Case analysis of long-term negative psychological responses to psychedelics

Abstract

Recent controversies have arisen regarding claims of uncritical positive regard and hype surrounding psychedelic drugs and their therapeutic potential. Criticisms have included that study designs and reporting styles bias positive over negative outcomes. The present study was motivated by a desire to address this alleged bias by intentionally focusing exclusively on negative outcomes, defined as self-perceived ‘negative’ psychological responses lasting for at least 72 h after psychedelic use. A strong justification for this selective focus was that it might improve our ability to capture otherwise missed cases of negative response, enabling us to validate their existence and better examine their nature, as well as possible causes, which could inspire risk-mitigation strategies. Via advertisements posted on social media, individuals were recruited who reported experiencing negative psychological responses to psychedelics (defined as classic psychedelics plus MDMA) lasting for greater than 72 h since using. Volunteers were directed to an online questionnaire requiring quantitative and qualitative input. A key second phase of this study involved reviewing all of the submitted cases, identifying the most severe—e.g., where new psychiatric diagnoses were made or pre-existing symptoms made worse post psychedelic-use—and inviting these individuals to participate in a semi-structured interview with two members of our research team, during which participant experiences and backgrounds were examined in greater depth. Based on the content of these interviews, a brief summary of each case was compiled, and an explorative thematic analysis was used to identify salient and consistent themes and infer common causes. 32 individuals fully completed an onboarding questionnaire (56% male, 53% < age 25); 37.5% of completers had a psychiatric diagnosis that emerged after their psychedelic experience, and anxiety symptoms arose or worsened in 87%. Twenty of the seemingly severer cases were invited to be interviewed; of these, 15 accepted an in-depth interview that lasted on average 60 min. This sample was 40% male, mean age = 31 ± 7. Five of the 15 (i.e., 33%) reported receiving new psychiatric diagnoses after psychedelic-use and all fifteen reported the occurrence or worsening of psychiatric symptoms post use, with a predominance of anxiety symptoms (93%). Distilling the content of the interviews suggested the following potential causal factors: unsafe or complex environments during or surrounding the experience, unpleasant acute experiences (classic psychedelics), prior psychological vulnerabilities, high- or unknown drug quantities and young age. The current exploratory findings corroborate the reality of mental health iatrogenesis via psychedelic-use but due to design limitations and sample size, cannot be used to infer on its prevalence. Based on interview reports, we can infer a common, albeit multifaceted, causal mechanism, namely the combining of a pro-plasticity drug—that was often ‘over-dosed’—with adverse contextual conditions and/or special psychological vulnerability—either by young age or significant psychiatric history. Results should be interpreted with caution due to the small sample size and selective sample and study focus.

Psychedelic Therapy: A Primer for Primary Care Clinicians—Psilocybin

“…In a recent case analysis of long-term negative psychological responses to psychedelics, all participants who received a psychiatric diagnosis after their psychedelic experience had already had some kind of preexisting mental illness. 59 There were also many other risk factors, such as an unsafe or stressful setting, polysubstance use, and questionable drug purity or quality. All these risks are mitigated or eliminated in clinical trials of psilocybin, where strict screening procedures and appropriate monitoring of patients during and after treatment are implemented to ensure safety and minimize risks.…”

Psychotherapeutisches Setting und Integration bei psychedelikaassistierter Therapie

“…Die Behandlung mit Psychedelika stellt eine intensive psychotherapeutische Intervention dar, die über eine Destabilisierung psychologischer Dynamiken wirkt [13]. Da sie intensive oder als überwältigend erlebte Veränderungen mentaler Zustände auslösen kann, ist eine an psychotherapeutischen Prinzipien ausgerichtete Nachbearbeitung gerade bei als belastend erlebten Erfahrungen essenziell [14]. Hier spielt die Integration eine wichtige Rolle für die Sicherheit der PAT.…”

Psilocybin-enhanced fear extinction linked to bidirectional modulation of cortical ensembles

“…Upon first pass metabolism, psilocybin is dephosphorylated into its active metabolite psilocin -a potent serotonin receptor agonist 16,17 . While psilocybin's subjective effects tend to be accompanied by feelings of extreme "bliss", "unity", and "meaningfulness" 2,18 , in a subset of patients, psilocybin can induce extremely anxiogenic and even traumatic experiences, in some cases associated with long-term psychosis and suicidal ideation [19][20][21][22] . A variety of factors can contribute to whether a person will have a "good or bad trip," including genetic or endophenotypic predispositions 23,24 , mindset or mood prior drug consumption (set), and environment in which the drug is consumed (setting) [25][26][27][28][29][30] .…”

“…Upon first pass metabolism, psilocybin is dephosphorylated into its active metabolite psilocin -a potent serotonin receptor agonist 16,17 . While psilocybin's subjective effects tend to be accompanied by feelings of extreme "bliss", "unity", and "meaningfulness" 2,18 , in a subset of patients, psilocybin can induce anxiogenic and even traumatic experiences, in some cases associated with long-term psychosis and suicidal ideation [19][20][21][22][23][24] . To develop safe therapies with minimal adverse side-effects, it is critical to identify the relevant neural subpopulations differentially modulated by psilocybin to produce long-lasting therapeutic effects.…”