This review (2020) examines the viability of microdosing psychedelics as a method to improve cognition and well-being. Available evidence indicates a variety of (perceived) benefits, including improvements in mood, focus, and creativity, with some people experiencing no discernible effects or expressing concerns about selective negative consequences like increased anxiety. However, most insights stem from observational studies using convenience samples that are biased or unrepresentative of the general population.
Psychedelic substances are currently experiencing a renaissance in interest for both therapeutic as well as recreational applications. It has been proposed that microdosing, i.e., ingesting sub-perceptual doses of a psychedelic, could confer some of the benefits of these substances to users while minimizing the risks associated with full-dose use. This review aimed to summarize and examine the extant literature on psychedelic microdosing. Exploratory evidence published to date indicates a variety of benefits reported by microdosers including improvements in mood, focus, and creativity, with some null reports, and a minority of people reporting selective negative consequences such as increased anxiety and physiological discomfort. Methodological limitations of current evidence, however, make definitive conclusions hard to draw. Recommendations for future research are given.
Interest in psychedelic substances has resurged for both therapeutic and recreational purposes, yet rigorous research remains limited because of legal restrictions and stigma. Earlier studies suggest full-dose psychedelic experiences can produce therapeutic benefits for conditions such as substance dependence, end-of-life anxiety, depression and OCD, and recreational use has been associated with increased openness, prosocial behaviour, positive affect and creative problem-solving. At the same time, full-dose experiences can be challenging and, in rare cases, lead to persistent adverse outcomes such as panic attacks, flashbacks and hallucinogen persisting perception disorder (HPPD). Microdosing, commonly defined in the paper as ingesting between one tenth and one twentieth of a typical psychedelic dose so that effects are subperceptual, has been proposed as a way to capture some benefits while reducing risks associated with full-dose use. Bornemann sets out to summarise the extant literature on psychedelic microdosing to evaluate whether it is a viable strategy to enhance cognition and well-being and to identify potential risks. The review places qualitative and quantitative evidence on a spectrum of evidential strength and aims to clarify where more rigorous research is needed.
Papers cited by this study that are also in Blossom
Anderson, T., Petranker, R., Christopher, A. et al. · Harm Reduction Journal (2019)
Anderson, T., Petranker, R., Rosenbaum, D. et al. · Psychopharmacology (2019)
Andersson, M., Persson, M., Kjellgren, A. · Harm Reduction Journal (2017)
Aronson, H., Silverstein, A. B., Klee, G. D. · JAMA Psychiatry (1980)
Bornemann conducted searches in Scopus, PubMed, ProQuest, Google Scholar and an additional search engine using the terms: microdosing AND (psychedelics OR lsd OR psilocybin OR mdma OR dmt OR mescaline OR psychoactive). The initial search was performed on 11 May 2019 and was amended on 12 November 2019, with further ad hoc searches to locate full-dose psychedelic studies that included microdose control conditions. Inclusion criteria required studies to report novel results, be published in scientific venues, and involve human microdosing effects; review articles, popular-press pieces and animal studies were excluded. Titles and abstracts were screened for relevance, and 21 documents met inclusion criteria and were read in full. The final corpus comprised eleven observational studies, one quasi-experimental study, and nine experimental studies. Bornemann notes that much of the existing evidence is qualitative and structures the review subsections in order of increasing evidential strength, indicating which cited studies are qualitative versus quantitative. An overview table is referenced in the text but is not present in the extracted material.
