Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects

Growing interest has been seen in using lysergic acid diethylamide (LSD) and psilocybin in psychiatric research and therapy. However, no modern studies have evaluated differences in subjective and autonomic effects of LSD and psilocybin or their similarities and dose equivalence. We used a double-bl...

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Published in:	Neuropsychopharmacology (New York, N.Y.) Vol. 47; no. 6; pp. 1180 - 1187
Main Authors:	Holze, Friederike, Ley, Laura, Müller, Felix, Becker, Anna M, Straumann, Isabelle, Vizeli, Patrick, Kuehne, Sebastian Silva, Roder, Marc A, Duthaler, Urs, Kolaczynska, Karolina E, Varghese, Nimmy, Eckert, Anne, Liechti, Matthias E
Format:	Journal Article
Language:	English
Published:	England Nature Publishing Group 01.05.2022
Subjects:	Acute effects Autonomic nervous system Blood pressure Brain-derived neurotrophic factor Cognition Cortisol Double-Blind Method Double-blind studies Female Hallucinogens Healthy Volunteers Heart rate Humans LSD Lysergic Acid Diethylamide Lysergide Male Oxytocin Pharmacokinetics Placebos Plasma levels Prolactin Psilocybin Psilocybin - pharmacology Psychedelic drugs
ISSN:	0893-133X, 1740-634X, 1740-634X
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Abstract	Growing interest has been seen in using lysergic acid diethylamide (LSD) and psilocybin in psychiatric research and therapy. However, no modern studies have evaluated differences in subjective and autonomic effects of LSD and psilocybin or their similarities and dose equivalence. We used a double-blind, randomized, placebo-controlled, crossover design in 28 healthy subjects (14 women, 14 men) who underwent five 25 h sessions and received placebo, LSD (100 and 200 µg), and psilocybin (15 and 30 mg). Test days were separated by at least 10 days. Outcome measures included self-rating scales for subjective effects, autonomic effects, adverse effects, effect durations, plasma levels of brain-derived neurotrophic factor (BDNF), prolactin, cortisol, and oxytocin, and pharmacokinetics. The doses of 100 and 200 µg LSD and 30 mg psilocybin produced comparable subjective effects. The 15 mg psilocybin dose produced clearly weaker subjective effects compared with both doses of LSD and 30 mg psilocybin. The 200 µg dose of LSD induced higher ratings of ego-dissolution, impairments in control and cognition, and anxiety than the 100 µg dose. The 200 µg dose of LSD increased only ratings of ineffability significantly more than 30 mg psilocybin. LSD at both doses had clearly longer effect durations than psilocybin. Psilocybin increased blood pressure more than LSD, whereas LSD increased heart rate more than psilocybin. However, both LSD and psilocybin showed comparable cardiostimulant properties, assessed by the rate-pressure product. Both LSD and psilocybin had dose-proportional pharmacokinetics and first-order elimination. Both doses of LSD and the high dose of psilocybin produced qualitatively and quantitatively very similar subjective effects, indicating that alterations of mind that are induced by LSD and psilocybin do not differ beyond the effect duration. Any differences between LSD and psilocybin are dose-dependent rather than substance-dependent. However, LSD and psilocybin differentially increased heart rate and blood pressure. These results may assist with dose finding for future psychedelic research.Trial registration: ClinicalTrials.gov identifier: NCT03604744.
