso-occlusive crises, and raised safety concerns, particularly with synthetic cannabinoids.

Conclusions: Cannabinoids may help manage SCD pain, though evidence remains mixed. No studies showed exacerbation of SCD symptoms, but safety concerns warrant careful use.

Clinical implications: The variability in outcomes underscores the need for personalized cannabis-based treatment plans and further research on standardized dosing and long-term safety.”

https://pubmed.ncbi.nlm.nih.gov/40713408/

https://www.painmanagementnursing.org/article/S1524-9042(25)00201-2/abstract

Medical Cannabis Use and Healthcare Utilization Among Patients with Chronic Pain: A Causal Inference Analysis Using TMLE

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“Introduction: Chronic pain affects approximately 20% of U.S. adults, imposing significant burdens on individuals and healthcare systems. Medical cannabis has emerged as a potential therapy, yet its impact on healthcare utilization remains unclear.

Methods: This retrospective cohort study analyzed administrative data from a telehealth platform providing medical cannabis certifications across 36 U.S. states. Patients were classified as cannabis-exposed if they had used cannabis in the past year, while unexposed patients had no prior cannabis use. Outcomes included self-reported urgent care visits, emergency department (ED) visits, hospitalizations, and quality of life (QoL), measured using the CDC’s Healthy Days measure. Targeted Maximum Likelihood Estimation with SuperLearner estimated causal effects, adjusting for numerous covariates.

Results: Medical cannabis users exhibited significantly lower healthcare utilization. Specifically, exposure was associated with a 2.0 percentage point reduction in urgent care visits (95% CI: -0.036, -0.004), a 3.2 percentage point reduction in ED visits (95% CI: -0.051, -0.012) and fewer unhealthy days per month (-3.52 days, 95% CI: -4.28, -2.76). Hospitalization rates trended lower but were not statistically significant. Covariate balance and propensity score overlap indicated well-fitting models.

Conclusions: Medical cannabis use was associated with reduced healthcare utilization and improved self-reported QoL among chronic pain patients.”

https://pubmed.ncbi.nlm.nih.gov/40700267/

“The findings of this study suggest, in line with existing research, that medical cannabis is likely an effective treatment option for patients with chronic pain. Moreover, we found that, in addition to an increase in QoL, medical cannabis exposure is associated with lower risk of urgent care and ED visits, when comparing patients who used medical cannabis for at least one year to cannabis-naïve patients. This underscores the potential for not only QoL gains associated with medical cannabis use, but also positive downstream effects on the healthcare system resulting from treatment.”

https://www.mdpi.com/2226-4787/13/4/96

Machine-learning of medical cannabis chemical profiles reveals analgesia beyond placebo expectations

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“Background: The efficacy of medical cannabis in alleviating pain has been demonstrated in clinical trials, yet questions remain regarding the extent to which specific chemical compounds contribute to analgesia versus expectation-based (placebo) responses. Effective blinding is notoriously difficult in cannabis trials, complicating the identification of compound-specific effects.

Methods: In a prospective study of 329 chronic pain patients (40% females; aged 48.9 ± 15.5) prescribed medical cannabis, we examined whether the chemical composition of cannabis cultivars could predict treatment outcomes. We used a Random Forest classifier with nested cross-validation to assess the predictive value of demographics, clinical features, and approximately 200 chemical compounds. Model robustness was evaluated using six additional machine learning algorithms.

Results: Here we show that incorporating chemical composition markedly improves the prediction of pain relief (AUC = 0.63 ± 0.10) compared to models using only demographic and clinical features (AUC = 0.52 ± 0.09; p < 0.001). This result is consistent across all models tested. While well-known cannabinoids such as THC and CBD provide limited predictive value, specific terpenoids, particularly α-Bisabolol and eucalyptol, emerge as key predictors of treatment response.

Conclusions: Our findings demonstrate that pain relief can be predicted from cannabis chemical profiles that are unknown to patients, providing evidence for compound-specific therapeutic effects. These results highlight the importance of considering the full range of cannabis compounds when developing more precise and effective cannabis-based therapies for pain management.”

https://pubmed.ncbi.nlm.nih.gov/40670615/

“Chronic pain affects millions of people, and many turn to medical cannabis for relief. However, scientists debate whether cannabis truly reduces pain or if patients feel better simply because they expect it to work (placebo effect). In this study, we looked at 329 people who used medical cannabis and analyzed the chemical makeup of their treatments. Using machine learning, we tested whether the specific chemicals in cannabis could predict who would get pain relief.

We found that patients’ pain improvement could be predicted from the chemical content of their cannabis, even though patients didn’t know what chemicals they were receiving. This suggests that cannabis provides real pain relief beyond just patient expectations.

