Category Archives: Pain

Therapeutic Potential of Cannabidiol-Rich Cannabis sativa to Mitigate the Severity of Inflammation and Pain: A Pre-Clinical Study

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“Ethnopharmacological relevance: Pain and inflammation are among the many conditions for which Cannabis sativa L. has historically been used. However, little research has been done on the potential therapeutic benefits of employing green extraction techniques to generate an extract from C. sativa that is high in cannabidiol for the treatment of severe pain and inflammation.

Aim of the study: This study investigates the potential chemico-pharmacological profile of a supercritical CO2 extract of Cannabis sativa genotype CIM-CS-64 (CSFE) for managing inflammation and pain responses using an experimental pharmacology approach.

Materials and methods: A combination of complementary analytical techniques (GC-FID, GC-MS, HPLC, HRMS, NMR) was used to examine the chemical composition of the CSFE to ensure comprehensive chemical coverage. The experiments were conducted on small laboratory animals to investigate the therapeutic efficacy of CSFE in mitigating inflammation and pain responses.

Results: Altogether, sixty-two compounds with cannabidiol, β-caryophyllene, cannabidivarin, cannabichromene, (E)-phytol, and α-bisabolol as major constituents were annotated in CSFE by GC-FID and GC-MS techniques. The HPLC analysis revealed the presence of CBD (9.75 ± 0.85%), CBDA (2.76 ± 0.69%) and Δ9-THC (4.40±0.16%) as major cannabinoids in the CSFE. In LPS-stimulated macrophages, the CSFE markedly reduced the production of pro-inflammatory cytokines (TNF-α and IL-6) at concentrations of 3, 10, and 30 μg/ml without causing any cytotoxicity. The results demonstrated a significant decrease in inflammation and considerable improvement in pain-relieving potential in a dose-dependent manner.

Conclusions: The present research revealed that CSFE possesses promising analgesic and anti-inflammatory properties in small laboratory animals.”

https://pubmed.ncbi.nlm.nih.gov/41213439/

“Altogether, sixty-two compounds with cannabidiol, β-caryophyllene, cannabidivarin, cannabichromene, (E)-phytol, and α-bisabolol as major constituents were annotated in CSFE by GC-FID and GC-MS techniques.

The HPLC analysis revealed the presence of CBD (9.75 ± 0.85 %), CBDA (2.76 ± 0.69 %) and Δ9-THC (4.40 ± 0.16 %) as major cannabinoids in the CSFE. In LPS-stimulated macrophages, the CSFE markedly reduced the production of pro-inflammatory cytokines (TNF-α and IL-6) at concentrations of 3, 10, and 30 μg/ml without causing any cytotoxicity.

The results demonstrated a significant decrease in inflammation and considerable improvement in pain-relieving potential in a dose-dependent manner.”

“The present research revealed that CSFE possesses promising analgesic and anti-inflammatory properties in small laboratory animals.”

“The findings validate the use of the plant for managing pain and inflammation in traditional medicine.”

https://www.sciencedirect.com/science/article/abs/pii/S037887412501548X?via%3Dihub

Combination CBD/THC in the management of chemotherapy-induced peripheral neuropathy: a randomized double blind controlled trial

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“Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) can greatly impair function, leading to disability or truncated treatment in cancer patients. Previous animal studies show that cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC) can ameliorate CIPN. This study assessed the effect of combined CBD and THC on CIPN symptoms amongst cancer patients treated with taxane- or platinum-based agents.

Materials and methods: This 12-week randomized, double-blind, placebo-controlled trial included participants with nonmetastatic breast, colorectal, endometrial, or ovarian cancer experiencing grade 2-3 CIPN. The active group received CBD (125.3-135.9 mg) combined with THC (6.0-10.8 mg) in gelcaps. The Quality-of-Life Questionnaire-CIPN twenty-item scale (QLQ-CIPN20) sensory subscale was used as the primary outcome. Additional outcomes assessed pain, sleep, and function. Neurologic exams evaluated touch, pressure, and vibration sense. Following the randomized controlled trial, participants were invited to enroll in a 12-week open-label observational study.