AbstractList	Growing interest has been seen in using lysergic acid diethylamide (LSD) and psilocybin in psychiatric research and therapy. However, no modern studies have evaluated differences in subjective and autonomic effects of LSD and psilocybin or their similarities and dose equivalence. We used a double-blind, randomized, placebo-controlled, crossover design in 28 healthy subjects (14 women, 14 men) who underwent five 25 h sessions and received placebo, LSD (100 and 200 µg), and psilocybin (15 and 30 mg). Test days were separated by at least 10 days. Outcome measures included self-rating scales for subjective effects, autonomic effects, adverse effects, effect durations, plasma levels of brain-derived neurotrophic factor (BDNF), prolactin, cortisol, and oxytocin, and pharmacokinetics. The doses of 100 and 200 µg LSD and 30 mg psilocybin produced comparable subjective effects. The 15 mg psilocybin dose produced clearly weaker subjective effects compared with both doses of LSD and 30 mg psilocybin. The 200 µg dose of LSD induced higher ratings of ego-dissolution, impairments in control and cognition, and anxiety than the 100 µg dose. The 200 µg dose of LSD increased only ratings of ineffability significantly more than 30 mg psilocybin. LSD at both doses had clearly longer effect durations than psilocybin. Psilocybin increased blood pressure more than LSD, whereas LSD increased heart rate more than psilocybin. However, both LSD and psilocybin showed comparable cardiostimulant properties, assessed by the rate-pressure product. Both LSD and psilocybin had dose-proportional pharmacokinetics and first-order elimination. Both doses of LSD and the high dose of psilocybin produced qualitatively and quantitatively very similar subjective effects, indicating that alterations of mind that are induced by LSD and psilocybin do not differ beyond the effect duration. Any differences between LSD and psilocybin are dose-dependent rather than substance-dependent. However, LSD and psilocybin differentially increased heart rate and blood pressure. These results may assist with dose finding for future psychedelic research.Trial registration: ClinicalTrials.gov identifier: NCT03604744 Growing interest has been seen in using lysergic acid diethylamide (LSD) and psilocybin in psychiatric research and therapy. However, no modern studies have evaluated differences in subjective and autonomic effects of LSD and psilocybin or their similarities and dose equivalence. We used a double-blind, randomized, placebo-controlled, crossover design in 28 healthy subjects (14 women, 14 men) who underwent five 25 h sessions and received placebo, LSD (100 and 200 µg), and psilocybin (15 and 30 mg). Test days were separated by at least 10 days. Outcome measures included self-rating scales for subjective effects, autonomic effects, adverse effects, effect durations, plasma levels of brain-derived neurotrophic factor (BDNF), prolactin, cortisol, and oxytocin, and pharmacokinetics. The doses of 100 and 200 µg LSD and 30 mg psilocybin produced comparable subjective effects. The 15 mg psilocybin dose produced clearly weaker subjective effects compared with both doses of LSD and 30 mg psilocybin. The 200 µg dose of LSD induced higher ratings of ego-dissolution, impairments in control and cognition, and anxiety than the 100 µg dose. The 200 µg dose of LSD increased only ratings of ineffability significantly more than 30 mg psilocybin. LSD at both doses had clearly longer effect durations than psilocybin. Psilocybin increased blood pressure more than LSD, whereas LSD increased heart rate more than psilocybin. However, both LSD and psilocybin showed comparable cardiostimulant properties, assessed by the rate-pressure product. Both LSD and psilocybin had dose-proportional pharmacokinetics and first-order elimination. Both doses of LSD and the high dose of psilocybin produced qualitatively and quantitatively very similar subjective effects, indicating that alterations of mind that are induced by LSD and psilocybin do not differ beyond the effect duration. Any differences between LSD and psilocybin are dose-dependent rather than substance-dependent. However, LSD and psilocybin differentially increased heart rate and blood pressure. These results may assist with dose finding for future psychedelic research.Trial registration: ClinicalTrials.gov identifier: NCT03604744. Growing interest has been seen in using lysergic acid diethylamide (LSD) and psilocybin in psychiatric research and therapy. However, no modern studies have evaluated differences in subjective and autonomic effects of LSD and psilocybin or their similarities and dose equivalence. We used a double-blind, randomized, placebo-controlled, crossover design in 28 healthy subjects (14 women, 14 men) who underwent five 25 h sessions and received placebo, LSD (100 and 200 µg), and psilocybin (15 and 30 mg). Test days were separated by at least 10 days. Outcome measures included self-rating scales for subjective effects, autonomic effects, adverse effects, effect durations, plasma levels of brain-derived neurotrophic factor (BDNF), prolactin, cortisol, and oxytocin, and pharmacokinetics. The doses of 100 and 200 µg LSD and 30 mg psilocybin produced comparable subjective effects. The 15 mg psilocybin dose produced clearly weaker subjective effects compared with both doses of LSD and 30 mg psilocybin. The 200 µg dose of LSD induced higher ratings of ego-dissolution, impairments in control and cognition, and anxiety than the 100 µg dose. The 200 µg dose of LSD increased only ratings of ineffability significantly more than 30 mg psilocybin. LSD at both doses had clearly longer effect durations than psilocybin. Psilocybin increased blood pressure more than LSD, whereas LSD increased heart rate more than psilocybin. However, both LSD and psilocybin showed comparable cardiostimulant properties, assessed by the rate-pressure product. Both LSD and psilocybin had dose-proportional pharmacokinetics and first-order elimination. Both doses of LSD and the high