Cannabinoid Receptor Type 1 in Parkinson's Disease: A Positron Emission Tomography Study with [F-18]FMPEP-d(2)

Abstract

<p><b>Background:</b> The endocannabinoid system is a widespread neuromodulatory system affecting several biological functions and processes. High densities of type 1 cannabinoid (CB1) receptors and endocannabinoids are found in basal ganglia, which makes them an interesting target group for drug development in basal ganglia disorders such as Parkinson's disease (PD). <br></p><p><b>Objective:</b> The aim of this study was to investigate CB1 receptors in PD with [¹⁸F]FMPEP-d₂ positron emission tomography (PET) and the effect of dopaminergic medication on the [¹⁸F]FMPEP-d₂ binding. <br></p><p><b>Methods:</b> The data consisted of 16 subjects with PD and 10 healthy control subjects (HCs). All participants underwent a [¹⁸F]FMPEP-d₂ high-resolution research tomograph PET examination for the quantitative assessment of cerebral binding to CB1 receptors. To investigate the effect of dopaminergic medication on the [¹⁸F]FMPEP-d₂) binding, 15 subjects with PD underwent [¹⁸F]FMPEP-d₂ PET twice, both <i>on</i> and <i>off</i> antiparkinsonian medication. <br></p><p><b>Results:</b> [¹⁸F]FMPEP-d₂ distribution volume was significantly lower in the <i>off</i> scan compared with the <i>on</i> scan in basal ganglia, thalamus, hippocampus, and amygdala (P < 0.05). Distribution volume was lower in subjects with PD <i>off</i> than in HCs globally (P < 0.05), but not higher than in HCs in any brain region. <br></p><p><b>Conclusions:</b> Subjects with PD have lower CB1 receptor availability compared with HCs. PD medication increases CB1 receptor toward normal levels. (c) 2022 The Authors. <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society<br></p>