Tiny Doses, Big Samples: The largest microdosing study to date

Last week, new research published in Nature: Scientific Reports added to the growing number of studies reporting the effects of sub-hallucinogenic microdoses of psychedelic compounds. Previous findings have been unclear and contradictory, as we described in a previous blog post. So, what did this new paper examine, and what does it add to the body of knowledge?

The international research team – headed by scientists at the University of British Columbia, alongside, among others, Beckley/Maastricht collaborator Kim Kuypers; Pam Kryskow, medical lead on the Roots To Thrive Ketamine Assisted Therapy program; and renowned mycologist Paul Stamets – used the world’s first mobile app for gathering psychedelic microdosing data, Microdose.me, developed by Quantified Citizen to enable researchers to conduct observational research in people who microdose psychedelics, by securely collecting data and allowing participants to perform surveys and assessments without the need for in-person attendance at a lab or clinic.

This novel approach meant the researchers were able to recruit the largest sample of participants in any psychedelic study to date, with over 8500 participants from 75 different countries. Participants were asked whether or not they were currently microdosing, and if they had any psychological, mental health or addiction concerns. Mental health was assessed using the DASS-21 scale, to obtain measures of depression, anxiety and stress levels.

When these scales were compared between microdosers and non-microdosers reporting mental health concerns, it was found that microdosers exhibited lower scores on all three, indicating that microdosing may be beneficial for treating certain mental health conditions.

However, there are some important caveats that must be considered before coming to any conclusions. An important confound is that people who microdose typically do not limit their use to small doses, and therefore a vast majority of participants were mixed users of both micro- and macro-doses. As a result, it’s difficult to tease apart the contribution of microdosing to mental health from that of full doses. As the number of participants who only had experience with microdosing was too small, the authors decided to instead compare the larger subgroup of people who reported mixed psychedelic use to a group only using large doses. They found that the mixed users had better mental health scores than the ones who only used full doses. These results suggest that microdosing might have an important part to play in the management of mental health, either on its own or when used in combination with larger doses. Future studies should attempt to clarify the extent to which microdosing has an effect in its own right, possibly by more precisely characterising lifetime exposure to large doses.

Another interesting observation was that of lower alcohol and tobacco use among the microdosing group. This finding is consistent with previous studies having reported healthier lifestyles in psychedelic users (e.g. Texeira et al 2021), but the extent to which it relates to microdosing more specifically remains to be demonstrated. In addition, given the higher occurrence of alcohol abuse in rural areas, and the lower percentage of microdosers there, it would be interesting to compare substance use within a subpopulation of urban/suburban residents.

While these findings are positive overall, and have been received with some optimism, they have not been without controversy. Some have pointed to the lack of placebo control and an absence of any mention of expectancy effects in the paper as reason to dismiss the results. While it is certainly possible that observed benefits were due to placebo, this was outside of the remit of the paper, which aimed to compare the practices, motivations and mental health of microdosers and non-microdosers. Furthermore, the paper does address response bias, which is more relevant than placebo or expectancy effects in the context of cross-sectional designs.

It’s important to bear in mind that this research was purely observational. As a result, data was self-reported by participants, using a widely-used and standardised scale. This means that there was less experimental control than would occur in a lab-based study. However, a benefit of this approach is that these researchers were able to investigate microdosing in a very ecologically valid manner. Participants reported the effects of their real-world microdosing practice using their own preferred doses and schedules, rather than a dosing regimen specified by an experimenter. Non-microdosers were encouraged to participate, and the relative ease of taking part meant that many submitted data throughout the study period. Although contrasting these two groups provides intriguing data, due to the observational nature of the research, it is only possible to establish correlations between microdosing and specific positive effects, rather than any causality.

Participant bias also represents an area of concern, as subjects self-selected for inclusion in a microdosing study and are therefore more likely to hold positive views towards the practice. This is, unfortunately, a problem widespread across the field of psychedelic science at this point, and is difficult to address in a study of this kind. But it is nonetheless worth noting that, while it is widely accepted in the psychedelic research field that the mindset with which people enter a psychedelic experience (one’s ‘set’), plays a key part in its quality and outcome, this same mindset is being disregarded as expectation bias when it comes to lower doses. Perhaps it is time to stop creating an illusory dichotomy between microdoses and full doses and, rather, recognise their similarities.

Other findings of note were the apparently widespread use of a practice known as ‘stacking’ – More than half of the microdosing sample reported combining their psilocybin microdoses with other, non-psychedelic substances such as Lion’s Mane mushrooms or chocolate. However, this was not found to have any influence on mental health outcomes.

In spite of certain limitations, this paper makes a solid contribution to the knowledge of microdosing and its real-world use, including its combination with other substances – a widespread practice that has not been well documented to date. It makes use of a substantially larger sample of microdosers than has been examined by prior research, and furthermore, a large and comparable group of non-microdosers for comparison. Despite promising findings of improvements to depression, anxiety, and stress in microdosers, it’s important to acknowledge, as the authors do, that the effects on psychiatric symptom severity were only small, albeit statistically significant.

It is easy to forget that we are, in the words of Amanda Feilding, at the very foothills of understanding the effects of psychedelics, and there is widespread eagerness to reach the summit. This is slow-going, however, and observational studies like this one, with large numbers of participants, are a good staging point from which to ascend further.

At the Beckley Foundation, we are convinced of the value of such ‘grassroots’ approaches to psychedelic research, and we will be collaborating with Quantified Citizen and the international team of researchers involved in this study on the second implementation of the Microdose.me remote microdosing research platform. As with any updates, this new version will address some existing bugs, including the implementation of a novel placebo control procedure.

More on this soon!

Jon Sharp & Valerie Bonnelle