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#!/

Is hemp (Cannabis sativa) safe to feed pregnant sheep?

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“Cannabis sativa (varieties for industrial use or animal feed are termed hemp), and its extracted byproducts are being considered for animal feed due to their high protein content. However, if hemp disrupts fertility and reproduction in livestock, it should not be used as a feed source.

We hypothesized that the phytocannabinoids in hemp would disrupt fertility and reproduction, cause craniofacial defects (cyclops, cleft palate, misshapen head), and low birth weight in lambs. To test this hypothesis, 22 timed pregnant ewes were dosed with hemp in the form of dried ground hemp plant material at 150 mg/kg body weight per day total cannabinoids, and from gestational days 10 to 20 and a separate 22 timed pregnant ewes were dosed similarly with dried ground grass hay as a control.

The most prevalent cannabinoids in the plant material were cannabidiolic acid (CBDA) at a concentration of 23.2 mg/g, and cannabidiol (CBD) at a concentration of 5.8 mg/g. Delta 9-tetrahydrocannabidiol was present in the plant material at a concentration of 0.3 mg/g. The hemp used in this study had crude protein concentrations of 15.6%, neutral detergent fiber concentrations of 42.2%, and in vitro true digestibility concentrations of 83.6%.

After 10 d of dosing with hemp, a serum sample was obtained from each of the ewes, CBDA was measured at a concentration of 652 ± 38 ng/mL and CBD was measured at 16 ± 0.9 ng/mL. THC was not detected in the serum. The average gestation length for lambs from the hemp treated ewes was 148 ± 0.38 d, and the average gestation length for lambs from the grass hay treated ewes was 149 ± 0.38 d (P = 0.23). The numbers of male and female lambs did not significantly vary from expected (50:50) (P = 0.32). There were no significant fetal deformities (P > 0.05) or weight differences between the treatment groups (P > 0.05), and as expected, the lamb weights significantly increased over time (P < 0.05).

These results suggest that Cannabis sativa may have the potential with further research to be a suitable protein source for gestating sheep.”

https://pubmed.ncbi.nlm.nih.gov/40756673/

“Cannabis sativa L. is a plant of many uses.”

“The study data suggests that hemp, or its byproducts, may be a suitable feed source for sheep, including pregnant ewes.”

https://academic.oup.com/tas/article/doi/10.1093/tas/txaf093/8211445?login=false

Will you precrastinate? Sensitivity to potential performance costs and effort in chronic cannabis users and non-users

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“We examined whether those who chronically use cannabis (chronic users), compared to those who do not use cannabis (non-users), tend to precrastinate (start or complete a subgoal as soon as possible) and engage in reactive (vs. proactive) decision-making incurring greater potential costs in task performance and perhaps costs in cognitive and physical effort. Participants walked down a hallway and retrieved two full cups of water (one near and one far from their starting position) in the order of their choice and carried both back to their start location with the goal of not spilling. First-cup choice (near or far) and attributions of first-cup choice were recorded.

Counter to expectations, chronic users tended to choose the far cup first (i.e., avoided precrastination), the more efficient choice, and this tendency was not different from non-users. Participants’ attributions confirmed that those who chose the far cup first likely engaged in proactive decision-making while those who chose the near cup first likely engaged in reactive decision-making. Additionally, chronic users and non-users utilized proactive control in the AX-Continuous Performance Task even though chronic users had lower short-term and working memory span scores.

These results contradict research suggesting chronic users (vs. non-users) are more impulsive, lack inhibitory control, tend to invest physical effort regardless of reward, and tend not to invest cognitive effort for reward. We suggest that chronic cannabis use may not impair decision making as profoundly as previously thought if individuals are motivated by potential consequences of their decisions in tasks with low memory demand.”

https://pubmed.ncbi.nlm.nih.gov/40760056/

https://link.springer.com/article/10.1007/s00426-025-02139-8

NON-PSYCHOACTIVE CANNABIS EXTRACT PROMOTES EXTINCTION AND REDUCES REINSTATEMENT BY PRIMING DOSE IN SMOKED COCAINE-INDUCED CONDITIONED PLACE PREFERENCE

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“The therapeutic potential of Cannabis sativa L. and cannabidiol (CBD) for substance use disorders is being actively investigated using murine addiction models. However, the efficacy of cannabis or its constituents in attenuating dependence indicators associated with smoked cocaine consumption remains unclear.

This study employed a Conditioned Place Preference (CPP) paradigm using anhydroecgonine methyl ester and cocaine (AEME-COC) as the reinforcing agent to model smoked cocaine consumption in mice.

