A randomised placebo-controlled study of the effects of lysergic acid diethylamide microdosing (15 μg) on pain perception in healthy volunteers.

Background: Preliminary research indicates that psychedelics may hold promise as analgesic agents. This study investigated the potential analgesic effects of lysergic acid diethylamide (LSD) microdosing on pain tolerance and subjective pain perception in healthy participants.

Methods: Utilizing a randomised, placebo-controlled design, participants received 15 μg of LSD or placebo over four administrations.

Implementing psychedelic-assisted therapy: History and characteristics of the Swiss limited medical use program.

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 alternative treatments, or such treatments have already extensively been used with insufficient outcome.

Development and Validation of a Rapid LC-MS/MS Method for Plasma Analysis of Ketamine, Norketamine, Dehydronorketamine, and Hydroxynorketamine.

Ketamine, a well-established dissociative anesthetic, has recently gained significant attention for its rapid-acting antidepressant effects, particularly in treatment-resistant depression. In this study, we developed and validated a state-of-the-art liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the bioanalysis of ketamine and its metabolites, norketamine, dehydronorketamine (DHNK), and (2R,6R)-hydroxynorketamine (HNK), in human plasma. The method features a small sample volume, a streamlined protein precipitation protocol, and a rapid sample runtime.

Pharmacokinetics, Pharmacodynamics, and Urinary Recovery of Oral Mescaline Hydrochloride in Healthy Participants.

Background And Objective: 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.

Methods: Data from 105 single-dose administrations (100-800 mg) in 49 participants from two phase I trials were analyzed with compartmental pharmacokinetics and pharmacokinetic-pharmacodynamic modeling.

Clinical pharmacology.

To design therapeutic trials and select the most appropriate substance and dose for an indication, a detailed understanding of clinical pharmacology is crucial. In recent years, several studies have explored the human pharmacology of different psychedelics and 3,4-methylendioxymethylamphetamin (MDMA). This chapter summarizes pharmacological characteristics of the serotonergic psychedelics psilocybin, lysergic acid diethylamide (LSD), mescaline, N,N-dimethyltryptamine (DMT), 5-methoxy-DMT (5-MeO-DMT), and MDMA.

Efficacy and safety of low- versus high-dose-LSD-assisted therapy in patients with major depression: A randomized trial.

Background: This trial aimed to assess the efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with moderate-to-severe major depressive disorder.

Methods: This was a randomized, parallel, double-blind, low-dose controlled trial (Clinicaltrials.gov: NCT03866252).

Pharmacokinetics and Pharmacodynamics of Intranasal Diacetylmorphine in Heroin-Assisted Treatment for Severe Opioid Use Disorder.

Background: Intranasal diacetylmorphine (IN DAM) represents a promising new route of administration, which is currently under investigation as a novel treatment approach for opioid use disorder in Switzerland. This study characterized the pharmacokinetics and pharmacodynamics of therapeutically relevant intranasal doses of DAM and its metabolites in patients with severe opioid use disorder.

Methods: In this prospective observational study, patients on intranasal heroin-assisted treatment (HAT) in Basel, Switzerland, self-administered their usual dose of IN DAM before receiving their daily maintenance dose.

The effect of MDMA on anterior pituitary hormones: a secondary analysis of a randomized placebo-controlled trial.

Background: 3,4-Methylenedioxymethamphetamine (MDMA), a psychoactive substance, has been proposed as a novel provocation test for oxytocin deficiency. Limited evidence suggests that MDMA may also stimulate the anterior pituitary. Therefore, this analysis aimed to investigate the acute effect of MDMA on the anterior pituitary in healthy adults.

Absolute Oral Bioavailability and Bioequivalence of LSD Base and Tartrate in a Double-Blind, Placebo-Controlled, Crossover Study.

Lysergic acid diethylamide (LSD) is currently being investigated as a potential treatment for psychiatric and neurological disorders. Different LSD formulations (base or tartrate, oral or intravenous) are being used. Unclear is whether LSD base and tartrate pharmacokinetics are equivalent.

Liquid chromatography-tandem mass spectrometry-based pharmacokinetic and metabolic analysis of 4-bromo-2,5-dimethoxyphenethylamine and its metabolites in human plasma.

4-Bromo-2,5-dimethoxyphenethylamine (2C-B) is widely used recreationally and has recently gained interest as a treatment for mental health disorders. In this study, a liquid chromatography-tandem mass spectrometry method to quantify 2C-B and its metabolites 4-bromo-2,5-dimethoxyphenylacetic acid (BDMPAA) and 4-bromo-2-hydroxy-5-methoxyphenylacetic acid (B-2-HMPAA) in human plasma was developed and validated. Moreover, pharmacokinetic analysis was performed on samples from clinical study participants who received 30 mg of 2C-B.

A Field-Wide Review and Analysis of Study Materials Used in Psilocybin Trials: Assessment of Two Decades of Research.

Introduction: Serotonergic psychedelics, serotonin 2A receptor agonists such as psilocybin that can result in substantially altered states of consciousness, are used in recreational and research settings. The safety of psychedelic experiences in research settings is supported by controlled physical environments, presence of clinical and medical staff to address emergent issues, screening for personal and family history of potential contraindications, and psychoeducational preparation with psychological support. Research settings typically provide psychoeducation to participants verbally and in writing (e.

