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Pharmacol Biochem Behav. 2019 Jul 5;184:172739. doi: 10.1016/j.pbb.2019.172739. [Epub ahead of print]

Acute separate and combined effects of cannabinoid and nicotinic receptor agonists on MMN-indexed auditory deviance detection in healthy humans.

Author information

1
University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada; School of Psychology, University of Ottawa, Ottawa, ON, Canada.
2
Interdisciplinary Sciences, Carleton University, Ottawa, ON, Canada.
3
University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
4
Biomedical Sciences, University of Ottawa, Ottawa, ON, Canada.
5
School of Psychology, University of Ottawa, Ottawa, ON, Canada.
6
University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada.
7
Department of Psychiatry, University of Ottawa, Ottawa, ON, Canada.
8
University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada; School of Psychology, University of Ottawa, Ottawa, ON, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada; Department of Psychiatry, University of Ottawa, Ottawa, ON, Canada. Electronic address: verner.knott@theroyal.ca.

Abstract

The high prevalence of concomitant cannabis and nicotine use has implications for sensory and cognitive processing. While nicotine tends to enhance function in these domains, cannabis use has been associated with both sensory and cognitive impairments, though the underlying mechanisms are unclear. Additionally, the interaction of the nicotinic (nAChR) and cannabinoid (CB1) receptor systems has received limited study in terms of sensory/cognitive processes. This study involving healthy volunteers assessed the acute separate and combined effects of nabilone (a CB1 agonist) and nicotine on sensory processing as assessed by auditory deviance detection and indexed by the mismatch negativity (MMN) event-related potential. It was hypothesized that nabilone would impair auditory discriminability as shown by diminished MMN amplitudes, but not when administered in combination with nicotine. 20 male non-smokers and non-cannabis-users were assessed using a 5-stimulus 'optimal' multi-feature MMN paradigm within a randomized, placebo controlled design (placebo; nabilone [0.5 mg]; nicotine [6 mg]; and nicotine + nabilone). Treatment effects were region- and deviant-dependent. At the temporal regions (mastoid sites), MMN was reduced by nabilone and nicotine separately, whereas co-administration resulted in no impairment. At the frontal region, MMN was enhanced by co-administration of nicotine and nabilone, with no MMN effects being found with separate treatment. These neural effects have relevance for sensory/cognitive processes influenced by separate and simultaneous use of cannabis and tobacco and may have treatment implications for disorders associated with sensory dysfunction and impairments in endocannabinoid and nicotinic cholinergic neurotransmission.

KEYWORDS:

Cannabis; Mismatch negativity; Nabilone; Nicotine; Schizophrenia; Tobacco

PMID:
31283908
DOI:
10.1016/j.pbb.2019.172739

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