From Clinical Manifestations to Neural Mechanisms: A Systematic Review of Neurobehavioral Consequences of Pregabalin Misuse and Abuse

BACKGROUND/OBJECTIVE: Pregabalin is a γ-aminobutyric acid (GABA) analog. It is prescribed for neuropathic pain, fibromyalgia, anxiety disorders, and seizures. Pregabalin misuse and abuse have increased rapidly worldwide in recent years, raising public concerns owing to its addictive potential and associated neurotoxicity. To systematically characterize the neurobehavioral effects of pregabalin misuse and abuse, recent research was synthesized, and the relevant literature was reviewed to identify key findings, explore limitations, and outline future directions. METHODS: This systematic review followed the PRISMA guidelines. PubMed, Embase, Web of Science, CNKI, and Wanfang were searched for literature covering case series, cross-sectional, prospective, and retrospective studies, and animal experiments. The study's focus was to synthesize evidence of the neurobehavioral consequences of pregabalin misuse and abuse, and explore the association between clinical symptoms and neurobiological mechanisms. RESULTS: A total of 23 studies met the inclusion criteria. Acute overdose consistently produced neuroinhibitory symptoms and reward-seeking behaviors. Repeated or chronic exposure was associated with dose-dependent cognitive impairment, psychiatric comorbidity, addiction, and withdrawal syndrome. Preclinical studies revealed dopaminergic dysregulation, oxidative stress, and neuroadaptive remodeling. DISCUSSION: Human evidence consistently links acute overdose to neuroinhibitory symptoms and reward-seeking behaviors, with severity correlating with dose. Preclinical studies provide a plausible mechanistic hypothesis: acute pregabalin exposure may activate mesolimbic dopamine signaling while chronic high-dose exposure is associated with monoamine disruption, oxidative stress, inflammatory activation, and receptor remodeling in animal models. Direct translation of these findings to human pathophysiology warrants further investigation. CONCLUSION: Pregabalin misuse and abuse is associated with serious neurobehavioral risks, including acute neurotoxicity, chronic cognitive and psychiatric impairment, and addiction risk. However, the evidence base remains limited, and causal inference is constrained by the predominance of observational human studies and the preliminary nature of animal mechanistic data. Further research should refine risk stratification and inform public health strategies for early identification and intervention.