Tag Archives: THC

Computational and Comparative In Vitro Evaluation of GC-MS Profiled Cannabis sativa Inflorescence Extracts’ Metabolites on Selected Diabetes Therapeutic Targets

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A new 2026 study found that Cannabis sativa flower extracts showed activity against several biological targets involved in diabetes. Researchers tested the extracts for effects on carbohydrate-digesting enzymes, glucose uptake and oxidative stress, then used computational modeling to examine how 36 cannabis metabolites interacted with diabetes-related proteins.

The hexane extract showed the strongest overall activity, including inhibition of α-amylase and α-glucosidase and the greatest increase in glucose uptake in the yeast model. Glucose uptake with the hexane extract rose from 25% at 62.5 µg/mL to 54% at 500 µg/mL.

The docking analysis identified several cannabinoids — including Δ9-THC, 8-hydroxy-Δ9-THC, cannabivarin and tetrahydrocannabinol-7-oic acid — as promising candidates for further study against diabetes-related targets such as DPP-4, SGLT-2 and PTP1B. The authors concluded that cannabis inflorescences may be a promising source of compounds for future antidiabetic drug research.

“Cannabis sativa, a medicinal plant rich in cannabinoids, terpenoids, and flavonoids, has been shown to have various pharmacological activities.

This study investigated the antidiabetic potential of C. sativa inflorescence extracts using in vitro and computational models.

Dried C. sativa inflorescences were extracted sequentially with hexane, dichloromethane, and methanol, before their metabolites were identified by GC-MS. The extracts were tested for α-amylase and α-glucosidase inhibition, glucose uptake activity, and antioxidant effects using DPPH and nitric oxide (NO) inhibition assays. Thirty-six metabolites were further docked against diabetes-related proteins.

Among the extracts, the hexane extract showed the strongest bioactivity with notable α-amylase inhibition (IC50: 727 µg/mL), DPPH free radical scavenging (IC50: 478.62 µg/mL), and nitric oxide inhibition activity (IC50: 356.51 µg/mL). Docking analyses revealed strong binding affinities for 8-hydroxy-delta-9-THC, cannabivarin, and 9-tetrahydrocannabinol with DPP-4, PTP1B, and other target proteins.

These findings highlight the potential of C. sativa inflorescences as a source of antidiabetic agents, warranting further in vivo and clinical validation.”

https://pubmed.ncbi.nlm.nih.gov/42763912

“This study provides preliminary evidence that C. sativa inflorescence extracts contain phytoconstituents with antioxidant, enzyme-inhibitory, and potential antidiabetic activities under the experimental conditions investigated. Among the extracts, the hexane extract exhibited the strongest enzyme inhibition and capacity to interact with free radicals.

In addition, compounds including Δ9-tetrahydrocannabinol, 8-hydroxy-Δ9-THC, cannabivarin, and tetrahydrocannabinol-7-oic acid exhibited favorable binding affinities toward diabetes-related protein targets, identifying them as promising candidates for further investigation.”

https://onlinelibrary.wiley.com/doi/10.1002/cbdv.71684

Dose Response Relationship of Medical Cannabis and Symptom Control in Patients With Pancreatic Cancer: An Analysis of the CANPAN Trial

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A new analysis of the CANPAN trial found a clear dose-response relationship between THC and symptom improvement in patients with pancreatic cancer. The trial enrolled 32 cannabis-naïve patients with newly diagnosed locally advanced or metastatic pancreatic adenocarcinoma, and 23 used medical cannabis during their assigned eight-week treatment period.

Higher average daily THC doses were significantly associated with greater improvements in anxiety and insomnia. Patients receiving at least 10 mg of THC per day improved in an average of four symptoms, compared with 2.1 symptoms among patients receiving less than 10 mg per day.

The authors say these findings provide important dose-response information for future pancreatic-cancer trials, particularly for psychological symptoms and multi-symptom control. The results add to evidence from the CANPAN trial that personalized medical cannabis may have a role in managing symptoms experienced by people undergoing treatment for pancreatic cancer.

“Background: In a pilot waitlist-control randomized trial, a personalized medical cannabis intervention improved certain symptoms among patients with pancreatic cancer over 8 weeks. Longer-term and dose-response data can guide future trial design.

Methods: CANPAN enrolled 32 cannabis-naïve patients with newly diagnosed locally advanced/metastatic pancreatic adenocarcinoma (NCT06605430). Patients were randomized to early (0-8 weeks) or delayed (9-16 weeks) cannabis intervention. Primary efficacy results over the first 8 weeks were previously reported. We investigated cannabis use and patient-reported outcome (PRO) completion over 9-16 weeks, and the relationship between tetrahydrocannabinol (THC) dose and symptom efficacy.

Results: Among 32 participants, 23 (72%) used cannabis during their assigned 8-week period (12/16 in early arm and 11/16 in delayed arm). Of these, 16 (50%) had both pre-cannabis and 8-week post-cannabis initiation PRO data available. At the end of the 16-week study period, PRO data were available for 16 (50%) participants (9/16 early arm, 7/16 delayed arm). Median daily THC dose 4 weeks after starting cannabis was similar in early vs delayed arms (10 mg vs 9.3 mg). A higher average daily THC dose was associated with improvements in anxiety (r 0.52, p = 0.038) and insomnia (r 0.53, p = 0.033). A ≥ 10 mg daily THC dose (vs < 10 mg) was associated with mean improvement in 4 vs 2.1 symptoms.

