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Central nervous system effects of haloperidol on THC in healthy male volunteers.
J Psychopharmacol. 2010 Nov; 24(11):1697-708.JP

Abstract

In this study, the hypothesis that haloperidol would lead to an amelioration of Δ9-tetrahydrocannabinol (THC)-induced 'psychotomimetic' effects was investigated. In a double-blind, placebo-controlled, partial three-way crossover ascending dose study the effects of THC, haloperidol and their combination were investigated in 35 healthy, male mild cannabis users, measuring Positive and Negative Syndrome Scale, Visual Analogue Scales for alertness, mood, calmness and psychedelic effects, saccadic and smooth pursuit eye measurements, electroencephalography, Body Sway, Stroop test, Visual and Verbal Learning Task, hormone levels and pharmacokinetics. Compared with placebo, THC significantly decreased smooth pursuit, Visual Analogue Scales alertness, Stroop test performance, immediate and delayed word recall and prolactin concentrations, and significantly increased positive and general Positive and Negative Syndrome Scale score, Visual Analogue Scales feeling high, Body Sway and electroencephalography alpha. Haloperidol reversed the THC-induced positive Positive and Negative Syndrome Scale increase to levels observed with haloperidol alone, but not THC-induced 'high' feelings. Compared with placebo, haloperidol significantly decreased saccadic peak velocity, smooth pursuit, Visual Analogue Scales mood and immediate and delayed word recall and significantly increased Body Sway, electroencephalography theta and prolactin levels. THC-induced increases in positive Positive and Negative Syndrome Scale but not in Visual Analogue Scales feeling high were reversed by haloperidol. This indicates that psychotic-like effects induced by THC are mediated by dopaminergic systems, but that other systems are involved in 'feeling high'. Additionally, the clear reductions of psychotic-like symptoms by a clinically relevant dose of haloperidol suggest that THC administration may be a useful pharmacological cannabinoid model for psychotic effects in healthy volunteers.

Authors+Show Affiliations

Centre for Human Drug Research, Leiden, The Netherlands. mariekemoolenaar@online.nlNo 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
Randomized Controlled Trial

Language

eng

PubMed ID

20142302

Citation

Liem-Moolenaar, Marieke, et al. "Central Nervous System Effects of Haloperidol On THC in Healthy Male Volunteers." Journal of Psychopharmacology (Oxford, England), vol. 24, no. 11, 2010, pp. 1697-708.
Liem-Moolenaar M, te Beek ET, de Kam ML, et al. Central nervous system effects of haloperidol on THC in healthy male volunteers. J Psychopharmacol (Oxford). 2010;24(11):1697-708.
Liem-Moolenaar, M., te Beek, E. T., de Kam, M. L., Franson, K. L., Kahn, R. S., Hijman, R., Touw, D., & van Gerven, J. M. (2010). Central nervous system effects of haloperidol on THC in healthy male volunteers. Journal of Psychopharmacology (Oxford, England), 24(11), 1697-708. https://doi.org/10.1177/0269881109358200
Liem-Moolenaar M, et al. Central Nervous System Effects of Haloperidol On THC in Healthy Male Volunteers. J Psychopharmacol (Oxford). 2010;24(11):1697-708. PubMed PMID: 20142302.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Central nervous system effects of haloperidol on THC in healthy male volunteers. AU - Liem-Moolenaar,Marieke, AU - te Beek,Erik T, AU - de Kam,Marieke L, AU - Franson,Kari L, AU - Kahn,René S, AU - Hijman,Ron, AU - Touw,Daan, AU - van Gerven,Joop M A, Y1 - 2010/02/08/ PY - 2010/2/10/entrez PY - 2010/2/10/pubmed PY - 2011/3/1/medline SP - 1697 EP - 708 JF - Journal of psychopharmacology (Oxford, England) JO - J. Psychopharmacol. (Oxford) VL - 24 IS - 11 N2 - In this study, the hypothesis that haloperidol would lead to an amelioration of Δ9-tetrahydrocannabinol (THC)-induced 'psychotomimetic' effects was investigated. In a double-blind, placebo-controlled, partial three-way crossover ascending dose study the effects of THC, haloperidol and their combination were investigated in 35 healthy, male mild cannabis users, measuring Positive and Negative Syndrome Scale, Visual Analogue Scales for alertness, mood, calmness and psychedelic effects, saccadic and smooth pursuit eye measurements, electroencephalography, Body Sway, Stroop test, Visual and Verbal Learning Task, hormone levels and pharmacokinetics. Compared with placebo, THC significantly decreased smooth pursuit, Visual Analogue Scales alertness, Stroop test performance, immediate and delayed word recall and prolactin concentrations, and significantly increased positive and general Positive and Negative Syndrome Scale score, Visual Analogue Scales feeling high, Body Sway and electroencephalography alpha. Haloperidol reversed the THC-induced positive Positive and Negative Syndrome Scale increase to levels observed with haloperidol alone, but not THC-induced 'high' feelings. Compared with placebo, haloperidol significantly decreased saccadic peak velocity, smooth pursuit, Visual Analogue Scales mood and immediate and delayed word recall and significantly increased Body Sway, electroencephalography theta and prolactin levels. THC-induced increases in positive Positive and Negative Syndrome Scale but not in Visual Analogue Scales feeling high were reversed by haloperidol. This indicates that psychotic-like effects induced by THC are mediated by dopaminergic systems, but that other systems are involved in 'feeling high'. Additionally, the clear reductions of psychotic-like symptoms by a clinically relevant dose of haloperidol suggest that THC administration may be a useful pharmacological cannabinoid model for psychotic effects in healthy volunteers. SN - 1461-7285 UR - https://www.unboundmedicine.com/medline/citation/20142302/Central_nervous_system_effects_of_haloperidol_on_THC_in_healthy_male_volunteers_ L2 - http://journals.sagepub.com/doi/full/10.1177/0269881109358200?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -