RATIONALE: Attention-deficit hyperactivity disorder (ADHD) shows substantial heterogeneity in symptoms and cognitive deficits. According to the Triple Pathway Model, this variability may stem from impairments in three neuropsychological domains: inhibition, motivation, and temporal processing. Repeated low-dose administration of psychedelics is being explored as a treatment for ADHD, but...
Despite growing interest in the therapeutic potential of 3,4-methylenedioxymethamphetamine (MDMA), no targeted measure to systematically assess side effects of MDMA-assisted psychotherapy (MDMA-AP) exists. Our aim was to develop an MDMA-Assisted Psychotherapy Side Effects Tool (M-SET) to capture side effects over the course of MDMA-AP. Informed by a systematic review and a review of other...
The Altered States of Consciousness Scale (3/5D-ASC or 11-ASC) is widely used to assess non-ordinary states of consciousness, particularly for psychedelic research. However, its original dimensional model (3D-ASC within 5D-ASC) and later 11-subscale structure (11-ASC) have a hierarchically incompatible higher/lower-order structure. Although the 11-ASC offers superior model fit, the 3D-ASC...
Background: Evidence is growing that psychedelic substances have positive effects in the setting of Palliative Care (PC), focusing on special needs in this patient population. After a scoping review of the literature, no published expert recommendations guiding best practice for psychedelic-assisted therapy (PAT) towards the end of life were identified. Objective: To draw conclusions from...
Mescaline is a classic serotonergic psychedelic with a long history of human use. The present study analyzed the pharmacokinetics, pharmacokinetic-pharmacodynamic relationship, and urinary recovery of oral mescaline hydrochloride. Data from 105 single-dose administrations (100-800 mg) in 49 participants from two phase I trials were analyzed with compartmental pharmacokinetics and...
Psychoactive substances are compounds that can influence perception, consciousness, cognition, and emotions. The psychoactive substances caffeine, nicotine, cannabis, and psilocybin all originate from natural sources and can be used without complex processing or synthesis. Their natural availability has contributed to a long-standing history of human use and cultural significance. Caffeine and...
Microdosing psychedelics, including lysergic acid diethylamide (LSD), has gained attention for its potential benefits in several psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). However, LSD's efficacy in reducing ADHD symptoms remains unknown. To determine the safety and efficacy of repeated low doses of LSD in reducing ADHD symptoms compared with placebo. This...
Treating amotivated states remains difficult. Classical psychedelic drugs (5-HT2A receptor agonists) such as LSD and psilocybin have shown therapeutic potential in treating such symptoms, but their development has been hindered by their undesirable hallucinogenic effects. There is increasing evidence that administration of psychedelics at dose levels too low to evoke a hallucinogenic effect...
However, psilocybin is but one of scores of compounds belonging to two main chemical classesphenethylamines and tryptamines -along with ergolines and an expanding array of other (mostly heterocyclic) alkaloids -that act as agonists of the serotonin 5-HT2A, 5-HT2C and 5-HT1A receptors responsible for the various phenomenological and putative therapeutic effects of classic psychedelics (8). In...
Little is known about motives of healthy volunteers to participate in psychedelic trials and how they appraise their study experience retrospectively. This paper explored reasons why healthy people register for psychedelic trials, factors that they considered to contribute to either positive or negative study experiences, and under which circumstances they would seek a psychedelic experience...
This study hypothesized that 3,4-methylenedioxymetamfetamine intoxication presents with distinct clinical features and outcomes when combined with other substances of misuse, compared to mono-3,4-methylenedioxymetamfetamine intoxication. This study investigated the clinical presentation of acute mono-3,4-methylenedioxymetamfetamine intoxication, 3,4-methylenedioxymetamfetamine intoxication with...
This article describes the Swiss limited access program for psychedelic/3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy. The Swiss Federal Office of Public Health can issue authorizations for the limited medical use of otherwise prohibited substances. To be eligible, patients suffer from a mostly incurable disease, the prohibited substance can alleviate the suffering, and there are no...
Background: The Altered States of Consciousness Scale (3/5D-ASC or 11-ASC) is widely used to assess non-ordinary states of consciousness, particularly for psychedelic research. However, its original dimensional model (3D-ASC within 5D-ASC) and later 11-subscale structure (11-ASC) have a hierarchically incompatible higher/lower-order structure. Although the 11-ASC offers superior model fit, the...
