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Psychopharmacology

, Volume 236, Issue 9, pp 2635–2640 | Cite as

Effects of haloperidol on the delta-9-tetrahydrocannabinol response in humans: a responder analysis

  • Swapnil Gupta
  • Joao P. De AquinoEmail author
  • Deepak C. D’Souza
  • Mohini Ranganathan
Original Investigation

Abstract

Rationale

Δ-9-Tetrahydrocannabinol (Δ-9-THC) produces psychotomimetic effects in humans. However, the role of dopamine signaling in producing such effects is unclear. We hypothesized that dopaminergic antagonism would reduce the psychotomimetic effect of Δ-9-THC.

Objective

The objective of this study was to evaluate whether pre-treatment with haloperidol would alter the psychotomimetic and perceptual-altering effects of Δ-9-THC, measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and the Clinician-Administered Dissociative Symptom Scale (CADSS) in humans.

Methods

In a two-test-day double-blind study, 28 healthy individuals were administered with active (0.057 mg/kg) or placebo oral haloperidol, followed 90 and 215 min later by intravenous administration of active (0.0286 mg/kg) Δ-9-THC and placebo, respectively. This secondary analysis was conducted because of the observation in other studies and in our data that a significant proportion of individuals may not have an adequate response to THC (floor effect), thus limiting the ability to test an interaction. Therefore, this analysis was performed including only responders to THC (n = 10), defined as individuals who had an increase of at least one point on the PANSS positive scale, consistent with prior human laboratory studies.

Results

In the 10 responders, Δ-9-THC-induced increases in PANSS positive scores were significantly lower in the haloperidol condition (1.1 + 0.35) compared with the placebo condition (2.9 + 0.92).

Conclusion

This responder analysis showed that haloperidol did reduce the psychotomimetic effect of Δ-9-THC, supporting the hypothesis that dopaminergic signaling may participate in the psychosis-like effects of cannabinoids.

Keywords

Cannabinoid Haloperidol Antipsychotic Dopamine Psychosis 

Notes

Acknowledgments

We also acknowledge support from the (1) Department of Veterans Affairs, (2) National Institute of Drug Abuse, (3) National Institute of Alcoholism and Alcohol Abuse.

Funding information

This research project was funded in part by grants from the National Institute of Mental Health (R25MH071584 to JPD).

Compliance with ethical standards

Conflict of interest

DCD has received in the past 3 years and currently receives research grant support administered through Yale University School of Medicine from Pfizer Inc. All other authors report no biomedical financial interests or potential conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PsychiatryYale University School of MedicineNew HavenUSA
  2. 2.Connecticut Mental Health CenterNew HavenUSA
  3. 3.Clinical Neuroscience Research UnitConnecticut Mental Health CenterNew HavenUSA
  4. 4.VA Connecticut Healthcare System, Clinical Neurosciences DivisionU.S. Department of Veterans AffairsWest HavenUSA

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