Insights Into Cannabis and Cannabinoids: Chemical Properties, Legal Perspectives, and Therapeutic Applications

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“Cannabis sativa L. has been used for thousands of years in various cultural, medical, and industrial settings. This review brings together evidence from historical records, plant chemical studies, clinical trials, and laws to explain the chemical properties, healing potential, and regulatory environment of cannabis and its components.

We look at over 500 identified compounds, including cannabinoids (CBs), terpenes, flavonoids, and alkaloids, along with their effects on health. The therapeutic areas covered include chronic pain, epilepsy, cancer, mental health issues, and inflammation. We also address side effects, interactions with other drugs, and approved CB-based medications.

Despite the various healing effects, gaps still exist in our understanding of the best dosing, long-term safety, and standardized product formulations. This review highlights current research directions and emphasizes the need for thorough randomized controlled trials to support the evidence-based use of cannabis in modern medicine.”

https://pubmed.ncbi.nlm.nih.gov/41822997

https://onlinelibrary.wiley.com/doi/10.1002/cbdv.202503030

Inhibitory effects of Δ8-tetrahydrocannabinol on nicotine metabolism and implications as a smoking cessation agent

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“Tobacco use remains the leading cause of preventable death worldwide. The major metabolic pathway for nicotine, the addictive component in tobacco, is via cytochrome P450 (CYP) 2A6-mediated metabolism to cotinine.

Cannabidiol has been shown to reduce cigarette consumption in vivo and inhibit CYP2A6-mediated nicotine metabolism in vitro. In the present study, Δ-8-tetrahydrocannabinol (Δ8-THC), an isomer of Δ-9-tetrahydrocannabinol, was examined as a potential inhibitor of CYP2A6-mediated nicotine metabolism.

While Δ-9-tetrahydrocannabinol showed no significant inhibition of nicotine metabolism to cotinine, Δ8-THC demonstrated unbound IC50 values of 0.57 ± 0.04 μM in microsomes from recombinant wild-type CYP2A6 overexpressing human embryonic kidney 293 cells and 0.70 ± 0.16 μM in human liver microsomes (HLMs). A similar unbound IC50 value was observed for recombinant CYP2A6∗5 microsomes (0.52 ± 0.17 μM) and was modestly elevated in recombinant CYP2A6∗2 microsomes (1.00 ± 0.12 μM). IC50 shift experiments were consistent across pooled HLM (5.3-fold) and microsomes from liver specimens exhibiting the CYP2A6 (∗2/∗2) and (∗9/∗9) genotypes (6.1- and 4.0-fold, respectively) but were reduced in CYP2A6 (∗35/∗35) microsomes (1.0-fold). Irreversible inhibition kinetics in pooled HLMs by Δ8-THC yielded a kinact value of 0.022 ± 0.001 min-1 and an unbound KI value of 0.232 ± 0.062 μM. Static modeling predicted that oral dosing with 10 mg Δ8-THC increased the nicotine plasma area under the curve by 189%, with further increases observed at 20 mg and 40 mg; interactions were also observed with inhalation doses ≥70 mg.

These findings suggest that, based on CYP2A6 genotype, Δ8-THC could be a candidate for smoking cessation therapy.

SIGNIFICANCE STATEMENT: This study is the first, to the best of our knowledge, to identify Δ-8-tetrahydrocannabinol as a potent and irreversible inhibitor of nicotine metabolism to cotinine. The extent of inhibition is modulated by genetic variation in cytochrome P450 2A6. These findings suggest that further investigations focusing on Δ-8-tetrahydrocannabinol and its potential as a candidate for smoking cessation therapy are warranted.”

https://pubmed.ncbi.nlm.nih.gov/41830876

“In conclusion, the present study is, to our knowledge, the first to demonstrate the irreversible inhibition of nicotine metabolism by Δ8-THC in vitro, highlighting its potential as a smoking cessation agent.”

https://dmd.aspetjournals.org/article/S0090-9556(26)00004-8/fulltext

Cannabidiol in Epilepsy: Restoring Locomotion and Seizure Control

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“Epilepsy remains a global challenge, with about one-third of affected patients being resistant to treatment. Seizures and motor abnormalities characterized by movement difficulties are common in epilepsy, highlighting the need for treatments that can both improve motor outcomes and control seizures.

The therapeutic potential of Cannabidiol (CBD) in this regard necessitates a review that explores its effects and underlying mechanisms of action. This study reviewed studies from major scientific databases on the use of CBD in animal and human models of epilepsy. We also integrated tools of network pharmacology and molecular modeling to investigate how CBD may interact with various biological targets. The cannabinoid broadly demonstrates minimal or no changes in motor outcomes, reinforcing its low toxicity and tolerability.

