The study titled "Perceptions of psychedelic personality change, determinants of use, setting and drug moderation: Toward a holistic model" by Weiss et al. (2023) offers significant insights into how psychedelics influence personality changes, factors leading to their use, and the importance of set and setting in moderating these effects. This research is pivotal for understanding the complex dynamics of psychedelic experiences and their potential implications for harm reduction and safety.Psychedelics have been shown to induce long-term personality changes, including increased openness and emotional stability, and decreased neuroticism. These changes are influenced by various factors such as the psychological set (mindset of the user) and the physical and social setting in which use occurs. The study identifies eight thematic factors of personality change post-psychedelic use, namely Unitive Spiritual, Gratitude Absorption, Purpose Freedom, Compassion Understanding, Emotional Stability, Openness Perspective, Connection to Self, and Neuroticism Caution. These factors underscore the multidimensional impact of psychedelics on personality, emphasizing growth in areas related to spirituality, emotional processing, and interconnectedness.Notably, the study also highlights that interest in psychedelic use is associated with certain personality traits, such as higher levels of openness and neuroticism. Users typically report being more open and extraverted compared to non-users, suggesting a predisposition towards traits that might be amplified or modulated by psychedelic experiences.These findings have several implications for harm reduction and safety in the context of psychedelic use. Firstly, they reinforce the importance of set and setting in shaping the psychedelic experience and its outcomes. Understanding the optimal conditions for psychedelic use can help minimize risks and enhance the therapeutic potential of these substances. Secondly, the personality changes associated with psychedelic use, such as increased openness and reduced neuroticism, suggest that psychedelics could play a role in mental health treatment, particularly for conditions characterized by rigid thought patterns or heightened anxiety.For harm reduction organizations, these insights emphasize the need for education and guidance on the factors that influence psychedelic experiences, including the selection of a supportive setting, preparation of the individual's mindset, and understanding the potential for profound personality changes. By focusing on these elements, harm reduction efforts can support safer use of psychedelics, harnessing their potential benefits while mitigating risks.In conclusion, the study by Weiss et al. (2023) provides a comprehensive model of the interplay between personality, psychedelic use, and the moderating effects of set and setting. This research offers valuable guidance for individuals and organizations dedicated to promoting safety and understanding in the use of psychedelics, highlighting the transformative potential of these experiences when approached with caution and respect (Weiss et al., 2023).