Steven L. Mandel is an American anesthesiologist and advocate for the use of ketamine in the treatment of mental health. [1]
Steven L. Mandel is an American anesthesiologist and advocate for the use of ketamine in the treatment of mental health. [1]
Mandel is an anesthesiologist, [2] who began his career working in cosmetic surgery offices in California. Following the death of a family member to suspected suicide, [3] anxiety and PTSD [4] he went on to co-found Ketamine Clinics Los Angeles, [2] which he established in 2013. At his clinic, Mandel administers sub-anesthetic doses of ketamine for patients with chronic depression, suicidal ideation, [3] via intravenous infusions. [5] [6] He has also advocated for scientific inquiry into other psychedelics and their potential use as mental health treatments. [7] He is also the founder and first president of the American Society of Ketamine Physicians, Psychotherapists and Practitioners (ASKP3). [8]
Mandel received a graduate degree in psychology from the University of Cincinnati Graduate School, his MD from the University of Southern California Keck School of Medicine, and did residencies in anesthesiology at the Massachusetts General Hospital and UCLA. [9]
Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a treatment for depression, a pain management tool, and as a recreational drug. Ketamine is a novel compound that was derived from phencyclidine in 1962, in pursuit of a safer anesthetic with fewer hallucinogenic effects.
Anesthesia or anaesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia, paralysis, amnesia, and unconsciousness. An individual under the effects of anesthetic drugs is referred to as being anesthetized.
Dissociatives, colloquially dissos, are a subclass of hallucinogens which distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of such action, dissociatives are unique in that they do so in such a way that they produce hallucinogenic effects, which may include dissociation, a general decrease in sensory experience, hallucinations, dream-like states or anesthesia. Despite most dissociatives’ main mechanism of action being tied to NMDA receptor antagonism, some of these substances, which are nonselective in action and affect the dopamine and/or opioid systems, may be capable of inducing more direct and repeatable euphoria or symptoms which are more akin to the effects of typical “hard drugs” or common drugs of abuse. This is likely why dissociatives are considered to be addictive with a fair to moderate potential for abuse, unlike psychedelics. Despite some dissociatives, such as phencyclidine (PCP) possessing stimulating properties, most dissociatives seem to have a general depressant effect and can produce sedation, respiratory depression, nausea, disorientation, analgesia, anesthesia, ataxia, cognitive and memory impairment as well as amnesia.
Psychedelic therapy refers to the proposed use of psychedelic drugs, such as psilocybin, MDMA, LSD, and ayahuasca, to treat mental disorders. As of 2021, psychedelic drugs are controlled substances in most countries and psychedelic therapy is not legally available outside clinical trials, with some exceptions.
Xylazine is a drug used for sedation, anesthesia, muscle relaxation, and analgesia in animals such as horses, cattle, and other non-human mammals. It is an analog of clonidine and an agonist at the α2 class of adrenergic receptor.
Toxic encephalopathy is a neurologic disorder caused by exposure to neurotoxic organic solvents such as toluene, following exposure to heavy metals such as manganese, as a side effect of melarsoprol treatment for African trypanosomiasis, adverse effects to prescription drugs, or exposure to extreme concentrations of any natural toxin such as cyanotoxins found in shellfish or freshwater cyanobacteria crusts. Toxic encephalopathy can occur following acute or chronic exposure to neurotoxicants, which includes all natural toxins. Exposure to toxic substances can lead to a variety of symptoms, characterized by an altered mental status, memory loss, and visual problems. Toxic encephalopathy can be caused by various chemicals, some of which are commonly used in everyday life, or cyanotoxins which are bio-accumulated from harmful algal blooms (HABs) which have settled on the benthic layer of a waterbody. Toxic encephalopathy can permanently damage the brain and currently treatment is mainly just for the symptoms.
Joshua Philip Prager M.D., M.S. is an American physician. Prager specializes in pain medicine and is the executive director of Center for the Rehabilitation Pain Syndromes (CRPS) at UCLA Medical Plaza.
NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the N-Methyl-D-aspartate receptor (NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce is referred to as dissociative anesthesia.
Esketamine, also known as (S)-ketamine or S(+)-ketamine, is the S(+) enantiomer of ketamine, is a dissociative hallucinogen drug used as a general anesthetic and as an antidepressant for treatment of depression. It is sold under the brand names Spravato, Ketanest, among others. Esketamine is the active enantiomer of ketamine in terms of NMDA receptor antagonism and is more potent than racemic ketamine.
Dennis S. Charney is an American biological psychiatrist and researcher, with expertise in the neurobiology and treatment of mood and anxiety disorders. He is the author of Neurobiology of Mental Illness, The Physician's Guide to Depression and Bipolar Disorders and Molecular Biology for the Clinician, as well as the author of over 600 original papers and chapters. In 2022, he was listed #52 on Research.com's "Top Medicine Scientists in the United States," with an h-index of 194 with 146,109 citations across 651 publications. Charney is known for demonstrating that ketamine is effective for treating depression. Ketamine's use as a rapidly-acting anti-depressant is recognized as a breakthrough treatment in mental illness.
Allen J. Frances is an American psychiatrist. He is currently Professor and Chairman Emeritus of the Department of Psychiatry and Behavioral Sciences at Duke University School of Medicine. He is best known for serving as chair of the American Psychiatric Association task force overseeing the development and revision of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Frances is the founding editor of two well-known psychiatric journals: the Journal of Personality Disorders and the Journal of Psychiatric Practice.
