The Two Sides of Microdosing: Medical Marvel or Psychedelic Placebo?

One of the biggest trends in psychedelic exploration today is not (necessarily) a journey to the jungle to sip an Amazonian brew. Nor working with a therapist to resolve childhood trauma. It’s taking teeny tiny amounts of psychedelics. Doses that are so small, in fact, that (theoretically) people don’t notice them at all. This is a phenomenon known as “microdosing.” Over the past dozen years, microdosing in “sub-perceptual” doses – meaning there are no discernible cognitive effects – has become one of the most talked about uses for psychedelic drugs like LSD and psilocybin (the active ingredient in “magic mushrooms”).

If you take just 1/10th or 1/20th the amount that would deliver a full-blown trip, proponents swear they feel sharper, calmer, and less anxious – even more creative and productive. Despite the fact that they don’t feel “high.” No hallucinations. No mind-blowing insights. Just an improved sense of well-being, like a cup of coffee without the jitters or addiction.

Are The Benefits of Psychedelic Microdosing “All in Our Heads”?

“Millions of people are now microdosing all over the world – compared to practically nobody a decade ago,” says Rotem Petranker of McMaster University, who has published multiple studies on microdosing. “It’s deeply important that we understand what’s going on and if it really works, because it’s such a new field.”^(1, 2)

However, since microdosing exploded in popularity, many have been deeply skeptical, speculating about whether or not the perceived benefits are due to the placebo effect. This is a phenomenon that exists in all biological research in which patients perceive an increase or reduction in specific symptoms if informed they would experience effects due to a particular medication. Patients might report a rainbow of symptoms, when in reality they’ve only been given an inert sugar pill.

The fact that the brain has the ability to create a given reality, or set of sensations, based purely on given expectations is wild and fascinating in and of itself. However, in the case of microdosing, the genuine concern is that psychedelic substances may not have “true” benefits at low doses.

But it’s not just crucial to know if microdosing comes down to the placebo effect for intellectual reasons, says Dr. David Erritzoe of Imperial College London. Dr. Erritzoe is one of the leading researchers studying a range of uses for psychedelics, including the efficacy of microdosing. It’s absolutely crucial to know if it’s just the placebo effect because in order for psychedelic drugs to become legal, prescribed medicines, we need to know that they have an effect. The good news is it should be possible to control studies in microdosing, whereas for large doses, it is apparently harder to test with a proper placebo control.

“The jury is still out, and I’m personally keeping an open mind, but there haven’t been any convincing studies so far with microdosing effects beyond placebo levels,” says Dr. Erritzoe – including his own research (more on that in a moment). “And that might not matter to the microdosing community – but it matters to the regulators who would eventually approve these drugs and get them into conventional health care systems. They need the evidence from appropriately designed and conducted trials, and we just don’t have those yet. Without that evidence, clinicians will never be able to prescribe these to the people who need them.” ⁽³⁾

Several investigations have found the effects of microdosing psychedelics to be indiscernible from placebos, such as a 2022 study from the University of Chicago, which concluded “repeated low doses of LSD are safe, but produce negligible changes in mood or cognition in healthy volunteers.” Case closed? ⁽³⁾

Microdosing and Citizen Science

“A lot of the people who are behind microdosing are true believers – for them, it’s an article of faith,” says York University’s Petranker. “So no matter what evidence is published showing it to be nothing more than the placebo effect, they will disregard it. And that is a problem.” 

One study that particularly flustered microdosing evangelists came from Imperial College London in 2019, which essentially found the same results as the Chicago study: the anecdotal benefits of microdosing can be explained by the placebo effect alone.⁽⁴⁾

Believers took great issue with the study’s results and structure. However, Balazs Szigeti, lead author of the Imperial study, says their results were unfairly maligned and misinterpreted.

“A lot of people misunderstood our paper and thought we were saying microdosing doesn’t do anything – and that’s just not true. That’s bull crap,” he says. “What we showed is that microdosing clearly has a positive effect across a wide range of psychological parameters – such as changes in mindfulness and paranoia – but the effects were just not greater than the placebo effect. People were confused by this. We clearly showed that microdosing has an effect – it’s just not greater than the placebo effect.”

Microdosing evangelists maintained that the study design was inherently flawed and the results are, therefore, of little value.

