Durydivka Oleh, Palivec Petr, Gazdarica Matej, Mackie Ken, Blahos Jaroslav, Kuchar Martin
Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20, Prague 4, Czech Republic.
Forensic Laboratory of Biologically Active Substances, Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technicka 3, Prague, Czech Republic.
Sci Rep. 2024 Apr 22;14(1):9181. doi: 10.1038/s41598-024-58845-7.
The Cannabis sativa plant has been used for centuries as a recreational drug and more recently in the treatment of patients with neurological or psychiatric disorders. In many instances, treatment goals include relief from posttraumatic disorders, anxiety, or to support treatment of chronic pain. Ligands acting on cannabinoid receptor 1 (CB1R) are also potential targets for the treatment of other health conditions. Using an evidence-based approach, pharmacological investigation of CB1R agonists is timely, with the aim to provide chronically ill patients relief using well-defined and characterized compounds from cannabis. Hexahydrocannabinol (HHC), currently available over the counter in many countries to adults and even children, is of great interests to policy makers, legal administrators, and healthcare regulators, as well as pharmacologists. Herein, we studied the pharmacodynamics of HHC epimers, which activate CB1R. We compared their key CB1R-mediated signaling pathway activities and compared them to the pathways activated by Δ-tetrahydrocannabinol (Δ-THC). We provide evidence that activation of CB1R by HHC ligands is only broadly comparable to those mediated by Δ-THC, and that both HHC epimers have unique properties. Together with the greater chemical stability of HHC compared to Δ-THC, these molecules have a potential to become a part of modern medicine.
大麻植物几个世纪以来一直被用作消遣性毒品，最近也用于治疗神经或精神疾病患者。在许多情况下，治疗目标包括缓解创伤后疾病、焦虑，或辅助治疗慢性疼痛。作用于大麻素受体1（CB1R）的配体也是治疗其他健康状况的潜在靶点。采用循证方法对CB1R激动剂进行药理学研究正当时，目的是使用从大麻中提取的明确且特性良好的化合物为慢性病患者提供缓解。六氢大麻酚（HHC）目前在许多国家可在柜台买到，供成人甚至儿童使用，受到政策制定者、法律管理人员、医疗监管机构以及药理学家的极大关注。在此，我们研究了激活CB1R的HHC差向异构体的药效学。我们比较了它们关键的CB1R介导的信号通路活性，并将其与δ-四氢大麻酚（δ-THC）激活的通路进行比较。我们提供的证据表明，HHC配体对CB1R的激活仅在大致上与δ-THC介导的激活相当，并且两种HHC差向异构体都具有独特的性质。与δ-THC相比，HHC具有更高的化学稳定性，这些分子有可能成为现代医学的一部分。
