“Background: The opioid crisis has continued in the United States, resulting in a healthcare crisis. Medical marijuana (MM) offers an alternative to those with addictions or in search of pain and inflammation management without the negative aspects of opioids.
Methods: A survey of more than 2,000 Louisianians on the frequency and amount of MM use revealed significant relationships between race, age, reason for use, prescription use, and whether they stopped using MM, as well as time in the MM program and the method of ingestion.
Results: Respondents reported lower levels of pain with MM usage by an average of 3.4 points on a ten-point scale (Z = -35.77, ρ ≤ .001). Those using prescriptions for pain were 1.5 times more likely to use MM less frequently (OR = 1.524, 95% CI: 1.114 – 2.074, ρ ≤ .01). Concordantly, those reporting that they had stopped using prescriptions for pain increased the odds of using more MM by 26.5 percent (OR = .735, 95% CI: .586 – .923, ρ ≤ .001).
Conclusions: These relationships support the idea that MM substitutes for prescription painkillers.”
“Cannabis has attracted growing interest for its therapeutic potential, especially in pain management.
This study explores the antinociceptive effects of two promising non-psychoactive cannabinoids, cannabivarin (CBV) and tetrahydrocannabivarin (THCV), using Caenorhabditis elegans (C. elegans), a nematode model that expresses homologs of mammalian cannabinoid and vanilloid receptors.
Thermotaxis assays were employed to quantify the antinociceptive effects of CBV and THCV in C. elegans. Wild-type animals were exposed to increasing concentrations of each compound to establish dose-response relationships. To investigate potential molecular targets, additional experiments were performed using mutant strains deficient in vanilloid receptor homologs (OCR-2 and OSM-9) and cannabinoid receptor homologs (NPR-19 and NPR-32). Mass spectrometry-based proteomics combined with network biology analyses were used to identify the biological pathways associated with drug response.
Results confirmed that both compounds elicit dose-dependent antinociceptive effects. Mutant analyses support the involvement of vanilloid and cannabinoid signaling pathways in mediating these responses.
These findings highlight the potential of CBV and THCV as non-psychoactive analgesic agents and support further research into their mechanisms of action and translational relevance for mammalian pain management.”
“Pain is one of the most pervasive health problems associated with a negative impact on thinking, mood, psychological, and social communication.
The medicinal plants and their derived compounds have recently attracted great interest as potential candidates for defeating pain because of their worldwide safety, availability, and affordability.
This review was constructed to summarize all in vitro and in vivo studies and clinical trials regarding plant-derived compounds’ analgesic and antinociceptive effects. Further, we focus on structural aspects, molecular mechanisms, and pharmacological effects. A literature survey was performed in “PubMed,” “Science Direct,” and “Google Scholar,” using the keywords “Pain, Analgesic activity, Flavonoids, Phenolics, Medicinal plants, Volatile oils, Tannins, Saponins, Alkaloids” to assess the activities of each compound.
The main natural compounds studied were flavonoids, alkaloids, phenolic acids, lignans, anthraquinones, and volatile oils. Different in vitro studies utilized nucleus pulposus cells, VK2/E6E7, End1/E6E7, and LPS-stimulated RAW264.7 cells to assess analgesic effects. The frequently defined animal models of analgesic activity included acetic acid-induced abdominal constrictions, hot-plate test, tail-flick test, formalin test, complete Freund’s adjuvant-induced pain, and hind paw incisional surgery.
For the natural compounds described, the opioids, serotonergic, and cannabinoid receptors appeared to be the most promising targets for pain management. This review suggested a wealthy resource of natural compounds as analgesic and antinociceptive candidates for pharmacists and drug researchers to launch a new drug with promising efficacy and safety.”
“While chronic pain is challenging to manage, it always co-exists with depression. Currently, chronic pain and depression are usually treated separately with distinct approaches, yet effectiveness remains elusive. Consequently, the development of integrated therapeutic strategies for pain while addressing depression is a high public health priority and unmet need that affects millions of people.
