Classic Psychedelics and Suicide
According to the American Foundation for Suicide Prevention (AFSP, 2025), suicide remains a major public health crisis in the United States. In 2023, there were approximately 49,000 deaths by suicide, and an estimated number of 1.5 million suicide attempts. The disparities exist across demographics: males are 3.8 times more likely to die by suicide than females. Suicide is an epidemic that is leading the cause of death among older adults (age 75 and up). In addition, suicide is the second leading cause of death among younger individuals (ages 10–34).
Despite these devastating statistics, the efficacy of current psychiatric interventions often lags, necessitating the rigorous exploration of novel, rapid-acting treatment modalities. On April 18, 2026, Psychedelics received an executive order from President Trump (The White House, 2026). In addition, Texas has passed $50 million in funding for Ibogaine research (UTHealth Houston, 2024), and clinical trials to address the opioid crisis (National Library of Medicine, 2024). A 2024 report by National Survey Investigating Hallucinogenic Trends (NSIHT) said that there are about 12 million adults (18 years and older) who reported at least one psychedelic use in their lifetime, with psilocybin mushrooms being most consumed. The term Psychedelic, created by psychiatrist Humphry Osmond, means “mind-manifesting” (Barksdale et al., 2025). Psychedelics can also be referred to as plant medicines and entheogenic substances, and they are either naturally occurring substances (e.g., the Iboga plant, Mescaline cactus, or Psilocybin mushrooms) or synthetic (e.g., Ketamine). Psychedelic plant medicines have been part of the spiritual and traditional healing practices of Indigenous cultures from various countries around the globe (e.g., Ayahuasca in Brazil, Psilocybin mushrooms in South America, Iboga in West Africa, and Peyote in North America) (Santos et al., 2021).
Psychedelics are known to produce a wide range of psychological therapeutic effects, including potential benefits for several DSM-5 disorders. For instance, psilocybin and ketamine have been found to reduce symptoms of treatment-resistant depression and anxiety (Borissova & Rucker,2024; Carhart-Harris et al.,2016; Grabski et al.,2020; Dwerko et al., 2025; Serafini et al., 2014). LSD and psilocybin have shown a therapeutic impact on alcoholism (Bogenschutz et al., 2015; Fuentes et al., 2020), and MDMA has led to reduced symptoms of PTSD among veterans (Riaz et al., 2023). Psilocybin has impacted existential issues and anxiety among cancer patients (Tarbi et al., 2025). There are extensive studies on how psychedelics promote neuroplasticity (Agnorelli et al., 2025; Calder et al., 2023; Kwan et al., 2022 ). As a caution, it is also important to not that there are also barriers to the therapeutic effects of psychedelics such as personal or family history of psychosis, chronic heart problems, and etc. (Feduccia et al., 2023). Classic psychedelics are compounds that primarily interact with and blocks serotonin 5HT2A receptors, which are involved in perception, mood, and cognition. This interaction allows increased communication between different regions of the brain, a phenomenon described by the Serotonergic 5HT2A Receptor Agonism Model (Hendricks et al., 2015; Johnson et al., 2019; Ruffell et al., 2023; Uthaug et al., 2019). During altered states of consciousness under Psilocybin, brain regions that do not typically communicate become more interconnected, potentially providing individuals with new perspectives, emotional insights, and subjective experiences (Barksdale et al., 2025; Nichols & Nichols, 2025).
Psilocybin- psychoactive mushrooms that naturally grow across the globe. Psilocybin mushrooms are also being cultivated and grown in settings such as home cultivation environments.
LSD - a synthesized psychedelic compound originally derived from ergot, a fungus that grows on rye grain.
Ayahuasca - a DMT-containing ceremonial brew traditionally made from the Banisteriopsis caapivine and Psychotria viridis, a flowering plant within the coffee family.
Mescaline - a naturally occurring psychedelic compound found in various cacti, including San Pedro, Peyote, and Peruvian Torch, traditionally used in ceremonial and spiritual practices.
Bufo alvarius - also known as the Colorado River toad, this species produces a psychoactive secretion containing 5-MeO-DMT and is primarily found in regions of Colorado, New Mexico, Arizona, and northern Mexico.
Research suggests that lifetime psychedelic use is associated with reduced suicidal thinking, psychological distress, and suicide attempts among adults in the United States (Hendricks et al., 2015). A systematic review examining psychedelics as an intervention for suicide-related outcomes reported promising findings regarding reductions in suicidality (Meshkat et al., 2025; Wong et al., 2025). Mixed finding from a review of 64 studies found that some research demonstrated reductions in suicidality, some showed no significant effects, and others reported worsening suicidality leading to hospitalization (Zeifman et al., 2021). In one case study, psilocybin was associated with increased suicidal ideation and risk (Wabha et al., 2024). This finding may reflect a phenomenon also observed in some antidepressant treatments, where suicidal ideation may temporarily worsen prior to therapeutic improvement. Such findings highlight the importance of continued ethical, clinically supervised, and evidence-based research regarding the safety and application of psychedelic-assisted interventions for suicidality.
Multiple evidence-based theories explain the complex phenomenon of suicide. This research utilizes the Three-Step Theory (3ST) by Klonsky and May (2015) and the Interpersonal Theory of Suicide (ITS) by Thomas Joiner (2005). The Three-Step Theory views suicide in four factors: pain, connectedness, hopelessness, and capacity for suicide (Kolonsky et al. 2021). Then the Interpersonal Theory view suicide as ones feeling of burdensome, and mainly relates to social connection to others. These theories address factors related to suicide such as somatic, neurological, psychological, relational, cultural, and existential. The therapeutic actions of classic psychedelics are hypothesized to intervene directly at the core psychological factors driving suicidality as listed by the Three-Step Theory (3ST) and the Interpersonal Theory of Suicide (ITS). For instance, the pain component of the 3ST is directly addressed by studies showing that psychedelics possess analgesic and pain-reducing effects (Goel et al., 2023). Furthermore, classic psychedelics have the potential to address the interpersonal and social issues central to both theories—such as Thwarted Belongingness (ITS) and lack of Connectedness (3ST)—through evidence of increased pro-social behavior and enhanced empathy (Schmid et al., 2025; Xang et al., 2025).
