Can microdosing psychedelics boost mental health? Here’s what the evidence suggests

2022-02-05

When Jaclyn Downs, a 43-year-old nutritionist in Lancaster, Pennsylvania, stumbled upon the concept of microdosing psilocybin, or taking a tiny amount of a psychedelic for a subtle effect, she immediately recalled an incident in college where friends made tea with “magic mushrooms,” which contain the drug. Downs had only one sip, but she spent the rest of the night feeling grounded, peaceful, and present. Looking back, she realized what she had experienced was a microdose.

Three years ago Downs began microdosing to prepare for certain situations, such as when she had to stay later at a social event than she might want to. The drug soothed her angst and made her a better conversationalist, she says. Six months ago, she began a more structured routine, taking a tincture of microdose psilocybin every three days. It has made her calmer and more accepting, she says, especially when her six- and nine-year-old daughters argue with one another or push back on her requests. “Before I was more reactive—getting angry or irritated—but now I respond more evenly,” Downs says. “The general atmosphere of our home is more positive.”

In recent years, psychedelic drugs have evolved from a taboo topic to one gaining acceptance in mainstream quarters of society. Psychedelics are even heading for general medical approval, having been designated as a “breakthrough therapy” by the U.S. Food and Drug Administration.

But many who are intrigued by the promise of psychedelics—a category that includes psilocybin, lysergic acid diethylamide (LSD), ayahuasca, mescaline, and other substances that alter consciousness—are eager to reap the benefits without having to take a dose strong enough to provoke an hours-long journey down the rabbit hole. A growing number are turning to microdosing, regularly ingesting five to 10 percent of the mind-bending amount in a quest to enhance well-being, improve work, or diminish depression and other psychological demons without triggering the drug’s full effects.

But experts say there is little scientific evidence so far to support this approach.

“As far as we know, there are not many risks associated with microdosing. But it’s not at all clear, aside from user testimonials, that there are benefits,” says John Krystal, chair of psychiatry at the Yale School of Medicine, who has closely followed the field.

A key reason is that microdosing, as it is done in real life, is challenging to study. Users generally consume a dose for one or two mornings, skip the next one or two, and repeat this regimen for months or years. Because psychedelics are illegal, U.S. law prohibits researchers from giving them to people to take on this schedule at home. But providing the drug and overseeing users day after day in a laboratory isn’t practical, says Albert Garcia-Romeu, a researcher at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore.

That presents a problem for both the scientists and the microdosers. When active users respond to surveys about their experiences for observational research, the scientists can’t be sure each person is taking the same amount. After all, there aren’t standardized products a person can pick up at the local pharmacy. It’ s especially challenging for someone to determine an exact psilocybin microdose from a batch of dried mushrooms or a lick of an LSD tab, says Jerome Sarris, executive director of the Psychae Institute in Melbourne, Australia.

A growing phenomenon

No one knows how many people in the U.S. currently microdose, although its popularity seems to be growing. An analysis in 2018 of a Reddit discussion group devoted to microdosing recorded 27,000 subscribers; in early 2022, the group had 183,000. At a recent business conference focusing on psychedelic drugs in Miami, when audience members were asked how many currently microdose, hundreds of hands went up.

“When it first became popular about a decade ago, microdosing was hush hush, with tech entrepreneurs and businesspeople the primary users,” says Steven Holdt, the 24-year-old founder of Tune In Psychedelics, an app that lets microdosers track their dosing schedules and record drug effects for their own information. In the past few years, a broad range of people have jumped on board, Holdt says, thanks to podcasts on the topic, articles in mainstream newspapers, and writer Ayelet Waldman’s popular book, A Really Good Day, which chronicled how microdosing LSD lifted her intractable depression.

Erica Zelfand, a naturopathic physician in Portland, Oregon, says dozens of her patients currently microdose, mostly in a bid to improve their depression or attention deficit disorder. Zelfand supports their efforts but makes it clear they are lab rats in a grand experiment. “I let them know that we don’t have the research yet. And we especially don’t know the long-term risks,” she says. To help build a body of knowledge, she encourages patients to report their experiences on crowdsourced research sites like microdose.me or microdosingsurvey.com.

