Possible Interaction: Gamma-Aminobutyric Acid and Tetrahydrocannabinol (THC)

“Injection of delta 1-tetrahydrocannabinol THC ) into mice increased the uptake into brain synaptosomes of radioactive DA, NE, 5-HT and GABA , with the effect on GABA being the greatest; uptake of leucine was not stimulated, indicating that THC does not facilitate the transport of amino acids in general.”

“Additional evidence suggests that THC may act indirectly on dopamine firing by modulating GABA and glutamate release.”

“Several other mechanisms might explain vulnerability to THC effects including polymorphisms of genes for COMT (Henquet et al, 2006), AKT1, and DAT1 (Bhattacharyya et al, 2012, 2014), and γ-aminobutyric acid (GABA) deficits.”

“HighlightsMaternal exposure to THC induces long‐term alterations of hippocampal GABA system.”

“Biochemical analyses revealed that adolescent THC exposure results in reduced GAD67 and basal GABA levels within the adult PFC.”

“These results suggest that Delta(9)-THC inhibits GABA release, but does not directly alter GABA(A) receptors or GABA uptake in the hippocampus.”

“Whereas Delta(9)-THC did not affect photolysis-evoked GABA currents, these responses were prolonged by a GABA uptake inhibitor.”

“Chronic Delta(9)-THC also produced tolerance to the inhibition of synaptic GABA , but not glutamate release by the agonist WIN55,212-2.”

“In the studies presented here administration of the potent dimethylheptyl derivative of (-)-delta-tetrahydrocannabinol , which has previously been shown to reduce the turnover rate of acetylcholine in the hippocampus, reduces the turnover rate of GABA in the septum.”

“These results suggest that Δ9-THC inhibits TRACh in the cholinergic septal-hippocampal pathway by increasing the release of GABA from septal GABAergic interneurons.”