General effects: Early observational and qualitative reports commonly describe microdosing days as pleasant, with one self-study protocol (no sample size provided) reporting roughly 80% of narrative accounts as positive or neutral. An online questionnaire administered to psychedelic-focused forums (n = 1116) found about one fifth of respondents who reported microdosing also reported negative effects, described as mainly psychological and acute. Interview-based and forum-analysing qualitative studies generally reported mostly positive experiences—particularly improvements in depression and anxiety for some respondents—alongside reports of challenges such as accidental overdosing, concerns about long-term consequences and problems related to illegality and stigma (for example, measuring doses, hiding the practice, and uncertain substance purity). One study of college students reported that almost 69% of past-year microdosers indicated at least one negative consequence, with hallucinations reported by 44.2%, though the paper notes these may reflect dosing errors rather than microdosing per se. Creativity: Several qualitative analyses, including a content analysis of Reddit posts, found frequent self-reports of enhanced creativity. Quantitatively, one online questionnaire study reported higher creativity scores among current and former microdosers relative to non-microdosers, though directionality is unclear. The single quasi-experimental study assessed festival attendees on measures of divergent and convergent thinking and reported significant improvements on both tasks under an estimated microdose of psychedelic truffles, while fluid intelligence did not change; this study lacked a placebo control and laboratory conditions. By contrast, other experimental work has reported null results: a double-blind, placebo-controlled study of LSD in 20 volunteers (0, 6, 13, 26 μg) found no robust creative performance differences except a marginal change at the highest dose (which produced noticeable subjective effects and hence may not be a true microdose), and at least one observational study and other experimental trials reported no significant creativity changes. Overall, evidence on creativity is mixed. Focus and productivity: Anecdotal and qualitative reports, drawn from interviews, forum analyses and questionnaires, commonly describe increased productivity, better focus and reduced procrastination among microdosers, though some accounts report impaired focus. One longitudinal observational study that collected daily e-mails (n = 98) and follow-up questionnaires (n = 63) reported reduced distractibility and increased absorption at a 6-week follow-up, offering some systematic evidence for longer-term effects. Experimental placebo-controlled studies have generally been null for working memory, focus and productivity, apart from marginal increases in vigour at higher doses that may exceed microdose ranges. Studies administering multiple low doses of LSD (placebo, 5, 10, 20 μg) to older adults showed minimal cognitive effects and dose-related increases in vigilance reduction, dizziness and sleepiness; confinement to bed during administration was noted as a possible confound. Time perception studies yielded inconsistent results: one LSD microdose study found overestimation of supra-second intervals in the 2000–4000 ms range, whereas other research with psilocybin microdoses reported increased instability of internal time representation. Mood and general well-being: Qualitative accounts frequently describe elevated mood, increased energy, greater openness and improved social relations. Quantitative cross-sectional work reported lower dysfunctional attitudes, reduced negative emotionality and increased measures such as wisdom and open-mindedness among current and former microdosers compared with non-microdosers, though causality is uncertain. One longitudinal study reported decreases in stress at 6 weeks but also increases in neuroticism in some participants. Two higher-dose clinical studies that included low-dose arms provided mixed information: a low-dose psilocybin condition was attributed some positive behaviour and mood changes at 6 months but lacked a placebo; another psilocybin study with a full placebo arm observed slight drowsiness, greater sensitivity and intensification of pre-existing mood states in the lowest dose (45 μg/kg, N = 8) amidst mostly null mood findings. Qualitative reports also indicated decreased use of substances such as caffeine, alcohol and tobacco, and preliminary qualitative evidence suggested improvements in OCD, PTSD and narcolepsy. A quantitative online sample (N = 410) rated microdosing as more effective than conventional treatments for conditions such as ADD/ADHD and anxiety disorders in their self-report comparisons. An experimental psilocybin microdose study reported some OCD symptom improvement without a placebo control and without dose-condition differences, raising expectancy concerns. Depression: Several qualitative self-report studies suggested anti-depressive effects. In clinical research on cancer patients that compared high and low psilocybin doses, 32% of patients who received the low dose met a clinical response criterion for depression (defined as 50% reduction from baseline), although the low-dose effect was much smaller than the full-dose effect. Anxiety: Findings for anxiety are inconsistent. Qualitative reports include both relief from social anxiety and increases in anxiety; one survey found 35% of past-year microdosers reported at least one episode of increased anxiety. When asked directly, 59.2% of respondents in one study reported that microdosing had helped with anxiety. Quantitatively, a low-dose arm in cancer-patient psilocybin research showed a 24% clinical response rate for anxiety but also that 15% experienced an anxiety episode during the session. A small study using 20 μg of LSD as a control condition (low-dose) reported slight increases in state and trait anxiety, but the low-dose sample was very small (n = 4). Overall, the net effect of microdosing on anxiety remains unclear. Physiological effects: Most physiological data are qualitative. Reports about tolerance are mixed, with some users reporting buildup and others not; ingestion a few times per week did not seem to produce substantial tolerance in one qualitative account. Some participants reported reductions in migraine frequency, supported by qualitative reports of subhallucinogenic doses used for chronic migraine and cluster headache relief; a quantitative survey found participants rated microdosing as more effective than conventional options for such nervous system conditions. Conversely, qualitative and some experimental reports noted insomnia, increased heart rate, headaches, nausea and general physiological discomfort. Mild headaches were observed in an LSD microdose experimental study, and a full-dose study with a low-dose arm reported physiological discomfort in 12% of patients in the low-dose condition. No systematic long-term physiological studies were reported; the paper flags cardiovascular safety (noting that LSD and psilocybin are 5-HT2B agonists potentially implicated in valvular heart disease) as a future research priority.
