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August

Psychedelics Have a Shaky-Science Problem

The Atlantic

www.theatlantic.com › ideas › archive › 2024 › 10 › psychedelics-medicine-science › 680286

No psychiatric treatment has attracted quite as much cash and hype as psychedelics have in the past decade. Articles about the drugs’ surprising results—including large improvements on depression scores and inducing smokers to quit after just a few doses—earned positive coverage from countless journalists (present company included). Organizations researching psychedelics raised millions of dollars, and clinicians promoted their potential to be a “new paradigm” in mental-health care. Michael Pollan’s 2018 psychedelics book, How to Change Your Mind, became a best seller and a Netflix documentary. Psychedelics were made out to be a safe solution for society’s most challenging mental-health problems.

But the bubble has started to burst: It’s been a bad year for fans of psychedelics.

A few months ago, two articles appeared, one in The New York Times and another in Business Insider, that portrayed major figures in psychedelics research as evangelists whose enthusiasm for the drugs compromised the integrity of their findings. In August, the FDA rejected the first application for therapy assisted by MDMA, the drug commonly known as ecstasy, saying that it “could not be approved based on data submitted to date,” according to the company that brought the application, Lykos. And five people, including two doctors, were recently charged in the death of the Friends actor Matthew Perry, who was found unconscious in his pool after he took large doses of the psychedelic ketamine. (Three of the five have reached plea agreements; the other two pleaded not guilty.)

These incidents, though unrelated, point to a problem for psychedelic research: Many of the studies underpinning these substances’ healing powers are weak, marred by a true-believer mentality among its researchers and an underreporting of adverse side effects, which threatens to undermine an otherwise bright frontier in mental-health treatment.

[Read: Psychedelics open your brain. You might not like what falls in.]

Psychedelics are by nature challenging to research because most of them are illegal, and because blinding subjects as to whether they’ve taken the drug itself or a placebo is difficult. (Sugar pills generally do not make you hallucinate.) For years, scientific funding in the space was minimal, and many foundational psychedelic studies have sample sizes of just a few dozen participants.

The field also draws eccentric types who, rather than conducting research with clinical disinterest, tend to want psychedelics to be accepted by society. “There’s been really this cultlike utopian vision that’s been driving things,” Matthew W. Johnson, himself a prominent psychedelic researcher at Sheppard Pratt, a mental-health hospital in Baltimore, told me.

Johnson, who has published many studies on psilocybin, the active compound in magic mushrooms, recently left his lab at Johns Hopkins after a dispute with Roland Griffiths, a senior researcher with whom he worked closely. Griffiths, who died last year, said in talks that psychedelics might be “critical to the survival of the human species.” He also behaved like a “spiritual leader,” according to a complaint by Johnson obtained by The New York Times, ran “his psychedelic studies more like a ‘new-age’ retreat center,” and recommended spiritual literature and meditation classes to study participants. Johnson argued that Griffiths’s emphasis on the metaphysical risked steering study participants toward his desired outcomes.

Albert Garcia-Romeu, the current associate director of the Hopkins psychedelics lab, disputes this description of Griffiths and the lab in general. “I never saw him behave like a ‘spiritual leader,’ or running the lab like a ‘new-age retreat center,’ whatever that means,” Garcia-Romeu told me. He noted that researchers have long used psychedelics to explore spiritual experiences but that “there was no imposition of any particular beliefs going on.”

Still, Griffiths isn’t the only one who zealously promoted psychedelics. Take Rick Doblin, the founder of an organization called the Multidisciplinary Association for Psychedelic Studies, or MAPS. He, too, is prone to grandiose thinking, saying he believed psychedelics could be “an antidote to evil” or might lead to a more “spiritualized humanity.” Doblin also encouraged marijuana use at work, arguing that there are “smokable tasks,” which some people “do better while under the influence of marijuana, such as working on complicated spreadsheets.” (Betty Aldworth, the director of education at MAPS, told me that Doblin was “adamant about the science being valid and proving out the answers to these questions through clinical trials.” Doblin did not reply to a request for comment.)

Neşe Devenot, a Johns Hopkins writing instructor and a former MAPS volunteer, told me that many people in the psychedelics field let their political and spiritual beliefs “influenc[e] the type of data that is being collected. The researchers should have more clinical equipoise and not be so assured of what works.”

Inside Lykos, a MAPS spinoff, many staffers were sold on the presumed benefits of MDMA, according to Stat News. One trial participant said her Lykos therapists told her she was “helping make history” and was “part of a movement.” The company failed to collect data on some of the side effects of MDMA, such as euphoria, that might have revealed the drug’s potential for abuse, Stat reported. (In a statement to Stat News, the company stood by its studies, saying that they were conducted with appropriate checks and balances and that the company did add data on positive side effects to some protocols.)

Last month, The Wall Street Journal reported that several participants in the Lykos studies said they felt pressured to report only good outcomes. Three of them said that their thoughts of suicide worsened after they took the MDMA, but that these deteriorations weren’t captured by the study results. (In response to the Journal, Lykos said it reported any significant increases in suicidality to the FDA.)

