King's College London

Psilocybin is the active compound found in 'magic mushrooms’. It is being tested as a possible treatment for a number of mental health conditions. Psilocybin produces profound alterations of experience. This may be important for its therapeutic effect, but researchers can’t currently determine this due to the nature of the drug.

Typically for a clinical trial, some people receive the drug and some receive a placebo (a dummy pill). For psilocybin, people often are aware which one they receive due to the effects of the drug, making it hard to separate the effects of the altered experience from other possible effects it may have.

One way to separate these two possibilities is to reduce the chance that people know if they received the drug or a placebo. SLEEPY (Sleep Blinding Psilocybin, A Feasibility Study) aims to find out whether psilocybin can be given to people to act while they sleep, so that they are less likely to know whether they have received psilocybin or a placebo (an inactive treatment).

Researchers will investigate whether this approach is practical and whether psilocybin affects sleep. The study will also explore participants’ experiences during the night, as well as measures of wellbeing and memory.

If successful, SLEEPY would establish the first practical oral sleep-blinding paradigm for psilocybin. It would create a new way to investigate how much the effects of psilocybin depend on people’s expectations of treatment and their conscious psychedelic experience.

Background

Depression is a common and serious condition. Current treatments do not work well for 1 in 3 people. Psilocybin is a new drug that might help when other treatments fail., which may be approved soon. However, there are still important unanswered questions about how it works.

One question is the role of people’s expectations of treatment. Normally when testing drugs researchers usually hide whether people receive a drug or inactive pill (a placebo). This does not work with psilocybin because its effects are obvious. This makes it hard to understand how much of any difference found in trials is down to people’s expectations. A second question is if the intense, and often meaningful, experiences people have after taking a psychedelic drug are needed for their therapeutic effects. At present is it impossible to separate these effects from the action of the drug making testing this impossible.

Giving psilocybin to people while they sleep might help to solve this problem. It may make people unsure if they received the drug or a placebo and may also alter their conscious experience. This study aims to develop this method to test psilocybin.

The SLEEPY study will recruit healthy people, not on current psychotropic medication who are aged 18-65, and who have used psilocybin before.

The first phase has three stages each using different participants:

Stage 1: Awake participants will take delayed-release psilocybin. Researchers will check how long it takes to start working.

Stage 2: Psilocybin will be given before participants go to sleep on site. If it disrupts sleep, researchers will test sedatives to help participants stay asleep.

Stage 3: Researchers will test the effects of psilocybin and sedatives together on awake participants. This will show how the drugs work together.

In the second phase 16 participants will take psilocybin during one session and an inactive pill during another. The two sessions will be four weeks apart. Participants will not know which drug they received each time. 

In addition to assessing whether people know what they received, researchers will collect data on sleep using electroencephalography (EEG). EEG is a safe, non-invasive method of measuring the brain’s electrical activity using small sensors placed on the scalp. The researchers will also conduct interviews asking participants of remembered nighttime experiences, collect questionnaires on wellbeing and conduct two memory tasks.