Book Review: The Psychedelic Handbook by Rick Strassman

Sam Woolfe
20 min readOct 3, 2022


Dr Rick Strassman, currently an Adjunct Associate Professor of Psychiatry at the University of New Mexico, is one of the leading pioneers of modern psychedelic research. His studies on DMT, which took place between 1990 and 1995, broke the 20-year gap in psychedelic research. This halting of prolific and promising inquiry was because the US Controlled Substances Act (1970), which placed all classic psychedelics in the Schedule I category, increased the difficulties in doing controlled trials. This legislation was also preceded by the post-60s backlash against these compounds (LSD in particular), so scientists were less inclined to study them.

Strassman’s work on DMT, which kickstarted what has become known as the ‘psychedelic renaissance’, led to the highly successful book DMT: The Spirit Molecule (2000) and a documentary of the same name, released in 2012. Both detailed the strange entities and worlds that his study volunteers encountered. His next book, DMT and the Soul of Prophecy (2014), would draw parallels between DMT trips and the prophetic experiences described in the Hebrew Bible — the visions of Hebrew prophets, such as Ezekiel, Moses, Adam, and Daniel.

A Broad View of Psychedelics

His latest book, The Psychedelic Handbook: A Practical Guide to Psilocybin, LSD, Ketamine, MDMA, and DMT/Ayahuasca, as you can see from the subtitle, goes beyond the DMT experience. It covers not just the psychedelics mentioned in the subtitle but also mescaline (and the cacti that contain it, peyote and San Pedro), 5-MeO-DMT, ibogaine, and salvia.

Part I explores the question “What Are Psychedelic Drugs?” This looks at their history, effects, set and setting, types, the many names for them, benefits, and risks. Part II focuses on how these drugs work — both in the brain (drawing on neuroscience, pharmacology, and neuroendocrinology) and in the mind (with Freudian, Buddhist, and Medieval metaphysical perspectives included). This section also includes a discussion on the role of the placebo effect in psychedelic experiences, as well as the potential benefits of ‘non-psychedelic psychedelics’ (more on these latter substances later).

Part III offers information on the most popular psychedelics, including their history, pharmacology, doses, routes of administration, effects/side effects, therapeutic uses, risks, and legal status. Part IV, the final section, focuses on practical guidelines for use, offering tips on long- and short-term preparation, dosage, intentions, setting, tripping with others, trip sitters, bad trips, and integration. In addition, Strassman discusses what we know (and don’t know) about microdosing and the differences between decriminalising and legalising psychedelics.

Strassman states that he is approaching the topic of psychedelics here neither “as an advocate or adversary of psychedelic drugs,” adding, “I do not believe that we know enough about what psychedelics do, how they do it, or their positive and negative potential to unequivocally come down on one side or the other.” This is a refreshing perspective to hear from a researcher, especially since many others in the field are outspoken advocates, and messages about these drugs from researchers, the media, and users can at times be overly optimistic and positive, failing to give attention to known and possible risks.

So Strassman, from the outset, is arguing that the purpose of this book is not to promote psychedelic use, but rather “to summarize what we do know, and what we do not, and why it matters: scientifically, psychologically, and spiritually.” He takes this stance despite being (newly) open about his personal use of psychedelics. As he writes, “By various means and in various settings, I am personally familiar with the effects of every substance I discuss in this handbook.” You can also hear more about Strassman’s personal experiences with psychoactive substances during his appearance on the Joe Rogan Experience podcast (episode #1854).

For those already deeply interested in psychedelics and in the psychedelic ‘space’ (whether it be in a recreational, research, or business context), much of the information contained in the book will be familiar. However, there were several topics and perspectives that I’m glad were raised, which I thought contributed to Strassman’s measured approach to these substances. This kind of approach is, unfortunately, lacking in a lot of content related to the subject, but it is needed in order for people to make a truly informed decision about using psychedelics.

