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LSD (lysergic acid diethylamide) and psilocybin (the active substance in "magic mushrooms") are widely used for recreational purposes. Both substances are also increasingly used in psychiatric and psychological research to induce and investigate alterations in waking consciousness and associated brain functions (functional brain imaging, "model psychosis") . However, it has never been studied whether there are differences in the alterations in mind produced by these two substances. Both LSD and psilocybin are thought to induce hallucinations primarily via stimulation of the 5-HT2A receptor. However, there are differences in the receptor activation profiles between the two substances that may also induce different subjective effects. LSD potently stimulates the 5-HT2A receptor but also 5-HT2B/C, 5-HT1 and D1-3 receptors . Psilocin (the active metabolite of the prodrug psilocybin) also stimulates the 5-HT2A receptor but additionally inhibits the 5-HT transporter. In contrast to LSD, psilocybin has no affinity for D2 receptors. Both substances are used in neuroscience as pharmacological tools. However, there are no modern studies comparing these two substances directly within the same clinical study and research subjects and using validated psychometric tools. Therefore, the investigators will compare the acute effects of LSD, psilocybin and placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LSD-100, LSD-200, Psilocybin-15, Psilocybin-30, Placebo | Experimental | Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase |
|
| LSD-200, Psilocybin-15, Psilocybin-30, Placebo, LSD-100 | Placebo Comparator | Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase |
|
| Psilocybin-15, Psilocybin-30, Placebo, LSD-100, LSD-200 | Placebo Comparator | Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase |
|
| Psilocybin-30, Placebo, LSD-100, LSD-200, Psilocybin-15 | Placebo Comparator | Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase |
|
| Placebo, LSD-100, LSD-200, Psilocybin-15, Psilocybin-30 | Placebo Comparator | Cross-over within-subjects design with all treatment conditions, separated by a wash-out phase |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LSD | Drug | LSD 0.1 mg per os, single dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Altered states of consciousness | total 5D-ASC score (5-Dimensional Altered States of Consciousness Rating Scale) | 18 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Subjective effects assessed by VAS | VAS (Visual analog scale) | 18 Months |
| Subjective effects assessed by AMRS scales | AMRS scales (Adjective mood Rating scale) |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma levels of LSD and psilocin | assessment of plasma levels of LSD and psilocin | 18 Months |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Matthias E Liechti, MD, MAS | University Hospital, Basel, Switzerland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Pharmacology & Toxicology, University Hospital Basel | Basel | 4056 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36507738 | Derived | Holze F, Becker AM, Kolaczynska KE, Duthaler U, Liechti ME. Pharmacokinetics and Pharmacodynamics of Oral Psilocybin Administration in Healthy Participants. Clin Pharmacol Ther. 2023 Apr;113(4):822-831. doi: 10.1002/cpt.2821. Epub 2022 Dec 31. | |
| 35217796 | Derived | Holze F, Ley L, Muller F, Becker AM, Straumann I, Vizeli P, Kuehne SS, Roder MA, Duthaler U, Kolaczynska KE, Varghese N, Eckert A, Liechti ME. Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects. Neuropsychopharmacology. 2022 May;47(6):1180-1187. doi: 10.1038/s41386-022-01297-2. Epub 2022 Feb 25. |
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| ID | Term |
|---|---|
| D008238 | Lysergic Acid Diethylamide |
| D011562 | Psilocybin |
| ID | Term |
|---|---|
| D008237 | Lysergic Acid |
| D004873 | Ergolines |
| D004876 | Ergot Alkaloids |
| D000470 | Alkaloids |
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| LSD | Drug | LSD 0.2 mg per os, single dose |
|
| Psilocybin | Drug | Psilocybin 15 mg per os, single dose |
|
| Psilocybin | Drug | Psilocybin 30 mg per os, single dose |
|
| 18 Months |
| Psychotomimetic effects | ESI (Eppendorf Schizophrenia Inventory) | 18 Months |
| Mystical-type experiences assessed by SCQ | SCQ (States of consciousness questionnaire) | 18 Months |
| Mystical-type experiences assessed by MS scales | MS scales (Mysticism scale) | 18 Months |
| Effects on emotion processing | FERT (Face Emotion Recognition Task) | 18 Months |
| Autonomic effects assessed by heart rate | Heart rate | 18 Months |
| Autonomic effects assessed by blood pressure | Blood pressure (diastolic and systolic) | 18 Months |
| Autonomic effects assessed by body temperature | Body temperature | 18 Months |
| D006571 |
| Heterocyclic Compounds |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D026121 | Indole Alkaloids |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D014363 | Tryptamines |
| D054836 | Indolizidines |
| D007212 | Indolizines |