by Isabelle Grabski
figures by MacKenzie Mauger

When you hear the term “psychedelics,” you might think of hallucinogenic and mystical experiences. Popular psychedelics include LSD (lysergic acid diethylamide), magic mushrooms (containing the psychedelic psilocybin), and DMT (N,N-dimethyltryptamine, part of the spiritual medicine ayahuasca), all of which can cause intense psychological experiences colloquially known as “trips.” However, there is an emerging push within the scientific community to study these known recreational drugs as treatments for psychiatric conditions that could potentially be more effective with fewer side effects than traditional psychiatric medications.

This psychiatric interest in psychedelics is nothing new: in the 1950s and 60s, thousands of patients were experimentally given various psychedelics to treat alcoholism and other mental health disorders. It was only when the U.S. 1971 Controlled Substances Act was passed that much of this research came to a grinding halt. After a nearly 40 year pause in this work, scientists are beginning to resume this research. Landmark trials from 2014 and 2016 have already shown that LSD and psilocybin respectively improved mood and anxiety in patients with various life-threatening illnesses for up to a year after treatment, with many more studies underway. 

Alongside this renewed interest in psychedelics is an increasing popular approach known as microdosing. Microdosing is when patients take a dose of psychedelics that is too small to produce any perceptible effects, generally between 5 to 10% of a standard dose. Despite the small amount of drug taken, there is evidence to suggest that microdosing can still bring about some of the benefits observed with full-dose treatment without causing the intense and sometimes negative hallucinatory experiences. Nevertheless, some scientists are skeptical that these results are spurious, or worse, that microdosing may even be harmful. 

The potential mechanisms of microdosing

Psychedelics are known to primarily affect serotonin, a chemical messenger that helps nerve cells communicate with other cells in the body. Serotonin is popularly portrayed in the media as being responsible for happiness, but in reality, its functionality is much more complex and widespread. In fact, serotonin is associated not just with mood, but also with cognition, sleeping, eating, thermoregulation, memory, and even physiological processes like vomiting. 

Since serotonin is so widely important in the body, there are molecular regions called serotonin 2A receptors located throughout the central nervous system. Chemicals can bind to these receptors in order to stimulate or block the serotonin system. Although this mechanism is not fully understood, these receptors are believed to be the targets of psychedelics. One hypothesis is that when these drugs bind to the serotonin 2A receptors, the brain cortex, responsible for cognitive, sensory, and motor functions, becomes excited, ultimately leading to hallucinations and other effects. Some studies have even found psychedelics to increase neuroplasticity, which leads to the creation of more connections between neurons and could potentially explain the novelty of these intense psychological experiences. Microdosing is thus theorized to work in the same fashion, albeit to a milder degree.

Some research also suggests that microdosing may work by fighting inflammation in the body. Inflammation is the result of the body’s immune system protecting you from infection, but can cause damage when the immune system is activated without any real danger. Long-lasting or chronic inflammation is implicated in a number of disorders, including auto-immune diseases and even mental health conditions like depression. Studies on animals have shown anti-inflammatory effects from microdosing, leading some scientists to speculate that this could point to another potential mechanism of action.

The early research on microdosing

Research on microdosing is still new, and thus there are a relatively limited number of studies available to understand its effects on humans. As for 2020, the first clinical trials exploring microdosing as a treatment for mental health conditions are now underway. Until those results are available, most human research has been limited to surveys of those who have tried microdosing on their own.

These survey results have largely been positive. For example, in one international survey, 79% of respondents reported improvements in their mental health after microdosing. In other surveys, participants described experiencing better creativity and productivity, in addition to decreased levels of anxiety and depression. Although promising, these results must be taken with a grain of salt. Because these are surveys, there is no way to confirm or enforce the dosage, scheduling, and type of psychedelic used, and indeed, some studies have already noted that experiences can vary depending on these factors. Moreover, these results are susceptible to the so-called placebo effect, in which just the knowledge that you are taking some kind of a treatment can cause you to experience benefits, even if the treatment is not directly causally related to the effects. If this is the case, then microdosing might have very little to do with the reported improvements.

There has been some animal research to back these survey findings. In one prominent study, researchers at UC Davis administered microdoses of DMT to rats and observed responses similar to those arising from antidepressants. Both microdosed and untreated rats were placed in a pool with no escape, and the microdosed rats continued swimming in an attempt to escape after the untreated rats had already given up. This suggests some degree of improved resilience and optimism in the microdosed rats. Another study microdosed some rats with psilocin (another psychoactive component of magic mushrooms) and others with a different psychedelic called ketamine, and found both to mildly alleviate anxiety in rats experiencing a stressful maze. 

Results from animal research, of course, are not automatically transferable to humans. Nevertheless, these findings suggest that beneficial effects from psychedelics are plausible, spurring greater motivation for ongoing clinical trial research. 

Safety concerns

The question, however, is not just whether microdosing is effective, but also whether it’s safe. Until clinical trials are complete, we will not have a full answer, but there is already research to suggest that certain people may be vulnerable to negative side effects. In particular, some people may have psychotic episodes or other mental health issues triggered by taking psychedelics, especially if they have a history of psychosis or pre-existing risk for serious psychiatric disorders like schizophrenia or bipolar disorder. Although microdosing involves a much lower amount of the drug, it is still possible that the negative consequences may hold true.

Furthermore, survey research has revealed side effects specific to microdosing. Some people have reported unwanted symptoms such as migraines, over-stimulation, difficulty sleeping, physical discomfort, and sometimes even anxiety, despite the promise of these drugs to alleviate it. It is not yet well-understood how these symptoms relate to the exact dosage, scheduling, and type of drug taken, but they do show that negative effects can potentially occur. 

All in all, it is still far too early to say whether microdosing is a viable way to harness the potential of psychedelics for mental health treatment. Much more research needs to be done to understand not only how it works, but what the potential consequences and side effects are. If clinical trials confirm the safety and efficacy of microdosing psychedelics, these could represent a new avenue for mental health treatment. 

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Isabella Grabski is a 3rd-year Ph.D. student in Biostatistics at Harvard University.

MacKenzie Mauger is a second-year Ph.D. student in the Biological and Biomedical Sciences program at Harvard Medical School, where she is studying the role of condensate formation in epigenetic memory. You can find her on Twitter as @MacKenzieMauger

Cover Image: “Beach Mushrooms” by vladeb is licensed under CC BY-ND 2.0

For More Information:

• This review article summarizes the beneficial and harmful effects of microdosing.
• Check out this article to learn about the potential mechanisms of microdosing. 
• This article summarizes the current state of microdosing for psychiatric treatment.
• To learn about potential therapeutic benefits of microdosing psychedelics, read this scientific paper.