The model was utilized to evaluate the preclinical efficacy of a non-psychoactive cannabis extract (NPCE) and CBD on extinction parameters and reinstatement induced by stress and priming doses. Experiment 1 compared conditioning phase (Cond) and extinction times between subjects administered cocaine and those receiving AEME-COC. Experiment 2 investigated the effects of CBD and NPCE on extinction latency in AEME-COC-induced CPP. Experiment 3 examined the competitive 5-HT1A receptor antagonist WAY-100135 and CB2 receptor inverse agonist AM630 on NPCE-mediated inhibition of stress-induced and priming-induced reinstatement of AEME-COC-induced CPP.

The results showed that subjects administered cocaine exhibited greater exploration of the conditioned compartment during Cond compared to those administered AEME-COC, with the latter group displaying prolonged extinction latency (Experiment 1).

NPCE, but not CBD, significantly reduced the extinction latency of AEME-COC-induced CPP (Experiment 2). In Experiment 3, NPCE selectively inhibited priming-induced reinstatement but did not affect stress-induced reinstatement. The 5-HT1A receptor attenuated NPCE’s inhibitory effects on priming-induced reinstatement, whereas the CB2 receptor had no significant modulatory impact on this indicator.

These findings suggest that NPCE influences smoked cocaine dependence indicators primarily through serotonergic receptor modulation.”

https://pubmed.ncbi.nlm.nih.gov/40752858/

https://www.sciencedirect.com/science/article/pii/S0031938425002495?via%3Dihub

Assessing the Role of Cannabis in Managing Spasticity in Multiple Sclerosis: A Systematic Review and Meta-Analysis

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“Background: Multiple sclerosis (MS) is a complex, heterogeneous disease, and its management remains challenging due to varying symptoms and patient responses to treatments. While injectable therapies like glatiramer acetate and beta-interferon are common, they have limitations such as side effects and varying efficacy. Cannabis has garnered attention as a potential alternative treatment, particularly for symptoms like spasticity and pain.

Objective: This study aims to evaluate the efficacy of cannabis-based therapies for managing MS-related spasticity.

Methods: Nine clinical trials involving 2544 MS patients were included, with studies conducted between 2003 and 2021 across multiple countries. Cannabinoid therapies studied included whole-plant extracts, oils, and smoked cannabis containing delta-9-tetrahydrocannabinol and/or cannabidiol. Spasticity was assessed using standardized scales, including the Ashworth scale (AS), visual analog scale, and numeric rating scale (NRS). Effect sizes were pooled using random or fixed effects models, and heterogeneity and publication bias were evaluated using I², Tau², and funnel plots.

Results: The overall meta-analysis revealed a standardized mean difference (MD) of 39.19 (95% CI: 34.32-44.05) in spasticity scores, indicating notable improvement post-treatment. Subgroup analyses showed a MD of 20.36 (95% CI: 20.35-20.37) for AS and 1.18 (95% CI: 1.16-1.21) for NRS. However, substantial heterogeneity (I² = 100% for overall and AS analyses; 91% for NRS) and asymmetry in funnel plots suggest possible publication bias and study variability. Short-term studies demonstrated modest changes (MD = 4.53, 95% CI: -0.06 to 9.12), while long-term studies yielded larger effects (MD = 75.81, 95% CI: 66.39-85.22). Adverse events were generally mild, including dizziness and dry mouth.

Conclusion: Cannabis-based therapies are associated with clinically meaningful improvements in MS-related spasticity, particularly over longer durations. Despite the promising findings, high heterogeneity and suspected bias necessitate caution. Further high-quality randomized trials with standardized protocols and comprehensive safety assessments are warranted to validate efficacy and long-term outcomes.”

https://pubmed.ncbi.nlm.nih.gov/40753057/

Pilot Study of Cannabidiol for Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in Breast Cancer

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“Introduction: Aromatase inhibitor (AI) therapy reduces breast cancer recurrence risk. However, some patients stop treatment early because of AI-associated musculoskeletal symptoms (AIMSS). AIMSS is due in part to systemic inflammation. Cannabidiol (CBD) has anti-nociceptive and anti-inflammatory properties, making it a potential treatment option for AIMSS.

Methods: Women with stage 0-3 hormone receptor-positive breast cancer experiencing AIMSS enrolled in this phase 2 clinical trial. Patients received CBD (Epidiolex), titrated over 4 weeks to 100 mg BID, for a total of 15 weeks. Patient-reported outcomes were collected serially. The primary endpoint was the number of patients with at least a 2-point reduction in worst pain from baseline to 15 weeks. Statistical analysis was completed using paired t-tests and linear mixed models.

