An acute dose, randomized trial of the effects of CDP-Choline on Mismatch Negativity (MMN) in healthy volunteers stratified by deviance detection level

Abstract

Background: Alpha 7 nicotinic acetylcholine receptors (α7 nAChR) are prioritized molecular targets for the development of new pharmacological treatments for impaired cognition in schizophrenia. The use of schizophrenia-associated biomarkers both as endpoints and for segmentation of homogeneous populations for early detection of cognitive enhancing agents has been advanced to enhance the drug discovery process. Methods: In this study, the mismatch negativity (MMN) event-related brain potential (ERP), considered one of the few fully developed biomarkers in schizophrenia, was employed: a) to stratify 24 healthy volunteers into subgroups exhibiting low, medium, or high auditory sensory discrimination based on pre-attentive detection of deviant auditory features, and b) to assess their acute response to a low (500 mg) and moderate dose (1000 mg) of CDP-choline, a dietary supplement with selective agonist actions at α7 nAChRs.

Targeting neuronal dysfunction in schizophrenia with nicotine: Evidence from neurophysiology to neuroimaging

“…Another possibility is that nicotinic effects were influenced by differences baseline MMN; nicotine increases MMN amplitude in healthy subjects with low baseline MMN but has the opposite effect in healthy subjects with high baseline MMN (Knott et al, 2014a). In line with these findings, a similar pattern of baseline dependence was observed in healthy subjects given an acute dose of choline (Knott et al, 2015). All three patient studies also had relatively low sample sizes ( n = 10–12) and the effects of nicotine on MMN in schizophrenia are therefore inconclusive.…”

Mismatch negativity in tobacco-naïve cannabis users and its alteration with acute nicotine administration

“…With respect to drug interactions, adolescent exposure to nicotine has been found to modify acute functional response to cannabinoid agonists in rats (Viveros et al, 2006) and chronic nicotine use has been shown to mask disruptions in cognitive neurocircuitry associated with adolescent cannabis use (Jacobsen et al, 2007). Cannabidol, a non-psychoactive ingredient of the cannabis plant has been shown to inhibit the function of the α7 nicotinic acetylcholine receptor (Mahgoub et al, 2013), which is diminished in numbers in SZ (Freedman et al, 2000) and when stimulated with a selective agonist has resulted in increased sensory memory in healthy individuals with low MMN amplitudes (Knott et al, 2015).…”

Citicoline (CDP‐choline) add‐on therapy to risperidone for treatment of negative symptoms in patients with stable schizophrenia: A double‐blind, randomized placebo‐controlled trial

“…In contrast, Christensen et al () showed that repeated administration of A‐582941, an α7 nAChR agonist, with no positive allosteric modulator, increases α7 nAChR levels in several brain regions (especially prefrontal cortex). It is also suggested that, nAChR agonist effects display an inverted U‐shaped dose response curve, with maximal effects being observed at low and ultralow doses (Knott et al, ). Relatively high dose citicoline was utilized in this study and fairly satisfactory results were gained.…”

“…Relatively high dose citicoline was utilized in this study and fairly satisfactory results were gained. Nonetheless, it is not clear whether this high dose has reduced the actual nAChR agonist effect (Knott et al, ).…”