Bornemann interprets the body of evidence as indicating a variety of potential benefits of microdosing, including improvements in mood, focus and creativity, while acknowledging that some people report no benefits or selective negative outcomes such as increased anxiety. The discussion highlights substantial methodological limitations across the literature: many studies use convenience samples that are likely biased, qualitative and cross-sectional designs that limit causal inference, small sample sizes in experimental arms, lack of placebo controls in several investigations and the near absence of long-term follow-up data. One consequence of sampling bias is potential underrepresentation of people who tried microdosing and stopped because of negative or absent effects. Placebo effects are discussed as a significant unresolved issue. Two arguments against a purely placebo explanation are noted: one study reported specific patterns of dosing and effects that the authors judged unlikely to arise solely from expectancy, and another found no association between participants' stated expectations and their reported effects. Conversely, other investigators observed that many reported advantages were also described as disadvantages by different participants, consistent with strong expectancy or contextual influences; the paper also notes that individual genetic and epigenetic differences might account for heterogeneity in responses. Considering the placebo-controlled work so far, Bornemann observes a trend that more rigorous studies yield more modest or null results. Questions about mechanisms and dose equivalence are raised. Although microdoses use the same active substances as full doses and therefore may engage similar receptor systems, reported phenomenology and tolerance patterns do not necessarily mirror full-dose effects. The paper suggests neuroimaging studies—such as investigations of default-mode network (DMN) effects—could clarify whether microdoses produce brain changes analogous to those hypothesised for therapeutic full-dose administrations. A further concern is inconsistency in the operational definition of a microdose: experimental studies reviewed define very low psilocybin doses across a wide range (for example, 12 μg/kg to 45 μg/kg), and some higher 'low-dose' conditions produce perceptual effects that violate subperceptual definitions. Bornemann recommends standardised experimental procedures to resolve dose-range ambiguities and to identify a dose that maximises putative benefits while remaining subperceptual. Finally, practical barriers to strong research—legal restrictions, stigma and the high cost of legally acquiring substances—are emphasised, and the author concludes that although preliminary findings are promising, caution is warranted and future work should prioritise double-blind, placebo-controlled experimental paradigms and longitudinal studies.
