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.

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.

BACKGROUND: Classic psychedelics show promise in the treatment of mental health conditions; however, more scalable intervention protocols are needed to maximize access to these novel therapeutics. In this proof-of-concept study, perceptions of safety, subjective effects, and beliefs about the clinical utility of lysergic acid diethylamide (LSD) were evaluated among healthy participants (N = 31) administered 50 to 100 µg LSD in a treatment paradigm conceptualized as more scalable than traditional approaches to administering classic psychedelics. METHODS: Semi-structured interviews assessed participants' expectations, experience, and thoughts on the safety and efficacy of the study design. These interviews were transcribed for thematic analysis relating to perceptions of safety, subjective effects, and beliefs about the clinical utility of LSD. RESULTS: Most participants felt safe throughout the study, with a minority reporting concerns related to having a challenging experience that diminished over time. Participants attributed their feelings of safety to the study structure and support of their attendants, which allowed them to "let go" and immerse themselves in the experience without pre-occupation. Furthermore, participants reported transcendent, mystical-type experiences characteristic of classic psychedelics, with almost half highlighting the prominent role played by music during the acute period of drug action. Finally, participants endorsed support for the clinical utility of LSD in controlled environments, expressing the belief that LSD is safe and has the potential to help others. CONCLUSION: Findings provide preliminary support for the feasibility of this scalable interventional paradigm and set the stage for future critical research with clinical populations.

Correction to: The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial.

The manufacturer of the drug product was Onyx Scientific Limited UK, to cGMP standards.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers.

Research has shown that psychedelics, such as lysergic acid diethylamide (LSD), have profound anti-inflammatory properties mediated by 5-HT2A receptor signaling, supporting their evaluation as a therapeutic for neuroinflammation associated with neurodegenerative disease. OBJECTIVE: This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of orally repeated administration of 5 µg, 10 µg, and 20 µg LSD in older healthy individuals. In the current paper, we present safety, tolerability, pharmacokinetics, and pharmacodynamic measures that relate to safety, tolerability, and dose response. METHODS: This was a phase 1 double-blind, placebo-controlled, randomized study. Volunteers were randomly assigned to 1 of 4 dose groups (5 µg, 10 µg, 20 µg LSD, and placebo), and received their assigned dose on six occasions (i.e., every 4 days). RESULTS: Forty-eight older healthy volunteers (mean age = 62.9 years) received placebo (n = 12), 5 µg (n = 12), 10 µg (n = 12), or 20 µg (n = 12) LSD. LSD plasma levels were undetectable for the 5 µg group and peak blood plasma levels for the 10 µg and 20 µg groups occurred at 30 min. LSD was well tolerated, and the frequency of adverse events was no higher than for placebo. Assessments of cognition, balance, and proprioception revealed no impairment. CONCLUSIONS: Our results suggest safety and tolerability of orally administered 5 µg, 10 µg, and 20 µg LSD every fourth day over a 21-day period and support further clinical development of LSD for the treatment and prevention of Alzheimer's disease (AD).

The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial.

RATIONALE: Previous research demonstrating that lysergic acid diethylamide (LSD) produces alterations in time perception has implications for its impact on conscious states and a range of psychological functions that necessitate precise interval timing. However, interpretation of this research is hindered by methodological limitations and an inability to dissociate direct neurochemical effects on interval timing from indirect effects attributable to altered states of consciousness. METHODS: We conducted a randomised, double-blind, placebo-controlled study contrasting oral administration of placebo with three microdoses of LSD (5, 10, and 20 µg) in older adults. Subjective drug effects were regularly recorded and interval timing was assessed using a temporal reproduction task spanning subsecond and suprasecond intervals. RESULTS: LSD conditions were not associated with any robust changes in self-report indices of perception, mentation, or concentration. LSD reliably produced over-reproduction of temporal intervals of 2000 ms and longer with these effects most pronounced in the 10 µg dose condition. Hierarchical regression analyses indicated that LSD-mediated over-reproduction was independent of marginal differences in self-reported drug effects across conditions. CONCLUSIONS: These results suggest that microdose LSD produces temporal dilation of suprasecond intervals in the absence of subjective alterations of consciousness.

The development of the causative construction in Persian child language.

The acquisition of systematic patterns and exceptions in different languages can be readily examined using the causative construction. Persian allows four types of causative structures, including one productive multiword structure (i.e. the light verb construction). In this study, we examine the development of all four structures in Persian child speech between the ages of 1;11 and 6;7, in correspondence with their caregivers' speech. We define developmental stages based on dendrograms derived from variability clustering (Gries & Stoll, 2009). These stages are further substantiated by qualitative data, including overgeneralization errors and alternating structures. We find that Persian-speaking children learn to exploit two (i.e. lexical and light verb construction causatives) of the four constructions. They go from relying on lexical causatives to forming progressively constrained templates for the more complex light verb construction. This first study of the development of Persian causatives supports a usage-based account of verb-by-verb learning in child language development.