Cognitive Effects of Very Low Nicotine Content Cigarettes, With and Without Nicotine Replacement, in Smokers With Schizophrenia and Controls

Abstract

Introduction: Beneficial effects of nicotine on cognitive functioning may contribute to the markedly high rates of smoking among people with schizophrenia. A reduction in the nicotine content of cigarettes to non-addictive levels is being considered as a regulatory strategy for reducing tobacco dependence in the United States. We examined whether switching to very low nicotine content (VLNC) cigarettes impairs cognitive functioning in smokers with and without schizophrenia, andwhether nicotine replacement reverses these effects. Methods: Smokers with schizophrenia (SS, n = 29) and control smokers matched on smoking rate but without psychiatric illness (CS, n = 28) smoked usual-brand cigarettes, VLNC cigarettes while wearing 2 placebo patches (PLA), or VLNC cigarettes while wearing 2 nicotine patches totaling 42 mg (NIC) for 5 hr, and then completed computerized assessments of visual sustained attention, motor speed, visual working memory, processing speed, inhibitory control, and response variability. Results: Across conditions, SS were slower than CS in tasks of motor speed and visual working memory, and had poorer target detectability on a visual sustained attention task. Across groups, functioning in domains of visual sustained attention, inhibitory control, processing speed, and response variability was impaired in the VLNC + PLA condition relative to the usual-brand and VLNC + NIC conditions. Conclusions: Dramatically reducing the nicotine content of cigarettes may impair cognitive functioning in heavy smokers with and without schizophrenia, but the use of nicotine replacement while smoking VLNC cigarettes may preserve cognitive functioning in these smokers.

A review of the effects of very low nicotine content cigarettes on behavioral and cognitive performance

“…Eleven of nineteen (58%) studies were rated Good or Excellent quality (Supplementary Table 2 provides details on study quality). Seventeen studies included smokers who were abstinent for ≥2 h and two studies (AhnAllen et al, 2015; McClernon et al, 2016) included smokers who were abruptly switched from NNC to VLNC cigarettes for ≥2 h. Ten performance domains were identified across studies: reaction time, short-term memory, sustained attention, inhibitory control, long-term memory, response variability, motor control/functioning, visuospatial processing, learning, and verbal fluency. Most studies measured multiple domains.…”

“…Of the nineteen studies, 79% (15/19) reported that performance was significantly worse among those who smoked a VLNC versus NNC cigarette (Rose et al, 2004; AhnAllen et al, 2015; McClernon et al, 2016; Bates et al, 1995; Colrain et al, 1992; Gilbert et al, 1997; Hale et al, 1999; Harrell and Juliano, 2012; Juliano et al, 2011; Kelemen, 2008; Lee et al, 2011; Marzilli et al, 2006; Peters and McGee, 1982; Warburton et al, 1992; Marzilli and Hutcherson, 2002). This effect was observed across 7 of 10 (70%) of the performance domains, including reaction time (73% or 8/11 studies), short-term memory (30% or 3/10), sustained attention (66% or 4/6 studies), inhibitory control (25% or 1/4 studies), long-term memory (100% or 3/3 studies), and response variability (100% or 2/2 studies).…”

“…Eleven studies examined reaction time (RT) (Rose et al, 2004; AhnAllen et al, 2015; McClernon et al, 2016; Bates et al, 1995; Hale et al, 1999; Harrell and Juliano, 2012; Juliano et al, 2011; Kelemen, 2008; Marzilli et al, 2006; Marzilli and Hutcherson, 2002; Smith et al, 2002), with four examining simple RT and eight examining complex RT. Among the four that examined simple RT, all noted worse performance among those who smoked VLNC compared to NNC cigarettes (AhnAllen et al, 2015; Bates et al, 1995; Marzilli et al, 2006; Marzilli and Hutcherson, 2002).…”

“…Among the four that examined simple RT, all noted worse performance among those who smoked VLNC compared to NNC cigarettes (AhnAllen et al, 2015; Bates et al, 1995; Marzilli et al, 2006; Marzilli and Hutcherson, 2002). This effect was discerned across variable study designs, including three studies that examined acute exposure to a VLNC cigarette after 2–12 h of smoking abstinence (Bates et al, 1995; Marzilli et al, 2006; Marzilli and Hutcherson, 2002), and a fourth that examined 5 h of VLNC exposure (AhnAllen et al, 2015). In addition to reporting similar results, the extended exposure study also demonstrated that performance was recovered by providing nicotine replacement therapy (NRT).…”

Cigarette Consumption and Related Factors in Schizophrenia, Schizoaffective Disorder and Delusional Disorder

“…Nicotine, by binding to nACH (nicotinergic acetylcholine) receptors, facilitates the transmission of dopamine and GABA (gamma aminobutyric acid) in various brain regions such as the prefrontal cortex, thalamus, ventral tegmental area, and nucleus accumbens (7). Through these effects, it is reported that improvement is observed in negative symptoms, cognitive deficits in working memory, processing speed, attention areas in schizophrenia patients (8)(9)(10)(11)(12). Nicotine has also been shown to alleviate extrapyramidal symptoms caused by neuroleptics (13,14).…”