Repeated low doses of LSD (15 mcg) affect arousal, attention, and memory depending on a person's baseline cognitive state. In a randomized placebo-controlled trial with 53 healthy participants, LSD reduced resting-state EEG delta, theta, and alpha power (indicating stimulation) and enhanced pre-attentive processing during acute dosing sessions. LSD also blunted visual long-term potentiation (a marker of perceptual learning and memory) by the fourth dosing session. Stimulatory effects were strongest in individuals with low baseline arousal and attention, while inhibitory effects on memory were strongest in those with high baseline memory performance. Some EEG changes persisted at a one-week follow-up, suggesting possible neuroadaptations from repeated low-dose LSD.
THC increases striatal glutamate concentrations and reduces functional connectivity between the nucleus accumbens and cortical areas, indicating increased dopaminergic activity. These changes were dose dependent, occurring in the full dose group where THC serum concentrations exceeded 2 ng/ml at T-max. Average glutamate changes correlated strongly with functional connectivity alterations. THC-induced changes in functional connectivity correlated with feelings of subjective high and decreased performance on an attention task. The findings suggest THC elicits subjective and cognitive alterations via increased striatal dopaminergic activity and loss of corticostriatal connectivity, associated with increased striatal glutamate.