Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers

Bershad, Anya K.; Schepers, Scott T.; Bremmer, Michael; Lee, Royce; Wit, Harriet de

doi:10.1016/j.biopsych.2019.05.019

Cited by 118 publications

(192 citation statements)

References 44 publications

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“…Polito and Stevenson (2019) found that on the day participants reported microdosing, their self-reported creativity, focus, and well-being were significantly elevated compared to baseline. Bershad et al (2019) found that acute effects of a microdose of LSD included an increased feeling of vigor and friendliness, similar to our findings of increased energy and social benefits. The literature is not of one voice, however, as a recent survey that found some people who report microdosing with psychedelic substances experienced negative psychological effects (Hutten, Mason, Dolder, & Kuypers, 2019).…”

Section: Most Commonly Reported Benefits and Challengessupporting

confidence: 90%

“…One study, conducted at a popular microdosing conference, found that administering small amounts (1g) of psilocybin-containing truffles acutely improved divergent, but not convergent creativity (Prochazkova et al, 2018). An experimental study using small amounts (1-26μg) of LSD found that a single microdose enhanced feelings of "vigor" and social relatedness (Bershad, Schepers, Bremmer, Lee, & de Wit, 2019). Neither of these intervention studies reported any adverse effects, consistent with the relatively benign safety profile of these substances (Johnson, Griffiths, Hendricks, & Henningfield, 2018;Nutt, King, & Phillips, 2010).…”

Section: Introductionmentioning

confidence: 90%

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Microdosing psychedelics: Subjective benefits and challenges, substance testing behavior, and the relevance of intention

et al. 2020

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Background: Microdosing psychedelics is the practice of taking small, sub-hallucinogenic doses of lysergic acid diethylamide or psilocybin-containing mushrooms. Despite its surging popularity, little is known about the specific intentions to start microdosing and the effects of this practice. Aims: First, we aimed to replicate previous findings regarding the subjective benefits and challenges reported for microdosing. Second, we assessed whether people who microdose test their substances before consumption. Third, we examined whether having an approach-intention to microdosing was predictive of more reported benefits. Methods: The Global Drug Survey runs the world’s largest online drug survey. Participants who reported last year use of lysergic acid diethylamide or psilocybin in the Global Drug Survey 2019 were offered the opportunity to answer a sub-section on microdosing. Results: Data from 6753 people who reported microdosing at least once in the last 12 months were used for analyses. Our results suggest a partial replication of previously reported benefits and challenges among the present sample often reporting enhanced mood, creativity, focus and sociability. Counter to our prediction, the most common challenge participants associated with microdosing was ‘None’. As predicted, most participants reported not testing their substances. Counter to our hypothesis, approach-intention – microdosing to approach a desired goal – predicted less rather than more benefits. We discuss alternate frameworks that may better capture the reasons people microdose. Conclusion: Our results suggest the perceived benefits associated with microdosing greatly outweigh the challenges. Microdosing may have utility for a variety of uses while having minimal side effects. Double-blind, placebo-controlled experiments are required to substantiate these reports.

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Section: Most Commonly Reported Benefits and Challengessupporting

confidence: 90%

Section: Introductionmentioning

confidence: 90%

Microdosing psychedelics: Subjective benefits and challenges, substance testing behavior, and the relevance of intention

et al. 2020

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“…There were no differences in heart rate and basal body temperature after intake of LSD compared with placebo. 37 This study shows that repeated administration of low doses of LSD can be regarded as safe on the parameters assessed, though the authors suggest focussing on heart parameters in future studies due to concerns about potential 5-HT2B receptor-mediated ECG abnormalities after repeated use. 48 In a recent functional imaging study, participants underwent a scan session 90 min after taking placebo and LSD tartrate (13 mcg).…”

