Background

Evidence suggests that an overlap exists between the neurobiology of psychotic disorders and the effects of cannabinoids on neurocognitive and neurochemical substrates involved in reward processing.

Aims

We investigate whether the psychotomimetic effects of delta-9-tetrahydrocannabinol (THC) and the antipsychotic potential of cannabidiol (CBD) are underpinned by their effects on the reward system and dopamine.

Methods

This narrative review focuses on the overlap between altered dopamine signalling and reward processing induced by cannabinoids, pre-clinically and in humans. A systematic search was conducted of acute cannabinoid drug-challenge studies using neuroimaging in healthy subjects and those with psychosis

Results

There is evidence of increased striatal presynaptic dopamine synthesis and release in psychosis, as well as abnormal engagement of the striatum during reward processing. Although, acute THC challenges have elicited a modest effect on striatal dopamine, cannabis users generally indicate impaired presynaptic dopaminergic function. Functional MRI studies have identified that a single dose of THC may modulate regions involved in reward and salience processing such as the striatum, midbrain, insular, and anterior cingulate, with some effects correlating with the severity of THC-induced psychotic symptoms. CBD may modulate brain regions involved in reward/salience processing in an opposite direction to that of THC.

Conclusions

There is evidence to suggest modulation of reward processing and its neural substrates by THC and CBD. Whether such effects underlie the psychotomimetic/antipsychotic effects of these cannabinoids remains unclear. Future research should address these unanswered questions to understand the relationship between endocannabinoid dysfunction, reward processing abnormalities, and psychosis.

中文翻译：

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大麻素、奖励处理和精神病

 背景

有证据表明，精神障碍的神经生物学与大麻素对参与奖励处理的神经认知和神经化学底物的影响之间存在重叠。

 目标

我们研究了 delta-9-四氢大麻酚 (THC) 的拟精神病作用和大麻二酚 (CBD) 的抗精神病潜力是否是由它们对奖励系统和多巴胺的影响所支撑的。

 方法

这篇叙述性评论的重点是临床前和人类中大麻素引起的多巴胺信号改变和奖励处理之间的重叠。使用神经影像学对健康受试者和精神病患者进行急性大麻素药物挑战研究的系统检索

 结果

有证据表明，精神病中纹状体突触前多巴胺的合成和释放增加，以及奖赏处理过程中纹状体的异常参与。尽管四氢大麻酚的急性挑战对纹状体多巴胺产生了适度的影响，但大麻使用者普遍表明突触前多巴胺能功能受损。功能性 MRI 研究发现，单剂量的 THC 可能会调节涉及奖赏和显着性处理的区域，如纹状体、中脑、岛叶和前扣带回，其一些作用与 THC 引起的精神病症状的严重程度相关。 CBD 可能以与 THC 相反的方向调节参与奖励/显着性处理的大脑区域。

 结论

有证据表明 THC 和 CBD 可以调节奖励处理及其神经底物。这些作用是否是这些大麻素的拟精神病/抗精神病作用的基础尚不清楚。未来的研究应该解决这些悬而未决的问题，以了解内源性大麻素功能障碍、奖励处理异常和精神病之间的关系。