Abstract

The studies on the therapeutic effectiveness of psychedelics are producing promising results in a variety of settings such as life‐threatening illnesses, treatment-resistant depression, post‐traumatic stress disorder, and alcohol addiction. Despite these encouraging observations, a relevant portion of patients does not seem to benefit from the above mentioned interventions or end up relapsing. Consequently, research should focus on devising ways to improve response rates and stability of clinical gains, and existing literature on the underlying mechanisms of action of classic psychedelics highlights some interesting areas in need of development. More specifically, it was hypothesized that such gains may be mediated by an increase in neuroplasticity and the consequently increased sensitivity to the environment that compounds such as 5‐HT2AR agonists produce. This line of research sheds new light on the role that setting plays for individuals who take psychedelics and urges the scientific community to define the best models for clinical purposes. The study provides a review of psychological interventions currently used psychedelics: MDMA, psilocybin, LSD, Ketamine, Ayahuasca. In particular, both structured psychedelic‐assisted psychotherapeutic approaches ﴾e.g., Medication-Assisted Psychotherapy; MDMA Assisted Psychotherapy; Ketamine Psychedelic Therapy; Preparation, Support Integration﴿ and adapted approaches ﴾e.g., Motivational Enhancement Therapy, Mindfulness-Based Therapy, CognitiveBehavioral Conjoint Therapy﴿. Exploring these principles, procedures, underlying hypotheses and tenets could open a new line of research that has the potential to provide support to the idea that psychedelics are not just therapeutic agents per se but rather enabling factors of Psychedelic Psychotherapy: a tool exploiting increased contextual sensitivity to achieve and consolidate psychological health, relational satisfaction, deeper self‐awareness, and existential fulfillment. Finally, this research could reinforce arguments aimed at shifting public perception of such agents, a crucial component of the cultural feedback loop that may impact long‐term clinical outcomes in patients.