Psychopharmacology

, Volume 198, Issue 4, pp 587–603

Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Δ-9-tetrahydrocannabinol in humans

Authors

    • Schizophrenia Biological Research CenterVA Connecticut Healthcare System
    • Abraham Ribicoff Research FacilitiesConnecticut Mental Health Center
    • Department of PsychiatryYale University School of Medicine
    • Psychiatry Service, 116AVA Connecticut Healthcare System
  • Gabriel Braley
    • Schizophrenia Biological Research CenterVA Connecticut Healthcare System
    • Department of PsychiatryYale University School of Medicine
  • Rebecca Blaise
    • Schizophrenia Biological Research CenterVA Connecticut Healthcare System
    • Department of PsychiatryYale University School of Medicine
  • Michael Vendetti
    • Schizophrenia Biological Research CenterVA Connecticut Healthcare System
    • Department of PsychiatryYale University School of Medicine
  • Stephen Oliver
    • Schizophrenia Biological Research CenterVA Connecticut Healthcare System
    • Department of PsychiatryYale University School of Medicine
  • Brian Pittman
    • Abraham Ribicoff Research FacilitiesConnecticut Mental Health Center
  • Mohini Ranganathan
    • Schizophrenia Biological Research CenterVA Connecticut Healthcare System
    • Department of PsychiatryYale University School of Medicine
  • Savita Bhakta
    • Schizophrenia Biological Research CenterVA Connecticut Healthcare System
    • Department of PsychiatryYale University School of Medicine
  • Zoran Zimolo
    • Schizophrenia Biological Research CenterVA Connecticut Healthcare System
    • Department of PsychiatryYale University School of Medicine
  • Thomas Cooper
    • Department of Psychiatry, College of Physicians and SurgeonsColumbia University
  • Edward Perry
    • Schizophrenia Biological Research CenterVA Connecticut Healthcare System
    • Department of PsychiatryYale University School of Medicine
Original Investigation

DOI: 10.1007/s00213-007-1042-2

Cite this article as:
D’Souza, D.C., Braley, G., Blaise, R. et al. Psychopharmacology (2008) 198: 587. doi:10.1007/s00213-007-1042-2

Abstract

Introduction

Cannabinoids produce a spectrum of effects in humans including euphoria, cognitive impairments, psychotomimetic effects, and perceptual alterations. The extent to which dopaminergic systems contribute to the effects of Δ-9-tetrahydrocannabinol (Δ-9-THC) remains unclear. This study evaluated whether pretreatment with a dopamine receptor antagonist altered the effects of Δ-9-THC in humans.

Materials and methods

In a 2-test-day double-blind study, 28 subjects including healthy subjects (n = 17) and frequent users of cannabis (n = 11) were administered active (0.057 mg/kg) or placebo oral haloperidol in random order followed 90 and 215 min later by fixed order intravenous administration of placebo (vehicle) and active (0.0286 mg/kg) Δ-9-THC, respectively.

Results

Consistent with previous reports, intravenous Δ-9-THC produced psychotomimetic effects, perceptual alterations, and subjective effects including “high.” Δ-9-THC also impaired verbal recall and attention. Haloperidol pretreatment did not reduce any of the behavioral effects of Δ-9-THC. Haloperidol worsened the immediate free and delayed free and cued recall deficits produced by Δ-9-THC. Haloperidol and Δ-9-THC worsened distractibility and vigilance. Neither drug impaired performance on a motor screening task, the Stockings of Cambridge task, or the delayed match to sample task. Frequent users had lower baseline plasma prolactin levels and blunted Δ-9-THC induced memory impairments.

Conclusions

The deleterious effects of haloperidol pretreatment on the cognitive effects of Δ-9-THC are consistent with the preclinical literature in suggesting crosstalk between DAergic and CBergic systems. However, it is unlikely that DA D2 receptor mechanisms play a major role in mediating the psychotomimetic and perceptual altering effects of Δ-9-THC. Further investigation is warranted to understand the basis of the psychotomimetic effects of Δ-9-THC and to better understand the crosstalk between DAergic and CBergic systems.

Keywords

SchizophreniaCannabinoidsDopamineAntipsychoticCognitionMemoryAddictionAttentionHaloperidolEndocrine

Supplementary material

213_2007_1042_MOESM1_ESM.doc (36 kb)
Table S1Motor results (means [±SD]) (DOC 36.0 KB)

Copyright information

© Springer-Verlag 2007