Category Archives: Pain

Analgesic and toxicological evaluation of cannabidiol-rich Moroccan Cannabis sativa L. (Khardala variety) extract: Evidence from an in vivo and in silico study

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“The legalization of cannabis for industrial and medicinal purposes has significantly expanded worldwide.

This study delves into the analgesic potential toxicity study of chloroformic extract from the Moroccan Cannabis sativa L. (C. sativa) cultivar, Khardala (KH extract). Our findings reveal that the lethal dose of KH extract is ≥5,000 mg/kg, with mice given 2,000 mg/kg exhibiting neurotoxic symptoms, including piloerection, aggressiveness, and fear, along with marked hepato-renal toxicity indicated by elevated levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, and creatinine in both male and female subjects.

Importantly, no toxicity was observed at 250 mg/kg and 500 mg/kg doses. Remarkably, at a dose of 500 mg/kg, the KH extract demonstrated a potent analgesic effect superior to cannabidiol (CBD), suggesting a synergistic interaction among the extract’s bioactive compounds, such as CBD, cannabidivarin (CBDV), Delta 9 tetrahydrocannabinol (THC), cannabigerol (CBG), Delta 9 tetrahydrocannabivarin (THCV), and β-caryophyllene. 

In silico analysis supports these findings, showing the strong binding potential of THC, THCV, CBG, and CBDV to delta opioid receptors, with G-scores >-5.0 kcal/mol, highlighting the promising analgesic efficacy of this cannabis cultivar extract.

This study underscores the therapeutic potential of the KH cultivar, positioning it as a promising candidate for pain management therapies.”

https://pubmed.ncbi.nlm.nih.gov/40917785/

“In summary, this study contributes to the growing body of research on C. sativa, highlighting the potential therapeutic applications of KH extract in pain management.”

https://www.degruyterbrill.com/document/doi/10.1515/biol-2025-1141/html

UK Medical Cannabis Registry: A Clinical Outcomes Analysis for Complex Regional Pain Syndrome

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“Background: Complex regional pain syndrome is characterized by severe, persistent pain. Emerging evidence suggests that cannabis-based medicinal products may represent a new therapeutic option. However, to date, no clinical studies have evaluated the effects of cannabis-based medicinal products in individuals with complex regional pain syndrome. The aim of this study is to assess changes in patient-reported outcome measures and the prevalence of adverse events associated with cannabis-based medicinal products prescribed for complex regional pain syndrome.

Methods: This case series assessed changes in patient-reported outcome measures over 6 months in complex regional pain syndrome patients enrolled in the UK Medical Cannabis Registry. Adverse events were measured and graded using the Common Terminology Criteria for Adverse Events version 4.0.

Results: A total of 64 patients were identified for inclusion. At baseline, pain severity measured by the Brief Pain Inventory Short Form was 6.69 ± 1.42. This improved at 1 (5.85 ± 1.73), 3 (5.91 ± 1.82), and 6 months (6.05 ± 1.72; p < 0.050). Participants also reported improvements in severity as measured by the Short Form-McGill Pain Questionnaire-2 and pain visual analogue scale at the same time points (p < 0.050). Participants also reported improvements in anxiety symptoms, sleep quality, and general health-related quality of life (p < 0.050), as measured by validated measures. Five patients (7.81%) reported 50 (78.13%) adverse events.

Discussion: This study represents the outcomes in individuals with complex regional pain syndrome prescribed cannabis-based medicinal products. These suggest initiation of cannabis-based medicinal products is associated with improvements in patient-reported outcome measures. While these findings are consistent with the literature, they must be interpreted with caution, considering the limitations of this study.