The Risks of Psychedelics

First, there is the complicated topic of the risk of psychedelics, and actually, in Part I, Chapter 3, “What Are Psychedelics Good For? What Are Their Risks?” Strassman dedicates more space to this area than to the benefits. As he writes:

In this chapter, it may seem as if I emphasize negative effects of psychedelics more than positive ones. It is not my intention to paint psychedelics in a negative light but to provide a balanced perspective regarding potential risks and potential benefits. It is not difficult to find glowing accounts of the results of psychedelic drug use, both within and outside the research environment. These are real reports dealing with real data. On the other hand, with the rush of enthusiasm regarding psychedelics, I advise caution in too quickly dismissing psychedelics’ potential adverse effects. These rarely receive anywhere near the attention that more promising ones do.

Strassman notes that physical addiction is not possible with most psychedelics because tolerance builds quickly, making daily use impossible, and physical withdrawal symptoms don’t occur upon cessation of use. Nevertheless, psychological addiction, while rare, is possible. Despite psychedelics causing problems, someone may “wish to return to the same state repeatedly to cope, or to reinforce beliefs that no one else shares.” Strassman adds that “tolerance to DMT — and probably 5-methoxy-DMT [5-MeO-DMT] — does not develop with repeated administration, so out of control use, while infrequent, does occur.”

Strassman wants to emphasise, too, that the terms we use to refer to psychedelics can distort our view of their effects. He states that “just as terms like “entheogen” glorify potential benefits of psychedelic drugs, renaming adverse effects “challenging experiences” minimizes their risks.” He adds:

Is a chronic unremitting psychosis requiring long-term hospitalization and powerful antipsychotic medication a challenging experience? Likewise, a fatal arrhythmia from a bronchodilator is hardly “challenging.” Medically and psychiatrically, they are severe adverse reactions with catastrophic outcomes…the term [challenging experiences] does a disservice by providing false comfort to those suffering more dramatic adverse reactions by making it less likely that they seek necessary care. “After all, it’s just a challenging experience.”

Strassman also draws attention to the poorly understood condition known as hallucinogen persisting perception disorder (HPPD), which involves lingering perceptual (and sometimes emotional and somatic) changes that are a cause of distress. The author, however, uses the term “post-hallucinogen perceptual disorder”, but argues “this is not especially useful because perceptual effects are only one aspect of a broader syndrome”, which is true. He finds the term “flashback” the most suitable term, which originated in the 60s and still, to many people, contributes to the stigma surrounding psychedelics.

Nonetheless, Strassman points out, “Flashbacks are not rare. Data from early research indicated that they occurred in up to 77 percent of those who had at least one psychedelic drug experience.” More modern research, highlighted by the Perception Restoration Foundation — a non-profit dedicated to HPPD awareness and research — offers mixed evidence about the conditions’s prevalence in psychedelic users, but it doesn’t seem to be as high as 77%. HPPD may be more frequent in those who use psychedelics more often, at higher doses, for a longer period of time, and may be more likely to occur after especially traumatic experiences. The causes are unclear, but flashbacks may occur in the way PTSD symptoms do; feelings prominent during the traumatic psychedelic trip — or a situation/setting in which the experience took place — may trigger other elements of that experience.

One risk that has been entering public consciousness more recently is unethical practices in psychedelic therapy. The abuse and adverse reactions experienced by participants in a MAPS-sponsored study on MDMA therapy, in particular, have raised awareness about this risk. Strassman addresses this, underscoring that unscrupulous practitioners “may manipulate, abuse, or otherwise take advantage of someone in a psychedelically induced vulnerable and suggestible state.”

Unscrupulous practitioners can take advantage of those under the influence of psychedelics in a variety of ways: “sexually, physically, emotionally, spiritually, or financially.” Strassman adds:

One factor making it so hard to sound the alarm is the charisma of the perpetrators, their standing in the psychedelic community — spiritual, academic, or therapeutic — and the gaslighting and blame projecting that they often invoke as their first line of defense. “It’s nothing, you’re overreacting.” “You’re imagining it.” “It must be some problem you have.” “They seduced me.” “I was only doing it for their benefit.” And so on. We are now witnessing a welcome frankness of discussions of this phenomenon.