The FDA is reportedly now looking into Lykos’s data, and the journal Psychopharmacology retracted three papers stemming from MAPS’ early MDMA trials because of “protocol violations amounting to unethical conduct.” (MAPS’ Aldworth says the studies should have been revised instead of retracted. Lykos did not respond to a request for comment.)

The underreporting of adverse events and overhyping of tepid data appear to be widespread in psychedelic research. One review concluded that in many studies of psychedelics, adverse events “were not systematically assessed” and are therefore probably underreported.

And although esketamine (a ketamine-like nasal spray) was approved by the FDA in 2019, one 2021 review noted that there is “a paucity of data concerning long-term safety” of ketamine and esketamine, and a 2023 review found that esketamine’s negative side effects have been systematically underreported in journal articles. Some researchers overstate ketamine’s benefits and underplay its risks, according to a recent review article.

Many people taking ketamine for mental-health issues use the drug repeatedly for weeks or months, but little long-term safety data on the drug exist, says Boris Heifets, an anesthesiology and psychiatry professor at Stanford. For some, the drug’s dissociative effects can become addictive—Matthew Perry was injecting the drug six to eight times a day, prosecutors said, and he spent $55,000 on it in the month before he died. “You’re giving a drug that most definitely has abuse potential, and you’re giving it out online, without supervision, to anybody who can convince you they’re depressed,” Heifets told me. “It’s honestly a little fucked up.”

[Read: A new chapter in the science of psychedelic microdosing]

In a recent study conducted by Heifets, surgeons administered ketamine or a saline placebo to patients who were undergoing surgical anesthesia. Unlike patients in many psychedelic studies, these were truly blinded: They were unconscious, so those who got ketamine didn’t have a ketamine trip. It turned out that about half of both groups, ketamine and placebo, felt less depressed afterward. And those who felt less depressed assumed they had gotten ketamine.

In other words, ketamine did work, a little. But so did the placebo. Heifets attributes this effect to the extensive care and attention that all the study participants received before the procedure. The researchers told them that their mental health is important, and listened to them talk about their problems—in some cases, for hours. They told them that ketamine might make them feel better. To Heifets, this shows that rather than jumping to ketamine, doctors would do well to connect depressed people with caring, attentive therapists as a first step. (But “good luck finding one,” he acknowledged.)

These scientific shortcomings don’t seem to be dampening the enthusiasm about psychedelics. Hundreds of ketamine clinics across the country purport to treat conditions as varied as anxiety and chronic pain, and online services will send ketamine to people’s homes. An initiative to legalize psychedelics will be on the ballot in Massachusetts in November. Veterans’ groups and others are clamoring for the legalization of psychedelic therapies. This is understandable, because these drugs do show promise, especially for treating depression, PTSD, and certain types of addiction. The alternatives—bouncing between SSRIs or scrambling to find an in-network therapist—are bleak, and they fail plenty of desperate people. No new PTSD treatments have been approved in two decades. Some people truly have been cured of their ailments with short, monitored courses of psychedelics.

But the intense interest in psychedelics makes it only more important that the science behind them is as rigorous as possible, untainted by the personal views of researchers. Suggesting that people should get off proven medications in order to try MDMA or psilocybin is dangerous unless those drugs are backed by airtight evidence. And when dealing with psychologically vulnerable people, researchers would do well to align expectations with the reality of what psychedelics can actually accomplish.

The Fight Over Abortion Pills Is Just Beginning

The Atlantic

www.theatlantic.com › health › archive › 2024 › 10 › abortion-pills-roe-dobbs › 680294

For all the upheaval that followed the overturn of Roe v. Wade, it did not dramatically change the most basic fact about abortions in America: the number. Since 2022, abortions in the United States have held steady—even increased slightly, based on the best of limited data. One major reason? The rise of abortion pills, which are now used in the majority of abortions in America. Every month, thousands of women in states where abortion is banned have been able to discreetly order the pills by mail and take them at home. Even with abortion bans in place, the availability of these pills makes these rules less absolute than the anti-abortion movement would like.

“Abortion pills pose the single greatest threat to unborn children in a post-Roe world,” according to Project 2025, the Heritage Foundation’s conservative policy playbook. They are “death by mail,” according to Students for Life; Kristan Hawkins, the organization’s president, told me that “it’s a travesty what has unfolded under the Biden-Harris FDA.” And the anti-abortion movement is formulating plans to target the pills through a number of legal and political avenues—some of which could apply regardless of who is elected president next month.

