The neurobehavioral pharmacology of ketamine: implications for drug abuse, addiction, and psychiatric disorders.
Keith A Trujillo, Monique L Smith, Brian Sullivan, Colleen Y Heller, Cynthia Garcia, Melvin Bates
ILAR journal 2011 DOI: 10.1093/ilar.52.3.366 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Animals in preclinical research, with reference to human clinical and recreational use |
| Intervention | Ketamine |
| Dose | subanesthetic doses; very low subanesthetic doses |
| Topics | Ketamine Addiction Esketamine |
| Keywords | Animals Humans Substance-related disorders Analgesics Antidepressive agents Behavior, addictive |
| Key findings | The authors report that, contrary to the usual view of ketamine as a locomotor stimulant at subanesthetic doses, they found locomotor depressant effects at very low subanesthetic doses, indicating a complex rather than monotonic dose-response relationship. The review also covers ketamine's analgesic, schizophrenia-modeling, antidepressant, and abuse-related uses, along with its mechanisms, neuroadaptations, and reward. |
Abstract
Ketamine was developed in the early 1960s as an anesthetic and has been used for medical and veterinary procedures since then. Its unique profile of effects has led to its use at subanesthetic doses for a variety of other purposes: it is an effective analgesic and can prevent certain types of pathological pain; it produces schizophrenia-like effects and so is used in both clinical studies and preclinical animal models to better understand this disorder; it has rapid-acting and long-lasting antidepressant effects; and it is popular as a drug of abuse both among young people at dance parties and raves and among spiritual seekers. In this article we summarize recent research that provides insight into the myriad uses of ketamine. Clinical research is discussed, but the focus is on preclinical animal research, including recent findings from our own laboratory. Of particular note, although ketamine is normally considered a locomotor stimulant at subanesthetic doses, we have found locomotor depressant effects at very low subanesthetic doses. Thus, rather than a monotonic dose-dependent increase in activity, ketamine produces a more complex dose response. Additional work explores the mechanism of action of ketamine, ketamine-induced neuroadaptations, and ketamine reward. The findings described will inform future research on ketamine and lead to a better understanding of both its clinical uses and its abuse.
Comparable studies
Other narrative reviews on ketamine for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder Patients with treatment-resistant depressive symptoms as part of major depressive... | 2018 | Narrative review | |
| Can psychedelic compounds play a part in drug dependence therapy? Patients with substance dependency | 2015 | Review | |
| Therapeutic potential of ketamine for alcohol use disorder. | 2021 | Review | |
| Non-parenteral Ketamine for Depression: A Practical Discussion on Addiction Potential and Recommendations for Judicious Prescribing | 2022 | Review | |
| Ketamine, an Old–New Drug: Uses and Abuses | 2023 | Review |