Should cannabis be used in the management of endometriosis?

pubmed logo

“Introduction: Endometriosis is a chronic inflammatory condition that affects around 1 in 7 women of reproductive age. Current medical treatments tend to be sub-optimal to manage the range of symptoms, with low levels of patient satisfaction. Cross-sectional and retrospective data suggests that people with endometriosis are consuming cannabis to help manage their symptoms.

Areas covered: This review discusses the evidence for consumption of medicinal cannabis to help manage endometriosis symptoms, including potential mechanisms of action from both animal models and human studies, usage in the community, the current evidence from clinical trials and observational studies, and the safety and potential drug interactions.

Expert opinion: While there is a lack of high-quality clinical trial evidence, significant self-reported evidence from cross-sectional surveys and retrospective observational data suggests that those consuming medicinal cannabis report reductions in endometriosis symptoms such as pelvic pain, dysmenorrhea and gastrointestinal symptoms, and improve mental health and sleep. Given the low levels of satisfaction with current treatment options, consideration should be given to trialing medicinal cannabis as part of the interdisciplinary management of endometriosis in those who express interest and who do not demonstrate any significant contraindications.”

https://pubmed.ncbi.nlm.nih.gov/41070712/

  • “Less than 25% of women with endometriosis report satisfaction with current conventional treatments with high discontinuation rates due to ineffectiveness and side effects.
  • Dysregulation of the endocannabinoid system in endometriosis, including reduced CB₁ receptors and elevated endocannabinoid levels, provides biological plausibility for therapeutic intervention through TRPV1 modulation and PPARγ activation.
  • Cannabis consumption is associated with self-reported reductions in pain, gastrointestinal symptoms and nausea, and improvements in sleep quality and mental health.
  • Cannabis consumption is associated with reductions in potentially addictive medications such as opioids and benzodiazepines; however these reductions should be done under the guidance of a physician.
  • Despite promising preclinical data and substantial observational evidence, robust randomized controlled trial data in humans remains lacking, preventing recommendation of more widespread adoption as a treatment.”

https://www.tandfonline.com/doi/full/10.1080/17446651.2025.2572339

Anti-obesity effect of unsaponifiable matter from hemp seed in 3T3-L1 adipocytes and high-fat diet-induced obese mice

pubmed logo

“The favorable lipid profile of hemp seed could be a potential source of unsaponifiable matter rich in fat-soluble phytochemicals such as phytosterols, vitamin E, and cannabidiol (CBD). Despite its nutritional value, studies investigating the functional properties of hemp seed, particularly its anti-obesity potential, remain limited.

The aim of this study was to obtain unsaponifiable matter from hemp seed (HUSM), analyze its fat-soluble phytochemicals and evaluate its anti-obesity activity using both in vitro and in vivo experimental models.

The results showed that HUSM contained abundant carotenoids, vitamin E, phytosterols, policosanols, and CBD, with trace amounts of THC (0.06%), Furthermore, HUSM inhibited adipocyte differentiation and lipid accumulation in a dose-dependent manner, significantly reducing lipid accumulation by up to 79% without cytotoxicity in 3T3-L1 adipocytes.

HUSM treatment led to reduced abdominal size and body weight gain, decreased adipose tissue and liver size, and lower plasma triglycerides, total cholesterol, and LDL cholesterol levels. These effects were mediated through the AMPK signalling pathway, which plays a pivotal role in regulating adipogenesis and lipogenesis. Additionally, HUSM improved adipokine balance, reducing leptin and increasing adiponectin levels, indicating recovery of dysfunctional adipose tissues.

These findings highlight the potential of HUSM as a natural anti-obesity therapeutic, offering new avenues for the treatment and prevention of obesity and related metabolic disorders through the AMPK signalling pathway.”

https://pubmed.ncbi.nlm.nih.gov/41047880/

https://pubs.rsc.org/en/content/articlelanding/2025/fo/d5fo02231b

No differences in neural responses or performance during cannabis cue-specific inhibitory control tasks between recreational cannabis users and non-users: Insights from fNIRS

pubmed logo

“Background: Impaired inhibitory control has been observed in regular cannabis users. Theories suggest that regular cannabis use is maintained by reward-driven behaviour, which may be underpinned by adaptations in neural reward and inhibitory control systems, thus increasing vulnerability to dependency.