High versus low doses

None of the current studies on microdosing reach standards that enable scientists to draw firm conclusions. But results from recent studies using a single high-dose psychedelic have illuminated the mental-health potential of these long-shunned drugs. One potent dose of synthetic psilocybin along with psychological support improved treatment-resistant depression, according to unpublished results from a randomized study of more than 200 people released in November by the company Compass Pathways, whose proprietary formulation is one of the F.D.A. breakthrough-therapy designees. And in May 2021 scientists reported in the journal Nature that a high dose of MDMA (aka Molly or Ecstasy, which is not a classic psychedelic but produces a similar effect) greatly diminished severe post-traumatic stress disorder (PTSD).

But these results can’t be generalized to microdoses, says Matthew Johnson, acting director of the Johns Hopkins Center, which has conducted numerous studies on high-dose psychedelics.

A review of psychedelic research that Sarris published in January 2022 underscored problems facing studies that seek to discover both micro- or high-dose effects of a psychedelic drug: few large randomized trials have been done in humans.

Studies of medications in people typically begin with what is known as a phase one clinical trial, designed to determine levels of safety and tolerability in a small number of people. Such a study has not yet been undertaken for microdosing, although the drug manufacturer Diamond Therapeutics announced in November that it is about to embark on such a trial, minutely escalating the quantity of psilocybin until the ideal microdose, one that causes positive effects with the fewest negative ones, is found.

A handful of laboratory studies that included a small number of healthy people have sought to uncover the effects of microdosing after taking one or a few doses. A 2020 review published in Therapeutic Advances in Psychopharmacology counted 14 of these small experimental studies, with most finding that microdosing LSD or psilocybin yields subtle positive changes to emotions and to thought processes involved in problem-solving. The reviewers noted that some users did feel anxious or overly euphoric. Since all studies were done in healthy individuals it isn’t known whether microdosing might consistently benefit people with mental-health concerns.

One European study of 30 people, published in April 2021, found that people who microdosed psychedelics for several weeks were more in awe when viewing videos and artworks than during the weeks they took a placebo. But the study was flawed because many people were able to figure out what they were taking based on side effects like increased sweating so the researchers were unable to separate people’s actual experiences from their expectations.

Placebo effect?

Larger studies have primarily asked current users about their experiences. One tapped more than a thousand microdosers who reported increased energy, better work results, and more positive moods. Another compared 4,000 microdosers to a similar group of nonusers and found that among people with prior mental-health issues, those who microdosed reported having lower levels of anxiety and depression.

But in addition to the issue of users taking non-standardized doses, participants were all microdosing before the studies began, so they may have been biased. “We have to be cautious about not overinterpreting the encouraging retrospective reports that have appeared in the literature,” Yale’s Krystal says. “The concern about first-person experiences is that there is often tremendous potential for placebo effects to color the interpretation.”

In fact, the best study of microdosing to date shows just this effect. This was a “citizen science initiative” involving some 200 LSD and psilocybin microdosers. Some of the participants were chosen at random by scientists at Imperial College London to swap their drugs for placebos, with neither group knowing for sure which they were getting. After a month everyone was surveyed about their well-being, life satisfaction, cognition, and other factors. Psychological outcomes improved significantly for people taking the psychedelics—but they also did for those downing the placebos.

This was a clever way to study a large number of microdosers in the current regulatory environment, says Garcia-Romeu, who helped to evaluate the research for the journal eLife. The fact that so many placebo-takers reported benefits “calls into question the whole phenomenon of microdosing,” he says.

Nonetheless, imaging studies do make clear that something is happening.

In one, 20 healthy people were scanned with an fMRI several hours after taking a microdose of LSD or a placebo. The amygdala, considered the emotion center of the brain, changed how it interacted with other brain regions in the microdosers, indicating the potential to better regulate negative emotions, says study coauthor Katrin Preller, a neuropsychologist at the University of Zurich. In fact, those whose brains experienced the improved connectivity also subjectively reported feeling more upbeat, Preller says. Another study used electroencephalography (EEG) to measure brain activity in 22 LSD microdosers and documented more activity in the brain than usually occurs during rest, something also seen with high-dose psychedelics.

