Psychedelic Anesthetic Helps Treat Depression

Originally appearing here. A number of recent studies have demonstrated the potent, quick-acting and long-lasting antidepressant effects of the dissociative anesthetic ketamine, a legal prescription drug that has been approved by the FDA as a surgical anesthetic. Ketamine is also popular as a recreational drug, due to its euphoric and psychedelic properties. New studies by Carlos Zarate, M.D. of the National Institute of Mental Health have shown that a single infusion of ketamine can relieve symptoms of severe, even suicidal, depression in some patients within a few hours, and that relief generally persists for several days. Four studies have now demonstrated ketamine’s powerful and enduring antidepressant effects. In one of the studies, subjects received the ketamine as an anesthetic for orthopedic surgery—so they were not even conscious during the mind-altering portion of the drug’s action in the brain, yet regardless of this the antidepressant effects occurred post-operatively. Another study demonstrated fast-acting relief within just forty minutes. Remarkably, these studies show that ketamine even works on subjects who haven’t responded to conventional antidepressants like Prozac or Paxil. This is because Ketamine works differently than traditional antidepressants, which modulate the brain chemicals (neurotransmitters) serotonin, norepinephrine, or dopamine. Ketamine and other dissociative anesthetics selectively bind to the NMDA (N- methyl-D-aspartic acid ) receptors in the brain, blocking the neurotransmitter glutamate from activating these receptors. Because glutamate is an essential neurotransmitter that activates neurons, this blocking effect seems to prevent the processing of sensory information by the brain. Ketamine is one of the safest anesthetics known, because of this it is routinely used in both human and veterinary surgery. It is generally the first choice for people in frail health, the elderly, and small children, because of its low toxicity. However, despite its stellar safety record, ketamine is rarely used in general surgeries due to what has been called the “emergence reaction” in medical terminology. The “emergence reaction” has been described by many people as a dreamlike period of interactive visions, or a psychedelic experience–and this has frightened some people in hospital settings, as shamanic journeys are not something that most hospital staff are prepared to deal with. The hallucinogenic effects of ketamine constitute the primary reason why it is not currently (or commonly) being used to treat depression, as it is already legal for physicians in the U.S. to do so. Regardless, ketamine is commonly used in small doses as a recreational drug at parties and clubs, and in larger doses by some people as a shamanic tool to explore the human mind or alternative realities. Ketamine was first popularized as a shamanic tool for exploring alternative states of consciousness by the late neuroscientist John C. Lilly, who wrote extensively about his adventures with “vitamin K” in his books The Center of the Cyclone and The Scientist. Many people report out-of-body experiences on ketamine and effects similar to lucid dreaming. Several months ago I wrote about the grey legal market of designer psychedelic drugs, chemical analogs of illegal psychedelics that are openly sold on the internet–with a wink–for non-human consumption research purposes. Many of these drugs haven’t been tested and no one really knows how safe or dangerous they are to consume. The only way to learn what is known about these relatively obscure substances is to study the reviews of them on web sites like Erowid and Bluelight, where courageous users share reports and compare notes. One new designer drug in particular was recently brought to my attention, and I personally think that it may have substantial potential as a therapeutic agent. The drug is a dissociative anesthetic called methoxetamine or MXE, and it is a chemical analog of ketamine. MXE has many of the same psychoactive properties as ketamine, except that it’s more potent and longer lasting. It lasts almost four times longer and is about twice as strong. The Santa Cruz Multidisciplinary Association for Psychedelic Studies funded several studies by psychiatrist Evgeny Krupitsky of St. Petersburg, Russia, from the mid to late 1990s, demonstrating that ketamine combined with psychotherapy showed promise as a treatment for alcoholism and heroin addiction. I suspect that MXE might be more effective than ketamine in this regard for two reasons. MXE lasts more than three times as long as ketamine (3 hours, rather than 45 minutes), and according to many anecdotal reports, it appears to be much easier to remember, articulate, and learn from the experience. Also, like ketamine, the antidepressant afterglow from MXE is quite substantial for many people, and can last for up to a week. MXE is currently unscheduled, and since it is an analog of a legal prescription drug, there are fewer restrictions on researching it than a Schedule 1 drug, like cannabis or LSD. MXE was developed by an underground chemist specifically for grey market distribution, and from what I can gather, the drug is perfectly legal to possess in the U.S. because there are no laws that make analogs of legal prescription drugs illegal. Ketamine, and perhaps MXE, appear to hold largely untapped promise in medicine–as antidepressants and as psychedelic therapy agents–because ketamine is already among the selections in Western medicine’s pharmacopoeia. In addition to being part of a different chemical class of drugs than the other psychedelics, ketamine is in a separate legal class as an FDA-approved schedule III drug. This designation means that any physician can administer ketamine for an off-label use if he or she believes it will help the patient–so there is no legal reason why a forward-thinking psychiatrist couldn’t start a psychedelic therapy practice with ketamine in the U.S. tomorrow. The dissociative anesthetic ketamine, which is both a legal anesthetic and a popular recreational drug, could have fast-acting, though perhaps short-lived, antidepressant properties. In the 1990s, MAPS helped fund a Russian study which demonstrated that ketamine combined with psychotherapy showed promise as a treatment for alcoholism and heroin addiction. Now, a series of new studies are once again renewing interest in the therapeutic properties of ketamine and its chemical cousins. Also check out Karl Jensen’s Ketamine: Dreams and Realities on the MAPS Store for a comprehensive overview of the therapeutic and spiritual uses of ketamine.