Sleep Blinding Psilocybin: A Feasibility Study

Context Depression is a common condition that affects people around the world and causes serious problems in their lives. However, current treatments do not work well for 1 in 3 people. Psilocybin, or "magic mushrooms”, are a new medication that might help when other treatments fail. Psilocybin changes how people think and feel, creating a dreamlike state. However, we do not fully understand how it works. There are three main ideas about how psilocybin helps: Expectation: People might feel better because they expect the drug to work. This is called the placebo effect. The excitement around psychedelics might make this effect stronger. Meaningful experiences: The dreamlike state caused by psilocybin can be powerful. It may help people make changes that improve their mood. Brain changes: Psilocybin may cause changes in the brain, like growing new brain cells. The Challenge To test medication, researchers usually hide whether people get a drug or inactive pill. This does not work with Psilocybin because its effects are obvious. This makes it hard to understand why psilocybin works. Giving psilocybin to people while they sleep might solve this problem as sleeping people may not notice the effects of the drug. People also may not have the same meaningful experiences when asleep. A small study in the U.S. tested this by giving psilocybin through a vein to sleeping people. Participants woke up unless they were also given clonidine, a sedative medication. When given both psilocybin and clonidine people did not know if they got a drug or a placebo. We do not know if combining these changes how psilocybin works. Making psilocybin to give through a vein is slow and expensive. We also understand less about psilocybin given through a vein than as a tablet. A tablet would be cheaper and easier to use which could make larger studies possible. Therefore, we want to test if using a tablet is possible. We will used a delayed release tablet taken just before going to sleep. Aims and Objectives Find out how quickly delayed-release psilocybin works. Figure out the best way to give psilocybin to people while keeping them asleep. Understand if combining sedatives and psilocybin changes how psilocybin works. Test if people can tell if they got psilocybin or an inactive pill while asleep. Create a guide for other researchers to use this method in future studies. Potential Applications and Benefits Understanding how psilocybin works is very important. This method would be used to help study this in the future. Currently, there is uncertainty about how much "expectation" affects medications like psilocybin. This uncertainty has made some governments cautious to approve medications like these. Learning more about this could help these medications become available to people sooner. We have also talked to both people with depression and participants in past trials. They believe it is very important to understand why psilocybin works. This knowledge could help patients better understand their treatment. Understanding how psilocybin works would also guide researchers who are developing new medications based on psilocybin. Some other drugs have obvious effects, making them hard to test using regular methods. This method could also be used to help test these other drugs.