The emergence of ketamine--previously known as a combat anesthetic and club drug--as a treatment for depression. Ketamine, approved in 2019 by the Food and Drug Administration for the treatment of depression, has been touted by scientists and media reports as something approaching a miracle cure. This volume in the MIT Press Essential Knowledge series chronicles the ascent of a drug that has been around for fifty years--in previous incarnations, a Vietnam-era combat anesthetic and a popular club drug--that has now been reinvented as a treatment for depression. Bita Moghaddam, a leading researcher in neuropharmacology, explains the scientific history and the biology of ketamine, its clinical use, and its recently discovered antidepressant effects, for the nonspecialist reader.

This book presents the latest data from basic research and clinical trials supporting the effectiveness of ketamine as a treatment for depression, bipolar disorder, and suicidal behavior, setting these positive findings within the context of the serious problem of ketamine abuse. The first part of the book focuses on the evidence regarding ketamine abuse, with specific reference to Asian countries, and discusses countermeasures and complication management. It then addresses the mechanisms underlying the antidepressant and side effects of ketamine, which have remained elusive, describing and discussing important new research findings. Further, it explains insights gained from whole brain imaging in rodents and from behavioral pharmacology, and presents evidence regarding the role of gut microbiota, the NMDA receptor GluN2D subunit, and the lateral habenula in the actions of ketamine. These advances form the basis for the safer use of ketamine in patients with treatment-resistant depression and are expected to lead to the development of new antidepressants. --

Ketamine, also called K, Special K, and Kit Kat, causes bizarre experiences unlike any other psychedelic drug. The Little Book of Ketamine describes the recreational and spiritual use of Ketamine, including: What K is, how it is made, and how it is used; How K affects the brain; Hallucinations, near-death and out-of-body experiences; Spiritual enlightenment through K and afterlife experiences; Dosages, administration, and safety precautions; Accounts of K-Trips by experienced users; How it feels to go to K-Land; Ketamine and the law. The Little Book of Ketamine reviews the history of Ketamine from its discovery to its use in night clubs and raves, as well as describing extraordinary stories of Ketamine's effects while being mindful of what is myth and what is reality. "Ketamine is a very odd and intriguing entheogen, outpacing all others in sheer range of experience and utter strangeness. It unlocks powers so intense and improbable it is hard to believe such a substance could even exist." —James Kent TRP

Some important constraints of anesthesia must be taken into consideration when the pharmacological properties of modern anesthetics are discussed. The most imp- tant of these could be that the target effect be achieved preferably within seconds, at most within a few minutes. Similarly, offset of drug action should be achieved within minutes rather hours. The target effects, such as unconsciousness, are pot- tially life-threatening, as are the side effects of modern anesthetics, such as respi- tory and cardiovascular depression. Finally, the patient’s purposeful responses are not available to guide drug dosage, because, either the patient is unconscious, or more problematically, the patient is aware but unable to communicate pain because of neuromuscular blockade. These constraints were already recognised 35 years ago, when in 1972 Volume XXX entitled “Modern Inhalation Anesthetics” appeared in this Handbook Series. The present volume is meant as a follow up and extension of that volume. At the beginning of the 1970’s anesthesia was commonly delivered by inhalation, with only very few exceptions. The clinical understanding of that time considered anesthesia as a unique state achieved by any of the inhalation anesthetics, in- pendent of their specific molecular structure. “The very mechanism of anesthetic action at the biophase” was discussed within the theoretical framework of the “u- tary theory of narcosis”.

This book brings together an international group of clinicians and researchers from a broad swath of inter-related disciplines to offer the most up-to-date information about clinical and preclinical research into ketamine and second-generation “ketamine-like” fast-acting antidepressants. Currently available antidepressant medications act through monoaminergic systems, are ineffective for many individuals suffering from depression, and are associated with a delayed onset of peak efficacy of several months. The unexpected emergence of ketamine, an anesthetic N-methyl-D-aspartate (NMDA) receptor antagonist, as a rapid-acting antidepressant has reinvigorated CNS drug discovery research and catalyzed investigation in patient populations historically ignored in antidepressant drug development programs, particularly treatment-resistant patients and those with suicidality. Recent industry and academic research efforts have coalesced to explore NMDA receptor and glutamatergic molecular targets that lack ketamine’s psychotomimetic side effects and abuse liability but retain its rapid onset of efficacy. However, many fundamental questions remain regarding the neurobiological mechanisms underlying ketamine’s rapid antidepressant effects and the puzzling persistence of benefits observed in some patients following a single dose. This book examines how insights from these studies are forging new conceptual models of the neurobiology of stress-related affective, anxiety, and addictive disorders and the nature of treatment resistance. It also discusses how ketamine’s rapid antidepressant effects provide a scientific platform to facilitate innovation in clinical trial designs pertaining to patient selection, choice of control group, outcome measures, and dose-optimization. This book brings together data and insights from this rapidly expanding and extraordinarily promising field of study. Readers will be able to extract integrated themes and useful insights from the material contained in these diverse chapters and appreciate the paradigm-shifting contributions of ketamine to modern psychiatry and clinical neuroscience research.

Ketamine for Treatment-Resistant Depression: Neurobiology and Applications provides a simple, evidence-based overview for neuropsychiatrists and translational researchers on this medication, its mechanisms of actions, eligibility of patients for treatment, and the preparation and implementation of ketamine clinics. - Provides efficacy research on ketamine as a treatment for depression - Identifies best practices for clinical use, both long-term and acute - Discusses the molecular mechanisms and neurobiology of action

Given the unacceptably high rates of suffering, disability and premature death experienced by people with treatment-resistant depression and the surprisingly low rates of problems arising from the use of ketamine to treat the disorder, this is a therapy that all patients and their doctors should be discussing. This book summarises the research that has been carried out into ketamine for the treatment of depression over the past 15 years and, most importantly, describes different ways of using ketamine that are both practical and cost–effective. Currently most ketamine therapy is given intravenously in specialised clinics at considerable expense, but the author has successfully treated patients with low-dose sublingual ketamine and his patients have been able to safely take this at home. Profits from the sales of this book will assist further research into the use of ketamine for the treatment of depression.