Results: Of 230 participants identified, 124 met eligibility, 54 were enrolled, 46 were randomized, and 43 completed 12 weeks of treatment. This was lower than our goal of 100 randomized participants. The mean age was 60 +/- 9 years, 88% were female, 63% had breast cancer. All participants had completed chemotherapy. The primary analysis showed no differences in outcome measures between active and placebo groups, likely due to sample size. Although an increase in bilirubin (one participant in active group, and one in placebo) and alkaline phosphatase (one participant in active group) was seen, this did not exceed the exit criteria. A secondary analysis showed that the active group experienced greater improvement in the QLQ-CIPN20 measures of sensory impairment relative to placebo (-10.4 (95% -20.5, -0.3), p = 0.044). There was also improvement in light touch and vibration sensation of the feet on neurological exam that approached significance. There was no effect on other measures, including pain, and no between-group differences in side effects. The uncontrolled observational study showed similar results.

Discussion: The primary analysis showed no between-group difference in CIPN symptoms. The secondary analysis indicated that CBD with THC could improve sensory impairment and might increase touch and vibration sense, although these findings require confirmation in a future, more fully powered study. Nonetheless, our results show that combination CBD/THC can be safely delivered to participants with CIPN and suggest that these cannabinoids should be further investigated for this indication.”

https://pubmed.ncbi.nlm.nih.gov/41211445/

“Overall, this study suggests that combination CBD/THC could help with the sensory impairment seen in CIPN. Since the disorder is prevalent and incurs significant hardship, even a modest sensory improvement could enhance patients’ quality of life, given the lack of alternatives.”

https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1590168/full

The impact of tetrahydrocannabinol on central pain modulation in chronic pain: a randomized clinical comparative study of offset analgesia and conditioned pain modulation in fibromyalgia

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“Tetrahydrocannabinol (THC) has shown efficacy in alleviating chronic pain, particularly in disorders characterized by central sensitization. Offset analgesia (OA) and conditioned pain modulation (CPM) are key biomarkers used to evaluate central pain modulation.

This study aimed to compare the effects of THC on OA and CPM in fibromyalgia syndrome (FMS), a prototypical condition of central sensitization.

Methods

In a randomized, double-blind, placebo-controlled crossover design, 23 FMS patients participated in two experimental sessions. Each session included the McGill Pain Questionnaire, visual analogue scale (VAS) assessments, and evaluations of OA and CPM, conducted both before and after sublingual administration of either THC (0.2 mg/kg) or placebo.

Results

THC significantly reduced spontaneous pain ratings on the McGill scale compared to both baseline and placebo (P = 0.01 and P = 0.02, respectively). THC also significantly enhanced OA relative to baseline and placebo (P = 0.04 and P = 0.008), while no effect was observed on CPM (P = 0.27). Notably, baseline OA magnitude significantly predicted THC-induced pain relief (R² = 0.404, P = 0.003), whereas CPM did not show a significant association (P = 0.121).

Conclusions

This is the first study to evaluate THC’s distinct effects on central pain modulation using both OA and CPM. THC selectively enhanced OA without influencing CPM, highlighting differential neural mechanisms underlying these paradigms. Furthermore, OA predicted treatment response, suggesting its potential as a biomarker for personalized cannabinoid-based therapies in FMS and other central sensitization disorders.”

https://pubmed.ncbi.nlm.nih.gov/41199355/

“Cannabis, particularly its psychoactive component delta-9-tetrahydrocannabinol (THC), has attracted increasing attention as a therapeutic option for chronic pain management. Clinically, THC has been shown to reduce pain intensity, improve quality of life and attenuate hyperalgesia in various chronic pain conditions, including neuropathic pain and fibromyalgia “

“THC is thought to exert its analgesic effects in part by modulating disrupted pain networks. Specifically, THC interacts with the endocannabinoid system.”

“To conclude, this study corroborates the possible effectiveness of THC in alleviating experimental and spontaneous pain in FMS, a study case of central sensitization, and shows an enhancement of OA responses after THC treatment in FMS patients compared to baseline and placebo.”

“This, in turn, reinforces the potential of OA as a reliable marker of pain modulation in FMS and may pave the way for personalized cannabinoid-based therapies for chronic pain in the future.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00348-x

The Endocannabinoid System: Pharmacological Targets and Therapeutic Potential in CNS Disorders

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“The endocannabinoid system (ECS) influences a wide range of brain functions, including synaptic transmission, neuroplasticity, emotion, and immune regulation within the central nervous system, with CB1 and CB2 receptors mediating various neurophysiological and pathophysiological outcomes. Thus, growing interest in its therapeutic potential has prompted extensive research into how cannabinoid receptors contribute to the pathophysiology of neurological and psychiatric disorders, particularly CB1 and CB2.