Despite their continued illegality in most parts of the world, many have observed that psychedelic substances have been experiencing a resurgence of interest in both therapeutic as well as recreational applications in recent years. Good research remains scarce and difficult to do, owing to the substances' legal status and lingering social stigma, but slow progress is being made. Therapeutically, recent research indicates that psychedelics could play a beneficial role in the treatment of substance dependence, end-of-life anxiety and depression, treatmentresistant depression, and obsessive-compulsive disorder (OCD;. Recreationally, psychedelic use has been associated with increases in openness, prosocial behavior and attitudes, positive affect and emotion, and boosts in creativity and problem-solving ability, as well as mystical experiences capable of effecting lasting changes in subjective evaluations of personal meaning and significance. Despite these promising results, psychedelic trips can also be immensely challenging experiences, and, in rare cases, have been associated with enduring psychological problems like panic attacks, flashbacks, and hallucinogen persisting perception disorder (HPPD;. Although most studies documenting negative effects to date have emphasized the relatively low risk compared to other drugs, the intense experiences occasioned by full-dose psychedelic use are not always desirable. In contrast, microdosing is the practice of ingesting subperceptual doses of a psychedelic, usually defined as between one tenth and one twentieth of a normal dose. Researchers have proposed that this practice may provide a strategy to access the potential benefits of these substances while minimizing the risks associated with full-dose use. The present paper summarizes the literature on microdosing in order to investigate whether it can be a viable strategy to improve cognitive functioning and well-being, and to analyze any potential risks that may be associated with the practice.
In order to find relevant studies, I searched Scopus, Pub-med, ProQuest, Google Scholar, and sEURch for the following search terms: microdosing AND (psychedelics OR lsd OR psilocybin OR mdma OR dmt OR mescaline OR psychoactive). The search was originally CONTACT Joel Bornemann jaolb@web.de Erasmus School of Social and Behavioural Sciences, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands performed on 11 May, 2019, and amended on 12 November, 2019. Additional ad hoc searches were performed at a later date to identify full-dose psychedelic studies that included a microdose control condition. Titles and abstracts were read to determine the relevance of the studies to the present research question. Studies were excluded if they did not report novel results (e.g., review articles), if they were not published in a scientific journal (i.e., popular press), and if they did not involve the effects of microdosing psychedelics on humans (e.g., animal studies). Twenty-one documents met inclusion criteria and were read fully. Additional searches of the reference lists of selected studies did not yield further sources. The final selection of sources consists of eleven observational studies, one quasi-experimental study, and nine experimental studies. An overview of all included publications can be seen in Table. Due to the relative paucity of research in this area, much of the evidence to date remains qualitative in nature. Since qualitative data should be treated as exploratory, and only quantitative data as possessing the inferential strength to confirm or disconfirm hypotheses, the subsections of this review are structured in order of increasing evidential strength, and indications have been added to clarify the quantitative or qualitative nature of every cited study.
The general effect of a psychedelic microdose has been described as "a really good day"). Although information is scarce, a number of observational, qualitative studies have provided preliminary statistics on the distribution of general effect patterns in their respective populations. Specifically,designed a website offering a microdosing protocol for people interested in conducting a self-study. The protocol recommended microdosing every third day (i.e., a microdosing day followed by two non-microdosing days) for a period of one month. Among the hundreds of participants that have sent in narrative reports (a specific number of participants is not provided), they report that roughly 80% of accounts were positive or neutral in content. Another recent study involving an online questionnaire administered to volunteers on psychedelic-focused online fora (n = 1116) reported that about one fifth of participants who reported microdosing also reported experiencing negative effects. Unfortunately, the study did not specify what those negative effects were, beyond stating that they were more commonly psychological rather than physiological, and limited to the acute. Additionally, the study found that the most commonly reported reason for stopping a microdosing practice was not the experience of negative effects, but rather the feeling that the practice was ineffectual.interviewed 21 participants recruited through internet fora and noted that patterns of results became clear, so that new information was deemed unlikely to emerge. He reported mostly positive experiences, especially in the domains of depression and anxiety, among some null reports. However, he also reported a number of challenges participants faced. Among these, besides overdosing experiences and concerns about longterm consequences, were reports of backfiring effects associated with more long-term use. More precisely, some participants felt that the benefits obtained by microdosing early on actually reversed and served to exacerbate their mental health problems after a longer period of use., investigating self-reported comorbid drug use in college students, found that almost 69% of people who reported microdosing in the past year also reported at least one negative consequence of the practice. However, similar to the overdosing concerns reported by, the most commonly cited negative consequence was the experience of hallucinations (44.2%). Since these are most likely a result not of microdosing per se, but rather of a failure to dose correctly, it can be argued that it should not count as a negative consequence of microdosing itself. Moreover, the consequences of microdosing were not the primary focus of this study, and the portion of the study that did examine microdosing effects focused exclusively on negative consequences, possibly leading to an overly pessimistic conclusion. Nonetheless, since this study is the only one in the literature striking a more negative tone, it is included in the present review with these considerations in mind. Lastly, in terms of negative effects of microdosing, several qualitative studies have found that the most frequently cited concerns had nothing to do with microdosing itself, but were consequences of the illegality and/or stigma associated with the substances. Such concerns included the difficulty of having to measure doses oneself, having to hide the practice from others, and uncertainty about the purity of the substances due to reliance on the black market. In summary, evidence collected to date indicates that many microdosers experience positive effects with some people reporting no discernible effects and a number of reported challenges that will be discussed in later sections.
