Category Archives: Pain

Medical Cannabis and Opioid Receipt Among Adults With Chronic Pain

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“Importance: Medical cannabis is increasingly considered a substitute for prescription opioid medications for chronic pain, driven by the urgent need for opioid alternatives to combat the ongoing epidemic.

Objective: To determine the association between participation in the New York State (NYS) medical cannabis program and prescription opioid receipt among adults with chronic pain.

Design, setting, and participants: This cohort study used data from the NYS Prescription Monitoring Program (PMP) from September 2018 through July 2023. Adults prescribed opioids for chronic pain who were newly certified for medical cannabis use in NYS were recruited from a large academic medical center and nearby medical cannabis dispensaries in the Bronx, New York. Monthly dispensation of medical cannabis to study participants was monitored for 18 months. Data analyses were performed from February 3, 2025, to July 15, 2025.

Exposure: Portion of days covered each month by pharmacist report of dispensed medical cannabis.

Main outcomes and measures: Prescription opioid receipt, defined as NYS PMP-reported prescription monthly opioid dispensation (mean daily dose in morphine milliequivalents [MME]), was assessed with marginal structural models adjusted for time-invariant and time-varying confounders, including self-reported unregulated cannabis use. Nonprescribed opioid use was also assessed during the study period.

Results: Among 204 participants, the mean (SD) age at baseline was 56.8 (12.8) years, and 113 (55.4%) were female. At baseline, participants’ mean (SD) pain severity score was 6.6 (1.8) out of 10, and mean (SD) pain interference score was 6.8 (1.9) out of 10. Baseline mean (SD) daily MME was 73.3 (133.0). During the 18-month follow-up period, participants’ mean (SD) daily MME decreased to 57.4 (127.8). This reduction in mean daily MME was associated with the monthly portion of days covered with medical cannabis; compared with no medical cannabis dispensed, participants dispensed a 30-day supply of medical cannabis were exposed to 3.53 fewer MME per day (β = -3.53; 95% CI, -6.68 to -0.04; P = .03).

Conclusions and relevance: In this cohort study, participation in NYS’s medical cannabis program was associated with reduced prescription opioid receipt during 18 months of prospective follow-up, accounting for unregulated cannabis use.”

https://pubmed.ncbi.nlm.nih.gov/41359313

“These findings suggest that participation in a pharmacist-directed medical cannabis program may help reduce prescription opioid receipt among adults with chronic pain.”

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2842414

Full-spectrum cannabis extracts for women with chronic pain syndromes: a real-life retrospective report of multi-symptomatic benefits after treatment with individually tailored dosage schemes

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“Chronic pain syndromes (CPS) are debilitating conditions for which cannabis extracts and cannabinoids have shown promise as effective treatments. However, accessibility to these treatments is limited due to the absence of suitable formulations and standardized dosage guidelines. This is particularly critical for women, who present sex-specific differences in pain burden, pain perception, and pain-related cannabinoid pharmacology.

We conducted a retrospective open-label cross-sectional study on 29 female CPS patients who received full-spectrum cannabis extracts (FCEs) with standardized compositions produced by two patient-led civil societies. An individually tailored dosage protocol was used, with dosage schemes adjusted based on individualized clinical assessments of initial conditions and treatment responses. Patients received either CBD-dominant extracts, THC-dominant extracts, or a combination of both. To evaluate the results, we conducted a comprehensive online patient-reported outcome survey covering core CPS symptoms, comorbidities, personal burden, and quality of life-including open-ended questions to capture the practical and subjective impacts of CPS and FCEs treatment on patients’ lives.

Despite most patients already using medications for pain and mood disorders, all reported some level of pain relief, and most reported improvements in cognitive function, motor abilities, professional activities, irritability, anxiety, melancholy, fatigue, and sleep quality. Qualitative content analysis of open-ended responses revealed that FCEs had relevant positive effects on practical and subjective domains, as well as personal relationships. No patients had to discontinue extract use due to adverse effects, and most reduced or ceased their use of analgesic and psychiatric medications. The optimal dosage regime, including CBD-to-THC proportions, was established through a response-based protocol, varied considerably, and showed no clear link to specific pain types.

These real-life results strongly suggest that a broad scope of benefits can be achieved by using flexible dosing schemes of cannabis extracts in managing diverse CPS conditions in female patients. Therefore, this study highlights the significance of tailoring treatment plans to individual CPS cases. Moreover, it demonstrates the feasibility of utilizing quality-controlled cannabis extracts produced by civil societies as either adjuncts or primary pharmacotherapeutic options in CPS management.”

https://pubmed.ncbi.nlm.nih.gov/41357862

“Studies with isolated cannabinoids revealed relief of chronic pain, inflammation, depression, and other CPS-associated comorbidities in animal models.

Isolated cannabidiol (CBD) has shown analgesic and anti-inflammatory effects in humans, while tetrahydrocannabinol (THC) seems to produce pain relief by modulating neuronal activity in pain-associated areas of the central nervous system, such as the periaqueductal area, and the descending supraspinal inhibitory pathways, often involved in cases of CPS. Accordingly, THC isolated oil promoted significant relief of chronic neuropathic pain in comparison to placebo.”

