Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy.
Institute of Applied Physics "Nello Carrara", National Research Council (IFAC-CNR), Via Madonna del Piano 10, 50019 Sesto Fiorentino, Italy.
Int J Mol Sci. 2022 Oct 12;23(20):12144. doi: 10.3390/ijms232012144.
Cannabinoids, used for centuries for recreational and medical purposes, have potential therapeutic value in stroke treatment. Cannabidiol (CBD), a non-psychoactive compound and partial agonist of TRPV2 channels, is efficacious in many neurological disorders. We investigated the effects of CBD or Δ9-tetrahydrocannabinol (THC) in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation (OGD), an in vitro model of ischemia. Neuronal TRPV2 expression decreased after OGD, but it increased in activated, phagocytic microglia. CBD increased TRPV2 expression, decreased microglia phagocytosis, and increased rod microglia after OGD. THC had effects contrary to those of CBD. Our results show that cannabinoids have different effects in ischemia. CBD showed neuroprotective effects, mediated, at least in part, by TRPV2 channels, since the TRPV2 antagonist tranilast blocked them, while THC worsened the neurodegeneration caused by ischemia. In conclusion, our results suggest that different cannabinoid molecules play different roles in the mechanisms of post-ischemic neuronal death. These different effects of cannabinoid observed in our experiments caution against the indiscriminate use of cannabis or cannabinoid preparations for recreational or therapeutic use. It was observed that the positive effects of CBD may be counteracted by the negative effects caused by high levels of THC.
大麻素用于娱乐和医疗目的已有几个世纪的历史，它们在中风治疗中具有潜在的治疗价值。大麻二酚（CBD）是一种非精神活性化合物和 TRPV2 通道的部分激动剂，在许多神经疾病中都有效。我们研究了 CBD 或 Δ9-四氢大麻酚（THC）在氧葡萄糖剥夺（OGD）暴露的大鼠器官型海马切片中的作用，OGD 是缺血的体外模型。OGD 后神经元 TRPV2 表达减少，但在激活的吞噬性小胶质细胞中增加。CBD 增加 TRPV2 表达，减少小胶质细胞吞噬作用，并增加 OGD 后的杆状小胶质细胞。THC 的作用与 CBD 相反。我们的结果表明，大麻素在缺血中有不同的作用。CBD 表现出神经保护作用，至少部分是通过 TRPV2 通道介导的，因为 TRPV2 拮抗剂曲尼司特阻断了这些作用，而 THC 则加重了缺血引起的神经退行性变。总之，我们的结果表明，不同的大麻素分子在缺血后神经元死亡的机制中发挥不同的作用。在我们的实验中观察到的大麻素的这些不同作用告诫人们不要将大麻或大麻素制剂用于娱乐或治疗目的。观察到 CBD 的积极作用可能会被 THC 水平升高引起的负面作用所抵消。
