Objectives : Psychedelics are powerful psychoactive substances. Natural psychedelics have been used for millennia by human civilizations, in particular in Latin America, while synthetic psychedelics were discovered in the 50s, giving rise to a lot of research before they were prohibited. More recently, their therapeutic properties have been studied especially to help patients with psychiatric conditions, psychological distress or substance use disorders. This article is a systematic review of the literature which aims to provide an overview of all studies that assessed the efficacy of psychedelics, i.e. psilocybin, ayahuasca and lysergic acid diethylamide (LSD), on psychiatric diseases and addictions. Methods : We conducted this literature review following the PRISMA recommendations. MEDLINE, PsycInfo, Web of Science and Scopus were searched from January 1990 to May 2020 with the following keywords “(ayahuasca OR psilocybin OR lysergic acid diethylamide) AND (depression OR anxiety OR major depressive disorder OR bipolar disorder OR anxiety disorder OR substance use disorder OR dependence)”. Results : Twenty-five articles met the inclusion criteria. Five articles studied psychedelic efficacy in the treatment of life-threatening diseases related to anxiety and depression: four were randomized controlled crossover trials (three with psilocybin for a total of 92 patients, and one with LSD, n=12), and one was a long-term follow-up study. Eleven articles explored the efficacy of psychedelics in the treatment of major depressive episodes: two were open-labeled trials (one with ayahuasca, n=17, one with psilocybin, n=20), one was a randomized controlled trial using ayahuasca against placebo (n=29), and the others were long-term follow-up studies or assessed more precise dimensions of the depressive disorder, such as suicidality, emotion processing or personality traits. Eight articles studied the efficacy of psychedelics in the treatment of addictions: two were open-labeled studies using psilocybin (one in alcohol use disorder, n=10, and one in tobacco use disorder, n=15), and the others were long-term follow-up studies or retrospective observational descriptive studies on alcohol, tobacco, opioids, cannabis, and psychostimulants. One study explored the efficacy of psilocybin in obsessional-compulsive disorder (n=9). Overall, these studies found a quick and important response after psychedelic administration that lasted for several months, even after a single dose. However most of these studies were descriptive or open-label studies conducted on small size samples. No severe adverse events occurred. Conclusions : Psychedelics are promising treatments for anxiety, depression and addiction, their efficacy is quick and sustainable, and they are well tolerated. These effects need to be confirmed in larger studies and compared to standard care.