Tag Archives: Cannabinoids

(+)-Trans-Cannabidiol Is an Agonist at Human CB2 Receptors

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A new 2026 study reports that (+)-trans-cannabidiol [(+)-CBD] acts as an agonist at human CB2 cannabinoid receptors, activating a major receptor of the endocannabinoid system involved in immune and inflammatory signaling.

Researchers found that (+)-CBD produced a strong, concentration-dependent CB2 response, reaching roughly 90% of the maximum effect produced by the reference cannabinoid agonist CP55940. Additional testing indicated that the compound acts through the receptor’s primary, or orthosteric, binding site.

The findings show that different molecular forms of cannabidiol can interact with cannabinoid receptors in very different ways. The researchers conclude that (+)-CBD may deserve further study in CB2-sensitive disease states, adding another layer to our understanding of how cannabinoid chemistry can influence the human endocannabinoid system.

“(-)-trans-Cannabidiol ((-)-CBD) is a principal phytocannabinoid from Cannabis sativa. (-)-CBD has complex pharmacology but is a relatively weak inhibitor of CB1 and CB2 receptor signaling. Cannabidiol has two chiral centres and thus four stereoisomers. (+)-trans-CBD ((+)-CBD) has a higher affinity than (-)-CBD at CB1 and CB2, but its pharmacodynamic effects at these receptors are incompletely described.

We examined the activity of (+)-CBD at human CB1 and CB2 receptors using a fluorescence-based assay of membrane potential in AtT20 cells stably expressing CB1 or CB2 receptors.

(+)-CBD produced a rapid, concentration-dependent hyperpolarization in CB2-expressing cells (pEC50 6.63 ± 0.08) with a maximal effect 90% of the response to CP55940. The CB2 response was blocked by pertussis toxin pretreatment and competitively inhibited by the CB2 antagonist AM630 (Schild slope 1.1 ± 0.1). (+)-CBD was a low-efficacy, low-potency CB1 agonist and inhibited somatostatin-receptor effects at high concentrations (10-30 μM). (+)-CBD had no effect on the membrane potential of AtT20 wild-type cells. In silico modeling of ligand interactions with CB2 indicated that (+)-CBD but not (-)-CBD formed an H-bond with Ser285, a residue crucial for agonist activation of CB2.

Our data suggests (+)-CBD acted as a CB2 agonist via the orthosteric binding site on the receptor. Synthetic CBD, including (+)-CBD, has previously been administered in clinical trials, presumably without consideration of its potential CB2 agonist activity.

Given the relative safety of (-)-CBD in people, (+)-CBD may be a useful drug to explore CB2-sensitive disease states.”

https://pubmed.ncbi.nlm.nih.gov/42745361

“This study emphasizes the importance of understanding the molecular actions of the enantiomers of chiral cannabinoids. Although the safety of (+)-CBD cannot simply be assumed to be the same as (−)-CBD, the identification of (+)-CBD as a robust CB2 agonist suggests that (+)-CBD may be worth exploring as a therapeutic agent in chronic inflammatory conditions or other diseases where CB2 activation may prove beneficial.”

https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.70325

The anterior cingulate cortex mediates cisplatin-induced mechanical allodynia and represents a target for cannabigerol antinociception

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Chemotherapy-induced peripheral neuropathy can cause persistent burning, tingling, numbness and pain long after cancer treatment ends. A new 2026 study investigated how the brain contributes to this neuropathic pain and whether cannabigerol (CBG), a non-euphoric cannabinoid, can reduce it.

Using a mouse model of cisplatin-induced neuropathy, researchers found that CBG significantly reversed mechanical allodynia. They also identified the anterior cingulate cortex, a brain region involved in processing pain, as an important part of the neuropathic pain response. Directly administering CBG into this region produced antinociceptive effects.

The findings suggest that CBG can act within central pain-processing circuits and identify the anterior cingulate cortex as a potential target for cannabinoid-based treatment of chemotherapy-induced neuropathic pain. The researchers say the results highlight the potential for “centrally targeted, non-euphoriant cannabinoid-based therapies.”

“Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and debilitating consequence of cancer treatment with limited effective therapeutic options. While peripheral nerve injury is a key driver, emerging evidence suggests that maladaptive plasticity within central pain circuits, including the anterior cingulate cortex (ACC), contributes to the maintenance of neuropathic pain.

Here, we tested the hypothesis that the ACC is a critical substrate for cisplatin-induced mechanical allodynia and a target for cannabigerol (CBG)-mediated antinociception.

Adult male C57BL/6 mice received cisplatin (5 mg/kg, i.p., once weekly for four weeks) to induce CIPN. Mechanical allodynia was assessed using electronic von Frey testing.

Systemic administration of CBG (20 mg/kg, i.p.) significantly reversed mechanical allodynia in CIPN mice without affecting baseline thresholds in non-neuropathic animals, indicating a state-dependent effect. Chemogenetic inhibition of ACC neurons using hM4Di DREADDs similarly attenuated mechanical allodynia, identifying the ACC as a functionally relevant component of the CIPN pain state. To determine whether CBG acts within this circuit, bilateral intra-ACC microinjections of CBG (20 nM and 20 µM) were performed, both of which produced transient antinociceptive effects.

These findings demonstrate that the ACC contributes to the maintenance of mechanical allodynia in CIPN and establish this region as a site of action for CBG.

Together, our results support a model in which the ACC represents a convergent cortical mechanism underlying pathological pain and highlight the potential for centrally targeted, non-euphoriant cannabinoid-based therapies.”

https://pubmed.ncbi.nlm.nih.gov/42744343/

“In conclusion, this study identifies the ACC as a hub in the maintenance of mechanical allodynia in a model of CIPN. By demonstrating that chemogenetic inhibition of the ACC reverses hypersensitivity and that both systemic and local administration of CBG produce antinociceptive effects, our findings link circuit-level dysfunction to a pharmacologically targetable mechanism within this region. These results support a model in which increased or dysregulated ACC neuronal activity may represent a convergent feature of pathological pain states. Importantly, these findings demonstrate that CBG can act within the ACC to modulate mechanical allodynia. Future studies identifying the receptor targets and circuit mechanisms through which CBG acts within the ACC will be essential for refining therapeutic strategies for chronic pain.”

https://journals.sagepub.com/doi/10.1177/17448069261491110

Cannabidiol Ameliorates Blood-Brain Barrier Dysfunction and Inhibits Memory Astrocytes Activation in Mice With Sickness-Like Behaviors

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A new 2026 study published in CNS Neuroscience & Therapeutics found that cannabidiol (CBD) improved blood-brain barrier dysfunction, reduced neuroinflammation, and alleviated depressive-like behaviors in mice. The researchers found that sickness-like mice showed weakened blood-brain barrier integrity, reduced protective tight-junction proteins, abnormal astrocyte activation, and increased inflammation in the brain.

A single dose of CBD improved these changes, restoring important blood-brain barrier markers while reducing abnormal astrocyte activity and neuroinflammation. The researchers also identified a particularly interesting target called “memory astrocytes”—astrocytes that can respond more rapidly and strongly when exposed to a second inflammatory challenge.

The study found that CBD inhibited this memory-astrocyte-associated secondary inflammatory response, helping protect the blood-brain barrier and improve behavior. The researchers concluded that CBD may improve blood-brain barrier dysfunction associated with depression and identified memory-astrocyte-mediated neuroinflammation as a potential therapeutic target.

“Background: Blood-brain barrier (BBB) dysfunction has been increasingly implicated in the pathophysiology of depression; however, effective therapeutic strategies targeting this pathology remain limited. This study aimed to investigate the effect of cannabidiol (CBD) on improving depressive-like behaviors and BBB impairment, as well as its underlying mechanism.

Methods: Depressive-like behaviors in mice were assessed via exploratory and despair-like tests. BBB integrity was evaluated by examining tight junction protein expression in endothelial cells and AQP4 reduction from the perivascular membrane. Astrocyte activation and neuroinflammation were also measured. The therapeutic effects of a single CBD dose were examined.

