It’s a Sunday afternoon in November in Amsterdam and I am having trouble preparing my drugs. On a chopping board in front of me is a gnarled chunk of psilocybin or “magic” truffle. It looks like a cluster of nut brittle, with a slight greenish tinge like pistachio. As I bring down my paring knife to cut a small piece off the truffle, it escapes my blue-gloved hand and goes skittering across the table. The man sitting next to me spots it on the floor and I retrieve the fragment, placing it on a small square of baking paper before moving on to the next one.
The work is convivial. Fifteen of us are gathered around, either sat at the table or sprawled on cushions in the trendy flat that serves as our workspace for the day. The walls are lined with bookshelves and a record player turns with a steady stream of hits from the 60s and 70s – David Bowie, The Beatles, The Doors. A fire crackles in the corner. On one wall there is a painting of the dwarf planet Pluto.
Plastic bowls of truffles sit at regular intervals along the table. We are methodical in our work, cutting or breaking the truffles into pieces around the size of a small peanut – not too small, though, because psilocybin oxidises. We don’t want them to lose their effect.
I am at a workshop hosted by the Psychedelics Society of the Netherlands and fellow volunteer organisation Microdosing.NL, and we are learning how to prepare a microdose – an almost imperceptibly small dose of a psychedelic drug such as LSD or psilocybin, the compound found in magic mushrooms. In this case, we’re using magic truffles (a quirk of Dutch law means that, while magic mushrooms were outlawed in 2007, truffles – which form from the mycelium of the same fungi – remain legal).
The workshop is overseen by researchers from nearby Leiden University, who are running one of the first placebo-controlled studies on microdosing. Microdosing is the practice of regularly taking tiny amounts of psychedelics with the hope of improving cognitive functioning or psychological wellbeing in some way. But there is little to no scientific evidence to support claims that microdosing has such beneficial effects – or that it has any effects at all. Now, several research groups, including this one from Leiden, are trying to gather some of the first solid data on what, if anything, microdosing actually does.
The people attending the workshop today have volunteered to take part in a study that will see them take either microdoses or placebos at regular intervals over the next four weeks. During this time they will complete several testing sessions at the university to assess their cognition, creativity, mood and wellbeing. This is just one of several workshops; the study will include around 63 participants in total, with most in their 20s and 30s and a near-even gender balance.
Once we’ve finished our chopping, we place the bits of truffle onto the plastic trays of a dehydrator, a kitchen appliance that can also be used to make dried foods such as banana chips or beef jerky. After 30 minutes on a high setting, they are ready to come out. The fragments lose around 70 percent of their weight and volume in the dehydrator and are now completely dry; poured back into the bowls, they sound like Skittles. They are still not quite small enough. Armed with nail scissors, we snip them into smaller flakes and weigh them on a digital scale into measures of precisely 0.25 grams. We then carefully pack the pieces into an opaque pill capsule. Two taken together make a microdose of 0.5 grams, or less than a tenth of a “full” dose. (There is no consensus on what exactly counts as a microdose, but recreational users generally report taking between 0.1 and 0.5 grams of mushrooms or 5 to 20 micrograms of LSD.)
We put the capsules into plastic bags of 20 – enough for one person to take two capsules every three days for a month. The truffle bowls are replaced with bowls of crisps and crudités as research assistant Neil Schön disappears upstairs with the bags. Not everyone will receive their truffles today; out of sight, Schön is randomising the bags, mixing them with another set that look exactly the same but contain a placebo instead.
Each participant has been assigned a number, and Schön calls them out one by one to collect their bags. As if by instinct, the first thing everyone does is to hold their bag up to the light and shake the contents, trying to figure out if their doses contain psychedelics or placebos. One man complains that his must be placebos; the pieces sound too small when he shakes them. Research assistant Josephine Marschall reassures him that he can’t possibly know – he is unlikely to have received the same truffles back that he prepared, and someone else may have chopped theirs smaller. “The sound should be exactly the same,” she insists. He does not look convinced.
