Imaging of cannabinoid type 1 receptor availability in attention deficit/hyperactivity disorder: an [18F]MK 9470 positron emission tomography study

注意缺陷多动障碍（ADHD）是一种神经发育障碍，通常持续到成年，其特征是注意缺陷、多动和冲动。在神经递质水平上已经观察到多巴胺能系统和其他系统的功能障碍，但ADHD的机制尚不完全清楚。多动症的治疗方案包括心理治疗和/或药物治疗，兴奋剂哌甲酯和安非他明是作用于多巴胺能和去甲肾上腺素能系统的首选物质。尽管它们有积极的作用，但它们的有效性受到质疑，因为它们不能满足多动症患者更广泛的临床需求，尤其是从长期来看。研究内源性大麻素系统是一种新的、有前途的方法。由于其在大脑中的广泛分布以及与其他神经递质系统的相互作用，内源性大麻素系统越来越被认为在精神疾病中起着关键作用。我们在本研究中更详细地讨论了冲动性是由额纹状体网络介导的，根据“ADHD双通路模型”，区分了与抑制相关的执行功能和与奖励相关的功能的潜在缺陷。在内源性大麻素系统中，纹状体中大麻素1型受体的可用性与冲动的表达呈负相关。这意味着，在多巴胺假说的背景下，ADHD中多巴胺能参与纹状体和冲动性，以及多巴胺与内源性大麻素系统的相互作用，可以想象，内源性大麻素系统参与了ADHD的病因和发病机制。这项计划研究的新颖之处是，据我们所知，首次使用大麻素1型受体配体[18F]MK-9470和正电子发射断层扫描，研究内源性大麻素系统在（未经治疗的）ADHD研究参与者纹状体中的作用。进一步的研究涉及到大麻素1型受体在整个纹状体，纹状体的背侧和腹侧部分的有效性(参见。“ADHD双通路模型”)以及未治疗的ADHD研究参与者和服用哌甲酯治疗的ADHD研究参与者血液中内源性大麻素的浓度。计划研究的结果是开发目前缺乏的ADHD新药物治疗方法的重要起点。研究结果将有助于改进ADHD的循证治疗策略。

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that often persists into adulthood and is characterised by symptoms of attention deficit, hyperactivity and impulsivity. Dysfunction in the dopaminergic system and other systems has been observed at the neurotransmitter level, but the mechanisms underlying ADHD are incompletely understood. Treatment options for ADHD include psychotherapy and/or pharmacotherapy, with the stimulants methylphenidate and amphetamine being the first-choice substances acting on dopaminergic and noradrenergic systems. Despite their positive effects, their effectiveness is questioned because they do not meet the broader clinical needs of ADHD patients, especially in the longer term. A new and promising approach is to study the endocannabinoid system. Because of its widespread distribution in the brain and interaction with other neurotransmitter systems, the endocannabinoid system is increasingly recognised as playing a key role in psychiatric disorders. Impulsivity, which we discuss in more detail in this study, is mediated by a fronto-striatal network, and according to the "dual pathway model of ADHD", a distinction is made between underlying deficits in inhibition-related executive functions and reward-related functions. With regard to the endocannabinoid system, a negative correlation was shown between cannabinoid type 1 receptor availability in the striatum and the expression of impulsivity. This means that against the background of the dopamine hypothesis, the dopaminergic involvement in the striatum and in impulsivity in ADHD, as well as the interaction between the dopamine and the endocannabinoid system, it is conceivable that the endocannabinoid system is involved in the aetiology and pathogenesis of ADHD. The novel aspect of the planned study is to investigate the role of the endocannabinoid system in the striatum of (untreated) study participants with ADHD, to the best of our knowledge for the first time, using the cannabinoid type 1 receptor ligand [18F]MK-9470 and positron emission tomography. Further aspects relate to the investigation of cannabinoid type 1 receptor availability in the whole striatum, in the dorsal and ventral parts of the striatum (cf. "dual pathway model of ADHD") and the concentration of endocannabinoids in the blood of untreated study participants with ADHD and methylphenidate-treated study participants with ADHD. The result of the planned study is an important starting point for the development of new pharmacological therapy approaches for ADHD, which are currently lacking. The results will help to improve evidence-based therapeutic strategies for the treatment of ADHD.