Conclusion: Cannabis-based medicinal products were associated with improvements in pain severity and interference. Participants also reported improvements in important metrics of health-related quality of life. This supports further research through high-quality randomized controlled trials to ascertain the efficacy of cannabis-based medicinal products in improving complex regional pain syndrome symptoms.”

https://pubmed.ncbi.nlm.nih.gov/40898690/

“In conclusion, the results imply that initiation of CBMPs was associated with improved pain relief and health-related quality of life in complex regional pain syndrome patients.”

https://onlinelibrary.wiley.com/doi/10.1002/brb3.70823

Delta-9-tetrahydrocannabinol and Cannabidiol for Pain: Preclinical and Clinical Models

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“Cannabinoids are increasingly being used to manage pain resulting from a variety of conditions.

Both preclinical animal models and human studies have played a crucial role in advancing our knowledge of cannabinoids, their involvement in pain mechanisms, and their potential utility as novel analgesics.

This chapter first reviews basic pain neurobiology and the most common experimental pain paradigms, which provide a basis for our discussion of preclinical, human laboratory, and clinical research characterizing the effectiveness of cannabinoids for managing pain.

While a substantial body of literature exists describing these effects, findings are complex and largely mixed, dependent on the cannabinoid administered, route of administration, and pain modality/syndrome tested. Herein, we highlight the need for more rigorous, placebo-controlled research defining the therapeutic efficacy of cannabinoids.

The chapter concludes by emphasizing the need for further investigation of other cannabis constituents (e.g., minor cannabinoids and terpenes), potential interactions between cannabinoids and other analgesic medications, as well as other emerging issues in the intersection between cannabinoids and pain management.”

https://pubmed.ncbi.nlm.nih.gov/40877567/

https://link.springer.com/chapter/10.1007/7854_2025_604

Opioid reduction in patients with chronic non-cancer pain undergoing treatment with medicinal cannabis

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“Introduction: Opioid sparing by co-prescription of cannabinoids may enable patients to reduce their opioid consumption prescribed for chronic benign pain.

Methods: One cohort attending a small private pain clinic (N = 102), already taking opioids, was co-prescribed cannabinoids and another cohort (N = 53) attending a separate pain clinic nearby received only opioids. The two groups were studied prospectively for a year before their drug consumption was assessed.

Results: At baseline, median opioid consumption was 40 mg/day in both cohorts. Medicinal cannabis was administered daily in an oil formulation usually starting at 2.5 mg/day and was titrated to maximize benefits. At 12 months, the median dose contained 15 mg delta-9-tetrahydrocannabinol and 15 mg cannabidiol. At one-year follow-up, 46 of 102 cases had dropped out compared with only one of 53 controls. Opioid consumption had decreased significantly at one-year follow-up, the final median dose being lower in cases (2.7 mg/day) than controls (42.3 mg/day) (p < 0.05 in an intention-to-treat analysis). Disability and insomnia had also decreased in cases.

Conclusion: The introduction of cannabinoids can produce useful reductions in opioid consumption in real-world settings, with additional benefits for disability and insomnia. However, this treatment is tolerated by only a subgroup of patients.”

https://pubmed.ncbi.nlm.nih.gov/40788193/

“Plain language summary

Morphine-like drugs (opioids) decrease pain but can cause severe breathing problems and death if these drugs are consumed in excessive amounts. Stopping these drugs suddenly (going “cold turkey”) can cause severe adverse effects and, as time goes on, increasing amounts may be required to reduce pain. It might be possible to reduce opioid consumption by also taking medicinal cannabis; otherwise, reduction can be difficult to achieve. Cannabis treatment is safe when the hallucinatory component of cannabis is kept to low levels, causing minimal euphoric effects (a “stoned” sensation).In this study, two groups of patients with chronic pain were studied. Both were taking opioid drugs, but one group also took medicinal cannabis. About half of the medicinal cannabis group were not able to keep taking it due to unpleasant side effects. In the remainder, opioid consumption decreased significantly after both 6 and 12 months. Physical activity and sleep also improved. These findings indicate that medicinal cannabis can help patients to reduce their opioid consumption and improve their physical activity and sleep.”