The Stamets Microdosing Study

World-famous mycologist (mushroom scientist) Paul Stamets is a fan of “naturalistic studies” – but was still not a fan of the controversial Imperial study. “It was disconnected from the real-world microdosing use of only dosing three to five times a week, at non-intoxicating doses,” he says. “In this and many other studies, the participants could tell that they were getting a lower dose [70% of participants could tell if they’d taken a placebo or a real dose]. But the definition of a microdose is that you cannot feel it. Hence, they were not really microdosing.”

Stamet’s own research, published in the prestigious journal Nature Scientific Reports, surveyed 8,703 people via an app and found that microdosers had lower levels of anxiety and depression compared to non-microdosers. He feels that is a far more valid demonstration of the beneficial effects of microdosing on mood. ⁽⁵⁾

Petranker isn’t convinced. “To be honest, we shouldn’t be that confident in any of the studies on microdosing published so far because the quality of the research has been so low that everything should be taken with a big grain of salt – and we need to wait for more high-quality lab studies,” he argues.

The general consensus is that we still can’t be sure if it’s just the placebo effect. But – some ask – does that really matter?

“I feel like some people want to look at the microdosing research and say, ‘Oh, it’s just placebo effect, nothing to see here,’” says Dr. Vince Polito of Macquarie University in Australia, who has authored multiple studies on microdosing. “But to me, a more profound scientific reaction is, ‘Well, if it is just the placebo effect, that’s an amazing placebo effect.’ Millions of people all around the world are claiming that microdosing has induced all sorts of changes. So what is really going on here? Has there ever been a placebo that has been so widespread and so enthusiastically reported in the media? There has to be something here worth exploring.” ⁽⁸⁾

“But it does matter if it’s simply a placebo effect in order to convince regulators that these are valid medicines that should be legalized so clinicians will prescribe them,” says Dr. Erritzoe.

“With regard to our microdosing study where we used a new citizen science method, I sometimes find it a bit strange to be criticized for limitations we are aware of and have communicated in the actual paper. Of course this was not a conventional randomised clinical trial and accordingly had built-in limitations,” says Dr. Erritzoe.

In order to both lower the costs of the trial and enable the study of microdosing in a more “naturalistic” setting than a lab, the Imperial researchers designed a unique “double-blind” methodology. 

Participants – all 191 of them – made their own microdose pills at home using the psychedelic of their choice, as well as placebos, indistinguishable in appearance. Neither the researchers nor the participants knew which pill they would take on a given day. Only the scanned QR codes would deliver information to the database. ⁽⁴⁾

Every medical study is subject to “confirmation bias,” in which researchers find the result they were hoping for (because wouldn’t we all?). By allowing “citizen scientists” to create their own drugs at home, the Imperial scientists hoped this could minimize their own subconscious capacity to skew the results.

“What I didn’t like about that study, and about citizen science studies in general, is that you have no way of knowing what the actual dose was for every person. It could have been too high or too low, which invariably would affect the results,” comments York University’s Petranker. “Plus, there’s the set and setting issue: you have no idea what people are doing. If the Imperial researchers are only 60% confident that what they found is true – then if they want to increase that confidence to 80%, they should do it in a lab, where you can control the environment.”

This is an ongoing debate in microdosing studies – and indeed all psychedelic studies. Is a “naturalistic” environment more appropriate for research, as it more reliably reflects real life? Or should studies be confined to the lab where researchers can control all external factors? Even if “naturalistic” environments make for messier data, many researchers feel it is far more suitable to the study of psychedelics. Anyone high on acid forced to sit still under halogen lights and complete puzzles will never behave in the same fashion as they would at a rave with their friends or out for a walk in the woods.

“And what would make for a more ‘naturalistic’ environment than recruiting people into the study because they’re already planning to microdose with their own compounds. With this kind of a ‘real world’ or naturalistic study, I would argue that the doses used by the participants should be a good representation of the microdosing practice out there… What could be more representative of the microdosing community?” asks Dr. Erritzoe.

Is There More to Microdosing Than Meets the Eye?

I certainly have many friends who swear by microdosing for a range of mental health conditions: postpartum depression, anxiety, and more. For my part, as soon as I heard about the trend of microdosing, I instantly assumed it to be nothing more than a placebo. Why? Because I was raised by a hippy mom utterly devoted to homeopathy.

Homeopathy never did a thing for me, personally. By contrast, the first time I tried Tylenol – at the age of nineteen when a boyfriend’s mother gave it to me for period pains – it felt like manna from heaven.