Aims: This study investigated neural correlates of cannabis cue-specific inhibitory control in regular cannabis users and non-users using functional near-infrared spectroscopy (fNIRS).

Methods: Thirty regular cannabis users and thirty non-user controls completed two inhibitory control tasks (Go/No/Go and Stop-Signal Task), and a measure of attentional bias (Cannabis Stroop task). fNIRS recorded prefrontal and orbitofrontal haemodynamic responses (oxygenated haemoglobin and deoxygenated haemoglobin). Group comparisons and exploratory regressions examined cannabis use characteristics as predictors of behavioural and neural outcomes.

Results: No significant group differences were found in behavioural performance or haemodynamic activity across tasks. Exploratory regressions showed no significant associations between cannabis use characteristics and behavioural or neural outcomes after adjusting for covariates.

Conclusions: No evidence of impaired inhibitory control, attentional bias, or differences in prefrontal function were found in non-dependent cannabis users. Future studies should investigate whether such deficits emerge with heavier or dependent use.”

https://pubmed.ncbi.nlm.nih.gov/41037310/

“In summary, this study found no significant differences in behavioural performance or neural activation between regular cannabis users and non-user controls during cue-specific inhibitory control tasks.”

https://journals.sagepub.com/doi/10.1177/02698811251358814

Can cannabinoids alleviate behavioral symptoms in older adults with dementia? A systematic review

pubmed logo

“Background: Behavioral and psychological symptoms of dementia (BPSD) affect patients’ and caregivers’ well-being. Cannabinoids may offer a promising therapeutic option for managing BPSD.

Aims: This systematic review aims to explore the strengths of using this class of substances in the context of dementia care.

Methods: We conducted a comprehensive search across Embase Ovid, PubMed, Cochrane Library, APA PsycInfo, and Web of Science, identifying 1839 studies, with 14 selected for full review. Quality was assessed using the Newcastle-Ottawa and the modified Jadad Scales.

Results/outcomes: Ten studies (278 participants) were finally included. They showed cannabinoids helped reduce agitation and nocturnal disturbances.

Conclusions/interpretation: In conclusion, cannabinoids show promise in managing BPSD in dementia, with good tolerability and safety. Further studies could solidify these findings.”

https://pubmed.ncbi.nlm.nih.gov/41035223/

https://journals.sagepub.com/doi/10.1177/02698811251375895

VER-01 Shows Enhanced Gastrointestinal Tolerability, Superior Pain Relief, and Improved Sleep Quality Compared to Opioids in Treating Chronic Low Back Pain: A Randomized Phase 3 Clinical Trial

pubmed logo

“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.”

https://pubmed.ncbi.nlm.nih.gov/41028525/

“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.”

https://link.springer.com/article/10.1007/s40122-025-00773-z

Full-spectrum extract from Cannabis sativa DKJ127 for chronic low back pain: a phase 3 randomized placebo-controlled trial

pubmed logo

“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.”

https://pubmed.ncbi.nlm.nih.gov/41023483/

“In conclusion, this phase 3 study provides robust evidence supporting the efficacy and safety of VER-01 in the treatment of CLBP.”

https://www.nature.com/articles/s41591-025-03977-0

Investigating the Antimicrobial Efficacy of Cannabinoids and Their Derivatives Against Neisseria Gonorrhoeae by Computational Analysis

pubmed logo

“Neisseria gonorrhoeae is a Gram-negative diplococcus that causes gonorrhea through sexual contact. This ancient STD remains a major public health concern due to reproductive health impacts, antimicrobial resistance (AMR), and lack of a vaccine.

Cannabis sativa contains antibacterial cannabinoids, though its role in combating antibiotic resistance is underexplored. The 2Fe-2S iron-sulfur cluster protein is a potential antibiotic target, as these clusters are vital for bacterial proteins involved in electron transport, enzyme activity, and gene regulation. Disrupting them may impair bacterial survival and function.

In this investigation, the 2Fe-2S iron sulfur cluster binding domain-containing protein (NGFG_RS03485), identified as a potential therapeutic target from the core proteome of 12 Neisseria gonorrhoeae strains, was selected for this study. Potential antimicrobial agents were explored through molecular docking studies involving 16 cannabinoid analogs-9 obtained from literature sources and 7 identified via fingerprint similarity searches.