“These findings indicate that medicinal cannabis can help patients to reduce their opioid consumption and improve their physical activity and sleep.”

https://www.tandfonline.com/doi/full/10.1080/17581869.2025.2544511

Medical cannabis for the management of pain in chronic pancreatitis with recurrent exacerbations: a case report

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“Introduction: Control of pain in patients affected by chronic pancreatitis with recurrent exacerbations is a challenging condition, with conventional therapies often providing limited relief. This case report describes the use of medical cannabis as a novel approach in a patient with refractory chronic pancreatitis, contributing to the growing interest in alternative treatments for pain and inflammation in similar complex cases.

Case presentation: A 54-year-old woman with a 24-year history of chronic pancreatitis caused by recurrent acute pancreatitis presented with persistent, severe abdominal pain and recurrent exacerbations despite undergoing numerous conventional interventions, including cholecystectomy, enzyme supplementation, repeated endoscopic retrograde cholangiopancreatographies (ERCPs), and stent placements. Imaging and laboratory findings confirmed chronic pancreatitis, with evidence of Oddi sphincter stenosis and microlithiasis. The patient was initially managed with standard pain relief therapy, digestive enzymes, and endoscopic interventions, all of which failed to provide lasting relief. In February 2024, she began treatment with a medical cannabis formulation rich in Cannabidiol, under the supervision of her healthcare provider. This intervention led to substantial pain reduction, cessation of acute episodes, improved appetite, and enhanced quality of life.

Conclusion: This case illustrates that medical cannabis may offer a promising alternative for managing chronic pancreatitis, especially when conventional treatments prove ineffective. This outcome underscores the need for further research on cannabinoids as a therapeutic option in chronic pain and inflammation management for pancreatitis and other challenging conditions.”

https://pubmed.ncbi.nlm.nih.gov/40781340/

“This case illustrates the potential of medical cannabis as an effective treatment option for chronic, treatment-resistant pancreatitis, a condition notoriously difficult to manage with conventional therapies. The patient’s experience demonstrates how cannabinoids can provide substantial pain relief, reduce inflammation, and improve quality of life, even when standard interventions fail to yield lasting benefits. Her case underscores the importance of exploring alternative therapies for complex, chronic conditions like pancreatitis, suggesting that medical cannabis may offer a transformative option for patients with few viable treatment paths.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00303-w

Cannabidiol exerts anti-inflammatory effects but maintains T effector memory cell differentiation: A Single-Cell Study in Humans

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“Cannabidiol is widely available and often used for pain management.

Individuals with kidney disease or renal allografts have limited analgesia options. We conducted a Phase 1 human study to compare the peripheral immune cell distribution before (pre-cannabidiol) and after exposure to cannabidiol at steady state (post-cannabidiol).

This ex vivo study included specimens from 23 participants who received oral cannabidiol (up to 5 mg/kg twice daily) for 11 days. Lymphocytes were isolated and stimulated with anti-CD3/CD28 antibodies, with or without tacrolimus. Pharmacodynamic responses were assessed via CellTiter-Glo® proliferation, scRNA-seq, cytokine assays, and flow cytometry. Steady-state plasma concentrations of CBD were quantified via tandem mass spectrometry.

We identified an increased proportion of T effector memory (TEM) cells post-cannabidiol (22% increase, P-value of 3.2 x 10 -32 ), which correlated with CBD plasma concentrations ( Pearson Corr= 0.77, P-value < 0.01 ). Post-cannabidiol cytokine assays revealed elevated proinflammatory IL-6 protein levels and anti-inflammatory IL-10 levels ( adjusted P-values < 0.0001 ). Cannabidiol reduced overall T and B lymphocyte proliferation with additive immunosuppressive effects to tacrolimus. In flow cytometry, the proportion of TEM and TEMRA increased post-cannabidiol with tacrolimus ( P-values < 0.05 ).

Cannabidiol exhibits mixed immunomodulatory effects with pro- and anti-inflammatory signals. Understanding the clinical safety of cannabidiol use is important given the paucity of pain control options available for immunocompromised transplant populations.”

https://pubmed.ncbi.nlm.nih.gov/40766582/

https://www.biorxiv.org/content/10.1101/2025.07.30.667742v1

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