After a several years of bubbling just beneath the surface, psychedelic drugs are having their latest moment of public acceptance.

The people of Denver voted in May to loosen regulations around psychedelic mushrooms, while MDMA research is making clearer how it can help those battling mental illness and PTSD. Another drug, DMT, has been shown to reduce clinical anxiety in rats.

Meanwhile, groups as disparate as Silicon Valley executives and suburban UK moms are endorsing psychedelic microdosing as a sort of productivity hack. However, the scientific research is only starting to catch up with the anecdotes of its benefits. Keeping a steady drip of psilocybin in your body all day may have benefits like increased focus, energy, and creativity, but it’s only the beginning, and rigorous study may reveal more about the practice, including its negative effects, say scientists.

What Is a Microdose?

Microdosing — taking a tiny amount of a drug — is most popular with psychedelics like psilocybin, which the main active compound in magic mushrooms or in the more socially acceptable CBD.

A “tiny” dose is typically between 1/20 and 1/10 of a recreational dose. Even at that dosage, psychedelics have gained a reputation for inducing “smart drug” effects. So much so, that healthy people have turned to them to improve their creativity or boost mood.

What are the Effects of Microdosing?

A survey published in July in the International Journal of Neuropsychopharmacology notes that out of 1,116 respondents who microdosed, the overarching motive for microdosing was to enhance performance: “stimulating productivity … increasing focus, energy levels, and creativity and inducing positive mood” have all been cited in studies in recent years.

In a different survey of 278 microdosers, also published in July, some 26.6 percent reported improved mood. Meanwhile, 14.8 percent reported improved focus. But there were drawbacks: 18 percent reported physical discomfort, and 6.7 reported an uptick in anxiety.

“This framework aims to inform researchers and clinicians as experimental microdosing research begins in earnest in the years to come,” write the researchers of their survey results, published in the Harm Reduction Journal.

The thing is, there’s no much in the way of research on microdosing. But that could change, say scientists.

Kim Kuypers, Ph.D., a researcher at the Maastricht University who studies the effects of psychedelics on creativity, mood and empathy, tells Inverse that she thinks the benefits of microdosing are worth serious study.

She says as much in this critique she co-authored, which was published Sunday in The Journal of Psychopharmacology.

“Rigorous placebo-controlled clinical studies need to be conducted with different low doses of the drug to determine whether there is any evidence for the claims being made by microdosers,” write Kuypers and her co-author, David Nutt, Ph.D., a professor at Imperial College London.

" It might be the next medicine for people

“I think we really should look into the anecdotal claims,” Kuypers told Inverse via email on Monday. “We want to make clear that scientific evidence about microdosing and its effects is really meager, and research is needed. It might be the next medicine for people (suffering from ADHD, cluster headache), but it might also not be.”

Kuypers worked with with an extensive background in psychedelics research, on the analysis “designed to address questions that need to be answered by future scientific studies, and to offer guidelines for these studies.”

Microdosing is supposed to be "sub-perceptual," so you barely take enough of the drug to feel something, you but should be able to act normally. Wikimedia Commons

Does Microdosing Work?

The idea of microdosing is that the effects are “sub-perceptual.” That means that you’re supposed to take a low enough dose so that it doesn’t impede normal life, but it still has an effect on productivity, focus, and creativity.

But are these surveys evidence that microdosing “works”? In their paper, Nutt and Kuypers argue that anecdotes have outpaced the hard evidence.

In the first-ever placebo controlled microdosing study on LSD, published in 2018, microdosing changed the way people perceived time, but it wasn’t associated with any large changes in concentration, mentation, or perception.

In contrast, some studies have evaluated the experiences of people who already microdose — one out of the Netherlands showed that microdosing did seem to improve fluid thinking.

Dried magic mushrooms. Wikimedia Commons

Kuypers tells Inverse that she just completed a study that will be published later this year on LSD’s effects on creativity, memory, and attention, and those results suggest that the highest microdoses of LSD (20 micrograms) improved attention — but also impaired working memory.

These placebo-controlled studies can help separate the hype around microdosing from the effects, says Kuypers.

“Placebo-controlled studies are being conducted, that is the only way to go to test whether the claims that are being made are real,” she writes.

