The Psychosis-like Effects of Δ⁹-Tetrahydrocannabinol Are Associated with Increased Cortical Noise in Healthy Humans

Background Drugs that induce psychosis may do so by increasing the level of task-irrelevant random neural activity or neural noise. Increased levels of neural noise have been demonstrated in psychotic disorders. We tested the hypothesis that neural noise could also be involved in the psychotomimetic effects of delta-9-tetrahydrocannabinol (Δ⁹-THC), the principal active constituent of cannabis. Methods Neural noise was indexed by measuring the level of randomness in the electroencephalogram during the prestimulus baseline period of an oddball task using Lempel-Ziv complexity, a nonlinear measure of signal randomness. The acute, dose-related effects of Δ⁹-THC on Lempel-Ziv complexity and signal power were studied in humans (n = 24) who completed 3 test days during which they received intravenous Δ⁹-THC (placebo,.015 and.03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design. Results Δ⁹-THC increased neural noise in a dose-related manner. Furthermore, there was a strong positive relationship between neural noise and the psychosis-like positive and disorganization symptoms induced by Δ⁹-THC, which was independent of total signal power. Instead, there was no relationship between noise and negative-like symptoms. In addition, Δ⁹-THC reduced total signal power during both active drug conditions compared with placebo, but no relationship was detected between signal power and psychosis-like symptoms. Conclusions At doses that produced psychosis-like effects, Δ⁹-THC increased neural noise in humans in a dose-dependent manner. Furthermore, increases in neural noise were related with increases in Δ⁹-THC-induced psychosis-like symptoms but not negative-like symptoms. These findings suggest that increases in neural noise may contribute to the psychotomimetic effects of Δ⁹-THC.