Tag Archives: chronic pain

Evaluating the impact of cannabinoid extracts on chronic pain and quality of life in endometriosis patients – a pilot study

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Women with endometriosis and chronic pelvic pain experienced significant improvements after adding a balanced oral THC cannabis extract to their existing treatment. In this prospective pilot study, 27 women completed three months of treatment, with benefits appearing within the first month and continuing through the study period.

Pain intensity fell significantly, along with the number of pain days and the need for conventional pain medicines. Use of both NSAIDs and opioid analgesics decreased, while fatigue, anxiety, central sensitization and pain-related disability also improved.

Quality of life improved across every measured EHP-30 domain, including pain, emotional well-being, work impairment, self-image and sexual relationships. The authors concluded that balanced THC cannabinoid medicines appear to be a potentially effective adjunct treatment for chronic pelvic pain and related symptoms in women with endometriosis.

“Endometriosis is a chronic gynecological disorder characterized by persistent pain and impaired quality of life, with limited effective treatment options. Emerging evidence indicates that cannabinoids may provide analgesic and symptom-relieving effects in chronic pain conditions.

This prospective single-center cohort study investigated the effects of standardized oral cannabis extracts (cannabinoid-based medicinal products, CBMPs) on pain and quality of life in women with endometriosis.

Thirty premenopausal women aged 18-45 years with confirmed endometriosis and chronic pelvic pain were enrolled; 27 completed the 3-month treatment period. Participants received oral CBMPs containing a balanced THC: CBD ratio. Pain intensity, frequency of pain episodes, analgesic use, fatigue, anxiety, central sensitization, disability, and quality of life were assessed using validated questionnaires (VAS, EHP-30, PDI, CFS, GAD-7, CSI).

Significant improvements were observed after one month of treatment, with continued benefit over three months. Pain intensity decreased markedly (p = 0.0004), accompanied by reductions in the number of pain days and analgesic use, including both NSAIDs (e.g., ibuprofen, diclofenac) and opioid analgesics (e.g., tramadol, tilidin, oxycodone) (p < 0.001). Fatigue (p = 0.0013), anxiety (p < 0.0001), central sensitization (p < 0.0001), disability (p < 0.0001), and overall quality of life (EHP-30) improved significantly.

Treatment was well tolerated; side effects were predominantly mild (severity score 1 on a 0-3 scale) and transient, occurring mainly during the titration phase and declining thereafter. Although limited by its single-center design, lack of placebo control, and short follow-up, this study provides preliminary evidence that oral CBMPs may represent a safe and effective adjunct therapy for managing pain and related symptoms in women with endometriosis. Larger randomized controlled trials are warranted to confirm these findings and establish optimal dosing strategies.”

https://pubmed.ncbi.nlm.nih.gov/42771648

“In conclusion, oral CBMPs with balanced THC: CBD ratios seem to be a safe and potentially effective adjunct therapy for chronic pelvic pain and related symptoms in women with endometriosis. By targeting both nociceptive and neuropsychological aspects of the condition, CBMPs can supplement existing pharmacological and lifestyle strategies, providing a more comprehensive approach to symptom management. These findings establish a basis for future controlled studies to refine dosing, investigate mechanisms, and assess long-term outcomes in this complex patient group.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356768

The anterior cingulate cortex mediates cisplatin-induced mechanical allodynia and represents a target for cannabigerol antinociception

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Chemotherapy-induced peripheral neuropathy can cause persistent burning, tingling, numbness and pain long after cancer treatment ends. A new 2026 study investigated how the brain contributes to this neuropathic pain and whether cannabigerol (CBG), a non-euphoric cannabinoid, can reduce it.

Using a mouse model of cisplatin-induced neuropathy, researchers found that CBG significantly reversed mechanical allodynia. They also identified the anterior cingulate cortex, a brain region involved in processing pain, as an important part of the neuropathic pain response. Directly administering CBG into this region produced antinociceptive effects.

The findings suggest that CBG can act within central pain-processing circuits and identify the anterior cingulate cortex as a potential target for cannabinoid-based treatment of chemotherapy-induced neuropathic pain. The researchers say the results highlight the potential for “centrally targeted, non-euphoriant cannabinoid-based therapies.”

“Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and debilitating consequence of cancer treatment with limited effective therapeutic options. While peripheral nerve injury is a key driver, emerging evidence suggests that maladaptive plasticity within central pain circuits, including the anterior cingulate cortex (ACC), contributes to the maintenance of neuropathic pain.

Here, we tested the hypothesis that the ACC is a critical substrate for cisplatin-induced mechanical allodynia and a target for cannabigerol (CBG)-mediated antinociception.

