Category Archives: Pain

Use of Cannabidiol and Cannabigerol in the Treatment of Trigeminal Neuralgia and Postherpetic Pain

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“The use of cannabidiol (CBD) as an adjuvant in the treatment of trigeminal neuralgia (TN) and postherpetic neuropathy has shown beneficial effects in patients refractory to conventional treatments.

This case study describes a 57-year-old patient diagnosed with TN in 2019, initially treated with low-power laser therapy and oxcarbazepine. In 2021, she developed vesicular-bullous lesions on the right side of the supraorbital region, accompanied by severe pain confirmed by positive serology for shingles. Following the diagnosis of postherpetic neuropathy, the drug dose was adjusted and combined with laser therapy. However, the pain remained significant and reduced quality of life.

In 2023, treatment was started with CannaMeds CBD Full Spectrum – 3000 mg/30 ml + CannaMeds CBG Isolate 1500 mg/30 ml. After 15 days, the patient appeared pain-free, allowing the laser to be discontinued and the drug dose to be reduced.

CBD is a treatment option for patients who do not respond to conventional treatments.”

https://pubmed.ncbi.nlm.nih.gov/41281696

“It is difficult to find an effective treatment for these conditions, because over time patients no longer respond to treatment. Therefore, the use of CBD and cannabigerol could be an adjuvant treatment option for patients who do not respond to conventional treatment for neuropathic pain.”

https://journals.lww.com/cocd/fulltext/2025/07000/use_of_cannabidiol_and_cannabigerol_in_the.10.aspx

Cannabis Laws and Opioid Use Among Commercially Insured Patients With Cancer Diagnoses

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“Importance: Pain is a prevalent cancer-related symptom, but limited research investigates whether cannabis is an effective analgesic for cancer pain.

Objective: To examine the association of medical and recreational cannabis dispensary availability on prescription opioid dispensing among commercially insured patients with cancer.

Design, setting, and participants: This cross-sectional study used synthetic control to investigate the association of cannabis dispensary openings with pain medication dispensing among patients with cancer. Data were extracted from Optum’s deidentified Clinformatics Data Mart database from January 1, 2007, to December 31, 2020. The study population included patients aged 18 to 64 years with a cancer diagnosis and at least 6 months of continuous enrollment. Associations were estimated by age, race and ethnicity, and sex. Data were analyzed between December 2024 and February 2025.

Exposures: Exposures included indicators for whether a medical or recreational cannabis dispensary was open in each state-quarter.

Main outcomes and measures: The outcome measures for opioids prescriptions were (1) the rate of patients with a prescription per 10 000 patients, (2) the quarterly mean days’ supply per prescription, and (3) the quarterly mean number of prescriptions per patient.

Results: The study included a mean (SD) of 3.05 (0.86) million patients annually across the US (mean [SD] age, 43.7 [9.6] years; mean [SD] 59.0% [0.32%] female). Medical cannabis dispensary openings were associated with significant reductions in all opioid outcomes. The rate of patients with cancer with opioid prescriptions changed by -41.07 per 10 000 (95% CI, -54.78 to -27.36 per 10 000; P < .001), the quarterly mean days’ supply by -2.54 days (95% CI, -3.16 to -1.92 days; P < .001), and the mean number of prescriptions per patient by -0.099 (95% CI, -0.121 to -0.077; P < .001). Recreational dispensary openings were also associated with reductions in opioid outcomes, though estimated treatment effects were smaller. The rate of prescriptions changed by -20.63 per 10 000 (95% CI, -35.35 to -5.91 per 10 000; P = .049), the mean daily supply by -1.09 days supplied per prescription (95% CI, -1.72 to -0.46 days; P = .04), and the mean number of prescriptions per patient by -0.097 (95% CI, -0.134 to -0.060; P = .01).

Conclusions and relevance: This study’s findings indicate cannabis may be a substitute for opioids in the management of cancer-related pain. However, further research directly observing cannabis use is needed to evaluate the efficacy of cannabis as a treatment for cancer-related pain.”

https://pubmed.ncbi.nlm.nih.gov/41105418

“Results of this study suggest that cannabis may serve as a substitute for opioids in managing cancer-related pain, underscoring the potential of cannabis policies to impact opioid use.”

https://jamanetwork.com/journals/jama-health-forum/fullarticle/2840030

A Longitudinal Assessment of Endometriosis Patients Prescribed Cannabis-Based Medicinal Products: A Case Series From the UK Medical Cannabis Registry

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“Background: Although there is growing evidence supporting the use of cannabis-based medicinal products (CBMPs) for the management of chronic pain, there is a paucity of data on their effect on endometriosis-associated chronic pain.

