Revealing the therapeutic potential of synthetic cannabinoids: a systematic review of cannabinoid receptor binding dynamics and their implications for cancer therapy
Abstract Background Cancer remains a major global health issue, prompting the need for innovative treatment approaches that extend beyond conventional methods such as chemotherapy and radiation. The endocannabinoid system (ECS), primarily the cannabinoid receptors CB1R and CB2R, presents a promising...
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| Format: | Article |
| Language: | English |
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BMC
2025-06-01
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| Series: | Journal of Cannabis Research |
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| Online Access: | https://doi.org/10.1186/s42238-025-00289-5 |
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| author | Sahar S. Alghamdi Hussah N. Albahlal Danah E. Aloumi Sarah Bin Saqyah Arwa Alsubait Jehan Alamre Mohammed Alrashed Nada Alsuhabeny Afrah E. Mohammed |
| author_facet | Sahar S. Alghamdi Hussah N. Albahlal Danah E. Aloumi Sarah Bin Saqyah Arwa Alsubait Jehan Alamre Mohammed Alrashed Nada Alsuhabeny Afrah E. Mohammed |
| author_sort | Sahar S. Alghamdi |
| collection | DOAJ |
| description | Abstract Background Cancer remains a major global health issue, prompting the need for innovative treatment approaches that extend beyond conventional methods such as chemotherapy and radiation. The endocannabinoid system (ECS), primarily the cannabinoid receptors CB1R and CB2R, presents a promising opportunity for cancer therapy by selectively targeting cell signaling pathways. This systematic review intends to explore the mode of action of synthetic cannabinoids as potential anticancer agents and their impact on tumor growth in various cancer cell lines. Methods Of the 287 articles identified between January 1990 and July 2024, 27 studies met strict criteria focusing on their anticancer effects. Data extraction and quality assessment were conducted using GRADE criteria and the Cochrane Risk of Bias tool, ensuring robust evaluation of the studies' reliability. Results Various pharmacological actions of synthetic cannabinoids function as agonists, antagonists, and inverse agonists at the CB1R and CB2R receptors. Key findings indicate that CB2R agonists significantly reduce cancer cell proliferation through diverse mechanisms, with selective CB2R agonists effectively inhibiting cancer cell growth and survival. Studies involving CB1R antagonists, particularly in conjunction with CB2R agonists, highlight their role in blocking CB1R to either validate or enhance the efficacy of CB2R agonists in mitigating tumor growth. Inverse agonists targeting CB2R have shown moderate success in inducing cancer cell death by disrupting survival pathways. Notably, synthetic cannabinoid agonists display significant potential in targeting CB1 and CB2 receptors to inhibit tumor proliferation and promote apoptosis across various cancer types. Conclusion The systematic review concludes that CB2R agonists can effectively inhibit tumor growth while inducing apoptosis in various cancers. Although CB1R agonists show potential in modulating cancer pathways, there is a notable lack of research on CB1 inverse agonists, emphasizing the need for further investigation. Additionally, the study advocates for greater exploration of mixed receptor agonist and receptor mode of action to validate these promising therapeutic approaches. Graphical Abstract |
| format | Article |
| id | doaj-art-7cbd4a6033944ed0871b22e529239e4f |
| institution | DOAJ |
| issn | 2522-5782 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Cannabis Research |
| spelling | doaj-art-7cbd4a6033944ed0871b22e529239e4f2025-08-20T03:10:39ZengBMCJournal of Cannabis Research2522-57822025-06-017112210.1186/s42238-025-00289-5Revealing the therapeutic potential of synthetic cannabinoids: a systematic review of cannabinoid receptor binding dynamics and their implications for cancer therapySahar S. Alghamdi0Hussah N. Albahlal1Danah E. Aloumi2Sarah Bin Saqyah3Arwa Alsubait4Jehan Alamre5Mohammed Alrashed6Nada Alsuhabeny7Afrah E. Mohammed8Department of Pharmaceutical Sciences, College of Pharmacy, King Saud Bin Abdulaziz University for Health SciencesDepartment of Pharmaceutical Sciences, College of Pharmacy, King Saud Bin Abdulaziz University for Health SciencesDepartment of Pharmaceutical Sciences, College of Pharmacy, King Saud Bin Abdulaziz University for Health SciencesDepartment of Pharmaceutical Sciences, College of Pharmacy, King Saud Bin