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Cannabinoid modulation of drug reward and the implications of marijuana legalization

机译：大麻奖励药物的调制及其对大麻合法化的影响

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Marijuana is the most popular illegal drug worldwide. Recent trends indicate that this may soon change; not due to decreased marijuana use, but to an amendment in marijuana's illegal status. The cannabinoid type 1 (CB1) receptor mediates marijuana's psychoactive and reinforcing properties. CB1, receptors are also part of the brain endocannabinoid (eCB) system and support numerous forms of learning and memory, including the conditioned reinforcing properties of cues predicting reward or punishment. This is accomplished via eCB-dependent alterations in mesolimbic dopamine function, which plays an obligatory role in reward learning and motivation. Presynaptic CB1 receptors control midbrain dopamine neuron activity and thereby shape phasic dopamine release in target regions, particularly the nucleus accumbens (NAc). By also regulating synaptic input to the NAc, CB1 receptors modulate NAc output onto downstream neurons of the basal ganglia motor circuit, and thereby support goal-directed behaviors. Abused drugs promote short- and long-term adaptations in eCB-regulation of mesolimbic dopamine function, and thereby hijack neural systems related to the pursuit of rewards to promote drug abuse. By pharmacologically targeting the CB1 receptors, marijuana has preferential access to this neuronal system and can potently alter eCB-dependent processing of reward-related stimuli. As marijuana legalization progresses, greater access to this drug should increase the utility of marijuana as a research tool to better understand the eCB system, which has the potential to advance cannabinoid-based treatments for drug addiction.
机译：大麻是全球最受欢迎的非法毒品。最近的趋势表明，这种情况可能很快就会改变。不是由于减少了大麻的使用，而是由于对大麻的非法身份的修正。大麻素1型（CB1）受体介导大麻的心理活性和增强特性。 CB1受体也是大脑内源性大麻素（eCB）系统的一部分，支持多种形式的学习和记忆，包括预测奖励或惩罚的线索的条件增强特性。这是通过依赖eCB的中脑边缘多巴胺功能改变来实现的，这种改变在奖励学习和动机中起着必不可少的作用。突触前的CB1受体控制中脑多巴胺神经元的活性，从而影响目标区域（尤其是伏伏核）中阶段性多巴胺的释放。通过还调节到NAc的突触输入，CB1受体将NAc输出调节到基底神经节运动回路的下游神经元上，从而支持目标定向行为。滥用药物会促进中脑边缘多巴胺功能的eCB调节的短期和长期适应，从而劫持与追求奖励以促进滥用药物有关的神经系统。通过药理学上靶向CB1受体，大麻可以优先进入该神经元系统，并且可以有效改变eCB依赖的奖励相关刺激的处理。随着大麻合法化的进展，更多地使用这种药物应增加大麻作为研究工具的效用，以更好地了解eCB系统，eCB系统有可能促进基于大麻的药物成瘾治疗。

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