Exploring the potential of D-cycloserine and cannabidiol to enhance cue exposure therapies in substance dependence

Lead Research Organisation: University College London
Department Name: Clinical Health and Educational Psych


Addiction is one of the key long-term harmful effects of drug and alcohol use. Unfortunately, psychological and pharmacological treatments for addiction are often unsuccessful. Some progress has been made in behavioural treatments for addiction which may involve exposing addicts to reminders of their drug / alcohol use, while preventing them from actually taking the drug/drinking. This is called exposure and response prevention (ERP) therapy. However, many who complete this type of treatment still relapse when they are in environments where temptations or reminders of drug use are present. This happens because memories which influence drug-use are particularly strong and automatically trigger drug taking / drinking.
However, it is possible that if psychological treatment is combined with a drug which improves learning, old, drug-taking memories might be ?over-written? more successfully. One drug called D-Cycloserine (DCS) has been successfully used in treating anxiety disorders when combined with ERP. Another drug, cannabidiol (CBD), has proved effective in addicted animals when it is combined with a version of ERP. Since there are some parallels in the psychological processes which occur in drug / alcohol addiction and anxiety disorders, we want to investigate whether DCS and CBD can improve psychological treatment for drug / alcohol addiction. If they can, this may prove to be an important breakthrough in the treatment of the very harmful disorder of addiction.

Technical Summary

Treatments for addiction often fail. Even those who successfully respond or adhere to treatments often relapse into harmful drug-taking. This research will investigate the possibility of enhancing an existing behavioural treatment for addiction, namely cue exposure / response prevention, through synergy with two putative nootropic drugs: D-Cycloserine (DCS) and cannabidiol (CBD).
DCS has already emerged as a potentiator of exposure therapy in anxiety disorders. Given the likely overlapping neurocognitive processes in anxiety disorders and substance dependence disorders (Otto et al, 2005), we intend to investigate the potential of DCS as an enhancer of exposure therapies in drug and alcohol dependence. We hypothesise that following exposure to drug / alcohol cues, subjective, physiological and cognitive responses will undergo extinction as suggested by reduced cue reactivity in those treated with DCS.
In addition, preclinical data suggests that CBD is also a promising candidate which could enhance exposure therapies, although its potential has yet to be tested in humans. We hypothesise, that similar to DCS, CBD will enhance extinction learning in addicted / dependent individuals.
In addition to investigating their mechanisms of action in a laboratory study, we will examine the effects of DCS and CBD in three separate placebo controlled studies in drug and alcohol using populations, allowing the generalizability of their effect to be tested.
We envisage that this research will have important implications for substance abuse and addiction services in the UK.
Description MRC project grant (Neuroscience / Mental Health)
Amount £477,509 (GBP)
Funding ID MR/M007006/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 11/2014 
End 11/2017
Description PhD Studentship
Amount £62,360 (GBP)
Organisation Economic and Social Research Council 
Sector Public
Country United Kingdom
Start 10/2010 
End 09/2014