Results: Mice with depressive-like phenotypes showed reduced exploratory behavior and increased despair-like behavior. In the BBB, the expression of tight junction proteins in endothelial cells was downregulated; in astrocytes, decreased AQP4 expression was observed, abnormal activation was enhanced, and neuroinflammation was elevated. A single dose of CBD alleviated all the above pathological changes. Further studies demonstrated that CBD exerted its effects by inhibiting memory astrocyte-associated secondary neuroinflammation, thereby alleviating depressive-like behaviors in mice with depressive-like phenotypes.

Conclusion: Experimental results show that CBD treatment can improve BBB dysfunction in depression and further indicates that targeted inhibition of memory astrocytes-mediated neuroinflammation may promote the treatment of depression.”

https://pubmed.ncbi.nlm.nih.gov/42747207

“Cannabidiol (CBD), a natural extract from cannabis, possesses multiple biological functions including cardioprotection, anti-inflammation, anti-cancer, anti-oxidation, and neuroprotection. Additionally, it plays indispensable roles in relieving depression and regulating BBB function]. CBD ameliorates depression by upregulating brain-derived neurotrophic factor, inhibiting neuroinflammation, alleviating oxidative stress, and modulating neurotransmitter transmission.”

https://onlinelibrary.wiley.com/doi/10.1002/cns.71168

The Endocannabinoid System in Endometriosis-Associated Pain: Mechanisms, Molecular Targets, and Therapeutic Implications

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A new 2026 review published in Reproductive Sciences examines the endocannabinoid system (ECS) as a therapeutic target for endometriosis-associated pain, a condition that can cause severe pelvic pain, painful menstruation, painful intercourse, and other chronic symptoms. The authors highlight the ECS because of its established roles in regulating pain, inflammation, and immune activity.

The review found that cannabinoids may influence three major mechanisms involved in endometriosis-associated pain: inflammation, pain signaling and sensitization, and the growth of endometriotic lesions. Cannabinoids interact with both cannabinoid and non-cannabinoid receptors found in endometriotic tissue, while also reducing inflammatory signaling from immune cells such as mast cells and macrophages.

The researchers conclude that the endocannabinoid system is a promising therapeutic target for endometriosis-associated pain, with cannabinoid therapies showing potential to regulate nociception, inflammation, and lesion proliferation. They call for clinical trials to further evaluate cannabinoid-based treatments for people living with endometriosis.

“Endometriosis is a chronic gynecological disorder affecting approximately 10% of reproductive-age women, characterized by the ectopic growth of endometrial tissue and severe pain, including dysmenorrhea, chronic pelvic pain, dyspareunia, dysuria, and dyschezia. Current treatments are limited in efficacy and associated with significant side effects, underscoring the urgent need for novel therapeutic strategies.

The endocannabinoid system (ECS) has emerged as a promising therapeutic target, given its well-established roles in pain modulation, inflammation, and immune regulation. Epidemiological evidence demonstrates that women with endometriosis increasingly use cannabis for symptom self-management, yet the underlying mechanisms remain poorly characterized.

This review integrates preclinical and human evidence to comprehensively evaluate the mechanistic basis of cannabinoid efficacy in endometriosis-associated pain. Evidence from in vitro studies and animal models indicates that cannabinoids target three main mechanisms of endometriosis-associated pain, including inflammation, nociceptive signaling, and lesion proliferation.

Cannabinoids suppress pain signaling and sensitization by interacting with cannabinoid and non-cannabinoid receptors expressed in endometriotic lesions. Cannabinoids attenuate endometriosis-induced inflammation by inhibiting proinflammatory cytokine signaling and reducing the release of inflammatory mediators by mast cells and peritoneal macrophages. Cannabinoids also exert antiproliferative effects in endometriosis models, thereby suppressing the growth of endometriotic lesions.

In conclusion, the ECS is a promising therapeutic target for endometriosis-associated pain, as it regulates nociception, inflammation, and proliferation. These promising findings highlight the potential therapeutic benefits of cannabinoids for endometriosis-associated pain, warranting the need for clinical trials to evaluate the safety and effectiveness of cannabinoid therapies in endometriosis.”

https://pubmed.ncbi.nlm.nih.gov/42745018

https://link.springer.com/article/10.1007/s43032-026-02201-9

Δ9-Tetrahydrocannabinol treatment impairs CD8+ T cell differentiation into interferon gamma-competent CD45RO+ cells

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New research published in The Journal of Pharmacology and Experimental Therapeutics shows that Δ9-tetrahydrocannabinol (THC) can alter the development of CD8+ T cells involved in inflammatory immune responses. Researchers found that THC reduced secretion of interferon gamma (IFNγ), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNFα), three signaling molecules involved in immune activation and inflammation.

