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Can Newer Psychedelics Heal Without a Trip?

The development is one of the most exciting areas of growth and discovery.

Key points

  • The term "psychedelic" has become almost inextricably equated with mind-altering experiences, danger, and the edge of the law.
  • But psychedelics are the leading potential treatment for mental well-being, for the most part safe and non-addictive.
  • Stigmas prevail around "the trip"—and now there's a race to discover psychedelics that have no hallucinogenic effects at all.

In the minds of most people, psychedelics are all about “the trip.” The term has become almost inextricably equated with mind-altering experiences bending reality toward wild fantasy, that, for many, impressions are locked: psychedelics are bound to associations bordering danger and the edges of the law.

In popular culture, from the menace-laced scenes in Fear and Loathing in Las Vegas to the far-out god-of-rock Jim Morrison of “The Doors” biopic; from Bob Dylan to the Beatles, the films and words of artists inspired by these substances are packaged with an underlying warning: “Don’t try this at home.”

It has surprised many to learn that psychedelics offer significant benefits even when detached from their hallucinogenic properties—in particular for new treatments of mental well-being. And they’re mostly considered safe and non-addictive.

At a time when mental health challenges are on the rise in our increasingly complicated and often frustrating world—the World Health Organization estimates COVID alone caused a 25 percent spike in depression—we cannot afford to ignore such a game-changer, regardless of stigmatic associations.

Anti-psychotic medicines essentially alter the brain’s chemistry, whereas psychedelics also trigger “neural plasticity,” which means, in effect, that the brain rewires itself. Clinical trials on animals—and also, lately, on humans—suggest this can ease depression, anxiety, addiction, PTSD, and other disorders.

Until recently, though, research was stymied by concerns about the compounds’ hallucinogenic effects, and, in particular, fears that wide recognition of their medicinal properties could end up promoting recreational use.

One avenue for addressing this has been a race to discover psychedelics that have no hallucinogenic effects at all. This may sound like a contradiction in terms—perhaps like music without notes—but, in fact, there are signs that such compounds are within our reach. Essentially, researchers are tweaking psychedelics’ chemical structures to isolate the molecular interactions that offer antidepressant effects, creating new compounds that activate the brain's cellular circuits in a way that may help relieve depression without causing hallucinations. Although, to date, these have only been tested in animals, down this path lies a tremendous potential for an entirely new family of pharmaceuticals.

While that plays out, the more common current method of non-hallucinogenic use of psychedelics is via a practice called “microdosing”—taking 5-10 percent of a full dose of a psychedelic, which provides the benefits without the high. Patients would have no indication that they are ingesting a hallucinogenic substance.

LSD, perhaps the most well-known psychedelic, has also shown promise for treating alcohol addiction and depression. It is the most common psychedelic for microdosing, achieving the benefits without the trip. The same is true of MDMA, widely known as the club drug "ecstasy;" it remains illegal, but the FDA allows its use in research and treatment for life-threatening illnesses.

Another commonly applied substance is psilocybin, the active chemical in magic mushrooms. Already legal in Oregon and the subject of considerable research in that state and elsewhere, it is likely to become an accepted mental health therapy, with FDA approval widely expected within a few years.

Taken in pill form as a full dose and in a clinical setting with psychotherapy involved, it has the potential to treat depression as well as alcoholism, nicotine addiction, and other substance abuse. As just one example, researchers at the University of Wisconsin at Madison are studying psilocybin’s effect on cardiac repolarization (improving heart function). Another full-dose example is ketamine, which is most often used as an anesthetic by veterinarians.

Ketamine is legal for medical use, and many ketamine clinics are operating in the U.S. and Canada. Researchers have been able to explore its potential use in humans, finding evidence that it ameliorates psychiatric disorders by promoting neuron regrowth after atrophy in the prefrontal cortex—a condition that can cause schizophrenia, depression, and anxiety. In 2019, a form of ketamine called esketamine was approved by the FDA for limited use in treating depression, and it has also shown promise as a treatment for suicidal patients.

My own research, as I’ve written before on these pages, is focused on an innovative compound, MEAI, which shows potential to treat alcoholism, a debilitating global affliction with almost no effective treatment, as well as eating disorders. These treatments, too, are non-hallucinogenic.

The potential of non-hallucinogenic psychedelics is significant. It is one of the most exciting areas of growth and discovery, and could offer humanity a revolutionary improvement in well-being.

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