My mother, however, passionately believed in the magic power of those flower potions – so much so that she spent a fortune on all the tablets, tinctures, and books. When she took them, she swore she felt better. She probably did. The placebo effect is the real deal: the power of the mind is not to be underestimated.⁽⁶⁾

In fact, there are placebos that GPs can legally prescribe to patients, such as Obecalp (placebo spelled backward). Can’t do any harm, right? If you think this is a rare occurrence, consider that an Oxford University survey found that 97% of British GPs had deliberately prescribed placebos to their patients at least once. Chew on that for a minute.^(7, 8)

Before writing this piece, I’d always been blasé about microdosing. If people want to put in the effort to take tiny doses of mushrooms, and if they believe it helps them, what’s the harm? But as a part of this research, I dove deeper – and found many things that shocked me and changed my mind.

Such a 2020 study in the journal Psychopharmacology from the German Institute for Addiction and Prevention Research found that over 50% of survey respondents on prescribed antidepressants abandoned their pharmaceutical medications after adopting microdosing. More impressive: over 27% who had relied on pain medications such as opioids stopped taking them after commencing microdosing.⁽⁹⁾

“That is remarkable,” says Dr. Polito. “Even if it’s just a placebo effect, that’s the kind of thing that deserves more attention and exploration.”

That is indeed impressive – and inspired me to explore microdosing for true medical benefits, rather than the capacity to help people focus on boring tasks at work. Digging through scientific papers, I discovered that multiple modern studies had found microdoses of LSD to alleviate pain. So much so, that the “effect size [about 20%] was comparable in magnitude to those observed with opioids such as oxycodone and morphine,” according to the authors of the 2020 study. Holy smokes.⁽¹⁰⁾

Dr. Polito has also found in his own research, published last year, that, “the most consistently reported effect was a reduction in perceived pain.” The possibilities for treating chronic pain, cluster headaches, endometriosis, and making a dent in the opioid crisis are phenomenal.^{(11, 12, 10)}

The concept of using tiny doses of psychedelics for pain isn’t even new. As far back as 1977, researchers investigated low doses of LSD to alleviate “phantom limb” pain in amputees. And hundreds of years ago, before the Spaniards wiped them out, the Aztecs were known to encourage the consumption of only “two or three” mushrooms for “fevers and for rheumatism.”⁽¹³⁾

All of this clearly suggests to me – as a biologist – that there must be real biochemical effects from microdosing psychedelic drugs. This can’t just be a trick of the mind (as powerful as that can be).

Amanda Feilding, often known as the “grand dame” of psychedelic research, who has campaigned for psychedelic research since the 1970s and co-authored many of the studies mentioned in this story, says the very best evidence that microdosing is the real deal comes from a 2020 study that found low doses of LSD elevated levels of a chemical called “brain-derived neurotrophic factor” (BDNF) in the blood of healthy volunteers.⁽¹⁴⁾ 

BDNF is the very same chemical produced by ketamine therapy, exercise, and other drugs. It is known as “fertilizer for the brain.” It sparks the creation of new nerve cells in the brain, and new connections between those nerve cells – processes called “neurogenesis” and “synaptogenesis.” Think of it as a renovation for the brain.(15)

“This really is the best evidence that it’s not just the placebo effect,” says Feilding.

I used to dismiss microdosing as a placebo. Now I’m convinced there must be much more to it. But what a strange idea – who would have thought tiny doses of these powerful molecules would have medical potential?

Origin of Microdosing, a Personal Story

Most credit author James Fadiman (now 83 years old) for being the first to come up with the idea of microdosing when he laid out the concept of taking 1/10th of a normal LSD dose every three or four days in his 2011 book, The Psychedelic Explorer’s Guide.

Others say Feilding should be credited as the first to discover the benefits of a small but beneficial dose of LSD – “the sweet spot,” as she calls it – when she started taking small amounts of LSD routinely in the 1970s.

For my part, I know one person who microdosed before either of them: My mother.

Martha Harron, my irreplaceable mum, was introduced to psilocybin at a cafe in London in 1968. Unlike others, she didn’t consume psilocybin mushrooms in large amounts to get blasted. Instead, she ate tiny bits every day, all summer. 

“It just made everything very pleasant. And if I was called in to work, I could function perfectly fine,” she told me. “I didn’t hallucinate. I could still read novels. I just felt calm.”

