Combining CDP-choline and galantamine: Effects of a selective α7 nicotinic acetylcholine receptor agonist strategy on P50 sensory gating of speech sounds in healthy volunteers

Background: Schizophrenia (SCZ) patients and relatives have deficits in early cortical sensory gating (SG) typically measured by suppression of electroencephalography-derived P50 event-related potentials (ERPs) in a conditioning-testing (S-1-S-2) paradigm. Associated with alpha 7 nicotinic acetylcholine receptor (alpha 7 nAChR) dysfunction and shown to be improved with nicotine and alpha 7 nAChR agonists, SG has recently been shown to be improved in low P50 suppressing SCZ patients following acute CDP-choline treatment. Aims: This pilot study in healthy humans assessed the SG effects of an alpha 7 nAChR strategy combining CDP-choline with galantamine, a positive allosteric modulator (PAM) of nAChRs, aimed at increasing and prolonging nicotinic receptor activity. Methods: The combined effect of CDP-choline (500 mg) and galantamine (16 mg) on speech P50 gating indices rP50 (S-2/S-1) and dP50 (S-1-S-2) was examined in 30 healthy participants stratified into low and high baseline P50 suppressors in a randomized, double-blind, placebo-controlled and counterbalanced design. Results: In low suppressors, CDP-choline/galantamine (vs. placebo) improved rP50 and dP50 gating, and reduced S(2)P50 amplitudes. No P50 gating effects were observed in high suppressors; however, CDP-choline/galantamine (vs. placebo) increased their S(2)P50 amplitudes. Conclusion: Findings from this pilot study with CDP-choline/galantamine in a healthy, SCZ-like surrogate deficient gating sample are consistent with the association of alpha 7 nAChR mechanisms in SG impairment in SCZ and support further research trials with CDP-choline and galantamine targeting sensory processes.