OPEN Foundation

N. Family

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

December 18, 2019 / LSD, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications, Safety / By / , , , ,

Abstract

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).
Family, N., Maillet, E. L., Williams, L. T., Krediet, E., Carhart-Harris, R. L., Williams, T. M., … & Raz, S. (2019). Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers. Psychopharmacology, 1-13., https://doi.org/10.1007/s00213-019-05417-7
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The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial.

November 26, 2018 / Consciousness, LSD, Papers, Psychology, Psychopharmacology, Publications / By / , , , , ,

Abstract

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.
Yanakieva, S., Polychroni, N., Family, N., Williams, L. T., Luke, D. P., & Terhune, D. B. (2018). The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial. Psychopharmacology, 1-12., 10.1007/s00213-018-5119-x
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Semantic activation in LSD: evidence from picture naming

August 11, 2016 / Consciousness, LSD, Other subjects, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Lysergic acid diethylamide (LSD) is a classic psychedelic drug that alters cognition in a characteristic way. It has been suggested that psychedelics expand the breadth of cognition via actions on the central nervous system. Previous work has shown changes in semantic processing under psilocybin (a related psychedelic to LSD) that are consistent with an increased spread of semantic activation. The present study investigates this further using a picture-naming task and the psychedelic, LSD. Ten participants completed the task under placebo and LSD. Results revealed significant effects of LSD on accuracy and error correction that were consistent with an increased spread of semantic activation under LSD. These results are consistent with a generalised “entropic” effect on the mind. We suggest incorporating direct neuroimaging measures in future studies, and to employ more naturalistic measures of semantic processing that may enhance ecological validity.

Family, N., Vinson, D., Vigliocco, G., Kaelen, M., Bolstridge, M., Nutt, D. J., & Carhart-Harris, R. L. (2016). Semantic activation in LSD: evidence from picture naming. Language, Cognition and Neuroscience, 1-8. http://dx.doi.org/10.1080/23273798.2016.1217030
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LSD enhances the emotional response to music

August 11, 2015 / LSD, Other subjects, Papers, Psychology, Psychopharmacology, Publications / By / , , , , , ,

Abstract

RATIONALE:

There is renewed interest in the therapeutic potential of psychedelic drugs such as lysergic acid diethylamide (LSD). LSD was used extensively in the 1950s and 1960s as an adjunct in psychotherapy, reportedly enhancing emotionality. Music is an effective tool to evoke and study emotion and is considered an important element in psychedelic-assisted psychotherapy; however, the hypothesis that psychedelics enhance the emotional response to music has yet to be investigated in a modern placebo-controlled study.

OBJECTIVES:

The present study sought to test the hypothesis that music-evoked emotions are enhanced under LSD.

METHODS:

Ten healthy volunteers listened to five different tracks of instrumental music during each of two study days, a placebo day followed by an LSD day, separated by 5-7 days. Subjective ratings were completed after each music track and included a visual analogue scale (VAS) and the nine-item Geneva Emotional Music Scale (GEMS-9).

RESULTS:

Results demonstrated that the emotional response to music is enhanced by LSD, especially the emotions “wonder”, “transcendence”, “power” and “tenderness”.

CONCLUSIONS:

These findings reinforce the long-held assumption that psychedelics enhance music-evoked emotion, and provide tentative and indirect support for the notion that this effect can be harnessed in the context of psychedelic-assisted psychotherapy. Further research is required to test this link directly.

Kaelen, M., Barrett, F. S., Roseman, L., Lorenz, R., Family, N., Bolstridge, M., … & Carhart-Harris, R. L. (2015). LSD enhances the emotional response to music. Psychopharmacology, 1-8. https://dx.doi.org/10.1007/s00213-015-4014-y
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30 April - Q&A with Rick Strassman

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