A single modest dose of oral THC (15 mg dronabinol) worsened verbal learning and attention in people with schizophrenia and co-occurring cannabis use disorder, without exacerbating psychotic symptoms several hours after administration. Smoked low-dose THC cigarettes did not produce these cognitive effects. Higher blood THC levels were linked to increased negative symptoms. Drug liking was greater with THC than placebo. The findings suggest that oral THC may impair cognition in this population even at modest doses, while not acutely worsening psychosis.
In a pilot study, patients with schizophrenia and cannabis use disorder showed over-connectivity in the default mode network (DMN) at rest, which correlated with more severe positive symptoms, and reduced anticorrelation between the DMN and the executive control network (ECN). After smoking a 3.6% THC cannabis cigarette or ingesting a 15 mg THC pill, DMN hyperconnectivity decreased and DMN-ECN anticorrelation increased. The degree of anticorrelation in healthy controls and in patients after cannabinoid administration positively correlated with working memory performance. The results suggest that DMN connectivity can change, which may inform future treatments targeting circuit-level dysfunction.