Cannabidiol Inhibits Endocannabinoid Signaling in Autaptic Hippocampal Neurons

Summary & key facts

Researchers put mouse brain cells in a dish to study how cannabidiol, or CBD, changes signaling at a type of receptor called CB1 that responds to the brain’s own cannabis-like chemicals. They found that CBD did not change normal excitatory signaling by itself. But CBD did reduce two kinds of natural, CB1-dependent feedback that quiet down excitatory signals. The pattern of effects fits with CBD acting at a secondary spot on the CB1 receptor and making the receptor less responsive. These experiments were done on isolated neurons in a lab, so the results show a possible way CBD can change brain signaling, but they do not prove what CBD does in people or during normal brain activity.

Key facts:

• The team used mouse hippocampal neurons grown as single self-connecting cells to study endocannabinoid signaling in a controlled lab system.
• CBD by itself did not change basic excitatory synaptic currents, so it did not directly shut down normal transmission in these neurons.
• When researchers triggered the neurons to release their own endocannabinoid messenger, CBD reduced two forms of that natural feedback: depolarization-induced suppression of excitation and metabotropic suppression of excitation.
• The change was concentration-dependent: low, medium, and higher concentrations of CBD progressively weakened the endocannabinoid signaling, shifting the response so more stimulation was needed for the same effect.
• The pattern of results is consistent with CBD acting as a negative allosteric modulator of the CB1 receptor, meaning CBD likely binds to a secondary site on CB1 and reduces how strongly the receptor responds to the brain’s own cannabinoids.
• CBD did not affect signaling that works through GABA-B receptors, which suggests the CBD effect was relatively specific to the endocannabinoid/CB1 pathway.
• Because the study used mouse neurons in a dish, the findings might not match what happens in a living brain or in people, and the concentrations used in cells are not the same as doses people take.

Topics

Cannabis and Cannabinoid Research Neuroscience and Neuropharmacology Research Sleep and Wakefulness Research

Categories

Health Sciences Medicine Pharmacology

Tags

Allosteric regulation Antagonist Biochemistry Biology Cannabidiol Cannabinoid Cannabinoid receptor Cannabis Chemistry Depolarization-induced suppression of inhibition Endocannabinoid system Excitatory postsynaptic potential Glutamate receptor Medicine Metabotropic glutamate receptor Neuroscience Neurotransmission Pharmacology Psychiatry Receptor

Substances

Cannabis