This study aims to determine if the combination of the two phytocannabinoids Beta-Caryophyllene (BCP) and cannabidiol (CBD) is effective for chronic pain while simultaneously showing antidepressant effects.
We used a chronic inflammatory pain model (Complete Freund’s Adjuvant, CFA) and a battery of pain and depression-like behavior tests in mice. Proteomics and immunohistochemistry (IHC) were used to explore the potential mechanisms of the effect of the combination on pain and depression.
We found that mice treated with the CBD and BPC combination produced a synergistic pain-relieving effect in the chronic inflammatory pain model and exhibited antidepressant properties.
Our IHC data also show that the CBD and BCP combination significantly reduced the neuroinflammation produced by CFA, and the proteomics showed downregulation of selected proteins involved in inflammation by the combination, compared to the individual effects of CBD and BCP.
In conclusion, our current findings show that, in the CFA pain model, the combination of CBD and BCP produces a synergistic pain-relief effect while also having antidepressant properties. Additionally, our data show that the anti-inflammatory action of this combination may explain its beneficial effects on pain and depression. Therefore, our data suggest this combination as a potentially effective treatment for chronic pain and related depression.”
“In conclusion, our current findings show that, in the CFA pain model, the combination of CBD and BCP produces a synergistic analgesic effect while also having antidepressant properties. Additionally, our data show that the anti-inflammatory action of this combination may explain its beneficial effects on pain and depression. Therefore, our data suggest this combination as a potentially effective treatment for the co-occurrence of chronic pain and depression.”
“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.”
“These findings indicate that medical or recreational cannabis laws may be significantly associated with reduced opioid use among patients diagnosed with cancer.”
“Medicinal cannabis has been the subject of extensive research, with recent studies demonstrating its potential in managing chronic pain and enhancing quality of life.
This case report examines the use of medicinal cannabis in a patient treated at the School of Dentistry of Araçatuba (FOA-UNESP). The patient, a 28-year-old female with no comorbidities, presented with chronic muscular TMD and reported poor sleep quality. Full-spectrum cannabis oil (1:1 ratio of THC to CBD), was prescribed for a period of 60 days, with a maximum dosage of 10 drops per day. Pain intensity was measured using the Visual Analog Scale (VAS), while sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Evaluations were conducted at three intervals: baseline, day 30, and day 60. To ensure patient safety, pre- and post-treatment blood tests were performed, and dosage adjustments were made every three days under the supervision of the study’s medical team.
The results revealed significant improvements in pain management, with the patient’s orofacial pain score decreasing from 7 to 3 on the NRS. Additionally, sleep quality improved, as reflected by a lower PSQI score (global sleep quality at level 6 at the end), indicating more restorative sleep. Throughout the treatment period, the patient experienced mild side effects, including drowsiness and gastrointestinal discomfort, which were effectively managed through dosage modifications.
In conclusion, full-spectrum cannabis oil shows promise as a therapeutic strategy for managing orofacial pain and improving sleep quality, providing significant relief in conditions where other interventions are ineffective or poorly tolerated. Further research is warranted to better understand the therapeutic mechanisms and potential side effects of medicinal cannabis in the management of chronic pain and related conditions.”
“In conclusion, the use of Full Spectrum Cannabis Oil in this case was associated with a clinically meaningful reduction in chronic orofacial pain and improvement in sleep quality, with no adverse effects or laboratory abnormalities observed during the treatment period. These outcomes suggest that individualized cannabinoid-based therapy may be a safe and effective approach for selected patients with temporomandibular disorders and comorbid sleep disturbances.”
“Introduction: Chronic low back pain (CLBP) affects over half a billion people worldwide. Current pharmacologic treatments, comprising mainly non-steroidal anti-inflammatory drugs and opioids, offer limited efficacy and pose significant risks, warranting the development of tolerable, safe and effective alternatives.