The study revealed that four cannabinoids form favorable bonds with active regions against our targeted protein; with a high binding affinity formed from the molecular docking; 1,3-Benzenediol, 2-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-, (1R-trans). Dronabinol, Cannabinolic acid A (CBNA), Cannabigerolic acid (CBGA), and Ferruginene C are derivatives identified. Drug-likeness assessments were conducted to evaluate the pharmacokinetic and toxicity properties of the cannabinoids and compared against the antibiotics.”

https://www.mdpi.com/2079-7737/14/9/1272

“Neisseria gonorrhoeae, the bacterium responsible for gonorrhoea, has developed increasing resistance to multiple antibiotics, making new treatment strategies urgently needed. This study explores the potential of cannabinoids and their derivatives as antimicrobial agents targeting N. gonorrhoeae.

Using computational methods, including molecular docking and fingerprint-based compound searches, the study identified five promising cannabinoid compounds with strong binding affinities to the 2Fe-2S iron–sulfur cluster binding domain-containing protein, a critical bacterial enzyme involved in electron transport and cellular function. These include 1,3-Benzenediol (a cannabidiol derivative), Ferruginene C, Dronabinol, Cannabinolic acid A (CBNA), and Cannabigerolic acid (CBGA). Their interactions were visualized using PyMOL and PLIP, revealing significant hydrogen bonding and hydrophobic interactions at active binding sites. Additionally, drug-likeness and pharmacokinetic assessments were performed, showing favorable absorption and low toxicity for several compounds compared to standard antibiotics.

Importantly, these cannabinoids showed potential to disrupt bacterial metabolic processes without inducing typical resistance pathways. The findings support further exploration of Phyto cannabinoids as natural alternatives for treating multidrug-resistant N. gonorrhoeae, with the 2Fe-2S cluster protein as a novel target. Further in vivo validation is recommended to confirm their therapeutic efficacy and safety.”

https://pubmed.ncbi.nlm.nih.gov/41007416/

Nanotechnology for the Efficacious Delivery of Medicinal Cannabis and Pharmaceutical Medicines

pubmed logo

“The application of nanoparticles as nanomedicines, particularly for the targeted and efficacious delivery of drugs is an expanding platform in the field of cannabinoid and pharmaceutical drug delivery. By refocusing the route of drug administration beyond the oral gut pathway, this technology provides significant advancements that are especially relevant for cancer treatments.

Orally administered drugs face significant challenges as they traverse the gastrointestinal tract (GIT) and are subject to first-pass GIT metabolism. Physiological conditions encountered in the GIT such as food effects, hormones, gastric pH, emptying time, and intestinal transit time vary widely across individuals. Fluid composition and enzymatic activity in the small intestine and large bowel also influence drug dissolution and absorption. These factors in conjunction with the intestinal cohort of bacteria can metabolize drugs before absorption, contributing to poor and variable drug bioavailability, which can be exacerbated by gut dysbiosis.

Drug delivery that bypasses the oral-GIT route and hence first-pass metabolism offers a plausible solution for enhanced safety and drug efficacy.”

https://pubmed.ncbi.nlm.nih.gov/41011252/

“Bypassing the first-pass metabolism in the gut is a fundamental and important characteristic of nanomedicines. It is thus possible to identify nanoparticles that form clear solutions in a stable aqueous matrix. Producing relatively insoluble drug components without altering their chemical structures is an important feature of nanomedicine drug delivery platforms.