Abdulaziz University for Health SciencesDepartment of Pharmaceutical Sciences, College of Pharmacy, King Saud Bin Abdulaziz University for Health SciencesKing Abdulaziz Medical City, National Guard Health Affairs (NGHA)Department of Pharmaceutical Sciences, College of Pharmacy, King Saud Bin Abdulaziz University for Health SciencesDepartment of Pharmaceutical Sciences, College of Pharmacy, King Saud Bin Abdulaziz University for Health SciencesDepartment of Biology, Faculty of Science, Princess Nourah Bint Abdulrahman UniversityAbstract Background Cancer remains a major global health issue, prompting the need for innovative treatment approaches that extend beyond conventional methods such as chemotherapy and radiation. The endocannabinoid system (ECS), primarily the cannabinoid receptors CB1R and CB2R, presents a promising opportunity for cancer therapy by selectively targeting cell signaling pathways. This systematic review intends to explore the mode of action of synthetic cannabinoids as potential anticancer agents and their impact on tumor growth in various cancer cell lines. Methods Of the 287 articles identified between January 1990 and July 2024, 27 studies met strict criteria focusing on their anticancer effects. Data extraction and quality assessment were conducted using GRADE criteria and the Cochrane Risk of Bias tool, ensuring robust evaluation of the studies' reliability. Results Various pharmacological actions of synthetic cannabinoids function as agonists, antagonists, and inverse agonists at the CB1R and CB2R receptors. Key findings indicate that CB2R agonists significantly reduce cancer cell proliferation through diverse mechanisms, with selective CB2R agonists effectively inhibiting cancer cell growth and survival. Studies involving CB1R antagonists, particularly in conjunction with CB2R agonists, highlight their role in blocking CB1R to either validate or enhance the efficacy of CB2R agonists in mitigating tumor growth. Inverse agonists targeting CB2R have shown moderate success in inducing cancer cell death by disrupting survival pathways. Notably, synthetic cannabinoid agonists display significant potential in targeting CB1 and CB2 receptors to inhibit tumor proliferation and promote apoptosis across various cancer types. Conclusion The systematic review concludes that CB2R agonists can effectively inhibit tumor growth while inducing apoptosis in various cancers. Although CB1R agonists show potential in modulating cancer pathways, there is a notable lack of research on CB1 inverse agonists, emphasizing the need for further investigation. Additionally, the study advocates for greater exploration of mixed receptor agonist and receptor mode of action to validate these promising therapeutic approaches. Graphical Abstracthttps://doi.org/10.1186/s42238-025-00289-5CB1 ReceptorCB2 ReceptorSynthetic CannabinoidCancerAgonistAntagonist |
| spellingShingle | Sahar S. Alghamdi Hussah N. Albahlal Danah E. Aloumi Sarah Bin Saqyah Arwa Alsubait Jehan Alamre Mohammed Alrashed Nada Alsuhabeny Afrah E. Mohammed Revealing the therapeutic potential of synthetic cannabinoids: a systematic review of cannabinoid receptor binding dynamics and their implications for cancer therapy Journal of Cannabis Research CB1 Receptor CB2 Receptor Synthetic Cannabinoid Cancer Agonist Antagonist |
| title | Revealing the therapeutic potential of synthetic cannabinoids: a systematic review of cannabinoid receptor binding dynamics and their implications for cancer therapy |
| title_full | Revealing the therapeutic potential of synthetic cannabinoids: a systematic review of cannabinoid receptor binding dynamics and their implications for cancer therapy |
| title_fullStr | Revealing the therapeutic potential of synthetic cannabinoids: a systematic review of cannabinoid receptor binding dynamics and their implications for cancer therapy |
| title_full_unstemmed | Revealing the therapeutic potential of synthetic cannabinoids: a systematic review of cannabinoid receptor binding dynamics and their implications for cancer therapy |
| title_short | Revealing the therapeutic potential of synthetic cannabinoids: a systematic review of cannabinoid receptor binding dynamics and their implications for cancer therapy |
| title_sort | revealing the therapeutic potential of synthetic cannabinoids a systematic review of cannabinoid receptor binding dynamics and their implications for cancer therapy |
| topic | CB1 Receptor CB2 Receptor Synthetic Cannabinoid Cancer Agonist Antagonist |
| url | https://doi.org/10.1186/s42238-025-00289-5 |
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