Abortion pills had accounted for a steadily growing share of abortions in the U.S. for years, but in 2021, the FDA made them significantly easier to obtain: The pills are actually two different drugs, mifepristone and misoprostol, and the agency nixed a long-standing requirement to prescribe mifepristone only in person. With that, abortion pills became available by mail. The FDA cited COVID-related risks in its 2021 decision, but anti-abortion advocates immediately decried the move—and the policy has remained in place beyond the pandemic. After the overturning of Roe in 2022, 21 states passed new abortion bans or restrictions, but more than a dozen states, including New York and California, took steps to keep abortion pills available by mail, even in restricted states, by passing “shield laws.” These laws explicitly protect doctors, midwives, and nurse practitioners who use telehealth to prescribe the pills by mail across state lines.

Since then, an average of 6,000 to 7,000 people a month living in states with complete or six-week bans have been able to get abortion pills via telehealth, according to data from the Society for Family Planning, which surveys abortion providers in the United States. This number does not include people who had an abortion outside the formal health-care system, for instance by using pills ordered from overseas. And in states where abortion remains legal, the number of abortions—and the proportion involving abortion pills—also rose from 2020 to 2023, according to Guttmacher Institute data. (The number of women traveling to other states for abortions also doubled in this time, which is another reason abortions have not significantly fallen post-Roe.)

“The anti-abortion movement hasn’t quite figured out what to do with this,” says Greer Donley, a law professor at the University of Pittsburgh, who helped draft the nation’s first shield law. The shield laws have not yet been directly challenged in court. And when anti-abortion groups tried to go after the FDA’s original approval of mifepristone via a lawsuit, the Supreme Court dismissed the case this year for lack of standing.

Still, last week, three states—Missouri, Kansas, and Idaho—sought to revive that case, asking courts to reinstate certain restrictions on mifepristone. And although a President Kamala Harris would be likely to stick to the current FDA policy for abortion pills, a Trump administration could change those policies directly. It could, as my colleague Rose Horowitch has reported, curtail access to mifepristone simply by reinstating the in-person requirement for dispensing the drug—or just pull the FDA’s approval of mifepristone altogether. (In August, Donald Trump expressed openness to cracking down on abortion pills; his running mate, J. D. Vance, walked that position back a few days later.) Anti-abortion activists are hoping that Trump will enforce the long-dormant Comstock Act, a 150-year-old anti-obscenity law that bans the mailing of material “intended for producing abortion, or for any indecent or immoral use.” This could criminalize the mailing of abortion pills, even without the passage of a federal abortion ban, though anti-abortion activists have also suggested that Trump keep quiet about Comstock until he wins. (Trump, for his part, refused to share his views on the Comstock Act for months, before finally saying that he would not enforce it.)

Regardless of who becomes president, the anti-abortion movement is devising ways to restrict abortion pills through state governments too. Shield laws, for example, could be directly challenged if a red-state prosecutor goes after a doctor prescribing the pills from a shield-law state. Linda Prine, a doctor with the nonprofit Aid Access, which sends pills to states with abortion bans, told me she no longer leaves her home state of New York. Providers working under shield laws, she said, are all being “super careful.”

Anti-abortion groups could also test the limits of shield laws in more indirect ways. In Texas, says John Seago, the president of Texas Right to Life, pro-abortion groups have put up billboards advertising abortion pills: “You can go to people putting up the billboard. That’s aiding and abetting.” His group has also encouraged Texas lawmakers to introduce new laws that create liability for internet-service providers or credit-card-processing companies involved in abortion-pill transactions.

In Louisiana, where abortion is already banned, a law went into effect this month further restricting both mifepristone and misoprostol as “controlled dangerous substances.” The law is named after a Louisiana woman whose husband secretly slipped misoprostol into her drinks, and anti-abortion activists have used cases like hers to argue that the pills need more regulation. “A faceless, doctorless process to obtain abortion drugs enables abusers to poison or coerce women and girls,” Emily Davis, the vice president of communications for Susan B. Anthony Pro-Life America, said in a statement. But the law is also affecting routine medical care unrelated to abortion: The two drugs are commonly used in miscarriage and postpartum management, and hospitals in Louisiana have been doing timed drills to make sure staff can quickly access the locked closets where the medications now need to be kept.

Anti-abortion groups are also trying creative approaches to regulating abortion pills—such as through environmental regulations. Hawkins told me that Students for Life will be working with state legislatures next year on laws such as those requiring the disposal of fetal tissue from abortions as medical waste. These laws are designed to put the onus on the provider of abortion pills—presumably a doctor operating under a shield law—and states could then go after the provider for environmental-cleanup fees or fines, Kristi Hamrick, the organization’s vice president of media and policy, told me.


The new prevalence of abortion pills has opened up a new frontier, and the political and legal fights ahead may look quite different from those in the past. “We innovate, and we keep coming back. Our work is definitely just beginning,” Hawkins said. Seago, in Texas, told me he does not expect every attempt to restrict abortion pills to work. In the decades before Roe was overturned, he said, states introduced a number of different restrictions to limit access to abortion. Some worked. Some didn’t. With abortion pills, he told me, “we’re not expecting a silver bullet.” But activists like him are demanding that lawmakers try to stop their use nonetheless.