These nanomedicines provide flexibility that allows the development of nanoparticle aqueous formulations of oro-mucosal, nasal, ocular, and transdermal products without the use of alcohol for enhanced delivery which bypasses the first-pass passage and metabolism of the GIT.”

https://www.mdpi.com/1424-8247/18/9/1385

Tetrahydrocannabivarin (THCV) Dose Dependently Blocks or Substitutes for Tetrahydrocannabinol (THC) in a Drug Discrimination Task in Rats

pubmed logo

“Delta-9-Tetrahydrocannabivarin (THCV), a naturally occurring cannabinoid and structural analog of THC, exhibits a dual pharmacological profile as a CB1 receptor agonist/antagonist and a partial CB2 agonist. This study evaluated the effects of THCV in a THC discrimination model in rats. Male Sprague-Dawley rats (n = 16, 300-340 g, PND60) were trained under a fixed ratio 20 (FR20) schedule to discriminate THC (3 mg/kg) from vehicle. Substitution tests were conducted with THC (0.325-3 mg/kg), THCV (0.75-6 mg/kg), and THC-THCV combinations. THCV produced an inverted U-shaped substitution curve, significantly differing from vehicle (p = 0.008). At 3 mg/kg, THCV partially substituted for THC (54.6% ± 17.82, p = 0.003). Response rate significantly increased during the substitution test with 3 mg/kg of THCV (p = 0.042). THCV (6 mg/kg) reversed THC (0.75 mg/kg)-induced responding (p = 0.040), with no significant change in response rate (p = 0.247). However, THCV combined with THC (1.5 mg/kg) affected response rates (p = 0.012), with 6 mg/kg significantly reducing rates vs. 3 mg/kg (p = 0.013). Blood THC and 11-OH-THC levels remained unchanged when THC was combined with THCV. The findings suggest THCV can partially mimic or block THC’s discriminative effects in a dose-dependent manner, possibly acting as a partial CB1 agonist.”

https://pubmed.ncbi.nlm.nih.gov/41008636/

“Taken together, our findings highlight THCV’s unique pharmacological profile, characterized by partial agonism dose-dependent substitution for THC, and antagonism at higher doses. Importantly, THCV substituted for THC in a graded manner without evidence of pharmacokinetic interactions, and it also produced stimulant-like effects that distinguish it from THC. These results suggest that THCV may act as a dose-dependent modulator of cannabinoid receptor activity, capable of both mimicking and opposing THC’s discriminative stimulus effects. Such bidirectional properties are consistent with its complex receptor pharmacology and underscore the importance of dose in determining behavioral outcomes. Future studies should expand on these findings by examining sex- and strain-dependent variability, assessing the role of CB1 and CB2 receptor mechanisms using antagonist approaches, and exploring THCV’s actions across a broader range of behavioral paradigms, including those related to reward, cognition, and feeding behavior. Together, these efforts will help to clarify the pharmacology of THCV and further delineate its position within the cannabinoid spectrum.”

https://www.mdpi.com/2218-273X/15/9/1329

Cannabis Improves Metabolic Dysfunction and Macrophage Signatures in Obese Mice

pubmed logo

“Obesity rates continue to rise, highlighting the need for new treatments that are effective, safe, and widely accessible. Aligned with the easing of restrictions on cannabis use, interest in its therapeutic potential is evolving. As such, we examined the effects of the cannabis plant with high cannabidiol (CBD) content or high Δ9-tetrahydrocannabinol (THC) content on metabolic and immune dysregulation in obese mice.

Briefly, female C57BL/6 mice were randomized into four groups (n=15/group): 1) Lean, 2) Obese Placebo, 3) Obese CBD, and 4) Obese THC. Lean mice consumed a low-fat diet for the study duration. Obese mice consumed a high-fat diet for 16 weeks prior to a 4-week cannabis (3x/week; high CBD = ~4.2 mg/kg and high THC = ~7.3 mg/kg) intervention.

Consistent with our hypothesis, obesity increased Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and metabolic dysfunction-associated steatohepatitis (MASH) both of which were significantly mitigated by either high (10.5%) CBD or high (18.16%) THC cannabis (p<0.05). Interestingly, these changes appeared to occur independent of significant weight loss or measurable changes in food intake.

Diet-induced obesity also increased infiltrating macrophages, pan macrophages, and M1-like pro-inflammatory macrophages in adipose tissue and liver. These effects were rescued by high CBD and high THC (p<0.05), providing evidence consistent with causation for the improvements in HOMA-IR and MASH.

Despite the legal complexities surrounding cannabis use, these data suggest both CBD and THC can be a viable therapy to target macrophages and improve metabolic health and immune dysregulation with obesity.”

https://pubmed.ncbi.nlm.nih.gov/40960937/

https://journals.physiology.org/doi/abs/10.1152/ajpcell.00503.2025