Direct Comparison of Altered States of Consciousness Induced by LSD and Psilocybin

Direct Comparison of Altered States of Consciousness Induced by LSD and Psilocybin in a Random-order Placebo-controlled Cross-over Study in Healthy Subjects

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.

Inclusion Criteria:

1. Age between 25 and 65 years.
2. Understanding of the German language.
3. Understanding the procedures and the risks that are associated with the study.
4. Participants must be willing to adhere to the protocol and sign the consent form.
5. Participants must be willing to refrain from taking illicit psychoactive substances during the study.
6. Participants must be willing to drink only alcohol-free liquids and no coffee, black or green tea, or energy drink after midnight of the evening before the study session, as well as during the study day.
7. Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.
8. Women of childbearing potential must have a negative pregnancy test at the beginning of the study. Pregnancy tests are repeated before each study session.
9. Women of childbearing potential must be willing to use double-barrier birth control
10. Body mass index 18-29 kg/m2.

Exclusion Criteria:

1. Chronic or acute medical condition
2. Current or previous major psychiatric disorder
3. Psychotic disorder in first-degree relatives
4. Illicit substance use (with the exception of cannabis) more than 10 times or any time within the previous two months.
5. Pregnant or nursing women.
6. Participation in another clinical trial (currently or within the last 30 days)
7. Use of medications that may interfere with the effects of the study medications (any psychiatric medications)
8. Tobacco smoking (>10 cigarettes/day)
9. Consumption of alcoholic drinks (>10/week)
10. Bodyweight < 50 kg