These findings show that medical cannabis has genuine therapeutic effects for pain management.”

“In conclusion, to the best of our knowledge, our study provides compelling evidence that the efficacy of MC in pain relief is not merely a placebo response but is strongly influenced by its diverse chemical composition. Our findings challenge the traditional focus on THC and CBD as the primary therapeutic agents in cannabis and highlight the importance of considering the full spectrum of chemical compounds present in MC. By embracing a more comprehensive approach to understanding MC’s therapeutic potential, we can work towards developing safer, more effective, and more precisely targeted treatments for the millions of individuals suffering from chronic pain worldwide.”

https://www.nature.com/articles/s43856-025-00996-3

The Role of the Endocannabinoid System in the Mechanism of Action of Nonopioid Analgesics

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“The endocannabinoid system (eCBS) plays a crucial role in pain modulation through its components, including endocannabinoids, cannabinoid receptors (CB1 and CB2), and metabolic enzymes.

Recent research highlights the interaction between the eCBS and non-opioid analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and pyrazolones. These agents may enhance endogenous endocannabinoid levels or influence eCBS signaling pathways, providing a multifaceted approach to pain relief.

This review examines the pharmacological mechanisms underlying these interactions, focusing on the potential of non-opioid eCBS interactions, detailing synergistic effects that could improve analgesic efficacy while minimizing side effects. Additionally, we explore the therapeutic implications of co-administering non-opioid analgesics with eCBS modulators to create more effective pain management strategies.

The combined modulation of non-opioid pathways and the eCBS represents a promising treatment for acute and chronic pain, warranting further clinical investigation and translational research in this evolving field.”

https://pubmed.ncbi.nlm.nih.gov/40659176/

“Emerging Therapeutic Strategies: The integration of non-opioid medications with eCBS modulators represents a novel approach in pain management strategies, aiming to minimize opioid use while maximizing therapeutic efficacy and safety profiles during chronic pain management.”

https://www.sciencedirect.com/science/article/abs/pii/S0014299925007009?via%3Dihub

Prevention of Allodynia and Hyperalgesia by Cannabidiol in a Rat Model of Chemotherapy-Induced Peripheral Neuropathy

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“This study demonstrates the utility of a rat model of chemotherapy-induced peripheral neuropathy (CIPN) to assess the ability of the non-psychoactive cannabinoid cannabidiol (CBD) to modulate the development of this syndrome in vivo. The method utilizes the chemotherapeutic agent paclitaxel to generate an allodynic phenotype in the animals.

This study describes how to handle and solubilize CBD, administer the chemotherapeutic agent, assess mechanical and cold sensitivity, and apply high-speed videography to measure nocifensive behavior in animals.

Using the procedures outlined, the data support that CBD prevents the allodynic phenotype from developing in the treated animals. No difference was observed in the CBD-treated animals from day 0 (pre-paclitaxel baseline) to day 7 (post-sensitization) in mechanical or thermal sensitivity, while the vehicle-treated animals became significantly more sensitive.

This response to treatment is durable up to the latest time point where data were collected (7 weeks). The addition of high-speed videography allows for a more granular and unbiased assessment of this behavioral phenotype (e.g., classification of analgesia and anti-allodynia).

This demonstrates both the utility of this model for cannabinoid drug characterization and the potential role of CBD in mitigating neuropathic pain.”

https://pubmed.ncbi.nlm.nih.gov/40622941/

“Co-administration of CBD with paclitaxel prevents the development of chemotherapy-induced peripheral neuropathy in rats. This protocol describes cannabinoid handling, inducing an allodynic phenotype in rats via chemotherapeutic administration, assessing mechanical and thermal allodynia, and using high-speed videography to distinguish allodynia and hyperalgesia.”

https://app.jove.com/t/68079/prevention-allodynia-hyperalgesia-cannabidiol-rat-model-chemotherapy

Cannabidiol interactions with Δ-9-tetrahydrocannabinol on antinociception after carrageenan-induced inflammatory pain in male and female rats

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“Cannabis products used for pain typically contain Δ-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) in varied amounts, but data on the effects of specific cannabinoid formulations on different pain types are lacking.

This study used the carrageenan-induced inflammatory pain model to test oral Δ9-THC, CBD, or their combination on acute edema and pain hypersensitivity.

Male and female Sprague-Dawley rats (n = 10-14 per sex/group) were pretreated (1 hour) with vehicle (sesame oil), Δ9-THC (1, 3, and 10 mg/kg, p.o.), CBD (10, 30, 100 mg/kg, p.o.), or select doses of Δ9-THC + CBD combinations prior to an intraplantar λ-carrageenan injection into the hind paw.

