Unveiling Cannabinoids and Terpenes Diversity in Cannabis sativa L. from Northern India for Future Breeding Strategies

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“Cannabis sativa L. is an important medicinal plant with high commercial value.

In recent years, the research interest in cannabidiol (CBD) and terpene-rich cannabis has been rapidly expanding due to their high therapeutic potential.

The present study aims to explore the phytocannabinoids and terpenes diversity in Cannabis sativa collected from different parts of northern India.

Our findings revealed that the cannabinoids and terpenes synthesize together in capitate stalked and capitate sessile glandular trichomes, whereas bulbous glands synthesize only terpenes. The North Indian C. sativa is mainly dominated by tetrahydrocannabinol (THC). The CBD-rich plant diversity is nominal (1.11%) in studied north Indian C. sativa. The essential oil profiling reveals (E)-caryophyllene (10.30-36.80%) as the major constituent, followed by α-humulene (0.50-15.29%) and α-bisabolol (0.00-16.40%) in the North Indian population.

The cannabinoids and terpenes content showed significant diversity among and within the five studied populations. The correlation analysis between cannabinoids and terpenes indicates that α-pinene, β-pinene, and limonene positively correlated with CBD content. Similarly, α- and β-selinene correlate positively with tetrahydrocannabinolic acid (THCA) content. This study could help to identify the key cultivars from India and establish a consistent chemotype for future breeding programs.”

https://pubmed.ncbi.nlm.nih.gov/39853702/

https://onlinelibrary.wiley.com/doi/10.1002/cbdv.202402278

Cannabidiol suppresses proliferation and induces cell death, autophagy and senescence in human cholangiocarcinoma cells via the PI3K/AKT/mTOR pathway

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“Background and aim: Cholangiocarcinoma (CCA) is usually diagnosed at a late stage, leading to treatment failure. Cannabidiol (CBD), exhibits diverse anti-cancer effects in various cancers, offering avenues for improving CCA treatment. This study investigated the effects of CBD on human CCA cells and the underlying mechanisms in vitro and in vivo.

Experimental procedure: The effects of CBD on three CCA cell lines (KKU-213B, KKU-100, KKU-055) were assessed using the SRB assay, clonogenic assay, cell cycle arrest, and 3D holotomography. Morphological changes were examined using transmission electron microscopy, while mitochondrial ROS levels and mitochondrial membrane potential were studied using MitoSOX, JC-1, and DCFH-DA. Cellular senescence induction was evaluated via SA-β-gal staining. Protein associatedwith autophagy and cellular senescence were analyzed using Western blot and/or immunofluorescent assays. A xenograft model demonstrated the anti-tumor activity of CBD and the induction of cellular senescence through immunohistochemistry targeting PCNA, β-gal, and p21.

Results and conclusion: CBD effectively inhibited CCA cell proliferation, suppressed colony formation and induced G0/G1 phase cell cycle arrest. Morphological examination revealed lipid droplets/vesicles in CCA cell lines. CBD induced autophagy by upregulating LC3BII, downregulating p62, and inhibiting the p-PI3K, p-AKT, and p-mTOR pathways. Additionally, CBD disrupted mitochondrial homeostasis by elevating ROS, reducing membrane potential, and induced cellular senescence by increasing the expression of p53 and p21. In-vitro results were confirmed by xenograft models. Overall, CBD suppresses proliferation and induces cell death, autophagy and senescence in CCA cells via the PI3K/AKT/mTOR pathway, which indicates a therapeutic option for CCA treatment.”

https://pubmed.ncbi.nlm.nih.gov/39850601/

“Although CBD has shown anti-tumor activity in various solid tumors, including CCA, its mechanism of action remains poorly understood.”

“The study reported here has shown that CBD has a significant anti-tumor effect on CCA cells through various mechanisms, including the inhibition of cell proliferation both in vitro and in vivo, the reduction of colony formation ability and the induction of multiple cellular processes, notably autophagy, cell cycle arrest, cellular senescence, mitochondrial dysfunction, lipid droplet formation, and ROS overproduction.

The significant findings from our study strongly suggest that CBD, through its targeting of the PI3K/AKT/mTOR pathway, holds great promise as a therapeutic agent for treating CCA and potentially other cancers.”

“Various herbal agents, including CBD, have shown promise for the treatment of CCA.”

https://www.sciencedirect.com/science/article/pii/S2225411024000506?via%3Dihub

Oral cannabidiol did not impair learning and memory in healthy adults

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“Background: The effect of oral Cannabidiol (CBD) on interference during learning and memory (L&M) in healthy human volunteers has not been studied.

