[Therapeutic applications of classical serotonergic psyche-delics: neurobiological mechanisms and neural networks]

Psychedelics have received renewed scientific attention in recent decades because of their potential to induce long-term changes in behaviour and cognition with potential therapeutic applications in various psychiatric indications.

To provide a brief overview of the neurobiological action of classical serotonergic psychedelics, their impact on neural networks and implications for potential clinical applications.

We provide a non-exhaustive review of the current literature by subsequently and thematically outlining: 1. the empirical evidence concerning the action of psychedelics on the level of individual neuronal cells; 2.their effects on the level of neural networks; and 3. their influence on neuroplasticity and 4. different mechanistic hypotheses about the potential therapeutic effects of psychedelic substances. We illustrate this through key studies that provided important historical breakthroughs and show how these findings were integrated into the current theories.

Studies evidence the central role of 5-HT2A receptors for the subjective effects of psychedelics, as well as affinity for many other receptors. Through a complex cascade of downstream effects, psychedelic substances lead to dynamic changes in different neural circuits and increased neuroplasticity which potentially persists even after the subjective effects have subsided. Several theoretical concepts offer complementary explanations for the relationship between the effects at neurobiological and psychological levels.

Although the underlying neurobiological mechanisms are not yet fully understood and methodological challenges remain, the current research offers valuable insights into how a single or a few administrations of a psychedelic substance could lead to symptom improvements that can last for weeks, months, or even longer, if used in a supportive setting and in combination with psychotherapy.