Breaking the cycle: a systematic review of neurobiological mechanisms and psychotherapeutic innovations in ketamine addiction.
Christopher Lomas
Journal of Addictive Diseases March 6, 2025 DOI: 10.1080/10550887.2025.2464356 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Longitudinal Peer reviewed |
|---|---|
| Population | Adolescents, women, polysubstance users |
| Topics | Addiction Esketamine Ketamine |
| Keywords | Substance abuse Treatment innovation Cbt Emdr Ketamine addiction Special k Triage Neurobiological markers Neurobiology Neurologically informed psychotherapy Treatment framework Addiction treatment Psychotherapy approaches |
| Citations | 2 |
| Key findings | Non-prescribed ketamine addiction involves prefrontal-limbic dysconnectivity, maladaptive neuroplasticity, and HPA axis dysregulation, with adolescents, women, and polysubstance users as high-risk groups. |
Abstract
This systematic review synthesizes current evidence on non-prescribed ketamine use, emphasizing its neurobiological impacts and psychotherapeutic interventions. Patterns of misuse demonstrate the complex interplay of neurobiological, socio-economic, demographic and psychological factors with adolescents, women and polysubstance users identified as high-risk groups. Neurobiological findings highlight prefrontal-limbic dysconnectivity, maladaptive neuroplasticity alongside hypothalamic-pituitary-adrenal (HPA) axis dysregulation as central mechanisms underlying this addiction. The review evaluates the comparative efficacy of psychotherapies whilst proposing an innovative framework that aligns therapeutic timing with neuroplastic recovery phases. Emerging evidence identifies biomarkers, e.g., brain-derived neurotrophic factor (BDNF) and heart rate variability (HRV), as promising tools for guiding personalized and phase-specific interventions. Gaps in research include the limited representation of low-resource settings and insufficient longitudinal data on biomarker integration and therapy sequencing. Recommendations propose a comprehensive neurobiologically informed model which carefully integrates digital platforms, culturally tailored strategies and biomarkers to enhance treatment outcomes.
Comparable studies
Other systematic reviews and meta-analyses on ketamine for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine use: a review Ketamine users | 2011 | Systematic review | |
| Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review | 2021 | Systematic review | |
| Therapeutic Potentials of Ketamine and Esketamine in Obsessive–Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature | 2021 | Systematic review | |
| Efficacy of ketamine intervention to decrease alcohol use, cravings, and withdrawal symptoms in adults with problematic alcohol use or alcohol use disorder: A systematic review and comprehensive analysis of mechanism of actions. People with harmful alcohol use, alcohol craving, or alcohol withdrawal states,... | 2022 | Systematic review | n = 634 |
| Ketamine Treatment for Alcohol Use Disorder: A Systematic Review. Adult patients with alcohol use disorder, heavy drinkers, or those undergoing alcohol... | 2023 | Systematic review | n = 854 |