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

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)587-603
Number of pages17
Issue number4
StatePublished - Jul 2008
Externally publishedYes


  • Addiction
  • Antipsychotic
  • Attention
  • Cannabinoids
  • Cognition
  • Dopamine
  • Endocrine
  • Haloperidol
  • Memory
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology


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