This review has integrated findings from studies published between 2015 and 2025, covering conditions, like depression, anxiety, pain, multiple sclerosis, and Parkinson’s disease. We have also examined recent advances in receptor pharmacology and experimental technologies, including cryo-EM, optogenetics, and chemogenetics.

Although ECS-targeted therapeutics hold considerable promise, some key challenges remain in establishing safe and effective dosing protocols and integrating these approaches into clinical frameworks.

This review has provided an updated perspective on the system’s role in brain health and its potential to inform future therapeutic directions. Thus, ECS-targeted strategies may become increasingly important in managing and treating central nervous system disorders.”

https://pubmed.ncbi.nlm.nih.gov/41178765/

https://www.eurekaselect.com/article/151549

Cannabis Use Patterns Among Adults Living With Chronic Pain Before and During the COVID Pandemic: Insights From the COVID-19 Cannabis Health Study

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“Background: This study aims to identify sociodemographic factors associated with cannabis use for chronic pain management before and after COVID-19 was declared a pandemic. Furthermore, it seeks to compare cannabis use patterns in adults with and without chronic pain.

Methods: We analyzed US-based responses from the COVID-19 Cannabis Health Study, a cross-sectional online survey administered via REDCap between March 2020 and March 2022. All respondents were cannabis consumers in the past year. Cannabis use patterns and chronic pain were self-reported via the COVID-19 Cannabis Health Questionnaire. Statistical analysis included Chi-square tests, Fisher’s exact tests, t-tests, and multivariable logistic regression with a two-tailed alpha of 0.05 for significance.

Results: Among 2243 participants, 50.3% consumed cannabis to manage chronic pain. Younger age (< 40 years; aOR: 3.20, 95% CI: 2.59-3.96), Hispanic/Latino ethnicity (aOR: 2.20, 95% CI: 1.56-3.05), and higher income levels (> $100,000 annually; aOR: 1.69, 95% CI: 1.25-2.29) were associated with higher odds of consuming cannabis to manage chronic pain. Participants using cannabis for chronic pain were more likely to use a CBD/THC ratio. The pandemic led to increased dosages and changes in consumption methods: 40.5% increased their cannabis dose, smoking as the primary method declined from 62.2% before the pandemic to 34.5% afterward, while edibles rose from 7.9% to 30.9%, and tinctures from 3.2% to 8.6%. Route changes varied with chronic pain status.

Conclusion: There was a shift from smoking to nonsmoking methods to manage chronic pain. Those who were younger and those of Hispanic/Latino ethnicity had higher odds of using cannabis for chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/41179652/

“In recent years, cannabis has emerged as a promising alternative for pain management, driven by increasing evidence of its analgesic properties.”

https://onlinelibrary.wiley.com/doi/10.1155/prm/9631487

Long-Term Efficacy and Safety of Inhaled Cannabis Therapy for Painful Diabetic Neuropathy: A 5-Year Longitudinal Observational Study

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“Background/Objectives: Diabetic neuropathy (DN) is a prevalent complication of diabetes mellitus, affecting up to 50% of long-term patients and causing significant pain, reduced quality of life, and healthcare burden. Conventional treatments, including anticonvulsants, antidepressants, and opioids, offer limited efficacy and are associated with adverse effects. Emerging evidence suggests that cannabis, acting via the endocannabinoid system, may provide analgesic and neuroprotective benefits. This study evaluates the long-term effects of inhaled cannabis as adjunctive therapy for refractory painful DN. Inhaled cannabis exhibits rapid onset pharmacokinetics (within minutes, lasting 2-4 h) due to pulmonary absorption, targeting CB1 and CB2 receptors to modulate pain and inflammation. 

Methods: In this prospective, observational study, 52 patients with confirmed painful DN, unresponsive to at least three prior analgesics plus non-pharmacological interventions, were recruited from a single clinic. Following a 1-month washout, patients initiated inhaled medical-grade cannabis (20% THC, <1% CBD), titrated individually. Assessments occurred at baseline and annually for 5 years, including the Brief Pain Inventory (BPI) for pain severity and interference; the degree of pain relief; Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) score; HbA1c; and medication usage. Statistical analyses used repeated-measures ANOVA, Kruskal-Wallis tests, Welch’s t-tests, and Pearson’s correlations via Analyze-it for Excel. 

