Microdosing Research: A Call for Rigorous Standards and Integrity
Written on
Microdosing studies of psychedelics have garnered widespread attention, but the scientific community must address the fundamental flaws in the current research landscape. The accumulation of small, low-quality studies does not contribute to meaningful scientific advancement; rather, it reinforces existing biases and poor research methodologies.
Are the glowing anecdotes shared by social media influencers and enthusiasts regarding the benefits of microdosing for mood and creativity merely the result of placebo effects? Initially, I approached this inquiry with an open mind, ready to accept a tentative conclusion based on existing literature, expecting it might lead to the familiar statement: “We do not know yet; further research is necessary.”
As an editor and science writing coach, I have long urged writers to move beyond generic calls for more research and instead draw specific, actionable conclusions. I often challenge authors to contemplate under what circumstances they might determine that no further investigation is warranted.
Authors should consider rephrasing critical research questions to make them more answerable or identify more pertinent questions. It might also be beneficial for researchers to postpone investigations until adequate resources are available for comprehensive, replicable studies.
Unfortunately, those captivated by vague or flawed concepts rarely heed such advice. It is hoped that individuals who are less invested in promoting these ideas will be encouraged to either withdraw from further involvement or redirect their efforts more productively.
During my research, I discovered a pivotal resource: a commentary by David Nutt, a respected authority on psychedelics, published in the 2019 Journal of Psychopharmacology. This commentary included insights from other notable experts.
What stood out was the consensus that credible research supporting the efficacy of microdosing is lacking. Even those who expressed enthusiasm for the practice were quick to clarify the absence of scientific evidence for its benefits. I found it surprising that no one suggested researchers should shift their focus to more compelling questions, which might have stronger preliminary support.
I also came across an insightful article by Milena Marnkovic, who reflected on the virtual 4th Interdisciplinary Conference on Psychedelic Research. She articulated a shared confusion regarding the state of microdosing research:
“Despite a dozen studies published recently discussing the alleged advantages of microdosing, researchers often present their work as unprecedented. They frequently note that their findings show no significant difference between placebo and microdoses, yet they insist more research is essential before concluding that microdosing lacks performance-enhancing effects. When will this certainty materialize?”
Researchers may find themselves unable to reject the null hypothesis (p > .05), indicating no difference between a psychedelic microdose and an inert placebo. However, failing to reject the null does not equate to proving it true.
It would be more convincing for researchers to conduct superiority trials, in which they delineate in advance the magnitude of difference needed between microdoses and placebos to establish superiority. If such a trial were to fail to reject the null hypothesis, confidence in the conclusion that microdosing offers no benefits would be stronger.
Regrettably, a superiority trial would require a larger participant pool than any microdosing study conducted to date.
I feel emboldened to express my previously reserved skepticism. Currently, the lack of resources and various challenges in psychedelic research render microdosing studies too small and methodologically flawed to yield informative results.
Neglecting these issues perpetuates poor research practices. Investigators attempting to generate novel findings under these unfavorable conditions may resort to selective reporting and pursuing statistically significant outcomes of p < .05.
Commentators who attempt to synthesize study results and identify patterns may also fall prey to the same pitfalls, mistaking noise for meaningful signals. Numerous examples of this can be found within the peer-reviewed literature.
We require fewer microdosing studies until conditions improve for high-quality research. Even when that time arrives, I anticipate that the findings will remain ambiguous. Negative results will likely fail to convince researchers or fervent self-experimenters that microdosing produces only placebo responses.
Microdosing Research: A Behavioral Science Perspective
Microdosing research focuses on human reactions to drugs; it fundamentally represents behavioral science rather than purely pharmacological inquiry. The crux of these studies lies in whether highly motivated participants can perceive the subtle effects of potent substances like LSD and psilocybin when taken in low doses that do not elicit dramatic psychological changes.
The ability of participants to interpret their own subjective experiences is central to this discussion. We already understand that psychological responses to full doses of psychedelics are influenced by numerous non-specific factors, not solely by the pharmacological effects of the substances.
The profound and enduring mental health benefits attributed to psychedelics depend heavily on the alignment of these non-specific factors within therapeutic contexts.