“Our study provides compelling real-world evidence of the broad, integrative benefits of full-spectrum cannabis extracts (FCEs) for women with chronic pain syndromes (CPS).”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1538518/full


Medicinal use of non-prescribed cannabis: a cross-sectional survey on patterns of use, motives for use, and treatment access in the Netherlands

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“Background: Despite the Netherlands having one of the world’s oldest medical cannabis programs, the majority of people who use cannabis for medicinal purposes continue to rely on non-prescribed sources. This study investigates patterns of use, motives for use, perceived effectiveness, and barriers to accessing prescribed cannabis among individuals self-medicating with non-prescribed cannabis.

Methods: A cross-sectional online survey was conducted between January and April 2023, using convenience sampling primarily via social media. Participants (N = 1059) were adults (18 years or older) residing in the Netherlands who self-reported current use of non-prescribed cannabis-based products to manage physical or mental health symptoms.

Results: Cannabis was used to manage a wide range of conditions, most commonly chronic pain, sleep disorders, depression, and ADHD/ADD, with three out of four participants reporting use for multiple conditions. Most participants obtained cannabis from coffeeshops, although one in four also reported home cultivation as a source. Participants typically smoked cannabis with tobacco, reported (near-)daily use for therapeutic purposes, and indicated a monthly expenditure of €100. The majority was not aware of the THC and CBD content of their products. Perceived effectiveness was rated as high, and more than half of those with a history of prescription medication use reported substituting cannabis for these medications. Only a minority of participants had ever used, or were currently using, prescribed cannabis. Commonly cited barriers included perceived lower quality, higher cost, and lower ease of access compared with non-prescribed cannabis.

Conclusions: The widespread use of non-prescribed cannabis for medicinal purposes in the Netherlands reflects both unmet health needs and barriers within the regulated medical cannabis system. Risky use practices – such as smoking cannabis with tobacco and using products without knowing their cannabinoid content – raise public health concerns. The findings highlight the need for harm reduction strategies and policies that better align medical cannabis regulation with patients’ real-world behaviours and care needs.”

https://pubmed.ncbi.nlm.nih.gov/41331499

https://link.springer.com/article/10.1186/s42238-025-00355-y

Modulatory Effects of “Minor” Cannabinoids in an in vitro Model of Neuronal Hypersensitivity

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“Aim: Effective treatment for neuropathic pain remains an unmet clinical need. The therapeutic benefits of the Cannabis plant are well known, especially for pain relief. Here, we have assessed ten “minor” cannabinoids for their analgesic effects in an established model of neuronal hypersensitivity, a key mechanism which underlies neuropathic pain.

Methods: Adult rat DRG neurons were cultured in medium containing 100 ng/mL nerve growth factor (NGF) and 50 ng/mL glial cell-line derived neurotrophic factor (GDNF) for 48 hours to sensitize the neurons. Ca2+ imaging was used to measure the responses to pain stimulation using capsaicin, and to determine the modulatory effects of the cannabinoids, in individual neurons.

Results: Control neurons (nociceptors) showed robust responses of Ca2+ influx to capsaicin application, while neurons treated with ten minor cannabinoids tetrahydrocannabiorcol (THCC), cannabitriol (CBT), cannabidivarin (CBDV), cannabinol (CBN), cannabichromene (CBC), cannabichromevarin (CBCV), cannabicitran (CBCT), cannabigerol monomethyl ether (CBGM), tetrahydrocannabutol (THCB) or tetrahydrocannabiphorol (THCP), at concentrations of 0.001-100 μM, showed differential dose-related effects on the responses to capsaicin. Ca2+ influx in response to capsaicin application was completely inhibited for each compound in 35-78% capsaicin-sensitive neurons, while other neurons showed reduced responses. The opioid receptor agonist morphine and α2δ1- Ca2+ channel inhibitor gabapentin were also tested for comparison and showed similar results. All the cannabinoids tested here inhibited calcium influx in response to capsaicin, and two, namely, CBN and THCC elicited calcium influx at higher doses. Inhibition of Ca2+ influx due to cannabichromene (CBC) was reversed by the potassium channel inhibitor Tertiapin Q.

Conclusion: All the cannabinoids tested here inhibited TRPV1 signalling. CBC targeted K+ channels to block TRPV1 mediated Ca2+ influx, demonstrating potential analgesic effects in vitro.”

https://pubmed.ncbi.nlm.nih.gov/41322279

“The therapeutic benefits of the Cannabis plant are well known, especially for pain relief.”

“In conclusion, our results show that the minor cannabinoids potently inhibit TRPV1 signaling in sensitized DRG neurons, and for CBC by blocking Ca2+ influx via K+ channel activation. This conclusion is based on the reversal of CBC-mediated inhibition in the presence of the K+ channel inhibitor Tertiapin Q. Further studies are necessary to confirm the mechanism, pathways and targets involved in the observed inhibitory effects of the other minor cannabinoids. This will facilitate the identification of cannabinoid combinations likely to have the maximum effect in providing analgesia for inhibiting neuronal sensitization that underlies chronic pain.”

https://www.dovepress.com/modulatory-effects-of-minor-cannabinoids-in-an-in-vitro-model-of-neuro-peer-reviewed-fulltext-article-JPR

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