Scientists are split over whether the benefits some microdosers experience are a placebo effect or something more.
Credit...River Cousin
By Dana G Smith
NEW YORK TIMES
Feb. 28, 2022
Joseph started microdosing psychedelics five years ago to try to improve his mental health. “I was just kind of in this depression, in this rut,” he said. “I was unhappy and angry and agitated all the time, and it went against the way that I saw myself.”
Depression and anxiety run in Joseph’s family, and he’d been prescribed Prozac as a kid. But when symptoms of depression returned in his early 30s, he didn’t want to go back to a prescription drug.
Joseph, an Austin-based designer (he asked to withhold his full name, citing privacy concerns surrounding mental health issues and illegal drug use), came across research from Johns Hopkins University about psilocybin, the active ingredient in hallucinogenic, or “magic,” mushrooms. In a small study, full doses of the drug helped cancer patients cope with depression and anxiety. Then he read anecdotes of Silicon Valley influencers claiming increased energy from taking tiny doses of psychedelics. So he decided to start microdosing a few times a week, eating a “small nibble” — about half an inch — of mushrooms to see if it would improve his mood.
Almost immediately he started seeing a benefit. “It just kind of boosted my morale,” he said. “I was in a little bit better mood. I had a little bit more pep to my step. I was having a little bit more fun, feeling a little bit more excited about things.”
Microdosing is typically defined by experts as taking 5 percent to 10 percent of a full dose of a psychedelic, usually LSD or psilocybin, as a way to get the supposed mental health benefits of the drug without the hallucinogenic high. For instance, in a clinical setting, a 155-pound man might take 20 milligrams of psilocybin for a full psychedelic experience. For a microdose, he’d take only one to two milligrams. At that level, taken several times a week, some claim the drugs improve their mood, boost their creativity and give the world a brighter, shinier quality, like it’s in high-definition.
“It’s akin to walking outside and the sun is suddenly out,” said Erin Royal, 30, a bartender in Seattle who microdoses one or two times a week with mushrooms she forages from nearby forests. “It reminds you that you are a person who can feel positive things and notice things that are beautiful.”
In practice, only about a third of people who microdose carefully measure the amount of the psychedelic they are taking; most take just enough to begin feeling some effects, which usually start after an hour and last four to six hours. That requires some trial and error — particularly when eating mushrooms, which can vary in psilocybin concentration. (The most commonly reported negative side effect of microdosing is accidentally taking too much, which isn’t dangerous but can be inconvenient if you’re at the office. Researchers also say frequent repeated doses of a psychedelic could theoretically stress the heart.)
Research into the mental health benefits of full doses of psychedelics is promising, and one early-phase study even found that psilocybin, at high doses, may be as effective as a selective serotonin-reuptake inhibitor for treating depression. Full doses of psychedelics help the brain develop new cellular connections, a process called neuroplasticity, and there’s some evidence that microdoses produce similar changes.
So many of the scientists who pioneered research into full doses of psychedelics have started studying whether a microdose might also be beneficial. But evidence is limited, and experts are divided about how microdosing helps people — or if it does at all.
Much of the early research into microdosing has been anecdotal, consisting of enthusiastic survey responses from users who experienced enhanced attention and cognition, feelings of well-being and relief from anxiety and depression. Lab studies of psilocybin and LSD microdoses tend to support these claims, showing improvements in mood, attention and creativity. But these studies have generally been small, and they didn’t compare a microdose to a placebo.
“You probably only participate at this point in a trial in microdosing if you really have a strong belief that this might help you,” said Dr. David Erritzoe, clinical director of the Centre for Psychedelic Research at Imperial College London. And when people expect to benefit from a drug, they typically do.
The two largest placebo-controlled trials of microdosing were published last year, and they both suggest that the benefits people experience are from the placebo effect. In the studies, volunteers used their own drugs to participate and, unknown to them, received either active doses or a placebo packaged in identical capsules. At the end of several weeks, almost everyone’s mood and well-being had improved, regardless of what they had taken.
“I was initially surprised but also a bit disappointed by the results, because when we set up the study we were quite optimistic that microdosing could have an effect” beyond a placebo, said Michiel van Elk, an assistant professor of cognitive psychology at Leiden University in the Netherlands who led one of the trials.
Dr. Erritzoe, who ran the other study, found that the drug’s efficacy was tied to users’ expectations. If they took a placebo but thought it was a microdose, they felt better, and if they had an active dose but wrongly guessed it was a placebo, they did not.
A third placebo-controlled trial, published earlier this month from the University of Chicago, tried to get around user expectations by giving participants four microdoses of LSD over the course of two weeks, but without telling them about the purpose of the study or even what they were taking. Once again, there was no difference between the LSD and placebo groups.
Still, some scientists point to evidence showing that microdosing has a direct impact on the brain to argue that its benefits are real. Using neuroimaging technology, researchers have shown changes in brain activity and connectivity after single small doses of LSD that are similar to what’s seen with larger amounts of the drug. And a study in Denmark found that a microdose of psilocybin activated nearly half of the specific type of serotonin receptors that psychedelics act on to produce their hallucinogenic effects.
