Lori Tipton is among the growing number of people who say that MDMA, also known as ecstasy, saved their lives.

Raised in New Orleans by a mother with untreated bipolar disorder who later killed herself and two others, Tipton said she endured layers of trauma that eventually forced her to seek treatment for crippling anxiety and hypervigilance. For 10 years nothing helped, and she began to wonder if she was “unfixable.”

Then she answered an ad for a clinical trial for MDMA-assisted therapy to treat post-traumatic stress disorder. Tipton said the results were immediate, and she is convinced the drug could help a lot of people. But even as regulators weigh approval of the first MDMA-based treatment, she’s worried that it won’t reach those who need it most.

“The main thing that I’m always concerned about is just accessibility,” the 43-year-old nonprofit project manager said. “I don’t want to see this become just another expensive add-on therapy for people who can afford it when people are dying every day by their own hand because of PTSD.”

MDMA is part of a new wave of psychoactive drugs that show great potential for treating conditions such as severe depression and PTSD. Investors are piling into the nascent field, and a host of medications based on MDMA, LSD, psychedelic mushrooms, ketamine, the South American plant mixture ayahuasca, and the African plant ibogaine are now under development, and in some cases vying for approval by the Food and Drug Administration.

Proponents hope the efforts could yield the first major new therapies for mental illness since the introduction of modern antidepressants in the 1980s. But not all researchers are convinced that their benefits have been validated, or properly weighed against the risks. And they can be difficult to assess using traditional clinical trials.

The first MDMA-assisted assisted therapy appeared to be on track for FDA approval this August, but a recent report from an independent review committee challenged the integrity of the trial data from the drug’s maker, Lykos Therapeutics, a startup founded by a psychedelic research and advocacy group. The FDA will convene a panel of independent investigators on June 4 to determine whether to recommend the drug’s approval.

Proponents of the new therapies also worry that the FDA will impose treatment protocols, such as requiring multiple trained clinicians to monitor a patient for extended periods, that will render them far too expensive for most people.

Tipton’s MDMA-assisted therapy included three eight-hour medication sessions overseen by two therapists, each followed by an overnight stay at the facility and an integration session the following day.

“It does seem that some of these molecules can be administered safely,” said David Olson, director of the University of California-Davis Institute for Psychedelics and Neurotherapeutics. “I think the question is can they be administered safely at the scale needed to really make major improvements in mental health care.”

Breakthrough Therapies?

Psychedelics and other psychoactive substances, among the medicines with the oldest recorded use, have long been recognized for their potential therapeutic benefits. Modern research on them started in the mid-20th century, but clinical trial results didn’t live up to the claims of advocates, and they eventually got a bad name both from their use as party drugs and from rogue CIA experiments that involved dosing unsuspecting individuals.

The 1970 Controlled Substances Act made most psychoactive drugs illegal before any treatments were brought to market, and MDMA was classified as a Schedule 1 substance in 1985, which effectively ended any research. It wasn’t until 2000 that scientists at Johns Hopkins University were granted regulatory approval to study psilocybin anew.

Ketamine was in a different category, having been approved as an anesthetic in 1970. In the early 2000s, researchers discovered its antidepressant effects, and a ketamine-based therapy, Spravato, received FDA approval in 2019. Doctors can also prescribe generic ketamine off-label, and hundreds of clinics have sprung up across the nation. A clinical trial is underway to evaluate ketamine’s effectiveness in treating suicidal depression when used with other psychiatric medications.

Ketamine’s apparent effectiveness sparked renewed interest in the therapeutic potential of other psychoactive substances.

They fall into distinct categories: MDMA is an entactogen, also known as an empathogen, which induces a sense of connectedness and emotional communion, while LSD, psylocibin, and ibogaine are psychedelics, which create altered perceptual states. Ketamine is a dissociative anesthetic, though it can produce hallucinations at the right dose.