Half a century later, in 2019, my mother was diagnosed with stage four lung cancer – the most devastating moment of my life. Fortunately, she matched for the drug Keytruda, a form of “immunotherapy” – a revolutionary treatment for cancer that deservedly won the Nobel Prize.

“However, this means you can’t have cannabis – even hash brownies – because it will alter your metabolism, and we need your metabolism to work at a certain rate for the
drug to work,” her oncologist explained.

“OK – but can I have psilocybin?” she asked.

“What’s that?” he replied. Which was pretty hilarious, as Keytruda had been developed at Johns Hopkins University in Baltimore – the same institute that has led research into psilocybin for two decades.

Frustrated and amused, I called Professor David Nutt of Imperial College London – the elder statesman of all psychedelic research in the UK. I asked if it was safe for my mother to have psilocybin while on Keytruda. He laughed heartily when I related that my mother’s oncologist hadn’t heard of psilocybin.

“Of course, it’s perfectly f’ing safe, and if I was her I would do the same f’ing thing,” he replied.

So – as any good daughter would – I kept my mother supplied with high-quality mushroom chocolates (which don’t taste vile like actual mushrooms). She consumed these delicious chocolates in tiny doses all summer as she rambled around her garden. She didn’t hallucinate. She didn’t see God. She didn’t experience “ego dissolution” – all the things that might happen with a large dose. She just felt “more pep, more energy, and more positivity.”

Which was immeasurably valuable to somebody living with incurable cancer.

I lost my irreplaceable, brilliant mother in May 2021 – which was inevitable with stage four lung cancer. We had no delusions that psilocybin could save her life. But without a shadow of a doubt, those little doses of magic mushrooms made the last two years of her life indescribably, immeasurably better. Without them, she might have just sulked at home, ruminating over her inevitable and premature death, enjoying nothing. Instead, she and I spent countless days pulling weeds, planting flowers, “making mud pies,” and enjoying life.

Microdosing and End-of-Life Care

One of Amanda Feilding’s main goals for future research with the new company, Beckley Psytech, is end-of-life care.

“I truly think this is the most promising application for microdosing: palliative care. It hits mood, it hits cognitive functioning, and it hits pain,” Feilding says. The focus of the work isn’t limited to people who still have all their wits together, but are living with a terminal disease (like my mother). Feilding wants to treat people living with the curse of Alzheimer’s.

Maybe, just maybe, “sub-perceptual” amounts of these medicines might lessen anxiety and lift mood. Which could be immeasurably beneficial for those whose daily lives are bewildering, and frequently, terrifying.

There’s even the possibility that minuscule doses of LSD can boost BDNF. If true, microdosing could potentially protect against the development of Alzheimer’s and other neurodegenerative diseases, says Feilding: “Consider the known effects on inflammation, neuroplasticity, and neurogenesis – all of which link with neurodegenerative diseases.”⁽¹⁴⁾

Feilding is not the only person who thinks microdosing psychedelics could protect against Alzheimer’s and other neurodegenerative diseases. In a 2020 study, 48 healthy older volunteers (average age, 63) also suggested that low doses of LSD should be further explored for the possibility of not only treating dementia but preventing it, through its beneficial effects on the body’s serotonin system, as well as dampening inflammation.⁽¹⁶⁾

Over a Zoom call, Feilding showed me photographs of dementia patients before and after microdosing. The contrast was clear (even if a photograph happened to be taken at the right moment).

We all know someone living with dementia or a family impacted by the condition. Anything that might improve their quality of life without the potentially dangerous side effects merits some consideration. Whether it’s the placebo effect or not, every scientist agrees: we need more solid research.

Feilding has plans for more research into pain management, neuroplasticity, chronic pain, and – of course – protecting against neurodegenerative diseases. Dr. Polito is planning a long-term longitudinal study on depression – crucial, as all double-blind studies have been conducted on “healthy” volunteers, not people suffering from the crushing black dogs of depression. Other researchers at Imperial are planning an extensive, thorough review of all the studies – essential in this kind of work. If something with so few side effects could potentially replace opioids, SSRIs, and other heavy pharmaceuticals, surely it’s worth exploring.

As for me: I used to think it was homeopathic nonsense. Not anymore – and I’m going to give it a go myself. It’s not as if I have anything to lose. And based on what I know now – I have quite a lot to gain.

Sources

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