“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.”
https://pubmed.ncbi.nlm.nih.gov/34259916
“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.”
https://link.springer.com/article/10.1007/s00432-021-03710-7
