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KEY POINTS Depression affects 16 million Americans and 350 million people worldwide.

One third of Americans do not respond to the more than 20 antidepress ant drugs approved by the FDA.

The antidepressant drug market is a whopping $17 billion.

R esearchers are now studying drugs like LSD, MDMA, also known as ecstasy, ketamine and psilocybin as treatments for depression.

As a social worker with 30 years' experience working in hospice care, Christina Ingenito expected to face death gracefully when her time came. But when a breast cancer diagnosis at 59 left this once ebullient woman "severely clinically depressed" — her words — she turned to an unusual research project for help. In 2016, Ingenito became one of 18 subjects in the first-ever FDA-cleared study to explore the therapeutic effects of MDMA — commonly known as ecstasy — on people with life-threatening illnesses who are suffering from depression. After four standard (i.e., sober) therapy sessions with the two psychologists leading the study, Ingenito embarked on three "medicine journeys," as she calls them: marathon eight-hour therapy sessions fueled by capsules of MDMA. "Incredible" is how she describes the experience now. "From the very first moment that I felt the medicine in my body, it radically transformed all the trauma that I had been holding, not only from the diagnosis but previously from my life as well. My anxiety is gone; the depression is gone; my life force is back." Today she is free from both cancer and depression. Depression now affects 16 million Americans and 350 million adults worldwide, according to the NIMH, making it one of the most common disabilities in the world. But even with more than 20 antidepressants approved by the FDA over the past 60 years, many people still struggle with the condition: One-third of Americans simply don't respond to any of the currently available medicines, studies say, and there hasn't been a significant breakthrough in decades. As the years of desperation mount, doctors are finding themselves turning to new and unexpected sources for the next big antidepression drug. Though there is no shortage of antidepression drugs currently available, analysts believe there is still plenty of opportunity in the nearly $17 billion global market.

The agony and ecstasy

The notion that a "party drug" like MDMA could be used for more than recreation may have been out of fashion for many years, but it's not a new idea. Before it was outlawed in the 1960s, LSD showed promise as a treatment for depression and alcoholism. Dr. Phillip Wolfson, an author of Ingenito's study, was one of several mental health professionals experimenting with MDMA as a therapy aid in the early 1980s before it was outlawed. But a combination of prohibition and social stigma rendered it nearly impossible to get government permission, much less funding, to perform any sort of research with such drugs. Now a handful of studies — and the persistent researchers behind them — are pointing to a future where drugs like LSD, MDMA, ketamine and psilocybin (the active ingredient in hallucinogenic mushrooms) could find a second life not just as therapeutic aids but as potential blockbusters. More from Modern Medicine:

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Insurers, doctors battle over new heart disease drugs "MDMA has a blockbuster aspect in many, many areas," said Dr. Wolfson in a telephone interview. "It could be used for PTSD, depression, couples' work, relationship work and probably OCD." The evidence, he claims, is in the studies now being published. Though results of Ingenito's study are still being analyzed, preliminary data suggests the MDMA sessions dramatically alleviated depression in the subjects. That follows an earlier study that tested MDMA as a treatment for PTSD in which 80 percent of subjects no longer suffered from the condition after just two sessions.

From the very first moment that I felt the medicine in my body, it radically transformed all the trauma that I had been holding. Christina Ingenito cancer survivor

Early studies with psilocybin have been similarly encouraging. In a 2016 NYU study looking at whether the drug could alleviate anxiety and depression in cancer patients, more than 80 percent of subjects reported significant improvements. A smaller 2012 study yielded similar results. Ketamine — which goes by the street name Special K — has been studied more than most illicit drugs, thanks to its legal status in the United States as a tranquilizer (usually for animals). And results have been so encouraging that both Allergen and Johnson & Johnson currently have ketamine-inspired antidepressants in late-stage clinical trials.

Of course, ketamine and MDMA are powerful drugs with serious side effects that would need to be managed. Ketamine's paralyzing effect can be so powerful, it's often classified as a date-rape drug, and users sometimes asphyxiate because they can't clear their own airwaves. MDMA can induce symptoms resembling a panic attack — sweating, nausea, chills, involuntary teeth clenching — and is occasionally associated with heat stroke.



Due to the risks, there is a clinical study under way at Stanford University to test if ketamine acts like an opioid.

Still in its infancy

Promising as the research on some illicit drugs is, scientists caution that many of these treatments are still years away from commercial availability, and the testing itself is, in many cases, still in its infancy.

Under the influence of LSD, the brain's visual cortex has increased connectivity with other brain regions (right) than when imaged under placebo (left). Source: Imperial College London