Cognitively-enhanced tDCS of the dorsolateral prefrontal cortex to reduce craving in cocaine addiction

Icahn School Of Medicine At Mount Sinai, New York NY

Investigators

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Abstract

Over the past decade, the US has been affected by a re-emerging stimulant use public health crisis and alarming increases in crack/cocaine-related overdose deaths. In contrast to other types of addiction, there are no FDA approved treatments for crack/cocaine use disorder (CUD). Developing and testing evidence-based treatment options for this population, and exploring the underlying neural substrates, are therefore urgently needed. Core symptoms of addiction are craving and enhanced reactivity to drug cues, attributed to impairments in prefrontal cortical-mediated functions that include reduced inhibitory control. Using a battery-powered portable device that can be used safely, remotely and repetitively, we have shown in a Phase-1 pilot trial that 15 sessions of real (vs. sham) transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) reduced craving in individuals with CUD. Combining tDCS with cognitive/emotional training is optimal, as supported by human (and mechanistic) studies. Therefore, here tDCS will be administered during a dlPFC-dependent learning strategy, namely cognitive reappraisal (CR) of drug cues, shown to reduce motivated processing of and spontaneous attention bias to these salient cues in CUD, improving clinical outcomes in drug addiction. With four groups (total N=120), comprised of real- vs. sham dlPFC tDCS crossed over with CR vs. no CR, we will perform a double-blind randomized trial in the natural setting where individuals with CUD receive inpatient treatment. We will also test the feasibility of training in self-administration (for the ultimate design of remotely delivered trials). Our working hypothesis is that synergistically enhancing dlPFC function by combining tDCS with CR, a cognitive training, will decrease craving and cue-reactivity in CUD. Specifically, we hypothesize a real-tDCS vs. sham beneficial effect. In exploratory analyses, we will test whether this effect is modulated by CR (vs. no CR). Our main outcome measure, craving (and drug use measures), will be assessed at all study sessions and at a one month follow-up. Using a reliable and valid inhibitory control fMRI task before and after the tDCS trial (in all four groups) will allow ascertaining whether dlPFC recovery (post>pre tDCS) underlies the expected craving reductions (expected to be strongest during real-tDCS+CR) and identify biomarkers predictive of outcomes. Thus, in this project we will explore an entirely novel learning paradigm approach, using electrically enhanced neurocognitive training to modulate the neural networks underlying inhibitory control with the therapeutic goal of reducing craving (and hence drug use and relapse) in treatment-seeking inpatients with CUD. In addition to testing this novel intervention, the identification at baseline of predictive MRI-based measures could later be used for the design of timely prevention efforts. Establishing feasibility of self-administration and harnessing ecological validity by venturing to the clinic to enhance recovery in inpatients with CUD at the time/place it is most needed, we aim to empower patients with drug addiction with real-time lifesaving tools.