Susan, a 32-year-old, curly-haired woman who works in the startup industry, asks for her and her friend’s bags to be exchanged. They know they’re placebos, she says. They weighed them. Marschall sends the weighed bags back upstairs with Schön for a swap and forbids anyone else from approaching the scales. “Please do not try to figure out if you have the placebo, because that does kind of ruin the entire project,” she tells the group. Then, she instructs everyone to take their first dose. They each swallow two capsules, with water or herbal tea (as I am unable to attend the follow-up sessions, I do not partake).
Marschall then sends participants off with instructions for the rest of the trial: Take two capsules on each day marked red on the calendar provided. On testing days, they should take it one hour before they come to the lab. They should not drink alcohol or coffee within six hours before testing, and they should not take any other psychoactive substances – except if they have a regular cannabis habit (this is the Netherlands after all), in which case they should continue their normal routine, as withdrawal effects may skew the results.
“And please keep taking your tablets even if you think they’re placebo,” beseeches Luisa Prochazkova, the PhD student leading the research, as people start filing out and volunteers clear the table of truffle residue and empty capsules. “From previous experience, we know that people are usually wrong about these things.”
People who microdose don’t want to get high. Consumed in such small quantities, these drugs do not have the “trippy” effects typically associated with psychedelics; if you’re seeing things, you’ve taken too much. Instead, proponents of microdosing report a grab-bag of anecdotal benefits, which range from enhanced cognitive function to increased focus or creativity, or general improved psychological wellbeing.
Microdosing as a phenomenon was largely undocumented until 2011, when US psychedelics researcher James Fadiman published a book called The Psychedelic Explorer’s Guide, which includes a chapter on “sub-perceptual doses”. He and fellow researcher Sophia Korb have been collecting people’s personal reports on microdosing since 2010. Speaking on the phone, I ask Fadiman, who is 79 and lives in Menlo Park, California, about the history of microdosing – who came up with the idea of taking these drugs in such small doses? “Well, by mistake, probably me,” he says.
Although people have likely experimented with doses of all sizes for as long as these substances have existed, Fadiman came up with the dosing regime that many in the microdosing community now follow: one twentieth to one tenth of a recreational dose of your psychedelic drug of choice, taken every three days. He says that he came upon this after speaking to a friend of Albert Hofmann, the Swiss scientist who first synthesised LSD and who died in 2008. They were talking about Hofmann’s interest in the potential of small LSD doses for medical purposes, and Fadiman thought he heard “ten micrograms”. Intrigued, he asked people in the psychedelics community if they would like to try taking this amount. “I began to get reports that there were useful effects,” he says. It was only later that he learned Hofmann had actually envisaged a dose of around 25 micrograms, which most people would consider high for a microdose.
Around five years ago, microdosing really captured the zeitgeist, gaining a reputation as a Limitless-style productivity-enhancing “smart drug” popular among the Silicon Valley set. But Fadiman and many others I meet in the psychedelics community are keen to distance microdosing from this Silicon Valley narrative. Most people who write in, he says, have a specific problem they hope microdosing can help with. Depression is the most common complaint, but some targets are rather more unexpected. People have reported microdosing to tackle chronic pain, and several women claim it helps them with difficult menstrual periods. Of the healthy people who file reports, Fadiman frequently hears from people who microdose not to be more productive but because they want to be nicer. “People say ‘My spouse likes that I’m microdosing’ or ‘I’m nicer to people at work, especially the ones I don’t like,’” he says.
Up to now, however, most evidence for microdosing is purely anecdotal or based on surveys and self-reporting. A 2018 study led by Prochazkova at a previous Psychedelics Society event found some evidence that people performed better at creative tasks after microdosing, but a lack of placebo control put a big caveat on the results. One intriguing paper published at the end of last year looked at the effects of microdosing on time perception and did include a placebo control. This was based on a broader clinical trial funded by Eleusis Benefit Corporation, a pharmaceutical company based in New York, but further results from that trial have not yet been published, and it was conducted specifically with older adults (aged 55 to 75).