Section: Older Research With Lsdmentioning

confidence: 81%

“…Both LSD and psilocybin were shown to have no, to very subtle, effects on mood state, selective cognitive processes (time perception, convergent and divergent thinking), and brain regions involved in affective processes. 32,33,40 While low LSD doses were experienced as pleasant, 37,41 it was also shown that drug disliking and anxiety increased, 37,39 and that a cycling pattern of depressive and euphoric mood changes can occur. 40 It is as yet unclear whether psychedelic microdosing is of therapeutic value for depression due to the limited amount of studies (with small sample sizes) that have been conducted.…”

Section: Discussionmentioning

confidence: 99%

“…27 Bershad et al investigated the effects of three doses of LSD tartrate (6.5, 13 and 26 mcg LSD, corresponding to 5, 10 and 20 mcg of base LSD) in a placebo-controlled within-subject study on subjective experience and cognitive measures. 37 Subjects felt under the influence after taking 13 and 26 mcg LSD. They also felt better, friendlier and more anxious compared with placebo.…”

Section: Older Research With Lsdmentioning

confidence: 99%

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The therapeutic potential of microdosing psychedelics in depression

Kuypers

2020

Therapeutic Advances in Psychopharmacology

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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.

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Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants

Holze

Liechti

Hutten

et al. 2020

Clin Pharma and Therapeutics

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Microdoses" of lysergic acid diethylamide (LSD) are used recreationally to enhance mood and cognition. Increasing interest has also been seen in developing LSD into a medication. Therefore, we performed a pharmacokineticpharmacodynamic study using very low doses of LSD. Single doses of LSD base (5, 10, and 20 µg) and placebo were administered in a double-blind, randomized, placebo-controlled crossover study in 23 healthy participants. Test days were separated by at least 5 days. Plasma levels of LSD and subjective effects were assessed up to 6 hours after administration. Pharmacokinetic parameters were determined using compartmental modeling. Concentrationsubjective effect relationships were described using pharmacokinetic-pharmacodynamic modeling. Mean (95% confidence interval) maximal LSD concentrations were 151 pg/mL (127-181), 279 pg/mL (243-320), and 500 pg/ mL (413-607) after 5, 10, and 20 µg LSD administration, respectively. Maximal concentrations were reached after 1.1 hours. The mean elimination half-life was 2.7 hours (1.5-6.2). The 5 µg dose of LSD elicited no significant acute subjective effects. The 10 µg dose of LSD significantly increased ratings of "under the influence" and "good drug effect" compared with placebo. These effects began an average of 1.1 hours after 10 µg LSD administration, peaked at 2.5 hours, and ended at 5.1 hours. The 20 µg dose of LSD significantly increased ratings of "under the influence," "good drug effects," and "bad drug effects." LSD concentrations dose-proportionally increased at doses as low as 5-20 µg and decreased with a half-life of 3 hours. The threshold dose of LSD base for psychotropic effects was 10 µg. Lysergic acid diethylamide (LSD) is a well-known classic serotonergic psychedelic that is widely used for recreational purposes. 1 LSD is well-absorbed, 2,3 and maximal LSD concentrations are reached 1.5-2 hours after oral administration. 4 LSD is mainly metabolized to inactive O-H-LSD, which is renally eliminated. 3 The plasma half-life of LSD is 3-4 hours. 3,4 Increasing interest has been seen in using LSD for the treatment of various disorders, including depression and anxiety, 5 substance use, 6 and cluster headache, 7 among others. 8 LSD "microdosing" has recently become popular. 9,10 The practice of microdosing refers to the use of very low doses of LSD that are taken at 2-to-5-day intervals to improve cognitive function and mood. 11-13 However, little is known about the effects of very low doses of LSD. More data are needed to

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Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers

Cited by 118 publications

References 44 publications

Microdosing psychedelics: Subjective benefits and challenges, substance testing behavior, and the relevance of intention

Microdosing psychedelics: Subjective benefits and challenges, substance testing behavior, and the relevance of intention

The therapeutic potential of microdosing psychedelics in depression

Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants

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