The larger point of the critique, Nutt conveyed to Inverse via email on Monday, is that there are some roadblocks standing in the way of our understanding of microdosing. Those roadblocks aren’t helped by the fact that while microdosing is trendy, it is still illegal in the United States.

"We hope to inspire some better-designed studies and also to try to get regulators to be more sympathetic

“We want people to know just how limited the research data on microdosing are at present,” Nutt says. “We hope to inspire some better-designed studies and also to try to get regulators to be more sympathetic to this kind of research by reducing the burden of regulations for sub-psychedelic doses.”

What Are the Risks of Microdosing?

Psychedelics have been used by humans for thousands of years. For instance, ayahuasca, a brew containing DMT, has a long history of use for religious purposes in South America. Cultural history in that vein “demonstrates a lack of serious adverse events,” Kuypers and Nutt write in their paper, but that’s not to say that microdosing is risk-free. Overdoing on psychedelics in general comes with costs. (Remember that 6.7 of microdosers reported an uptick in anxiety in one study.)

In 2011, when a team of scientists at Purdue University and Louisiana State gave rats repeated low doses (but not microdoses) of LSD, every other day, they noted that the rats showed negative behavior changes like “increased aggression or scruffy appearance.”

"We do not know whether it has consequences on the long term

They argued that the angry rats could stand as an animal model for psychosis, and wasn’t caused by withdrawal. In humans, unethical experiments conducted by the CIA from the 1950s and 60s involving long, repeated, large doses of LSD did lasting psychological harm to unwitting participants. And for people with underlying psychiatric conditions, an attached commentary to this paper notes that we still don’t know what additional risks microdosing might pose.

What are the Long-Term Effects of Microsdosing?

In terms of future worries for microdosers, Kuypers and Nutt add that there may be a theoretical connection to heart risks. These concerns are based on the idea that psychedelics activate the brain’s serotonin receptors, an effect that can damage heart valves in the long-term.

In the 1970s, the diet drug Fen-Phen, which repeatedly flooded the body with serotonin, was eventually pulled from the market after it was shown to have connections to heart valve complications. But so far, the team notes that they haven’t seen evidence that this is a real concern with psychedelics.

The big hole in our understanding, as Kuypers points out, is that we’re not sure what would happen if someone were to repeatedly take microdoses of a psychedelic drug for an extended period of time.

“We do not know whether it has consequences on the long term,” says Kuypers. “This is the reason why I want to discover the exact effects of a microdose on a psychological but also biological level so that we understand for which symptoms it might work, and not ‘sell’ it as cognitive enhancer to everybody.”

Pholiotina smithii Wikimedia Commons

What Promise Does Microdosing Hold?

Aside from the promise that psychedelics already hold for a variety of mental health conditions, microdosing on psychedelics also has its appeals outside of the world of “smart drugs.”

The appeal, says Nutt, comes down to the dosing schedule and the idea that you might be able to tap into the therapeutic effects of a psychedelic, without having to trip. In that sense, he envisions a future when they may be able to be taken in a chronic fashion — similar to SSRIs (drugs to treat depression) that could be taken each day to manage a condition like depression.

“It’s plausible, but as a different mode of treatment to acute single megadose psychedelics,” Nutt says.

That future can only be unlocked if more serious work is done on psychedelics — and in particular, on microdoses. The promise, and certainly excitement, is there. But it may take a few years before all of the evidence catches up to the hype.

Partial Abstract:

Aim: This critique paper is designed to address questions that need to be answered by future scientific studies and to offer guidelines for these studies.

Approach: Owing to its proximity for a possible approval in clinical use and short-lasting pharmacokinetics, our focus is predominantly on psilocybin. Psilocybin is allegedly, next to lysergic acid diethylamide (LSD), one of the two most frequently used psychedelics to microdose. Where relevant and available, data for other psychedelic drugs are also mentioned.

Conclusion: It is concluded that while most anecdotal reports focus on the positive experiences with microdosing, future research should also focus on potential risks of (multiple) administrations of a psychedelic in low doses. To that end, (pre)clinical studies including biological (e.g. heart rate, receptor turnover and occupancy) as well as cognitive (e.g. memory, attention) parameters have to be conducted and will shed light on the potential negative consequences microdosing could have.