This means the effects of microdosing remain very much unproven. “Basically, there is not really any evidence that these things that people describe are real effects of microdosing, or whether it could be placebo,” says David Erritzoe, a neuropsychopharmacologist at Imperial College London.
Erritzoe is one of the lead researchers on another ongoing study into microdosing, which has similar aims to the Leiden research but differs in methodology. It is conducted remotely, meaning that participants do not come to the lab and are not told how to prepare their drugs or how much to take. Instead, they sign up online and are given instructions on how to set up the experiment themselves. The study is designed primarily for psychedelics that come on blotter paper, including LSD and “research chemicals” such as 1P-LSD or AL-LAD – compounds that are analogous to LSD but are in some countries differently regulated (they are prohibited in the UK).
To incorporate a placebo control, the study includes a novel self-blinding protocol that requires volunteers to put their microdoses – tiny snips of a single tab – into opaque gel capsules and then place them into clear plastic bags. They do the same with some placebo capsules, and randomise the bags through a process of hiding them in envelopes labelled with QR codes. Participants complete a series of online tasks, also at home, to measure their cognitive performance and mental wellbeing throughout the four-week study. Only at the end do they find out which weeks they were microdosing and which they were taking placebos, by scanning the QR codes on the envelopes.
This is critical, Erritzoe says, as microdosing may be particularly susceptible to the placebo effect. This is because the placebo response is linked to expectations; if you think something is going to have an effect then it is more likely to, even if it’s just a sugar pill. Given that the drugs used in microdosing are illegal in many countries, people who decide to take them presumably wouldn’t take the risk unless they really believe they will gain some benefit.
Balász Szigeti, another researcher on the Imperial study, adds that people who microdose are a highly self-selecting group. They usually have previous experience with psychedelics, and it is usually positive – hence their interest in microdosing in the first place. But these positive preconceptions could enhance the placebo response. “When you get people really excited about doing something, that’s when you can get a really strong placebo response,” Szigeti says. He points out that many people report benefit from homeopathic treatments, even though they have been shown to be no more effective than a placebo.
Almost every microdoser I speak to, including some taking part in the Imperial study, is adamant they would be able to tell the difference between a real microdose and a placebo. Erritzoe is less convinced. He has previously worked on an MDMA study where some participants thought they were on the drug when they actually took a placebo – and that was with full doses. The only way to really know, he says, is to set up a controlled experiment on yourself. “I claim that I can taste the difference between Coke Zero and Diet Coke,” he says. “And I definitely can, because I have self-blinded myself.”
Both the Leiden and Imperial teams rely heavily on the microdosing community to support their work and take part in their studies, with prospective participants finding out about the studies largely through Facebook groups and Reddit forums such as r/microdosing, which has almost 50,000 subscribers. The main advantages of this approach are cost and scale. The disadvantage, however, is that it’s hard to control; the researchers rely on people to take their microdoses as scheduled and not break the placebo control.
I speak to one of the Imperial study participants, 29-year-old marketing entrepreneur Lars, over Skype. Having microdosed previously, he tells me that he can tell when he’s taken a microdose because it quickly makes him feel energetic, happy and focused – “like you just drank a really good coffee.” Halfway through our conversation he lifts a clear plastic baggie up to the webcam. It’s labelled ‘Friday’ and contains one coloured pill – the one he should have taken this morning. “It’s today, but I know it’s a placebo so I didn’t really need to take it,” he says.
A three-hour train journey south of Amsterdam, near the Netherlands’ border with Belgium, another research group is trying to get around this limitation by conducting some of the first lab-based microdosing tests. In this study, led by Jan Ramaekers and Kim Kuypers at Maastricht University, the researchers actually provide and administer the drug – in this case LSD – which is specially synthesised to research-level standards by a certified laboratory in Switzerland.
