Objectives: Attention-deficit hyperactivity disorder (ADHD) in adulthood shows high co-occurrence rates with cocaine use disorder (CoUD). The self-medication hypothesis (SMH) provides a theoretical explanation for this comorbidity. This study investigates the neurobiological mechanisms that could support SMH in adult patients with ADHD-CoUD. Materials and Methods: We included 19 ADHD-CoUD (84.2% male; age: 32.11 [7.18]) and 16 CoUD (68.7% male; age: 36.63 [8.12]). All subjects underwent an 18F-FDG-PET brain scan. We tested brain metabolism differences between ADHD-CoUD and CoUD patients using voxel-based and regions of interest (ROIs)-based analyses. The correlation between dependence/abstinence duration and regional brain metabolism was also assessed in the two groups. Lastly, we investigated the integrity of brain metabolic connectivity of mesocorticolimbic and nigrostriatal dopaminergic systems, and large-scale brain networks involved in ADHD and addictions. Results: The voxel-wise and ROIs-based approaches showed that ADHD-CoUD patients had a lower metabolism in the thalamus and increased metabolism in the amygdala and parahippocampus, bilaterally, compared to CoUD subjects and HC. Metabolism in the thalamus negatively correlated with years of dependence in ADHD-CoUD patients. Moreover, connectivity analyses revealed that ADHD-CoUD had a more preserved metabolic connectivity than CoUD in the dopaminergic networks and large-scale networks involved in self-regulation mechanisms of attention and behaviours (i.e., ADMN, ECN, SAN). Conclusions: We demonstrated distinct neuropathological substrates underlying substance-use behaviours in ADHD-CoUD and CoUD. Furthermore, we provided neurobiological evidence in support of SMH, demonstrating that ADHD-CoUD might experience short-term advantages of cocaine assumption (i.e., compensation of dopaminergic deficiency and related cognitive-behavioural deficits).

Parkinson’s disease (PD) is a multifaceted neurodegenerative disorder characterized by dopaminergic neuronal loss and widespread α-synuclein pathology. Nuclear medicine imaging offers essential in vivo tools for early diagnosis, differential assessment, and monitoring disease progression. This review summarizes key PET and SPECT radiotracers targeting dopaminergic synthesis and transport, vesicular storage, post-synaptic receptors, neuroinflammation, and protein aggregation, highlighting their roles in clinical evaluation and phenotyping. Clinically, these modalities support earlier recognition of PD, distinction from atypical parkinsonian syndromes, and assessment of non-motor involvement. Future directions include the development of selective α-synuclein tracers and multimodal imaging strategies to refine prodromal detection and guide personalized therapeutic interventions.