Rather than simply preventing cells from producing IFNγ, THC appeared to change how the T cells developed. THC reduced the differentiation of CD8+ T cells into mature CD45RO+ cells capable of secreting IFNγ. A selective CB2 receptor agonist produced similar effects, suggesting that activation of the cannabinoid CB2 receptor may play an important role in THC’s immune-modulating activity.

The researchers examined these effects partly because IFNγ-producing CD8+ T cells contribute to persistent neuroinflammation associated with HIV-associated neurocognitive disorders. They concluded that reducing CD8+ T-cell-derived IFNγ in the central nervous system may potentially improve cognitive outcomes during HIV infection, while noting that the findings may also have relevance to other inflammatory diseases involving IFNγ-producing CD8+ T cells.

“Chronic human immunodeficiency virus (HIV) infection results in a persistent state of neuroinflammation, even with combined antiretroviral therapy. Neuroinflammation contributes to pathology termed HIV-associated neurocognitive disorder, which is exacerbated by interferon gamma (IFNγ)-producing CD8+ T cells in the central nervous system.

Many people living with HIV self-report using Cannabis sativa to mitigate symptoms of chronic infection and side effects of treatment. C. sativa is composed of various phytocannabinoids, including Δ9-tetrahydrocannbinol (THC), which possesses immune-modulating properties.

This study aims to determine whether C. sativa use by people living with HIV, and specifically THC, affects IFNγ secretion by CD8+ T cells.

We found that HIV status does not influence T cell IFNγ responses, and C sativa use modestly reduces the average secretion of IFNγ by CD8+ T cells from HIV+ donors. Treatment of CD8+ T cells with THC and the selective cannabinoid receptor 2 agonist, JWH-015, reduced T-cell cytokine secretion, with THC eliciting greater suppression than cannabidiol.

These results suggest that THC treatment does not directly impair IFNγ gene expression or protein production, as determined by polymerase chain reaction and flow cytometry. However, THC treatment impaired CD8+ T cell differentiation into IFNγ-competent CD45RO+ cells.

These studies are of clinical relevance because reduction of CD8+ T-cell-derived IFNγ in the central nervous system may improve cognitive outcomes during HIV infection. Furthermore, these findings may be generalizable to other inflammatory diseases in which IFNγ-producing CD8+ T cells have been implicated.

SIGNIFICANCE STATEMENT: Δ9-Tetrahydrocannbinol (THC) treatment reduces CD8+ T cell interferon gamma (IFNγ) secretion isolated from HIV- and HIV+ individuals. THC and the selective cannabinoid receptor 2 agonist, JWH-015, both reduced CD8+ T cell secretion of IFNγ, interleukin 2, and tumor necrosis factor α, suggesting the involvement of cannabinoid receptor 2. Although THC treatment does not suppress IFNγ mRNA or protein levels, it reduces the number of IFNγ-secreting cells by impairing CD8+ T-cell differentiation into IFNγ-competent CD45RO+ cells.”

https://pubmed.ncbi.nlm.nih.gov/42748512

https://jpet.aspetjournals.org/article/S0022-3565(26)01210-3/abstract

Need this THC study explained? thcXplained.com

Medical Cannabis and the Hallmarks of Cancer: A Critical Narrative Review

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A 2026 critical narrative review examines medical cannabis through one of the most important frameworks in cancer biology: the hallmarks of cancer. Rather than looking only at symptom relief, the authors reviewed evidence for how cannabinoids, including THC and CBD, may interact with biological processes that allow cancer to develop, survive, grow and spread.

The review discusses cannabinoid effects involving cancer-cell proliferation, programmed cell death, angiogenesis, invasion, metastasis, tumor metabolism, immune responses and the tumor microenvironment. It also examines major cancer-related signaling pathways, including PI3K/AKT, RAS/RAF/ERK, mTOR, EGFR, Wnt/β-catenin and p53.