Ramaekers and Kuypers meet me at the university’s faculty of psychology and neuroscience on a bitterly cold day in December. Speaking in Ramaekers’ office, Kuypers says that they originally laughed when they read newspaper stories about people microdosing. “We said, ‘Well that’s placebo effect or homeopathic stuff,’” she says. “We were not really interested in it.”
But as the buzz grew around microdosing, they decided it was worth running a placebo-controlled trial. After all, Kuypers says, there’s no point in people taking a drug if it doesn’t really do anything. She adds, however, that she would feel bad for people who currently swear by microdosing if it turns out to have no effect beyond the placebo response. “It’s good that they are healed,” she says. “It might be bad if we say it’s placebo.”
“But they wouldn’t believe us anyway,” Ramaekers interjects.
“True,” Kuypers says. “We’re mythbusters, that’s how I feel.”
Ramaekers leads me down a corridor to a small room with a bed, a desk with a computer and a private bathroom. Breathing apparatus hangs from the ceiling; the space is sometimes used as a sleep lab. Each of the study’s 24 participants visit this lab on four occasions. On three of those visits, they receive a different microdose of LSD: five micrograms, ten micrograms, or 20 micrograms. On the other, they receive a placebo. They aren’t told which day corresponds to which dose. Part of the point of the study, Ramaekers says, is to test out the effect of different small doses. “Nobody really knows if a microdose is five or ten, 20, 30, 50 [micrograms],” he says. “That was one of the main reasons that we wanted to do this: to get an idea if you could actually find a single dose that objectively would already change performance.”
In the lab, he shows me a tiny bottle containing 25 micrograms of liquid LSD – more than any of the microdoses the participants will receive but a very small amount nonetheless. To administer it, he takes up the relevant amount in a syringe and adds a placebo liquid to fill the chamber. It is taken orally. A major advantage of doing the trial in the lab is that the researchers have full control over the dose. “We really know that the drug is in their body,” Ramaekers says.
After letting the dose kick in, participants complete a series of tasks on the computer. Project manager Nadia Hutten talks me through some of the different exercises. One, designed to test divergent thinking – essentially an ability to come up with creative ideas – presents subjects with a word and asks them to list as many different uses for the object as they can in three minutes. Say the word is “newspaper”; you could write “read it” but also “roll it up and swat a fly” or “wrap up fish and chips”. Another creative challenge starts with three words – Hutten gives the example of “tree”, “hand” and “pyramid” – and gives participants 15 minutes to write a story that includes them.
Other tasks include a matching pairs-style game and an empathy test that presents the user with photographs of people and asks them to select which adjective best describes the subject’s emotional state. The most boring exercise is a ten-minute reaction test that requires you to focus on a dot on the screen and press a button as soon as a number appears. It then tells you how fast you were in milliseconds. Hutten says the same test has been shown to be sensitive to the effects of sleep deprivation. “We want to see with the LSD if it’s more energetic or more relaxing,” she says.
Study participant Hector Rubin, 20, has already completed his four microdosing sessions. He sits on the bed in the sleep lab room, swinging his black Chelsea boots over the edge. Originally from Canada, he is currently studying European Studies at Maastricht University and heard about the microdosing study through a student Facebook group. The post said that participants would be paid €300 for their time. “I thought, this is a good way to make money – and try LSD,” he says.
Although he can’t know for sure, Rubin is confident that he could tell which dose he took in which session. “I know for a fact the day I took 20 because I was seeing things,” he says. One of the photographs in the empathy test showed an old man with very wrinkled skin, and in his last session he could see the lines on the man’s face moving. (Ramaekers is skeptical that 20 micrograms could cause visual effects.)
Aside from the small sample size, the Maastricht study is limited in that it only tests the short-term effects of microdosing after one distinct dose. In real life, people tend to microdose once every three days or so over a period of months. “The next logical step would be to do a follow-up where you have people take the microdose over a prolonged period of time as they would normally do in real life, with a dose that has an established effect,” Ramaekers says. But all this costs money. Getting lab-grade psychedelics is expensive and requires licenses to import and store. Then there’s the manpower required to prepare and run the studies after going through the often-lengthy process of getting them approved by an ethics board.