Evidence suggests that CBD has potential for seizure control by prolonging the time to seizure onset and decreasing seizure severity. The antiepileptic effects of CBD involve the modulation of multiple targets or genes. This multitarget interaction network may underlie its neuroprotective effects by regulating endocannabinoid signaling, neurotransmission, inflammation, and metabolic pathways. Chemical bonding between CBD and key protein residues reinforces evidence supporting its interaction with these targets.

Despite the limited clinical data and algorithmic constraints of network pharmacology, the present findings reveal the potential of CBD to improve epileptic outcomes. The multitarget mechanisms of this phytocannabinoid offer valuable insights that may guide and advance epilepsy research.”

https://pubmed.ncbi.nlm.nih.gov/41833036

https://www.eurekaselect.com/article/153518

Role of Oncoviruses in Cancer Progression and Emerging Phytochemical-Based Therapies from Medicinal Plants

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“Oncoviruses continues to be an unattended cause of the global cancer load as they cause about 12-15 % of human malignancies in the world. The oncogenic infections that become persistent, such as Human Papillomavirus (HPV), Epstein-Barr Virus (EBV), Hepatitis B and C viruses (HBV, HCV), Human T cell Leukemia Virus-1 (HTLV-1), and Kaposi Sarcoma-associated Herpesvirus (KSHV), are associated with malignant transformation by continuous destabilization of host cell cycle regulation, immune surveillance, and metabolic homeostasis. These viruses abuse critical oncogenic signaling networks like PI3K/AKT/mTOR, NF -KB, JAK/STAT, MAPK, Wnt/β-catenin, and p53-dependent networks, hence, facilitating unchecked proliferation, chronic inflammation, genomic instability, and tumor progression.

Although there have been improvements in the traditional forms of treatment, such as chemotherapy, radiotherapy, antiviral agents, immunotherapy, and gene-based treatments, yet clinical outcomes are still hampered by drug resistance, viral latency, systemic toxicity, and inaccessibility, and other severe side effects especially in low- and middle-income nations. Hence, there is a dire need to introduce new medicinal plant-based therapeutic approaches against oncovirus.

This review analyses the molecular pathways of viral oncogenesis critically and discusses the clinical translation and a promising future potential of phytochemicals derived from medicinal plants like Phyllanthus emblica, Datura stramonium, Cannabis sativa, Andrographis paniculata, Aegle marmelos, Calotropis procera, and Prosopis cineraria proven to have bioactive compounds functioning as antivirals, immune-modulator, pro-apoptotic, and cell cycle regulatory effects in the preclinical models along with multi-targets.”

https://pubmed.ncbi.nlm.nih.gov/41824191

https://link.springer.com/article/10.1007/s12033-026-01561-6

Hyaluronic Acid-Functionalized Liposomes for Co-delivery of 5-Fluorouracil and Cannabidiol Against Colorectal Cancer

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“Purpose: Colorectal cancer (CRC) is a formidable global health challenge, ranking as the third most prevalent cancer. Conventional treatments like surgery, radiation, and chemotherapy are limited by adverse effects, driving the search for more effective alternatives.

Methods: This study investigates the synergistic potential of co-delivering 5-fluorouracil (5-FU) and cannabidiol (CBD) using hyaluronic acid (HA)-decorated liposomes. While 5-FU is a cornerstone of CRC treatment, CBD offers promise as an anti-tumor agent. The HA-decorated liposomes enable potential targeted drug delivery to CD44 receptors, which are overexpressed in CRC, while minimizing systemic toxicity by reducing the concentrations of anticancer drugs required.

Results: The liposomal formulation displays optimal physicochemical properties (a sub100nm size and an appropriate negative zeta potential) and acceptable encapsulation and loading efficiencies, ensuring effective drug release. In vitro studies demonstrate that the targeted liposomes have superior anticancer effects, inducing apoptosis (up to 59.1%), cell cycle arrest in the Sub-G1 and G0-G1 phases, reduction of cell viability to 6.98% in human colorectal adenocarcinoma (HT-29) cells, induction of oxidative stress, and inhibition of colony formation. Additionally, HepG2 (non-CD44-expressing) cells were used as a control to evaluate CD44-targeting efficiency. Gene expression analysis by real-time PCR indicates modulation of key genes associated with cell cycle progression and apoptosis.

Conclusion: This multifaceted approach presents a promising strategy for CRC therapy, but requires additional optimization and rigorous in vivo investigations to facilitate successful clinical translation. In particular, optimization of drug-release kinetics and thorough in vivo validation are essential to advance this platform toward clinical application.”

https://pubmed.ncbi.nlm.nih.gov/41835056

https://apb.tbzmed.ac.ir/Article/apb-43401

Exosomal cannabidiol: A promising candidate for targeted oral delivery against breast cancer

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“Breast cancer (BCa) remains a leading cause of cancer-related deaths in women worldwide. Triple-negative BCa (TNBC) is highly metastatic with treatment limited by off-target toxicity.