Results: Of 39 eligible patients, 28 completed protocol-directed study treatment. Eleven discontinued treatment due to toxicity (n = 5) or per patient preference (n = 6). Seventeen of 39 patients met the primary endpoint (43.6%, 95% CI [28%, 60%]). Worst pain improved 0.13 per week of treatment (p < 0.001) for all patients; average improvement in worst pain was 1.95 points at the end of 15 weeks. Of the 28 patients who completed the study, average reduction in worst pain was 2.36 points (95% CI [-3.22, -1.49]) between baseline and Week 15.

Conclusion: Treatment with CBD was safe, tolerable, and associated with improvement in joint pain for a subset of patients. Additional studies are needed to further understand the impact of CBD on AIMSS and which patients are most likely to benefit from CBD treatment.”

https://pubmed.ncbi.nlm.nih.gov/40751295/

“Treatment with CBD was associated with an improvement in AIMSS for a subset of patients. Use of CBD was safe and tolerable for women with hormone receptor-positive breast cancer.”

https://onlinelibrary.wiley.com/doi/10.1002/cam4.71117

Efficacy and safety of cannabidiol in a single-center pediatric drug-resistant epilepsy cohort: a retrospective study

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“Background: Pharmacoresistance to conventional antiseizure medications has been described in approximately 30% of the pediatric epileptic patients, making pharmacological management particularly challenging for physicians. Currently, cannabidiol (CBD) is approved as an adjunctive therapy in combination with clobazam for Dravet Syndrome (DS), Lennox-Gastaut Syndrome (LGS), and as adjunctive treatment for Tuberous Sclerosis Complex (TSC). Studies on drug-resistant epilepsy (DRE) suggested that CBD antiepileptic properties may benefit a wider range of pharmacoresistant epilepsy syndromes.

Objective: Our observational, retrospective, monocentric study aimed to evaluate the effect and safety of CBD in a real-world pediatric cohort with DRE.

Methods: We recruited 15 pediatric patients (7 females, 8 males; mean age: 12.33 ± 4.37 years) affected by pharmacoresistant epilepsy treated with CBD as adjunctive therapy. Inclusion criteria required a diagnosis of DRE, initiation of CBD treatment before 18 years of age, and at least 6 months period of follow-up after CBD initiation. Clinical, demographic, and instrumental data were retrospectively extracted from the medical records and caregivers’ reports. Based on seizure reduction, patients were stratified into “responders” (>50%), “partial responders” (30-50%), and “non-responders” (<30%) groups.

Results: CBD was used as an add-on therapy in 8/15 patients on-label (for DS, LGS, and TSC) and in 7/15 off-label. The maximum dose of CBD administered was 21 mg/kg/day, with an average dose of 16.5 mg/kg/day. 11/15 patients showed a reduction in seizure frequency: 7 were responders (2/7 seizure-free) and 5 were partial responders. Additionally, 11/15 patients showed improved social and environmental participation, as assessed using the Clinical Global Impression scale. Interestingly, brain magnetic resonance imaging revealed structural abnormalities in 5/15 patients, with 6/15 showing malformations of cortical development (4/6 responders, including 1 seizure-free).

Conclusion: CBD demonstrated a good safety and tolerability profile and appeared to be a promising therapeutic option for the management of DRE. It offers a valuable alternative for seizure control and has a positive impact on social interaction, with overall improvement in the quality of life for patients and their caregivers.”

https://pubmed.ncbi.nlm.nih.gov/40740850/

“In conclusion, CBD may represent a promising therapeutic option capable of enhancing the clinical management of DRE. Indeed, it offers a valuable alternative for seizure treatment and positively impacts social interaction and quality of life for the patients and their caregivers.”

https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1616480/full

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

The impact of cannabis use on ageing and longevity: a systematic review of research insights

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“With aging emerging as a global challenge linked to chronic diseases, identifying interventions that support a healthy lifespan and health span has become imperative. Cannabinoids derived from cannabis, particularly cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), have gained attention for their potential to promote healthy aging through interactions with the endocannabinoid system. While CBD has often been highlighted for its benefits, emerging evidence indicates that THC, under certain conditions and doses, may also play a therapeutic role in aging. Despite this interest, significant knowledge gaps persist in understanding cannabis’s role in promoting healthy aging and longevity.Aim

