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


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.
D'Souza
Deepak Cyril
DC
Schizophrenia Biological Research Center, VA Connecticut Healthcare System, West Haven, CT, USA. deepak.dsouza@yale.edu
Braley
Gabriel
G
Blaise
Rebecca
R
Vendetti
Michael
M
Oliver
Stephen
S
Pittman
Brian
B
Ranganathan
Mohini
M
Bhakta
Savita
S
Zimolo
Zoran
Z
Cooper
Thomas
T
Perry
Edward
E
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001519:Behavior / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects*; D013759:Dronabinol / Q000494:pharmacology*; D005059:Euphoria / Q000187:drug effects; D005260:Female; D006213:Hallucinogens / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000523:psychology / Q000652:urine; D008570:Memory, Short-Term / Q000187:drug effects; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects*; D009483:Neuropsychological Tests; D009490:Neurosecretory Systems / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects; D015813:Substance Abuse Detection; D014796:Visual Perception / Q000187:drug effects
D014150:Antipsychotic Agents; D006213:Hallucinogens; D013759:Dronabinol; D006220:Haloperidol