Despite the drugs’ differences, Olson said they all create neuroplasticity and allow the brain to heal damaged neural circuits, which imaging shows can be shriveled up in patients with addiction, depression, and PTSD.

“All of these brain conditions are really disorders of neural circuits,” Olson said. “We’re basically looking for medicines that can regrow these neurons.”

Psychedelics are particularly good at doing this, he said, and hold promise for treating diseases including Alzheimer’s.

A number of psychoactive drugs have now received the FDA’s “breakthrough therapy” designation, which expedites development and review of drugs with the potential to treat serious conditions.

But standard clinical trials, in which one group of patients is given the drug and a control group is given a placebo, have proven problematic, for the simple reason that people have no trouble determining whether they’ve gotten the real thing.

The final clinical trial for Lykos’ MDMA treatment showed that 71% of participants no longer met the criteria for PTSD after 18 weeks of taking the drug versus 48% in the control group.

A March report by the Institute for Clinical and Economic Review, an independent research group, questioned the company’s clinical trial results and challenged the objectivity of MDMA advocates who participated in the study as both patients and therapists. The institute also questioned the drug’s cost-effectiveness, which insurers factor into coverage decisions.

Lykos, a public benefit company, was formed in 2014 as an offshoot of the Multidisciplinary Association for Psychedelic Studies, a nonprofit that has invested more than $150 million into psychedelic research and advocacy.

The company said its researchers developed their studies in partnership with the FDA and used independent raters to ensure the reliability and validity of the results.

“We stand behind the design and results of our clinical trials,” a Lykos spokesperson said in an email.

There are other hazards too. Psychoactive substances can put patients in vulnerable states, making them potential victims for financial exploitation or other types of abuse. In Lykos’ second clinical trial, two therapists were found to have spooned, cuddled, blindfolded, and pinned down a female patient who was in distress.

The substances can also cause shallow breathing, heart issues, and hyperthermia.

To mitigate risks, the FDA can put restrictions on how drugs are administered.

“These are incredibly potent molecules and having them available in vending machines is probably a bad idea,” said Hayim Raclaw of Negev Capital, a venture capital fund focused on psychedelic drug development.

But if the protocols are too stringent, access is likely to be limited.

Rachel del Dosso, a trauma therapist in the greater Los Angeles area who offers ketamine-assisted therapy, said she’s been following the research on drugs like MDMA and psilocybin and is excited for their therapeutic potential but has reservations about the practicalities of treatment.

“As a therapist in clinical practice, I’ve been thinking through how could I make that accessible,” she said. “Because it would cost a lot for [patients] to have me with them for the whole thing.”

Del Dosso said a group therapy model, which is sometimes used in ketamine therapy, could help scale the adoption of other psychoactive treatments, too.

Artificial Intelligence and Analogs

Researchers expect plenty of new discoveries in the field. One of the companies Negev has invested in, Mindstate Design Labs, uses artificial intelligence to analyze “trip reports,” or self-reported drug experiences, to identify potentially therapeutic molecules. Mindstate has asked the FDA to green-light a clinical trial of the first molecule identified through this method, 5-MeO-MiPT, also known as moxy.

AlphaFold, an AI program developed by Google’s DeepMind, has identified thousands of potential psychedelic molecules.

There’s also a lot of work going into so-called analog compounds, which have the therapeutic effects of hallucinogens but without the hallucinations. The maker of a psilocybin analog announced in March that the FDA had granted it breakthrough therapy status.

“If you can harness the neuroplasticity-promoting properties of LSD while also creating an antipsychotic version of it, then that can be pretty powerful,” Olson said.

This article was produced by KFF Health News, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Subscribe to KFF Health News’ free Morning Briefing.

For the past year, police Detective Tim Lillard has spent most of his waking hours unofficially investigating his wife’s death.

The question has never been exactly how Ann Picha-Lillard died on Nov. 19, 2022: She succumbed to respiratory failure after an infection put too much strain on her weakened lungs. She was 65.