“Ideas are not the problem,” Kuypers says. “It’s the money and then also the capacity – you need people running the studies.”
“That’s also money,” Ramaekers adds.
Psychedelics research isn’t exactly at the top of every funding body’s list. But one woman has been trying to get studies on these drugs off the ground for decades. Amanda Feilding is founder and director of the Beckley Foundation, which she started in 1998 to support scientific research into psychoactive substances, most notably psychedelics and cannabis. The Beckley Foundation is collaborating with both the Imperial and the Maastricht microdosing studies.
I visit Feilding shortly before Christmas at her home in rural Oxfordshire, which also serves as a base for the Beckley Foundation. I arrive at the down a long private road through a wood. Fallen leaves have turned to mulch at the sides of the muddy track, which are occasionally punctuated by stone mushroom-shaped bollards covered in moss. The house is a large, crumbling, red-brick property with a moat and a garden full of meticulously-cropped topiary. Feilding meets me in a smaller stone building in the grounds; the main house is impossible to sufficiently heat in winter, so the Foundation has decamped here. She wears a bottle-green blazer over a burgundy velvet tunic and speaks with an upper class accent (having married a Scottish nobleman in 1995, Feilding holds the title of Countess of Wemyss).
Growing up, this was Feilding’s family home. Now 76 years old, she tells me that her childhood passion had always been “altered states of consciousness and mystical experiences”. She attended a convent school but left at 16 when the nuns refused to buy her books about Buddhism and mysticism. Stuck in the house, surrounded by fields and woods and little else, she dedicated herself to her specialty. “Here, we had no toys and no friends,” she says. “Actually, one had nothing more to do except mooch around thinking about themselves or consciousness or nature or whatever.”
Then, she discovered LSD. “That's when I started dedicating myself to the study of humanity and how these compounds and practices can affect consciousness,” she says. At one point in her early exploration in the 60s, she was taking LSD every day. She felt very productive: “I fell in love with that state of consciousness.”
After LSD was made illegal in the UK and US in the late 60s, research using the drug effectively came to a standstill. But in the past 20 years, interest has steadily been revived, leading to what many researchers refer to as a psychedelic renaissance. Jan Ramaekers says that a turning point came in the early 2000s, when scientists found evidence to support the use of ketamine as an antidepressant. Ketamine is not considered a “classical psychedelic” like LSD or psilocybin, but it has some psychedelic-like effects. “That opened up the interest and stressed the importance of psychedelic drugs as a group, and revealed, again, the potential of this class of drugs, which for a long time has been neglected,” he says. Combined with a large unmet need among patients seeking treatments for conditions such as depression and increased media interest, these drugs once again became the subject of scientific intrigue.
Since then, several studies have made promising (albeit often still tentative) findings about full-dose psychedelics, many of which have been supported by the Beckley Foundation. In 2016, researchers from the Beckley/Imperial programme published the first imaging scans of the human brain on LSD – a study Feilding says she had been wanting to do for 50 years. The same year, they also published results of a small clinical study that found evidence for the efficacy of psilocybin-assisted therapy in patients with treatment-resistant depression.
Despite recent advances, however, progress is not as fast as Feilding would like. “My trouble is, because I live in a lovely house like the one I live in, people think I’m rich and sit in a room and sign cheques all day,” she says. In fact, the Beckley Foundation relies on donations for its work, which Feilding credits to “a few really generous, sweet philanthropists.” She estimates that the organisation has £400,000 – £500,000 a year, although she’d like to get that to £2 million. She finds funding, however, to be the least interesting part of her job, and she is also involved in the scientific work, providing ideas for study designs and input on protocols.