The effects of microdosing

Despite the paucity of research, people are turning to microdoses for a variety of reasons. Holdt says microdosing psilocybin helps him have fun around other people. He suffers from social anxiety, so without the drugs his mind constantly ruminates about all the things he might say or do. “Microdosing helps me stop that inner monologue so I can be more comfortable and present,” he says. He has had the same effect using high-dose psychedelics, which he first experienced in high school, but says the subtler effects of microdosing make it easier to incorporate into everyday life. “You don’t need to take a day off work or have someone watching you [to make sure a trip doesn’t turn ugly],” he says.

Many microdosers find it helps them with work. Dusty, a 40-year-old audio engineer in Philadelphia (who asked that only his nickname be used), says the tiny bit of LSD he takes once each week boosts his productivity, desire to collaborate, and creativity on the job. For example, when setting up sound systems for live concerts, “there are a million little problems that you need to solve every day, and there’s not always a good road map,” he says. On days he microdoses, he’s noticed he has “a little extra excitement to solve a problem that leads to long-term solutions, rather than just making it work for now.”

Others microdose to self-treat mental-health conditions. Karen Gilbert, a 69-year-old retired nurse in Lopez Island, Washington, is hoping microdosing psilocybin, which she started in November, might help with the depression she has suffered for more than two decades. One of Zelfand’s patients, Gilbert says she noticed a difference almost immediately. “For the first time in a long time I am excited about the projects I want to do, which are feeling like opportunities rather than obligations,” she says.

Zelfand herself tried microdosing a few times but didn’t enjoy the effects. “I don’t feel well when I do it. It seems to make me a little edgy,” she says.

Some of Zelfand’s patients have had similar unwanted experiences. People with general anxiety disorders and, especially, bipolar disorder should probably avoid microdosing because it can lead to agitation or mania, she says.

Experts also worry that microdosing on a regular basis for a long period of time could theoretically weaken heart valves, like the damage caused by the diet drugs phentermine and fenfluramine (Phen/Fen) in the 1990s. Both Phen/Fen and psychedelics act on one of the body’s serotonin receptors, known as 5-HT2B, Johns Hopkins’ Garcia-Romeu says.

Even if microdosing proves to be safe and effective, some experts fear widespread recreational use could render it useless later in life if it turns out to be valuable for important mental-health purposes but people are tolerant to it after frequent use. “If we introduce more of these types of substances, that might undercut their therapeutic efficacy when we really need them for medicine, such as for end-of-life distress,” says Conor Murray, a neuroscientist at UCLA who conducted the EEG research.

And while they don’t trigger the same wild thoughts and images as taking high doses of these drugs do, some microdosers have reported some impairment, Johnson says. “If this turns out to be the case, it may be hard to drive, take care of your toddler, or make important decisions at work.”

Plus, of course, psychedelics are illegal, which means there’s no quality control on supply. What’s more, “people have lost their jobs because they’re microdosing, and they can and do get incarcerated,” Garcia-Romeu says.

But even those who are concerned about the growing use of psychedelics say microdosing may eventually prove beneficial for some people. Johnson from Johns Hopkins thinks depression might be relieved by microdosing—although he’s much more jazzed about the prospect that a person could get more relief after one or two high-dose sessions, something his research is bearing out.

Krystal believes until more is known about microdosing, people should hold off. “Right now, it should only be done in the context of experimental research,” he says. “There, protections can be in place, and the data generated will inform our understanding about these doses and drugs.”

Additional microdosing studies could also yield insights about our brains. For example, experts don’t fully understand the role of another serotonin receptor activated by psychedelics, 5-HT2A, Johnson says. “We have a whole lot to learn about [this receptor]. Is it involved with naturally occurring mystical experiences like near death experiences, even alien abduction encounters?” he wonders. “How can we use microdosing research to understand more about the nature of the human mind?”

nationalgeographic.com, 05 February 2022
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