Method: A two-arm crossover, randomized, double-blind, placebo-controlled trial was conducted at Colorado State University Pueblo (CSU Pueblo) to evaluate the effects of 246 mg oral CBD on L&M in healthy adults. Among 57 healthy volunteers enrolled, 35 were included in the analyses. For assessment of L&M, Montreal Cognitive Assessment (MOCA) was used to evaluate verbal baseline cognitive function; RAVLT-R tests (List A and List B recalls, Proactive and Retroactive Interference ratios, and Forgetting Speed ratio) were used to evaluate verbal declarative memory; and total prose recall was used to evaluate verbal logical memory. Linear Mixed Models with Bonferroni Corrections were used to compare L&M results between primary outcomes (CBD vs. placebo) and secondary demographic outcomes, with a two-tailed statistical significance of P < 0.05.

Results: CBD administration did not affect any of the dependent variables measured compared to the placebo group. There were no effects of THC, history of CBD use, or sex on CBD’s modulation of L&M. However, a highly significant interaction effect between treatment groups (CBD vs. placebo) and age of subjects was observed for the PI ratio (P = 0.008; n = 35).

Conclusions: The results of this study suggest that administration of oral CBD alone does not significantly impair L&M in healthy adults. However, age might influence CBD related modulation of proactive interference during human L&M. Future research involving a larger group of older adults is needed to confirm this potential effect.”

https://pubmed.ncbi.nlm.nih.gov/39849639/

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00262-2

Cannabis oil in treating Parkinson’s disease: improvement of motor and non-motor symptoms: a case report

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“Parkinson’s disease (PD) is characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta, which leads to a reduction in the production of dopamine. Medication with levodopa becomes less effective as the disease progresses. Despite the excellent results observed in clinical practice with the medicinal use of Cannabis in the treatment of PD, the level of scientific evidence is still limited due to the small number of studies published in this field.

We present the case of a 77-year-old man diagnosed 22 years ago with PD in an advanced stage, with significant bradykinesia, tremor, and rigidity along with the inability to maintain an upright position and walk, exacerbated by a femur fracture. He also had advanced dysphagia, resulting in a gastrostomy. Although lucid, he showed no interest in conversation and tended to become depressed and isolated. He used Prolopa® with no satisfactory therapeutic response.

After starting treatment with Cannabis sativa oil, he is now able to walk around the house frequently and eat pasty food regularly without choking or broncho-aspiration episodes. There has also been a significant improvement in non-motor symptoms; he is more active, cheerful, communicative, and attentive to his surroundings.

Further studies are needed to elucidate these results and the mechanisms of action of cannabinoids through which they exert possible neuroprotective and neuroreparative effects.

These compelling results suggest that cannabis oil may offer a valuable and effective therapeutic option for individuals with Parkinson’s disease.”

https://pubmed.ncbi.nlm.nih.gov/39841751/

“Considering Parkinson’s disease a neurodegenerative process, in this report we present a unique case where, in addition to slowing the progression of the disease, there was recovery of motor and cognitive functions in a patient with advanced stage Parkinson’s disease, after starting treatment with full-spectrum cannabis oil.”

https://www.scielo.br/j/bjb/a/nqQFzz3NtnydWM8KWdfYyWz/?lang=en

The proof is in the pudding: patient engagement in studying cannabidiol in mild cognitive impairment

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“Background: Patient engagement (PE) in clinical trials has gained importance yet remains uncommon, particularly in patients with mild cognitive impairment (MCI), a critical precursor to Alzheimer’s disease (AD). Cannabidiol (CBD) shows potential in slowing MCI progression due to its neuroprotective and anti-inflammatory properties. In CBD research, PE is underutilized too. To design a study on CBD for MCI, we administered an online survey to individuals with MCI to better understand their preferences for trial setup and outcomes.

Methods: We asked 209 individuals with MCI to complete an online survey assessing (i) willingness to participate in a trial using CBD; (ii) importance of improvements in various domains; (iii) acceptance of adverse events (AEs); (iv) reasons for AE-related dropout; (v) willingness to undergo blood sampling and lumbar puncture to assess AD pathology; and (vi) willingness to participate in a trial with a 50% chance of receiving a placebo. Data were analyzed with descriptive statistics.

Results: N = 118 agreed to participate and N = 88 completed the survey. Participants prioritized improvement in cognitive abilities (87.5%), followed by quality of life (63.6%), daily activities (55.7%), sleep (55.7%), pain (52.3%), mood (52.3%), behavior (48.9%), and anxiety (43.2%). Headache (55.7%) was the least accepted AE followed by nausea (46.6%), fatigue (35.2%), and diarrhea (35.2%). Persistent diarrhea (90.9%) and severe fatigue (84.1%) were the main reasons for potential dropout. While most would undergo blood sampling (67.0%), only a minority (21.6%) would accept lumbar puncture. One-third were ready to participate (34.1%), while 54.5% were interested pending details. Among those in favor of participation, 71.6% would participate even with a 50% chance of placebo.