Taken together, the research shows that cannabinoids can influence multiple hallmarks of cancer through several interconnected mechanisms. The authors describe the evidence as showing biologically plausible antitumor activity and highlight cannabinoids as an important area for continued cancer research and development.

“Cancer remains a highly complex and heterogeneous disease, causing major morbidity and mortality worldwide despite advances in diagnosis and treatment. The hallmarks of cancer enlighten the biological mechanisms supporting tumourigenesis and malignant evolution, while helping to identify potential therapeutic targets.

Medical cannabis has mostly been used in oncology for supportive care, but increasing preclinical evidence suggests interference with cancer-related signalling pathways.

This narrative review summarizes the current evidence on cannabinoids, in particular the phytocannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), framing their prospective anticancer effects in the hallmarks of cancer.

Preclinical studies imply that CBD exerts antiproliferative effects by modulating oncogenic signalling pathways, including EGFR, PI3K/AKT, RAS/RAF/ERK, mTOR and Wnt/β-catenin, while also influencing tumour suppressor pathways involving p53, p21 and p27, causing cell cycle arrest. CBD has additionally been shown to promote programmed cell death via mitochondrial dysfunction and autophagy, altering cancer metabolism as well. Furthermore, CBD has shown anti-invasive and antiangiogenic properties and also appears to modulate immune responses and interactions with the tumour microenvironment, including emerging links with the microbiome.

Overall, cannabinoids exhibit biologically plausible antitumour activity across multiple cancer hallmarks and may present promising candidates for combination therapeutic strategies.

Nonetheless, the current evidence remains predominantly preclinical, and robust translational studies and clinical trials are needed to clarify their pharmacokinetic and pharmacodynamic profiles, determine their clinical efficacy and safety while assessing their potential integration into multimodal cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/42737454/

“Cannabinoids have demonstrated biologically plausible promising antitumour effects by interacting with several cancer hallmarks, including tumour angiogenesis, resistance to programmed cell death, metastasis and invasion, as well as immune evasion and phenotypic plasticity.”

“Cannabinoids can interfere with several biological mechanisms involved in cancer development and progression and even though their role in oncology remains mostly supportive with predominance in symptom control, preclinical studies increasingly suggest that cannabis can also influence tumour biology.”

https://www.mdpi.com/1422-0067/27/17/7549

Delta-8-tetrahydrocannabinol ameliorates murine autoimmune hepatitis and is associated with epigenetic modulation of immune responses

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A new 2026 study published in International Immunopharmacology found that delta-8-tetrahydrocannabinol (Δ8-THC) significantly reduced autoimmune hepatitis in mice while altering the immune responses responsible for liver inflammation. Researchers found that Δ8-THC reduced inflammatory immune cells and helped preserve immune cells involved in protecting the liver.

The researchers also uncovered a possible mechanism. Δ8-THC increased two microRNAs, miR-100-5p and miR-199a-3p, which suppressed mTOR signaling and shifted CD4+ T-cell development away from inflammatory Th1 and Th17 cells and toward regulatory T cells that help control excessive immune activity.

The authors concluded that Δ8-THC showed both hepatoprotective and anti-inflammatory activity and highlighted its potential therapeutic value for autoimmune and inflammatory disorders. The study adds new evidence that cannabinoids may influence disease not only by reducing inflammation, but by changing the molecular and epigenetic pathways that regulate immune responses.

“Aim of the study: Cannabinoids have gained attention for their ability to modulate immune responses and suppress inflammation. However, the effect of Δ8-THC, a minor cannabinoid found in Cannabis, has not been explored in autoimmune hepatitis. To address knowledge gap, the present study aimed to investigate the hepatoprotective and immunoregulatory properties of Δ8-THC in experimental autoimmune hepatitis and to identify molecular and epigenetic mechanisms underlying its immunoregulatory effects.

Methods: miRNA sequencing and flow cytometric analysis were performed using hepatic immune cells from female C57BL/6 mice treated with ConA (12.5 mg/kg, i.v.) and Δ8-THC (20 mg/kg, i.p.). Differential miRNA expressions were analyzed using the edgeR, and miRNA targets were predicted using Ingenuity Pathway Analysis. Target gene expression was validated by qRT-PCR and Western blot. Functional assays including miRNA mimic/inhibitor transfection and CD4+ T-cell differentiation were performed to validate target gene regulation by miRNAs and its role in CD4+ T-cell differentiation.

