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-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.
D'Souza
Deepak Cyril
DC
Schizophrenia Biological Research Center, VA Connecticut Healthcare System, West Haven, CT 06516, USA. deepak.dsouza@yale.edu
Abi-Saab
Walid Michel
WM
Madonick
Steven
S
Forselius-Bielen
Kimberlee
K
Doersch
Anne
A
Braley
Gabriel
G
Gueorguieva
Ralitza
R
Cooper
Thomas B
TB
Krystal
John Harrison
JH
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
D011619:Psychotropic Drugs; D013759:Dronabinol