Tag Archives: cannabis

Effect of solvent polarity on phenolic antioxidant extraction from Cannabis sativa L. leaves and inflorescences: mixture design optimization and HPLC-DAD/ESI-MS2 profiling

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A new 2026 study shows that how cannabis is extracted can dramatically change which beneficial compounds are recovered. Researchers tested water, ethanol and acetone mixtures on Cannabis sativa leaves and inflorescences and found that solvent composition significantly affected total phenolics, cannabinoids and antioxidant activity.

Inflorescences produced their highest total phenolic content — 16.05 mg GAE/g dry weight — with an acetone-rich mixture, while leaves reached 13.65 mg GAE/g with one-third ethanol and two-thirds acetone. Chemical profiling identified 32 compounds, including phenolic acids, flavonoids, hydroxycinnamic acid amides, lignanamides and cannabinoid derivatives.

The extracts also showed notable antioxidant activity across DPPH, ABTS, FRAP, CUPRAC and TAC assays. The authors concluded that cannabis leaves and flowers may be valuable targeted sources of antioxidant phytochemicals for pharmaceutical, nutraceutical and cosmetic applications.

“Cannabis (Cannabis sativa L.) is a source of bioactive compounds with promising applications in the nutraceutical, pharmaceutical, and cosmetic fields.

Applying a mixture design approach with three solvents (water, acetone and ethanol), this study investigated how solvent composition modulates the recovery of phenolic compounds from cannabis inflorescences and leaves. Extracts were assessed for total phenolic content (TPC) and antioxidant activities using DPPH, ABTS, FRAP, CUPRAC, and TAC assays, and their chemical profiles were characterized by HPLC-DAD/ESI-MS2.

Solvent composition significantly affected extraction efficiency across plant organs. For inflorescences, the highest TPC value (16.05 mg GAE per g dry weight) was obtained with an acetone-enriched mixture (1/6 water-1/6 ethanol-2/3 acetone), whereas leaves reached their maximum (13.65 mg GAE per g DW) with 1/3 ethanol-2/3 acetone.

Multi-response optimization identified 1/3 water-1/3 ethanol-1/3 acetone for inflorescences and 50% water-30% ethanol-20% acetone for leaves as the optimal solvent mixtures.

HPLC-DAD/ESI-MS2 analysis identified 32 compounds belonging to several classes, including phenolic acids, flavonoids, hydroxycinnamic acid amides, lignanamides, and cannabinoid derivatives. These classes showed diverse content depending on the solvent and plant matrix. The acetone rich mixture produced the highest total cannabinoids (10.56 and 8.45 mg CBN equivalents per g dry weight) for inflorescences and leaves, respectively.

These results reveal clear organ and solvent-dependent selectivity in Moroccan Cannabis. These differences were reflected in the antioxidant activities, with extracts showing notable reducing and radical-scavenging capacities across DPPH, ABTS, FRAP, CUPRAC, and TAC assays.

These findings support the targeted valorization of cannabis leaves and inflorescences as sources of antioxidant phytochemicals for pharmaceutical and cosmetic applications.”

https://pubmed.ncbi.nlm.nih.gov/42751042

“The chemical diversity of Cannabis sativa metabolites has stimulated extensive research into their extraction and characterization. In this study, water, ethanol, and acetone were combined to enhance the extraction of phenolic compounds and antioxidants from Cannabis sativa L. leaves and inflorescences.

Multi-response optimization showed that each plant matrix required a specific optimal solvent mixture, confirming matrix-dependent extraction behavior: 1/3 water–1/3 acetone–1/3 ethanol for inflorescences and 50% water–30% ethanol–20% acetone for leaves. HPLC-DAD/ESI-MS2 enabled the tentative identification of several compound classes, including cannabinoids, hydroxycinnamic acid amides, flavonoids, and lignanamides. Inflorescences were characterized by higher total cannabinoid contents, whereas leaves contained higher levels of hydroxycinnamic acid amides. These differences highlight both the importance of solvent selection and the distinct chemical composition of Cannabis sativa L. organs.

Overall, these results support the potential valorization of the optimized Cannabis sativa leaf and inflorescence extracts as sources of antioxidant and bioactive compounds for prospective applications in natural cosmetic formulations, such as antioxidant creams, serums or other topical skincare products, as well as in nutraceutical formulations, including functional supplements enriched with plant-derived antioxidants. However, additional studies on formulation stability, bioavailability, efficacy, and safety are required before practical application.”

https://pubs.rsc.org/ra/article/doi/10.1039/d6ra05874d/1356587/Effect-of-solvent-polarity-on-phenolic-antioxidant

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Need this THC study explained? thcXplained.com

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Combined Cannabidiol and Δ9-Tetrahydrocannabinol Modulate Inflammation and Nociceptive Signaling in Human Dental Pulp Cells

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A new study using human dental pulp cells found that combining cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) produced stronger anti-inflammatory effects than either cannabinoid alone. The combination reduced the pro-inflammatory cytokines IL-6, IL-12, and IL-1β while increasing the anti-inflammatory cytokine IL-10.