Cannabidiol (CBD) has anti-cancer and anti-inflammatory activity in BCa.

This study addresses the poor oral bioavailability of CBD by utilizing exosomes (Exo) as a drug delivery system.

CBD was loaded onto non-functionalized exosomes and folic acid-functionalized exosomes (FA-Exo), achieving an average CBD drug load of ∼20%. The FA-ExoCBD averaged 136 ± 2.9 nm in size. TNBC cell lines MDA-MB-231 and taxol-resistant MDA-MB-231TR were sensitive to growth inhibition by CBD than estrogen receptor positive (ER+) MCF-7 and its taxol-resistant derivative MCF-7TR. Exosomal formulations (ExoCBD and FA-ExoCBD) demonstrated time-dependent CBD release under physiologically relevant simulated gastric and intestinal conditions and withstand acidic conditions, retained canonical exosomal markers (CD81 and Alix) as well as physical parameters of exosomes including size, PDI and zeta potential.

CBD downregulated key anti-apoptotic and anti-inflammatory markers.

Oral FA-ExoCBD showed enhanced tumor targeting, tumor retention and inhibition of orthotopic MDA-MB-231-tumor growth in NOD Scid mice than ExoCBD or free CBD. RNA-Seq analysis of tumor tissues revealed that both CBD and FA-ExoCBD treatments modulated over 1000 genes, with FA-ExoCBD significantly downregulating IL13RA2 (associated with lung metastasis) and tumor biomarkers TRPM2 and SAMHD1, while upregulating tumor suppressors PRDM1, PCDHGB2, and ICAM1.

These findings highlight the potential of FA-ExoCBD to enhance CBD’s anticancer efficacy through targeted gene modulation. Overall, FA-ExoCBD improves CBD’s therapeutic profile by enhancing efficacy, tumor selectivity, improved bioavailability and anticancer efficacy.”

https://pubmed.ncbi.nlm.nih.gov/41812824

https://www.sciencedirect.com/science/article/abs/pii/S0304383526001795?via%3Dihub


Potential of Using Cannabidiol as a Therapeutic Molecule Against Various Cell Signaling Molecules Involved in Breast Cancer Complications: A Bioinformatics Approach

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“Background: Breast cancer progression involves key processes such as uncontrolled cell proliferation, resistance to apoptosis, metastasis, and angiogenesis. Cannabidiol (CBD), a non-psy-choactive compound from Cannabis sativa, has shown promise for its anti-cancer properties. This study aimed to explore the interaction of CBD with proteins involved in these processes.

Methods: Molecular docking was performed to assess the binding affinity of CBD to four critical proteins: CDK6 (cell cycle regulator), BCL2 (anti-apoptotic protein), MMP2 (invasion-related en-zyme), and VEGFR2 (angiogenesis-related receptor). Known inhibitors, palbociclib, ABT-199, doxycycline, and axitinib, were used as reference compounds for comparison.

Results: Cannabidiol exhibited strong binding affinities for CDK6, BCL2, MMP2, and VEGFR2. The docking scores were comparable to those of the respective standard inhibitors, suggesting effec-tive interactions with the active sites of the target proteins.

Discussion: These findings suggest that CBD may simultaneously target multiple cancer-related pathways, offering a potential multi-target therapeutic approach for breast cancer. Its comparable efficacy to standard inhibitors, combined with a favorable safety profile, supports its potential for further development. However, experimental validation through in vitro and in vivo studies is neces-sary to confirm its therapeutic effectiveness.

Conclusion: CBD demonstrates promising multi-target activity against critical signaling molecules in breast cancer and may serve as a safer, natural therapeutic candidate. Further preclinical and clin-ical investigations are warranted.”

https://pubmed.ncbi.nlm.nih.gov/41830580

https://www.eurekaselect.com/article/153254

Effects of Cannabidiol on TAFAZZIN-Deficient B-Lymphoblastoid Cells

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“Barth Syndrome (BTHS) is a debilitating X-linked genetic disorder caused by mutations in the gene encoding TAFAZZIN, an enzyme responsible for the remodeling of cardiolipin. While cyclic neutropenia is a well-recognized immunological feature of this disease, emerging evidence suggests that lymphopenia may also occur.

The objective of this study was to examine the effects of cannabidiol (CBD) on growth, cardiolipin content, and mitochondrial abnormalities in BTHS patient-derived B-lymphoblastoid cells.

CBD (1 μM) restored the growth of BTHS B-lymphoblastoids to healthy control levels, but did not alter cell cycle distribution or sub-G1 cell populations, which surprisingly also did not differ from healthy control B-lymphoblastoids. CBD treatment also fully restored the total cellular cardiolipin concentration and reversed the elevation in monolysocardiolipin/cardiolipin ratio in BTHS B-lymphoblastoids to healthy cell levels, but did not restore the cardiolipin fatty acyl composition.

