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 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. 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) Delta-9-THC, respectively. RESULTS: 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. CONCLUSIONS: 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.
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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 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. 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) Delta-9-THC, respectively. RESULTS: 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. CONCLUSIONS: 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.
Authors: John H Krystal; Edward B Perry; Ralitza Gueorguieva; Aysenil Belger; Steven H Madonick; Anissa Abi-Dargham; Thomas B Cooper; Lisa Macdougall; Walid Abi-Saab; D Cyril D'Souza Journal: Arch Gen Psychiatry Date: 2005-09
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Authors: F Rodríguez De Fonseca; J J Fernández-Ruiz; L L Murphy; M Cebeira; R W Steger; A Bartke; J A Ramos Journal: Pharmacol Biochem Behav Date: 1992-06 Impact factor: 3.533
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