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Better Living Through Psychedelic Chemistry? LSD, Psilocybin and Ketamine in the Headlines

Like many others, I am hoping that what we learn from these drugs might open new pathways to treat some very disabling mental and additive conditions, enable some of us to quiet our fears when ill with cancer or close to passing, and possibly add a touch more creativity and flexibility to our world.
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"Taking LSD was a profound experience, one of the most important things in my life. LSD shows you that there's another side to the coin, and you can't remember it when it wears off, but you know it. It reinforced my sense of what was important -- creating great things instead of making money, putting things back into the stream of history and of human consciousness as much as I could." -- Steve Jobs

The Centre for Neuropsychopharmacology at the Imperial College in London recently reported a study of 20 healthy volunteers who received LSD, not on a blotter but administered IV, on one occasion and a placebo on a second occasion. The pharmaceutical quality LSD produced "robust psychological effects" -- as we would imagine (the placebo did not) -- not just right away but notably two weeks after the drug was taken: The study reported increased optimism and openness two weeks after taking LSD. While the acute effects (at the time the drug was administered) included psychotic-like thinking (e.g., paranoia and delusions), these did not persist, and curiously the subjects did not report distress but rather were apt to describe a positive mood and even a "blissful" experience

LSD exerts its neurochemical effects on our brain's serotonin system. One particular serotonin receptor, 2A, seems to be central to its effects because if it is blocked by an antagonist specific to this receptor site the psychedelic effects of psilocybin (another drug that amplifies serotonin action in the brain) do not occur.

The London research subjects were screened to exclude people under 21 years of age, with histories of mental and substance use disorders themselves (or in their families), having a significant general medical condition, or being pregnant. But that does not exclude a lot of people who might consider taking LSD. The authors, incidentally, are not new to the science of psychedelics and in seeking routes to change our reality in beneficial ways. More about this shortly.

LSD is not the only mind-altering agent that has been making headlines.

Another is psilocybin, or "magic mushrooms," which has been used at Johns Hopkins and New York University (as well as by the Imperial College) for the treatment of anxiety in cancer patients. Researchers at UCLA have also done pilot work using psilocybin for smoking addiction. Over 500 administrations of psilocybin at Hopkins and NYU have not produced any serious negative side effects. Some wonder about its beneficial effects on addictions other than smoking as well as its utility in treating people with clinical depression.

Still another agent is Ketamine, which has had considerable media attention for its rapid treatment of resistant depression. It has long been approved by the FDA as an anesthetic agent for surgery. Ketamine has also been shown to have prompt effects in diminishing the symptoms of obsessive-compulsive disorder (OCD), a seriously emotionally painful and functionally impairing condition. The problem here is that it generally does the job for a week, then the effects disappear calling for weekly administration if it is to provide ongoing help. Ketamine does not act through the serotonin system; instead, its action is by the glutamate receptor (seldom discussed despite its ubiquity in the brain). Ketamine has been used as a club drug, often called Special K, because of its euphoric effects. Ketamine is different from the club drug Ecstasy, or MDMA, which is a highly addictive, stimulant-like drug.

What is fascinating about the research on psychedelic drugs is the conceptual thinking scientists have offered -- beyond what receptor site the drug may impact.

American author Tom Wolfe wrote: We're shut off from our own world. Primitive man once experienced the rich and sparkling flood of the senses fully. Children experience it for a few months-until "normal" training, conditioning, close the doors on this other world, usually for good. Somehow, the drugs opened these ancient doors. And through them modern man may at last go, and rediscover his divine birthright..."

Neuroscientists, including Washington University professor Marcus Raichle and others, tend to be less poetic than Tom Wolfe. They have proposed what is called the default-mode network. I recently watched my 4-year-old nephew run around excitedly, full of wonder at the world around him. He was joyous -- at least until he got too tired and then he was a pretty unhappy camper. But soon, as he ages, inescapably for his sake and that of civilization, he will be drained of this wonder by the default-mode network. We need this layer of brain tissue, which develops as childhood proceeds, to exert an inhibitory effect on our emotions and impulses. Otherwise, we would be at the mercy of predators and never get to school or work on time. The default-mode network has been likened to an "orchestra conductor" or "corporate executive" in the brain that manages our mental state and enables us to function in the real world.

What the psychedelic drugs appear to do, supported by functional MRI studies, is to transiently shut down the default network, allowing us to enter a world freer of constraint and control and one redolent with wonder. Bliss, some call it. Remarkably, as well, the effect of disabling the default network can be enduring. Research subjects, not only Steve Jobs, report that their overly controlled states of mind, including those with addiction or OCD or even those of use whose doors of perception may simply be too closed, are more flexible, open and even happier after using psychedelic agents. Excessive control seems to have its limits.

Hunter Thompson, the founder of gonzo journalism and the author of Fear and Loathing in Las Vegas (and other audacious works) commented: "As for LSD, I highly recommend it. We had a fine, wild weekend and no trouble at all. The feeling it produces is hard to describe. 'Intensity' is a fair word for it ... just sit in the living room and turn on the music -- after the kids have gone to bed. But never take it in uncomfortable or socially tense situations. And don't have anybody around whom you don't like."

I am not recommending finding a local drug dealer or knocking on the door of your neighborhood university brain researcher to get some LSD, psilocybin or Ketamine. But like many others, I am hoping that what we learn from these drugs might open new pathways to treat some very disabling mental and additive conditions, enable some of us to quiet our fears when ill with cancer or close to passing, and possibly add a touch more creativity and flexibility to our world.

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The opinions expressed herein are solely my own as a psychiatrist and public health advocate. I receive no support from any pharmaceutical or device company.

My book for families who have a member with a mental illness is The Family Guide to Mental Health Care (Foreword by Glenn Close) -- is now available in paperback. I am completing a book about some secrets of psychiatric practice.

Follow Lloyd I. Sederer, MD on Twitter: http://www.twitter.com/askdrlloyd.