Aims: This study aimed to perform an analysis of pain-specific and general health-related quality of life (HRQoL) outcomes for patients with endometriosis-associated chronic pain treated with CBMPs.

Materials and methods: Primary outcomes included changes in patient-reported outcome measures (PrOMs) from baseline to 1, 3, 6, 12 and 18 months. A repeated measures ANOVA was applied to assess changes in PrOMs at 1 to 18 months from baseline. Secondary outcomes included incidence and frequency of adverse events (AEs).

Results: Sixty-three patients met inclusion criteria. Initiation of CBMPs was associated with improvements in all pain-specific PrOMs from baseline to 18 months (p < 0.050). EQ-5D-5L index value showed improvements between baseline and all months (p < 0.050). Anxiety and sleep quality PrOMs showed improvements from baseline to 18 months (p < 0.050). Minimal clinically significant differences (11%-37%), moderately important improvements (5%-22%) and substantial improvements (0%-11%) were observed in the Brief Pain Inventory (BPI) and pain severity visual analogue scale. Sixty-two adverse events were reported by 16 (25.40%) participants.

Conclusions: This study observed an association between CBMP treatment and improvements in pain and HRQoL in patients with endometriosis. Causality cannot be inferred due to the nature of this observational study; however, these findings provide complementary evidence for the development of randomised controlled trials to assess the efficacy of CBMPs for endometriosis-associated chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/41305963

“Cannabis-based medicinal products (CBMPs) that contain phytocannabinoids, such as (−)-trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), have been identified with potential to manage endometriosis-related pain.”

“Overall, these results provide a signal towards improvement in short-term pain severity and interference for endometriosis patients after the initiation of CMBP treatment, although there was diversity at different pain intervals.”

https://obgyn.onlinelibrary.wiley.com/doi/10.1111/ajo.70078

Advances in the Quest for Safe and Effective Drugs That Target the Cannabinoid Receptor Type 1 (CB1)

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“Pain management costs the world billions of dollars each year, and there are limited nonopioid options to treat people suffering from chronic pain. Opioids are excellent analgesics but are liable to abuse and fatal overdoses. This Microperspective summarizes challenges and opportunities pertaining to creating nonopioid drugs that could be used to treat chronic pain, substance abuse, fatty liver, or obesity by targeting the cannabinoid receptor type 1 (CB1).”

https://pubmed.ncbi.nlm.nih.gov/41257001

https://pubs.acs.org/doi/10.1021/acsmedchemlett.5c00402

Minor Cannabinoids CBD, CBG, CBN and CBC differentially modulate sensory neuron activation

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“The use of minor cannabinoids has been advanced, in part, by the idea of providing relief from pain and inflammation without the burden of unwanted psychogenic effects associated with Δ 9 THC. In this regard, investigators have focused on the effects of minor cannabinoid activation / desensitization of peripheral sensory neurons on nociceptive signaling and/or peripheral inflammation.

With a focus on peripheral nociception, four common minor cannabinoids: cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN) and cannabichromene (CBC) were studied in primary cultures of mouse Dorsal Root Ganglion (DRG) neurons.

We queried if calcium responses induced by the four cannabinoids differed in potency of activation, neuronal size preference, and dose-response relationships. Additionally, we determined the dependence of CBD and CBN on key channel-receptors that are known to mediate pain and/or antinociception.

Individually, CBD, CBG and CBC directed greater response magnitudes when compared to CBN. All four minor cannabinoids activated overlapping but distinct size populations of sensory neurons. CBD and CBG activated the widest range of DRG neuron sizes (smaller-larger) overlapping with smaller capsaicin-sensitive neurons. In contrast, CBN and CBC activated predominantly larger sensory neurons. CBD diverged from other minor cannabinoids in directing a linear dose-response profile whereas CBG and CBC directed sigmoidal dose-response profiles and CBN activated DRG neurons with an inverted U-shaped dose-response relationship. CBD-induced activation of DRG neurons was dependent on co-expression of the nociceptive channel TRPV1 plus cannabinoid receptor 1 (CB 1 R), whereas CBN-induced activation was independent of TRPV1.

