The Science of Microdosing Psychedelics by Torsten Passie MD

The first thing to note about this excellent new offering from Psychedelic Press is that it really is a science book. I have a science background, and I had to look up two words in the first three pages. However, I didn’t have to look up any more after that. I am starting this review with that observation, in case you think The Science of Microdosing Psychedelics will hand you ready-digested conclusions about microdosing practice; it will not.

It is, however, a very readable account of all the research you’ve never heard of. You may be under the impression that the microdosing of psychedelics started a few years ago, when James Fadiman coined the term. This is not the case. Some of the earliest experiments with LSD from the late 1940s onwards included some very low dose trials. This shouldn’t surprise us – after all, in those earliest studies, the researchers were studying a brand new drug, so they brought very few preconceptions along to their trials. The attitude was more a case of: Let’s try it out at this dosage and under these conditions, and see what happens. Albert Hofmann’s report of his notorious bicycle-riding first trip indicated to some researchers that the 250mg he took was probably a bit high for most tests, so they started much lower. Much of this research has been sidelined, gathering dust on archive shelves, until Dr Passie came along and dug it out, evaluated, contextualized and summarized it for this book.

The chapters cover the history of LSD research (there is very little on the other major psychedelics), evaluation of the claims made for microdosing, a good look at the differences between micro- and minidosing through personal reports and some detailed pharmacology and tolerance studies. Possible adverse effects are discussed, as are possible mechanisms of action, the issues of creativity and placebo and a brief look at microdosing other psychedelics.

The first question that naturally comes up with microdosing: Is it a real pharmacological thing, molecules all the way, or is it a placebo effect? I mean, you probably don’t care too much, if you’re using tiny doses and getting what you want from them. But it’s an important question for anyone who is thinking about the future of this practice, and whether it has one. In the preface, respected psychedelics researcher David Nichols writes:

It is an astonishing fact that despite all the hype about microdosing in recent years and an obvious thirst for knowledge about its potential effects, nobody has carried out a systematic search of the scientific literature on the use of low doses in psychedelics. This gap in knowledge is filled by Dr Torsten Passie’s book.

This issue is taken up again in discussing studies that show up sub-perceptual effects, such as the 1958 paper that shows doses as low as 7mg affecting GSR (galvanic skin response); a measure of skin conductivity that relates to the moistness of the skin and therefore to underlying autonomic and maybe emotional states. So acid has distinct effects on physical states even at doses the subject does not notice. There are other markers that Passie mentions (p151) that should help us to distinguish between placebo and non-placebo effects.

Anecdotal evidence spreads like wildfire on the internet, but what is actually happening here? How much is molecules and how much imagination impacting the body? To some extent, the difference between a dose you can feel and a dose you can’t (sub-perceptual) may come down to experience and sensitivity. What constitutes a sub-perceptual microdose for you, indistinguishable from placebo, may be an obvious low dose for me. This question leads onto another, which is discussed at various points in the book: If microdosing is, as originally defined by Fadiman and others, as ‘sub-perceptual’, that is, you don’t have any consciously-noted effects from the dose, then how can you claim it enhances creativity, for instance? This is a fairly common claim in microdosing circles, but surely a change in consciousness that is sufficient to cause a loosening-up of the creative process would be noticeable to the subject?

So we come on to the issue of microdoses vs minidoses. Some of the effects claimed for microdoses may be better classified as minidoses, doses you can actually feel the effects of. Back in my late teens I really liked acid and used it a lot. The doses my friends and I took in the late 1960s to early ‘70s must have varied enormously – from almost-useless yellow pills that may or may not have had liquid LSD dripped onto them, to the notorious small purple pills known as Purple Haze that, as one friend put it, tore the top of your head off and left your brain flailing in the wind. When we scored weak acid, the effects were often more disappointing than would be indicated by a linear dose-effects relationship; there was a feeling that everything had been stirred up, the massive emotional decompression of a full trip had begun, but not completed. At the end of such a half-trip, we would feel jittery and maybe even a bit down – not a ‘bad trip’, that only happened with higher doses, but a feeling of incompleteness, because identity had not been scrambled, melted down and reconstituted anew. Usually, there would be a later phase when the stirred-up emotions would start to integrate, maybe the next day, and it was generally unpleasant. I came to know this effect as ‘delayed aura meltdown’. Sometimes the jarring effects would hang around until the next, stronger trip, in which identity would get completely melted and recast in a more healthy-feeling form.

As a result, it was a while before I met anyone who took low doses deliberately, but it seemed to suit some people better than me. A friend in Cardiff in 1970 used to talk about ‘dropping quarters’ – i.e. taking ¼ of a Purple Haze for a recreational dose. This definitely fits into the minidoses rather than microdose category. Dr Passie’s book mentions reports of Peruvian footie fans who take what are probably minidoses of mescaline/San Pedro to go to matches.

Torsten Passie MD

The reports in this book show that minidoses are not always pleasant, and they span the whole emotional range from ‘everything is wonderful’ to pretty dark. Often, there is a sense of irritation, which may include a kind of hypersensitivity to light and sound. However, Dr Passie also uses the concept of irritation in a more generally-applicable sense, to refer to the way that low-dose psychedelics can stir things up and leave us with a feeling that things have not been resolved. The ‘irritation’ caused by low doses, as well as being a bit difficult to deal with, may be the trigger for any creative effects that occur once the mind has been jolted out of its usual ruts.

So what is a microdose? On p3, Passie defines microdoses as 1/100 of ‘the expected pharmacologically effective dose.’ This is the accepted pharmacological definition, and quite confusing, because throughout the rest of the book he uses James Fadiman’s definition, which is 1/10 of the usual dose. So for LSD, that amounts to doses in the region 10-25mg. However, some people can easily detect 25mg, so this is already shading into minidoses.

