Psychedelic drugs—once promising research subjects that were decades ago relegated to illicit experimentation in dorm rooms—have been steadily making their way back into the lab for a revamped 21st-century-style look. Scientists are rediscovering what many see as the substances’ astonishing therapeutic potential for a vast range of issues, from depression to drug addiction and acceptance of mortality. A frenzy of interest has captivated a new generation of researchers, aficionados and investors, triggering some understandable wariness over promises that may sound a little too good to be true. But late last year the highly respected institution Johns Hopkins University—the U.S.’s oldest research university—launched a dedicated center for psychedelic studies, the first of its kind in the country and perhaps the world’s largest. With work now underway, the center is aiming to enforce the strictest standards of scientific rigor on a field that many feel has veered uncomfortably close to mysticism and that has relied heavily on subjective reports. Early results have been promising and seem poised to keep the research on a roll.

Psilocybin (a psychoactive compound found in certain mushrooms) and LSD were widely studied in the 1950s and 1960s as treatments for alcoholism and other maladies. They later gained a reputation in the media and the public eye as dangerous and became strongly associated with the counterculture. Starting in 1966, several states banned their use. In 1968 LSD was outlawed nationwide, and in 1970 Congress passed the Controlled Substances Act, classifying that drug and psilocybin, along with several others, as having a high potential for abuse and no accepted medical use. But in recent years a rapidly growing number of studies reporting encouraging results in treating depression, addiction and post-traumatic stress disorder (PTSD) have brought them back out of the shadows, spurred on by positive media coverage.

In a major boost to the reviving field, Johns Hopkins’s Center for Psychedelic and Consciousness Research is exploring the use of psychedelics—primarily psilocybin—for problems ranging from smoking addiction to anorexia and Alzheimer’s disease. “One of the remarkably interesting features of working with psychedelics is they’re likely to have transdiagnostic applicability,” says Roland Griffiths, who heads the new facility and has led some of the most promising studies evaluating psilocybin for treating depression and alcoholism. The myriad applications suggested for these drugs may be a big part of what makes them sound, to many, like snake oil—but “the data [are] very compelling,” Griffiths says. And psychedelics may not only hold hope for treating mental disorders. As Griffiths puts it, they provide an opportunity to “peer into the basic neuroscience of how these drugs affect brain activity and worldview in a way that is ultimately very healthy.”

As author Michael Pollan chronicles in his 2018 best seller How to Change Your Mind, researchers were examining the therapeutic effects of psychedelics in the 1950s—a decade before then Harvard University psychologist Timothy Leary and his colleague Richard Alpert started their notorious study in which they gave psilocybin to students (ultimately leading to Leary’s and Alpert’s dismissal from the university). In the 1950s–1970s, studies conducted with LSD—which acts on the same brain receptors as psilocybin—reported strong results in treating substance use disorders, including alcohol and heroin addiction. But when LSD became illegal in 1968, funding for this work gradually dried up. Most psychedelics research stopped or went underground.

Psychedelics’ New Wave

Griffiths and some of his colleagues helped revive the field around 2000, when they obtained government approval to give high doses of psilocybin to healthy volunteers. The researchers published a foundational study in 2006 showing a single dose was safe and could cause sustained positive effects and even “mystical experiences.” A decade later they published a randomized double-blind study showing psilocybin significantly decreased depression and anxiety in patients with life-threatening cancer. Each participant underwent two sessions (a high-dose one and a low-dose one) five weeks apart. Six months afterward, about 80 percent of the patients were still less clinically depressed and anxious than before the treatment. Some even said they had lost their fear of death.

Armed with these promising results, Griffiths and his colleagues turned their attention to other clinical applications. They decided to investigate tobacco addiction—in part because it is much easier to quantify than emotional or spiritual outcomes. Johns Hopkins researcher Matthew Johnson led a small pilot study in 2014 to see whether psilocybin could help people quit smoking. It was an open-label study, meaning the participants knew they were getting the drug and not a placebo.