Conclusions: Our study identified cognitive improvement as highly relevant for patients, indicating cognitive assessment tools as primary endpoints in MCI research. Given concerns about AEs, dose titration should be carefully considered to enhance acceptance and prevent AEs. Blood sampling seems well-accepted for AD biomarker assessment. Despite potential AEs, participation in a trial using CBD for MCI is seen as attractive, even under placebo-controlled conditions. This cross-sectional study emphasizes the importance of patient engagement in designing high-quality trials for using CBD to treat MCI.”

https://pubmed.ncbi.nlm.nih.gov/39844123/

“In summary, this study is the first to incorporate PE into a trial on the use of CBD for MCI, as there are currently no existing PE activities in this area. It provides valuable insights into the concerns, aims, and needs of people with MCI and offers initial implications for planning and conducting future studies involving this population. Our main message is to encourage the incorporation of PE activities in the drug research process, not only to reflect the goals and needs of patients but also to improve the quality of research.”

https://bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/s12906-025-04753-w

Mechanisms and strategic prospects of cannabinoids use: Potential applications in antimicrobial food packaging-A review

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“This review focuses on antimicrobial packaging for food safety, critically examining the activity and efficacy of cannabinoids against commonly found microorganisms and exploring their antimicrobial mechanisms.

Specifically, the review considers cannabinoids derived from industrial hemp plants, which are characterized by low levels of psychoactive components. It also outlines viable strategies to control the sustained release of cannabinoids from the packaging, enabling extended storage and enhanced safety of food products.

Research demonstrates that cannabinoids are effective against both foodborne bacteria and fungi, with their antimicrobial action primarily attributed to microbial membrane instability.

Cannabinoids can be utilized to prepare effective antimicrobial films and edible coatings; however, the number of studies in this area remains limited.

The potential of cannabinoids to contribute to intelligent packaging systems is also discussed, with an emphasis on the regulatory aspects and challenges associated with incorporating cannabinoids into food packaging. Finally, the review identifies future research directions to address current limitations and advance hemp-based antimicrobial food packaging solutions.”

https://pubmed.ncbi.nlm.nih.gov/39840610/

https://ift.onlinelibrary.wiley.com/doi/10.1111/1541-4337.70113

Treatment With Full-Spectrum Cannabidiol Oil Improved the Pathological Findings of Dystrophic Mutant Mice

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“Introduction/aims: Duchenne muscular dystrophy (DMD) is caused by pathogenic variants in the DMD gene, making muscle fibers susceptible to contraction-induced membrane damage. Given the potential beneficial action of cannabidiol (CBD), we evaluated the in vitro effect of full-spectrum CBD oil on the viability of dystrophic muscle fibers and the in vivo effect on myopathy of the mdx mouse, a DMD model.

Methods: In vitro, dystrophic cells from the mdx mouse were treated with full-spectrum CBD oil and assessed with cell viability and cytotoxic analyses. In vivo, fourteen-day-old mdx mice received 10 mg/kg/day of the full-spectrum CBD oil for 14 days. We analyzed creatine kinase (CK) levels, liver damage markers, and histopathology of the diaphragm (DIA) and quadriceps (QUA [myonecrotic fibers with positive IgG staining, regenerated fibers/central nuclei, the minimum Feret’s diameter, the fibrosis area, the inflammatory area, the presence of macrophages, and NF-kappa B content]).

Results: In vitro treatment with full-spectrum CBD oil showed a dose-dependent cytotoxic effect; however, in vivo 10 mg/kg treatment was safe and effectively improved DMD histopathological assessment parameters in DIA and QUA: reduction of central nuclei: 1.7% ± 2.0% versus 22.4% ± 5.3% and 11.1% ± 10.7% versus 32.3% ± 4.6%; reduction of IgG+ myofibers: 0.6% ± 0.7% versus 8.4% ± 1.6% and 0.9% ± 0.3% versus 7.5% ± 1.0%; increase in myofiber size: 85.2 ± 3.2 versus 64.3 ± 4.0 μm and 106.5 ± 8.6 versus 81.2 ± 4.8 μm; decrease in inflammatory area: 6.2% ± 2.7% versus 15.1% ± 2.6% and 5.3 ± 4.1 versus 17.3% ± 2.8%; reduced macrophage area: 0.05% ± 0.1% versus 10.8% ± 4.3% and 1.0% ± 0.7% versus 10.3% ± 4.9%; NF-κB levels: 0.6% ± 0.1% versus 1.7% ± 0.2% and 1.7% ± 0.1% versus 5.2% ± 2.1%; and fibrosis: 5.6% ± 1.8% versus 12.0% ± 3.7% and 1.3% ± 0.5% versus 4.7% ± 1.5%. It also reduced serum CK.

