Psilocybin and LSD have shown potential as rapid-acting antidepressants, prompting the scientific community to investigate their safety, tolerability, and therapeutic applications more closely. The research paper "Safety issues of psilocybin and LSD as potential rapid acting antidepressants and potential challenges" published in the "Expert Opinion on Drug Safety" journal by Rossi, G., Hallak, J., José Carlos Bouso Saiz, and R. G. dos Santos in 2022, highlights several key findings relevant to the context of psychedelic harm reduction and public understanding of risks associated with these substances.The study reviews randomized, double-blind, and controlled trials assessing the antidepressant effects of psilocybin and LSD. A significant takeaway is that there were no serious adverse events (AEs) related to the administration of psilocybin and LSD. Most adverse events were manageable, expected, and transient. However, it acknowledges safety and tolerability concerns regarding some effects, such as dissociation, paranoia, and confusion. These findings suggest a need for further research with larger sample sizes to confirm the therapeutic effects of psilocybin and LSD and to investigate their safety and tolerability in greater detail.From a harm reduction perspective, these findings underscore the importance of developing safety protocols for the use of psilocybin and LSD as therapeutic agents. The absence of serious adverse events in controlled clinical settings suggests that, under proper supervision and with adequate preparation and support, the use of these substances can be relatively safe. Nonetheless, the potential for experiencing challenging psychological effects calls for careful consideration of set (mindset of the individual) and setting (the physical and social environment) in therapeutic contexts, as well as the implementation of screening procedures to identify individuals who may be at higher risk of adverse reactions.In summary, psilocybin and LSD offer promising avenues for rapid antidepressant treatment, with a generally favorable safety profile in controlled clinical settings. However, their potential for inducing challenging psychological effects necessitates further research and underscores the importance of harm reduction practices in therapeutic use. The development of comprehensive safety protocols and the consideration of individual patient factors are essential for mitigating risks and maximizing the therapeutic potential of these substances (Rossi, G., Hallak, J., José Carlos Bouso Saiz, & R. G. dos Santos, 2022).