Adult male C57BL/6 mice received cisplatin (5 mg/kg, i.p., once weekly for four weeks) to induce CIPN. Mechanical allodynia was assessed using electronic von Frey testing.

Systemic administration of CBG (20 mg/kg, i.p.) significantly reversed mechanical allodynia in CIPN mice without affecting baseline thresholds in non-neuropathic animals, indicating a state-dependent effect. Chemogenetic inhibition of ACC neurons using hM4Di DREADDs similarly attenuated mechanical allodynia, identifying the ACC as a functionally relevant component of the CIPN pain state. To determine whether CBG acts within this circuit, bilateral intra-ACC microinjections of CBG (20 nM and 20 µM) were performed, both of which produced transient antinociceptive effects.

These findings demonstrate that the ACC contributes to the maintenance of mechanical allodynia in CIPN and establish this region as a site of action for CBG.

Together, our results support a model in which the ACC represents a convergent cortical mechanism underlying pathological pain and highlight the potential for centrally targeted, non-euphoriant cannabinoid-based therapies.”

https://pubmed.ncbi.nlm.nih.gov/42744343/

“In conclusion, this study identifies the ACC as a hub in the maintenance of mechanical allodynia in a model of CIPN. By demonstrating that chemogenetic inhibition of the ACC reverses hypersensitivity and that both systemic and local administration of CBG produce antinociceptive effects, our findings link circuit-level dysfunction to a pharmacologically targetable mechanism within this region. These results support a model in which increased or dysregulated ACC neuronal activity may represent a convergent feature of pathological pain states. Importantly, these findings demonstrate that CBG can act within the ACC to modulate mechanical allodynia. Future studies identifying the receptor targets and circuit mechanisms through which CBG acts within the ACC will be essential for refining therapeutic strategies for chronic pain.”

https://journals.sagepub.com/doi/10.1177/17448069261491110

The Endocannabinoid System in Endometriosis-Associated Pain: Mechanisms, Molecular Targets, and Therapeutic Implications

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A new 2026 review published in Reproductive Sciences examines the endocannabinoid system (ECS) as a therapeutic target for endometriosis-associated pain, a condition that can cause severe pelvic pain, painful menstruation, painful intercourse, and other chronic symptoms. The authors highlight the ECS because of its established roles in regulating pain, inflammation, and immune activity.

The review found that cannabinoids may influence three major mechanisms involved in endometriosis-associated pain: inflammation, pain signaling and sensitization, and the growth of endometriotic lesions. Cannabinoids interact with both cannabinoid and non-cannabinoid receptors found in endometriotic tissue, while also reducing inflammatory signaling from immune cells such as mast cells and macrophages.

The researchers conclude that the endocannabinoid system is a promising therapeutic target for endometriosis-associated pain, with cannabinoid therapies showing potential to regulate nociception, inflammation, and lesion proliferation. They call for clinical trials to further evaluate cannabinoid-based treatments for people living with endometriosis.

“Endometriosis is a chronic gynecological disorder affecting approximately 10% of reproductive-age women, characterized by the ectopic growth of endometrial tissue and severe pain, including dysmenorrhea, chronic pelvic pain, dyspareunia, dysuria, and dyschezia. Current treatments are limited in efficacy and associated with significant side effects, underscoring the urgent need for novel therapeutic strategies.

The endocannabinoid system (ECS) has emerged as a promising therapeutic target, given its well-established roles in pain modulation, inflammation, and immune regulation. Epidemiological evidence demonstrates that women with endometriosis increasingly use cannabis for symptom self-management, yet the underlying mechanisms remain poorly characterized.

This review integrates preclinical and human evidence to comprehensively evaluate the mechanistic basis of cannabinoid efficacy in endometriosis-associated pain. Evidence from in vitro studies and animal models indicates that cannabinoids target three main mechanisms of endometriosis-associated pain, including inflammation, nociceptive signaling, and lesion proliferation.

Cannabinoids suppress pain signaling and sensitization by interacting with cannabinoid and non-cannabinoid receptors expressed in endometriotic lesions. Cannabinoids attenuate endometriosis-induced inflammation by inhibiting proinflammatory cytokine signaling and reducing the release of inflammatory mediators by mast cells and peritoneal macrophages. Cannabinoids also exert antiproliferative effects in endometriosis models, thereby suppressing the growth of endometriotic lesions.