For Tim Lillard, the question has been why.

Lillard had been in the hospital with his wife every day for a month. Nurses in the intensive care unit had told him they were short-staffed, and were constantly rushing from one patient to the next.

Lillard tried to pitch in where he could: brushing Ann’s shoulder-length blonde hair or flagging down help when her tracheostomy tube gurgled — a sign of possible respiratory distress.

So the day he walked into the ICU and saw staff members huddled in Ann’s room, he knew it was serious. He called the couple’s adult children: “It’s Mom,” he told them. “Come now.”

All he could do then was sit on Ann’s bed and hold her hand, watching as staff members performed chest compressions, desperately trying to save her life.

A minute ticked by. Then another. Lillard’s not sure how long the CPR continued — long enough for the couple’s son to arrive and take a seat on the other side of Ann’s bed, holding her other hand.

Finally, the intensive care doctor called it and the team stopped CPR. Time of death: 12:37 p.m.

Lillard didn’t know what to do in a world without Ann. They had been married almost 25 years. “We were best friends,” he said.

Just days before her death, nurses had told Lillard that Ann could be discharged to a rehabilitation center as soon as the end of the week. Then, suddenly, she was gone. Lillard didn’t understand what had happened.

Lillard said he now believes that overwhelmed, understaffed nurses hadn’t been able to respond in time as Ann’s condition deteriorated. And he has made it his mission to fight for change, joining some nursing unions in a push for mandatory ratios that would limit the number of patients in a nurse’s care. “I without a doubt believe 100% Ann would still be here today if they had staffing levels, mandatory staffing levels, especially in ICU,” Lillard said.

Last year, Oregon became the second state after California to pass hospital-wide nurse ratios that limit the number of patients in a nurse’s care. Michigan, Maine, and Pennsylvania are now weighing similar legislation.

But supporters of mandatory ratios are going up against a powerful hospital industry spending millions of dollars to kill those efforts. And hospitals and health systems say any staffing ratio regulations, however well-intentioned, would only put patients in greater danger.

Putting Patients at Risk

By next year, the United States could have as many as 450,000 fewer nurses than it needs, according to one estimate. The hospital industry blames covid-19 burnout, an aging workforce, a large patient population, and an insufficient pipeline of new nurses entering the field.

But nursing unions say that’s not the full story. There are now 4.7 million registered nurses in the country, more than ever before.

The problem, the unions say, is a hospital industry that’s been intentionally understaffing their units for years in order to cut costs and bolster profits. The unions say there isn’t a shortage of nurses but a shortage of nurses willing to work in those conditions.

The nurse staffing crisis is now affecting patient care. The number of Michigan nurses who say they know of a patient who has died because of understaffing has nearly doubled in recent years, according to a Michigan Nurses Association survey last year.

Just months before Ann Picha-Lillard’s death, nurses and doctors at the health system where she died had asked the Michigan attorney general to investigate staffing cuts they believed were leading to dangerous conditions, including patient deaths, according to The Detroit News.

But Lillard didn’t know any of that when he drove his wife to the hospital in October 2022. She had been feeling short of breath for a few weeks after she and Lillard had mild covid infections. They were both vaccinated, but Ann was immunocompromised. She suffered from rheumatoid arthritis, a condition that had also caused scarring in her lungs.

To be safe, doctors at DMC Huron Valley-Sinai Hospital wanted to keep Ann for observation. After a few days in the facility, she developed pneumonia. Doctors told the couple that Ann needed to be intubated. Ann was terrified but Lillard begged her to listen to the doctors. Tearfully, she agreed.

With Ann on a ventilator in the ICU, it seemed clear to Lillard that nurses were understaffed and overwhelmed. One nurse told him they had been especially short-staffed lately, Lillard said.