Results: Δ8-THC markedly suppressed ConA-induced autoimmune hepatitis by restoring immune homeostasis within the liver through suppression of inflammatory monocytes, neutrophils, and natural killer cells, and preservation of tolerogenic Kupffer cells. In addition, Δ8-THC reshaped the hepatic lymphoid compartment, diminishing inflammatory CD4+ T-cell responses while favoring regulatory T-cell expansion. These effects were associated with the preservation of miR-100-5p and miR-199a-3p expression in the liver, whereas both miRNAs were markedly downregulated following ConA treatment. mTOR, a central regulator of T-cell differentiation, was identified as a target of these miRNAs. Consistent with these findings, Δ8-THC reduced mTOR expression and upregulated hepatoprotective miRNAs in both in vivo and in vitro models. Functional analyses with miRNA overexpression and inhibition approaches verified the direct regulation of mTOR by these miRNAs in T cells and RAW 264.7 cells. In naïve CD4+ T cells, miRNA gain- and loss-of-function experiments demonstrated that miR-100-5p/miR-199a-3p-mediated suppression of mTOR promotes regulatory T-cell differentiation while limiting Th1 and Th17 polarization.

Conclusion: Our results identify Δ8-THC as a promising hepatoprotective and anti-inflammatory compound that ameliorates ConA-induced autoimmune hepatitis by influencing CD4+ T-cell differentiation potentially through the miR-100-5p/miR-199a-3p-mTOR axis, highlighting its potential therapeutic value in autoimmune and inflammatory disorders.”

https://pubmed.ncbi.nlm.nih.gov/42753324

“In conclusion, our findings suggest that Δ8-THC can mitigate ConA-induced hepatitis, potentially through epigenetic regulation involving microRNAs. Specifically, Δ8-THC improved liver function and reduced systemic and intrahepatic inflammation in ConA-exposed mice. These effects were associated with increased expression of miR-100-5p and miR-199a-3p in the liver, suggesting that these miRNAs may regulate mTOR signaling and contribute to the suppression of proinflammatory responses and promotion of anti-inflammatory pathways. Functional studies supported the involvement of these miRNAs in the regulation of mTOR signaling, CD4+ T-cell differentiation, and inflammatory responses.”

https://www.sciencedirect.com/science/article/pii/S1567576926012518?via%3Dihub

Ten-year outcomes of medical cannabis for chronic low back pain: opioid reduction, pain relief, and functional improvement in 1,000 patients

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A 2026 study published in the European Spine Journal followed 1,000 patients with chronic low back pain who had been using opioids for at least a year before beginning medical cannabis treatment. Researchers tracked changes in opioid use, pain, disability, and other medications over as long as 10 years.

Among the 638 patients who completed the full 10-year follow-up, average opioid use fell by 89.8%, while pain scores dropped by 84.2%. More than 91% of patients achieved at least a 50% reduction in opioid use, and 96.6% achieved at least a 30% reduction in pain. Disability scores also improved substantially over the study period.

The reductions were not limited to opioids. Use of benzodiazepines, gabapentinoids, antidepressants, and other pain medications also declined. With a decade of follow-up, this study provides unusually long-term evidence that medical cannabis may play an important role in reducing pain, improving function, and decreasing dependence on multiple medications in people living with chronic low back pain.

“Purpose: To evaluate 10-year outcomes of medical cannabis therapy on opioid use, pain intensity, functional disability, concomitant medication use, and adverse events in cannabis-naïve chronic low back pain (CLBP) patients, with particular attention to clinically meaningful outcomes defined by established minimal clinically important difference (MCID) thresholds.

Methods: Single-center longitudinal observational study of 1,000 consecutive cannabis-naïve CLBP patients from a registry database (2015-2024), reported following STROBE guidelines.

Primary outcome: morphine milligram equivalents (MMEQ).

