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Basic Science and Pathogenesis.

Paula Subirana1, Núria Sánchez1, Francisco Ciruela1

  • 1Universitat de Barcelona, Barcelona, Barcelona, Spain.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
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Natural cannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD), modulate brain activity in an Alzheimer

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Alzheimer's Disease Research

Background:

  • Previous studies showed that non-psychotropic doses of THC and CBD reduce cognitive decline and hippocampal glutamate levels in APP/PS1 mice.
  • Alzheimer's disease (AD) is associated with cognitive decline and non-cognitive symptoms, potentially linked to neurotransmitter dysregulation.

Purpose of the Study:

  • To investigate if natural cannabinoids (THC and CBD) modulate dopaminergic activity in limbic areas relevant to non-cognitive AD symptoms.
  • To assess the effect of chronic THC and CBD treatment on neurotransmitter dynamics in an animal model of Alzheimer's disease.

Main Methods:

  • Utilized glutamate and dopamine biosensors with fiber photometry to measure neurotransmitter levels in the hippocampus and nucleus accumbens (NAcc).
  • Experiments were conducted in both anesthetized and awake APP/PS1 mice during electrophysiological recordings and behavioral tests (novel object recognition, open field, sociability, prepulse inhibition).

Main Results:

  • Chronic THC and CBD treatment normalized hippocampal glutamate peaks during a memory task in early-stage AD mice.
  • Advanced-stage AD mice showed altered dopamine dynamics in the NAcc, resembling psychotic-like traits, which were partially improved by THC and CBD treatment.

Conclusions:

  • The combination of THC and CBD modulates hippocampal glutamatergic activity and subsequently reduces dopaminergic alterations in limbic areas in an AD mouse model.
  • These findings suggest that natural cannabinoids may offer a therapeutic strategy for both cognitive and non-cognitive symptoms of Alzheimer's disease.