In conclusion, the ECS is a promising therapeutic target for endometriosis-associated pain, as it regulates nociception, inflammation, and proliferation. These promising findings highlight the potential therapeutic benefits of cannabinoids for endometriosis-associated pain, warranting the need for clinical trials to evaluate the safety and effectiveness of cannabinoid therapies in endometriosis.”

https://pubmed.ncbi.nlm.nih.gov/42745018

https://link.springer.com/article/10.1007/s43032-026-02201-9

Ten-year outcomes of medical cannabis for chronic low back pain: opioid reduction, pain relief, and functional improvement in 1,000 patients

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A 2026 study published in the European Spine Journal followed 1,000 patients with chronic low back pain who had been using opioids for at least a year before beginning medical cannabis treatment. Researchers tracked changes in opioid use, pain, disability, and other medications over as long as 10 years.

Among the 638 patients who completed the full 10-year follow-up, average opioid use fell by 89.8%, while pain scores dropped by 84.2%. More than 91% of patients achieved at least a 50% reduction in opioid use, and 96.6% achieved at least a 30% reduction in pain. Disability scores also improved substantially over the study period.

The reductions were not limited to opioids. Use of benzodiazepines, gabapentinoids, antidepressants, and other pain medications also declined. With a decade of follow-up, this study provides unusually long-term evidence that medical cannabis may play an important role in reducing pain, improving function, and decreasing dependence on multiple medications in people living with chronic low back pain.

“Purpose: To evaluate 10-year outcomes of medical cannabis therapy on opioid use, pain intensity, functional disability, concomitant medication use, and adverse events in cannabis-naïve chronic low back pain (CLBP) patients, with particular attention to clinically meaningful outcomes defined by established minimal clinically important difference (MCID) thresholds.

Methods: Single-center longitudinal observational study of 1,000 consecutive cannabis-naïve CLBP patients from a registry database (2015-2024), reported following STROBE guidelines.

Primary outcome: morphine milligram equivalents (MMEQ).

Secondary outcomes: Numeric Rating Scale (NRS) for pain intensity, Oswestry Disability Index (ODI) for functional disability, cannabis dosing patterns, adverse events, and concomitant medication use. Pre-specified MCID thresholds: ≥50% MMEQ reduction, ≥ 30% NRS reduction, ≥ 10-point ODI improvement. Statistical analyses included paired t-tests for completers and linear mixed-effects models for sensitivity analyses.

Results: Of 1,000 enrolled patients, 638 (63.8%) completed 10-year follow-up. Among completers, MMEQ decreased from 62.8 ± 35.7 to 6.4 ± 7.1 mg/day (- 89.8%, p < 0.001); NRS from 8.71 ± 1.23 to 1.37 ± 1.71 (- 84.2%, p < 0.001); ODI from 52.9 ± 11.9% to 36.8 ± 14.9% (16.1-point reduction, – 30.4%, p < 0.001). MCID responders: 91.2% for MMEQ, 96.6% for NRS, 62.1% for ODI. Substantial polypharmacy reductions occurred: tramadol/tapentadol – 84.0% points (pp), benzodiazepines – 73.5 pp, SSRIs – 71.9 pp, gabapentinoids – 30.7 pp. True tolerability adverse events occurred in 11.4% of visits; serious psychiatric events in 0.02%.

Conclusions: In this uncontrolled observational study, medical cannabis therapy was associated with reductions in opioid use, pain intensity, and functional disability over 10 years, accompanied by polypharmacy reduction and acceptable tolerability. Effect sizes substantially exceeded RCT benchmarks (e.g., – 0.6 NRS difference vs. placebo in a recent phase 3 trial), suggesting observational biases contribute to these findings. These hypothesis-generating data warrant validation in randomized controlled trials.”

https://pubmed.ncbi.nlm.nih.gov/42734834

“In this 10-year single-arm observational study, medical cannabis therapy was associated with reductions in opioid use (− 89.8%), pain intensity (− 84.2%), and functional disability (− 30.4%), with high proportions of patients achieving pre-specified MCID thresholds. Substantial polypharmacy reductions and acceptable tolerability were observed.”

https://link.springer.com/article/10.1007/s00586-026-10290-y

UK Medical Cannabis Registry: An Updated Analysis of Inflammatory Arthritis

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A new analysis from the UK Medical Cannabis Registry reports sustained improvements in pain, sleep, and health-related quality of life among patients with inflammatory arthritis who were prescribed cannabis-based medicinal products.

The study followed 192 patients for up to 24 months. Improvements were reported across multiple pain measures at every follow-up point, including pain severity, pain interference, and overall pain scores. Sleep quality and general quality of life also improved compared with baseline.