“The alarms would go off for the medications, they’d come into the room, shut off the alarm when they get low, run to the medication room, come back, set them down, go to the next room, shut off alarms,” Lillard recalled. “And that was going on all the time.”

Lillard felt bad for the nurses, he said. “But obviously, also for my wife. That’s why I tried doing as much as I could when I was there. I would comb her hair, clean her, just keep an eye on things. But I had no idea what was really going on.”

Finally, Ann’s health seemed to be stabilizing. A nurse told Lillard they’d be able to discharge Ann, possibly by the end of that week.

By Nov. 17, Ann was no longer sedated and she cried when she saw Lillard and her daughter. Still unable to speak, she tried to mouth words to her husband “but we couldn’t understand what she was saying,” Lillard said.

The next day, Lillard went home feeling hopeful, counting down the days until Ann could leave the hospital.

Less than 24 hours later, Ann died.

Lillard couldn’t wrap his head around how things went downhill so fast. Ann’s underlying lung condition, the infection, and her weakened state could have proved fatal in the best of circumstances. But Lillard wanted to understand how Ann had gone from nearly discharged to dying, seemingly overnight.

He turned his dining room table into a makeshift office and started with what he knew. The day Ann died, he remembered her medical team telling him that her heart rate had spiked and she had developed another infection the night before. Lillard said he interviewed two DMC Huron Valley-Sinai nurse administrators, and had his own doctor look through Ann’s charts and test results from the hospital. “Everybody kept telling me: sepsis, sepsis, sepsis,” he said.

Sepsis is when an infection triggers an extreme reaction in the body that can cause rapid organ failure. It’s one of the leading causes of death in U.S. hospitals. Some experts say up to 80% of sepsis deaths are preventable, while others say the percentage is far lower.

Lives can be saved when sepsis is caught and treated fast, which requires careful attention to small changes in vital signs. One study found that for every additional patient a nurse had to care for, the mortality rate from sepsis increased by 12%.

Lillard became convinced that had there been more nurses working in the ICU, someone could have caught what was happening to Ann.

“They just didn’t have the time,” he said.

DMC Huron Valley-Sinai’s director of communications and media relations, Brian Taylor, declined a request for comment about the 2022 staffing complaint to the Michigan attorney general.

Following the Money

When Lillard asked the hospital for copies of Ann’s medical records, DMC Huron Valley-Sinai told him he’d have to request them from its parent company in Texas.

Like so many hospitals in recent years, the Lillards’ local health system had been absorbed by a series of other corporations. In 2011, the Detroit Medical Center health system was bought for $1.5 billion by Vanguard Health Systems, which was backed by the private equity company Blackstone Group.

Two years after that, in 2013, Vanguard itself was acquired by Tenet Healthcare, a for-profit company based in Dallas that, according to its website, operates 480 ambulatory surgery centers and surgical hospitals, 52 hospitals, and approximately 160 additional outpatient centers.

As health care executives face increasing pressure from investors, nursing unions say hospitals have been intentionally understaffing nurses to reduce labor costs and increase revenue. Also, insurance reimbursements incentivize keeping nurse staffing levels low. “Hospitals are not directly reimbursed for nursing services in the same way that a physician bills for their services,” said Karen Lasater, an associate professor of nursing in the Center for Health Outcomes and Policy Research at the University of Pennsylvania. “And because hospitals don’t perceive nursing as a service line, but rather a cost center, they think about nursing as: How can we reduce this to the lowest denominator possible?” she said.

Lasater is a proponent of mandatory nurse ratios. “The nursing shortage is not a pipeline problem, but a leaky bucket problem,” she said. “And the solutions to this crisis need to address the root cause of the issue, which is why nurses are saying they’re leaving employment. And it’s rooted in unsafe staffing. It’s not safe for the patients, but it’s also not safe for nurses.”

