“This study evaluated the in vitro antioxidant and antiproliferative activity of hemp seed (Cannabis sativa L.) protein isolate, protein hydrolysate, and its fractions. The protein hydrolysate was obtained through sequential enzymatic digestion using pepsin and pancreatin, achieving a degree of hydrolysis of 48.11%. The hydrolysate was then fractionated by ultrafiltration.
Assays conducted on Caco-2 (colorectal cancer) and THP-1 (leukemia) cell lines revealed that the higher-molecular-weight fraction of (>10 kDa) exhibited the strongest, concentration-dependent antiproliferative effect, as determined by the neutral red uptake (NRU) assay for Caco-2 cells and the MTT assay for THP-1 cells. Furthermore, a significant intracellular antioxidant activity was observed, particularly in the whole hydrolysate and its low-molecular-weight fractions, as measured by the DCFH-DA assay in Caco-2 cells.
The results suggest the potential application of hemp seed protein hydrolysate and its fractions as antioxidant and chemoprotective supplements in oncologic therapies.”
“This study establishes that hemp seed protein hydrolysate (HSH) and its ultrafiltration fractions possess significant and dual biological activities. The principal finding is the identification of a potent, dose-dependent, and selective antiproliferative effect against colorectal adenocarcinoma (Caco-2) and monocytic leukemia (THP-1) cell lines, with the high-molecular-weight fraction (F1 > 10 kDa) demonstrating the greatest efficacy.
Collectively, these findings underscore the dual potential of hemp seed peptides as a reduction in cell viability agents and potent antioxidants, positioning them as promising candidates for development as functional food ingredients for chemoprevention and as adjuvants in oncological therapies.”
“The cannabidiol (CBD)-rich cannabis extract CAN296 shows anti-inflammatory and anticancer activity relevant to oral lichen planus (OLP), oral graft-versus-host disease (oGVHD), and oral squamous cell carcinoma (OSCC), but its high lipophilicity limits aqueous dispersion.
This study developed a stable Tween-based nanoemulsion optimized for oral mucosal delivery.
Ethanol-dissolved CAN296 was nanoemulsified using a 1% Tween/Span system. Physical stability was visually assessed; droplet size and morphology were examined by dynamic light scattering (DLS) and transmission electron microscopy (TEM); and wettability was measured by static contact angle (SCA). Additional evaluations included temperature stability (25 °C vs. 4 °C), in vitro release using a dialysis membrane, and scanning electron microscopy (SEM) of membrane-associated droplets.
Nanoemulsions with ≥80% Tween 80 incorporated CAN296 up to 800 µg/mL, clear at 400 µg/mL, and uniformly turbid at 800 µg/mL. DLS and TEM confirmed spherical nanoscale droplets, and SCA indicated favorable cohesion and wettability. Stability was maintained for 30 days at 4 °C. Dialysis studies demonstrated strong membrane association with limited diffusion, supported by SEM visualization of membrane-bound droplets.
The Tween-dominant (≥80%) nanoemulsion stably incorporated CAN296 up to 800 µg/mL, demonstrated nanoscale uniformity, improved 4 °C stability, and strong membrane retention under static conditions, suggesting potential for localized oral delivery.”
“Cannabis-derived extracts rich in cannabidiol (CBD) have significant therapeutic potential in immune-mediated and oncologic oral diseases due to their anti-inflammatory, immunomodulatory, and pro-apoptotic effects.”
“This research established a Tween-dominant nanoemulsion capable of stabilizing a robust concentration of CBD-rich cannabis extract. This optimized system remains stable under refrigeration, exhibits favorable wettability and membrane retention, and provides a physically stable, ethanol-compatible platform for oral mucosal delivery of cannabis extract.”
“Introduction: Cannabinoids hold promise in oncology for symptom relief and antitumor effects, though concerns about safety and efficacy persist. This study assessed the impact of JWH-182 and phytocannabinoids NC1 – Cannabixir® Medium dried flowers and NC2 – Cannabixir® THC full extract, in a murine breast cancer model with paclitaxel-induced peripheral neuropathy (CIPN).
Methods: Female BALB/c mice with breast tumors received paclitaxel alone or combined with cannabinoids, and outcomes included pain sensitivity, tumor progression (imaging and histopathology), cachexia (body weight, food intake, imaging), as well as hematological and organ toxicity profiles.
