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Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Delta-9-tetrahydrocannabinol in humans.
Psychopharmacology (Berl) 2008; 198(4):587-603P

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 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+Show Affiliations

Schizophrenia Biological Research Center, VA Connecticut Healthcare System, West Haven, CT, USA. deepak.dsouza@yale.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

18228005

Citation

D'Souza, Deepak Cyril, et al. "Effects of Haloperidol On the Behavioral, Subjective, Cognitive, Motor, and Neuroendocrine Effects of Delta-9-tetrahydrocannabinol in Humans." Psychopharmacology, vol. 198, no. 4, 2008, pp. 587-603.
D'Souza DC, Braley G, Blaise R, et al. Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Delta-9-tetrahydrocannabinol in humans. Psychopharmacology (Berl). 2008;198(4):587-603.
D'Souza, D. C., Braley, G., Blaise, R., Vendetti, M., Oliver, S., Pittman, B., ... Perry, E. (2008). Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Delta-9-tetrahydrocannabinol in humans. Psychopharmacology, 198(4), pp. 587-603. doi:10.1007/s00213-007-1042-2.
D'Souza DC, et al. Effects of Haloperidol On the Behavioral, Subjective, Cognitive, Motor, and Neuroendocrine Effects of Delta-9-tetrahydrocannabinol in Humans. Psychopharmacology (Berl). 2008;198(4):587-603. PubMed PMID: 18228005.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Delta-9-tetrahydrocannabinol in humans. AU - D'Souza,Deepak Cyril, AU - Braley,Gabriel, AU - Blaise,Rebecca, AU - Vendetti,Michael, AU - Oliver,Stephen, AU - Pittman,Brian, AU - Ranganathan,Mohini, AU - Bhakta,Savita, AU - Zimolo,Zoran, AU - Cooper,Thomas, AU - Perry,Edward, Y1 - 2008/01/29/ PY - 2007/06/18/received PY - 2007/11/28/accepted PY - 2008/1/30/pubmed PY - 2008/11/18/medline PY - 2008/1/30/entrez SP - 587 EP - 603 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 198 IS - 4 N2 - 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. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/18228005/Effects_of_haloperidol_on_the_behavioral_subjective_cognitive_motor_and_neuroendocrine_effects_of_Delta_9_tetrahydrocannabinol_in_humans_ L2 - https://dx.doi.org/10.1007/s00213-007-1042-2 DB - PRIME DP - Unbound Medicine ER -