Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Evaluating the impact of cannabinoid extracts on chronic pain and quality of life in endometriosis patients – a pilot study

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Women with endometriosis and chronic pelvic pain experienced significant improvements after adding a balanced oral THC cannabis extract to their existing treatment. In this prospective pilot study, 27 women completed three months of treatment, with benefits appearing within the first month and continuing through the study period.

Pain intensity fell significantly, along with the number of pain days and the need for conventional pain medicines. Use of both NSAIDs and opioid analgesics decreased, while fatigue, anxiety, central sensitization and pain-related disability also improved.

Quality of life improved across every measured EHP-30 domain, including pain, emotional well-being, work impairment, self-image and sexual relationships. The authors concluded that balanced THC cannabinoid medicines appear to be a potentially effective adjunct treatment for chronic pelvic pain and related symptoms in women with endometriosis.

“Endometriosis is a chronic gynecological disorder characterized by persistent pain and impaired quality of life, with limited effective treatment options. Emerging evidence indicates that cannabinoids may provide analgesic and symptom-relieving effects in chronic pain conditions.

This prospective single-center cohort study investigated the effects of standardized oral cannabis extracts (cannabinoid-based medicinal products, CBMPs) on pain and quality of life in women with endometriosis.

Thirty premenopausal women aged 18-45 years with confirmed endometriosis and chronic pelvic pain were enrolled; 27 completed the 3-month treatment period. Participants received oral CBMPs containing a balanced THC: CBD ratio. Pain intensity, frequency of pain episodes, analgesic use, fatigue, anxiety, central sensitization, disability, and quality of life were assessed using validated questionnaires (VAS, EHP-30, PDI, CFS, GAD-7, CSI).

Significant improvements were observed after one month of treatment, with continued benefit over three months. Pain intensity decreased markedly (p = 0.0004), accompanied by reductions in the number of pain days and analgesic use, including both NSAIDs (e.g., ibuprofen, diclofenac) and opioid analgesics (e.g., tramadol, tilidin, oxycodone) (p < 0.001). Fatigue (p = 0.0013), anxiety (p < 0.0001), central sensitization (p < 0.0001), disability (p < 0.0001), and overall quality of life (EHP-30) improved significantly.

Treatment was well tolerated; side effects were predominantly mild (severity score 1 on a 0-3 scale) and transient, occurring mainly during the titration phase and declining thereafter. Although limited by its single-center design, lack of placebo control, and short follow-up, this study provides preliminary evidence that oral CBMPs may represent a safe and effective adjunct therapy for managing pain and related symptoms in women with endometriosis. Larger randomized controlled trials are warranted to confirm these findings and establish optimal dosing strategies.”

https://pubmed.ncbi.nlm.nih.gov/42771648

“In conclusion, oral CBMPs with balanced THC: CBD ratios seem to be a safe and potentially effective adjunct therapy for chronic pelvic pain and related symptoms in women with endometriosis. By targeting both nociceptive and neuropsychological aspects of the condition, CBMPs can supplement existing pharmacological and lifestyle strategies, providing a more comprehensive approach to symptom management. These findings establish a basis for future controlled studies to refine dosing, investigate mechanisms, and assess long-term outcomes in this complex patient group.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356768

Modulation of spatial learning and memory by cannabinoid-estrogen interaction in an AD-like cognitive impairment: The role of cannabinoid receptors and BDNF protein

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A 2026 study found that a THC-standardized marijuana extract improved spatial learning and memory in an Alzheimer’s-like model of cognitive impairment. Researchers tested the extract in rats exposed to amyloid-beta, a protein closely associated with Alzheimer’s disease, and observed improvements in memory performance.

The cognitive improvements were accompanied by changes in cannabinoid receptor signaling and in BDNF, or brain-derived neurotrophic factor, a protein that supports neuron survival, brain plasticity, learning, and memory. The findings suggest that the brain’s cannabinoid system and BDNF may be involved in the neuroprotective-like effects observed with the THC-standardized extract.

The researchers also examined the interaction with estrogen and found that adding estradiol did not produce an additional synergistic improvement. As the authors concluded, “These preclinical findings suggest that a THC-standardized marijuana extract may exert neuroprotective-like effects in an AD-like cognitive impairment model.”

“Alzheimer’s disease (AD) is an increasingly prevalent neurodegenerative disorder worldwide, with women showing a higher risk of developing the disease. The decline in steroid hormones after menopause may contribute to the increased susceptibility of women to neurodegenerative conditions.

In parallel, cannabis-derived compounds have been reported to alleviate certain symptoms associated with neurological disorders. The present study was designed to investigate the effects of marijuana extract on cognitive impairment and hippocampal molecular markers in an ovariectomized AD-like rat model, and to evaluate whether co-administration with estradiol modifies these effects.

