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

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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.