Fisar Zdenek
Department of Psychiatry, 1st Faculty of Medicine, Charles University in Prague, Ke Karlovu 11, 128 01 Prague 2, Czech Republic.
Curr Drug Abuse Rev. 2009 Jan;2(1):51-75. doi: 10.2174/1874473710902010051.
Progress in understanding the molecular mechanisms of cannabis action was made after discovery of cannabinoid receptors in the brain and the finding of endogenous metabolites with affinity to them. Activation of cannabinoid receptors on synaptic terminals results in regulation of ion channels, neurotransmitter release and synaptic plasticity. Neuromodulation of synapses by the cannabinoids is proving to have a wide range of functional effects, making them potential targets as medical preparations in a variety of illnesses, including some mental disorders and neurodegenerative illnesses. Cannabis contains a large amount of substances with affinity for the cannabinoid receptors. The endocannabinoids are a family of lipid neurotransmitters that engage the same membrane receptors targeted by tetrahydrocannabinol and that mediate retrograde signal from postsynaptic neurons to presynaptic ones. Discovery of endogenous cannabinoids and studies of the physiological functions of the cannabinoid system in the brain and body are producing a number of important findings about the role of membrane lipids and fatty acids in nerve signal transduction. Plant, endogenous and synthetic cannabinoids are using in these studies. The role of lipid membranes in the cannabinoid system follows from the fact that the source and supply of endogenous cannabinoids are derived from arachidonic acid, an important membrane constituent. The study of structure-activity relationships of molecules which influence the cannabinoid system in the brain and body is crucial in search of medical preparations with the therapeutic effects of the phytocannabinoids without the negative effects on cognitive function attributed to cannabis.
在大脑中发现大麻素受体以及发现对其具有亲和力的内源性代谢产物之后,对大麻作用分子机制的理解取得了进展。突触末端大麻素受体的激活导致离子通道、神经递质释放和突触可塑性的调节。大麻素对突触的神经调节作用已被证明具有广泛的功能效应,使其成为包括某些精神障碍和神经退行性疾病在内的多种疾病的潜在医学制剂靶点。大麻含有大量对大麻素受体具有亲和力的物质。内源性大麻素是一类脂质神经递质,它们作用于与四氢大麻酚靶向相同的膜受体,并介导从突触后神经元到突触前神经元的逆行信号。内源性大麻素的发现以及对大脑和身体中大麻素系统生理功能的研究,正在产生许多关于膜脂质和脂肪酸在神经信号转导中作用的重要发现。植物性、内源性和合成性大麻素都用于这些研究。脂质膜在大麻素系统中的作用源于内源性大麻素的来源和供应都来自花生四烯酸这一重要膜成分这一事实。研究影响大脑和身体中大麻素系统的分子的构效关系,对于寻找具有植物大麻素治疗效果但无大麻对认知功能负面影响的医学制剂至关重要。