A placebo-controlled randomized trial of D-cycloserine augmentation of cue exposure therapy for smoking cessation

Abstract

Recent studies underscore the importance of studying d-cycloserine (DCS) augmentation under conditions of adequate cue exposure treatment (CET) and protection from reconditioning experiences. In this randomized trial, we evaluated the efficacy of DCS for augmenting CET for smoking cessation under these conditions. Sixty-two smokers attained at least 18 hours abstinence following 4 weeks of smoking cessation treatment and were randomly assigned to receive a single dose of DCS (n=30) or placebo (n=32) prior to each of two sessions of CET. Mechanistic outcomes were self-reported cravings and physiologic reactivity to smoking cues. The primary clinical outcome was 6-week, biochemically-verified, continuous tobacco abstinence. DCS, relative to placebo, augmentation of CET resulted in lower self-reported craving to smoking pictorial and in vivo cues (d = 0.8 to 1.21) in a relevant subsample of participants who were reactive to cues and free from smoking-related reconditioning experiences. Select craving outcomes were correlated with smoking abstinence, and DCS augmentation was associated with a trend toward a higher continuous abstinence rate (33% vs. 13% for placebo augmentation). DCS augmentation of CET can significantly reduce cue-induced craving, supporting the therapeutic potential of DCS augmentation when applied under appropriate conditions for adequate extinction learning.

The Treatment of Substance Use Disorders: Recent Developments and New Perspectives

“…Indeed, studies controlling for between-session sensitization experiences reported positive effects for DCS-augmented CET in patients with AUD [110] and TUD [122]. Moreover, all reported studies suffer from small sample sizes, making it difficult to detect the presumably small effect suggested from clinical trials in anxiety disorders [102].…”

“…Although groups did not differ in reported smoking behavior, expired carbon monoxide in the DCS group was significantly lower at the first of two follow-up sessions (d = 1.1). In line with this, Otto et al [106] investigated DCSaugmented CET after treatment-seeking TUD patients completed a smoking cessation treatment, showing reduced subjective craving and physiological reactivity to smoking cues (d = 0.8-1.21), but only a tendency of high-er abstinence rates at 6-week follow-up in DCS-treated participants relative to placebo. However, a third study found no effect of DCS + CET on cue-induced craving or attentional bias, but a statistical trend indicating DCS might have reduced tonic craving at 2-week follow-up, as assessed in the emotional subscale of the Tobacco Craving Questionnaire [107].…”

Transforming experiences: Neurobiology of memory updating/editing

“…NMDA receptor agonists (D-serine and D-cycloserine) facilitate the extinction of drug-induced conditioned place preference and reduce reinstatement ( Botreau et al, 2006 ; Myers and Carlezon, 2012 ; Hammond et al, 2013 ). In humans, D-cycloserine has been assessed prior to extinction sessions, with poor results in alcohol-dependent subjects and cocaine addicts ( Hofmann et al, 2012 ; Price et al, 2013 ; Santa Ana et al, 2015 ) and promising results in smokers ( Santa Ana et al, 2009 ; Kamboj et al, 2012 ; Otto et al, 2019 ). Clinical studies have used cue exposure therapy based on the extinction of the conditioned responses elicited by environmental stimuli.…”

Sex differences in the effects of a combined behavioral and pharmacological treatment strategy for cocaine relapse prevention in an animal model of cue exposure therapy

“…The optimized cue exposure therapy procedure includes pre-exposing subjects to cues before extinction training begins (i.e., a memory retrieval period) and administering an appropriate dose of D-cycloserine prior to sufficiently long extinction sessions that are typically spaced at weekly intervals [10,17]. With an optimized procedure, D-cycloserine improved cueexposure therapy for alcohol [18] and nicotine [19] to reduce craving and forestall relapse in alcohol-abusing individuals and smokers, respectively. Use of drug memory retrieval methods prior to extinction training also was shown to reduce cue-induced heroin craving in people and reinstatement of cocaine seeking in rats [20][21][22].…”