Category Archives: Pain

Cannabidiol reduces oxycodone self-administration while preserving its analgesic efficacy in a rat model of neuropathic pain

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“Prescription opioid misuse is a significant public health concern among individuals with chronic pain. Treating severe pain often requires high doses of opioids, increasing the risk of developing an opioid use disorder.

Cannabidiol (CBD) is a non-intoxicating component of cannabis that has shown therapeutic potential without abuse liability.

This study investigated the effects of CBD on oxycodone self-administration and hyperalgesia in an animal model of chronic neuropathic pain.

Adult male rats were trained to self-administer intravenous oxycodone (0.06 mg/kg/infusion). Subsequently, they underwent chronic constriction injury (CCI) of the sciatic nerve or received sham surgery. Paw withdrawal latency was measured using the Hargreaves test as an indicator of thermal pain sensitivity. CBD (0, 1, 3, and 10 mg/kg, IP) was administered before the self-administration sessions, and pain testing was conducted afterward. The rats acquired oxycodone self-administration, as indicated by more active than inactive lever presses. CCI surgery decreased the paw withdrawal latency, confirming the induction of neuropathic pain. CCI alone did not affect oxycodone self-administration, suggesting that neuropathic pain does not substantially influence opioid intake at the dose tested.

Treatment with CBD reduced oxycodone self-administration in both the sham and CCI rats. Oxycodone self-administration in the CCI rats reversed the CCI-induced decrease in paw withdrawal latency. However, CBD did not affect the antinociceptive effect of oxycodone in CCI rats.

Taken together, these findings demonstrate that CBD reduces oxycodone self-administration without affecting the antinociceptive effects of oxycodone in neuropathic pain.

This study supports the potential of CBD to reduce opioid use and misuse, regardless of pain status.”

https://pubmed.ncbi.nlm.nih.gov/41521216

https://www.nature.com/articles/s41598-025-31828-y

Intravesical Cannabidiol for Inflammation and Pain in Interstitial Cystitis/Bladder Pain Syndrome via TLR4/NF-κB and TRPV1 Modulation

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“Purpose: This study explored the anti-inflammatory and analgesic mechanisms of intravesical cannabidiol (CBD) in cyclophosphamide (CYP)-induced interstitial cystitis/bladder pain syndrome (IC/BPS) rats.

Materials and methods: Female Sprague-Dawley rats were divided into four groups of control, IC/BPS, IC/BPS+10 mg/kg CBD, and IC/BPS+100 mg/kg CBD (n=5/group). IC/BPS was induced by CYP injections, followed by intravesical CBD administration. Pain sensitivity and bladder function were assessed via Von Frey tests and cystometrograms. Histological, Western blot, and immunofluorescence analyses were performed on bladder tissues. SV-HUC1 cells were analyzed using western blot and scratch assays.

Results: CBD improved bladder function, reducing instability, prolonging intercontractile intervals, and enhancing detrusor contraction pressure. The CBD 100 mg/kg group showed greater pain relief in Von Frey tests compared with other groups. Histology revealed reduced inflammation, mast cell infiltration, and fibrosis in bladder tissues. CBD decreased TNF-α, COX2, IL-6, and TRPV1 levels and inhibited the TLR4/MyD88/pNF-κB pathway. In SV-HUC1 cells, CBD suppressed epithelial injury and downregulated TRPV1, TLR4, MyD88, p-NF-κB, and Bax/Bcl-xL, demonstrating anti-inflammatory and anti-apoptotic effects.

Conclusions: Intravesical CBD alleviates inflammation by inhibiting the TLR4/MyD88/pNF-κB pathway, reduces neuropathic pain via TRPV1 channels, and improves cell apoptosis and migration in CYP-induced IC/BPS model animals.”

https://pubmed.ncbi.nlm.nih.gov/41508393

“Cannabidiol (CBD) is a non-psychoactive cannabinoid with a variety of biological activities and a wide range of benefits such as antioxidant, anti-inflammatory, and immunomodulatory effects. Research has demonstrated the therapeutic significance of CBD in neurological disorders, cardiomyopathy, diabetes, and other diseases.”

