The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis.
Recent advances in the understanding of brain cannabinoid receptor function have renewed interest in the association between cannabinoid compounds and psychosis. In a 3-day, double-blind, randomized, and counterbalanced study, the behavioral, cognitive, and endocrine effects of 0, 2.5, and 5 mg intravenous delta-9-tetrahydrocannabinol (Delta-9-THC) were characterized in 22 healthy individuals, who had been exposed to cannabis but had never been diagnosed with a cannabis abuse disorder. Prospective safety data at 1, 3, and 6 months poststudy was also collected. Delta-9-THC (1) produced schizophrenia-like positive and negative symptoms; (2) altered perception; (3) increased anxiety; (4) produced euphoria; (5) disrupted immediate and delayed word recall, sparing recognition recall; (6) impaired performance on tests of distractibility, verbal fluency, and working memory (7) did not impair orientation; (8) increased plasma cortisol. These data indicate that Delta-9-THC produces a broad range of transient symptoms, behaviors, and cognitive deficits in healthy individuals that resemble some aspects of endogenous psychoses. These data warrant further study of whether brain cannabinoid receptor function contributes to the pathophysiology of psychotic disorders.
D'Souza
Deepak Cyril
DC
Schizophrenia Biological Research Center, VA Connecticut Healthcare System, West Haven, CT 06516, USA. deepak.dsouza@yale.edu
Perry
Edward
E
MacDougall
Lisa
L
Ammerman
Yola
Y
Cooper
Thomas
T
Wu
Yu-Te
YT
Braley
Gabriel
G
Gueorguieva
Ralitza
R
Krystal
John Harrison
JH
D000328:Adult; D001007:Anxiety / Q000139:chemically induced / Q000523:psychology; D001143:Arousal / Q000187:drug effects; D001288:Attention / Q000187:drug effects; D001519:Behavior / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006213:Hallucinogens / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007275:Injections, Intravenous; D008297:Male; D008570:Memory, Short-Term; D011939:Mental Recall / Q000187:drug effects; D010200:Panic / Q000187:drug effects; D011388:Prolactin / Q000097:blood; D011569:Psychiatric Status Rating Scales; D011594:Psychometrics; D011605:Psychoses, Substance-Induced / Q000523:psychology*; D013060:Speech / Q000187:drug effects; D014706:Verbal Learning / Q000187:drug effects
D006213:Hallucinogens; D013759:Dronabinol; D011388:Prolactin; D006854:Hydrocortisone