The nonsteroidal anti-inflammatory drug ketoprofen (10 and 20 mg/kg i.p.) or its vehicle (1:1:18 ethanol:Cremophor EL:saline [Millipor Sigma]) was administered to a separate group as a positive control. Measurements were conducted at baseline and 1, 3, and 5 hours after carrageenan injection. Carrageenan produced edema and hypersensitivity to radiant heat (hyperalgesia) and mechanical pressure (allodynia).

Δ9-THC alone sex- and dose-dependently decreased hyperalgesia and allodynia but not inflammation, with effects of Δ9-THC being greater in females than males, and the lowest Δ9-THC dose was proinflammatory in males. CBD alone did not affect pain sensitivity but had modest anti-inflammatory effects in males. Isobolographic and dose addition analyses indicated Δ9-THC + CBD was subadditive relative to Δ9-THC alone.

These data demonstrate that prophylactic oral Δ9-THC alleviates acute inflammatory pain with sex-dependent effects, and CBD diminishes Δ9-THC antinociception when combined.

The findings suggest oral Δ9-THC is superior to CBD or combined Δ9-THC + CBD for acute inflammatory pain.

SIGNIFICANCE STATEMENT: Despite the popularity of cannabis for pain management, empirical data on how specific cannabinoid formulations affect acute inflammatory pain are limited. This study in rats found that pure Δ-9-tetrahydrocannabinol (Δ9-THC) formulations were most effective at improving inflammatory pain compared to pure cannabidiol or Δ9-THC + cannabidiol combinations, and females were more sensitive than males to the antinociceptive effects of Δ9-THC.”

https://pubmed.ncbi.nlm.nih.gov/40609153/

https://jpet.aspetjournals.org/retrieve/pii/S0022356525398381

Cannabinoid receptor ligands with potential therapeutic applications and mechanisms of action: a versatile natural therapeutic agent

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“The endocannabinoid system (ECS) is a complex signaling network essential for regulating various physiological processes in the body. Selective cannabinoid receptor ligands have been developed to modulate specific ECS signaling pathways, offering potential therapeutic benefits. These ligands, with high selectivity and affinity for cannabinoid receptors, demonstrate potential in managing diverse medical conditions. Standardizing dosing is crucial to ensure reliable therapeutic effects, as cannabinoids may exhibit biphasic effects. Combination strategies involving both CB1 and CB2 receptor modulation show promise in managing complex conditions, including chronic pain, autoimmune disorders, and neurodegenerative diseases.”

https://pubmed.ncbi.nlm.nih.gov/40600897/

https://www.tandfonline.com/doi/full/10.1080/10286020.2025.2522396

How to ESCAPE from Pain? An Observational Study on Improving Pain and Quality of Life with the Cannamedical® Hybrid Cannabis Extract

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“Introduction: Chronic pain remains a challenge, with standard therapies often providing inadequate pain relief and causing undesirable side effects. Medicinal cannabis has emerged as promising alternative. This study assessed the impact of a cannabis hybrid extract on pain intensity and quality of life in daily clinical use.

Methods: ESCAPE was an observational study and included patients aged ≥ 18 years with chronic pain in Germany. The primary objective was to evaluate the effectiveness of the Cannamedical® Hybrid Cannabis Extract THC25:CBD25 on pain during four visits (V1-V4) in clinical practice, and key secondary objectives were pain interference and quality of life. Pain intensity was measured using the Numeric Rating Scale (NRS) of the Brief Pain Inventory (BPI) questionnaire. Pain interference was evaluated with the BPI pain interference subscore, and quality of life-particularly physical and mental health-was assessed with the Short Form-12 (SF-12) questionnaire. Additionally, patient and physician satisfaction with the extract was assessed.

Results: The study included 64 patients (50% female) with chronic pain (intention-to treat population; ITT). Cannabis-naïve patients of the ITT were defined as a subgroup and analyzed separately (N = 35). Mean (± SD) NRS-assessed pain intensity decreased during the study, in both the ITT (5.46 ± 1.73 at V1 vs. 3.37 ± 2.43 at V4) and in the cannabis-naïve subgroup (5.92 ± 1.34 at V1 vs. 2.37 ± 1.69 at V4). Mean pain interference subscore decreased between V1 and V4 for the ITT (5.39 ± 1.92 vs. 3.38 ± 2.46) and the cannabis-naïve group (5.68 ± 1.46 vs. 2.54 ± 1.99). Physical and mental health improved in both groups and high satisfaction with the hybrid cannabis extract was reported by patients and physicians.

Conclusion: Treatment with the Cannamedical® Hybrid Cannabis Extract THC25:CBD25 in daily clinical practice showed positive effects on patients’ pain and quality of life.”

https://pubmed.ncbi.nlm.nih.gov/40560527/

https://link.springer.com/article/10.1007/s12325-025-03262-z