The Department of Veterans Affairs recently began offering psychedelic substances to patients as a part of clinical trials, a major step in the quest to determine the therapeutic potential of illegal drugs the federal government has long deemed dangerous.
At least five trials are underway or being planned by a handful of government clinicians who see potential in using psychedelic experiences combined with psychotherapy to treat post-traumatic stress disorder, substance abuse and other conditions endemic among veterans of recent wars.
"This is a watershed moment," said Dr. Rachel Yehuda, director of mental health at the James J. Peters Veterans Affairs Medical Center in the Bronx, who is leading one of the studies. "This is a time for a lot of hope."
The theory at the heart of the research is that compounds such as MDMA, also known as Ecstasy, and psilocybin mushrooms, when taken in a safe setting under the guidance of skilled therapists, can yield powerful insights and disrupt harmful patterns of thought and behavior.
In the 1950s and 1960s, many scientists regarded psychedelics as a potentially revolutionary tool in the treatment of addiction and other psychiatric conditions. In one notable clinical study in 1963, patients at a Veterans Affairs clinic in Kansas took LSD to treat alcoholism.
But that promising wave of research came to a sudden halt soon afterward, as soaring recreational use of hallucinogens sparked a political backlash.
The first of these new psychedelic trials, at a Veterans Affairs clinic in California, began last summer after researchers received approval from the Drug Enforcement Administration and the Food and Drug Administration to treat combat veterans with post-traumatic stress disorder with MDMA. The trial in New York started in January. Three trials at clinics in San Diego and Portland, Oregon, are scheduled to start later this year using MDMA and synthetic psilocybin, an analog of hallucinogenic mushrooms.
The research became viable after the FDA designated MDMA and psilocybin as "breakthrough therapies" in 2017 and 2018, for treatment of PTSD and depression, respectively. Regulators give that label to new drugs when preliminary studies suggest they would be more effective than standard treatments for serious conditions.
The studies are happening amid a global rethinking of the dangers and potential benefits of substances that were outlawed and demonized during the presidencies of Lyndon Johnson and Richard Nixon. Both leaders became concerned that psychedelic drugs were fueling opposition to the war in Vietnam War and other government activities, according to historians.
But in recent years, campaigns to expand research into the medicinal use of psychedelic substances and to make related drug laws more lenient have gained support across the country.
In 2020, voters in Oregon passed two ballot measures that decriminalized possession of small amounts of drugs and called for the establishment of a therapeutic framework for psilocybin. Since then, Texas and Connecticut have approved measures allowing the study of psilocybin and MDMA for mental health treatment.
Psychedelic retreats have become booming business in countries in Latin America and Europe where the legal landscape is more permissive. Psychiatry departments at numerous universities in the United States now have centers where psychedelics are studied. And investors have begun applying for patents, hoping to find novel ways to profit from psychedelic therapy if and when it becomes legal.
Last year, the FDA reviewed 16 applications to treat psychiatric conditions with psychedelic substances, more than in the four previous years combined, according to an agency spokesperson.
In response to an emailed series of questions, the FDA said there are formidable challenges to establishing the safety and efficacy of medicinal psychedelics. For starters, there is no easy way to run studies with a placebo control because the sensory effects of the drugs are evident to participants and researchers. The FDA has also cautioned that patients might walk away from psychedelic sessions in a "hypersuggestible" state, which could lead to a merely short-lived sense of improvement.
"Popular media is inundated with overwhelmingly positive references to these drugs, which can potentially influence patients' and therapists' expectations," Dr. Javier Muniz, a senior official at the FDA division that evaluates new drugs, said in a recent online workshop. "The high degree of enthusiasm and anticipation is beyond anything we've ever seen with any unapproved psychiatric drug."
Proponents of accelerating psychedelic research have drawn attention to the mental health care crisis among veterans. In 2019, at least 6,261 veterans died by suicide, according to government data, a rate far higher than that of civilians. Nearly 16% of veterans who deployed to Iraq and Afghanistan have been diagnosed with PTSD.
