Flow diagram showing participation and completion rates through the study. The completion of the 4 weeks follow-up timepoint was optional.

Flow diagram showing participation and completion rates through the study. The completion of the 4 weeks follow-up timepoint was optional.

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Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such accounts are potentially biased by the placebo effect. This study used a ‘self-blinding’ citizen science initiative, where participants were given online instructions on how to in...

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Context 1
... rate was highly similar across the three groups ( 2 (12, N = 240)=0.64, p=0.99), see Figure 3. ...
Context 2
... participants microdosed with LSD (n = 147; 61%)/LSD analogue (n = 33; 14%), followed by psilocybin containing mushrooms (n = 57; 24%) and three individuals used other psychedelics (LSA: n = 1; DOB: n = 2). The average reported dose for LSD/LSD analogues was 13 ± 5.5 mg, while for psilocybin mushroom it was 0.2 ± 0.12 g, see Appendix 1- figure 3 for further details. ...

Citations

... Further support comes from the widely used practice of microdosing in which doses of psilocybin that are only a fraction (one tenth or less) of the psychedelic dose are taken by individuals in a nonmedicinal context. While results are not consistent and comprehensive studies are lacking, there is evidence that microdosing may have positive effects on mood, creative processes, and energy [168,169]. In a recent large internet-based study psilocybin was the most frequently microdosed psychedelic agent. ...
Article
Schizophrenia is a widespread psychiatric disorder that affects 0.5–1.0% of the world’s population and induces significant, long-term disability that exacts high personal and societal cost. Negative symptoms, which respond poorly to available antipsychotic drugs, are the primary cause of this disability. Association of negative symptoms with cortical atrophy and cell loss is widely reported. Psychedelic drugs are undergoing a significant renaissance in psychiatric disorders with efficacy reported in several conditions including depression, in individuals facing terminal cancer, posttraumatic stress disorder, and addiction. There is considerable evidence from preclinical studies and some support from human studies that psychedelics enhance neuroplasticity. In this Perspective, we consider the possibility that psychedelic drugs could have a role in treating cortical atrophy and cell loss in schizophrenia, and ameliorating the negative symptoms associated with these pathological manifestations. The foremost concern in treating schizophrenia patients with psychedelic drugs is induction or exacerbation of psychosis. We consider several strategies that could be implemented to mitigate the danger of psychotogenic effects and allow treatment of schizophrenia patients with psychedelics to be implemented. These include use of non-hallucinogenic derivatives, which are currently the focus of intense study, implementation of sub-psychedelic or microdosing, harnessing of entourage effects in extracts of psychedelic mushrooms, and blocking 5-HT2A receptor-mediated hallucinogenic effects. Preclinical studies that employ appropriate animal models are a prerequisite and clinical studies will need to be carefully designed on the basis of preclinical and translational data. Careful research in this area could significantly impact the treatment of one of the most severe and socially debilitating psychiatric disorders and open an exciting new frontier in psychopharmacology.
... As a recent practice with illegal substances, there have been great differences in substance, dose, frequency, and duration between users . However, microdosing was commonly conceptualized as the frequent use of psychedelic substances in low doses (e.g., 10-15 µgrams of LSD) (Szigeti et al., 2021). It has become a popular practice, with many thousands of individuals reporting benefits in creativity and productivity, and paving the road to "microdosing" becoming interchangeable with "nootropics" (Machek, 2019), "smart drugs" (d 'Angelo, Savulich, & Sahakian, 2017), or "mental tonics" (Pollan, 2019, p. 304). ...
... In a web-based prospective survey about microdosing, positive expectations seemed to index improvements in mental health (Kaertner et al., 2021). In a placebo-controlled study with a self-blinding protocol, there were no significant differences in psychological outcomes between microdosing and placebo groups (Szigeti et al., 2021). Whereas this online survey and self-blinding study, respectively, question whether microdosing differs from a placebo, most publications are sanguine about the beneficial effects of microdosing (cf. ...
... By the same token, psychedelics have been framed as meaning-response magnifiers, or as hyper-active placebo catalysts, perhaps by amplifying contextual factors and expectations (Hartogsohn, 2016(Hartogsohn, , 2020. Compared to regular doses with psychedelics, contextual factors (setting) may be less influential in lower doses, however psychological factors such as expectations and beliefs (set) would still play a big role in drug response as in microdosing (Kaertner et al., 2021;Szigeti et al., 2021). Positivity bias refers to an effect among individuals with extensive psychedelic experience who appear partial toward microdosing and praise its benefits (Anderson, Petranker, Rosenbaum, et al., 2019;Kaertner et al., 2021). ...