The marijuana extract used in this study was characterized by HPLC and was found to contain 8.5% Δ9-THC. AD-like cognitive impairment pathology was induced by intra-hippocampal administration of Aβ25-35 in OVX rats. Animals were treated with marijuana extract (60 mg/kg/day, corresponding to approximately 5.1 mg/kg/day Δ9-THC) either alone or in combination with 17β-estradiol (1 mg/kg every 4 days) for 28 days. Cognitive performance was evaluated using the Morris water maze (MWM). In addition, hippocampal CB1/CB2 receptor expression and BDNF protein levels were measured to examine potential molecular associations.

Our findings showed that chronic administration of the marijuana extract improved Aβ25-35-induced deficits in spatial learning and memory.

Alterations in CB1 receptor expression and BDNF levels accompanied these behavioral effects. Notably, co-treatment with estradiol did not produce a synergistic effect, suggesting a complex interaction between cannabinoid-related and estrogen-related signaling pathways.

These preclinical findings suggest that a THC-standardized marijuana extract may exert neuroprotective-like effects in an AD-like cognitive impairment model. However, because the extract was not fully phytochemically characterized and the mechanistic analyses were correlational, the results should be interpreted cautiously. Further studies are needed to clarify the underlying mechanisms and translational relevance of these findings.”

https://pubmed.ncbi.nlm.nih.gov/42756662

“In conclusion, chronic administration of THC-standardized marijuana extract improved spatial learning and memory performance in the AD-like cognitive impairment model, and these behavioral changes were accompanied by alterations in hippocampal CB1/CB2 gene expression and BDNF protein levels.”

https://www.ibroneuroreports.org/article/S2667-2421(26)00149-1/fulltext

Cannabinoids in Cancer: Molecular Mechanisms of Tumor Cell Death and Translational Opportunities

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Cannabinoids can attack cancer cells through far more than a single mechanism. This 2026 review describes how natural and synthetic cannabinoids can suppress tumor-cell growth, angiogenesis and metastasis while activating multiple forms of regulated cancer-cell death, including apoptosis, autophagy-dependent cell death, necroptosis, ferroptosis and parthanatos.

The researchers detail an interconnected network of molecular pathways affected by cannabinoids, including PI3K/AKT/mTOR, MAPK/ERK, NF-κB, TRIB3/AKT/mTORC1 and ceramide/ROS signaling. These pathways control whether cancer cells survive, proliferate, respond to stress or undergo programmed destruction, giving cannabinoids multiple potential points of attack against malignant cells.

The review also finds that cannabinoids may enhance conventional anticancer treatments by engaging complementary cell-death pathways. The authors conclude that cannabinoids represent promising anticancer agents and therapeutic adjuvants, with much of the direct anticancer evidence still coming from preclinical research and clinical translation now depending on better dosing, formulations and controlled human studies.

“Cannabinoids are terpenophenolic compounds derived from Cannabis sativa L. that exert a broad range of biological and pharmacological activities. Increasing evidence highlights their potential as modulators of cancer progression specifically through the suppression of tumor cell growth, angiogenesis, and metastasis across multiple tumor models.

This review provides a comprehensive overview of the molecular mechanisms by which natural and synthetic cannabinoids induce regulated cancer cell death.

Current evidence demonstrates that cannabinoids regulate multiple forms of cancer cell death, including apoptosis, autophagy-dependent cell death, necroptosis, ferroptosis, and parthanatos. These effects are mediated through complex and interconnected signaling pathways such as TRIB3/AKT/mTORC1, PI3K/AKT/mTOR, MAPK/ERK, NF-κB, ERK/JNK/p38-MAPK, and ceramide/Raf1/ERK/ROS.

In addition to their direct antitumor effects, cannabinoids can enhance the efficacy of conventional anticancer therapies through the coordinated regulation of complementary cell death pathways. They also provide clinically relevant supportive benefits in palliative care, alleviating chemotherapy-induced nausea, cachexia, and mood or sleep disturbances.

Collectively, these findings identify cannabinoids as promising anticancer agents and therapeutic adjuvants, predominantly in the preclinical setting. However, significant challenges remain regarding their safety, optimal dosing, formulation, and clinical efficacy. Further mechanistic studies, rigorous preclinical research, and well-designed clinical trials are required to establish the translation of cannabinoid-based therapies into precision oncology.”

https://pubmed.ncbi.nlm.nih.gov/42793092

“The cannabis plant, a member of the Cannabaceae family, has been traditionally utilized for centuries for spiritual and remedial healing.”

“The anticancer activity of cannabinoids was discovered in 1975 by Munson et al.. Cannabinoids suppress cancer cell proliferation, angiogenesis, tumor invasion, metastasis, and stemness while inducing different modes of cell death pathways.”

“In summary, this review highlights the growing body of evidence supporting the ability of cannabinoids to induce multiple forms of cell death across a broad spectrum of cancer types. Through the modulation of diverse molecular and signaling pathways, cannabinoids have emerged as promising anticancer agents, mostly in preclinical models, with the potential to target tumor growth, survival, and progression, ultimately triggering diverse cell death mechanisms.”

https://www.mdpi.com/2218-273X/16/9/1260

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

An Ultra-Low Dose of ∆9-Tetrahydrocannabinol Alleviates Alzheimer’s Disease-Related Cognitive Impairments and Modulates TrkB Receptor Expression in a 5XFAD Mouse Model

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An ultra-low dose of Δ9-THC improved Alzheimer’s disease-related cognitive impairment in 5xFAD mice, including animals treated after memory problems were already established. The study found improvements in learning and memory without relying on repeated high-dose THC exposure.