Adverse effects can, moreover, occur due to “the research team’s expectations and beliefs about psychedelics,” which would be related to the ‘setting’ of the experience, as this is an outside factor impacting the individual’s trip. There can be a “conflict that arises when someone’s experience under the influence of a psychedelic does not fit into the model’s assumptions and the corresponding beliefs of the model’s adherents. There are fine lines between guidance, direction, constraining, and coercion.”

One ubiquitous model that researchers use, for instance, is the “mystical experience model”, which is based on the belief, as Strassman says, that “attaining a specific questionnaire-quantified psychological goal is how psychedelics heal.” And so clinical research teams prepare participants by emphasising the benefits of the mystical state and offering advice on how to attain it during the session. Therapists and the music selection can steer the experience towards this goal while integration sessions can occur through the lens of the mystical experience. Due to these expectations, when someone doesn’t achieve the mystical experience or doesn’t have a ‘complete’ mystical experience, this can lead to disappointment and demoralisation, and perhaps even encourage the participant to believe that they ‘failed’ in some way.

The Role of the Placebo Effect

One area of psychedelics that isn’t discussed enough is the placebo effect, concerning macrodoses (the role of the placebo effect in microdosing, conversely, is getting more attention, owing to studies on this connection; see here and here).

Strassman admits that his chapter on the placebo effect involves “theoretical considerations, not established facts,” however this doesn’t make this “speculative territory” any less important. Strassman states that this hypothesis is that:

the panacea-like properties of psychedelics are due to their biological effects enhancing the placebo response. This they do through their psychoplastogenic properties — growing new nerve cells [neurogenesis] and increasing the complexity of their connections [neuroplasticity]. These psychoplastogenic mechanisms operate even without a psychedelic experience. Nevertheless, with or without a psychedelic experience, set and setting remain crucial in determining the outcome of any administration of a “psychedelic” drug.

Referring to the “panacea-like properties” of psychedelics does not mean that they can solve all of the world’s problems (see my earlier article on why this kind of psychedelic utopian thinking is misguided). Instead, Strassman means that psychedelics can help improve myriad forms of emotional distress, disease, and areas of life: depression, suicidality, alcoholism, tobacco and opiate dependence, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), pain, autism, anxiety, social anxiety, end-of-life despair, meditation, creativity, personality, nature appreciation, domestic conviviality, prisoner recidivism, the severity of eating disorders and headache, the symptoms of fibromyalgia, and even neurogenerative diseases like dementia, stroke, traumatic brain injury (TBI), Parkinson’s disease, and amyotrophic lateral sclerosis (ALS).

All of the research on these positive effects, however, doesn’t preclude psychedelics from having negative effects on the minds of their users. “We also know that neo-Nazi and other radical groups take psychedelics to strengthen their beliefs, and that Charles Manson administered LSD to his followers to cement their status as serial killers.” (See more on this connection here.)

Nevertheless, Strassman believes that “psychedelics’ biological effects…underlie their heal-all properties” (panacea means “all-healing” or “cure-all”). Panaceas can include an inactive placebo (like a sugar pill) and an active placebo (a substance that has some physiological effects, which can convince someone being treated that they have received a legitimate treatment, rather than an ineffective placebo).

“The specific effects of placebo are dependent upon set and setting; that is, what those receiving and those providing any intervention wish and expect to see,” says Strassman. Aspects of ‘set’ that are relevant to the placebo response are:

  • Selection bias: who decides to take a psychedelic. People take psychedelics because they are interested in them and expect to benefit from the experience.
  • Expectancy: a state of thinking or hoping that something will happen, which can be either positive or negative.
  • Suggestibility: the quality of being inclined to believe certain things and act on the suggestion of others.
  • Hypnotisability: an enhanced tendency to respond to suggestion, often achieved by inducing an altered state of consciousness — the ‘trance’. The more suggestible someone is, the more susceptible they are to hypnosis.