Article
To date, the clinical and scientific literature has best documented the effects of classical psychedelics, such as lysergic acid diethylamide (LSD), psilocybin, and dimethyltryptamine (DMT), in typical quantities most often associated with macrodosing. More recently, however, microdosing with psychedelics has emerged as a social trend and nascent therapeutic intervention. This variation in psychedelic practice refers to repeat, intermittent ingestion of less-than-macrodose amounts that do not cause the effects associated with full-blown “trips”. Microdosing paves the road to incorporating psychedelic drugs into a daily routine while maintaining, or even improving, cognitive and mental function. Unlike macrodosing with psychedelics, the influence of microdosing remains mostly unexplored. And yet, despite the paucity of formal studies, many informal accounts propose that microdosing plays an important role as both a therapeutic intervention (e.g., in mental disorders) and enhancement tool (e.g., recreationally—to boost creativity, improve cognition, and drive personal growth). In response to this relatively new practice, we provide an integrative synthesis of the clinical, social, and cultural dimensions of microdosing. We describe some of the overarching context that explains why this practice is increasingly in vogue, unpack potential benefits and risks, and comment on sociocultural implications. In addition, this article considers the effects that macro- and microdoses have on behavior and psychopathology in light of their dosage characteristics and contexts of use.
... None of these studies identified used psilocybin without psychotherapy and none evaluated micro-dosing (i.e., repeated low doses of psilocybin); however, one observational study suggested benefits of micro-dosing were equivalent to placebo. 69 The first study was an open-label, single-armed, feasibility trial involving two sessions (first dose 10 mg, second dose 25 mg oral psilocybin) of psilocybin-assisted psychotherapy spaced 7 days apart in 12 participants with TRD. There was a significant reduction in depressive symptoms (as measured by the Quick Inventory of Depressive Symptomatology Self-Report [QIDS-SR]) after 7 days (hedges' g = 3.1; P = 0.002) and 3 months (g = 2.0; P = 0.003) after the second (high dose; 25 mg) session. ...
Article
Objective Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder. Methods A systematic review was conducted to identify contemporary clinical trials of serotonergic psychedelics for the treatment of major depressive disorder and cancer-related depression. Studies published between January 1990 and July 2021 were identified using combinations of search terms, inspection of bibliographies and review of other psychedelic reviews and consensus statements. The levels of evidence for efficacy were graded according to the Canadian Network for Mood and Anxiety Treatments criteria. Results Only psilocybin and ayahuasca have contemporary clinical trials evaluating antidepressant effects. Two pilot studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator (escitalopram with supportive psychotherapy) in major depressive disorder, with additional randomized controlled trials showing efficacy specifically in cancer-related depression (Level 3 evidence). There was only one open-label trial of psilocybin in treatment-resistant unipolar depression (Level 4 evidence). Small sample sizes and functional unblinding were major limitations in all studies. Adverse events associated with psychedelics, including psychological (e.g., psychotomimetic effects) and physical (e.g., nausea, emesis and headaches) effects, were generally transient. Conclusions There is currently only low-level evidence to support the efficacy and safety of psychedelics for major depressive disorder. In Canada, as of 2022, psilocybin remains an experimental option that is only available through clinical trials or the special access program. As such, Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment and recommends its use primarily within clinical trials, or, less commonly, through the special access program in rare, special circumstances.
... Another form of psilocybin use, called "microdosing", consists of regular intake of very low doses (< 1-3 mg) in the treatment of various psychiatric disorders as well as in the search for improved cognitive and creative performance. The results are so far mitigated [20], especially against placebo [21], and require further exploration. ...
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Purpose of the Review We aim to provide an overview of the current state of knowledge about the efficacy of psilocybin in the treatment of depression, as well as its mechanisms of action. Recent Findings Psilocybin has a large, rapid, and persistent clinical effect in the treatment of resistant or end-of-life depression. Tolerance is good, with mild side effects limited to a few hours after dosing. The studies conducted to date have had small sample sizes. One clinical trial has been conducted against a reference treatment (escitalopram) without showing a significant superiority of psilocybin in the main outcome. The neurobiological mechanisms, mostly unknown, differ from those of SSRI antidepressants. Summary Psilocybin represents a promising alternative in the treatment of depression. Further research with larger sample sizes, particularly against reference treatments, is needed to better understand the neurobiological factors of its effects and to investigate its potential for use in everyday practice.
... Different serotonergic psychedelics are used for this purpose, such as lysergic acid diethylamide (LSD), dimethyltryptamine (DMT) ingested with a monoamine oxidase inhibitor (MAOI)-as in the concoction known as "ayahuasca"and psilocybin, the active compound of several mushrooms in the Psilocybe genus. The most frequently used compounds are LSD and psilocybin, the latter in the form of dried psychoactive mushrooms [7][8][9]26]. There is considerable variability in dose and dosing schedules [25]. ...
