Delta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction

Background: Recent advances in the neurobiology of cannabinoids have renewed interest in the association between cannabis and psychotic disorders. Methods: In a 3-day, double-blind, randomized, placebo-controlled study, the behavioral, cognitive, motor, and endocrine effects of 0 mg, 2.5 mg, and 5 mg intravenous Delta-9-tetrabydrocannabinol (Delta-9-7HC) were characterized in 13 stable, antipsycbotic-treated schizophrenia patients. These data were compared with effects in healthy subjects reported elsewhere. Results: Delta-9-tetrabydrocannabinol transiently increased 1) learning and recall deficits; 2) positive, negative, and general schizophrenia symptoms; 3) perceptual alterations; 4) akatbisia, rigidity, and dyskinesia; 5) deficits in vigilance; and 6) plasma prolactin and cortisol. Schizophrenia patients were more vulnerable to Delta-9-7HC effects on recall relative to control subjects. There were no serious short- or long-term adverse events associated with study participation. Conclusions: Delta-9-tetrabydrocannabinol is associated with transient exacerbation in core psychotic and cognitive deficits in schizophrenia. These data do not provide a reason to explain why schizophrenia patients use or misuse cannabis. Furthermore, Delta-9-7HC might differentially affect schizophrenia patients relative to control subjects. Finally, the enhanced sensitivity to the cognitive effects of Delta-9-THC warrants further study into whether brain cannabinoid receptor dysfunction contributes to the pathophysiology of the cognitive deficits associated with schizophrenia.