Deep Brain Stimulation to Understand and Treat Addiction

Deep Brain Stimulation for Disorders of Addiction: Mechanisms and a Pilot Blinded Randomized Cross-over Placebo Controlled Trial

This study is testing whether deep brain stimulation (DBS) can safely help people with severe alcohol use disorder who have not improved with standard treatments. DBS uses small electrical signals to change activity in brain areas linked to craving, self-control, and emotion. The study will test whether this treatment can reduce how often people drink and how much they drink each day. Researchers will also record brain activity to better understand how DBS affects craving and relapse.

Alcohol use disorder (AUD) is a leading cause of preventable illness and death worldwide and remains a major public health concern. In the United Kingdom, alcohol misuse is the greatest risk factor for death and disability among adults aged 15-49, yet many people relapse despite standard treatments. Treatment-refractory AUD therefore represents an urgent unmet clinical need. Addiction is increasingly viewed as a disorder of maladaptive brain network activity involving dysregulation of motivation, reward, stress, and executive-control systems.

Deep brain stimulation (DBS) delivers small electrical pulses to targeted brain areas to restore balanced network activity. DBS is established for movement and obsessive-compulsive disorders, and early studies suggest potential benefit for substance addictions.

This pilot trial tests dual-target DBS of the nucleus accumbens and ventral internal capsule to modulate circuits supporting craving, emotion, and self-control. Participants with severe, treatment-resistant AUD will undergo an initial open-label optimization phase followed by a randomized, blinded cross-over comparison of dual, single-site, and sham stimulation. Primary outcomes are changes in drinking frequency and quantity. Intracranial recordings from the implanted device will capture local field potentials to identify brain-signal patterns linked to craving and emotion, helping guide the development of future adaptive neuromodulation approaches for addiction.

Inclusion Criteria:

• Adults aged 18 to 60 years
• Diagnosed with Alcohol Use Disorder (AUD) according to DSM-5 criteria
• Primary diagnosis of treatment-refractory AUD (comorbid nicotine dependence, other psychoactive substance use disorders, moderate major depressive disorder, anxiety disorders or obsessive-compulsive disorder are permissible if AUD is principal)
• Disorder duration of AUD ≥ 5 years
• At least 3 unsuccessful attempts at achieving abstinence
• Failed prior psychotherapy and standard pharmacotherapy for AUD
• Medically and neurologically suitable for surgery and MRI-compatible
• Capable of providing informed consent and willing to comply with study procedures

Exclusion Criteria:

• Severe psychiatric disorder other than Alcohol Use Disorder (e.g., schizophrenia, schizoaffective disorder, bipolar disorder)
• Severe major depressive disorder (moderate depression acceptable)
• Current active suicidal ideation or history of serious suicide attempts
• Previous treatment with electroconvulsive therapy (ECT)
• Presence of implanted electrical devices, including:
• Cardiac pacemaker or defibrillator (or clinical indication for pacemaker placement)
• Implanted vagus nerve stimulator (VNS)
• Any other chronically implanted neurostimulation device
• Significant neurological history, including prior hemorrhagic or ischemic stroke, subarachnoid hemorrhage, or other major neurological illness
• Any significant medical condition that, in the opinion of the clinical team, would increase surgical or anesthetic risk
• Current pregnancy
• Contraindications to deep brain stimulation or neurosurgery, including:
• Inability to tolerate general anesthesia (as assessed by anesthesiology)
• Increased risk of bleeding (as determined by hepatology/hematology review)
• History of coagulopathy
• Current or previous anticoagulant use
• Uncontrolled hypertension (controlled hypertension with medication is acceptable)
• Stage 4 liver cirrhosis
• History of major cardiac arrhythmia (e.g., atrial fibrillation) or need for anti-arrhythmic medication
• History of requiring cardioversion
• History of repeated falls
• History of major head injury
• Marked cognitive impairment
• Seizure history, including multiple alcohol withdrawal seizures
• Marked cortical atrophy on neuroimaging
• Inadequate logistical or social support that would impair the safe conduct of deep brain stimulation therapy, including inability to reliably attend scheduled visits, lack of reasonable access to the study site, or inadequate home or caregiver support necessary for postoperative care, device management and follow-up.