Ketamine has emerged as a putative rapid-acting treatment option for psychiatric disorders, particularly treatment-resistant depression. Chronic recreational ketamine use is associated with ketamine-induced urological toxicity, raising concerns over the safety of repeated ketamine treatments. This systematic review aimed to synthesise urological findings from clinical trials and observational...
This study aimed to validate and culturally adapt the Altered States of Consciousness Rating Scale (OAV) and Five Dimensional-Altered States of Consciousness Questionnaire (5D-ASC) for Brazilian Portuguese to measure altered states of consciousness in the context of psychedelic research. A parallel back-translation model was employed with expert reviews to ensure linguistic and cultural...
Ketamine, a rapid-acting N-methyl-D-aspartate receptor antagonist used as a therapeutic for treatment-resistant depression (TRD), is usually administered intravenously or intranasally. This randomized, double-blind, placebo-controlled, Phase 1 study investigated safety and tolerability (primary endpoint), pharmacokinetics (PK) and pharmacodynamics (PD) of an immediate-release oral ketamine....
Mindfulness and compassion are therapeutically relevant and can be increased through different forms of meditation practices. However, meditation practice needs time and commitment. These resources are often limited in patients with mood disorders. Therefore, efficacious remedies that increase mindfulness and compassion could provide therapeutic options. This study aimed to investigate the...
Neuroimaging studies have linked the beneficial effects of subanaesthetic ketamine doses in psychiatric conditions characterized by chronic stress pathology (CSP) to altered functional connectivity (FC) within the pregenual anterior cingulate cortex (pgACC). Previous research indicates a potential role of glutamate concentration in FC changes; however, the precise relationship between glutamate...
Mental health implications of COVID-19 drug use patterns are still unclear. We used data-driven clustering in a large citizen science cohort recruited agnostically to an interest in drug-use to categorise people according to common patterns of drug use and analysed their mental health symptoms (GAD-7 and PHQ-9 items), from recruitment prior to COVID-19 restrictions in 2020 (N = 242,260) to...
The authors offer a model for curriculum for education and training in substance-assisted psychotherapy (SAP), that is, psychedelic, psycholytic, and entactogen/MDMA (3,4-methylenedioxymethamphetamine)-assisted psychotherapy, addressing both the detailed contents of training and the question of experiential training. All authors of this model have an abiding interest and extensive experience in...
We previously completed a double-blind randomised crossover study assessing intramuscular ketamine for treatment-resistant depression (TR-D), post-traumatic stress disorder (TR-PTSD) and obsessive-compulsive disorder (TR-OCD). Here, we report an extension study to explore the ongoing benefits and tolerability of maintenance oral ketamine. All participants from the original study were eligible...
Recent evidence suggests that psychedelics can induce rapid and long-lasting antidepressant effects. The generally acknowledged explanation for these traits is the phenomenon of neuroplasticity, although the exact underlying molecular mechanisms remain unclear. This study investigates the effects of psilocin, lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT) on synaptogenesis...
Research on the therapeutic potential of psychedelics has surged, prompting a re-examination of the role of set and setting in psychedelic-assisted therapy. Yet, these concepts are vague and typically defined over inclusively. We believe that set and setting research should be methodologically reductionist, focusing on specific components rather than set and setting as such. To that end, we...
The therapeutic use of psychedelics for mental health issues holds considerable promise. However, systematic assessment of adverse events associated with these substances has received relatively little attention. Here, we discuss several considerations concerning the assessment of adverse events in psychedelic-assisted therapies. We discuss the preference for using the term "adverse effects"...
Psychedelics offer promising outcomes in psychiatry. However, the preparation of participants (set) and the environmental conditions of taking a psychedelic (setting) are not standardized. We describe the set and setting for therapeutic use of psychedelic drugs in people with psychiatric disorders. In this systematic review, articles were identified in the PubMed and Web of Science databases...
The recent resurgence of classical psychedelic compounds, specifically 5-HT2A receptor agonists, as potential therapeutics has led to numerous initiatives aimed at better understanding the mechanisms underlying their effects. Psychedelic compounds are commonly known as hallucinogens. One of the major outstanding questions in the field is whether altered states of consciousness-the...