Results: All cannabinoids alleviated neuropathic pain, with NC1 most effective for central and thermal protection (72% and 100%, p < 0.0001), NC2 showing strong central and mechanical benefit (>60% and >33%), and JWH-182 intermediate (∼50%). Tumor growth was not significantly altered, but metastasis incidence was 41.7% for NC1, 58.3% for NC2, compared with 70% for PTX, suggesting antitumoral activity. Effects on cachexia were modest, JWH-182 tended to improve food intake, whereas NC1 and NC2 reduced it, yet body weight remained stable and significant muscle loss was observed only with NC2 (p < 0.05). Hematology showed immunomodulatory effects, with cannabinoids reversing lymphopenia (p = 0.0005), raising monocytes and neutrophils, and partly restoring platelets. Toxicity was highest with NC2 (renal and hepatic injury), moderate with NC1, and lowest for kidney with JWH-182 but with greater hepatic inflammation.
Conclusion: Cannabinoids show potential in oncology by relieving CIPN and influencing tumor dynamics, with mostly neutral effects on cachexia. GMP-certified formulations enhance translational value, though safety concerns warrant further study.”
“Cannabinoids have emerged as promising agents in oncology for both symptom relief and potential antitumor effects. By acting on cannabinoid receptors 1 and 2 (CB1R, CB2R), Tetrahydrocannabinol (THC) and Cannabidiol (CBD) help regulate pain, appetite, and inflammation, making them effective in managing CIPN, cancer pain, and cachexia.
Preclinical studies also suggest that cannabinoids can inhibit tumor growth, metastasis, angiogenesis, and reverse chemoresistance, with potential to enhance chemotherapy efficacy and reduce its toxicity.”
“Cancer remains a major global health challenge, necessitating new, effective therapies. Phytocannabinoids from Cannabis sativa L. show significant anticancer potential, yet their natural scarcity limits research and development.
This study presents an innovative extract engineering approach to generate rare varin-type cannabinoids from abundant precursors. Through this strategy, nine cannabinoid analogues were synthesised, including four rare varin-type compounds, and screened against five human cancer cell lines.
Among them, cannabinovarin (CBNV) and Δ6a,10a-THCV exhibited potent cytotoxicity against breast (MCF-7) and colon (HCT-116) cancer cells, with IC50 values of 15-30 µM. Mechanistic investigations revealed apoptosis induction via mitochondrial membrane disruption and reactive oxygen species generation.
These findings establish extract engineering as a rapid and efficient route to access rare cannabinoids, highlighting CBNV and Δ6a,10a-THCV as promising anticancer leads for further mechanistic and in vivo evaluation.”
“In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings.
Cannabinoids have been suggested and shown to be effective in the treatment of various conditions.
In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of cancer cells, as well as tumour angiogenesis.
Along with cannabinoids, cannabis contains several other compounds that have also been shown to exert anti-tumorigenic actions.”
“Dysregulation of the endocannabinoid system has been implicated in several diseases, including cancer.”
“Based on the preliminary evidence in various models, it appears that cannabinoids target key signaling pathways involved in all the hallmarks of cancer. Additionally to the cannabinoids, a large number of terpenes and flavonoids, some of them also present in cannabis, exhibit cytotoxicity against a variety of cancers.”
“Considering all the available literature at this time, much stronger experimental evidence (obtained in vitro, in vivo and even in a few clinical trials) support that THC and cannabidiol (CBD) have better anticancer activity than for the other cannabinoids.”
“Cannabis sativa L. is a plant that contains numerous chemically active compounds including cannabinoids such as trans-Δ-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and flavone derivatives, such as luteolin-7-O-glucuronide and apigenin glucuronide.”
“These extracts could be a source of compounds with potential benefit on human health, especially related to neurodegenerative disorders.”
“In conclusion, this study provided new insights into the biological activities of two different extracts of C. sativa. It was revealed that these extracts constitute a valuable and interesting natural source of bioactive molecules with great antioxidant properties, potentially capable of preventing neurodegenerative diseases.”
“Introduction: Cannabinoids are a group of terpenophenolic compounds derived from the Cannabis sativa L. plant. There is a growing body of evidence from cell culture and animal studies in support of cannabinoids possessing anticancer properties.
Method: A database search of peer reviewed articles published in English as full texts between January 1970 and April 2021 in Google Scholar, MEDLINE, PubMed and Web of Science was undertaken. References of relevant literature were searched to identify additional studies to construct a narrative literature review of oncological effects of cannabinoids in pre-clinical and clinical studies in various cancer types.
Results: Phyto-, endogenous and synthetic cannabinoids demonstrated antitumour effects both in vitro and in vivo. However, these effects are dependent on cancer type, the concentration and preparation of the cannabinoid and the abundance of receptor targets. The mechanism of action of synthetic cannabinoids, (-)-trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) has mainly been described via the traditional cannabinoid receptors; CB1 and CB2, but reports have also indicated evidence of activity through GPR55, TRPM8 and other ion channels including TRPA1, TRPV1 and TRPV2.