“In the present study, we investigated the potential therapeutic effects of CBD in IC/BPS. We conducted intravesical instillation of CBD in a rat model of IC/BPS and evaluated the effects on inflammation and bladder function and pain. We further analyzed its mechanism of action. Our study provides evidence of the potential effectiveness of CBD in the treatment of IC/BPS.”

https://wjmh.org/DOIx.php?id=10.5534/wjmh.250152

Cross-sectional comparison of cannabis use in adults with neuropathic versus non-neuropathic pain

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“Introduction: Cannabis has been decriminalized by many states and shows promise in treating both neuropathic and non-neuropathic pain through its interaction with the endocannabinoid system and anti-inflammatory effects. This study examines differences in cannabis use for adults whose most bothersome chronic pain condition is neuropathic vs. non-neuropathic.

Materials and methods: Survey data were collected from adults receiving care at a pain clinic. Participants completed demographic questions and standardized self-report measures (PROMIS Pain Intensity/Interference and the ID-Pain tool). Participants’ most bothersome pain condition(s) were categorized as neuropathic or non-neuropathic pain based on ID-Pain scores. Linear regression models assessed differences in frequency and duration of cannabis product use between groups, adjusting for age and sex.

Results: A total of 113 individuals were recruited; following exclusions and missing data, 104 participants (61.5% female) were included in the final analysis. Of these, 36.5% reported neuropathic pain as their most bothersome, and 63.5% reported non-neuropathic pain. Those with neuropathic pain reported significantly more days per month of Tetrahydrocannabinol/Cannabidiol (THC/CBD) combination (b = 5.96, p = 0.02), Cannabidiol-only (CBD-only) (b = 8.82, p = 0.03), and Tetrahydrocannabinol-only (THC-only) products (b = 7.04, p = 0.02). They also used THC-only (b = 0.97, p < 0.05) and THC/CBD (b = 1.09, p < 0.01) products more frequently per day. Neuropathic pain was positively associated with pain intensity (b = 4.10, p < 0.001) and interference (b = 4.95, p < 0.001).

Discussion: Adults whose most bothersome pain condition(s) were neuropathic used cannabis, especially THC and THC/CBD combination products, more frequently than those whose most bothersome pain was non-neuropathic. Participants with neuropathic pain also reported higher levels of pain intensity and interference. Further longitudinal research is needed to confirm whether increased use of THC-rich cannabis provides symptom relief for adults with neuropathic pain.”

https://pubmed.ncbi.nlm.nih.gov/41487383

“Cannabis interacts with the endocannabinoid system, making it a potential treatment for neuropathic pain.”

“Because previous studies found THC products to be more effective in managing neuropathic pain by interacting with the endocannabinoid system, it is possible that our participants also experienced benefit; this could explain their higher use of THC containing products.

https://www.frontiersin.org/journals/pain-research/articles/10.3389/fpain.2025.1677391/full

Effect of patient marijuana use on perioperative opioid requirements

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“The effect of chronic marijuana use on patients is unknown, including in the surgical setting. Marijuana produces many effects on the body, which should be considered when providing medical care.

Chronic marijuana use may affect surgical opioid requirements. To explore this possibility, an observational study was completed by conducting a retrospective chart review of patients who underwent surgery with general anesthesia.

Patients were identified in the electronic medical record via self-reporting as marijuana users (users) or nonmarijuana users (nonusers). Users and nonusers were case-matched based on age, gender, weight, and procedure. After case matching, 570 patients’ charts were analyzed, and intraoperative opioid, intraoperative propofol, and post-anesthesia care unit opioid requirements were compared.

Marijuana users required less intraoperative opioids (mean [standard deviation (SD)] 27.2 [20.5] morphine milligram equivalents [MMEs]) compared to those who were marijuana nonusers (31.3 [22.1] MME).

These results show a statistically significant difference in the intraoperative opioid requirement between case-matched users and nonusers (p = 0.02), with p = 0.013 after statistical adjustment for racial differences between the marijuana user and nonuser cohorts. Users and nonusers required similar amounts of intraoperative propofol (242.2 [220.2] and 257.8 [250.9], respectively) and post-operative opioids (7.3 [6.0] and 8.0 [9.0], respectively). The differences in intraoperative propofol and post-operative opioid requirements were not different statistically with p-values of 0.43 and 0.31, respectively.

