Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Delta-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 B. Cooper, Edward Perry
Psychopharmacology July 2008 DOI: 10.1007/s00213-007-1042-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 28 |
| Population | Healthy subjects and frequent cannabis users |
| Interventions | Haloperidol Delta-9-THC |
| Dose | Haloperidol: 0.057 mg/kg oral; Delta-9-THC: 0.0286 mg/kg intravenous |
| Duration | 2 test days |
| Topics | Cannabis |
| Key findings | Haloperidol pretreatment did not reduce THC-induced psychotomimetic, perceptual, or subjective effects, but worsened THC-induced memory and attention deficits. The authors argue dopamine D2 receptor mechanisms are unlikely to play a major role in THC's psychotomimetic effects. |
Abstract
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.
Comparable studies
Other randomized controlled trials on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants | 2012 | Randomized controlled trial | n = 48 |
| Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... | 2009 | Double-blind, randomized, placebo-controlled crossover trial | n = 15 |
| Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects | 2012 | Randomized controlled trial | n = 16 |
| Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... | 2009 | Randomized controlled trial | n = 15 |
| Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Healthy volunteers with a history of light cannabis use | 2019 | Randomized, double-blind, within-subjects crossover | n = 14 |
Citations in the library
Cited by 38
- Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Journal of Psychopharmacology October 5, 2012
- From drugs to deprivation: a Bayesian framework for understanding models of psychosis Psychopharmacology May 27, 2009
- Gone to Pot – A Review of the Association between Cannabis and Psychosis Frontiers in Psychiatry May 22, 2014
- Drug-Induced Psychosis: How to Avoid Star Gazing in Schizophrenia Research by Looking at More Obvious Sources of Light Frontiers in Behavioral Neuroscience 2011
- Human Laboratory Studies on Cannabinoids and Psychosis. Biological Psychiatry April 1, 2016
and 33 more in the library
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- Blunted psychotomimetic and amnestic effects of delta-9-tetrahydrocannabinol in frequent users of cannabis. Neuropsychopharmacology September 2008
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and 10 more in the library