Secondary outcomes: Numeric Rating Scale (NRS) for pain intensity, Oswestry Disability Index (ODI) for functional disability, cannabis dosing patterns, adverse events, and concomitant medication use. Pre-specified MCID thresholds: ≥50% MMEQ reduction, ≥ 30% NRS reduction, ≥ 10-point ODI improvement. Statistical analyses included paired t-tests for completers and linear mixed-effects models for sensitivity analyses.

Results: Of 1,000 enrolled patients, 638 (63.8%) completed 10-year follow-up. Among completers, MMEQ decreased from 62.8 ± 35.7 to 6.4 ± 7.1 mg/day (- 89.8%, p < 0.001); NRS from 8.71 ± 1.23 to 1.37 ± 1.71 (- 84.2%, p < 0.001); ODI from 52.9 ± 11.9% to 36.8 ± 14.9% (16.1-point reduction, – 30.4%, p < 0.001). MCID responders: 91.2% for MMEQ, 96.6% for NRS, 62.1% for ODI. Substantial polypharmacy reductions occurred: tramadol/tapentadol – 84.0% points (pp), benzodiazepines – 73.5 pp, SSRIs – 71.9 pp, gabapentinoids – 30.7 pp. True tolerability adverse events occurred in 11.4% of visits; serious psychiatric events in 0.02%.

Conclusions: In this uncontrolled observational study, medical cannabis therapy was associated with reductions in opioid use, pain intensity, and functional disability over 10 years, accompanied by polypharmacy reduction and acceptable tolerability. Effect sizes substantially exceeded RCT benchmarks (e.g., – 0.6 NRS difference vs. placebo in a recent phase 3 trial), suggesting observational biases contribute to these findings. These hypothesis-generating data warrant validation in randomized controlled trials.”

https://pubmed.ncbi.nlm.nih.gov/42734834

“In this 10-year single-arm observational study, medical cannabis therapy was associated with reductions in opioid use (− 89.8%), pain intensity (− 84.2%), and functional disability (− 30.4%), with high proportions of patients achieving pre-specified MCID thresholds. Substantial polypharmacy reductions and acceptable tolerability were observed.”

https://link.springer.com/article/10.1007/s00586-026-10290-y

UK Medical Cannabis Registry: An Updated Analysis of Inflammatory Arthritis

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A new analysis from the UK Medical Cannabis Registry reports sustained improvements in pain, sleep, and health-related quality of life among patients with inflammatory arthritis who were prescribed cannabis-based medicinal products.

The study followed 192 patients for up to 24 months. Improvements were reported across multiple pain measures at every follow-up point, including pain severity, pain interference, and overall pain scores. Sleep quality and general quality of life also improved compared with baseline.

Notably, many patients were prescribed THC-containing products, including dried cannabis flower and oils. The findings add long-term real-world evidence that prescribed cannabis medicines may help some people living with inflammatory arthritis.

“Aim: Cannabis-based medicinal products (CBMPs) are an emerging therapeutic option for pain in inflammatory arthritis, yet clinical evidence remains limited. This study aimed to evaluate changes in pain-specific and general health-related outcomes in patients with inflammatory arthritis treated with CBMPs and to characterize the safety profile by examining the incidence and nature of adverse events.

Methods: Patients treated with CBMPs for inflammatory arthritis-associated pain for ⩾24 months were identified from the UK Medical Cannabis Registry. Primary outcomes included changes in patient-reported measures: Brief Pain Inventory (BPI), Pain Visual Analogue Scale (Pain VAS), Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2), EuroQol 5-dimension 5-level (EQ-5D-5L), Generalized Anxiety Disorder-7 (GAD-7), and Single-Item Sleep Quality Scale (SQS) at 1, 3, 6, 12, 18, and 24 months vs baseline. Adverse events were recorded and analysed. Statistical significance was set at P < .050.

Results: A total of 192 patients met inclusion criteria. The CBMP initiation was associated with improvements in BPI Interference, BPI Severity, Pain VAS, SF-MPQ-2, SQS, and EQ-5D-5L index values at all follow-up time points (P < .010) and in GAD-7 scores up to 3 months (P < .001). Twenty-seven patients (14.06%) reported 296 adverse events: 126 (42.57%) mild, 132 (44.59%) moderate, and 38 (12.84%) severe. No life-threatening events occurred.