Multiple studies attest to an improvement of creativity associated with microdosing. Qualitatively,and, as well as a recent content analysis of the subreddit r/microdosing on the online forum Reddit, and a detailed analysis of the distribution of qualitatively reported microdosing effectsall reported that feelings of improved creativity were a common feature in the accounts they analyzed. Though their methods were exploratory, their results offer a promising finding warranting further investigation. In terms of quantitative studies,administered a battery of online questionnaires and tasks assessing aspects of personality, attitudes, mental health, and creativity to participants both with and without microdosing experience, and found higher creativity scores among both current and former microdosers when compared to participants without such experience. However, since this study included both current and former microdosers, it cannot be established that the effects observed were a result of a microdosing practice. It is equally possible that more creative people are more likely to seek out the microdosing experience. Addressing these concerns of directionality is the only quasi-experimental study conducted on psychedelic microdosing to date.assessed measures of general intelligence (Ravens Progressive Matrices), divergent thinking (Alternative Uses Task), and convergent thinking (Picture Concept Task) in visitors to a psychedelic festival in the Netherlands as part of an on-stage presentation. The latter two tasks were presumed to be indicators of creativity. Participants completed all three tasks once before drug consumption, and once under the presumed influence of an estimated microdose of psychedelic truffles. Results showed significant improvements in both convergent and divergent thinking with no significant changes in fluid intelligence. The authors interpreted their findings as suggesting that psychedelic substances may help creativity by improving task transitioning processes in the brain. Although this study did not include a placebo control group and was not conducted under laboratory conditions, it presents the strongest evidence of creativity boosts in psychedelic microdosing to date. In contrast, one observational study found no changes in creativity among microdosing participants, neither in self-report measures on acute microdose effects, nor at a 6-week post-rating of a more objective creativity task. Additionally,administered four single doses of LSD to 20 volunteers in an experimental, double-blind, placebocontrolled setting (doses: 0, 6, 13, and 26 μg) and similarly failed to find differences in creative performance on a Remote Associations Task beyond a marginal increase in attempts for the highest dose. Since the highest dose also significantly increased ratings on a "feel high" scale, however, it can be argued that it should not qualify as a microdose. In summary, then, the existing evidence on creativity changes associated with microdosing is mixed.