We reviewed recent literature to investigate the effect of cannabinoid use, particularly CBD and THC on aging and longevity. By synthesizing findings from preclinical models, clinical studies, and real-world evidence, we aimed to elucidate the potential of cannabinoids, in fostering healthy aging, mitigate age-related decline, and promote well-being in older populations.Method

We conducted a systematic review guided by PRISMA to investigate the impact of cannabinoids on aging and longevity. Studies involving preclinical models (e.g., Caenorhabditis elegans, rodents, zebrafish, and mice) and clinical populations aged 50 years and older were included. Exclusion criteria targeted acute effects and mechanisms of action in different medical conditions. Aging was explicitly defined as biological and psychological changes associated with advancing age, and longevity was defined as the extension of lifespan and factors influencing healthy aging.Findings

Eighteen studies investigating the direct impact of cannabinoids on aging and longevity were identified in preclinical models (11) and human studies (7). Preclinical studies have shown promising results regarding the potential benefits of cannabinoids including improved lifespan, cognitive function, inflammation, memory, sleep quality, and social interaction. The effects of THC appear more complex, with potential benefits at low doses and drawbacks at higher doses, highlighting their complex role in aging. However, the limited number of human studies hinders a comprehensive understanding. Clinical studies also suggest potential therapeutic applications for cannabinoids in aging populations, although further research is needed to understand their mechanisms of action and long-term effects fully.”

Conclusion

“Cannabinoids hold promise for supporting healthy aging and enhancing the quality of life in older populations. While preliminary research suggests intriguing possibilities, more studies are needed to solidify the link between cannabis use, the ECS, and healthy aging in humans. Rigorous clinical trials are crucial to evaluate their safety and efficacy. Longitudinal studies and well-designed clinical trials are critical to understanding the safety, efficacy, and long-term effects of cannabis use in aging populations. Future research should optimize dosages, investigate mechanisms of action, and explore the influence of cannabis use initiated in aging as opposed to lifetime exposure. Clarifying these aspects is vital for informing public health strategies and developing targeted therapeutic interventions for age-related conditions.”

“These findings open exciting avenues for exploring novel therapeutic interventions for age-related cognitive decline and neurological disorders.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00267-x

https://pubmed.ncbi.nlm.nih.gov/40731362/

Clinical predictors of mortality in dual diagnosis patients receiving integrated in-patient treatment-A cohort study with 21 years follow-up

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“Aims: To examine mortality, and identify predictors of mortality, in a cohort of dual diagnosis (co-existing psychiatric disorder and substance use disorder) patients.

Design: Cohort study based on national register and electronic health record data.

Setting and participants: Between 2002 and 2017, 2359 dual-diagnosis patients received treatment at a specialized Danish department and were followed until death, migration or a maximum of 21 years.

Measurements: Data on diagnosis, substance use, demographics, medication use and mortality were linked to national registers. Kaplan-Meier plots illustrated mortality differences across diagnostic groups, while the Cox model identified factors associated with mortality.

Findings: In this study, 23.5% of dual diagnosis patients died within ten years of discharge and 33.7% at end of follow-up. The highest mortality risk was among those with a primary substance use disorder (SUD) and no psychiatric diagnosis, with 45.9% dying. Alcohol [adjusted hazard ratio (aHR) = 1.42; 95% confidence interval (CI) = 1.18-1.71], opioids (aHR = 1.26; 95% CI = 1.03-1.54), as well as Charlson Comorbidity Index: 1 (aHR = 1.70; 95% CI = 1.41-2.04) and 2 + (aHR = 2.56; 95% CI = 1.94-3.36), increased mortality risk.

In contrast, cannabis use disorder (aHR = 0.77; 95% CI = 0.65-0.93) and being female (aHR = 0.83; 95% CI = 0.71-0.97) reduced it.

Psychiatric diagnoses F30-39 (aHR = 0.70; 95% CI = 0.56-0.87) and F40-49 (aHR = 0.76; 95% CI = 0.59-0.97) were associated with lower mortality risk compared with F20-29. Of 733 deaths with mortality cause data, nearly two-thirds were from natural causes, 8% from suicide and 20% from accidents or violence.

Conclusion: The observed high mortality rates among clinically confirmed dual diagnosis patients (co-existing psychiatric disorder and substance use disorder) in Denmark highlight the urgent need for comprehensive treatment for this population. The risk of death appears to be related to type of substance use, with alcohol and opioids associated with higher mortality rates than other substances.”

https://pubmed.ncbi.nlm.nih.gov/40726419/

https://onlinelibrary.wiley.com/doi/10.1111/add.70125