Psychedelics, including mescaline, may serve as novel treatments for depression and anxiety. However, data is scarce on the safety of mescaline. The present pooled analysis included two double-blind, randomized, placebo-controlled studies with a total of 48 participants and 96 mescaline administrations. Single oral-dose administrations (n = 16/dose) of mescaline at doses of 100-800 mg were...
Classic psychedelics have regained interest in research and therapy. Despite the long tradition of the human use of mescaline, modern data on its dose-dependent acute effects and pharmacokinetics are lacking. Additionally, its mechanism of action has not been investigated in humans. We used a randomized, double-blind, placebo-controlled, crossover design in 16 healthy subjects (8 women) who...
Implications for practice Psychedelic-assisted therapy with classical psychedelics (psilocybin, LSD) may be effective for treating anxiety, depression, and possibly existential distress, in people facing a life-threatening disease. Psychedelic-assisted therapy seemed to be well tolerated, with no treatment-emergent serious adverse events reported in the studies included in this review. However,...
The pharmacodynamic effects of lysergic acid diethylamide (LSD) are diverse and different in different individuals. Effects of other psychoactive substances have been shown to be critically influenced by non-pharmacological factors such as personality traits and mood states. The aim of this study was to determine pharmacological and psychological predictors of the LSD effects in healthy human...
The acute psychoactive, autonomic, and endocrine effects of the new psychoactive substance (NPS) 5,6-methylenedioxy-2-aminoindane (MDAI; 3.0 mg/kg, range 180-228 mg) were investigated in six healthy volunteers (four males, two females) in a non-blinded fashion without placebo. Subjective, cardiovascular, and endocrine responses were compared with two different doses of...
Zusammenfassung Seit den späten 1990er-Jahren erfahren Psychedelika eine Renaissance und ziehen international vermehrt die Aufmerksamkeit auf sich. Es gibt zunehmend wissenschaftliche Studien, die sich mit den Möglichkeiten und Risiken der Psychedelika-assistierten Therapie (PAT) befassen. Seit 2014 werden auf der Grundlage von Ausnahmebewilligungen der Schweizer Gesundheitsbehörde (Bundesamt...
There has been renewed interest in the use of 3,4-methylenedioxy-methamphetamine (MDMA) and serotonergic psychedelics in the treatment of multiple psychiatric disorders. Many of these compounds are known to produce prosocial effects, but how these effects relate to therapeutic efficacy and the extent to which prosocial effects are unique to a particular drug class is unknown. In this article,...
Hallucinations limit widespread therapeutic use of psychedelics as rapidly acting antidepressants. Here we profiled the non-hallucinogenic lysergic acid diethylamide (LSD) analog 2-bromo-LSD (2-Br-LSD) at more than 33 aminergic G protein-coupled receptors (GPCRs). 2-Br-LSD shows partial agonism at several aminergic GPCRs, including 5-HT2A, and does not induce the head-twitch response (HTR) in...
Abstract Background LSD and psilocybin are increasingly used in phase I trials and evaluated as therapeutic agents for mental disorders. The phenomenon of reoccurring drug-like experiences after the acute substance effects have worn off was described for both substances and especially attributed to LSD. According to the DSM-V, the persisting and distressing manifestation of these experiences is...
Lysergic acid diethylamide (LSD) is a classic psychedelic substance that is used recreationally and investigated in psychiatric research. There are no pharmacogenetic studies on LSD. In vitro metabolic studies indicate that several cytochrome P450 (CYP) isoforms (e.g., CYP2D6, CYP1A2, and CYP2C9) are involved in LSD metabolism, but in vivo data are scarce. The present study examined the...
Background: Lysergic acid diethylamide (LSD) and 3,4-methylenedioxymethamphetamine (MDMA) were used in psychotherapy in the 1960s–1980s, and are currently being re-investigated as treatments for several psychiatric disorders. In Switzerland, limited medical use of these substances is possible in patients not responding to other treatments (compassionate use). Methods: This study aimed to...
Concomitant use of cannabis and other psychoactive substances is common and it is often difficult to differentiate its acute effects from those of other substances. This study aimed to characterize the acute toxicity of cannabis with and without co-use of other substances. Retrospective analysis of cases presenting at the emergency departments of three large hospitals in Switzerland due to...