Part of the reason for the recent resurgence of psychedelic substances appears to be a movement, originally started in Silicon Valley, of microdosing to improve focus and productivity at work. Until recently, however, no published research was available to bear out these anecdotal reports. In the past two years, several qualitative studies have provided exploratory data on the issue.detailed reports of increased productivity and less procrastination in microdosing participants. The interview study conducted by, as well as the subreddit content analysis, and the questionnaire-based study by, all present self-reported accounts of cognitive improvements in microdosers including enhanced productivity and efficiency, and a decrease in mental fog. The latter study also reported accounts of impaired focus. However, as the authors point out, negative accounts regarding this variable were outweighed by positive ones in an almost 2:1 ratio., analyzing both daily e-mail reports of participants (n = 98) and comparing a battery of questionnaires assessing nine domains of functioning at baseline and at a 6-week post-rating (n = 63), also found lower levels of distractibility and increased absorption at follow-up. This study offers the first systematic piece of evidence for long-term effects of microdosing as opposed to the acute effects reported on active microdosing days or the day after. On the other hand, the experimental, placebo-controlled study bymentioned earlier found neither effects on working memory function, nor on focus and productivity compared with lower doses and a placebo, except for a marginal increase in vigor in the highest-dose condition. As previously mentioned, this higher dose does not meet the traditional definition of a microdose. Similarly,administered six doses of either a placebo, 5, 10, or 20 μg of LSD to healthy older adults and found very minimal effects on cognition except for a linear dose-dependent increase in vigilance reduction, dizziness, and sleepiness. However, as the authors note, the fact that volunteers were confined to bed on microdosing days could have been a confounding factor. A final aspect tangentially related to focus and productivity is the subjective experience of time in microdosing subjects.using a subset of thesample) have conducted one of only five experimental, placebo-controlled studies on human microdosing to date on this topic. An experimental paradigm requiring participants to estimate the duration of a computer-based stimulus found that people under the influence of an LSD microdose tended to overestimate supra-second intervals. However, this finding was restricted to the 2000-4000 millisecond range and is at odds with previous research showing that full doses of psilocybin and LSD tend to lead to underestimation of supra-second time intervals. Additionally,, utilizing a similar experimental paradigm requiring the reproduction of time intervals between 1.5 and five seconds, reported a significant increase in the loss rate of internal time representation in psilocybin microdoses (12 μg/kg) compared to placebo.
Both qualitative and quantitative studies have provided information on the effects of microdosing on mood and related topics. Qualitatively, early studies have reported effects such as an elevation of mood, increases in energy and self-efficacy, more openness toward friends and family, improved attitude toward life, and extroversion. Quantitatively,reported lower dysfunctional attitudes and negative emotionality, and increased wisdom and open-mindedness in current and former microdosers compared to a control group without microdosing experience. As already noted, however, the directionality of effects in this study is particularly unclear.found decreases in stress at the 6-week followup, but also reported increases in neuroticism in some participants at the same assessment. Finally, two experimental studies that investigated higher-dose psychedelic effects but included low-dose conditions for comparison are relevant here., who did not include a full placebo condition in their comparison of high and low doses of psilocybin in combination with other spiritual practice, reported that participants in the low-dose condition did attribute some changes on variables such as "positive behavior changes" and "positive mood changes" to their psychedelic experiences at a 6-month follow-up. However, the absence of a placebo condition, and the fact that many participants were likely led to expect a transformative experience, make interpretation of these results difficult. In contrast,, who did include a full placebo condition, reported slight drowsiness, increased sensitivity, and intensification of preexisting mood states amidst many null findings on mood and well-being in their lowest psilocybin condition (45 μg/kg; sample of N = 8). Similarly, the experimental studies byandfound no or only very few noteworthy alterations on mood and emotional processing.reported reduced use of substances such as caffeine, alcohol and tobacco in the qualitative reports they analyzed, whilepresented qualitative evidence for improvements in conditions such as obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and narcolepsy., who designed a quantitative online questionnaire asking participants to rate the effectiveness of microdosing for mental health and physiological issues in comparison to both conventional treatments and full-dose psychedelic experiences (N = 410), found that participants rated microdosing as significantly more effective than conventional treatments for conditions such as ADD/ ADHD and anxiety disorders. Finally,reported some improvements in OCD symptoms for microdoses of psilocybin (25 μg/kg) in an experimental setting. However, no placebo condition was included, and symptom reductions were not significantly different across dose conditions, increasing concerns about possible expectancy effects.
Although generally dwarfed by the seemingly strong anti-depressive effects of full psychedelic doses, the literature to date includes some indications that psychedelic microdoses may also help with depression and depressive symptoms. In addition to the qualitative self-report studies suggesting this, an anti-depressive effect was observed by both, as well as a study on depressive symptom reduction of cancer patients after high and low doses of psilocybin). In the latter study, although again dwarfed by the much higher efficacy of full doses, 32% of patients that had only received the low dose still exhibited a clinical response regarding their depression (defined as a 50% measure reduction relative to baseline) after the experience.