These factors are also interrelated. Those with high expectations may be more suggestible and the more suggestible someone is, the greater their expectation of effect. All of these mechanisms work together to create an enhanced placebo response. Strassman states:

Psychedelic drugs are unrivaled in their ability to produce any number of effects — those that the person who takes them desires as well as the desires of those who administer them. But psychedelics are not inert placebos acting solely through hypnosis or enhanced suggestibility. They also have powerful biological effects. These effects interact with set and setting. Therefore, one might consider psychedelics to magnify the placebo response through their biological properties.

Strassman proposes that “the subjective correlate of psychedelic activation of an enhanced-placebo response is a state of consciousness reaching a critical threshold of intensity”. Thus, when there is a feeling that something momentous has taken place, a feeling of profound meaningfulness and significance, this may activate the placebo response. Placebo activation may require a particular “psychedelic experience”.

Moreover, a psychedelic experience may reflect the activation of psychoplastogenic effects; “psychedelics’ antidepressant effects occur within the same time span — sixty to ninety minutes — in which we see increases in neuroplasticity in animal models,” writes Strassman. Psychoplastogenic effects also up opportunities to maximise the benefits of the psychedelic experience. Strassman adds that:

these [psychoplastogenic] effects continue over time — a couple of weeks to a month — and may correspond in humans to the afterglow or “critical period” during which milder but real benefit continues to accrue after one’s drug session. Remember, too, that this critical period is one in which the effects of psychotherapy may be especially powerful — that is, a time of enhanced suggestibility.

Yet these same increases in neurogenesis (the growth of new neurons) and neuroplasticity (the number and complexity of neural connections) may occur in the absence of psychedelic effects. Strassman writes:

Are the two phenomena [non-psychedelic psychoplastogens and the placebo effect] related? That is, do psychoplastogenic effects underlie placebo ones? If they do, this may occur by increasing suggestibility and hypnotizability, mechanisms that contribute to the placebo response. This is a key question and we can answer it experimentally. That is, do non-psychedelic psychoplastogens increase suggestibility?

Like placebo, psychedelic or non-psychedelic psychoplastogenic effects are nonspecific. They both require direction, and that direction involves set and setting. The new connections among nerve cells are not random but will reflect the biopsychosocial circumstances in which they take place. For example, the new, more complex connections that develop while watching violent pornography would develop differently from those occurring while meditating in the forest.

…I believe we will find that non-psychedelic psychoplastogens may be effective on their own, but they will be more so when combined with psychotherapy, meditation, and other methods that take advantage of expectancy and suggestibility.

‘Non-Psychedelic Psychedelics’

It will be helpful to continue the discussion of so-called ‘non-psychedelic psychedelics’. The term itself has caused controversy and a rift in the psychedelic space. The term suggests that a compound can still count as a psychedelic despite not having any psychedelic effects — that is, despite not being ‘mind-manifesting’, which is the literal definition of the term ‘psychedelic’.

This criticism is valid. However, I think the use of the term ‘non-psychedelic psychedelic’ is attempting to be more convenient than accurate. It refers to non-psychedelic versions of compounds like DMT and ibogaine, so in a sense calling them ‘psychedelics’ is just meant to point to the fact that they’re derived from tweaked versions of psychedelic compounds. The term is still misleading, nonetheless. These tweaked substances have also been referred to as “psychedelic-like molecules” or “psychedelic duds”. Calling them “non-psychedelic psychoplastogens”, as Strassman does, might be a more useful way to underscore what they are and what they do.

However, if you want to avoid associating them with psychedelics entirely, in spite of their connection to compounds with psychedelic effects, you can simply refer to them as psychoplastogens, as substances that enhance neurogenesis and neuroplasticity.

