title: Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction.
abstract: 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.
authors.affiliation: Schizophrenia Biological Research Center, VA Connecticut Healthcare System, West Haven, CT 06516, USA. deepak.dsouza@yale.edu
authors.forename: Deepak Cyril
authors.initials: DC
authors.lastname: D'Souza
authors.forename: Walid Michel
authors.initials: WM
authors.lastname: Abi-Saab
authors.forename: Steven
authors.initials: S
authors.lastname: Madonick
authors.forename: Kimberlee
authors.initials: K
authors.lastname: Forselius-Bielen
authors.forename: Anne
authors.initials: A
authors.lastname: Doersch
authors.forename: Gabriel
authors.initials: G
authors.lastname: Braley
authors.forename: Ralitza
authors.initials: R
authors.lastname: Gueorguieva
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Cooper
authors.forename: John Harrison
authors.initials: JH
authors.lastname: Krystal
mesh_terms: D000328:Adult; D017109:Akathisia, Drug-Induced / Q000503:physiopathology; D001143:Arousal / Q000187:drug effects; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage*; D004703:Endocrine System / Q000187:drug effects; D005260:Female; D006801:Humans; D007275:Injections, Intravenous / Q000379:methods; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects*; D009483:Neuropsychological Tests; D010465:Perception / Q000187:drug effects; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders; D011619:Psychotropic Drugs / Q000008:administration & dosage*; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D014706:Verbal Learning
chemical_list: D011619:Psychotropic Drugs; D013759:Dronabinol