Methods: This randomized controlled trial on adults with CLBP was designed to confirm the superior efficacy and gastrointestinal tolerability of VER-01, a novel, standardized full-spectrum extract from Cannabis sativa DKJ127 L., over opioids. Subjects were randomized (1:1) to receive VER-01 or a range of commercially available opioids. After a 3-week titration, subjects underwent 24 weeks of treatment, followed by 2 weeks of wash-out. The primary endpoint was the relative risk of constipation occurrence after 27 weeks treatment. Secondary endpoints included changes in pain and sleep scores, determined using an 11-point numeric rating scale (NRS), with key secondary endpoints defined for week 27.
Results: A total of 384 individuals were randomized to receive VER-01 (n = 192) or opioids (n = 192). Subjects receiving VER-01 were fourfold less likely to develop constipation than those receiving opioids (relative risk [RR] VER-01/opioids 0.25; 95% confidence interval [CI] 0.09-0.69; p = 0.007) and threefold less likely to use laxatives (RR 0.34; 95% CI 0.18-0.65; p < 0.001). Longitudinal analysis revealed that VER-01 was superior to opioids in terms of pain reduction over 6 months of treatment, although differences in secondary endpoints limited to week 27 alone were not significant. Throughout the 6 months of treatment, mean pain reduction was 2.50 NRS points with VER-01 versus 2.16 with opioids (mean difference [MD] 0.34; 95% CI 0.00-0.67; p = 0.048), and sleep improved by 2.52 points with VER-01 versus 2.07 with opioids (MD 0.45; 95% CI 0.11-0.79; p = 0.009). These benefits were particularly pronounced in participants with severe pain, with greater pain reduction (MD 0.58; 95% CI 0.01-1.15) and sleep improvement (MD 0.66, 95% CI 0.05-1.27) compared to opioids.
Conclusions: VER-01 demonstrated superiority over opioids in treating CLBP, both in terms of efficacy and gastrointestinal tolerability.”
“In summary, this study provides robust evidence that VER-01 offers better tolerability, as well as superior pain relief and sleep quality compared to opioids in patients with CLBP. These findings highlight its potential as a promising new pharmacological option within a multimodal treatment approach that could fundamentally shift the paradigm in the treatment of chronic pain.”
“Cannabidiol (CBD) has been getting attention from the scientific community regarding its potential for the treatment of different conditions, such as epilepsy, anxiety, and pain.
This potential can be useful in clinical practice as an alternative or as an adjuvant alongside conventional therapeutic approaches; however, its mechanisms of action should be best described for its more effective application. Thus, our study aimed to evaluate whether the peripheral opioid system is involved in the analgesic mechanism of cannabidiol administered systemically for the treatment of neuropathic pain.
Male Swiss mice were subjected to the sciatic constriction injury, and their nociceptive threshold was evaluated using the mechanical paw pressure test.
Cannabidiol 20 mg/Kg produced an antinociceptive effect. Bestatin (400 µg/paw), a selective aminopeptidase-N inhibitor, potentiates the intermediate analgesic response of CBD at the dose of 2 mg/Kg. Naloxone (50 µg/paw), a non-selective opioid receptor antagonist, reversed the CBD-mediated analgesia. CTOP (5, 10, and 20 µg/paw) and naltrindole (30, 60, and 120 µg/paw), μ and Δ opioid receptor antagonists, but not norBNI (200 µg/paw), a κ opioid receptor antagonist, partially reversed the CBD analgesia.
Thus, our study shows that cannabidiol may induce activation of opioid receptors in the periphery as a part of its analgesic mechanism in neuropathic pain.”
“CDB induces the activation of µ and δ opioid receptors as a part of its analgesia mechanism, leading us to suggest a possible interaction between opioid and cannabinoid systems as a complementary mechanism for generating peripheral analgesia in neuropathic mice treated with cannabidiol.”
“Chronic low back pain (CLBP) affects over half a billion people worldwide. Current pharmacologic treatments offer limited efficacy and carry substantial risks, warranting the development of safe and effective alternatives.