Discussion: Full-spectrum CBD oil may represent a promising new approach to treating DMD, but its potential toxicity must be considered.”

https://pubmed.ncbi.nlm.nih.gov/39840534/

https://onlinelibrary.wiley.com/doi/10.1002/mus.28337

Therapeutic potential of cannabidiol polypharmacology in neuropsychiatric disorders

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“Cannabidiol (CBD), the primary non-intoxicating compound in cannabis, is currently approved for treating rare, treatment-resistant seizures.

Recent preclinical research suggests that CBD’s multifaceted mechanisms of action in the brain, which involve multiple molecular targets, underlie its neuroprotective, anti-inflammatory, anxiolytic, and antipsychotic effects. Clinical trials are also exploring CBD’s therapeutic potential beyond its current uses.

This review focuses on CBD’s polypharmacological profile and discusses the latest preclinical and clinical findings regarding its efficacy in neuropsychiatric disorders.

Existing evidence suggests that CBD’s ability to modulate multiple signaling pathways may benefit neuropsychiatric disorders, and we propose further research areas to clarify its mechanisms, address data gaps, and refine its therapeutic indications.”

https://pubmed.ncbi.nlm.nih.gov/39837749/

https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(24)00271-2?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0165614724002712%3Fshowall%3Dtrue

First case report of effective and safe application of cannabidiol to treat concurrent ALG3-CDG and Lennox-Gastaut Syndrome

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“This study presents the first reported case of a Korean patient with Alpha-1,3-Mannosyltransferase-Congenital Disorder of Glycosylation (ALG3-CDG), characterized by a novel maternally inherited missense mutation and a previously reported paternally inherited nonsense mutation. The patient exhibited typical ALG3-CDG manifestations, including developmental delays, epilepsy, and multisystem involvement, alongside a diagnosis of Lennox-Gastaut Syndrome (LGS).

Cannabidiol therapy, combined with dietary management, led to seizure freedom for over 13 months, significant EEG improvement, and enhanced developmental outcomes.

This case underscores the potential of cannabidiol as a promising treatment strategy for patients with ALG3-CDG and refractory epilepsy, broadening therapeutic perspectives for this rare disorder.”

https://pubmed.ncbi.nlm.nih.gov/39831946/

https://link.springer.com/article/10.1007/s10072-025-08004-1

Exploring the antifungal potential of Cannabis sativa-derived stilbenoids and cannabinoids against novel targets through in silico protein interaction profiling

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“Cannabinoid and stilbenoid compounds derived from Cannabis sativa were screened against eight specific fungal protein targets to identify potential antifungal agents.

The proteins investigated included Glycosylphosphatidylinositol (GPI), Enolase, Mannitol-2-dehydrogenase, GMP synthase, Dihydroorotate dehydrogenase (DHODH), Heat shock protein 90 homolog (Hsp90), Chitin Synthase 2 (CaChs2), and Mannitol-1-phosphate 5-dehydrogenase (M1P5DH), all of which play crucial roles in fungal survival and pathogenicity.

This research evaluates the binding affinities and interaction profiles of selected cannabinoids and stilbenoids with these eight proteins using molecular docking and molecular dynamics simulations. The ligands with the highest binding affinities were identified, and their pharmacokinetic profiles were analyzed using ADMET analysis. The results indicate that GMP synthase exhibited the highest binding affinity with Cannabistilbene I (-9.1 kcal/mol), suggesting hydrophobic solid interactions and multiple hydrogen bonds. Similarly, Chitin Synthase 2 demonstrated significant binding with Cannabistilbene I (-9.1 kcal/mol). In contrast, ligands such as Cannabinolic acid and 8-hydroxycannabinolic acid exhibited moderate binding affinities, underscoring the variability in interaction strengths among different proteins.

Despite promising in silico results, experimental validation is necessary to confirm therapeutic potential. This research lays a crucial foundation for future studies, emphasizing the importance of evaluating binding affinities, pharmacokinetic properties, and multi-target interactions to identify promising antifungal agents.”

https://pubmed.ncbi.nlm.nih.gov/39834844/

“This study provides a comprehensive assessment of how selected cannabinoid and stilbenoid compounds interact with eight different fungal proteins, highlighting the promising potential of these compounds as antifungal agents. In conclusion, this study highlights the therapeutic potential of cannabinoids and stilbenoids and provides a solid foundation for the development of new antifungal therapies.”

https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1515424/full