dose of psilocybin produced qualitatively and quantitatively very similar subjective effects, indicating that alterations of mind that are induced by LSD and psilocybin do not differ beyond the effect duration. Any differences between LSD and psilocybin are dose-dependent rather than substance-dependent. However, LSD and psilocybin differentially increased heart rate and blood pressure. These results may assist with dose finding for future psychedelic research.Trial registration: ClinicalTrials.gov identifier: NCT03604744.Growing interest has been seen in using lysergic acid diethylamide (LSD) and psilocybin in psychiatric research and therapy. However, no modern studies have evaluated differences in subjective and autonomic effects of LSD and psilocybin or their similarities and dose equivalence. We used a double-blind, randomized, placebo-controlled, crossover design in 28 healthy subjects (14 women, 14 men) who underwent five 25 h sessions and received placebo, LSD (100 and 200 µg), and psilocybin (15 and 30 mg). Test days were separated by at least 10 days. Outcome measures included self-rating scales for subjective effects, autonomic effects, adverse effects, effect durations, plasma levels of brain-derived neurotrophic factor (BDNF), prolactin, cortisol, and oxytocin, and pharmacokinetics. The doses of 100 and 200 µg LSD and 30 mg psilocybin produced comparable subjective effects. The 15 mg psilocybin dose produced clearly weaker subjective effects compared with both doses of LSD and 30 mg psilocybin. The 200 µg dose of LSD induced higher ratings of ego-dissolution, impairments in control and cognition, and anxiety than the 100 µg dose. The 200 µg dose of LSD increased only ratings of ineffability significantly more than 30 mg psilocybin. LSD at both doses had clearly longer effect durations than psilocybin. Psilocybin increased blood pressure more than LSD, whereas LSD increased heart rate more than psilocybin. However, both LSD and psilocybin showed comparable cardiostimulant properties, assessed by the rate-pressure product. Both LSD and psilocybin had dose-proportional pharmacokinetics and first-order elimination. Both doses of LSD and the high dose of psilocybin produced qualitatively and quantitatively very similar subjective effects, indicating that alterations of mind that are induced by LSD and psilocybin do not differ beyond the effect duration. Any differences between LSD and psilocybin are dose-dependent rather than substance-dependent. However, LSD and psilocybin differentially increased heart rate and blood pressure. These results may assist with dose finding for future psychedelic research.Trial registration: ClinicalTrials.gov identifier: NCT03604744.
Author	Eckert, Anne Liechti, Matthias E Varghese, Nimmy Kuehne, Sebastian Silva Müller, Felix Kolaczynska, Karolina E Becker, Anna M Straumann, Isabelle Roder, Marc A Vizeli, Patrick Ley, Laura Duthaler, Urs Holze, Friederike
Author_xml	– sequence: 1 givenname: Friederike orcidid: 0000-0003-3143-1519 surname: Holze fullname: Holze, Friederike organization: Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland – sequence: 2 givenname: Laura surname: Ley fullname: Ley, Laura organization: Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland – sequence: 3 givenname: Felix surname: Müller fullname: Müller, Felix organization: Psychiatric University Hospital, University of Basel, Basel, Switzerland – sequence: 4 givenname: Anna M surname: Becker fullname: Becker, Anna M organization: Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland – sequence: 5 givenname: Isabelle surname: Straumann fullname: Straumann, Isabelle organization: Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland – sequence: 6 givenname: Patrick orcidid: 0000-0002-5954-4446 surname: Vizeli fullname: Vizeli, Patrick organization: Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland – sequence: 7 givenname: Sebastian Silva surname: Kuehne fullname: Kuehne, Sebastian Silva organization: Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland – sequence: 8 givenname: Marc A surname: Roder fullname: Roder, Marc A organization: Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland – sequence: 9 givenname: Urs orcidid: 0000-0002-7811-3932 surname: Duthaler fullname: Duthaler, Urs organization: Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland – sequence: 10 givenname: Karolina E surname: Kolaczynska fullname: Kolaczynska, Karolina E organization: Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland – sequence: 11 givenname: Nimmy surname: Varghese fullname: Varghese, Nimmy organization: Transfaculty Research Platform Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland – sequence: 12 givenname: Anne orcidid: 0000-0002-9341-3669 surname: Eckert fullname: Eckert, Anne organization: Transfaculty Research Platform Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland – sequence: 13 givenname: Matthias E orcidid: 0000-0002-1765-9659 surname: Liechti fullname: Liechti, Matthias E email: matthias.liechti@usb.ch, matthias.liechti@usb.ch organization: Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. matthias.liechti@usb.ch
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PublicationTitle	Neuropsychopharmacology (New York, N.Y.)
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Snippet	Growing interest has been seen in using lysergic acid diethylamide (LSD) and psilocybin in psychiatric research and therapy. However, no modern studies have...
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SubjectTerms	Acute effects Autonomic nervous system Blood pressure Brain-derived neurotrophic factor Cognition Cortisol Double-Blind Method Double-blind studies Female Hallucinogens Healthy Volunteers Heart rate Humans LSD Lysergic Acid Diethylamide Lysergide Male Oxytocin Pharmacokinetics Placebos Plasma levels Prolactin Psilocybin Psilocybin - pharmacology Psychedelic drugs
Title	Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects
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