A Battle Between Hospitals and Unions

In November, almost one year after Ann’s death, Lillard told a room of lawmakers at the Michigan State Capitol that he believes the Safe Patient Care Act could save lives. The health policy committee in the Michigan House was holding a hearing on the proposed act, which would limit the amount of mandatory overtime a nurse can be forced to work, and require hospitals to make their staffing levels available to the public.

Most significantly, the bills would require hospitals to have mandatory, minimum nurse-to-patient ratios. For example: one nurse for every patient in the ICU; one for every three patients in the emergency room; a nurse for triage; and one nurse for every four postpartum birthing patients and well-baby care.

Efforts to pass mandatory ratio laws failed in Washington and Minnesota last year after facing opposition from the hospital industry. In Minnesota, the Minnesota Nurses Association accused the Mayo Clinic of using “blackmail tactics”: Mayo had told lawmakers it would pull billions of dollars in investment from the state if mandatory ratio legislation passed. Soon afterward, lawmakers removed nurse ratios from the legislation.

While Lillard waited for his turn to speak to Michigan lawmakers about the Safe Patient Care Act in November, members of the Michigan Nurses Association, which says it represents some 13,000 nurses, told lawmakers that its units were dangerously understaffed. They said critical care nurses were sometimes caring for up to 11 patients at a time.

“Last year I coded someone in an ICU for 10 minutes, all alone, because there was no one to help me,” said the nurses association president and registered nurse Jamie Brown, reading from another nurse’s letter.

“I have been left as the only specially trained nurse to take care of eight babies on the unit: eight fragile newborns,” said Carolyn Clemens, a registered nurse from the Grand Blanc area of Michigan.

Nikia Parker said she has left full-time emergency room nursing, a job she believes is her calling. After her friend died in the hospital where she worked, she was left wondering whether understaffing may have contributed to his death.

“If the Safe Patient Care Act passed, and we have ratios, I’m one of those nurses who would return to the bedside full time,” Parker told lawmakers. “And so many of my co-workers who have left would join me.”

But not all nurses agree that mandatory ratios are a good idea. 

While the American Nurses Association supports enforceable ratios as an “essential approach,” that organization’s Michigan chapter does not, saying there may not be enough nurses in the state to satisfy the requirements of the Safe Patient Care Act.

For some lawmakers, the risk of collateral damage seems too high. State Rep. Graham Filler said he worries that mandating ratios could backfire.

“We’re going to severely hamper health care in the state of Michigan. I’m talking closed wards because you can’t meet the ratio in a bill. The inability for a hospital to treat an emergent patient. So it feels kind of to me like a gamble we’re taking,” said Filler, a Republican.

Michigan hospitals are already struggling to fill some 8,400 open positions, according to the Michigan Health & Hospital Association. That association says that complying with the Safe Patient Care Act would require hiring 13,000 nurses.

Every major health system in the state signed a letter opposing mandatory ratios, saying it would force them to close as many as 5,100 beds.

Lillard watched the debate play out in the hearing. “That’s a scare tactic, in my opinion, where the hospitals say we’re going to have to start closing stuff down,” he said.

He doesn’t think legislation on mandatory ratios — which are still awaiting a vote in the Michigan House’s health policy committee — are a “magic bullet” for such a complex, national problem. But he believes they could help.

“The only way these hospitals and the administrations are gonna make any changes, and even start moving towards making it better, is if they’re forced to,” Lillard said.

Seated in the center of the hearing room in Lansing, next to a framed photo of Ann, Lillard’s hands shook as he recounted those final minutes in the ICU.

“Please take action so that no other person or other family endures this loss,” he said. “You can make a difference in saving lives.”

Grief is one thing, Lillard said, but it’s another thing to be haunted by doubts, to worry that your loved one’s care was compromised before they ever walked through the hospital doors. What he wants most, he said, is to prevent any other family from having to wonder, “What if?”

This article is from a partnership that includes Michigan Public, NPR, and KFF Health News.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

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KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Subscribe to KFF Health News’ free Morning Briefing.