... Dosing periods are also highly variable, ranging between 1 week to several years [25]. In the case of psilocybin mushrooms, microdoses are within the range of 0.1 g to 0.5 g of dried mushroom material [18], with 0.1 g considered roughly equivalent to ≈4.6 µg of LSD [26]. ...
... Indeed, low doses of LSD can have effects that are different (or even opposite) to those expected by individuals who microdose [33][34][35][36]. Nevertheless, other reports have documented positive and dosedependent enhancements in mood, emotional cognition and aesthetic perception, as well as significant improvements in emotional state, anxiety, energy and creativity, among other relevant variables [26,35,37,38]. Importantly, some of these results could be explained by unblinding of the experimental condition, i.e., by subjects correctly distinguishing the placebo from the active dose [26,38]. ...
Article
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The use of low sub-perceptual doses of psychedelics (“microdosing”) has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies severely limits our knowledge of microdosing and its effects. Moreover, research conducted in standard laboratory settings could fail to capture the motivation of individuals engaged or planning to engage in microdosing protocols, thus underestimating the likelihood of positive effects on creativity and cognitive function. We recruited 34 individuals starting to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled experimental design, we investigated the acute and short-term effects of 0.5 g of dried mushrooms on subjective experience, behavior, creativity (divergent and convergent thinking), perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, but only for participants who correctly identified their experimental condition. These changes were accompanied by reduced EEG power in the theta band, together with preserved levels of Lempel-Ziv broadband signal complexity. For all other measurements there was no effect of microdosing except for few small changes towards cognitive impairment. According to our findings, low doses of psilocybin mushrooms can result in noticeable subjective effects and altered EEG rhythms, but without evidence to support enhanced well-being, creativity and cognitive function. We conclude that expectation underlies at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.
... Medicinal motives are likely to be related to positive prior expectancy, a major component of the action of all effective treatments, including placebo (Olson et al., 2020) and SSRIs (Hjorth et al., 2021). Positive expectancy has recently come under the spotlight in psychedelic research where for example, belief about receipt of a psychedelic appears to be major driver of outcomes (Kaertner et al., 2021;Olson et al., 2020;Szigeti et al., 2021;Van Elk et al., 2021). Whether expectancy is a (justifiably or experimentally) extricable component of any treatment, not just psychedelic therapy, is a question worthy of some thought (Carhart-Harris et al., 2021b). ...
Article
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Background Over the last two decades, a number of studies have highlighted the potential of psychedelic therapy. However, questions remain to what extend these results translate to naturalistic samples, and how contextual factors and the acute psychedelic experience relate to improvements in affective symptoms following psychedelic experiences outside labs/clinics. The present study sought to address this knowledge gap. Aim Here, we aimed to investigate changes in anxiety and depression scores before versus after psychedelic experiences in naturalistic contexts, and how various pharmacological, extrapharmacological and experience factors related to outcomes. Method Individuals who planned to undergo a psychedelic experience were enrolled in this online survey study. Depressive symptoms were assessed at baseline and 2 and 4 weeks post-psychedelic experience, with self-rated Quick Inventory of Depressive Symptomatology (QIDS-SR-16) as the primary outcome. To facilitate clinical translation, only participants with depressive symptoms at baseline were included. Sample sizes for the four time points were N = 302, N = 182, N = 155 and N = 109, respectively. Results Relative to baseline, reductions in depressive symptoms were observed at 2 and 4 weeks. A medicinal motive, previous psychedelic use, drug dose and the type of acute psychedelic experience (i.e. specifically, having an emotional breakthrough) were all significantly associated with changes in self-rated QIDS-SR-16. Conclusion These results lend support to therapeutic potential of psychedelics and highlight the influence of pharmacological and non-pharmacological factors in determining response. Mindful of a potential sample and attrition bias, further controlled and observational longitudinal studies are needed to test the replicability of these findings.
... 4 Recent studies reported on the effects of microdosing classic psychedelics, i.e., administration of less than 20% of the usual total dose in a semi-regular schedule. 5 Although there is a lack of robust research on ibogaine microdosing for psychiatric disorders, we report this practice in a patient with bipolar depression as a possibly innovative treatment alternative. ...
... [38][39][40] Not only have psychedelics been shown to enhance suggestibility, 41 their perceived benefits have also been associated with positive expectancies, particularly in the case of microdosing. 42,43 To evaluate the role played by expectancy in pain relief reports, we asked participants whether or not they had been using psychedelics with the specific intention of managing pain. In the group of respondents who did not use psychedelics for pain management, macrodoses of psychedelics were still perceived as exerting a significant analgesic effect, superior to that of conventional medication, while the analgesic effect of microdoses was reported as similar to that of conventional medication. ...
