The effect of baclofen on methamphetamine dependent subjects.

Methamphetamine addiction is a major and growing problem in Australia, with a considerable individual, family and community burden. The current trend is a rapid increase in the use of crystal methamphetamine, the most addictive form, from 10% of users in 2010 to over 50% in 2014. Current treatment options for methamphetamine addiction are all based on Cognitive Behavioural Therapy (CBT) and have very low rates of durable abstinence. There are no proven pharmacotherapy options to assist in attaining and maintaining abstinence. The rapid increase in the use of high purity, highly addictive forms of methamphetamine, coupled with a lack of effective treatment, portends a public health catastrophe in Australia as outlined in the National Ice Action Strategy announced in April 2015. The key focus of treatment is to stop addicted individuals succumbing to the intense drug cravings on exposure to “drug cues”: anything that evokes drug memories eg places or people associated with their methamphetamine use. The treatments based on CBT aim to alter the individual’s response to drug cues but the igniting of these intense cravings is outside of conscious control. A more effective treatment strategy is to weaken the intensity of drug cravings with anti-craving medication. Baclofen is a strong candidate for methamphetamine addiction treatment due to its proven effectiveness in suppressing drug cravings for cocaine, another stimulant drug which, like methamphetamine, acts via the dopamine reward pathways of the brain. A 2014 study on cocaine addiction used functional MRI (fMRI) to objectively study the brain activation patterns in cocaine addicts in response to cocaine associated images (drug cues). The subjects treated with baclofen showed a dramatic and specific suppression of activation of the brain’s reward pathways compared to the placebo group. This provides a mechanistic explanation for the clinical effectiveness of baclofen in suppressing cravings for and the use of cocaine in addicted individuals. The study proposed in this application will reproduce the fMRI/cocaine study in 18 methamphetamine addicted subjects to test the effectiveness of baclofen (vs placebo) in suppressing reward pathway activation in response to methamphetamine drug cues. If baclofen is effective, it would provide the foundation for clinical trials of baclofen therapy combined with standard CBT treatment for methamphetamine addiction. This study seeks to rapidly establish if baclofen has an anti-craving action in the methamphetamine addicted brain. A positive result will accelerate baclofen treatment being adopted into current treatment programs for methamphetamine addiction with the aim of increasing durable abstinence rates.