David Jay Brown is an American writer and interviewer. Brown has studied parapsychology and the effects of psychoactive drugs. With parapsychologist Rupert Sheldrake, he studied pets and people who apparently anticipate events. Brown has served as a guest editor for the Multidisciplinary Association for Psychedelic Studies (MAPS), and he has published many interviews of prominent thinkers.
Reid Robison is an American board-certified psychiatrist known primarily for his work with psychedelic medicines. As an early adopter and researcher of the use of ketamine in psychiatry, Robison has made significant contributions to ketamine-assisted psychotherapy (KAP) and other treatment modalities using ketamine for mental health conditions. He previously served as coordinating investigator for a study on MDMA-assisted psychotherapy for eating disorders, sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS), and he continues to lead research and psychiatric clinical trials involving psychedelics. To date, Robison has guided thousands of ketamine-assisted therapy sessions and Spravato dosing sessions. He currently serves as Medical Director of Center for Change, an eating disorder treatment center in Utah, and Chief Clinical Officer of Numinus, a Vancouver-based mental health company focused on psychedelic research and treatments. Robison is an adjunct professor at both the University of Utah and Brigham Young University.
The Spring Grove Experiment is a series of lysergic acid diethylamide (LSD) studies performed from 1963 to 1976 on patients with psychotic illnesses at the Spring Grove Clinic in Catonsville, Maryland. These patients were sponsored by a federal agency called the National Institute of Mental Health to be part of the first study conducted on the effects of psychedelic drugs on people with schizophrenia. The Spring Grove Experiments were adapted to study the effect of LSD and psychotherapy on patients including alcoholics, heroin addicts, neurotics, and terminally-ill cancer patients. The research done was largely conducted by the members of the Research Unit of Spring Grove State Hospital. Significant contributors to the experiments included Walter Pahnke, Albert Kurland, Sanford Unger, Richard Yensen, Stanislav Grof, William Richards, Francesco Di Leo, and Oliver Lee McCabe. Later, Spring Grove was rebuilt into the Maryland Psychiatric Research Center where studies continued to be performed for the advancement of psychiatric research. This study on LSD is the largest study on psychedelic drugs to date.
Ketamine has had a wide variety of medicinal and recreational uses since its discovery in 1962.
Psychoplastogens are a group of small molecule drugs that produce rapid and sustained effects on neuronal structure and function, intended to manifest therapeutic benefit after a single administration. Several existing psychoplastogens have been identified and their therapeutic effects demonstrated; several are presently at various stages of development as medications including Ketamine, MDMA, Scopolamine, and the serotonergic psychedelics, including LSD, psilocin, DMT, and 5-MeO-DMT. Compounds of this sort are being explored as therapeutics for a variety of brain disorders including depression, addiction, and PTSD. The ability to rapidly promote neuronal changes via mechanisms of neuroplasticity was recently discovered as the common therapeutic activity and mechanism of action.
Delix Therapeutics is an American biotech company based in Boston, Massachusetts. The company develops novel neuroplasticity-promoting therapeutics for central nervous system (CNS) diseases such as depression and post-traumatic stress disorder (PTSD). It was co-founded in 2019 by David E. Olson and Nick Haft.
Psychedelic treatments for trauma-related disorders are the use of psychedelic substances, either alone or used in conjunction with psychotherapy, to treat trauma-related disorders. Trauma-related disorders, such as post-traumatic stress disorder (PTSD), have a lifetime prevalence of around 8% in the US population. However, even though trauma-related disorders can hinder the everyday life of individuals with them, less than 50% of patients who meet criteria for PTSD diagnosis receive proper treatment. Psychotherapy is an effective treatment for trauma-related disorders. A meta-analysis of treatment outcomes has shown that 67% of patients who completed treatment for PTSD no longer met diagnostic criteria for PTSD. For those seeking evidence-based psychotherapy treatment, it is estimated that 22-24% will drop out of their treatment. In addition to psychotherapy, pharmacotherapy (medication) is an option for treating PTSD; however, research has found that pharmacotherapy is only effective for about 59% of patients. Although both forms of treatment are effective for many patients, high dropout rates of psychotherapy and treatment-resistant forms of PTSD have led to increased research in other possible forms of treatment. One such form is the use of psychedelics.
Ketamine-assisted psychotherapy(KAP) is the use of prescribed doses of ketamine, the drug, as an adjunct to psychotherapy sessions. KAP shows significant potential in treating mental disorders such as treatment-resistant depression (TRD), anxiety, obsessive–compulsive disorders (OCD), post-traumatic stress disorders (PTSD), and other conditions. It can also be used for those experiencing substance abuse and physical pain. While it is primarily used as a veterinary anaesthetic, ketamine has also been found to have rapid analgesic and hallucinogenic effects, which has sparked interest in its use as an antidepressant. Despite initial trials of its use in the treatment of mental disorders focussing primarily on its antidepressant effects, newer studies are attempting to harness its psychedelic effects to bring about altered states of consciousness, which will augment the adjunct psychotherapy. Ketamine's neuroplasticity-promoting effects strengthen the cognitive restructuring that takes place through traditional psychotherapy, thereby leading to long-lasting behavioural change. KAP offers promising directions for research on new antidepressant alternatives, but is still not sufficiently defined or evaluated as a treatment combination.
Robin Lester Carhart-Harris is a British psychopharmacologist who is Ralph Metzner Distinguished Professor and Director of Neuroscape Psychedelics Division in the Department of Neurology at the University of California, San Francisco. Previously, he founded and was Head of the Centre for Psychedelic Research at Imperial College London.
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