Neurophysin I: a reliable, novel, and robust biomarker for oxytocin.

Introduction: Oxytocin (OXT) deficiency is a recently identified novel psycho-neuroendocrine entity associated with anxiety and reduced prosocial behavior. However, diagnosis and clinical progress have been hindered by challenges in reliably measuring OXT. Neurophysin I (NP-I), an equimolarly co-released cleavage product of the OXT precursor peptide, offers a promising alternative biomarker due to its stability, although it requires validation.

Motivation and retrospective appraisal of psychedelic study participation: a qualitative study in healthy volunteers.

Rationale: Little is known about motives of healthy volunteers to participate in psychedelic trials and how they appraise their study experience retrospectively.

Objectives: 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 again.

Methods: This study used the data of 151 healthy volunteers who had ingested serotonergic psychedelics in one of six randomized, double-blind, placebo-controlled crossover trials at the same research site under similar conditions.

Differences in the clinical presentation of acute 3,4-methylenedioxymetamfetamine intoxication by co-intoxication and patient sex to European emergency departments.

Introduction: 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 exclusive co-usage of ethanol, and 3,4-methylenedioxymetamfetamine-co-intoxication with co-usage of other substances with or without ethanol, with a focus on patient sex differences.

Methods: A retrospective analysis was conducted using the Euro-DEN Plus database (2013-2022), which collects data on emergency department presentations with acute drug intoxication from 28 sentinel centres in 18 European countries.

Safety and Efficacy of Repeated Low-Dose LSD for ADHD Treatment in Adults: A Randomized Clinical Trial.

Importance: 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.

Objective: To determine the safety and efficacy of repeated low doses of LSD in reducing ADHD symptoms compared with placebo.

Acute Effects and Pharmacokinetics of LSD after Paroxetine or Placebo Pre-Administration in a Randomized, Double-Blind, Cross-Over Phase I Trial.

Psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), are being investigated for the treatment of depressive and anxiety disorders, for which concomitant treatment with selective serotonin reuptake inhibitors (SSRIs) is prevalent. The present study investigated the acute response to single doses of LSD (100 μg) after daily administration of paroxetine (10 mg for 7 days, followed by 20 mg for 35 days) or placebo (42 days) using a randomized, double-blind, cross-over design in 23 healthy participants. Paroxetine did not alter pleasant subjective effects of LSD but significantly reduced "bad drug effect," "anxiety," and "nausea.

Treatment of neuropathic pain with repeated low-dose MDMA: a case report.

A 64-year-old male patient who suffered from traumatic life experiences and neuropathic pain after oncological chemotherapy was treated with medium to high doses of lysergic acid diethylamide (LSD) and high doses and microdoses of methylenedioxymethamphetamine (MDMA). At the beginning of treatment, the patient did not experience any acute subjective effects of LSD at a dose of 200 µg. After increasing the LSD dose to 400 µg, he experienced subjective acute effects, and the first lasting therapeutic effects were observed.

Acute dose-dependent effects and self-guided titration of continuous N,N-dimethyltryptamine infusions in a double-blind placebo-controlled study in healthy participants.

N,N-dimethyltryptamine (DMT) is a serotonergic psychedelic that is known for its short-lasting effects when administered intravenously. Several studies have investigated the administration of intravenous boluses or combinations of a bolus and a subsequent continuous infusion. However, data on dose-dependent acute effects and pharmacokinetics of continuous DMT infusions are lacking.

The psychoplastogens ibogaminalog and ibogainalog induce antidepressant-like activity in naïve and depressed mice by mechanisms involving 5-HT receptor activation and serotonergic transmission.

The antidepressant-like activity of two psychoplastogens, ibogainalog (IBG) and ibogaminalog (DM506), was studied in naïve mice using the forced swim test (FST) and tail suspension test (TST). The behavioral results showed that a single administration of 25 mg/kg DM506 or 10 mg/kg IBG induced antidepressant-like activity in naïve mice in a volinanserin-sensitive manner that persisted for 72 h. Similar results were observed using the chronic immobilization stress (CIS) test, in which depression symptoms were reduced for 48 h.

Safety pharmacology of acute mescaline administration in healthy participants.

Aims: Psychedelics, including mescaline, may serve as novel treatments for depression and anxiety. However, data is scarce on the safety of mescaline.

Methods: The present pooled analysis included two double-blind, randomized, placebo-controlled studies with a total of 48 participants and 96 mescaline administrations.

Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response.

Background: Psychedelic-assisted therapy (PAT) is permitted in Switzerland under its limited medical use program. Data from patients in this program represent a unique opportunity to analyze the real-world practice of PAT.

Aims: This study compared the subjective effects of lysergic acid diethylamide (LSD) and psilocybin between patients undergoing PAT and healthy volunteers.

Large-scale brain connectivity changes following the administration of lysergic acid diethylamide, d-amphetamine, and 3,4-methylenedioxyamphetamine.

Psychedelics have recently attracted significant attention for their potential to mitigate symptoms associated with various psychiatric disorders. However, the precise neurobiological mechanisms responsible for these effects remain incompletely understood. A valuable approach to gaining insights into the specific mechanisms of action involves comparing psychedelics with substances that have partially overlapping neurophysiological effects, i.

Pharmacological and non-pharmacological predictors of the LSD experience in healthy participants.

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 subjects.