The standard treatments for PTSD at Veterans Affairs clinics include prolonged exposure therapy, during which patients are urged to repeatedly talk about the source of their trauma, and cognitive processing therapy, which is designed to help them reframe negative thoughts. Many patients are also prescribed anti-anxiety drugs and antidepressants.
Hundreds of veterans have traveled to psychedelic retreat centers abroad, and many have become advocates for expanding access to hallucinogens.
"There's a risk of doing nothing, as veterans are seeking care elsewhere," said Dr. Shannon T. Remick, a psychiatrist at the Veterans Affairs Healthcare System in Loma Linda, California, who is treating PTSD patients with MDMA. "It's our priority to make sure veterans are safe and getting the best care."
Remick's study includes 10 combat veterans who will each undergo three MDMA sessions along with psychotherapy. Participants will be tracked for at least a year.
Overall, the studies will involve a few dozen participants, a tiny segment of the Veterans Affairs patient population. But the researchers said they expect that colleagues across the bureaucracy will soon launch more and that larger ones are likely in the future.
In interviews, the clinicians leading psychedelic studies said the Veterans Affairs health care system is the ideal place to study the therapeutic potential, limitations and possible dangers of hallucinogens, which can include cardiovascular anomalies and episodes of psychosis.
"The VA is in some ways the best place for this type of research to happen," said Dr. Leslie Morland, a clinical psychologist at the Veterans Affairs Healthcare System in San Diego, who is studying the possibility that MDMA can enhance couples therapy in marriages strained by PTSD. "The VA is going to make sure that we have good data that supports the safety and efficacy before they offer it to veterans, as I think is appropriate."
Yehuda, a renowned expert on PTSD, said she was convinced psychedelics would become a revolutionary tool in mental health treatment. But researchers still have much to learn, she said.
"I think it's going to be a breakthrough for a bunch of people," she said. "But we just have to figure out who they are, and more importantly, who they aren't."
In her trial, MDMA sessions typically last eight hours, and patients are offered an initial and supplemental dose. Veterans ease into the experience listening to gentle music and are allowed to wear eye shades. A pair of therapists monitor the patient, speaking to them as little or as much as the patient appears to encourage.
Yehuda said sessions can be excruciatingly painful, a process she compared to giving birth.
"The most common misconception about MDMA with psychotherapy is that you're taking this magic pill that will take away your symptoms," she said. "What's happening is, you are getting in a state that is conducive to doing difficult work in a manner in which you are in the right window of tolerance where you can emotionally engage, where you can process the memory but not get so distressed by the memory that you become emotionally numb."
Yehuda said that existing therapies for PTSD often led to a reduction of distress. But she said the early results of MDMA trials showed something astounding in the field.
"Many people are showing what seems to look like remission," she said.
The clinicians leading the studies said they were trying to keep their enthusiasm in check as they build on a body of scientific research.
"We're taking vulnerable people - particularly, people with severe mental illness, PTSD, substance abuse disorders - and we're putting them in a vulnerable state of mind, a very suggestible state of mind," said Dr. Christopher Stauffer, a psychiatrist at the Veterans Affairs Healthcare System in Portland who is leading two psychedelic studies. "We have to be super careful about bias in all directions, from the researchers to the participants."
Still, Stauffer said it was imperative to innovate and take considered risks.
"We have a mental health crisis right now, and our current mental health system is not able to adequately manage it," he said.
Some of the VA studies are being partly funded and supported by the Multidisciplinary Association for Psychedelic Studies, a nonprofit organization that has been pressing the federal government to legalize medicinal psychedelics for years. Its executive director, Rick Doblin, said the government could have saved lives by recognizing the therapeutic value of hallucinogens decades ago.
"I'm hopeful that the treatment will eventually be widely available throughout the system," he said. "Yet I shudder to think of how many vets died of PTSD, often through suicide, during those years."
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