Results: Of 52 patients (mean age 45.3 ± 17.8 years; 71.2% male; diabetes duration 23.3 ± 17.8 years), 50 completed follow-up visits. Significant reductions occurred in BPI pain severity (9.0 ± 0.8 to 2.0 ± 0.7, p < 0.001), interference (7.5 ± 1.7 to 2.2 ± 0.9, p < 0.001), LANSS score (19.4 ± 3.8 to 10.2 ± 6.4, p < 0.001), and HbA1c (9.77% ± 1.50 to 7.79% ± 1.51, p < 0.001). Analgesic use decreased markedly (e.g., morphine equivalents: 66.8 ± 49.2 mg to 4.5 ± 9.6 mg). Cannabis dose correlated positively with pain relief (r = 0.74, p < 0.001) and negatively with narcotic use (r = -0.43, p < 0.001) and pain interference (r = -0.43, p < 0.001). No serious adverse events were reported; mild side effects (e.g., dry mouth or euphoria) occurred in 15.4% of patients. 

Conclusions: Inhaled cannabis showed sustained pain relief, improved glycemic control, and opioid-sparing effects in refractory DN over 5 years, with a favorable safety profile. These findings are associative due to the observational design, and randomized controlled trials (RCTs) are needed to confirm efficacy and determine optimal usage, addressing limitations such as single-center bias and small sample size (n = 52). Future studies incorporating biomarker analysis (e.g., endocannabinoid levels) could elucidate mechanisms and enhance precision in cannabis therapy.”

https://pubmed.ncbi.nlm.nih.gov/41153689/

“Inhaled cannabis add-on therapy mitigated symptoms of diabetic neuropathy over the course of a five-year observation period. Some reduction in glycosylated hemoglobin is observed as well as major reduction in the need for other prescription medications, including opiates and opioids. It is possible to state the following: (1). Inhaled cannabis significantly reduced pain and neuropathic symptoms over 5 years. (2). It decreased opioid use, supporting an opioid-sparing effect. (3). HbA1c improvements suggest a metabolic benefit, though causality is unproven. (4). No serious adverse events occurred, with mild effects in 15.4% of patients. (5). RCTs are needed to confirm efficacy and address accessibility barriers. Integration of objective pain assessment tools, such as salivary biomarker devices, could enhance the precision and reproducibility of cannabis therapy outcomes in DN.”

https://www.mdpi.com/2227-9059/13/10/2406

Cannabigerol Modulates Cannabinoid Receptor Type 2 Expression in the Spinal Dorsal Horn and Attenuates Neuropathic Pain Models

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“Background/Objectives: The expanding focus on novel therapeutic pathways for long-term pain relief has directed interest toward compounds obtained from Cannabis sativa. This study evaluated the antinociceptive potential of cannabigerol-enriched extract (CBG) in models of acute and chronic hypernociception, along with morphological outcomes. 

Methods: Formalin and hot plate tests were used on male Swiss mice to assess acute oral antinociception. To the chronic pain model, 8-week-old male Wistar rats underwent spinal nerve ligation (SNL), and CBG was administered orally by gavage once daily for 14 days. 

Results: CBG reduced nociceptive responses in the formalin test and hot plate tests, mainly at a dose of 30 mg/kg, showing antinociceptive activity. CBG attenuated SNL-induced thermal and mechanical hypersensitivity, accompanied by reduced microglial density and spinal morphological changes. Importantly, cannabinoid receptor type 2 (CB2R) signaling contributed to the antinociceptive effects of orally administered CBG, whereas cannabinoid receptor type 1 (CB1R), Brain-Derived Neurotrophic Factor (BDNF), and Tumor Necrosis Factor (TNF) did not appear to play major roles under our experimental conditions. 

Conclusions: Collectively, these findings support CBG as a promising alternative for chronic pain management.”

https://pubmed.ncbi.nlm.nih.gov/41155621/

“In summary, our study provides robust evidence that CBG exerts potent antinociceptive effects across acute, inflammatory, and neuropathic pain models.

Collectively, these results highlight CBG as a promising candidate for pain management and support further translational studies.”

https://www.mdpi.com/1424-8247/18/10/1508

Medical Marijuana and Opioid Usage: An Analysis of Patient Perceptions in Louisiana

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“Background: The opioid crisis has continued in the United States, resulting in a healthcare crisis. Medical marijuana (MM) offers an alternative to those with addictions or in search of pain and inflammation management without the negative aspects of opioids. 

