Faculty of Psychology and Neuroscience, Department of Neuropsychology and Psychopharmacology, Maastricht University, the Netherlands.
Faculty of Psychology and Neuroscience, Department of Neuropsychology and Psychopharmacology, Maastricht University, the Netherlands.
Eur Neuropsychopharmacol. 2020 Jul;36:191-205. doi: 10.1016/j.euroneuro.2020.01.006. Epub 2020 Feb 1.
Acute exposure to cannabis comes with neurocognitive impairment, leading to increased risk of human error and injury. Evidence however indicates that such acute effects are less prominent in chronic users, suggesting cannabis tolerance. Models of cannabis tolerance stress the importance of neurobiological or behavioral adaptations following repeated cannabis exposure. The pharmacodynamic model relates neuroadaptive changes in the brain to a blunted response to cannabis. Downregulation of CB1 receptors in chronic cannabis users has been associated with a normalization of dopaminergic output from the ventral tegmental area to the mesolimbic circuit, and a reduction of impairment during acute cannabis exposure. Such neuroadaptions are absent in occasional users, who show strong increments of dopamine and glutamate levels in the striatum, a loss of functional connectivity within the mesolimbic circuit and neurocognitive impairments when exposed to cannabis. Evidence for a behavioral model of cannabis tolerance that poses that users can have volitional control to overcome functional impairment during cannabis intoxication is relatively weak, and at best shows limited control over a limited number of behavioral functions. Cannabis tolerance is most likely to occur in users that consume high doses of cannabis continuously, at a high pace, for a prolonged period of time. Knowledge on frequency, dose and duration of cannabis use that is needed to achieve, maintain or lessen tolerance however is very limited, but will be of importance in the context of cannabis therapeutics and in legal settings when evaluating the impact of cannabis exposure on human function.
急性暴露于大麻会导致认知功能障碍，增加人为错误和受伤的风险。然而，有证据表明，慢性使用者的这种急性效应不那么明显，这表明大麻有耐受性。大麻耐受性模型强调了在反复接触大麻后神经生物学或行为适应性的重要性。药效动力学模型将大脑中的神经适应性变化与对大麻反应迟钝联系起来。慢性大麻使用者的 CB1 受体下调与腹侧被盖区到中脑边缘回路多巴胺输出的正常化有关，并且在急性大麻暴露期间损伤减少。偶尔使用者则没有这种神经适应性，他们在纹状体中表现出多巴胺和谷氨酸水平的强烈增加，中脑边缘回路的功能连接丧失，以及暴露于大麻时的认知功能障碍。关于存在一种可以通过自愿控制来克服大麻中毒期间功能障碍的大麻耐受性行为模型的证据相对较弱，而且充其量只能对有限数量的行为功能进行有限的控制。大麻耐受性最有可能发生在持续、高剂量、长时间使用大麻的使用者中。然而，关于实现、维持或减轻耐受性所需的大麻使用频率、剂量和持续时间的知识非常有限，但在大麻治疗和评估大麻暴露对人类功能的影响的法律背景下具有重要意义。
