, 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

  • Deepak Cyril D’Souza
  • Gabriel Braley
  • Rebecca Blaise
  • Michael Vendetti
  • Stephen Oliver
  • Brian Pittman
  • Mohini Ranganathan
  • Savita Bhakta
  • Zoran Zimolo
  • Thomas Cooper
  • Edward Perry
Original Investigation



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.


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.


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.


Schizophrenia Cannabinoids Dopamine Antipsychotic Cognition Memory Addiction Attention Haloperidol Endocrine 

Supplementary material

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


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Deepak Cyril D’Souza
    • 1
    • 2
    • 3
    • 5
  • Gabriel Braley
    • 1
    • 3
  • Rebecca Blaise
    • 1
    • 3
  • Michael Vendetti
    • 1
    • 3
  • Stephen Oliver
    • 1
    • 3
  • Brian Pittman
    • 2
  • Mohini Ranganathan
    • 1
    • 3
  • Savita Bhakta
    • 1
    • 3
  • Zoran Zimolo
    • 1
    • 3
  • Thomas Cooper
    • 4
  • Edward Perry
    • 1
    • 3
  1. 1.Schizophrenia Biological Research CenterVA Connecticut Healthcare SystemWest HavenUSA
  2. 2.Abraham Ribicoff Research FacilitiesConnecticut Mental Health CenterNew HavenUSA
  3. 3.Department of PsychiatryYale University School of MedicineNew HavenUSA
  4. 4.Department of Psychiatry, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA
  5. 5.Psychiatry Service, 116AVA Connecticut Healthcare SystemWest HavenUSA

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