title: Blunted psychotomimetic and amnestic effects of delta-9-tetrahydrocannabinol in frequent users of cannabis.
abstract: Cannabis is one of the most widely used illicit substances and there is growing interest in the association between cannabis use and psychosis. Delta-9-Tetrahydrocannabinol (Delta-9-THC) the principal active ingredient of cannabis has been shown to induce psychotomimetic and amnestic effects in healthy individuals. Whether people who frequently use cannabis are either protected from or are tolerant to these effects of Delta-9-THC has not been established. In a 3-day, double-blind, randomized, placebo-controlled study, the dose-related effects of 0, 2.5, and 5 mg intravenous Delta-9-THC were studied in 30 frequent users of cannabis and compared to 22 healthy controls. Delta-9-THC (1) produced transient psychotomimetic effects and perceptual alterations; (2) impaired memory and attention; (3) increased subjective effects of 'high'; (4) produced tachycardia; and (5) increased serum cortisol in both groups. However, relative to controls, frequent users showed blunted responses to the psychotomimetic, perceptual altering, cognitive impairing, anxiogenic, and cortisol increasing effects of Delta-9-THC but not to its euphoric effects. Frequent users also had lower prolactin levels. These data suggest that frequent users of cannabis are either inherently blunted in their response to, and/or develop tolerance to the psychotomimetic, perceptual altering, amnestic, endocrine, and other effects of cannabinoids.
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: Mohini
authors.initials: M
authors.lastname: Ranganathan
authors.forename: Gabriel
authors.initials: G
authors.lastname: Braley
authors.forename: Ralitza
authors.initials: R
authors.lastname: Gueorguieva
authors.forename: Zoran
authors.initials: Z
authors.lastname: Zimolo
authors.forename: Thomas
authors.initials: T
authors.lastname: Cooper
authors.forename: Edward
authors.initials: E
authors.lastname: Perry
authors.forename: John
authors.initials: J
authors.lastname: Krystal
mesh_terms: D000293:Adolescent; D000328:Adult; D000647:Amnesia / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology*; D001288:Attention / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000009:adverse effects*; D004334:Drug Administration Schedule; D004361:Drug Tolerance / Q000502:physiology*; D005260:Female; D006212:Hallucinations / Q000139:chemically induced; D006213:Hallucinogens / Q000009:adverse effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D002189:Marijuana Abuse / Q000378:metabolism / Q000503:physiopathology*; D008875:Middle Aged; D010468:Perceptual Disorders / Q000139:chemically induced; D011388:Prolactin / Q000097:blood; D011605:Psychoses, Substance-Induced / Q000503:physiopathology*; D013610:Tachycardia / Q000139:chemically induced; D055815:Young Adult
chemical_list: D006213:Hallucinogens; D013759:Dronabinol; D011388:Prolactin; D006854:Hydrocortisone