Conclusion: Cannabinoids have shown to be efficacious both as a single agent and in combination with antineoplastic drugs. These effects have occurred through various receptors and ligands and modulation of signalling pathways involved in hallmarks of cancer pathology. There is a need for further studies to characterise its mode of action at the molecular level and to delineate efficacious dosage and route of administration in addition to synergistic regimes.”
“Since time immemorial, the Cannabis plant has been used as a source of fibre, herbal remedy, medicinal and for religious purposes. Plant-based, endogenous and synthetic cannabinoid compounds have shown merits in not only alleviating the unwanted side effects of antineoplastic drug regiments, but have also shown promising evidence in decreasing tumour burden.”
“Plant-based, endogenous and synthetic cannabinoid compounds have shown merits in not only alleviating the unwanted side effects of antineoplastic drug regiments, but have also shown promising evidence in decreasing tumour burden, and one in vivo study so far concludes increasing survival rates in mice.
The antitumour effects of cannabinoids trend in modulating processes which include apoptosis and autophagy through first stimulating de novo synthesis of ceramide which induces activation of ER stress-related signalling proteins further leading to the inhibition of the AKT/mTORC1 axis promoting cell cycle arrest and additional mechanisms, such as cell death and aging.
Other pathways involved mechanistically are activation of MAPK/ERK signalling through calcium induction. Strategies that would optimize the anticancer effects of cannabinoids through interference of these signalling cross-talks may prove useful for therapeutic intervention. Nevertheless, we found that these effects were reached differently downstream depending on the type of cancer, the dosage of the compound and which receptor/ligands were activated.
We also found the co-administration of cannabinoids with chemotherapy drugs enhanced the potency of these effects. These synergistic effects should be targeted for translation to clinical application, especially in cancers which are refractory to chemotherapy.
Various extracted forms of cannabinoids from C. sativa have shown varying cytotoxic effects which should be explored in more detail in future studies as majority of the evidence originates from studies investigating mainly ∆9-THC and CBD’s actions. Whilst the emerging evidence of phytocannabinoid anticancer effects are promising, there remains a paucity of clinical evaluation which must be overcome.”
“Substantial preclinical evidence demonstrates the antiproliferative, cytotoxic, and antimetastatic properties of plant-derived cannabinoids (phytocannabinoids) such as cannabidiol and tetrahydrocannabinol. The cumulative body of research into the intracellular mechanisms and phenotypic effects of these compounds supports a logical, judicious progression to large-scale phase II/III clinical trials in certain cancer types to truly assess the efficacy of phytocannabinoids as anticancer agents.”
“delta 9-Tetrahydrocannabinol (delta 9-THC) was studied for potential carcinogenicity in rodents because it is the principal psychoactive ingredient in marihuana and it has potential medicinal uses.
There was no evidence that delta 9-THC was carcinogenic in rats or mice.”
“Purpose: To investigate the endocannabinoid system (ECS) and affective state responses to acute aerobic exercise in adult cancer patients versus their healthy peers.
Methods: Participants engaged in 30 min of quiet rest followed by 30 min of exercise. Exercise involved 5-min warm-up/cool-down procedures and 20 min of moderate-intensity training (64-76% of age-predicted maximal heart rate) on a treadmill or cycle. Blood samples and 10 Visual Analog Scales (VAS) were collected before and after each condition. Participants were also asked after exercise: ‘Did you experience a Runner’s high’. Blood samples were analysed for endocannabinoids: N-arachidonoylethanolamine (AEA; anandamide), 2-arachidonoylglycerol (2-AG) and 1-arachidonoylglycerol (1-AG), and endocannabinoid-like lipid mediators: palmitoylethanolamide (PEA), oleoylethanolamide (OEA) and stearoylethanolamide (SEA).
Results: Cancer patients had lower circulating AEA, OEA and log SEA versus controls across all timepoints (all p < 0.06). In the total cohort, exercise increased AEA, log 1-AG, OEA, PEA and log SEA (all p = 0.05) while log 2-AG did not change. Of 10 VAS, only Happiness increased with exercise in the total cohort (p = 0.02). There were no group x time effects or associations between ECS and VAS responses to exercise. Five patients per group (50%) reported experiencing a Runner’s high.
Conclusions: Exercise increased endocannabinoids and endocannabinoid-like lipid mediators in the total cohort. However, cancer patients exhibited lower AEA, OEA and SEA concentrations versus their peers, indicating potential ECS dysfunction.
Additional research is required to investigate the effect of various modalities and dosages of exercise on ECS markers and the clinical interpretation of these adaptations across a range of cancer populations.”