Whatever you want to call them, though, they’ve received some backlash. Some people believe that taking the trip — the spiritual experience — out of psychedelics is a typical neoliberal/capitalist tactic that aims to make as much money out of these compounds as possible. I agree with this criticism to an extent, but I also have some issues with this kind of cynical take. If companies want to push non-psychedelic psychoplastogens as ‘psychedelics’, piggybacking on the hype and fanfare surrounding these substances, then this is misleading (since they’re not mind-manifesting) and seems like a clear marketing ploy. I would say this applies in the case of Psychedelic Water, a legal drink that contains no psychedelic compounds (it contains kava, damiana, and green tea). Drinking it won’t result in any psychedelic effects. Despite this, the company has wrongly told customers that both kava and damiana are psychedelics (they’re not).

But I don’t agree with a wholesale rejection of non-psychedelic psychoplastogens just because companies stand to profit from them or based on the belief that using them for mental health is inferior to using psychedelics. These newly developed compounds offer promising benefits and have advantages over psychedelics for many people. Strassman states:

While classical psychedelics produce psychoplastogenic effects, their mind-altering properties may not be necessary, at least in animal models. This is because non-psychedelic doses of psychedelics in lower animals are as psychoplastogenic as psychedelic doses. In addition, there are compounds closely related to psychedelics that are psychoplastogenic but not psychedelic, again in lower animals. Two examples of these latter compounds are modified versions of DMT and of ibogaine. Research using animal models of depression, drug abuse, and anxiety have demonstrated positive effects of non-psychedelic psychoplastogens.

These compounds can be useful in cases of depression and schizophrenia, for example, because people with these conditions have fewer neurons and less complexity of their interconnections. Psychoplastogens may, therefore, be able to repair these deficits. Those suffering from TBI may benefit, too. Strassman adds:

If psychoplastogenic effects are separable from psychedelic ones, such treatments will be more widely acceptable. This is because many patients would rather not have to undergo a profound mind-altering experience to obtain relief from their psychiatric and/or neurological conditions.

Not wanting to take high doses of psychedelics to feel well is one limitation of psychedelic therapy I pointed out in a previous article. Doing so can be daunting and anxiety-inducing and, even if effective, someone may be hesitant about repeating the experience, especially if it was challenging. A high-dose psychedelic experience will naturally put off a large number of people with emotional distress from even considering the treatment. In addition, highly altered states, when supervised professionally, require a lot of rigour, care, time, and money. Non-psychedelic compounds, then, offer practical advantages.

Non-psychedelic psychoplastogens also remove the possibility of adverse psychological events, which can sometimes be severe and worsen mental health. Moreover, these compounds will be useful for people struggling with a psychotic disorder, such as schizophrenia, who might benefit from the psychoplastogenic effects of psychedelics but who could be harmed by a psychedelic experience. As Strassman underscores:

In most cases, psychedelics trigger mental illness in someone with a predisposition, either from a previous episode of, say, bipolar disorder, panic attacks, or schizophrenia, and/or because of a family history of such conditions. The psychedelic drug acts like any other traumatic event that may trigger an acute episode of a serious psychological disorder.

Promoting non-psychedelic psychoplastogens could be seen as only further committing to psychiatry’s biomedical model of distress, as opposed to offering people the meaningful experiences of connection and insight that they truly need. Of course, non-psychedelic psychoplastogens shouldn’t be viewed as a mental health panacea, but neither should psychedelics (neither truly address the manifold social, cultural, political, and technological forces that shape our mental health).

However, people still want their emotional suffering to be alleviated as quickly as possible, and achieving this (safely) through the use of psychoplastogens does not mean that environmental causes of distress will then be ignored. The only risk is in assuming that distress is purely a brain problem or only an individual’s problem. This would strengthen the limited narratives of the biomedical model and neoliberalism, respectively; but this valid critique doesn’t mean we can’t include a biological approach alongside others. Psychoplastogens can be combined with psychotherapy for more meaningful and sustained change, going beyond the purely biological perspective, and focus should be placed on the social roots of psychological distress as well. Approaches to mental health don’t have to result in a zero-sum game in which adopting one precludes another.

