Ketamine—50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms

Summary & key facts

Ketamine has been used as an anesthetic in people and animals for about 50 years. More recently, researchers have studied it for new uses like treating long-term pain, drug addiction, and post-traumatic stress. The big finding that pushed this work is that ketamine can lift severe depression very quickly. But scientists do not yet know exactly how it works, because its effects change with dose, it produces several active breakdown products, and it seems to change how brain connections adapt. This paper reviews those uses, looks at the doses tested for depression, and summarizes current ideas about how ketamine might act.

Key facts:

• Ketamine has been used in human and veterinary medicine as an important anesthetic for about 50 years.
• Researchers have studied ketamine for new medical uses beyond anesthesia, including chronic pain, drug addiction, and post-traumatic stress disorder.
• The discovery that ketamine can reduce depressive symptoms very quickly sparked a large increase in research on its psychiatric effects.
• Scientists do not yet have a clear, agreed explanation for how ketamine produces antidepressant effects.
• Understanding ketamine is hard because its effects depend on dose, it creates several active metabolites (breakdown products), and it appears to help the brain change connections between cells, a process called synaptic plasticity.
• This review summarizes ketamine’s different uses, focuses on the various doses used in antidepressant studies, and discusses recent hypotheses about how it works.

Abstract

Abstract Over the past 50 years, ketamine has solidified its position in both human and veterinary medicine as an important anesthetic with many uses. More recently, ketamine has been studied and used for several new indications, ranging from chronic pain to drug addiction and post-traumatic stress disorder. The discovery of the rapid-acting antidepressant effects of ketamine has resulted in a surge of interest towards understanding the precise mechanisms driving its effects. Indeed, ketamine may have had the largest impact for advancements in the research and treatment of psychiatric disorders in the past few decades. While intense research efforts have been aimed towards uncovering the molecular targets underlying ketamine’s effects in treating depression, the underlying neurobiological mechanisms remain elusive. These efforts are made more difficult by ketamine’s complex dose-dependent effects on molecular mechanisms, multiple pharmacologically active metabolites, and a mechanism of action associated with the facilitation of synaptic plasticity. This review aims to provide a brief overview of the different uses of ketamine, with an emphasis on examining ketamine’s rapid antidepressant effects spanning molecular, cellular, and network levels. Another focus of the review is to offer a perspective on studies related to the different doses of ketamine used in antidepressant research. Finally, the review discusses some of the latest hypotheses concerning ketamine’s action.

Topics

Stress Responses and Cortisol Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Anesthetic Antidepressant Biochemistry Biology Epistemology Facilitation Hippocampus In vitro Ketamine Mechanism (biology) Mechanism of action Medicine Neuroscience Pharmacology Philosophy Psychiatry Psychology

Substances

Ketamine

Conditions & symptoms

Addiction Chronic Pain Depression PTSD Addiction or harmful habbits Chronic pain Sadness or low mood