Based on this study population, marijuana users required less intraoperative opioids when compared to case-matched marijuana nonusers, with no difference in intraoperative propofol or post-operative opioid requirements.

Perspective: Typical preoperative screening includes queries about patient substance use including marijuana, but details such as frequency and length of use are infrequently asked. The addition of these details to the assessment may provide improved understanding of a patient’s surgical opioid requirements.”

https://pubmed.ncbi.nlm.nih.gov/41123263

https://wmpllc.org/ojs/index.php/jom/article/view/3918

Medical Cannabis and Opioid Receipt Among Adults With Chronic Pain

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“Question  Is participation in the New York State (NYS) medical cannabis program associated with reduced prescription opioid receipt among adults with chronic pain?

Findings  In this cohort study of 204 adults with chronic pain, participation in the NYS medical cannabis program, defined as monthly dispensation of medical cannabis reported by the dispensary pharmacist, was associated with significantly reduced prescription opioid receipt.

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

Abstract

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

Medical Cannabis Program Lowers Chronic Pain Opioid Prescriptions

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“Access to medical cannabis through a state-regulated program was associated with significantly lower rates of opioid prescriptions among adults with chronic pain, according to findings recently published in JAMA Internal Medicine.

The study included 204 adults enrolled in the New York State medical cannabis program, which provided monthly access to medical cannabis through a dispensary pharmacist, and 142 ultimately obtained the treatment. The data spanned from September 2018 through July 2023. Researchers measured prescription opioid receipt via mean daily dose in morphine milliequivalents (MME) and compared it with how many days’ worth of cannabis individuals were dispensed each month based on pharmacists’ reports.

After 18 months, the mean daily MME decreased by 22%, from 73 to 57.

The authors noted that instead of measuring medical cannabis exposure via its legalization status, they directly analyzed pharmacy dispensation amounts, a more accurate indicator of uptake. Randomized clinical trials are needed to see whether medical cannabis reduces opioid use, they added.”

https://pubmed.ncbi.nlm.nih.gov/41481315

https://jamanetwork.com/journals/jama/fullarticle/2843608

Neuropathic Pain and Related Depression in Mice: The Effect of a Terpene and a Minor Cannabinoid in Combination

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“Background/Objectives: Neuropathic pain is one of the most severe types of chronic pain. Although it is difficult to manage, it often co-occurs with depression. Yet, no medication addresses the neuropathic pain and depression comorbidity. Therefore, developing integrated treatment strategies that address both pain and depression is a major public health priority and an unmet need affecting millions. 

Methods: In this study, we investigated the effect of combining a terpene, Beta-Caryophyllene (BCP), and cannabidiol (CBD) on neuropathic pain and associated depression. We employed a chronic constriction injury (CCI) neuropathic pain model and a series of behavioral tests to evaluate how oral administration of this combination influences neuropathic pain and depression-like behaviors in mice. We employed immunohistochemistry and proteomics approaches to explore the mechanism. 

Results: The analgesic effect of combining CBD and BCP is synergistic in neuropathic pain and also shows an antidepressant effect. Additionally, we found that this combination decreases neuroinflammation associated with CCI and affects specific genes involved in the inflammation. 

Conclusions: This work provides preclinical scientific evidence supporting the potential usefulness of this combination for neuropathic pain and associated depression.”

https://pubmed.ncbi.nlm.nih.gov/41463111

“Cannabis plants contain various non-psychoactive compounds, including Caryophyllene (BCP). BCP is a natural bicyclic sesquiterpene that acts as a natural ligand for the cannabinoid type 2 receptor (CB2) and is an FDA-approved food additive. It has several benefits, such as pain relief, antidepressant effects, and anti-inflammatory properties.

Given this background, the main goal of this study is to test the hypothesis that combining CBD and BCP is effective for neuropathic pain while also demonstrating antidepressant effects.”

“In conclusion, the proposed project introduces the concept that the combination of CBD and BCP can effectively relieve neuropathic pain while also addressing depression. This knowledge will advance the field by providing preclinical scientific evidence supporting the potential usefulness of this combination for neuropathic pain and associated depression.”

https://www.mdpi.com/2227-9059/13/12/3103


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