Cannabinoid Receptor Type 1 in Parkinson's Disease: A Positron Emission Tomography Study with [18 F]FMPEP-d2

Mov Disord. 2022 Aug;37(8):1673-1682. doi: 10.1002/mds.29117. Epub 2022 Jun 8.

Abstract

Background: 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).

Objective: The aim of this study was to investigate CB1 receptors in PD with [18 F]FMPEP-d2 positron emission tomography (PET) and the effect of dopaminergic medication on the [18 F]FMPEP-d2 binding.

Methods: The data consisted of 16 subjects with PD and 10 healthy control subjects (HCs). All participants underwent a [18 F]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 [18 F]FMPEP-d2 binding, 15 subjects with PD underwent [18 F]FMPEP-d2 PET twice, both on and off antiparkinsonian medication.

Results: [18 F]FMPEP-d2 distribution volume was significantly lower in the off scan compared with the on scan in basal ganglia, thalamus, hippocampus, and amygdala (P < 0.05). Distribution volume was lower in subjects with PD off than in HCs globally (P < 0.05), but not higher than in HCs in any brain region.

Conclusions: Subjects with PD have lower CB1 receptor availability compared with HCs. PD medication increases CB1 receptor toward normal levels. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: CB1 receptor; PET; Parkinson's disease; dopaminergic medication; endocannabinoid system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiparkinson Agents / therapeutic use
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Humans
  • Parkinson Disease* / diagnostic imaging
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / metabolism
  • Positron-Emission Tomography
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB1 / therapeutic use

Substances

  • Antiparkinson Agents
  • Receptor, Cannabinoid, CB1