The good, the bad, and the intoxicated
January 1, 2021 DOI: 10.26481/dis.20210608nm via OpenAlex
Summary
THC administration increased striatal glutamate concentrations and altered functional connectivity in the brain, leading to subjective feelings of being high and decreased performance on attention tasks. This study involved 20 occasional cannabis users who received doses of THC (300 g/kg) and placebo. The results showed that THC's effects were dose-dependent, particularly evident when serum concentrations exceeded 2 ng/ml, with strong correlations between glutamate changes and functional connectivity alterations.
Study at a glance
| Design | double-blind, placebo-controlled study |
|---|---|
| Sample size | 20 |
| Population | occasional cannabis users |
| Key finding | THC elicits subjective and cognitive alterations via increased striatal dopaminergic activity and loss of corticostriatal connectivity. |
Abstract
Cannabis is the most commonly used illicit drug and is known to alter state of consciousness and impair neurocognitive function. However, the mechanisms underlying these effects have yet to be fully elucidated. Rodent studies suggest that 9-tetrahydrocannabinol (THC) activates dopaminergic neurons in the limbic system, subsequently enhancing dopamine, which is implicated in the rewarding effects of cannabis. Additional evidence suggests that THC may act indirectly on dopamine firing by modulating GABA and glutamate release. This double-blind, placebo-controlled study assessed the acute influence of two doses of THC on brain kinetics of glutamate, GABA, and dopamine, in relation to behavioral outcomes, by using magnetic resonance spectroscopy and functional magnetic resonance imaging. Twenty occasional cannabis users received acute doses of cannabis (300 g/kg THC) and placebo, in one of two dose regimes (full dose and divided dose), during two separate testing days. Administration of THC increased striatal glutamate concentrations, and dopamine as indicated by a reduction in functional connectivity (FC) between the nucleus accumbens (NAc) and cortical areas. Alterations in glutamate and FC were dose dependent and evident in the full dose group where THC serum concentrations exceeded 2 ng/ml at T-max. Average glutamate changes correlated strongly with FC alterations. Additionally, THC induced changes in FC correlated with feelings of subjective high and decreased performance on an attention task. Taken together, this suggests that THC elicits subjective and cognitive alterations via increased striatal dopaminergic activity and loss of corticostriatal connectivity, which is associated with an increase in striatal glutamate.