“I wouldn’t say it’s all placebo. Clearly, it’s an active drug,” said Harriet de Wit, a professor of psychiatry and behavioral neuroscience at the University of Chicago who led several of the studies. “We see brain changes that are a little bit like the high dose effect,” which suggests the smaller doses are acting on the same systems.
Some microdosing researchers, like Dr. de Wit and Dr. van Elk, remain optimistic that tiny amounts of hallucinogenic drugs will ultimately prove beneficial for mental health and cognition. They say that the design of the placebo-controlled trials may be to blame for their lack of significant findings. The studies may not have run for long enough, or the tests and questionnaires used during the studies may not fully capture the benefits some people experience from microdosing.
On the other side, Dr. Erritzoe said that just because a drug has an impact on the brain doesn’t mean it has any therapeutic value. “If you can’t see in a proper trial that it works for the symptoms, for things that people can actually detect and feel and experience in their lives, then it’s just not that interesting,” he said.
“I’m not trying to shoot down microdosing,” he added. “I’m just being cautious and saying at the moment, it does not look particularly optimistic.”
One of the biggest problems with microdosing research is that it’s hard to block the placebo effect in studies of a psychoactive substance. In Dr. Erritzoe’s trial, 72 percent of people correctly guessed what they had taken, which means it’s no longer blinded. For the studies showing effects in the brain, the biggest changes came at the higher end of the microdosing spectrum — 20 to 26 micrograms of LSD and 3 milligrams of psilocybin — an amount where people often start noticing the drug’s effects.
Out of the lab, most users dose themselves aiming for a similar subtle awareness that they’ve taken something. At that level, the microdose might be closer to a half dose, or their expectations could heighten the drug’s benefits because they can feel that it’s doing something.
As a result of these difficulties and the lack of conclusive findings, Dr. van Elk has abandoned microdosing research to go back to studying large doses of the drugs. Dr. Erritzoe said once his next study ends, he’ll probably do the same.
Both Joseph and Ms. Royal are aware that the benefits of microdosing could be a placebo effect. But for them, how it works matters less than the fact that it’s helped. These days, Joseph said his depression has improved thanks to a regular meditation practice, although he still microdoses occasionally if he starts feeling down.
After several years of microdosing, he said the biggest change he’s experienced is a general shift in his mind set — something that’s harder for scientists to measure. “I started because I read that it helps with depression,” he said. “But as I’ve moved on, it’s helped really a lot more with mental and personal growth and outlook on life — how you want to live and your existence in the world.”
Dana Smith is an award-winning health and science writer based in Durham, North Carolina. Her work has appeared in The Atlantic, The Guardian, Scientific American, Popular Science and more.
Feb. 28, 2022
Joseph started microdosing psychedelics five years ago to try to improve his mental health. “I was just kind of in this depression, in this rut,” he said. “I was unhappy and angry and agitated all the time, and it went against the way that I saw myself.”
Depression and anxiety run in Joseph’s family, and he’d been prescribed Prozac as a kid. But when symptoms of depression returned in his early 30s, he didn’t want to go back to a prescription drug.
Joseph, an Austin-based designer (he asked to withhold his full name, citing privacy concerns surrounding mental health issues and illegal drug use), came across research from Johns Hopkins University about psilocybin, the active ingredient in hallucinogenic, or “magic,” mushrooms. In a small study, full doses of the drug helped cancer patients cope with depression and anxiety. Then he read anecdotes of Silicon Valley influencers claiming increased energy from taking tiny doses of psychedelics. So he decided to start microdosing a few times a week, eating a “small nibble” — about half an inch — of mushrooms to see if it would improve his mood.
Almost immediately he started seeing a benefit. “It just kind of boosted my morale,” he said. “I was in a little bit better mood. I had a little bit more pep to my step. I was having a little bit more fun, feeling a little bit more excited about things.”
Microdosing is typically defined by experts as taking 5 percent to 10 percent of a full dose of a psychedelic, usually LSD or psilocybin, as a way to get the supposed mental health benefits of the drug without the hallucinogenic high. For instance, in a clinical setting, a 155-pound man might take 20 milligrams of psilocybin for a full psychedelic experience. For a microdose, he’d take only one to two milligrams. At that level, taken several times a week, some claim the drugs improve their mood, boost their creativity and give the world a brighter, shinier quality, like it’s in high-definition.
“It’s akin to walking outside and the sun is suddenly out,” said Erin Royal, 30, a bartender in Seattle who microdoses one or two times a week with mushrooms she forages from nearby forests. “It reminds you that you are a person who can feel positive things and notice things that are beautiful.”
In practice, only about a third of people who microdose carefully measure the amount of the psychedelic they are taking; most take just enough to begin feeling some effects, which usually start after an hour and last four to six hours. That requires some trial and error — particularly when eating mushrooms, which can vary in psilocybin concentration. (The most commonly reported negative side effect of microdosing is accidentally taking too much, which isn’t dangerous but can be inconvenient if you’re at the office. Researchers also say frequent repeated doses of a psychedelic could theoretically stress the heart.)
