Standardized Curcuma longa-Cannabis sativa extract derived from a traditional Thai formulation for psoriasis: anti-inflammatory activity, keratinocyte modulation, and skin-targeted delivery

Posted on by

A new study tested a standardized combination of Curcuma longa (turmeric) and Cannabis sativa derived from a traditional Thai topical formulation for psoriasis. The combined extract contained curcuminoids, ar-turmerone and cannabidiol, including 35.47 mg/g CBD, and was evaluated for anti-inflammatory activity, effects on psoriasis-related keratinocytes and its ability to remain concentrated in the skin.

At 12.5 µg/mL, the combined extract reduced nitric oxide production by 48.97% and PGE₂ production by 91.15%. It also altered psoriasis-associated gene expression in TNF-α/IL-17A-stimulated keratinocytes, showing activity against several biological processes involved in psoriasis.

The skin-delivery experiments found strong deposition of the extract’s markers in the skin, with none detected in the receptor compartment during the 24-hour test. The authors concluded that the standardized turmeric–cannabis combination showed anti-inflammatory, psoriasis-relevant and skin-targeted activity supporting further development as a localized phytotherapeutic approach for psoriasis.

“Ethnopharmacological relevance: Curcuma longa rhizomes and Cannabis sativa leaves are traditionally combined in Thai topical remedies using cottonseed oil. However, the pharmacological basis and dermal delivery of this combination remain unclear.

Aim of the study: This study evaluated a standardized Thai CL-CS combined extract (CLCS) by integrating phytochemical characterization, psoriasis-relevant biological activities, and ex vivo skin deposition and permeation, with comparison to the single extracts.

Materials and methods: CLCS was standardized by validated HPLC using curcuminoids, ar-turmerone, and cannabidiol as markers. Anti-inflammatory activity was evaluated in RAW264.7 macrophages, while psoriasis-relevant activity was assessed in TNF-α/IL-17A-stimulated HaCaT keratinocytes. Skin deposition and permeation were evaluated using porcine ear skin and Franz diffusion cells.

Results: CLCS contained bisdemethoxycurcumin (18.79 ± 1.54 mg/g), demethoxycurcumin (12.89 ± 1.02 mg/g), curcumin (22.12 ± 1.62 mg/g), ar-turmerone (75.35 ± 3.94 mg/g), and cannabidiol (35.47 ± 2.39 mg/g). IC50 values were 41.22 ± 1.70 and 22.91 ± 0.51 μg/mL in HaCaT and RAW264.7 cells, respectively. At 12.5 μg/mL, CLCS inhibited NO and PGE2 production by 48.97 ± 0.88% and 91.15 ± 3.66%, respectively, and modulated psoriasis-associated genes. Cottonseed oil containing 20% DG achieved the highest skin deposition of BCM, DCM, and CM, with no detectable markers in the receptor compartment over 24 h.

Conclusions: Standardized CLCS exhibited anti-inflammatory and psoriasis-relevant activities and preferential skin deposition, supporting its potential as a localized phytotherapeutic approach for psoriasis.”

https://pubmed.ncbi.nlm.nih.gov/42772617

“The present study provides an integrated chemical, biological, and skin-targeted delivery evaluation of a standardized CLCS co-extract derived from a traditional Thai topical formulation. The extract was successfully standardized by its characteristic bioactive constituents derived from both botanical components. CLCS demonstrated anti-inflammatory and psoriasis-relevant biological activities”

https://www.sciencedirect.com/science/article/abs/pii/S0378874126012833?via%3Dihub

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

Posted on by

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

Posted on by

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

Posted on by

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

Need this THC study explained? thcXplained.com

Effectiveness and safety of cannabidiol in adult patients with epilepsy: A multicenter, retrospective study

Posted on by

A new multicenter study found that cannabidiol was associated with substantial seizure reductions in adults living with severe, drug-resistant forms of epilepsy. The study followed 37 adults with Dravet syndrome, Lennox–Gastaut syndrome, or tuberous sclerosis complex who received CBD for at least 12 months.

After six months, 48.6% of patients had at least a 50% reduction in seizure frequency; after 12 months, 45.9% still met that threshold. Caregivers also reported improvements in alertness, behavior, interaction, or daily functioning in 29.7% of patients, while the median number of other antiseizure medications fell from four to three.

The authors concluded that CBD was associated with “clinically meaningful seizure reduction and acceptable tolerability” in this real-world adult population. Adverse events occurred in 64.9% of patients but were mostly mild, and 81.1% remained on CBD at 12 months.

“Objective: Cannabidiol (CBD) has demonstrated promising effectiveness and tolerability as adjunctive treatment in patients with severe childhood epilepsies. This study investigated the effectiveness and tolerability of CBD in adults with a history of Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), or tuberous sclerosis complex (TSC).

Methods: This was a multicenter, retrospective, observational study in adults with diagnosis of DS, LGS or TSC who received at least 12 months of CBD treatment. Medical records were reviewed and baseline characteristics, treatment retention, seizure frequency, cognitive behavioral improvements, concomitant ASM usage, and adverse events were assessed.

Results: Thirty-seven patients (median age 25 years; 67.5% male) with diagnosis of DS, LGS or TSC received CBD for at least 12 months. The CBD median maintenance dose was 10.45 mg/kg/day (IQR 7.455 – 13.975) (median maximum dose 11 mg/kg/day); median follow-up time was 28 months (IQR 22.75-58.25). Seizure frequency was reduced by ≥50% in 48.6% of patients at 6 months and 45.9% at 12 months. No statistically significant differences in median maintenance dose were observed across seizure reduction categories. During CBD treatment, caregivers reported subjective improvements in cognition in 29.7% of patients. Treatment with CBD was significantly associated with a reduction in the median number of concomitant ASMs at the end of follow-up (4 [3, 4]) vs. 3 [3, 4] (p = 0.022). AEs occurred in 64.9% of patients and were mostly mild; 16.2% had AEs leading to treatment discontinuation.

Significance: We present a series of adult patients treated with CBD according to label. The results are similar to those described in children. CBD treatment was associated with clinically meaningful seizure reduction and acceptable tolerability in this real-world cohort of adults with drug-resistant developmental and epileptic encephalopathies. These findings support the potential role of CBD in complex adult DEE populations while highlighting the need for prospective controlled studies to better define its independent treatment effect.

Plain language summary: This study looked at the long-term use of cannabidiol (CBD) in 37 adults with Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex. After 12 months, almost half of the patients had at least a 50% reduction in seizures. Some caregivers also reported improvements in cognition and behavior. Patients were able to reduce the number of other antiseizure medicines they were taking. Side effects were common but mostly mild, although a small number of patients stopped treatment because of them. Overall, CBD appeared effective and reasonably well tolerated, but further controlled studies are needed.”

https://pubmed.ncbi.nlm.nih.gov/42765195

“CBD has demonstrated promising effectiveness and tolerability in adult patients with a history of DS, LGS, or TSC. Treatment with CBD was associated with reductions in seizure frequency and in concomitant ASMs, which could improve treatment retention and reduce AEs. The findings support a growing body of evidence highlighting the efficacy of CBD across age groups and epilepsy etiologies in real-world clinical practice.”

https://onlinelibrary.wiley.com/doi/10.1002/epi4.70331

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

Posted on by

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

Posted on by

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

Posted on by

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

Posted on by

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

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

Posted on by

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