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.

KEYWORDS:

• D-cycloserine
• cue exposure
• addiction
• nicotine dependence
• extinction
• craving
• cue reactivity
• smoking cessation

Disclosure statement

In the past, Dr. Otto has served as a paid consultant for MicroTransponder Inc., Concert Pharmaceuticals, ProPhase, received speaker compensation from Big Health, and received royalty compensation for use of the SIGH-A from ProPhase. Dr. Cather has served as a paid consultant for Envivo and ProPhase. Dr. Smits has served as a paid consultant for MicroTransponder Inc. Dr. Evins has received research grant or study supply support from Pfizer and Forum Pharmaceuticals; she has received compensation to her institution for consultation from Pfizer and Reckitt Benckiser. No other authors have financial disclosures.

Additional information

Funding

This research was supported by grants R21DA030808 Cognitive Remediation with DCS to Improve Smoking Cessation Outcomes (Evins), K24030443 Mentoring in addiction treatment research (Evins). Mentoring support was also provided to Gladys N Pachas by the Interdisciplinary Research Training Institute on Hispanic Drug Abuse (NIDA R25DA026401). These funding sources had no other role than financial support.