Improving cue exposure outcomes in smokers using D-cycloserine
Dr. Sally Adams (UKCTCS)
10.15, Wednesday 10 July. Millennium Lounge, level 5
Introduction
Smoking-related cues play an important role in maintaining smoking behaviour and can be instigators of relapse. Therefore, cue exposure therapies (CETs) have been considered promising targets for intervention, but to date have met with limited success. CET is primarily based on classical conditioning, whereby a CET session acts as an extinction trial. Research using laboratory animals has shown that extinction learning can be enhanced using partial NMDA receptor agonists such as D-cycloserine (DCS). More recently, studies have investigated the effects of DCS on extinction learning and cue exposure outcomes in human participants in the fields of anxiety and, to a lesser extent, drug dependence.
Methods
This examines whether a standard 250mg dose of DCS enhances cue exposure outcomes in daily cigarette smokers (n = 50; 50% male; > 10 cigarettes/15 roll ups per day). Participants were randomised to either receive DCS or placebo in combination with CET. They attended four sessions approximately one week apart comprising screening/baseline (session one), drug administration and CET (sessions two and three), and cue reactivity tests (session four). Primary outcome measures were subjective craving and cardiovascular responses following a cue exposure test (session four). There is evidence to suggest that DCS may also increase the generalisability of cue exposure and therefore secondary analyses were conducted to examine whether the effects of combined CET/DCS generalised to other relevant smoking behaviours (attentional bias, concurrent choice and smoking topography).
Results
There was evidence of reduced craving across sessions, suggesting an effect of CET (P<.001). However, no drug group differences were observed on any of the primary (Ps >.12) or secondary (Ps >.26) outcome measures.
Discussion
This null finding echoes a growing body of literature reporting no or limited effect of DCS on drug-related CET in humans. The general failure to replicate the findings from the animal literature may be due to a failure to sufficiently use the animal literature to inform study design. Alternatively, animal paradigms fail to model the complexity of the human drug-cue experience and therefore the findings of single cue extinction may not be generalisable to the treatment of human smoking dependence.
Smoking-related cues play an important role in maintaining smoking behaviour and can be instigators of relapse. Therefore, cue exposure therapies (CETs) have been considered promising targets for intervention, but to date have met with limited success. CET is primarily based on classical conditioning, whereby a CET session acts as an extinction trial. Research using laboratory animals has shown that extinction learning can be enhanced using partial NMDA receptor agonists such as D-cycloserine (DCS). More recently, studies have investigated the effects of DCS on extinction learning and cue exposure outcomes in human participants in the fields of anxiety and, to a lesser extent, drug dependence.
Methods
This examines whether a standard 250mg dose of DCS enhances cue exposure outcomes in daily cigarette smokers (n = 50; 50% male; > 10 cigarettes/15 roll ups per day). Participants were randomised to either receive DCS or placebo in combination with CET. They attended four sessions approximately one week apart comprising screening/baseline (session one), drug administration and CET (sessions two and three), and cue reactivity tests (session four). Primary outcome measures were subjective craving and cardiovascular responses following a cue exposure test (session four). There is evidence to suggest that DCS may also increase the generalisability of cue exposure and therefore secondary analyses were conducted to examine whether the effects of combined CET/DCS generalised to other relevant smoking behaviours (attentional bias, concurrent choice and smoking topography).
Results
There was evidence of reduced craving across sessions, suggesting an effect of CET (P<.001). However, no drug group differences were observed on any of the primary (Ps >.12) or secondary (Ps >.26) outcome measures.
Discussion
This null finding echoes a growing body of literature reporting no or limited effect of DCS on drug-related CET in humans. The general failure to replicate the findings from the animal literature may be due to a failure to sufficiently use the animal literature to inform study design. Alternatively, animal paradigms fail to model the complexity of the human drug-cue experience and therefore the findings of single cue extinction may not be generalisable to the treatment of human smoking dependence.