CBD and THC together also influenced important pathways involved in pain signaling and healing. Researchers reported increased expression of the cannabinoid receptors CNR1 and CNR2, modulation of TRPV1, and enhanced cell proliferation and migration. The combination also promoted mineralized nodule formation and increased markers associated with odontogenic differentiation and new blood-vessel formation.

The researchers concluded that combined CBD and THC show promise for promoting dental pulp healing by simultaneously influencing inflammation, nociceptive signaling, tissue repair, angiogenesis, and cell migration. The findings provide new evidence that cannabinoids may have potential applications in future vital pulp therapies designed to preserve and regenerate living dental tissue.

“Introduction: Dental pulp inflammation, caused by caries, trauma, or restorative operations, produces pain and slows regeneration. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), cannabinoids of Cannabis sativa, have effects on inflammation and pain relief. However, the impact of these factors on dental pulp healing is not understood. This study investigated the combined effects of CBD and THC in controlling inflammation and nociception during dental pulp repair.

Methods: Human dental pulp cells were stimulated with lipopolysaccharide (LPS) and treated with CBD (2.5 μg/mL), THC (0.6 μg/mL), and their combination. Pro-inflammatory cytokines (IL-6, IL-12 and IL-1β) and anti-inflammatory cytokine IL-10 were analysed using qPCR and ELISA, while anti-nociceptive markers (CNR1, CNR2, and TRPV1) were evaluated by qPCR and Western blot. Cell viability, proliferation, and migration assays were performed to evaluate treatment effects on cellular behaviours associated with pulpal repair and regenerative potential.

Results: Compared with either treatment alone, the CBD/THC combination more effectively attenuated pro-inflammatory cytokines IL-6, IL-12, and IL-1β, enhanced CNR1 and CNR2 expression, modulated TRPV1, and increased IL-10 expression. Viability assays determined optimal non-cytotoxic concentrations for treatment. The combination enhanced cell proliferation and migration, promoted mineralized nodule formation, and significantly upregulated markers associated with tissue repair, odontogenic differentiation (DMP1), and angiogenesis (VEGF and bFGF).

Conclusion: Combined CBD and THC show promise for promoting dental pulp healing by modulating inflammation and nociceptive signaling, while supporting odontogenic differentiation, angiogenesis, and cell migration in human dental pulp cells. These findings provide in vitro evidence supporting combined cannabinoid treatment as a therapeutic strategy for vital pulp therapies.”

https://pubmed.ncbi.nlm.nih.gov/42722230

https://www.jendodon.com/article/S0099-2399(26)00500-5/abstract

Cannabis, a Miracle Drug with Polyvalent Therapeutic Utility: Preclinical and Clinical-Based Evidence

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/WebMaterial/ShowPic/1319420“Cannabis sativa L. is an annual herbaceous dioecious plant which was first cultivated by agricultural human societies in Asia. Over the period of time, various parts of the plant like leaf, flower, and seed were used for recreational as well as therapeutic purposes. The main chemical components of Cannabis sativa are termed as cannabinoids, among them the key psychoactive constituent is Δ-9-tetrahydrocannabinol and cannabidiol (CBD) as active nonpsychotic constituent. Upon doing extensive literature review, it was found that cannabis has been widely studied for a number of disorders. Very recently, a pure CBD formulation, named Epidiolex, got a green flag from both United States Food and Drug Administration and Drug Enforcement Administration for 2 rare types of epilepsies. This laid a milestone in medical cannabis research.

This review intends to give a basic and extensive assessment, from past till present, of the ethnological, plant, chemical, pharmacological, and legal aspects of C. sativa. Further, this review contemplates the evidence the studies obtained of cannabis components on Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, multiple sclerosis, emesis, epilepsy, chronic pain, and cancer as a cytotoxic agent as well as a palliative therapy. The assessment in this study was done by reviewing in extensive details from studies on historical importance, ethnopharmacological aspects, and legal grounds of C. sativa from extensive literature available on the scientific databases, with a vision for elevating further pharmaceutical research to investigate its total potential as a therapeutic agent.”

https://pubmed.ncbi.nlm.nih.gov/34676349/

“This study has analyzed and reviewed the historical, botanical, chemical, ethnopharmacological, and legal aspects of C. sativa from the first human use to the present medical applications with an analysis of its multiple therapeutic applications for various diseased conditions in the contemporary scientific context. There is an abundance of support for its several medicative uses as well as a possible benefit in various diseased conditions. Extensive pharmacological examination is still needed to better understand the clinical significance and uses of active cannabinoids in the treatment and prevention of chronic diseases. Also, cannabis can be chemically standardized and under prescription can be used. With the majority of the United States currently legalizing medicinal cannabis and/or restricted CBD-only use, physicians need to be educated on the history and correct clinical use of cannabis, as a result of which patients can know more and more about possible treatment utilizing cannabis. Medical cannabis has shown to have clinical efficacy in our past, and in present, data show its therapeutic effects. Extensive research in the field of cannabis can be very fruitful for the medicine world.”

https://www.karger.com/Article/FullText/515042