[Neurotrophic mechanisms of psychedelic therapy].

Psychedelic drugs, often referred to as hallucinogens, are quite distinct from other classes of psychotropic drugs. Although the subjective and behavioral effects they induce are quite dramatic, they possess little addictive potential when compared to nicotine, alcohol or opiates. Since the discovery of ketamine antidepressant effects, there has been growing interest for these molecules. Serotonergic psychedelics such as psilocybin and lysergic acid diethylamide (LSD) are gaining attention as potential treatments for depression and addiction, similarly to 3,4-methylenedioxymethamphetamine (MDMA) for post-traumatic stress disorder (PTSD), and ibogaine for addiction. Although they possess distinct pharmacological profiles, their kinetics of action are quite similar: the therapeutic effects are felt within the hours following administration, and last well beyond drug elimination by the organism. This strongly suggests the induction of neurogenic and plastic mechanisms, including the involvement of trophic factors. This review will explore the literature dealing with the effects of psychedelics on neurotrophins, as well as the plastic adaptations that they induce, in an attempt to understand their surprising therapeutic potential. We will show that although ketamine and serotonergic psychedelics have affinity for very different receptors (NMDA, 5-HT2A), they ultimately initiate similar plastic adaptations in the prefrontal cortex through the involvement of the brain-derived neurotrophic factor (BDNF). We will see that although MDMA uses the same receptors as serotonergic psychedelics to alleviate PTSD symptoms, its effect on BDNF levels seem paradoxical and quite different. Finally, we show how ibogaine could exert its anti-addictive properties through a completely different neurotrophic factor than other psychedelic drugs, the glial cell line-derived neurotrophic factor (GDNF). While the current literature concerning the psychiatric applications of psychedelic therapy is encouraging, it remains to be determined whether their benefits could be obtained without their psychotomimetic effects, or concerns over potential toxicity. Utilisation des psych d liques en psychiatrie : lien avec les neurotrophines. Les psych d liques, souvent appel s hallucinog nes, sont une classe de psychotropes tr s singuli re. Les effets subjectifs et comportementaux qu ils induisent sont tr s impressionnants, et malgr leur toxicit potentielle, le risque d addiction est relativement faible par rapport la nicotine, l alcool ou les opiac s. Depuis la d couverte des effets antid presseurs de la k tamine, il existe un regain d int r t pour cette classe de mol cules. En effet, la psilocybine et l acide lysergique di thylamide (LSD) gagnent de la popularit en tant que traitement pour la d pression et l addiction, la 3,4-m thyl nedioxym thamph tamine (MDMA) pour l tat de stress post-traumatique, et l iboga ne pour l addiction. Malgr des profils pharmacologiques distincts, ces diff rentes drogues partagent une cin tique d action similaire : leurs effets th rapeutiques se font ressentir dans les heures suivant l administration et perdurent au-del de leur limination par l organisme. Ceci sugg re des m canismes plastiques et neurog niques impliquant entre autres des facteurs trophiques. Cette revue explorera la litt rature concernant les effets de ces diff rents compos s sur les neurotrophines, ainsi que les adaptations plastiques qui sont mises en place dans les heures et jours suivant l administration, afin de comprendre leur potentiel th rapeutique tonnant.