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Scientists are investigating whether a specific type of brain stimulation, known as intermittent theta burst stimulation (iTBS), has a positive impact on tobacco addiction. In a study recently published in the journal Drug and Alcohol Dependence, they found that both active and placebo-like “sham” iTBS sessions reduced the number of cigarettes smoked daily by participants. The research highlights the complexities of treating addiction through neurological interventions and the need for continued research in this field.
iTBS is an advanced form of brain stimulation technology that has emerged from the broader field of repetitive transcranial magnetic stimulation (rTMS). Unlike traditional rTMS, which typically involves longer sessions of continuous stimulation, iTBS utilizes a pattern of bursts and intervals. Specifically, iTBS delivers groups of three pulses at a high frequency of 50 Hz, repeated every 200 milliseconds (5 Hz), making it a rapid and efficient method that mimics natural brain rhythms more closely than standard rTMS protocols.
This technique is designed to modulate neuronal activity in targeted areas of the brain, with the potential to alter neural networks that are associated with various psychiatric and neurological conditions, including depression and addiction. The overall session duration for iTBS is shorter — typically lasting only 2 to 3 minutes — which can make the treatment more tolerable and accessible for patients compared to the longer sessions required by traditional rTMS methods.
In their new study, the researchers sought to better understand the potential of iTBS as a treatment for tobacco use disorder, specifically targeting the medial prefrontal cortex of the brain. The medial prefrontal cortex plays a critical role in reward signaling and emotional regulation, which are key elements in addiction behaviors. Prior research had indicated that this region is active in response to drug cues and is involved in the valuation processes disrupted in addiction, making it a promising target for intervention.
“It’s really hard to quit smoking. Even with counseling and medication, fewer than 20% of people are able to quit. We’re always looking for new ways to help people quit smoking,” said study author Merideth A. Addicott, an associate professor of translational neuroscience at the Wake Forest University School of Medicine.
“Transcranial magnetic stimulation (TMS) is a type of intervention that can help change how the brain functions. It has been used to treat depression for years, and there is a lot of ongoing research into whether it might help with substance use disorders, such as tobacco use disorder. Researchers are still trying to figure out the best way to use TMS to make it effective for tobacco use disorder.”
During the course of the study, both active iTBS treatment and placebo-like sham stimulation were administered to participants targeting the medial prefrontal cortex. A total of 57 participants, all of whom were regular smokers desiring to quit, were recruited through various advertisements.
The treatments were spread over 14 visits, involving a total of 28 iTBS sessions. The primary metrics for measuring the effectiveness of the iTBS included changes in the number of cigarettes smoked daily, self-reported smoking abstinence, and biological markers such as urine cotinine levels a nicotine metabolite that confirms recent tobacco use.
The results indicated significant reductions in cigarette consumption for participants in both the active and sham stimulation groups. This decrease was sustained over the treatment period and follow-up. Surprisingly, there was no substantial difference between the active iTBS and sham groups in terms of the reduction in daily smoking or the rates of smoking cessation verified by urine cotinine levels. Specifically, about 16% of participants in the active treatment group and 15% in the sham group successfully abstained from smoking by the end of the study, as confirmed through biological verification.
The study also monitored secondary outcomes such as cravings, symptoms of tobacco withdrawal, and negative mood changes. These factors were similarly reduced across both groups over time, with no significant differences observed between those receiving active iTBS and those undergoing sham stimulation.
These findings suggest that while iTBS, as administered in this study, was associated with a reduction in cigarette use and improvement in related symptoms, the lack of difference between the active and sham groups raises questions about the specific effectiveness of iTBS in treating tobacco use disorder.
“In clinical trials, participants are randomly assigned to an active treatment and to a placebo, or sham, treatment,” Addicott explained. “TMS treatments are noisy and you can feel the stimulation on your scalp, like someone is tapping you. The sham TMS treatment mimics these effects in a very convincing way, so participants don’t know if they are receiving active or sham TMS.”
“We saw that participants who received active TMS treatment strongly reduced the number of cigarettes they were smoking per day. But so did the participants who received sham TMS treatment. This could have been due to a placebo effect, in that participants thought they are getting active TMS treatment, and could reduce their smoking more readily. It could also be the case that everyone in the study was highly motivated to reduce their cigarette use. But this makes it difficult to understand whether the active TMS treatment was having an effect or not.”
The researchers concluded that while TMS and iTBS are promising tools, further research is necessary to optimize their application in smoking cessation. This includes exploring different brain targets, adjusting stimulation parameters, and better understanding the mechanisms by which iTBS influences addictive behaviors.
“One way of improving TMS treatment for smoking cessation is to better understand what drives tobacco use, and what interferes with tobacco cessation,” Addicott said. “The idea behind a lot of TMS research for substance use disorders is to change the brain function that triggers cravings when people see the drug they use.”
“Alternatively, I’m interested in psychological distress. Many people who smoke report craving cigarettes when they are stressed. Another approach I would like to try is to use TMS to change the brain function that reacts negatively to stress, and potentially break the stress-smoking relationship.”
“This research is 100% dependent on people taking the time to participate,” Addicott added. “A major caveat to TMS treatment is that it requires numerous in-person visits to a clinic. Many participants may find this burdensome and drop out of the study. This makes it difficult to get enough participants to finish a study in order to understand if TMS had a beneficial effect. We really value our volunteers!”
The study, “A randomized controlled trial of intermittent theta burst stimulation to the medial prefrontal cortex for tobacco use disorder: Clinical efficacy and safety,” was authored by Merideth A. Addicott, Kaitlin R. Kinney, Santiago Saldana, Edward Hak-Sing Ip, Hannah DeMaioNewton, Warren K. Bickel, and Colleen A. Hanlon.