The evidence surrounding the effects of microdosing on anxiety is a little more contested. In terms of qualitative evidence,presented reports of participants experiencing relief from especially social anxiety, while bothandreported incidences of increased anxiety in the accounts they analyzed. In the latter study, 35% of people who reported microdosing in the past year also reported experiencing an increase in anxiety at least once. Additionally, both Lea, Amada, and Jungaberle (2019) andreceived reports saying both that microdosing helped with anxiety, as well as reports saying the opposite. In the latter study, the balance between positive and negative accounts regarding anxiety was found to be almost equal. However, this only held for openended questioning about benefits and challenges. When asked more directly whether microdosing had helped with anxiety issues, 59.2% of participants in the same study answered affirmatively. As for quantitative evidence,reported that participants rated microdosing as both more effective than traditional treatments, and less effective than higher psychedelic doses for treatment of anxiety disorders, while two full-dose experimental studies that included microdosing control conditions obtained conflicting results. Although the study on cancer patients found a 24% clinical response rate on anxiety after the low-dose session, it also reported that 15% of patients experienced an episode of anxiety during the session., also investigating a sample of people suffering from life-threatening illnesses, administered 20 μg of LSD in combination with therapy as a control condition to a high dose of LSD (200 μg), and found slight increases in both state and trait anxiety for people in the low-dose condition. However, the sample size in the low-dose condition was extremely small (n = 4). Moreover, as with other primarily full-dose psychedelic studies, the possible expectation of participants of having a psychedelic experience could have presented as a confounding factor, as the low-dose condition was used as a de facto placebo condition. In summary, then, it remains unclear what effect psychedelic microdoses may have on anxiety issues.
The research concerning the physiological effects of psychedelic microdosing remains almost exclusively qualitative. One issue often brought up in popular discussion is a potential buildup of tolerance to the substances.presented conflicting reports in this respect, and implied that effects might differ depending on microdose frequency. Even with daily ingestion, however, only some participants reported a significant buildup of tolerance, while others reported no tolerance. The only consistent finding in this study was that a microdose frequency of a few times per week did not seem to lead to any substantial tolerance effect. As for acute physiological effects of microdosing,reported reductions in migraines for some participants, which has been further reinforced by two qualitative self-report studies investigating subhallucinogenic doses of psychedelics as a last resort treatment for chronic migraine and cluster headaches. The quantitative study offound that participants rated microdosing as a more effective treatment than conventional options for nervous system diseases like migraines and cluster headaches. In contrast, there have also been qualitative reports of insomnia, increased heart rate, mild to severe headaches and nausea, and physiological discomfort. Mild headaches in response to LSD microdoses were also found in the experimental study by, and the fulldose experimental study byreported that 12% of patients in the low-dose condition experienced physiological discomfort. Finally, no research to date has examined any potential long-term physiological effects beyond the qualitative observation that microdosers have sometimes credited the practice with increasing their exercise, sleep, and healthy eating. Although the toxicity of psychedelic substances has generally been found to be low (e.g., van Amsterdam, Opperhuizen, and Brink 2011), the risk of possible adverse physical consequences in the long run warrants separate inquiry in the future. Since 5-HT 2B agonists (including LSD and psilocybin) have been suggested to be implicated as a potential mediating factor in valvular heart disease, one target of future research should be to investigate the possible cardiovascular effects of a long-term microdosing practice.
