The synthetic cannabinoid 5F-AMB, when injected into the brain of mice, reduces anxiety and impairs the acquisition of recognition memory by activating CB1 receptors. Systemic injection severely reduces movement, an effect partially blocked by a CB1 antagonist. Infusion into the medial prefrontal cortex impairs memory acquisition but does not affect anxiety, suggesting other brain regions mediate the anxiolytic effect.
5F-AMB, a synthetic cannabinoid abused worldwide, reduces both excitatory and inhibitory signaling in layer V pyramidal neurons of the medial prefrontal cortex by activating CB1 receptors on presynaptic terminals. Bath application of 5F-AMB decreased the frequency of spontaneous and miniature excitatory and inhibitory postsynaptic currents, an effect blocked by the CB1 antagonist AM251. The suppression of excitatory transmission was greater than that of inhibitory transmission, shifting the balance toward net inhibition of these neurons. This inhibitory effect may contribute to the memory and consciousness impairments observed after inhalation of 5F-AMB.