Of course, for the consumer at home, who depends on illegal supplies, it is very hard indeed to judge what doses we are getting. My first experience of deliberate microdosing was a quarter of a blotter dose that I took in an attempt to overcome jetlag when I arrived home at dawn from a transatlantic flight. It was entirely successful, I went into a trancey state and sleep followed easily. This was in the 1990s, when acid was sold for going to dance clubs, and the full blotter square was probably less than 50mg.

Some descriptions of mini/microdoses sound so much more like a full dose that it makes me wonder how much we were getting in tabs. This hinterland where micro shades into mini is illustrated with the earliest study on low-dose LSD, by Stoll in 1946-7, using 30mg on 19 healthy volunteers. The reports show that it is not a sub-perceptual dose – people were getting strong changes in body-image, rubber legs/rubber ground, sweating and cold, discomfort and slight nausea. They also got closed-eyes hallucinations and synaesthesia, letters dancing on the page, massive visual distortions of size, euphoria, apathy, ‘a domineering attitude’, fear and sadness. This shows how intense the effects of even such a small dose can be. The after-effects were significant too, including euphoria and a feeling of rebirth.

This report, however, contained the oddest thing I’ve ever read about an LSD experience. On the day following the dose, people reported hangover-like symptoms, including headache and ‘pain in the limbs’. I don’t think I’ve ever heard of such a thing from trippers and never rea

Diagram 23 from The Science of Microdosing Psychedelics by Torsten Passie

d anything similar in the literature. Quite the opposite, in fact; a lot of trippers, including me, feel extraordinarily fit and healthy the day after a trip. I can only imagine that the researchers let the volunteers become extremely dehydrated for some reason.

Passie makes sense of the dosage regimens of published studies with a useful table. Diagram 23 tells the whole dosage story.

One thing we all want to know is whether microdosing is any use for alleviating depression. The jury is still out on this one. Ups and downs of mood, which researchers call ‘lability’, seem to be typical of micro/low-end-minidosing, and this fits with experiences I have heard of. It seems more likely that the treatment of depression will find more use for larger doses. Passie comments on long-term repeated medium doses as follows (p159):

My hypothesis is that if man goes through a usual life cycle, he collects a lot of tensions in his everyday life, which may pile up so much that he may end up with chronic tensions resulting in psychosomatic diseases. This process could hypothetically be counteracted by ‘regularly shaking the brain thoroughly around’ through the activation of the serotonin system by LSD.

This reminds me of one of my own models for why I was doing acid back in my youth: I thought of myself as a metal vessel which was accumulating cracks. The acid, if the dose was high enough, melted down my sense of selfhood, and when I came down it was recast, without the cracks that had been impairing its function. The meltdown is of course an analogy for the ego-challenge and ego-loss stage of high dose psychedelics. If depression can be seen, as neuroscientists have said, as an habitual over-use of the DMN (default mode network), a behavioural trait we experience as excessive rumination, then it would stand to reason that a good dose of neuroplastic meltdown and ego-loss is exactly what we need.

A couple of lesser points: Sometimes people say microdose acid makes them smarter, but the clinical evidence does not support this: it seems that LSD, even at microdose levels, decreases your performance on IQ tests. However, IQ is far from everything, and ‘selective recall’ was robust, so it seems that acid flattens Hugr and leaves Minni untouched. One reference I expected to see was to the research that shows that low-dose psilocybin enhances eyesight, but this isn’t in the book. I had a quick google but couldn’t find anything relevant. I wonder where Terence McKenna got it, because I am sure it was in his work I read it, discussing it in his thesis that mushrooms gave our hunter ancestors a selective advantage.

Another issue that microdosing has brought to the fore is the socio-political impact of psychedelics. On p7, Douglas Rushkoff is quoted as saying, ‘LSD became Prozac. A chemical, which was endangering societal order, became a technology for social control.’ Allowing for the gigantic exaggeration that journalists, even ones as good as Rushkoff, cannot resist, because it increases the dramatic impact of what they are saying, he does have something of a point. Do we go for the  mind-blowing mega-dose or the safe, work-ethic enhancing dose that keeps capitalism trudging along? Well, I think we can have both. (Which we cannot with Prozac – all that happens if you take 10 times as much of that is that you will get sick.) LSD may have been one of the things that shook the world up and led to some improvements, but I doubt that a craze for high-dose experimentation will do the same trick again. Instead let us find out whether we can use the same molecule for healing, and to substitute for more toxic stimulant drugs. And for other uses that we may yet discover.

Dr Passie is a professor in the areas of psychotherapy and pharmacology. Imagine how straight you’d have to be to become a professor of pharmacology, how squeaky-clean your record, before they let you get your hands on all those drugs. But he is also an engaging author, with a touch of dry humour. I particularly enjoyed the phrase ‘unmotivated smiling’. That is my kind of prof of pharmacology, who can recommend a good ‘shaking up’ with medium-dose LSD.  Indeed, he comes over in the following interview as a well-rounded thinker, quite the opposite of most academics and medical scientists, and a very nice chap. Check out his smile, motivated or not. If you just want to watch the bit about microdosing, here it is.

A final couple of points: Since the book will form a reference for some people (me included) it really could have done with an index. And the cover… Until I held it in a particular light I didn’t realise that the lovely (Klein?) blue has a subtle glitter to it. Once found, it took me a while to see it again. A stylish touch! Should you buy it? If you want a handbook that tells you how to microdose, then no. This is a popular science book, but not a shallow one; if you want to read an indispensable book about the various dosage regimens of LSD and what happens under them, which might help you better understand your own microdosing experiences, and a scientific history of LSD testing thrown in, then definitely yes.


This review by David Lee originally appeared in the Psychedelic Press journal (Issue XXVI).

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