As classic psychedelics' therapeutic potential is studied and their popularity continues to rise, it is important to establish their relative risks and benefits. Previous surveys have tended to use convenience sampling on social media, select participants who have had either extremely positive or negative effects, and have not compared the risk/benefit profile of psychedelics to other...
While most psychedelic substances are considered to carry a relatively low risk of acute or long-term harm, co-use with other psychoactive substances may increase health and social harm. Using a large international survey of adults who use psychedelics, we sought to comprehensively characterize psychedelic co-use. We used data from the 2023 Global Psychedelic Survey, a web-based survey of...
Current models of psychedelic action in the brain propose changes along the dorsal-ventral and anterior-posterior axes but neglect to address the lateral axis. This article proposes a novel model of psychedelic action called HEALS (Hemispheric Annealing and Lateralization Under Psychedelics) which involves the reversal of the typical hierarchical relationship between the two hemispheres of the...
Recent discussions about the methodological rigor of psychedelic clinical trials have focused on potential underreporting or misreporting of adverse events (AEs), with many calling for their systematic assessment to help mitigate these issues. In their recent paper, Palitsky et al. offer a comprehensive framework for the assessment of AEs in psychedelic-assisted therapies, with consideration of...
Patients with refractory conditions often identify themselves with their illness, which affects multiple aspects of their lives. The pictorial representation of illness and self measure (PRISM) is a tool used to assess the enmeshment of individuals' perception of self with a particular medical condition, broadly termed self-condition enmeshment. This study aimed to evaluate changes in PRISM...
Oral esketamine for patients with treatment-resistant depression (TRD) could offer certain advantages over other routes, such as intravenous or intranasal, but it has not been systematically studied in a real-world setting. Here we present results from a relatively large naturalistic study to evaluate the effectiveness, tolerability, and safety of oral esketamine in patients with TRD. One...
Emerging evidence indicates the therapeutic potential of psychedelic compounds for post-traumatic stress, yet the mechanisms mediating their effects remain unclear. Delineating the effect of psychedelics on traumatic memory formation could shed light on target therapeutic mechanisms. Here, we report on 343 adult survivors of a single, large-scale terrorist attack taking place during a festival...
Microdosing is the practice of taking psychedelic drugs at doses that produce no or minimal perceptible subjective or behavioural effects. This study investigated the pharmacokinetics and pharmacodynamics of microdosed lysergic acid diethylamide (LSD). This was a Phase 1 double-blind placebo-controlled parallel-groups trial with 80 healthy male volunteers (four withdrawals due to anxiety)....
Objective: Psychedelics are able to trigger highly intense and profound alterations in self-consciousness, perception, affective, and cognitive processes. Indeed, recent studies show that ketamine and psilocybin could be used as fast-acting antidepressants. However, the molecular and neurochemical mechanisms of these psychedelics and their actions at the level of diverse brain structures...
New synthetic tryptamine derivatives have emerged in the underground market. They act on serotonin receptors mimicking the effects of hallucinogenic drugs such as DOM. The DEA has identified three tryptamine derivatives of concern, 5-MeO-DBT, 5-Cl-DMT, and 4-OH-MiPT. Swiss Webster mice were tested for locomotor activity. Discriminative stimulus effects were tested in male Sprague-Dawley rats...
The recent rejection of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy by the U.S. Food and Drug Administration (FDA) is a dramatic moment in the re-emergence of psychedelic research. In this perspective, I argue that it represents a case study for paradigmatic tensions within psychopharmacology. The regulatory system is still influenced by a paradigm that sees the therapeutic...
Ayahuasca is an Amazonian brew with 5-HT2A-dependent psychedelic effects taken by religious groups globally. Recently, psychedelics have been shown to impair the formation of recollections (hippocampal-dependent episodic memory for specific details) and potentially distort memory while remembering. However, psychedelics spare or enhance the formation of familiarity-based memory...