Conclusion: The CBMP therapy was associated with reductions in pain and improvements in health-related quality of life among individuals with inflammatory arthritis. Although causality cannot be inferred from this observational design, these findings support the need for randomized controlled trials to determine the efficacy of CBMPs for inflammatory arthritis-related pain.”

https://pubmed.ncbi.nlm.nih.gov/42724108

“Overall, results of this study demonstrate reductions in pain severity and improvements in HRQoL for patients receiving CBMP treatment for chronic pain linked to inflammatory arthritis over a period of 24 months of follow-up. The CBMPs were generally well-tolerated, although the risk of AE and individual responses should be considered before commencing CBMP treatment.”

https://journals.sagepub.com/doi/10.1177/11795441261480709

Cannabis as a source of novel therapeutics: A computational study combining LBDD and structure-based docking/dynamics to identify novel drug-like compounds for colorectal cancer

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Cannabis continues to provide researchers with chemical starting points for the development of new cancer therapies. In this 2026 study, scientists examined 33 cannabis-derived compounds with reported antiproliferative activity against HCT-116 colorectal cancer cells, then used computational modeling to investigate their potential interactions with CDK2, an enzyme involved in cell-cycle regulation and cancer-cell proliferation.

Using those cannabis compounds as a foundation, the researchers designed 20 new drug-like molecules. Several were predicted to have stronger antiproliferative activity than the most active compound in the original cannabis-derived dataset, with four candidates — V2, V5, V7 and V8 — also showing favorable predicted pharmacokinetic and drug-like properties.

V7 and V8 emerged as the strongest candidates. Molecular docking and 100-nanosecond molecular-dynamics simulations indicated stable interactions with the active site of CDK2, with V8 showing particularly favorable behavior. The findings suggest that compounds inspired by cannabis chemistry could provide promising leads for the development of new therapeutics targeting colorectal cancer.

“Cannabis represents a valuable source of bioactive compounds with significant therapeutic potential, thanks to its rich phytochemical profile, making it a prime candidate for cancer research.

Our study investigates the potential of cannabis-derived compounds to inhibit cyclin-dependent kinase 2 (CDK2), a crucial regulator of cell-cycle progression and colorectal cancer cell proliferation.

A comprehensive computational workflow integrating 3D-QSAR modeling, molecular docking, molecular dynamics simulations, drug-likeness assessment, and ADMET prediction was employed to investigate a dataset of 33 cannabis-derived compounds. The robustness and predictive performance of the generated CoMFA and CoMSIA models were confirmed through internal and external validation, leave-one-out cross-validation (LOOCV), and Y-randomization tests, yielding excellent statistical parameters for CoMFA (Q2=0.651, R2=0.986, SEE=0.069) and CoMSIA (Q2=0.665, R2=0.985, SEE=0.071).

Using contour map analysis, twenty new molecules (V1-V20) with enhanced antiproliferative activity against the HCT-116 colorectal cancer cell line were developed, and outperformed the original dataset’s most active one. Following drug-likeness screening and ADMET profiling, compounds V2, V5, V7, and V8 emerged as the most promising candidates, exhibiting favorable pharmacokinetic properties and drug-like characteristics.

Molecular docking studies revealed that V7 and V8 exhibit high stability within the CDK2 active site and possess stronger binding affinity than the reference compound. Furthermore, 100 ns molecular dynamics simulations demonstrated that both protein-ligand complexes reached stable conformational states, as confirmed by converged backbone RMSD profiles, low residue fluctuations (RMSF), persistent protein-ligand interactions, and complementary structural descriptors including radius of gyration (Rg), solvent-accessible surface area (SASA), and molecular surface area (MolSA).

Collectively, these analyses confirmed the structural stability and compactness of the investigated complexes throughout the simulation period, with V8 exhibiting the most favorable dynamic behavior.”

https://pubmed.ncbi.nlm.nih.gov/42749433

 “Overall, the present study establishes a robust computational framework for the rational identification and optimization of promising cannabis-derived CDK2 inhibitors for colorectal cancer.”

https://www.sciencedirect.com/science/article/pii/S1687157X26001071?via%3Dihub