Article
Full-text available
Although several studies and reports have shown the potential analgesic use of serotonergic psychedelics in cancer pain, phantom limb pain and cluster headache, evidence supporting their use for chronic pain is still limited. The past years have seen a considerable renewal of interest toward the therapeutic use of these compounds for mood disorders, resulting in a marked increase in the number of people turning to psychedelics in an attempt to self-medicate a health condition or improve their wellbeing. In western countries particularly, this population of users overlaps substantially with chronic pain sufferers, representing a unique opportunity to evaluate the effects these compounds have on pain and wellbeing. Here, we report results from an online survey conducted between August 2020 and July 2021 in a population of 250 chronic pain sufferers who had experience with psychedelics, either in microdoses (small sub-hallucinogenic doses), macrodoses (hallucinogenic doses), or both. Macrodoses, while less often used for analgesic purposes than microdoses, were reported to induce a higher level of pain relief than both microdoses and conventional pain medications (including opioids and cannabis). Although the effects were weaker and potentially more prone to expectation bias than with macrodoses, our results also suggested some benefits of psychedelics in microdoses for pain management. The reported analgesic effect appeared unrelated to mood improvements associated with psychedelic use, or the advocacy of psychedelic use. Taken together, our findings indicate interesting potential analgesic applications for psychedelics that warrant further clinical research.
... Novel tryptamines such as 5-MeO-DMT and purportedly high-risk phenethylamines such as DOI have been documented to be neuroplasticityinducing the latter appearing among surveyed microdosers ). As such, prospective studies set prior to use may be able to further clearer indices of their relative harms and benefits while issues pertaining to ecology and the legal status of NPs in such studies may be circumvented by employing volunteer-orientated citizen-science designs (Silvertown 2009) such as those used in microdosing studies (Szigeti et al. 2021). ...
Article
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Background Novel psychedelics (NPs) are an expanding set of compounds, presenting new challenges for drug policy and opportunities for clinical research. Unlike their classical derivatives, little is known regarding their use profiles or their subjective effects. Aims The purpose of this study was to compile usage patterns and adverse event rates for individual NPs belonging to each of three main psychedelic structural families. Targeting the most widely used representatives for each class, we expanded on their phenomenological distinctions. Methods A two-part survey was employed. We investigated the prevalence of novel phenethylamines, tryptamine and lysergamides in NP users ( N = 1180), contrasting the type and incidence of adverse events (AEs) using a set of logistic regressions. Honing in on 2–4-Bromo-2,5-dimethoxyphenyl)ethanamine (2C-B) (48.6%), 1-propionyl-lysergic acid diethylamide (1P-LSD) (34.2%) and 4-Acetoxy-N,N-dimethyltryptamine (4-AcO-DMT) (23.1%), we examined their phenomenological separability using a gradient boosting (XGBoost) supervised classifier. Results Novel phenethylamines had the highest prevalence of use (61.5%) seconded by tryptamines (43.8%) and lysergamides (42.9%). Usage patterns were identified for 32 different compounds, demonstrating variable dosages, durations and a common oral route of administration. Compared to phenethylamines, the odds for tryptamines and lysergamides users were significantly less for overall physical AEs. No significant differences in overall psychological AEs were found. Overall model area under the curve (AUC) stood at 0.79 with sensitivity (50.0%) and specificity (60.0%) for 2C-B ranking lowest. Conclusion NP classes may hold distinct AE rates and phenomenology, the latter potentially clouded by the subjective nature of these experiences. Further targeted research is warranted.
... Recent evidence reporting on psilocybin-assisted psychotherapy for depression has been promising, which has generated interest in the potential therapeutic effect and use of psilocybin to treat depressive symptoms of select psychiatric disorders [3,[8][9][10]. Clinical trials with serotonergic hallucinogens or 'psychedelics,' such as psilocybin, continue to be ongoing, although some evidence suggests that the placebo effect may be underplayed when discussing the potential benefits of the foregoing drugs [11]. ...
Article
Introduction: Hallucinogen persisting perception disorder (HPPD) affects a subset of persons who use hallucinogens and is defined as the repeated experience of hallucinations and other perceptual disturbances as a result of prior intoxications. As select hallucinogens are under development for the treatment of selectmental disorders, there is a need to better characterize this disorder. Areas covered: A scoping review of the literature on HPPD was completed from inception to July 2021. Topics covered in the review herein include treatments for HPPD, prevalence or incidence data on HPPD among different classes of hallucinogens, risk factors for HPPD, and data pertaining to the pathophysiology of HPPD. Expert opinion: Hallucinogen persisting perception disorder appears to be an uncommon yet serious event associated with prior hallucinogen exposure. The renewed interest in psychedelics as potential treatment options for select mental disorders, especially agents with hallucinogenic potential, provides the impetus to characterize HPPD in its frequency, risk and protective factors, key characteristics, as well as other clinical and treatment-related factors.