597. ARE SIDE EFFECTS NECESSARY FOR ANTIDEPRESSIVE TREATMENT: THE PSILOCYBIN EXPERIENCE
The International Journal of Neuropsychopharmacology – August 01, 2025
Source: OpenAlex
Summary
A critical debate in Psychology and Medicine centers on Psilocybin and other Psychedelics. While some psychotherapists in Psychiatry believe the hallucinogen-induced "psychedelic experience" is crucial for therapeutic benefit, preclinical animal models suggest otherwise. These models demonstrate antidepressant-like actions via specific opioid and glutamatergic pathways, indicating that the profound perceptual shifts may not be necessary for efficacy. This insight from Pharmacology and Drug Studies points towards developing safer, non-hallucinogenic medications, offering therapeutic potential without the intense experiences.
Abstract
Abstract Background Psycholicibin is now studied in clinical settings. Aims & Objectives To elaborate if side effects are part of the therapeutic process. Method Literature overview and personal statement. Results The recent development of the socalled “psychedelics” reminds us that unfortunately some medications which we used in psychiatry have a large burden of side effects, like the anticholinerg side effects of the older tricyclic antidepressants as well as the extrapyramidal motoric side effects of socalled typical neuroleptics. These side effects were sometimes also related to the efficacy of these medications. Interestingly, it seems that the neglection of side effects is still an unresolved issue in clinical psychopharmacology, since there are researchers and clinicians who argue that the psychedelic experience induced with psychedelics are associated with therapeutic efficacy. Furthermore, studies in this field not even mention these side effects as such and argue, when confronted with the issue, that these are necessary for the therapeutic outcome. Even more so, there are researchers and clinicians who think that these side effects allow the patients to understand their unconscious, like in the early days of psychoanalysis. However, recent preclinical animal models demonstrated antidepressant-like behavioral effects and synaptic actions that are not only linked to the serotonergic activation (mainly via the 5HT2A receptor), but also via opioid and glutamatergic pathways which share neurobiological mechanisms of network reconfiguration likely by intracellular plasticity cascades. Discussion & Conclusions It seems to be important from my point of view to develop antidepressant medications devoid of the side effect of psychedelic experience in order to produce a safer, non-hallucinogenic medication that has therapeutic potential for depressed patients.