Depression is devastating. It destroys the quality of life for tens of millions of Americans. Families are disrupted, and sometimes lives are cut short.

Antidepressants have been available since the early 1950s. The very first one was discovered by accident. A drug developed to treat tuberculosis, iproniazid, had the unexpected side effect of improving patients’ moods.

This led to a class of medications called MAO inhibitors such as phenelzine (Nardil) and tranylcypromine (Parnate). While these drugs helped ease major depression in some patients, they also had drawbacks. Side effects and food and drug interactions made it hard to use these drugs safely.

Since then, the pharmaceutical industry has developed dozens of other antidepressants such as amitriptyline (Elavil), fluoxetine (Prozac) and sertraline (Zoloft). Overall, these drugs work a bit better than placebos for alleviating major depression. They also come with their own sets of side effects.

Now, an entirely new kind of treatment is being explored by researchers at Johns Hopkins Medicine. Researchers there reported in 2016 that the psychedelic agent psilocybin could ease the existential despair of people who had been diagnosed with a life-threatening cancer (Journal of Psychopharmacology, Nov. 30, 2016). More than 80% of the volunteers for this study reported greater life satisfaction and lower death anxiety.

Now the research team has tested this compound derived from “magic mushrooms” against major depression (JAMA Psychiatry, Nov. 4, 2020). The volunteers for this study, who were not on other antidepressants, got two doses of psilocybin. They had significant reductions in the assessments of their depression five weeks and eight weeks after these sessions.

The scientists concluded: “Findings suggest that psilocybin with therapy is efficacious in treating MDD [major depressive disorder], thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression.”

This study demonstrated the value of this psychedelic compound when administered in a therapeutic setting with skilled psychological support. A renowned psychiatrist wrote in the accompanying editorial that this research should be followed up with “real-world validation” (JAMA Psychiatry, Nov. 4, 2020).

Research on all psychedelics has been extraordinarily difficult for decades because the federal government has classified such compounds as Schedule I. According to the Drug Enforcement Agency: “Psilocybin is a Schedule I substance under the Controlled Substances Act, meaning that it has a high potential for abuse, no currently accepted medical use in treatment in the United States, and a lack of accepted safety for use under medical supervision.”

Most scientists have been reluctant to undertake studies of any drugs in Schedule I. In addition, it has been hard to get funding for such research.

That may change in part because of the 2020 election. The state of Oregon and the District of Columbia have both decriminalized the therapeutic use of psilocybin. This should allow researchers more flexibility in studying its potential against hard-to-treat depression.

Joe Graedon is a pharmacologist. Teresa Graedon holds a doctorate in medical anthropology and is a nutrition expert. Their syndicated radio show can be heard on public radio. In their column, Joe and Teresa Graedon answer letters from readers. Write to them in care of King Features, 628 Virginia Drive, Orlando, FL 32803, or email them via their website:

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