Repeated low doses of LSD in healthy adults: A placebo‐controlled, dose–response study

Abstract

The resurgence of interest in using psychedelic drugs, including lysergic acid diethylamide (LSD), in psychiatry has drawn attention to the medically unsupervised practice of 'microdosing'. Thousands of users claim that very low doses of LSD, taken at 3-4-day intervals, improve mood and cognitive function., However, few controlled studies have described the effects of the drug when taken in this way. Here, in a double-blind controlled study, we studied the effects of four repeated doses of LSD tartrate (13 or 26 μg) or placebo, administered to healthy adults at 3-4 day intervals, on mood, cognitive performance and responses to emotional tasks. Participants were randomly assigned to one of three drug conditions: placebo (N = 18), 13 μg LSD (N = 19), or 26 μg LSD (N = 19). They attended four 5-hour drug-administration sessions separated by 3-4 days, followed by a drug-free follow-up session 3-4 days after the last session. LSD (26 μg) produced modest subjective effects including increased ratings of 'feeling a drug effect' and both stimulant-like and LSD-like effects, but the drug did not improve mood or affect performance on psychomotor or most emotional tasks. No residual effects were detected on mood or task performance on the drugfree follow-up session. We conclude that within the context of a controlled setting and a limited number of administrations, repeated low doses of LSD are safe, but produce negligible changes in mood or cognition in healthy volunteers.

Dose-response relationships of LSD-induced subjective experiences in humans

“…The studies included in our analysis vary greatly with regards to experimental setting. Bershad et al (2019) reports of “living-room style” environments with possibilities to relax, read or watch movies between measurements [44], similar to Preller et al (2017) (“in an esthetic living-room-like room”) [35] and de Wit et al (2022) [45]. In other studies, however, participants were also given tasks during LSD applications that involved greater effort, potentially inhibiting the manifestation of certain effects [75].…”

“…For instance, visual phenomena (11-ASC: Audio-Visual Synesthesia, Complex and Elementary Imagery ) show an x-axis intercept at around 10 μg, and at 20 μg reach around 10% of the maximum score. These effects are unlikely due to placebo effects, as those of the given studies which included a placebo condition reported only negligible effects [22,26,28,35,39,43– 45,66–69]. However, these estimates are strongly influenced by the fact that multiple studies investigated dosages below 20 μg, while there are no studies available in the dosage range from 20 to 50 μg, resulting in an overestimation of the curves slope at their onset.…”

“…First, administration methods varied across studies. Most studies administered LSD orally as capsules, while it was administered sublingually in two studies [44,45] and intravenously in one study [66]. Moreover, LSD formulations differed across studies: most studies applied LSD base (or provided the dosage calculated for LSD base), while some dosages referred to LSD salt in the form of LSD tartrate – the typical formulation sold on the black market.…”

“…These effects are unlikely due to placebo effects, as those of the given studies which included a placebo condition reported only negligible effects [22,26,28,35,39,[43][44][45][66][67][68][69]. However, these estimates are strongly influenced by the fact that multiple studies investigated dosages below 20 μg, while there are no studies available in the dosage range from 20 to 50 μg, resulting in an overestimation of the curves slope at their onset.…”

The risk of chronic psychedelic and MDMA microdosing for valvular heart disease

“…The majority of clinical microdosing studies tested single LSD doses (e.g., Bershad et al, 2019Bershad et al, , 2020Greiner, 1958;Hutten et al, 2020;Murray et al, 2021). Only two multiple-dose studies have been reported, with schedules consisting of a placebo, 5, 10, or 20 µg every 4th day over a 21-day period (Family et al, 2020;Yanakieva et al, 2019) and placebo, 13, or 26 µg LSD tartrate (equivalent to 10 or 20 µg LSD) once every 3 to 4 days for a total of four doses (de Wit et al, 2022). No cardiovascular-related adverse events were reported in either study, and no ECG abnormalities were observed in the study by Family et al However, several months of chronic dosing is typically needed for VHD symptoms to emerge (Elangbam, 2010), so these dosing periods were too short to assess possible VHD, especially with no echocardiography assessments.…”