Modern Medicine

How a party drug could become the next blockbuster antidepression treatment

Douglas Quenqua, special to
Key Points
  • Depression affects 16 million Americans and 350 million people worldwide.
  • One third of Americans do not respond to the more than 20 antidepressant drugs approved by the FDA.
  • The antidepressant drug market is a whopping $17 billion.
  • Researchers are now studying drugs like LSD, MDMA, also known as ecstasy, ketamine and psilocybin as treatments for depression.
These party drugs could become the answer for clinically depressed patients
These party drugs could become the answer for clinically depressed patients

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:
Scientists invent a pen that identifies cancer in 10 seconds
Scientists narrow down the risk factors that can cause autism
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.

There is now a Google test for depression and mental ill health
There is now a Google test for depression and mental ill health

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

For example, a team of researchers in the U.K. last year became the first ever to produce images of the human brain on LSD — a remarkable fact, considering how widely the drug has been consumed over the past 50 years. But the obstacles to working with the drug were simply too great, said Professor David Nutt, a neuropsychopharmacologist at Imperial College and an author of the study. "The illegal status of LSD meant that researchers were scared, and the costs of complying with the regulations were prohibitive, and governments wouldn't fund the research because the drugs were illegal."

Still, the results of the scans strongly suggested that LSD could help treat depression in much the way psilocybin does. "It switches off regions of the brain that are overactive in depression," Nutt said. It also disrupts communication between certain sections of the brain, producing an "ego dissolution" that helps users feel more connected to the world around them.

Such results are going a long way toward easing the path for researchers who want to explore these drugs. As is the existence of groups like MAPS (Multidisciplinary Association for Psychedelic Studies), which has helped secure private funding for much of the research on these drugs — a notoriously difficult endeavor given the stigma surrounding them.

Of course, MAPS is not the first group to advocate for the legal use of psychedelics. And hopes of a breakthrough in the area seem to arise every decade or so, suggesting the path to FDA approval may still be a long, arduous one.

But Dr. Wolfson, who has watched the enthusiasm for researching psychedelic drugs rise and fall over the decades, says he's never seen the surge of interest like he is seeing now. "Interest is peaking," said Dr. Wolfson, but "it hasn't peaked yet."

— By Douglas Quenqua, special to