Microdosing psychedelics: More questions than answers? An overview and suggestions for future research
Kim P.C. Kuypers, Livia Ng, David Erritzoe, Gitte M. Knudsen, Charles D. Nichols, David E. Nichols, Luca Pani, Anaïs Soula and David Nutt
Journal of Psychopharmacology, 2019, 1-10.
Background : In the past few years, the issue of ‘microdosing’ psychedelics has been openly discussed in the public arena where claims have been made about their positive effect on mood state and cognitive processes such as concentration. However, there are very few scientific studies that have specifically addressed this issue, and there is no agreed scientific consensus on what microdosing is.
Aim : This critique paper is designed to address questions that need to be answered by future scientific studies and to offer guidelines for these studies.
Approach : Owing to its proximity for a possible approval in clinical use and short-lasting pharmacokinetics, our focus is predominantly on psilocybin. Psilocybin is allegedly, next to lysergic acid diethylamide (LSD), one of the two most frequently used psychedelics to microdose. Where relevant and available, data for other psychedelic drugs are also mentioned.
Conclusion : It is concluded that while most anecdotal reports focus on the positive experiences with microdosing, future research should also focus on potential risks of (multiple) administrations of a psychedelic in low doses. To that end, (pre)clinical studies including biological (e.g. heart rate, receptor turnover and occupancy) as well as cognitive (e.g. memory, attention) parameters have to be conducted and will shed light on the potential negative consequences microdosing could have.
Keywords : Psychedelics, microdosing, psychoactive substances
Psychedelics are a class of psychoactive substances that induce complex behavioural, psychological and physiological effects primarily through activation of serotonin 5-HT2A receptors. In the past few years, the issue of ‘microdosing’ psychedelics has been openly discussed in the public arena with several books (Cruz, 2017; Kumar, 2016; Waldman, 2017) claiming value to the authors who tried this concept. However, there are very few scientific studies that have specifically addressed this issue, and there is no agreed scientific consensus on what microdosing entails (Cameron et al., 2019; Horsley et al., 2018). This paper is designed to address questions that need to be answered by future scientific studies and to offer guidelines for these studies. Although a number of classic psychedelics exist, two of them, lysergic acid diethylamide (LSD) and psilocybin, are allegedly most frequently used to microdose. The following review focuses predominantly on psilocybin due to its proximity for a possible approval in clinical use and short-lasting pharmacokinetics (Passie et al., 2002) in comparison with LSD (Dolder et al.,v 2017). However, where relevant and available, data for other psychedelic drugs are also mentioned.
As early as the 16th century, low doses of psilocybin, ‘teonanacatl’ or sacred mushroom, were used medically (Schultes, 1940). Bernardino de Sahagún, a Franciscan friar during the period of the Spanish conquest of the Americas (1519–1521), reported that, ‘teonanacatl were … medicinal for fevers and for rheumatism. Only two or three need to be eaten. Those who eat them see visions and feel a faintness of the heart. And they provoke lust to those who eat a number, or even a few, of them’. However, by 1640, 94% of the Aztec population was wiped out and alongside them, the traditions involving ‘teonanacatl’. Of note, the mentioning of visions here suggests this ancient ‘lowdose’ use does not refer to what is currently seen as microdosing, something that will be addressed below.
Psychedelic studies underwent a significant expansion following the discovery of the mind-altering properties of LSD by Albert Hofmann in 1943 (Hofmann, 1970). The subsequent growth of psychedelic use allegedly had a profound effect on innovation in science and technology. A popular example is that of Francis Crick, one of the co-discoverers of the double-helix structure of DNA, who used LSD, though this use was never confirmed nor denied by him (Roberts, 2008). Furthermore, Kary Mullis, who discovered a means to automate the polymerase chain reaction, claimed that the idea came to him after using LSD (Doyle, 2002). These discoveries greatly advanced the field of genetic research (Luke, 2006). In this atmosphere of innovation, Frederick Terman was appointed as Provost of Stanford, 1955–1965. During his tenure, Terman ‘set out to create a community of technical scholars in Silicon Valley’ (Leslie and Kargon, 1996). This community developed alongside the psychedelic capital of the world, San Francisco, and over time technology and psychedelics began to merge. By 2005, the founder of Apple and one of the most influential figures in Silicon Valley, Steve Jobs, highlighted that LSD had played a pivotal and transformative role in his life (Dormehl, 2012).
Although there was accumulating evidence to suggest that the intake of psychedelics led not only to hallucinations but also to an improvement of cognition and creativity, scientific progress in the field was prohibited by government agencies on account of the growing political concern over the recreational use of psychedelics (Belouin and Henningfield, 2018). Thus, the only study investigating psychedelics in problem solving was ended by the US Food and Drug administration (FDA) in 1966 (Harman et al., 1966). However, James Fadiman, a young researcher in this study, continued his research after the UN Convention on Psychotropic Substances of 1971 banned psychoactive substances and bundled his knowledge into a book, which now acts as a guide for those interested in microdosing. His book The Psychedelic Explorer’s Guide: Safe, Therapeutic, and Sacred Journeys (Fadiman, 2011) published in 2011, is often referred to as a protocol for those practising microdosing. Of note, no study to date has revealed statistically significant effects of microdosing on creativity under placebo-controlled circumstances (Passie, 2019).
Although microdosing became prominent due to the belief it improved cognition, a growing number of individuals began to microdose psychedelics to improve conditions of pain (Johnstad, 2018), cluster headache or migraine (Andersson et al., 2017). It seems that the efficacy of microdosing may derive from its nonpsychedelic dose range, which provides treatment without affecting cognition. Individuals also reported relief of pain with a long-term psychedelic microdosing regimen (Johnstad, 2018). Thus, psychedelic microdosing might constitute a different paradigm to single psychedelic therapeutic sessions with macrodoses where the nature and content of the experience plays a key role in predicting therapeutic outcome (Roseman et al., 2018; Schenberg, 2018). However, many questions remain about the definition, safety, potential mechanism and future research involving microdosing.