Safety, tolerability, pharmacokinetics, and subjective effects of 50, 75, and 100 µg LSD in healthy participants within a novel intervention paradigm: A proof-of-concept study

Abstract

Background: Classic psychedelics hold promise as therapeutics for psychiatric disorders, but require scalable intervention protocols. This proof-of-concept study evaluated the safety, tolerability, pharmacokinetics, and subjective effects of 50, 75, and 100 µg lysergic acid diethylamide (LSD) in healthy adults within a novel intervention paradigm. Methods: Up to three participants were administered LSD on the same day in separate rooms, each with a single attendant, after 1 day of preparation. An open-label design and a double-blind placebo-controlled design were used. Results: Ninety-one percent of participants completed the study. Thirty-two adults (mean age = 28.8 years) received 50 (n = 3), 75 (n = 7), 100 (n = 3) LSD, 50 µg followed by 75 µg LSD (n = 9) 1 week apart, or placebo followed by a 75 µg LSD (n = 10) 1 week apart. There were no serious adverse events. Twenty-eight percent of participants experienced at least one expected mild adverse event, with one expected moderate adverse event. The maximum blood plasma levels occurred between 1.2 and 2 h post-administration, with an apparent half-life between 2.8 and 4.3 h. LSD largely induced greater subjective effects versus placebo. Conclusion: In the current novel intervention paradigm, 50, 75, and 100 µg LSD are tolerable with favourable safety profiles in healthy adults, only mild adverse events during the day of drug administration, and mystical-type subjective experiences. Future studies are needed to evaluate safety, tolerability, subjective effects, and cost-effectiveness in clinical populations.

Perceptions of safety, subjective effects, and beliefs about the clinical utility of lysergic acid diethylamide in healthy participants within a novel intervention paradigm: Qualitative results from a proof-of-concept study

“…However, to get a richer understanding of safety, it is important to understand the subjective perceptions of safety among the participants. The objective measures of safety for the current protocol are reported elsewhere (Family et al, 2022). Accordingly, the focus of this article is to investigate participants’ perceptions of safety using qualitative data from a semi-structured interview conducted after their participation in the inpatient segment of the study, which included treatment with LSD.…”

“…This paradigm involved abbreviated preparation and integration, and a single attendant to assist each participant. As described in a companion article reporting quantitative outcomes (Family et al, 2022), participants spent full days at the research site and their participation was framed around exploring creative problem solving regarding a work-related issue, results of which will be reported elsewhere. This framing allowed for the development of an operational protocol for an interventional trial and differentiates the current protocol from previous studies that have administered classic psychedelics to healthy participants (Carhart-Harris et al, 2015, 2016Dolder et al, 2017;Preller et al, 2019;Schmid et al, 2015) that have evaluated only safety, pharmacokinetics, and/or neurobiological outcomes.…”

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

“…-placebo-controlled, cross-over, within-subject, balanced-order, double-dummy -fMRI and MEG (data published in other study [39]), further questionnaire assessment 2017), who noted that the subjective effects of LSD may not be primarily characterized by mystical and spiritual experiences, with the possible explanation that these findings are highly depend on the set and setting used in the study [34]. In contrast, the study by Family et al (2022) suggests that doses as low as 50 µg may already evoke full mystical-type experiences in certain individuals, depending on the set and setting [63]. Taken together, mystical-type experiences may be less predicted by LSD dose than by extra-pharmacological factors.…”

Springtime for psychopharmacology

“…Furthermore, respondents who reported prior psychiatric diagnoses, including depression, anxiety, substance misuse and post-traumatic stress disorder (PTSD) reported improvements in related symptoms. Family et al (2022) conducted a Phase I, proof-of-concept study with lysergic acid diethylamide (LSD) that used both open-label and double-blind placebo-controlled design. The study evaluated the safety, tolerability, pharmacokinetics and subjective effects of 50, 75 and 100 μg of LSD in healthy volunteers.…”

“…Family et al (2022) conducted a Phase I, proof-of-concept study with lysergic acid diethylamide (LSD) that used both open-label and double-blind placebo-controlled design. The study evaluated the safety, tolerability, pharmacokinetics and subjective effects of 50, 75 and 100 μg of LSD in healthy volunteers.…”