Thinking Beyond the Mystical Experience Model

Let’s return now to the mystical experience model, which, as we have seen, is the dominant model applied in clinical trials on psychedelic therapy. However, this is only one type of spiritual experience. There is the “mystical-unitive” spiritual experience but also the “interactive-relational” one (and it is the latter that Strassman focuses on in DMT and the Soul of Prophecy, as he believed it was what made the DMT experience and visions of the Biblical prophets similar). Strassman states:

In both, we are dealing with an altered state of consciousness with spiritual characteristics. Either or both may occur within or outside a religious tradition. Within a religious tradition, we may call them “religious experiences,” and they partake of imagery, vocabulary, and concepts consistent with that religion.

What characterises the unitive-mystical experience is unity, which also involves ego dissolution since as one’s sense of self dissolves, there is the sense of becoming one with everything. There is no inner or outer and no object or subject. One’s consciousness may merge with ‘God’, ‘the ground of all being’, ‘pure awareness’, the ‘white light’, or ‘ultimate reality’. There is a feeling of timelessness and spacelessness, a feeling of truth and certainty (a conviction of certainty that what one is expeirencing is ‘more real than real’), a positive mood, and ineffability (being unable to adequately put the experience into words).

In the interactive-relational spiritual experience, in contrast, the sense of self is maintained, as are time and space, although in an altered way. Mood effects are more variable, the state is full of information, which is often communicated verbally, and — as in the mystical-unitive state — what one is witnessing feels more real than real. Strassman points out that the Hebrew Bible contains no examples of the mystical-unitive state; rather, “the prophetic experience is solely interactive and relational.” Strassman gives the following example:

Take a look at Chapter 1 of Ezekiel, where the heavens open and the prophet witnesses a host of celestial beings, spinning wheels, rotating spheres, fire, and ice. Stunned, he falls to the ground, and an angel lifts him, thus beginning a verbal dialogue between human and the divine.

Nevertheless, there is a common belief that there is a universal spiritual experience (the mystical-unitive state) hardwired in us, which psychedelics activate. “This idea dominates discussions of the spiritual effects of psychedelics within and outside academics,” says Strassman. He continues:

This has had two unfortunate effects. One is that it establishes a goal for any particular psychedelic session. That is, if someone taking a psychedelic — and those administering it — values the attainment of a mystical-unitive state, a sense of disappointment results on both sides if they fail to do so. A more pernicious result is the belief that interactive-relational spiritual experiences are inferior to mystical-unitive ones. This is an opinion, a theological stance, and lacks supporting evidence.

I’ve also raised this criticism of having one narrative of spiritual experience dominate discussions about psychedelics. So I’m glad to see Strassman bringing attention to the issues this involves, as it seems to be neglected in the psychedelic community and in psychedelic research. Ignoring or devaluing the interactive-relational state can be seen as restrictive, prejudiced, and as a failure to respect the diversity of psychedelic experiences and religious beliefs. As Strassman underlines:

Comparing unfavorably the interactive-relational experience with the mystical-unitive one results in regarding unfavorably religious traditions for whom the interactive-relational experience is fundamental; that is, the basis of their tradition. As Judaism is the most well-known religion basing itself on the interactive-relational — that is, prophetic — experience, this has resulted in Jewish beliefs sitting in the crosshairs of psychedelicists — academic and lay — who promote the universal mystical-unitive state.

Strassman also challenges the idea that it is the mystical experience that specifically drives the therapeutic benefits of psychedelics. Strassman suggests, conversely, that “any number of other experiences correlate just as strongly with outcome.” Indeed, there is research also showing that the emotional aspect of the experience is associated with improvements in mental health (including increased connection to one’s emotions, emotional breakthroughs, enhanced emotional regulation, and acceptance of emotional distress). Strassman continues:

For example, a recent study demonstrated an association between scores on the Mystical Experience Questionnaire (MEQ) and decreased alcohol consumption in alcoholics. The MEQ is a rating scale that quantifies elements of the mystical-unitive state and determines if one’s “mystical experience” is “complete” or “incomplete.” However, the correlation between a generic measure of drug-effect intensity was also strong. That is, the intensity of the experience, not its specific quality, was important.