Notably, many patients were prescribed THC-containing products, including dried cannabis flower and oils. The findings add long-term real-world evidence that prescribed cannabis medicines may help some people living with inflammatory arthritis.

“Aim: Cannabis-based medicinal products (CBMPs) are an emerging therapeutic option for pain in inflammatory arthritis, yet clinical evidence remains limited. This study aimed to evaluate changes in pain-specific and general health-related outcomes in patients with inflammatory arthritis treated with CBMPs and to characterize the safety profile by examining the incidence and nature of adverse events.

Methods: Patients treated with CBMPs for inflammatory arthritis-associated pain for ⩾24 months were identified from the UK Medical Cannabis Registry. Primary outcomes included changes in patient-reported measures: Brief Pain Inventory (BPI), Pain Visual Analogue Scale (Pain VAS), Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2), EuroQol 5-dimension 5-level (EQ-5D-5L), Generalized Anxiety Disorder-7 (GAD-7), and Single-Item Sleep Quality Scale (SQS) at 1, 3, 6, 12, 18, and 24 months vs baseline. Adverse events were recorded and analysed. Statistical significance was set at P < .050.

Results: A total of 192 patients met inclusion criteria. The CBMP initiation was associated with improvements in BPI Interference, BPI Severity, Pain VAS, SF-MPQ-2, SQS, and EQ-5D-5L index values at all follow-up time points (P < .010) and in GAD-7 scores up to 3 months (P < .001). Twenty-seven patients (14.06%) reported 296 adverse events: 126 (42.57%) mild, 132 (44.59%) moderate, and 38 (12.84%) severe. No life-threatening events occurred.

Conclusion: The CBMP therapy was associated with reductions in pain and improvements in health-related quality of life among individuals with inflammatory arthritis. Although causality cannot be inferred from this observational design, these findings support the need for randomized controlled trials to determine the efficacy of CBMPs for inflammatory arthritis-related pain.”

https://pubmed.ncbi.nlm.nih.gov/42724108

“Overall, results of this study demonstrate reductions in pain severity and improvements in HRQoL for patients receiving CBMP treatment for chronic pain linked to inflammatory arthritis over a period of 24 months of follow-up. The CBMPs were generally well-tolerated, although the risk of AE and individual responses should be considered before commencing CBMP treatment.”

https://journals.sagepub.com/doi/10.1177/11795441261480709

Δ 9 -Tetrahydrocannabinol alleviates hyperalgesia in a humanized mouse model of sickle cell disease

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Δ9-THC reduced pain hypersensitivity in a humanized mouse model of sickle cell disease. In mice expressing more than 99% human sickle hemoglobin, acute THC treatment dose-dependently reduced both mechanical and cold hypersensitivity and also produced substantial antinociceptive effects in a tail-flick pain test.

At 1 mg/kg, THC reduced pain sensitivity without altering anxiety-like behavior or long-term memory. With repeated treatment, THC continued to provide sustained relief from mechanical hypersensitivity, although tolerance developed to its effects on cold hypersensitivity.

The researchers concluded that THC may represent a potential option for managing chronic pain associated with sickle cell disease. These findings are especially notable because sickle cell pain is often severe and difficult to control, while current treatment frequently depends on opioid analgesics.

“People with sickle cell disease (SCD) often experience chronic pain as well as unpredictable episodes of acute pain, which significantly affect their quality of life and life expectancy. Current treatment strategies for SCD-associated pain primarily rely on opioid analgesics, which have limited efficacy and cause serious adverse effects.

Cannabis has emerged as a potential alternative, yet its efficacy remains uncertain. In this study, we investigated the antinociceptive effects of Δ9-tetrahydrocannabinol (THC), cannabis’ intoxicating constituent, in male HbSS mice, which express >99% human sickle hemoglobin, and male HbAA mice, which express normal human hemoglobin A, as a control.

Acute THC administration (0.1-3 mg-kg-1, intraperitoneal, i.p.) dose-dependently reduced mechanical and cold hypersensitivity in HbSS, but not HbAA mice. In the tail-flick assay, THC (1 and 3 mg-kg-1, i.p.) produced substantial antinociceptive effects in HbSS mice. By contrast, THC (1 mg-kg-1, i.p.) did not alter anxiety-like behavior (elevated plus maze) or long-term memory (24-h novel object recognition). Subchronic THC treatment (1 and 3 mg-kg-1, i.p.) provided sustained relief of mechanical hypersensitivity but led to tolerance in cold hypersensitivity in HbSS mice.

Together, the findings identify THC as a possible therapeutic option for the management of chronic pain in SCD. Further research is warranted to elucidate its mechanism of action and possible interaction with other cannabis constituents. 

