Alghamdi Sahar S, Albahlal Hussah N, Aloumi Danah E, Bin Saqyah Sarah, Alsubait Arwa, Alamre Jehan, Alrashed Mohammed, Alsuhabeny Nada, Mohammed Afrah E
Department of Pharmaceutical Sciences, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, 11451, Riyadh, Saudi Arabia.
Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guards Health Affairs, Riyadh, Saudi Arabia.
J Cannabis Res. 2025 Jun 7;7(1):33. doi: 10.1186/s42238-025-00289-5.
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.
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.
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.
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.
癌症仍然是一个重大的全球健康问题，这促使人们需要创新的治疗方法，这些方法要超越化疗和放疗等传统方法。内源性大麻素系统（ECS），主要是大麻素受体CB1R和CB2R，通过选择性地靶向细胞信号通路，为癌症治疗提供了一个有前景的机会。本系统评价旨在探讨合成大麻素作为潜在抗癌药物的作用模式及其对各种癌细胞系中肿瘤生长的影响。
在1990年1月至2024年7月期间确定的287篇文章中，有27项研究符合聚焦其抗癌作用的严格标准。使用GRADE标准和Cochrane偏倚风险工具进行数据提取和质量评估，以确保对研究可靠性进行有力评估。
合成大麻素的各种药理作用在CB1R和CB2R受体上分别作为激动剂、拮抗剂和反向激动剂发挥作用。主要研究结果表明，CB2R激动剂通过多种机制显著降低癌细胞增殖，选择性CB2R激动剂可有效抑制癌细胞生长和存活。涉及CB1R拮抗剂的研究，特别是与CB2R激动剂联合使用时，突出了它们在阻断CB1R以验证或增强CB2R激动剂减轻肿瘤生长疗效方面的作用。靶向CB2R的反向激动剂在通过破坏生存途径诱导癌细胞死亡方面取得了一定成功。值得注意的是，合成大麻素激动剂在靶向CB1和CB2受体以抑制各种癌症类型的肿瘤增殖和促进凋亡方面显示出巨大潜力。
本系统评价得出结论，CB2R激动剂可有效抑制肿瘤生长，同时诱导各种癌症中的细胞凋亡。虽然CB1R激动剂在调节癌症通路方面显示出潜力，但对CB1反向激动剂的研究明显不足，强调了进一步研究的必要性。此外，该研究主张进一步探索混合受体激动剂和受体作用模式，以验证这些有前景的治疗方法。
