Longitudinal associations between psychedelic use and psychotic symptoms in the United States and the United Kingdom.

It has long been speculated that psychedelic use could provoke the onset of psychosis, but there is little evidence to support this conjecture. Using a longitudinal research design with samples representative of the US and UK adult populations with regard to sex, age, and ethnicity (n = 9732), we investigated associations between psychedelic use and change in the number of psychotic symptoms during the two-month study period. In covariate-adjusted regression models, psychedelic use during the study period was not associated with a change in the number of psychotic symptoms unless it interacted with a personal or family history of bipolar disorder, in which case the number of symptoms increased, or with a personal (but not family) history of psychotic disorders, in which case the number of symptoms decreased. Taken together, these findings indicate that psychedelic use may affect psychotic symptoms in individuals with a personal or family history of certain disorders characterized by psychotic symptomatology.

5-MeO-DMT: An atypical psychedelic with unique pharmacology, phenomenology & risk?

5-MeO-DMT is a tryptamine being developed as a potential antidepressant that may display a distinct therapeutic mechanism due to its unique pharmacology and subjective effects compared to typical psychedelics. In this article, we parallel the relatively distinct phenomenology and behavioral effects of the acute and post-acute effects of 5-MeO-DMT to those induced by epileptiform activity, particularly in instances within epileptogenic zones of the temporal lobes. This is done by reviewing aberrant 5-HT1A receptor functioning in epilepsy, noting that 5-MeO-DMT has notable 5-HT1A receptor agonist properties-and then comparing the acute behavioral and subjective effects induced by 5-MeO-DMT to those that occur in seizures. It might be that 5-MeO-DMT's therapeutic mechanism is partly mediated by evoking temporary epileptiform activity, suggesting a similarity to electroconvulsive therapy. It is also noted that "reactivations," the sudden re-experiencing of drug effects common after 5-MeO-DMT but not after typical psychedelics, may suggest that 5-MeO-DMT produces recurrent epileptiform activity. Overall, this review indicates that further evaluation of 5-MeO-DMT's unique mechanisms in research settings and among naturalistic users are warranted.

A Qualitative Analysis of First-Hand Accounts of Diphenhydramine Misuse Available on YouTube.

Deliriants are the least studied class of hallucinogens and display noticeable subjective effects, including dysphoria, hallucinations, and substantial alterations in thought. High doses of diphenhydramine (DPH), an over-the-counter antihistamine medication, can produce deliriant effects due to secondary anticholinergic activity. We sought to characterize the subjective experiences produced by DPH misuse to better understand deliriants more broadly and the context under which DPH misuse occurs. To conduct our analysis, 32 first-hand accounts of DPH misuse publicly available in YouTube videos were analyzed using inductive thematic analysis. Video makers discussed alterations in most sensory modalities, confusion, and a tendency for strongly unpleasant experiences. Occasionally, video makers reported positive effects, although these were rare and often overshadowed by negative aspects of the experience. Video makers frequently warned against misusing DPH, and these individuals occasionally reported adverse post-acute effects. Despite the prevalence of adverse experiences, patterns of repeated misuse were sometimes discussed. Motives for misusing DPH, when mentioned, included accessibility, affordability, and legality. Overall, findings suggest DPH misuse can produce substantial psychoactive effects that are often distressing and share some phenomenological overlap with experiences produced by psychosis.

Self-Entropic Broadening Theory: Toward a New Understanding of Self and Behavior Change Informed by Psychedelics and Psychosis.

The extremes of human experiences, such as those occasioned by classic psychedelics and psychosis, provide a rich contrast for understanding how components of these experiences impact well-being. In recent years, research has suggested that classic psychedelics display the potential to promote positive enduring psychologic and behavioral changes in clinical and nonclinical populations. Paradoxically, classic psychedelics have been described as psychotomimetics. This review offers a putative solution to this paradox by providing a theory of how classic psychedelics often facilitate persistent increases in well-being, whereas psychosis leads down a "darker" path. This will be done by providing an overview of the overlap between the states (i.e., entropic processing) and their core differences (i.e., self-focus). In brief, entropic processing can be defined as an enhanced overall attentional scope and decreased predictability in processing stimuli facilitating a hyperassociative style of thinking. However, the outcomes of entropic states vary depending on level of self-focus, or the degree to which the associations and information being processed are evaluated in a self-referential manner. We also describe potential points of overlap with less extreme experiences, such as creative thinking and positive emotion-induction. Self-entropic broadening theory offers a heuristically valuable perspective on classic psychedelics and their lasting effects and relation to other states by creating a novel synthesis of contemporary theories in psychology. SIGNIFICANCE STATEMENT: Self-entropic broadening theory provides a novel theory examining the psychedelic-psychotomimetic paradox, or how classic psychedelics can be therapeutic, yet mimic symptoms of psychosis. It also posits a framework for understanding the transdiagnostic applicability of classic psychedelics. We hope this model invigorates the field to provide more rigorous comparisons between classic psychedelic-induced states and psychosis and further examinations of how classic psychedelics facilitate long-term change. As a more psychedelic future of psychiatry appears imminent, a model that addresses these long-standing questions is crucial.

Special considerations for evaluating psilocybin-facilitated psychotherapy in vulnerable populations.

Psilocybin-facilitated psychotherapy shows potential transdiagnostic efficacy for a range of mental health conditions. Though vulnerable populations bear disproportionate mental health burden, they have been largely neglected in the clinical psilocybin literature. However, if the field is to best respond to the diverse needs of individuals from vulnerable populations, care must be taken to ensure these individuals are represented in the empirical research. This report calls attention to this concern by detailing the challenges and opportunities associated with evaluating psilocybin-facilitated psychotherapy in vulnerable populations. First, we show how working with vulnerable populations must be considered in the context of an often-problematic past and differential exposure to and experience with classic psychedelics. We then provide actionable recommendations for future research testing psilocybin-facilitated psychotherapy in vulnerable populations, including an emphasis on recruitment strategies, the appropriate communication and assessment of subjective effects, building therapeutic alliance, multicultural competence, and flexible study designs. On these premises we call for future work in this area, underscoring that there is vast room for improvement and expansion in this rapidly advancing field of study.