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Effects of haloperidol on the delta-9-tetrahydrocannabinol response in humans: a responder analysis.
Psychopharmacology (Berl). 2019 Sep; 236(9):2635-2640.P

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.

Authors+Show Affiliations

Department of Psychiatry, Yale University School of Medicine, 300 George St, Suite 901, New Haven, CT, 06510, USA. Connecticut Mental Health Center, 34 Park St, New Haven, CT, USA.Department of Psychiatry, Yale University School of Medicine, 300 George St, Suite 901, New Haven, CT, 06510, USA. joao.deaquino@yale.edu. Clinical Neuroscience Research Unit, Connecticut Mental Health Center, 34 Park St, 3rd Floor, New Haven, CT, USA. joao.deaquino@yale.edu. VA Connecticut Healthcare System, Clinical Neurosciences Division, U.S. Department of Veterans Affairs, West Haven, CT, USA. joao.deaquino@yale.edu.Department of Psychiatry, Yale University School of Medicine, 300 George St, Suite 901, New Haven, CT, 06510, USA. Clinical Neuroscience Research Unit, Connecticut Mental Health Center, 34 Park St, 3rd Floor, New Haven, CT, USA. VA Connecticut Healthcare System, Clinical Neurosciences Division, U.S. Department of Veterans Affairs, West Haven, CT, USA.Department of Psychiatry, Yale University School of Medicine, 300 George St, Suite 901, New Haven, CT, 06510, USA. Clinical Neuroscience Research Unit, Connecticut Mental Health Center, 34 Park St, 3rd Floor, New Haven, CT, USA. VA Connecticut Healthcare System, Clinical Neurosciences Division, U.S. Department of Veterans Affairs, West Haven, CT, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30919005

Citation

Gupta, Swapnil, et al. "Effects of Haloperidol On the Delta-9-tetrahydrocannabinol Response in Humans: a Responder Analysis." Psychopharmacology, vol. 236, no. 9, 2019, pp. 2635-2640.
Gupta S, De Aquino JP, D'Souza DC, et al. Effects of haloperidol on the delta-9-tetrahydrocannabinol response in humans: a responder analysis. Psychopharmacology (Berl). 2019;236(9):2635-2640.
Gupta, S., De Aquino, J. P., D'Souza, D. C., & Ranganathan, M. (2019). Effects of haloperidol on the delta-9-tetrahydrocannabinol response in humans: a responder analysis. Psychopharmacology, 236(9), 2635-2640. https://doi.org/10.1007/s00213-019-05235-x
Gupta S, et al. Effects of Haloperidol On the Delta-9-tetrahydrocannabinol Response in Humans: a Responder Analysis. Psychopharmacology (Berl). 2019;236(9):2635-2640. PubMed PMID: 30919005.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of haloperidol on the delta-9-tetrahydrocannabinol response in humans: a responder analysis. AU - Gupta,Swapnil, AU - De Aquino,Joao P, AU - D'Souza,Deepak C, AU - Ranganathan,Mohini, Y1 - 2019/03/27/ PY - 2018/11/16/received PY - 2019/03/19/accepted PY - 2020/09/01/pmc-release PY - 2019/3/29/pubmed PY - 2019/11/27/medline PY - 2019/3/29/entrez KW - Antipsychotic KW - Cannabinoid KW - Dopamine KW - Haloperidol KW - Psychosis SP - 2635 EP - 2640 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 236 IS - 9 N2 - 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. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/30919005/Effects_of_haloperidol_on_the_delta_9_tetrahydrocannabinol_response_in_humans:_a_responder_analysis_ L2 - https://dx.doi.org/10.1007/s00213-019-05235-x DB - PRIME DP - Unbound Medicine ER -