Overall, we observed that minor cannabinoids CBD, CBG, CBN and CBC differed in their activation of DRG neurons and directed unique activation properties across a diverse population of sensory neurons. Such differences underly the hypothesis that a combination (entourage) of complimentary minor cannabinoids can direct synergistic antinociceptive activity.”

https://pubmed.ncbi.nlm.nih.gov/41256665

https://www.biorxiv.org/content/10.1101/2025.10.02.680148v1

Sex differences in the capacity of minor phytocannabinoids to attenuate nociceptive insults in HIV-1 Tat-expressing mice

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“Objecives: Approximately 80 % of people living with HIV (PLWH) develop chronic pain and preclinical studies support the involvement of the HIV-1 regulatory protein, trans-activator of transcription (Tat). Phytocannabinoids may attenuate pain in PLWH; however, these data are controversial, and the biological mechanisms are difficult to untangle from psychosocial factors in people.

Methods: We have examined the therapeutic capacity of minor phytocannabinoids to attenuate Tat-promoted visceral hyperalgesia (acetic acid writhing assay) and reflexive nociception (warm water tail flick assay) in transgenic mice. We hypothesized that conditional expression of Tat1-86 in male and female mice [Tat(+) mice] would amplify pain responses compared to controls [Tat(-) mice], and that phytocannabinoids could ameliorate these effects.

Results: Irrespective of sex, Tat(+) mice demonstrated greater visceral pain responses than did Tat(-) controls. The phytocannabinoids, cannabigerolic acid (CBGA), cannabidiol (CBD), and cannabinol (CBN), attenuated Tat-induced visceral pain in both males and females. However, the effectiveness of these cannabinoids varied by sex with CBN being more efficacious in males, while cannabigerol (CBG) alleviated visceral pain only in Tat(+) females. Cannabidiolic acid (CBDA) and cannabidivarin (CBDV) were not effective in either sex. CBGA and CBG were also efficacious in the tail flick test among Tat(-) males and females, but demonstrated only small, sex-dependent effects to reverse Tat-induced nociception. CBD and CBN exerted little-to-no efficacy in this test.

Conclusions: These data suggest that phytocannabinoids exert analgesia for HIV-related pain, potentially aiding in the development of personalized pain management strategies.”

https://pubmed.ncbi.nlm.nih.gov/41221301/

“Overall, PLWH are more vulnerable to the development of chronic pain, resulting in physical disability and a reduced quality of life. The current pharmacological treatments for managing HIV-related pain lack efficacy and are associated with the risk of substance abuse. The medicinal use of non-psychoactive cannabis constituents for pain management might greatly benefit this population which is at a greater risk for opioid addiction and substance abuse.”

https://www.degruyterbrill.com/document/doi/10.1515/nipt-2024-0025/html

Dual Role of the Spinal Endocannabinoid System in Response to Noxious Stimuli: Antinociceptive Pathways and Neuropathic Pain Mechanisms

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“Neuropathic pain is a clinically challenging syndrome that is largely refractory to conventional therapies. It arises from lesions or diseases affecting somatosensory pathways, which trigger extensive neuroplastic and neuroimmune remodeling. Unlike nociceptive pain, which establishes a protective response to tissue injury, neuropathic pain arises from maladaptive signaling within the nervous system.

In this context, the spinal endocannabinoid system (ECS) has emerged as a pivotal modulator of nociceptive processing. However, its precise role in neuropathic pain remains debated due to its dual effects.

Numerous studies report antinociceptive and neuroprotective effects; however, emerging data indicate that under specific pathological conditions, ECS activation may paradoxically facilitate pain transmission.

This review examines spinal ECS context dependence, uncovering its bidirectional antinociceptive and pronociceptive effects in neuropathic pain. By integrating current evidence on cellular, molecular, and pathophysiological mechanisms, we delineate the factors that determine whether ECS modulation inhibits or promotes pain. A comprehensive understanding of these mechanisms is essential for optimizing cannabinoid-based strategies to maximize therapeutic benefits while minimizing adverse outcomes.

Finally, we highlight the spinal cord’s centrality as the principal site for the initiation and maintenance of neuropathic pain and advocate for rigorous translational research to clarify the therapeutic potential of spinal ECS-targeted interventions.”

https://pubmed.ncbi.nlm.nih.gov/41226728/

“From a therapeutic perspective, ECS duality represents both a challenge and an opportunity. Pharmacological manipulation of the ECS, through selective CB1R and CB2R agonists, FAAH and MAGL enzyme inhibitors, allosteric modulators, or combined strategies including glial modulators, constitutes a promising avenue for developing innovative treatments targeting neuropathic pain. However, the success of these interventions critically depends on a precise understanding of the pathophysiological context of eCB pathways and the evolutionary stage of the pathology.”

https://www.mdpi.com/1422-0067/26/21/10692

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