The therapeutic potential of microdosing psychedelics in depression

Abstract

Microdosing psychedelics is the repeated use of small doses of, for example, lysergic acid diethylamide (LSD) and psilocybin, typically for a few weeks. Despite the popular and scientific attention in recent years, and claims by users that it has therapeutic value in affective disorders like depression, little scientific knowledge is available to back this. The purpose of this review was to investigate whether there are scientific grounds to state that this practice could be helpful in the treatment of affective disorders, and safe to use repeatedly. To that end, the literature (PubMed, MedLine) was searched, looking for (controlled) experimental studies with low doses of LSD and/or psilocybin, in healthy volunteers and patient samples. After a selection process and the addition of relevant articles, 14 experimental studies entered this review. Findings show that both LSD (10–20 mcg) and psilocybin (<1–3 mg) have subtle (positive) effects on cognitive processes (time perception, convergent and divergent thinking) and brain regions involved in affective processes. Besides the pleasant experience, increased anxiety and a cycling pattern of depressive and euphoric mood were also found. With regard to safety, it was demonstrated that low doses are well tolerated (in healthy volunteers) and have no-to-minimal effects on physiological measures. While it is yet unclear whether psychedelic microdosing is of therapeutic value for depression, the aforementioned effects on selective processes suggest that low doses of psychedelics could play a role in depression by inducing some kind of cognitive flexibility, which might lead to decreased rumination. While previous studies were conducted mostly in small samples of healthy volunteers, future placebo-controlled clinical trials in depressed patients are required to understand the therapeutic value of microdosing psychedelics, how this differs from therapy using full psychedelic doses, and whether different psychedelics have different effect patterns. The proposed research will give new insights into the potential of future alternative psychiatric treatment forms that are fiercely needed.

Low Doses of Psilocybin and Ketamine Enhance Motivation and Attention in Poor Performing Rats: Evidence for an Antidepressant Property

“…In addition to usage at psychotomimetic doses, both ketamine and psilocybin have a long history of being self-adminstered at lower doses (colloquially referred to as "microdoses"), (Johnstad, 2018;Kuypers et al, 2019;Hutten et al, 2019;Polito and Stevenson, 2019;Rosenbaum et al, 2020). However, while there are a number of anecdotal reports describing beneficial effects of "micro" dose ketamine and psilocybin on mood and cognition, there are very few placebo controlled, scientific studies explicitly designed to investigate low doses of ketamine, and none explicitly using psilocybin (Kuypers et al, 2019;Kuypers, 2020). In the case of psilocybin, the actual doses are unknown since natural mushroom containing the agent are ingested.…”

Exploring the relationship between microdosing, personality and emotional insight: A prospective study

“…However, Bright et al (2021) found that microdosers had higher levels of depression and anxiety compared to a yoga control group. In a recent review of 14 microdosing studies, Kuypers (2020) observed that "while low LSD doses were experienced as pleasant, it was also shown that drug disliking and anxiety increased, and that a cycling pattern of depressive and euphoric mood changes can occur" (Kuypers, 2020, pp. 9-10).…”

Administration of N,N-dimethyltryptamine (DMT) in psychedelic therapeutics and research and the study of endogenous DMT

“…More recently, data and anecdotal reports concerning the physiological effects of administration of psychedelics in very low doses, or micro-dosing, have gained significant public attention. Micro-dosing of psychedelics refers to the ingestion of low to very low doses (5 and 10% of a standard hallucinogenic dose) on an established schedule (every other day) with the intention of avoiding hallucinogenic or short-term debilitating effects (Fadiman and Korb, 2019 ; Kuypers et al 2019 ; Kuypers, 2020 ; Liechti 2019 , Bershad et al 2019 Cameron et al 2020 ). However, regardless of the identity of the psychedelic, there are no scientifically established dose ranges that have been accepted for micro-doses of these substances (Kuypers et al 2019 ; Passie 2019 ; Lea et al 2020 ).…”