People take and/or give psychedelics within the set and setting of a particular model. If researchers and subjects believe that…mystical experiences are curative, and if rating scales measure the attainment of the state, it is likely that the attainment of that state will relate to outcome. That is, the drug effect — and the rating scale that establishes its attainment — confirms the model.

When we believe that attaining a particular subjective experience is “how psychedelics work,” we may be veering dangerously close to “magical thinking.” That is, the belief that “all you need to do is reach this state and it doesn’t matter what your problems are. They will magically succumb to the effect of the state.”

You cannot simply argue that objective brain-function changes that occur in the mystical or any other specific state prove that such states are indeed how “psychedelics work.” This is because those brain changes may simply reflect the operation of a nonspecific brain response to the psychedelic experience — for example, its intensity. That intensity may be the critical factor more than the attainment of any specific mental state.

A Sceptical Take on Microdosing

Another approach I appreciate in Strassman’s latest book is scepticism towards microdosing — taking ‘sub-perceptual’ or non-psychedelic doses of psychedelics. Strassman refers to one scientific study as an example, published in Scientific Reports: “Adults who microdose psychedelics report health-related motivations and lower levels of anxiety and depression compared to non-microdosers”. These are the benefits microdosers have long been reporting, and this scientific study seems to confirm this. Yet we need to be sceptical about studies like this; as Strassman stresses:

The most important principle in evaluating studies like this is: Association does not prove causality…do the results of this microdosing study I just referred to mean that microdosing reduces depression and anxiety? Or does it mean that the less depressed and anxious you are, the more likely you are to microdose? In addition, survey studies poll those who expect benefit from microdosing. Why else would they be doing so in the first place? Again, we are dealing with a host of placebo-related factors — expectation, selection bias, and suggestibility.

Indeed, more recent research has found that expectancy effects, which contribute to the placebo response, may account for the positive outcomes of microdosing (see here and here). If you expect to feel better from microdosing, and then begin doing so, the chances are you will feel better. And if non-psychoactive or non-psychedelic, psychoplastogenic effects enhance the placebo response, as Strassman has proposed, this would produce even more substantial effects.

Furthermore, microdoses can act as an active placebo. Microdoses that are tiny — say, 5 μg (micrograms) of LSD — may produce no noticeable subjective effects. However, small or very small microdoses — 10–20 μg — could result in mental/physical effects, such as stimulation, which aren’t actually therapeutic, but if you notice them you might be convinced that the microdosing is working, thus enhancing the placebo response.

In terms of the safety of microdosing, there are concerns that following this practice on a long-term basis could carry a heart risk (see here and here). Strassman offers his own perspective:

A theoretical concern of daily use of classical compounds is their potential to damage heart values by chronic stimulation of the serotonin 2B receptor. However, this may be a more theoretical than real concern, since I am unaware of any reports of valvular heart disease in chronic users of ayahuasca, who may drink it several times a week for decades within ayahuasca-using churches and shamanic settings.

Other than this potential physical risk, what is the downside to microdosing? Does it matter if it relies on the placebo effect? While the ‘true’ benefit of microdosing may be low, the ‘actual’ benefit may be higher. Placebo effects are real and can be powerful, “and to the extent that we can recruit those effects to our advantage, it is worth doing so,” argues Strassman. Nonetheless, selling microdosing courses and coaching, which can come with a high price tag, becomes an ethical issue if microdoses only deliver benefits based on the placebo effect. This could be seen as misleading, exploiting the hype surrounding microdosing, for which there is a lack of data to make any definite conclusions.

In summary, I think Strassman offers us a balanced, concise, and highly practical guide on psychedelics, ideal as an introduction for those interested in these substances or who have already dipped their feet. At the same time, the information presented can help users — however experienced or interested they are in psychedelics — make wiser decisions when using these substances.

Originally published at on October 3, 2022.



Sam Woolfe

I'm a freelance writer interested in philosophy, ethics, psychology, and mental health. Website: