Wang Xingbo, Xie Han, Shi Xiaoling, Wu Kusheng, Huang Wenlong
Department of Forensic Medicine, Shantou University Medical College, Shantou 515041, China.
Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, China.
Int J Mol Sci. 2025 Sep 19;26(18):9165. doi: 10.3390/ijms26189165.
Cannabis is increasingly utilized for both recreational and medical purposes, and the discovery of the endocannabinoid system (ECS) has renewed interest in its therapeutic potential. Nonetheless, the safety of cannabis and cannabinoid-containing products requires re-evaluation. In this study, zebrafish were employed as a translational in vivo model to comprehensively evaluate the toxicological profiles and the therapeutic potential of phytocannabinoids and synthetic cannabinoids. Current evidence, particularly from studies on key phytocannabinoids such as Δ-THC, CBD, and CBN, along with newly developed synthetic cannabinoids (such as JWH-018), demonstrates a spectrum of embryotoxic outcomes including developmental abnormalities, neurotoxicity, liver damage, reproductive impairments, and disturbances in metabolic regulation, especially during early life stages. By contrast, evidence for therapeutic benefits, such as alleviation of muscle spasms, pain and nausea, as well as neuroprotective and anti-inflammatory effects, is promising but comparatively less abundant and more heterogeneous in study design and outcome measures. Taken together, this imbalance indicates that toxicological risks are supported by more extensive and consistent data, whereas therapeutic efficacy, though encouraging, still requires more rigorous validation. This dual profile underscores the need for a robust, evidence-based framework for cannabinoid development and clinical application. Further investigations are essential to clarify mechanisms of toxicity and therapeutic action, optimize dosing regimens, define safe therapeutic windows, and evaluate long-term health outcomes.
大麻越来越多地用于娱乐和医疗目的，内源性大麻素系统（ECS）的发现重新引发了人们对其治疗潜力的兴趣。尽管如此，大麻及含大麻素产品的安全性仍需重新评估。在本研究中，斑马鱼被用作一种转化体内模型，以全面评估植物大麻素和合成大麻素的毒理学特征及治疗潜力。目前的证据，特别是来自对关键植物大麻素（如Δ-THC、CBD和CBN）以及新开发的合成大麻素（如JWH-018）的研究表明，一系列胚胎毒性结果包括发育异常、神经毒性、肝损伤、生殖障碍以及代谢调节紊乱，尤其是在生命早期阶段。相比之下，关于治疗益处的证据，如缓解肌肉痉挛、疼痛和恶心，以及神经保护和抗炎作用，虽然很有前景，但在研究设计和结果测量方面相对较少且更为多样。综上所述，这种不平衡表明毒理学风险有更广泛和一致的数据支持，而治疗效果虽然令人鼓舞，但仍需要更严格的验证。这种双重特征强调了建立一个强大的、基于证据的大麻素开发和临床应用框架的必要性。进一步的研究对于阐明毒性和治疗作用机制、优化给药方案、确定安全治疗窗口以及评估长期健康结果至关重要。
