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 |
Citations in the library
Cited by 21
- Ketamine and its metabolite (2R,6R)-hydroxynorketamine induce lasting alterations in glutamatergic synaptic plasticity in the mesolimbic circuit Molecular Psychiatry November 21, 2017
- Is Off-label repeat prescription of ketamine as a rapid antidepressant safe? Controversies, ethical concerns, and legal implications BMC Medical Ethics January 14, 2016
- Use and abuse of dissociative and psychedelic drugs in adolescence Pharmacology, Biochemistry, and Behavior January 27, 2021
- Age, Dose, and Locomotion: Decoding Vulnerability to Ketamine in C57BL/6J and BALB/c Mice. Biomedicines June 25, 2023
- The effects of (2R,6R)-hydroxynorketamine on oxycodone withdrawal and reinstatement. Drug and Alcohol Dependence December 1, 2023
and 16 more in the library
Cites 30
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate British Journal of Pharmacology June 1, 1983
and 25 more in the library