Serotonergic psychedelics show potential mental health benefits but carry risks, including psychological and serious adverse effects like suicide.

Co-use of a low dose of MDMA with psilocybin/LSD may reduce challenging experiences such as fear and grief, and enhance positive feelings like self-compassion, love, and gratitude, potentially improving the safety and efficacy of psychedelic-assisted therapies.

Emergency department admissions related to psychedelics in California have surged by 69% from 2016 to 2021, underscoring the need for increased safety measures and education.

One third of 608 surveyed psychedelic users experienced extended difficulties such as anxiety, social disconnection, and visual distortions for over a year, with one sixth suffering for more than three years, indicating that harm can occur even in 'safe' therapeutic or clinical settings, as evidenced by the 8% who had such experiences.

The effects of psychedelics are not solely determined by the drug itself, but are significantly shaped by physical, social, and cultural variables, suggesting the importance of integrating these non-drug factors into harm reduction strategies to enhance safety and efficacy.

Psychedelic use is associated with lower distress in employed, volunteering, retired, or permanently disabled individuals, but may increase distress in unemployed, full-time students, or homemakers.

Over half of Canadian Psychedelic Survey respondents experienced challenging psychedelic trips, with common issues including mental overload and social paranoia, and 45% perceived no benefits from these difficult experiences.

The ceremonial use of ayahuasca often leads to the reexperiencing of adverse life events, particularly among women, veterans, and individuals with PTSD, which is associated with cognitive reappraisal, psychological flexibility, and discomfort, but also results in significant reductions in trait neuroticism.

40% of adverse events, including feelings of suicidality, in esketamine trials are unreported, highlighting the need for thorough reporting and monitoring in psychedelic substance use.

While the majority of individuals who have used classic psychedelics do not report challenging or distressing experiences, factors such as co-use of mood stabilizers, lack of preparation, negative mindset, unsupportive environment, large doses, and major life events prior to use can increase the risk of difficult experiences and potential harm.