Methods: A survey of more than 2,000 Louisianians on the frequency and amount of MM use revealed significant relationships between race, age, reason for use, prescription use, and whether they stopped using MM, as well as time in the MM program and the method of ingestion. 

Results: Respondents reported lower levels of pain with MM usage by an average of 3.4 points on a ten-point scale (Z = -35.77, ρ ≤ .001). Those using prescriptions for pain were 1.5 times more likely to use MM less frequently (OR = 1.524, 95% CI: 1.114 – 2.074, ρ ≤ .01). Concordantly, those reporting that they had stopped using prescriptions for pain increased the odds of using more MM by 26.5 percent (OR = .735, 95% CI: .586 – .923, ρ ≤ .001). 

Conclusions: These relationships support the idea that MM substitutes for prescription painkillers.”

https://pubmed.ncbi.nlm.nih.gov/41136335/

https://www.tandfonline.com/doi/full/10.1080/10826084.2025.2575429

Cannabivarin and Tetrahydrocannabivarin Modulate Nociception via Vanilloid Channels and Cannabinoid-Like Receptors in Caenorhabditis elegans

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“Cannabis has attracted growing interest for its therapeutic potential, especially in pain management.

This study explores the antinociceptive effects of two promising non-psychoactive cannabinoids, cannabivarin (CBV) and tetrahydrocannabivarin (THCV), using Caenorhabditis elegans (C. elegans), a nematode model that expresses homologs of mammalian cannabinoid and vanilloid receptors.

Thermotaxis assays were employed to quantify the antinociceptive effects of CBV and THCV in C. elegans. Wild-type animals were exposed to increasing concentrations of each compound to establish dose-response relationships. To investigate potential molecular targets, additional experiments were performed using mutant strains deficient in vanilloid receptor homologs (OCR-2 and OSM-9) and cannabinoid receptor homologs (NPR-19 and NPR-32). Mass spectrometry-based proteomics combined with network biology analyses were used to identify the biological pathways associated with drug response.

Results confirmed that both compounds elicit dose-dependent antinociceptive effects. Mutant analyses support the involvement of vanilloid and cannabinoid signaling pathways in mediating these responses.

These findings highlight the potential of CBV and THCV as non-psychoactive analgesic agents and support further research into their mechanisms of action and translational relevance for mammalian pain management.”

https://pubmed.ncbi.nlm.nih.gov/41135090/

https://cdnsciencepub.com/doi/10.1139/cjpp-2025-0243

Plant-Derived Compounds: A Potential Treasure for Development of Analgesic and Antinociceptive Therapeutics

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“Pain is one of the most pervasive health problems associated with a negative impact on thinking, mood, psychological, and social communication.

The medicinal plants and their derived compounds have recently attracted great interest as potential candidates for defeating pain because of their worldwide safety, availability, and affordability.

This review was constructed to summarize all in vitro and in vivo studies and clinical trials regarding plant-derived compounds’ analgesic and antinociceptive effects. Further, we focus on structural aspects, molecular mechanisms, and pharmacological effects. A literature survey was performed in “PubMed,” “Science Direct,” and “Google Scholar,” using the keywords “Pain, Analgesic activity, Flavonoids, Phenolics, Medicinal plants, Volatile oils, Tannins, Saponins, Alkaloids” to assess the activities of each compound.

The main natural compounds studied were flavonoids, alkaloids, phenolic acids, lignans, anthraquinones, and volatile oils. Different in vitro studies utilized nucleus pulposus cells, VK2/E6E7, End1/E6E7, and LPS-stimulated RAW264.7 cells to assess analgesic effects. The frequently defined animal models of analgesic activity included acetic acid-induced abdominal constrictions, hot-plate test, tail-flick test, formalin test, complete Freund’s adjuvant-induced pain, and hind paw incisional surgery.

For the natural compounds described, the opioids, serotonergic, and cannabinoid receptors appeared to be the most promising targets for pain management. This review suggested a wealthy resource of natural compounds as analgesic and antinociceptive candidates for pharmacists and drug researchers to launch a new drug with promising efficacy and safety.”

https://pubmed.ncbi.nlm.nih.gov/41126401/

https://onlinelibrary.wiley.com/doi/10.1002/ptr.70113