Addiction is a major public health issue. It is a significant challenge worldwide, impacting millions of lives. DBS, a well-established and FDA-approved treatment for conditions like Parkinson’s disease (1997)^1,2, dystonia (2003)³, and severe OCD (2009)^4,5, is now being explored as a method for addiction treatment^6-8. Several small studies of DBS in addictions confirm safety and potential efficacy. Our study aims to provide robust evidence for the efficacy of DBS in treating refractory addictions, potentially transforming therapeutic approaches and improving patient outcomes.

Brain-PACER will also focus on the latest advancements in neurotechnology to understand underlying mechanisms of addiction and develop better personalised treatments focusing on preventing craving and relapse.

¹ Lachenmayer, M. L. et al. Subthalamic and pallidal deep brain stimulation for Parkinson’s disease—meta-analysis of outcomes. npj Parkinsons Dis. 7, 1–10 (2021). https://doi.org/10.1038/s41531-021-00223-5
² Deuschl, G. et al. A Randomized Trial of Deep-Brain Stimulation for Parkinson’s Disease. New England Journal of Medicine 355, 896–908 (2006). https://doi.org/10.1056/NEJMoa060281
³ Isaias, I. U., Alterman, R. L. & Tagliati, M. Deep Brain Stimulation for Primary Generalized Dystonia: Long-term Outcomes. Archives of Neurology 66, 465–470 (2009). https://doi.org/10.1001/archneurol.2009.20
⁴ Gadot, R. et al. Efficacy of deep brain stimulation for treatment-resistant obsessive-compulsive disorder: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 93, 1166–1173 (2022). https://doi.org/10.1136/jnnp-2021-328738
⁵ Menchón, J. M. et al. A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder. Mol Psychiatry 26, 1234–1247 (2021). https://doi.org/10.1038/s41380-019-0562-6
⁶ Bach, P. et al. Deep brain stimulation of the nucleus accumbens in treatment-resistant alcohol use disorder: a double-blind randomized controlled multi-center trial. Transl Psychiatry 13, 49 (2023). https://doi.org/10.1038/s41398-023-02337-1
⁷ Davidson, B. et al. Deep brain stimulation of the nucleus accumbens in the treatment of severe alcohol use disorder: a phase I pilot trial. Molecular Psychiatry 27, 3992–4000 (2022). https://doi.org/10.1038/s41380-022-01677-6
⁸ Chen, L. et al. Long-term results after deep brain stimulation of nucleus accumbens and the anterior limb of the internal capsule for preventing heroin relapse: An open-label pilot study. Brain Stimulation 12, 175–183 (2019). https://doi.org/10.1016/j.brs.2018.09.006

Addictions can be broadly thought of as an imbalance of an accelerator – motivation and drive underlying addiction rewards, and impaired braking – decision-making, control and flexibility. The Brain-PACER study employs DBS stimulation to address this imbalance by delivering precise electrical stimulation to brain regions to regulate the neural circuits responsible for addictive behaviours.

Target Areas for Brain-PACER DBS

• Nucleus Accumbens: This region is crucial for motivation, processing rewards and reinforcing behaviours. By modulating its activity, we aim to reduce the urge for repeated alcohol and drug use. This modulation can alter dopamine signalling, essential in the reward pathway, thereby helping to reduce cravings.
• Ventral Internal Capsule: This area contains pathways that connect different parts of the brain involved in decision-making and emotion. Stimulation here helps regulate decision-making and impulse control by linking the prefrontal cortex, responsible for higher-order executive functions, with deeper brain structures involved in reward. Stimulation here addresses the underlying neural mechanisms of addiction by improving impulse control and decision-making processes.

Stimulating these two areas aims to reduce cravings and improve control over addictive behaviours by modulating the brain circuits involved in reward, motivation, and decision-making.

DBS is a neurosurgical treatment that involves implanting a slender electrode in the brain and a pacemaker under general anaesthesia. These electrodes deliver electrical impulses to modulate neural activity, which can help alleviate symptoms of various neurological and psychiatric disorders. DBS has been safely and effectively used since the late 1980s, with FDA and CE-marked approvals for several neurological and psychiatric disorders, ensuring its credibility and reliability as a treatment option.

1. Implantation: During surgery, thin electrodes are carefully placed in precise locations of the brain. These locations are chosen based on the condition being treated. For addiction, the electrodes are placed in areas involved in reward, motivation, and decision-making.
2. Device Connection: The electrodes are connected to a small battery-powered device called a pulse generator, which is usually implanted under the skin near the collarbone. This device sends electrical impulses to the brain.
3. Stimulation: The electrical impulses from the pulse generator help regulate abnormal brain activity. In the case of addiction, these impulses may help reduce cravings and improve self-control by modulating brain circuits involved in these behaviours.
4. Adjustment: After the surgery, doctors can adjust the settings of the device to ensure it provides the most benefit. This process is usually done through a wireless connection to the pulse generator.

This treatment is reversible and adjustable, making it a flexible option for managing chronic conditions. By understanding and harnessing the brain’s electrical signals, DBS offers a way to improve the quality of life for many patients.

Brain-PACER is a large multicentre study conducted throughout the UK. Led by Professor Valerie Voon of the Voon Lab at the University of Cambridge Department of Psychiatry, the study is funded by the Medical Research Council (MRC) and operates under ethics approval of the Cambridge University Hospital and University of Cambridge.

In collaboration with Kings College Hospital, the Institute of Psychiatry, Psychology, and Neuroscience (IoPPN) at King’s College London, under the South London and Maudsley (SLaM) NHS Foundation Trust, and the University of Oxford, this study spans multiple institutions known for their high-quality research.