Significance Statement The study explores THC’s efficacy in alleviating pain in sickle cell disease (SCD) using a humanized mouse model. Findings indicate that acute THC administration reduces mechanical and cold hypersensitivity in SCD mice without impacting emotional and cognitive dysfunction. Subchronic THC treatment offers sustained relief of mechanical hypersensitivity but leads to cold hypersensitivity tolerance. These results offer insights into THC’s potential as an alternative pain management option in SCD, highlighting both its benefits and limitations.”

https://pubmed.ncbi.nlm.nih.gov/38955494/

“The results indicate that acute THC administration alleviates mechanical and cold hypersensitivity in HbSS mice in a dose-dependent manner without affecting emotional and cognitive dysfunction also present in these mice.”

https://www.sciencedirect.com/science/article/abs/pii/S0022356524178147

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Disease-modifying effects of natural Δ9-tetrahydrocannabinol in endometriosis-associated pain.

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In a mouse model of endometriosis, daily treatment with Δ9-THC reduced abdominal mechanical hypersensitivity and the unpleasantness associated with pain. THC also restored cognitive function in animals that had developed substantial memory deficits associated with endometriosis.

The effects went beyond pain relief. THC altered uterine innervation and, most notably, inhibited the development of endometrial cysts, suggesting a potential disease-modifying effect rather than simply masking symptoms.

These findings are important because endometriosis is a chronic condition in which pain, abnormal tissue growth, and neurological effects can all contribute to disease burden. The researchers concluded that the results support clinical investigation of THC as a potential treatment for women with endometriosis.

“Endometriosis is a chronic painful disease highly prevalent in women that is defined by growth of endometrial tissue outside the uterine cavity and lacks adequate treatment.

Medical use of cannabis derivatives is a current hot topic and it is unknown whether phytocannabinoids may modify endometriosis symptoms and development.

Here we evaluate the effects of repeated exposure to Δ9-tetrahydrocannabinol (THC) in a mouse model of surgically-induced endometriosis.

In this model, female mice develop mechanical hypersensitivity in the caudal abdomen, mild anxiety-like behavior and substantial memory deficits associated with the presence of extrauterine endometrial cysts.

Interestingly, daily treatments with THC (2 mg/kg) alleviate mechanical hypersensitivity and pain unpleasantness, modify uterine innervation and restore cognitive function without altering the anxiogenic phenotype. Strikingly, THC also inhibits the development of endometrial cysts.

These data highlight the interest of scheduled clinical trials designed to investigate possible benefits of THC for women with endometriosis.”

https://www.ncbi.nlm.nih.gov/pubmed/31931958

“These experiments suggest that THC may be a useful treatment for patients with endometriosis.”

https://elifesciences.org/articles/50356

Need this THC study explained? thcXplained.com

Cannabis as an adjunct to or substitute for opiates in the treatment of chronic pain.

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Abstract

“There is a growing body of evidence to support the use of medical cannabis as an adjunct to or substitute for prescription opiates in the treatment of chronic pain. When used in conjunction with opiates, cannabinoids lead to a greater cumulative relief of pain, resulting in a reduction in the use of opiates (and associated side-effects) by patients in a clinical setting. Additionally, cannabinoids can prevent the development of tolerance to and withdrawal from opiates, and can even rekindle opiate analgesia after a prior dosage has become ineffective. Novel research suggests that cannabis may be useful in the treatment of problematic substance use. These findings suggest that increasing safe access to medical cannabis may reduce the personal and social harms associated with addiction, particularly in relation to the growing problematic use of pharmaceutical opiates. Despite a lack of regulatory oversight by federal governments in North America, community-based medical cannabis dispensaries have proven successful at supplying patients with a safe source of cannabis within an environment conducive to healing, and may be reducing the problematic use of pharmaceutical opiates and other potentially harmful substances in their communities.”

http://www.ncbi.nlm.nih.gov/pubmed/22880540

Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors

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TRUTH: “Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors… nonpsychoactive cannabinoids can potentiate glycine receptors (GlyRs), an important target for nociceptive regulation at the spinal level… We report that systemic and intrathecal administration of cannabidiol (CBD), a major nonpsychoactive component of marijuana, and its modified derivatives significantly suppress chronic inflammatory and neuropathic pain without causing apparent analgesic tolerance… These cannabinoids may represent a novel class of therapeutic agents for the treatment of chronic pain and other diseases involving GlyR dysfunction.”

http://www.ncbi.nlm.nih.gov/pubmed/22585736