The researchers also found changes in TrkB receptor expression, a signaling pathway closely tied to brain plasticity, learning, memory, and neuronal survival. These changes suggest that THC’s effects may involve more than temporary symptom relief and may influence mechanisms connected to cognitive function.

The findings add to a growing body of preclinical research showing that very low doses of THC can produce different biological effects than higher doses, particularly in the aging and Alzheimer’s-disease brain. In this model, a single ultra-low dose was enough to improve cognitive performance and alter a key neurotrophic signaling pathway.

“Alzheimer’s disease (AD) is the most common form of dementia, but there is still no available treatment.

Δ9-tetrahydrocannabinol (THC) is emerging as a promising therapeutic agent.

Using THC in conventional high doses may have deleterious effects. Therefore, we propose to use an ultra-low dose of THC (ULD-THC). We previously published that a single injection of ULD-THC ameliorated cognitive functioning in several models of brain injuries as well as in naturally aging mice.

Here, 5xFAD AD model mice received a single treatment of ULD-THC (0.002 mg/kg) after disease onset and were examined in two separate experiments for cognitive functions, neurotropic, and inflammatory factors in the hippocampus.

We show that a single injection of ULD-THC alleviated cognitive impairments in 6- and 12-month-old 5xFAD mice. On the biochemical level, our results indicate an imbalance between the truncated TrkB receptor isoform and the full receptor, with AD mice showing a greater tendency to express the truncated receptor, and ULD-THC improved this imbalance. We also investigated the expression of three AD-related inflammatory markers and found an ameliorating effect of ULD-THC.

The current research demonstrates for the first time the beneficial effects of a single ultra-low dose of THC in a mouse model of AD after disease onset.”

https://pubmed.ncbi.nlm.nih.gov/36012711

“The current research demonstrates for the first time the beneficial effects of a single ultra-low dose of THC in a mouse model of AD after disease onset. As THC is a cheap, widely available substance already approved for use in other conditions, this research brings us closer to understanding its mechanisms and will possibly lead to new treatments.”

https://www.mdpi.com/1422-0067/23/16/9449/htm

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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

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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

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

Delta9-tetrahydrocannabinol induces apoptosis in C6 glioma cells

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Researchers investigated whether Δ9-tetrahydrocannabinol (THC) could directly affect the survival of C6 glioma cells, a laboratory model of brain cancer. THC produced a dramatic, dose-dependent decline in cell metabolism and triggered apoptosis, or programmed cell death. The researchers confirmed this through several markers, including loss of membrane symmetry and the characteristic fragmentation of DNA seen during apoptosis.

The study also found that THC stimulated sphingomyelin breakdown, a process linked to ceramide signaling and cell death. Importantly, THC induced apoptosis in several transformed neural cell types but did not produce the same apoptotic effect in primary astrocytes or neurons. Even though the glioma cells expressed CB1 receptors, blocking CB1 did not prevent THC-induced apoptosis, suggesting that the effect occurred through a CB1 receptor-independent mechanism.

The authors concluded that THC’s antiproliferative effect could provide a basis for exploring new therapeutic applications of cannabinoids, particularly because normal primary astrocytes and neurons were resistant to THC-induced apoptosis in this model.

“delta9-Tetrahydrocannabinol (THC), the major active component of marijuana, induced apoptosis in C6.9 glioma cells, as determined by DNA fragmentation and loss of plasma membrane asymmetry. THC stimulated sphingomyelin hydrolysis in C6.9 glioma cells. THC and N-acetylsphingosine, a cell-permeable ceramide analog, induced apoptosis in several transformed neural cells but not in primary astrocytes or neurons. Although glioma C6.9 cells expressed the CBI cannabinoid receptor, neither THC-induced apoptosis nor THC-induced sphingomyelin breakdown were prevented by SR141716, a specific antagonist of that receptor. Results thus show that THC-induced apoptosis in glioma C6.9 cells may rely on a CBI receptor-independent stimulation of sphingomyelin breakdown.”

https://pubmed.ncbi.nlm.nih.gov/9771884

“In the course of our studies on the metabolic effects of cannabinoids on C6 glioma cells we have observed that cannabinoids inhibit the growth of these cells.”

“The antiproliferative effect of THC described in the present report might provide the basis for a new therapeutic application of cannabinoids, especially since primary astrocytes and neurons are resistant to the apoptotic action of THC.”

“These observations thus indicate that THC-induced glioma cell death is a process that differs from necrotic death and displays several features characterizing an apoptotic, programmed cell death event.”

https://febs.onlinelibrary.wiley.com/doi/10.1016/S0014-5793%2898%2901085-0

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