Temporal interference methods for addiction treatment

Project summary/abstract (30 lines max)
Substance use disorders (SUDs) remain difficult to treat, but recent studies have shown remarkable, effortless
loss of addiction to both opioids and alcohol with invasive deep brain stimulation of the nucleus accumbens.
Likewise, disruption of the anterior insula has also led to spontaneous, effortless loss of addiction. While highly
effective, deep brain stimulation as a treatment for addiction is out of reach for the general population due to
the expense and risk of the brain surgery involved. If similar stimulation could be carried out non-invasively, it
could potentially make more effective treatment for a variety of SUDs broadly accessible, with profound
individual and public health implications. A new technology called temporal interference (TI) electrical
neurostimulation may provide such a means of non-invasive stimulation of deep brain regions, but it has not
yet been tested for efficacy in clinical samples. We recently provided a first step by demonstrating that TI can
effectively activate the nucleus accumbens as measured by simultaneous fMRI BOLD imaging. With the
technique now demonstrated, we propose a preliminary clinical trial to test the effects of 60 minutes of TI
stimulation on the nucleus accumbens and anterior insula on nicotine craving and use, both during TI
stimulation and for one week following, using ecological momentary assessment methods. Heavy smokers and
vape users will be recruited and will abstain from nicotine prior to stimulation. Subjects will be randomized into
three groups: nucleus accumbens, anterior insula, and sham control groups. They will receive TI stimulation (or
sham) for 60 minutes with self-reported cravings every 10 minutes and each day for one week after. Our
existing custom vape device will measure the volume of inhaled vapor to identify changes in actual nicotine
use during TI stimulation. All subjects will complete a set of questionnaires assessing their level of nicotine
dependence, their comfort during the stimulation experience, their cognitive abilities before and after
stimulation, and any changes in emotion and motivation before vs. after the stimulation. We will analyze the
results to identify decreases in nicotine craving and/or nicotine vapor inhalation during stimulation of nucleus
accumbens vs. sham and anterior insula vs. sham, and directly between nucleus accumbens and anterior
insula stimulation. Furthermore, we will identify the duration of such effects by running similar statistical tests
on the self-reported craving and nicotine use over the following 7 days. We will also assess safety and
tolerability, which were good in our pilot subjects. Positive results in this clinical trial will have profound
implications, as the TI technology can be mass produced and used as an “electroceutical”, with equipment
potentially similar in size and cost to a common cell phone.

Grant Number: 1R21DA062805-01
NIH Institute/Center: NIH
Principal Investigator: Joshua Brown