Rewiring reward in addiction: a systematic review of human evidence for deep brain stimulation and lesion approaches in substance use disorders
Abstract
Objective: Neurosurgical modulation of reward circuitry has been explored for severe, treatment-refractory substance use disorders (SUDs), yet the human literature remains fragmented across targets, modalities, and outcomes, limiting target selection and future trial design. We systematically reviewed human clinical evidence for deep brain stimulation (DBS) and lesion approaches targeting reward network nodes for SUDs, and summarized convergent preclinical findings to identify where the strongest clinical signal exists and to provide a framework for mechanism-informed future trials.
Methods: We systematically searched PubMed, PubMed Central, Embase, and Scopus (inception-September 9, 2025) for human DBS/ablation studies in primary SUDs targeting addiction-relevant nodes (e.g., nucleus accumbens [NAc], ventral capsule/ventral striatum/anterior limb of internal capsule [ALIC], subthalamic nucleus) and reporting extractable outcomes; in vivo addiction-model animal studies were included for mechanistic context. Findings were synthesized narratively.
Results: Forty-seven studies met inclusion criteria. The clearest controlled human signal came from bilateral NAc DBS in severe alcohol use disorder, with additional promising but less mature findings in heroin/opioid DBS. In the only randomized delayed-activation trial of bilateral NAc DBS for severe alcohol use disorder (n = 12), abstinent days increased from 27.6% to 56.0% at 6 months (p = 0.014) and 74.2% at 18 months (p =…
How strong is the evidence?
Evidence Hub reads this as a systematic review, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 12 participants or records.
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