This study summarized the extant literature on the topic of psychedelic microdosing. Overall, the evidence indicates a variety of benefits including improvements in mood, focus, and creativity, with some people experiencing no discernible effects or expressing concerns about selective negative consequences like increased anxiety. However, many of the samples drawn in the cited studies were convenience samples and therefore likely biased and unrepresentative of the general population. One possible consequence is underrepresentation of people who may have tried microdosing, but stopped due to experiencing either negative or no effects. Such persons would have been less likely to appear in the cited studies than a person who experienced only positive consequences of microdosing. Furthermore, research on long-term effects is nonexistent and much remains unknown in this area. One issue that needs further research is the possible role of placebo effects. Two arguments against a placebo-based explanation have been proposed. Firstly,suggested that the patterns of reports obtained in his exploratory study regarding both dosing regimens as well as effect patterns may be too specific to be due to placebo or nocebo effects. For example, placebo-based explanations may not explain why many people find specific dosing regimens effective but have had bad experiences with others. Secondly,conducted a follow-up study in which they asked participants to detail their expectations of microdosing effects, and found no association between people's expectations and the actually experienced effects from their first study. If people do not expect the rather specific effects that microdosing seems to have on them, the likelihood that these effects can be completely explained as a placebo seems reduced. On the other hand,note that, in their almost every effect that was mentioned as an advantage (e.g., increased energy) was also mentioned as a disadvantage (e.g., impaired, or too much, energy), suggesting that the phenomenon of microdosing may be heavily influenced by expectations and placebo. However, the authors point out that individual genetic and epigenetic differences may also account for some of these data. Taking into account the few placebo-controlled studies conducted so far, a general trend in the literature seems to be that the more scientifically rigorous the evidence, the more minimal and measured the results. Another question that needs to be resolved is in how far microdoses resemble full doses in terms of their underlying brain mechanism. Since one is ingesting the same substances, a reasonable expectation would be that the brain would be affected in a similar way (i.e., same receptors, same mechanism). However, it is a common experience of researchers that analogies from full doses do not commonly hold for microdoses and vice versa. For example,did not consistently find a buildup of tolerance to microdoses even with daily ingestion, whereas it has been reported that daily ingestion of full doses of LSD leads to a complete absence of acute effects as early as the fourth day of consecutive use. In contrast, many of the reported effects (e.g., mood improvements, anti-depressive effects) seem similar between doses at least in terms of direction. Neuroimaging studies could help determine to what extent analogies between full doses and microdoses are appropriate. In terms of anti-depressive effects, for example, it has been proposed that the effect of a full psychedelic dose on the default-mode network (DMN) might be an important mechanism in the apparent efficacy of (particularly) psilocybin to treatmentresistant depression. Clarifying whether and to what degree microdoses of the same substance affect the DMN may aid our understanding of how and why microdoses could or could not have similar anti-depressive properties. Lastly, it is important to note that there is no consensus on the precise definition of a microdose. In terms of psilocybin, for example, the experimental evidence here reviewed ranges in their definition of a "very low dose" from 12 μg/kg body weight (i.e., 0.84 mg/70 kg; e.g.,) to 45 μg/kg body weight (i.e., 3.15 mg/70 kg; e.g.,). In some of the studies using the higher end of this spectrum, participants selectively reported some perceptual distortions and visual illusions, violating the working definition employed by many researchers requiring a microdose to be sub-perceptual. Even without the perceptual aspect, however, it is still a reasonable expectation that there might be significant differences between a dose of 1/10th of a normal dose, and a dose of 1/20th. Failing to distinguish these two dose levels may make comparisons between studies more difficult. Standardized experimental procedures are needed to address confusion and confounds related to this issue. Research experiments within this 1/10th to 1/ 20th range may find the dose that maximizes the effects of the substances while still preserving the subperceptual nature of the experience. With regards to LSD, for example,recently suggested a threshold dose of 13 µg. In terms of psilocybin, the range still seems ambiguous (i.e., somewhere between 14 and 43 µg/kg or 1 and 3 mg/70 kg). Owing to the continued illegality and stigma surrounding psychedelic substances, methodologically strong research continues to be difficult due to lack of official approval and the high cost of legally acquiring the substances. Preliminary evidence on the phenomenon of microdosing looks promising, but a trend toward more minimal results in more scientifically rigorous data provides reason for caution. Therefore, future research should prioritize double-blind, placebo-controlled, experimental paradigms as well as longitudinal studies.
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Papers in Blossom that reference this study
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