title: The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis.
abstract: 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.
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: Edward
authors.initials: E
authors.lastname: Perry
authors.forename: Lisa
authors.initials: L
authors.lastname: MacDougall
authors.forename: Yola
authors.initials: Y
authors.lastname: Ammerman
authors.forename: Thomas
authors.initials: T
authors.lastname: Cooper
authors.forename: Yu-Te
authors.initials: YT
authors.lastname: Wu
authors.forename: Gabriel
authors.initials: G
authors.lastname: Braley
authors.forename: Ralitza
authors.initials: R
authors.lastname: Gueorguieva
authors.forename: John Harrison
authors.initials: JH
authors.lastname: Krystal
mesh_terms: 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
chemical_list: D006213:Hallucinogens; D013759:Dronabinol; D011388:Prolactin; D006854:Hydrocortisone