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

• DOI: 10.1007/s00213-007-1042-2
• Publication Date: 2008-01-28T11:49:20Z
• Authors: Deepak Cyril D’Souza; Gabriel Braley; Rebecca Blaise; Michael Vendetti; Stephen Oliver; Brian Pittman; Mohini Ranganathan; Savita Bhakta; Zoran Zimolo; Thomas Cooper; Edward Perry
• Keywords: Adult; Male; Behavior; Adolescent; Marijuana Smoking; Euphoria; Middle Aged; Motor Activity; Neuropsychological Tests; Neurosecretory Systems; 3. Good health; Substance Abuse Detection; 03 medical and health sciences; Cognition; Memory, Short-Term; 0302 clinical medicine; Hallucinogens; Haloperidol; Humans; Female; Dronabinol; Psychomotor Performance; Antipsychotic Agents

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 Delta-9-tetrahydrocannabinol (Delta-9-THC) remains unclear. This study evaluated whether pretreatment with a dopamine receptor antagonist altered the effects of Delta-9-THC in humans.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) Delta-9-THC, respectively.Consistent with previous reports, intravenous Delta-9-THC produced psychotomimetic effects, perceptual alterations, and subjective effects including "high." Delta-9-THC also impaired verbal recall and attention. Haloperidol pretreatment did not reduce any of the behavioral effects of Delta-9-THC. Haloperidol worsened the immediate free and delayed free and cued recall deficits produced by Delta-9-THC. Haloperidol and Delta-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 Delta-9-THC induced memory impairments.The deleterious effects of haloperidol pretreatment on the cognitive effects of Delta-9-THC are consistent with the preclinical literature in suggesting crosstalk between DAergic and CBergic systems. However, it is unlikely that DA D(2) receptor mechanisms play a major role in mediating the psychotomimetic and perceptual altering effects of Delta-9-THC. Further investigation is warranted to understand the basis of the psychotomimetic effects of Delta-9-THC and to better understand the crosstalk between DAergic and CBergic systems.