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Sex difference in brain CB1 receptor availability in man.

Heikki Laurikainen1, Lauri Tuominen2, Maria Tikka3

  • 1Turku PET Centre, Turku University Hospital, Finland; Department of Psychiatry, University of Turku and Turku University Hospital, Finland.

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|October 9, 2018
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Summary

Men have significantly higher brain cannabinoid CB1 receptor (CB1R) availability than women, particularly in specific brain regions. This difference may influence cognitive functions like visuospatial working memory.

Keywords:
EndocannabinoidSex differenceWorking memorycb1 receptor

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Area of Science:

  • Neuroscience
  • Endocrinology
  • Radiology

Background:

  • The endocannabinoid system (ECS) plays a crucial role in central nervous system neuromodulation, impacting brain development, plasticity, reward, and stress.
  • Cannabinoid CB1 receptor (CB1R) is a key mediator of ECS functions, with animal studies suggesting sex differences in its expression.
  • Previous human studies on sex differences in brain CB1R availability have produced conflicting results.

Purpose of the Study:

  • To investigate in vivo gender differences in CB1R availability in the human brain using positron emission tomography (PET).
  • To explore the relationship between CB1R availability and neuropsychological functioning, specifically visuospatial working memory.

Main Methods:

  • Utilized a specific CB1R tracer, [18F]FMPEP-d2, and PET imaging in 11 healthy males and 11 healthy females.
  • Quantified regional CB1R availability by measuring the distribution volume of the PET tracer.
  • Employed voxel-based analyses to correlate CB1R availability with performance on visuospatial working memory tasks.

Main Results:

  • Males exhibited significantly higher CB1R availability compared to females (41% higher on average, p=0.002).
  • This sex difference was pronounced in the posterior cingulate and retrosplenial cortices (p=0.001).
  • CB1R availability showed an inverse association with visuospatial working memory performance in both sexes (p<0.001).

Conclusions:

  • A substantial sex difference in brain CB1R availability was confirmed in vivo, with higher availability in males.
  • This observed difference has significant implications for designing studies on neuropsychiatric disorders involving the ECS.
  • The findings suggest a potential link between CB1R availability and working memory, warranting further investigation into its behavioral and clinical significance.