This multicenter, randomized, placebo-controlled phase 3 trial evaluated the efficacy and safety of VER-01 in CLBP. It enrolled 820 adults with CLBP (VER-01, n = 394; placebo, n = 426) and included a double-blind 12-week treatment phase (phase A), a 6-month open-label extension (phase B), followed by either a 6-month continuation (phase C) or randomized withdrawal (phase D). The primary endpoint of phase A was a change in mean numeric rating scale (NRS) pain intensity, with a change in total neuropathic pain symptom inventory (NPSI) score as a key secondary endpoint in participants with a neuropathic pain component (PainDETECT > 18). The primary endpoint for phase D was time to treatment failure.
The study met its primary endpoint in phase A, with a mean pain reduction of -1.9 NRS points in the VER-01 group (mean difference (MD) versus placebo = -0.6, 95% confidence interval (CI) = -0.9 to -0.3; P < 0.001). Pain further decreased to -2.9 NRS points in phase B, with effects sustained through phase C.
The study also met its key secondary endpoint of phase A, with a mean NPSI decrease of -14.4 (standard error, 3.3) points from baseline in the VER-01 arm (MD versus placebo = -7.3, 95% CI = -13.2 to -1.3; P = 0.017). Although phase D did not meet its primary endpoint (hazard ratio = 0.75, 95% CI = 0.44-1.27; P = 0.288), pain increased significantly more with placebo upon withdrawal (MD = 0.5, 95% CI = 0.0-1.0; P = 0.034). In phase A, the incidence of adverse events-mostly mild to moderate and transient-was higher with VER-01 than with placebo (83.3% versus 67.3%; P < 0.001). VER-01 was well-tolerated, with no signs of dependence or withdrawal.
VER-01 shows potential as a new, safe and effective treatment for CLBP.”
“Cannabis sativa root has traditionally been used to relieve pain and inflammation, but its pharmacological properties remain underexplored due to low levels of psychoactive cannabinoids.
This study aimed to investigate the anti-inflammatory and antinociceptive effects of the ethyl acetate fraction of Cannabis sativa root (CSREA) using in vivo rodent pain models. Mice were subjected to formalin and acetic acid-induced nociceptive tests, while rats were evaluated using a carrageenan-induced paw edema model.
CSREA significantly reduced pain-related behaviors in both early (0-10 min) and late phases (15-30 min) of the formalin test and decreased writhing responses in the acetic acid model. Notably, CSREA also improved survival rates following acetic acid injection. Inflammatory markers, including IL-6 and IL-1β, were significantly lowered in serum.
Furthermore, CSREA suppressed paw edema and redness in the carrageenan-induced rat model, demonstrating dose-dependent anti-inflammatory efficacy comparable to diclofenac. CSREA also downregulated pain-related gene expression (SCN9A, ASIC1A, TACR1) and regulated key enzymes involved in endocannabinoid metabolism (FAAH, MAGL, DAGL), suggesting its role in the molecular modulation of pain pathways.
These effects are likely mediated via modulation of the endocannabinoid system, particularly by rebalancing the CB1R/CB2R ratio. The findings suggest that CSREA holds promise as a natural therapeutic agent for managing pain and inflammation and warrants further investigation into its molecular mechanisms and long-term effects.”
“This study provides evidence for the in vivo analgesic and anti-inflammatory effects and underlying mechanism of CSREA in vitro. Our results from the formalin and writhing tests demonstrate that CSREA significantly reduced nociceptive pain-related behaviors and inflammatory cytokine levels indicating strong anti-nociceptive properties in a dose-dependent manner. In addition, CSREA markedly reduced paw edema in the carrageenan-induced rat model, suggesting its potential as a natural product with anti-inflammatory activity. These effects are likely mediated through modulation of the endocannabinoid system, particularly by altering cannabinoid levels as demonstrated in the in vitro model.”