Conclusions: The 50% complete data availability at 16 weeks, dose-response relationship with psychological symptoms, and threshold dose for multi-symptom efficacy will guide future trials. Similar cannabis use patterns across arms raise confidence in the waitlist-control design.”

https://pubmed.ncbi.nlm.nih.gov/42767994

https://academic.oup.com/oncolo/advance-article/doi/10.1093/oncolo/oyag374/8826188

Delta-9-tetrahydrocannabinol alleviates inflammation by modulating immune responses in LPS-induced murine inflammation model

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Delta-9-THC reduced inflammatory immune signaling across human immune cells and a mouse model of systemic inflammation. In LPS-stimulated cells, THC markedly suppressed type I interferon-related genes and pro-inflammatory cytokines including IL-1β and TNF-α, while also reducing immune-cell activation markers.

The effects extended beyond isolated cells. In mice exposed to systemic inflammation, THC reduced activation of splenic myeloid cells and T cells. Brain analysis also showed reduced neuroinflammatory signaling, including lower expression of inflammatory mediators, while pathways associated with neurogenesis, synaptic plasticity and neuronal function were enriched.

Importantly, the researchers describe THC’s effects as modulation rather than indiscriminate immune suppression, concluding that THC appears to dampen excessive inflammatory signaling while influencing cellular stress-adaptation pathways. They say these findings support further investigation of cannabinoid signaling in chronic inflammatory, neuroimmune and neurodegenerative disorders.

“Introduction: Δ9-Tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, has been reported to modulate immune responses; however, its effects on complex innate immune signaling pathways and inflammation remain incompletely understood. Here, we investigated the immunomodulatory effects of THC on lipopolysaccharide (LPS)-induced inflammation across cellular and in vivo models.

Methods: We integrated transcriptomic, cellular, and in vivo approaches to characterize the effects of THC on innate immune activation. Human THP-1 monocytic cells were treated with THC in the presence or absence of LPS, followed by transcriptomic and gene expression analyses to evaluate inflammatory, type I interferon, unfolded protein response (UPR), and autophagy pathways. Findings were validated in primary human monocytes by assessing immune activation markers. The effects of chronic THC exposure were further evaluated in a murine model of systemic inflammation by examining splenic myeloid and T-cell activation. RNA sequencing of brain tissue was performed to assess the effects of THC on neuroinflammatory and neuronal pathways.

Results: THC induced a stress-adaptive transcriptional program in THP-1 cells, characterized by upregulation of genes associated with the UPR and autophagy pathways. In contrast, THC markedly suppressed LPS-induced type I interferon-stimulated genes (ISGs) and pro-inflammatory cytokines, including IL-1β and TNF-α. In primary human monocytes, THC significantly reduced the expression of activation markers CD80, CD83, and CD209. Consistent with these findings, chronic THC exposure attenuated the activation of splenic myeloid and T cells in mice subjected to systemic inflammation. Brain transcriptomic analysis further demonstrated reduced expression of neuroinflammatory pathways following THC exposure, accompanied by enrichment of pathways associated with neurogenesis and synaptic plasticity.

Discussion: Our findings demonstrate that THC exerts broad immunomodulatory effects characterized by suppression of inflammatory and type I interferon responses while promoting cellular stress-adaptation pathways. These effects were observed across human monocytic cells, primary monocytes, and peripheral immune populations in vivo, and were accompanied by reduced neuroinflammatory signaling and increased neuronal plasticity-associated pathways in the brain. Together, these findings provide mechanistic insight into the immunomodulatory actions of THC and support further investigation of cannabinoid signaling as a potential regulator of chronic inflammatory and neuroimmune disorders.”

https://pubmed.ncbi.nlm.nih.gov/42818626

“Chronic THC exposure reduces LPS-induced immune activation in vivo.”

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1856131/full

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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

Cannabinoids and therapeutic potential in neuropsychiatry

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Cannabinoids are already used therapeutically in several areas of medicine, and a new review examines how that potential may extend into neuropsychiatry. The authors look beyond cannabis as a single drug, focusing instead on its individual cannabinoids and how different components may contribute to neurological and psychiatric effects.

The review highlights cannabidiol as the cannabinoid with the clearest established role in certain seizure disorders, while examining the broader literature on cannabinoids in neuropsychiatric illness. The authors argue that cannabis is more pharmacologically complicated than any one cannabinoid and that its therapeutic potential may depend on interactions among multiple plant components.

One of the review’s most important points is that combinations of cannabis components may ultimately prove more useful than isolated compounds alone. Rather than dismissing cannabis as having no medical utility in neuropsychiatry, the authors call for approaches that better investigate and use the therapeutic attributes of the plant.

“Cannabinoids have therapeutic utility in some specific areas of medicine, including as an anti-nausea adjunct for chemotherapy and as an anti-inflammatory agent, among others. However, as a therapeutic agent in neuropsychiatric conditions, the data is more limited. Cannabis itself is viewed as a recreational drug of abuse with no medical utility; however, the reality may be more complex when considering individual components of the plant.

Cannabinoid components may have some benefit as therapeutic agents in neuropsychiatry, with cannabidiol most often purported to be a therapeutic agent for some seizure disorders. However, recent studies suggest that the cannabis plant is proving to be broader and more complicated in how it delivers potential therapeutic effects. It may be that a combination of components is more effective than any one component.

This chapter reviews the medical usage of cannabinoids in neuropsychiatric illness, as reported in the literature, and proposes future approaches that may more effectively avail the attributes of this plant.”

https://pubmed.ncbi.nlm.nih.gov/42767714

“Cannabinoid treatments are carving a noteworthy niche in the pharmaceutical repertoire, offering new hope for conditions that have been historically difficult to manage, such as comorbid anxiety and epilepsy.”

https://www.sciencedirect.com/science/chapter/bookseries/abs/pii/S0074774226001303?via%3Dihub

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

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