Boosting and guiding neuroplasticity by combining ketamine with neurofeedback-assisted learning – towards an individualized and integrated pharmaco-psychotherapy for cocaine addiction
Abstract
Until today no pharmacotherapy has been approved for the treatment of cocaine use disorder (CUD) due to a lack of efficacy of tested compounds, and conventional psychotherapeutic approaches show only moderate effect sizes. Ketamine, mainly known as antagonist at the glutamatergic N-methyl-D-aspartate (NMDA)-receptor, increases glutamate levels in the nucleus accumbens (NAcc), at least in animals. Thus, it holds the potential to normalize accumbal glutamate homeostasis in CUD. Interestingly, clinical pilot studies indicate that ketamine is capable to reduce cocaine craving and use. However, its relevant mechanism of action in CUD and, accordingly, a suitable marker for personalized and more effective pharmacotherapy remains to be established. Furthermore, an enhanced sensitivity towards substance-related reward in addiction is often associated with increased craving and substance use, and on the other hand, the reduced sensitivity towards non-substance related rewards often results in neglection of other areas of life. Assisted by real time functional magnetic resonance imaging (rt-fMRI) neurofeedback training (NFT) during an individualized mental imagery task, individuals can learn to precisely regulate their reward system and enhance its sensitivity towards non-substance-related rewards, i.e. to reduce shifts in reward processing that characterize the disease. To boost this learning effect, we propose to combine rt-fMRI NFT with ketamine.
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