Clinical trials assessing psychedelics as mental health treatments require extensive counseling before, during, and after drug administration. Nevertheless, previous experiences with psychedelics and the persuasive influence of social media, along with the reputation of the therapeutic environment, remain significant factors.
Unlike many other drugs, the non-specific influences are inadequately controlled in studies where an inert substance is ingested under identical conditions. Traditional randomized controlled trials (RCTs) often involve blinding both researchers and participants regarding whether an active treatment or placebo is administered. However, the immediate effects of full-dose psychedelics quickly reveal which condition participants are in.
The situation becomes more intricate with microdosing, where the doses are intentionally reduced to mitigate intense effects. Some experienced users may learn to recognize subtle indications of having consumed a microdose, thus unblinding themselves, even if the microdose does not lead to significant changes in mood or cognition.
These seasoned users may generate personal placebo effects by interpreting minor psychological cues that lack correlation to any objective measures of enhanced cognition or creativity, momentarily feeling better simply by confirming their expectations.
Research Quality Concerns in Microdosing Studies
Recent microdosing research has been marred by several issues: small sample sizes, biased participant recruitment, unrepresentative samples of experienced individuals eager to showcase their perceived skills, inadequate experimental controls, brief follow-up periods, and lapses in participant retention.
Many of these challenges stem from the significant obstacles that complicate credible research on microdosing. These hurdles include the criminalization of psychedelics in many regions, limited access to substances of known purity and dosage, scant funding for research, and the fact that psychedelic use is largely confined to a small, experienced subset of the population willing to risk legal repercussions.
I have participated in the design and review of clinical trials in various NIH initiatives, and acceptable trials require expertise, resources, and substantial funding—none of which are readily available to those studying microdosing.
Insufficient Rigor in Microdosing Investigations
Microdosing research often overlooks the established principles and standards necessary for credible and reproducible scientific inquiry. It is rare for researchers to pre-register their study designs prior to participant recruitment, and they often do not adhere to their initial proposals when reporting findings, making comparisons to original plans impossible. Journal editors and reviewers frequently neglect to verify pre-registration or let researchers evade accountability too easily.
When conducting controlled clinical trials, researchers are expected to publicly commit to essential study details in advance, including clearly defined hypotheses, primary outcomes, participant numbers, and methods for minimizing bias. Plans for blinding researchers and participants need to be explicitly stated, as do strategies for maintaining integrity during data analysis.
Protocols can be archived in clinical trial registries, and journals can publish comprehensive details. Additionally, ethical research mandates that all participants are fully informed of risks and benefits and consent to participate without coercion or penalty for withdrawing.
While these requirements may appear tedious and bureaucratic, they serve to uphold scientific integrity. The cavalier self-experimentation often showcased by social media influencers contrasts sharply with the rigorous standards expected in genuine scientific research.
These regulations are intentionally restrictive, helping to minimize bias and control researchers' degrees of freedom in their studies, fostering confidence in the reported results.
Issues of poor research practices are not exclusive to psychedelic studies; they permeate various scientific fields, contributing to the ongoing reproducibility crisis and eroding trust in research integrity. A systematic review of early COVID-19 studies revealed that 80% were at risk of bias due to factors such as small sample sizes, inadequate follow-up, and flawed patient selection.
Many academic careers have been built on exploiting research flexibility to produce consistently favorable results, whether or not there was intent to deceive. Researchers often find themselves misled by noise rather than meaningful signals in flawed studies, compromising the integrity of their findings.
Scientists can easily succumb to bias and self-deception, especially under pressure to produce answers from available data or when their professional standing is at stake. Many questionable research practices arise from researchers conforming to prevailing biases and mimicking what they perceive others are doing to achieve publication.
Postscript
I do not aim to dismiss microdosing research entirely, but I feel no obligation to commend what I perceive as shortcomings. Future discussions will include constructive suggestions, alongside evidence supporting my claims that recent microdosing research results are often premature, exaggerated, or misleading.
For readers eager to explore these topics further, I encourage caution: be wary of exploiting the flexible interpretations that microdosing researchers and commentators have frequently adopted.
Focusing selectively on positive findings and employing questionable statistical practices can ultimately lead to accusations of violating scientific ethics. What may appear as compelling findings may well be mere noise.