Research into the mental health benefits of full doses of psychedelics is promising, and one early-phase study even found that psilocybin, at high doses, may be as effective as a selective serotonin-reuptake inhibitor for treating depression. Full doses of psychedelics help the brain develop new cellular connections, a process called neuroplasticity, and there’s some evidence that microdoses produce similar changes.
So many of the scientists who pioneered research into full doses of psychedelics have started studying whether a microdose might also be beneficial. But evidence is limited, and experts are divided about how microdosing helps people — or if it does at all.
Much of the early research into microdosing has been anecdotal, consisting of enthusiastic survey responses from users who experienced enhanced attention and cognition, feelings of well-being and relief from anxiety and depression. Lab studies of psilocybin and LSD microdoses tend to support these claims, showing improvements in mood, attention and creativity. But these studies have generally been small, and they didn’t compare a microdose to a placebo.
“You probably only participate at this point in a trial in microdosing if you really have a strong belief that this might help you,” said Dr. David Erritzoe, clinical director of the Centre for Psychedelic Research at Imperial College London. And when people expect to benefit from a drug, they typically do.
The two largest placebo-controlled trials of microdosing were published last year, and they both suggest that the benefits people experience are from the placebo effect. In the studies, volunteers used their own drugs to participate and, unknown to them, received either active doses or a placebo packaged in identical capsules. At the end of several weeks, almost everyone’s mood and well-being had improved, regardless of what they had taken.
“I was initially surprised but also a bit disappointed by the results, because when we set up the study we were quite optimistic that microdosing could have an effect” beyond a placebo, said Michiel van Elk, an assistant professor of cognitive psychology at Leiden University in the Netherlands who led one of the trials.
Dr. Erritzoe, who ran the other study, found that the drug’s efficacy was tied to users’ expectations. If they took a placebo but thought it was a microdose, they felt better, and if they had an active dose but wrongly guessed it was a placebo, they did not.
A third placebo-controlled trial, published earlier this month from the University of Chicago, tried to get around user expectations by giving participants four microdoses of LSD over the course of two weeks, but without telling them about the purpose of the study or even what they were taking. Once again, there was no difference between the LSD and placebo groups.
Still, some scientists point to evidence showing that microdosing has a direct impact on the brain to argue that its benefits are real. Using neuroimaging technology, researchers have shown changes in brain activity and connectivity after single small doses of LSD that are similar to what’s seen with larger amounts of the drug. And a study in Denmark found that a microdose of psilocybin activated nearly half of the specific type of serotonin receptors that psychedelics act on to produce their hallucinogenic effects.
“I wouldn’t say it’s all placebo. Clearly, it’s an active drug,” said Harriet de Wit, a professor of psychiatry and behavioral neuroscience at the University of Chicago who led several of the studies. “We see brain changes that are a little bit like the high dose effect,” which suggests the smaller doses are acting on the same systems.
Some microdosing researchers, like Dr. de Wit and Dr. van Elk, remain optimistic that tiny amounts of hallucinogenic drugs will ultimately prove beneficial for mental health and cognition. They say that the design of the placebo-controlled trials may be to blame for their lack of significant findings. The studies may not have run for long enough, or the tests and questionnaires used during the studies may not fully capture the benefits some people experience from microdosing.
On the other side, Dr. Erritzoe said that just because a drug has an impact on the brain doesn’t mean it has any therapeutic value. “If you can’t see in a proper trial that it works for the symptoms, for things that people can actually detect and feel and experience in their lives, then it’s just not that interesting,” he said.
“I’m not trying to shoot down microdosing,” he added. “I’m just being cautious and saying at the moment, it does not look particularly optimistic.”
One of the biggest problems with microdosing research is that it’s hard to block the placebo effect in studies of a psychoactive substance. In Dr. Erritzoe’s trial, 72 percent of people correctly guessed what they had taken, which means it’s no longer blinded. For the studies showing effects in the brain, the biggest changes came at the higher end of the microdosing spectrum — 20 to 26 micrograms of LSD and 3 milligrams of psilocybin — an amount where people often start noticing the drug’s effects.
Out of the lab, most users dose themselves aiming for a similar subtle awareness that they’ve taken something. At that level, the microdose might be closer to a half dose, or their expectations could heighten the drug’s benefits because they can feel that it’s doing something.
As a result of these difficulties and the lack of conclusive findings, Dr. van Elk has abandoned microdosing research to go back to studying large doses of the drugs. Dr. Erritzoe said once his next study ends, he’ll probably do the same.
Both Joseph and Ms. Royal are aware that the benefits of microdosing could be a placebo effect. But for them, how it works matters less than the fact that it’s helped. These days, Joseph said his depression has improved thanks to a regular meditation practice, although he still microdoses occasionally if he starts feeling down.
After several years of microdosing, he said the biggest change he’s experienced is a general shift in his mind set — something that’s harder for scientists to measure. “I started because I read that it helps with depression,” he said. “But as I’ve moved on, it’s helped really a lot more with mental and personal growth and outlook on life — how you want to live and your existence in the world.”
Dana Smith is an award-winning health and science writer based in Durham, North Carolina. Her work has appeared in The Atlantic, The Guardian, Scientific American, Popular Science and more.
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