Assessment of mitochondrial markers suggested that increased cardiolipin did not result from increased mitochondrial content. This improvement in cardiolipin concentration was associated with a significant increase in the maximal coupled state III respiration of BTHS B-lymphoblastoids, with all five tested BTHS donors exhibiting increased mitochondrial membrane potential following CBD treatment. CBD fully reversed the deficit in succinate dehydrogenase subunit A in BTHS cells, and partially reversed deficits in cytochrome c oxidase subunits I and IV, and partially restored supercomplex I/III2 levels, but did not rescue I/III2/IV levels.

This work suggested a potential role for CBD as a therapeutic in BTHS B-lymphopenia that merits further investigation.”

https://pubmed.ncbi.nlm.nih.gov/41823370

https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202503384R

Quantitative analysis of Cannabinoid Therapy in Prostate Cancer: Integrating Biomarkers, Imaging and Patient Outcomes

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“Cannabinoids are increasingly used by cancer patients for symptom relief, yet clinical evidence on their effect in prostate cancer remains limited. This study evaluated the association between cannabinoid therapy and disease activity, pain, and quality of life in men with prostate cancer.

The objectives were to assess the influence of cannabinoids on PSA levels, metabolic activity, tumour size via PET/CT scans, and patient-reported outcomes including pain levels and quality of life.

Methods: Ninety men with confirmed prostate cancer were prospectively followed in three groups: chemotherapy-only, cannabis-only, and combined chemotherapy + cannabis. PSA, PET/CT findings, and patient-reported outcomes (BPI, EQ-5D) were assessed at baseline, 3 months, and 6 months. Longitudinal changes were analysed using linear mixed-effects regression with group × time interactions, and between-group differences were tested with ANOVA. PET/CT categorical outcomes were evaluated using multinomial logistic regression to generate adjusted odds ratios

Results: Significant temporal differences in PSA levels were detected among groups (p < 0.001); both cannabis-containing regimens showed faster PSA decline, but final values were comparable across treatments. PET/CT analyses indicated a higher likelihood of remission or tumour reduction in the combined group (p = 0.013).

Cannabis use, alone or combined was associated with greater reductions in pain and improved emotional well-being compared with chemotherapy alone, while improvements in self-care and usual-activity scores were also observed.

Conclusion: Cannabinoid therapy, whether used independently or alongside chemotherapy, was associated with improved pain control and some indicators of tumour response, without evidence of harm. The findings warrant cautious interpretation and support further randomized studies to clarify cannabinoids’ adjunctive role in prostate cancer management.”

https://karger.com/mca/article/doi/10.1159/000550792/946276/Quantitative-analysis-of-Cannabinoid-Therapy-in

Efficacy of Exogenous Cannabinoids in Pre-Clinical Models of Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

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“Background: Exogenous cannabinoids are considered promising therapeutic candidates for inflammatory bowel disease (IBD). However, robust pre-clinical evidence supporting its efficacy remains limited. This systematic review and meta-analysis aimed to evaluate the therapeutic effects of exogenous cannabinoids in animal models of IBD.

Methods: Controlled experimental studies involving animal models of IBD that evaluated the effects of exogenous cannabinoids compared to untreated models were included. Four databases (PubMed, Embase, Web of Science, and the Cochrane Library) were searched up to August 26, 2025. Two independent reviewers conducted study selection, data extraction, and the risk-of-bias assessment. The risk-of-bias assessment was performed using the Systematic Review Center for Laboratory Animal Experimentation tool. Meta-analyses were performed using standardized mean differences (SMDs) and random-effects models. The study was registered in INPLASY (INPLASY202540009).

Results: Twenty-seven pre-clinical studies involving 408 animals were included. Compared with controls, exogenous cannabinoids significantly reduced disease activity index (SMD = -3.43; 95% confidence interval [CI]: -4.98 to -1.89; I2 = 83%) and histopathological score (SMD = -4.46; 95% CI: -6.37 to -2.54; I2 = 84%). It also decreased levels of myeloperoxidase (MPO), TNF-α, IL-6, and IL-1β. However, substantial heterogeneity was noted across several outcomes.

Interpretation: Exogenous cannabinoids show beneficial effects in pre-clinical IBD models, likely through anti-inflammatory, antioxidant, and barrier-enhancing mechanisms. These findings provide a supportive foundation for future translational research. Nevertheless, the overall certainty of the evidence is limited by unclear randomization, lack of blinding, high heterogeneity, and small sample sizes. Although some clinical trials have already begun exploring its therapeutic potential, further rigorous and standardized animal studies are needed to clarify mechanisms, optimize dosing, and reinforce the translational pathway.”

https://pubmed.ncbi.nlm.nih.gov/41804536