Feilding is particularly curious about LSD and creativity, which in turn fuels her interest in microdosing. She hopes to run a larger lab-based, placebo-controlled study off the back of her current work with Maastricht and Imperial, which will look at creativity and cognitive function. She originally wanted to include the ancient Chinese game of Go in the battery of tests, which she used to play while on LSD back in the 60s and sees as a perfect test of creativity. “It’s a microcosm of life,” she says. “You can see everything in Go terms when you play Go.”
She concedes, however, that getting study participants to play Go in a clinical environment would probably be too complex, at least at this stage of research. “This study needs to be more basic, in the sense of ‘Does a microdose have an effect or is it a placebo effect?’” she says. “And another thing – ’Is it safe’?” She, evidently, believes it is – “but, obviously, one would like to have it fully backed with scientific data.”
Feilding hopes that research into small doses will also help open up research into LSD and psychedelics more generally. “I look on it as oiling the doors to perception,” she says with characteristic poeticism. “Microdosing is the oil in the hinges which hopefully will help make the doors open when people realize what a gift of nature these compounds can be.”
Read more: Under pressure, Silicon Valley workers turn to LSD microdosing
As they wait to complete their data collection and analyses, the microdosing researchers currently running studies say they are not sure what to expect from their findings. “I think the jury is completely out,” says Imperial’s David Erritzoe.
Bernhard Hommel, principal investigator on the Leiden study, says the main thing he hopes for is something clear enough to inform future research. “We would love to have data that jumps in your face and says ‘this is not working’ or ‘it is’,” he says. “What is not cool is if you have too much to give up and too little to live. That's always a horror in a scientific life – if your effects are small but close to significant, but not quite clean enough, then you think, ‘What do I do with this? Is it there or not?’”
While the results of the tests are not yet available, some of the Leiden study participants have heard back about whether they were in the microdosing or placebo group. There were a lot of surprises.
Jonas, 28, hitchhiked to the truffle workshop all the way from Nijmegen, an hour and half’s drive away. He has plenty of experience with psychedelics, having tried magic mushrooms, LSD, ayahuasca, salvia, San Pedro cactus (which contains mescaline), plus a couple of different research chemicals, but was previously put off microdosing by the prevailing narrative of tech workers using it as a productivity booster. “I thought, now you’re just using it like Ritalin or other stuff to be able to conform to the expectations of society,” he says. He decided to join the study to see if microdosing could make him a “softer” person – “in the sense that I’ll be able to go more with the flow and be less confrontational, or confrontational in a smoother way.”
Straight after taking the first dose in the microdosing workshop, he says, he felt a very noticeable effect. He found it hard to focus and felt anxious when talking to people and awkward in his body. “I thought, ‘Woah this is too much for a microdose,’” he says. On subsequent dosing days, however, he didn’t notice anything. It turned out that he was in the placebo condition. He is uncertain what to make of his first experience, and is surprised a placebo response could be so vivid. “My mind keeps looking for other explanations, but I can’t really find a better one than that it was probably just a very strong placebo reaction.”
Kasper Van Hoek, 36 and from Groningen, has been diagnosed with ADHD and usually takes Ritalin but wanted to see if microdosing could help him with feelings of frustration. He was also in the placebo group but says that following the study protocol brought him benefits anyway. “I had a month to focus on how I function, how I process experiences,” he says. “That already helped a lot.” He has now started microdosing by himself and says that he feels more “balanced” – although he doesn’t know for sure if this is because of the drugs or just because he is more aware of his behaviour.
Meanwhile Carlos, who is 42 and works in the financial sector, was convinced he was in the placebo group; he didn’t notice anything except for some slight nausea after his first dose, which he put down to nerves. “I was very surprised to learn I was part of the actual dose,” he says. He’s curious to see what the study results show and is still interested in trying microdosing again, perhaps with a different substance or a larger dose.
Recently on the microdosing subreddit, someone posed the question, “How many of you will continue if the studies show no difference with placebo?” A few people said that they would stop, and some replied that they would just take higher doses. But several said they wouldn’t mind what the studies show, so long as they still get the effects. As one wrote, “If it's a placebo and it works, why stop?”
This article was originally published by WIRED UK
