In past years, clinical trials with psychedelic substances have been conducted to find alternative treatments for hard-to-treat mental health conditions such as treatment-resistant depression, cancer-related depression and anxiety symptoms and post-traumatic stress disorder. Clinical research has advanced under the regulation of national ethical and medication authorities for clinical trials, much as for any study testing a new intervention. Indeed, recent research on psychedelics has been conducted under the protected conditions of clinical trials, following international guidelines. However, psychedelic treatments present unique ethical and regulatory challenges that may not have been fully addressed within the traditional structures of clinical trial regulation. These challenges need to be addressed before these substances are approved for use in general clinical practice.