The work followed a classic model for psychedelic therapy in which the participant lies on a couch and wears eyeshades while listening to music. Researchers do not talk to or guide subjects during the trip, but before each session, they do try to prepare people for what they might experience. In Johnson and his colleagues’ study, participants also underwent several weeks of cognitive-behavioral therapy (talk therapy aimed at changing patterns of thinking) before and after taking psilocybin. The drug was given in up to three sessions—one on the target quit date, another two weeks later and a third, optional one eight weeks afterward. The subjects returned to the lab for the next 10 weeks to have their breath and urine tested for evidence of smoking and came back for follow-up meetings six and 12 months after their target quit date.

At the six-month mark, 80 percent of smokers in the pilot study (12 out of 15) had abstained from cigarettes for at least a week, as verified by Breathalyzer and urine analysis—a vast improvement over other smoking cessation therapies, whose efficacy rates are typically less than 35 percent. In a follow-up paper, Johnson and his colleagues reported that 67 percent of participants were still abstinent 12 months after their quit date, and 60 percent of them had not smoked after 16 months or more. Additionally, more than 85 percent of the subjects rated their psilocybin trip as one of the five most meaningful and spiritually significant experiences of their lives. The team is currently more than halfway through a larger, five-year study of 80 people randomized to receive either psilocybin or a nicotine patch at the new Johns Hopkins center. Recruitment for the study is ongoing.

The exact brain mechanism by which the therapy appears to work remains unclear. At the psychological level, Johnson says, there is evidence that the sense of unity and mystical significance many people experience on psilocybin is associated with greater success in quitting, and those who take the drug may be better able to deal with cravings. At the biological level, he adds, scientists have hypothesized that psilocybin may alter communication in brain networks, possibly providing more top-down control over the organ’s reward system. A team led by Johns Hopkins cognitive neuroscientist Frederick Barrett is now investigating further by using functional magnetic resonance imaging to measure brain activity before and after patients undergo the therapy.

Like any drug, psilocybin comes with risks. People with psychotic disorders such as schizophrenia (or a strong predisposition for them) are generally advised against taking the hallucinogen. People with uncontrolled hypertension are advised to abstain as well, because psilocybin is known to raise blood pressure. Although it appears to be one of the safest “recreational” drugs and is not considered addictive, there have been reports associating it with deaths—but these may have been the result of multiple drugs, impure substances or underlying medical issues. In the smoking study, a third of participants experienced some fear or anxiety at a high dose of the psilocybin, Johnson says. But he adds that the risks can be minimized by carefully selecting participants and administering the drug in a controlled environment.

The smoking study results are promising, but Johnson says its relatively small size is a limitation. Also, subjects in such studies cannot comprise a completely random sample of the population, because it would be unethical to recruit people without telling them they may be taking a psychedelic drug. Thus, participants tend to be people who are open to this category of experience and, potentially, more apt to believe in its efficacy. And it is also hard to tease apart the effects of psilocybin from those of the cognitive-behavioral therapy in the smoking study, Johnson notes. He and his colleagues at the new center plan to conduct a double-blind, placebo-controlled study—the gold standard for medical investigations—in the future. Johns Hopkins researchers are also starting or planning studies using psilocybin therapy for a wide range of other conditions, including opioid addiction, PTSD, anorexia, post-treatment Lyme disease syndrome, Alzheimer’s disease and alcoholism in people with depression.

David Nichols, a professor emeritus of pharmacology at Purdue University, who was not involved in the recent Johns Hopkins studies but had synthesized the psilocybin used in Griffiths’s 2006 and 2016 papers, has been conducting research on psychedelics since the late 1960s. Back then, “you probably could have counted on one hand the number of people in the world that were working in this field. There wasn’t any money; there was no interest. [Psychedelics] were just looked at as drugs of abuse,” he says. Now “there’s a whole society set up to study these, with probably 150 international scientists working on it.”

Nichols says he has supported Griffiths’s and Johnson’s work since its early days, as they gathered the initial data that excited wealthy donors enough to fund the latest research. Philanthropic funding “is the way it’s going to be—until the National Institutes of Health decide that this is a field worth funding,” he says. “There are still too many political considerations that are keeping that from happening, but eventually, we’ll get there. We’ll get institutional support. We’re just not there yet.”