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

Biol Psychiatry. 2005 Mar 15;57(6):594-608. doi: 10.1016/j.biopsych.2004.12.006.


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-tetrahydrocannabinol (Delta-9-THC) were characterized in 13 stable, antipsychotic-treated schizophrenia patients. These data were compared with effects in healthy subjects reported elsewhere.

Results: Delta-9-tetrahydrocannabinol transiently increased 1) learning and recall deficits; 2) positive, negative, and general schizophrenia symptoms; 3) perceptual alterations; 4) akathisia, rigidity, and dyskinesia; 5) deficits in vigilance; and 6) plasma prolactin and cortisol. Schizophrenia patients were more vulnerable to Delta-9-THC effects on recall relative to control subjects. There were no serious short- or long-term adverse events associated with study participation.

Conclusions: Delta-9-tetrahydrocannabinol 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-THC 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Akathisia, Drug-Induced / physiopathology
  • Arousal / drug effects
  • Cognition / drug effects*
  • Cognition / physiology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Dronabinol / administration & dosage*
  • Endocrine System / drug effects
  • Female
  • Humans
  • Injections, Intravenous / methods
  • Male
  • Mental Recall / drug effects
  • Middle Aged
  • Motor Activity / drug effects*
  • Neuropsychological Tests
  • Perception / drug effects
  • Psychiatric Status Rating Scales
  • Psychotic Disorders
  • Psychotropic Drugs / administration & dosage*
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology
  • Verbal Learning


  • Psychotropic Drugs
  • Dronabinol