AIMS: This study aimed to evaluate the safety, tolerability and pharmacokinetics of a novel oral modified-release psilocybin formulation (REL-P11) in normal-weight and overweight/obese healthy adults and to assess its suitability for controlled, subperceptual exposure, in light of emerging evidence supporting serotonergic modulation in metabolic disorders. METHODS: Simulation-based modelling...
Numerous analogues of the psychedelic and internationally controlled hallucinogen LSD have been described; however, only a limited number have been systematically investigated. This report presents the first case with an analytically confirmed ingestion of ETH-LAD (6-ethyl-6-nor-lysergic acid diethylamide), the N-ethyl derivative of LSD. An adolescent patient developed moderate to severe...
Psilocybin shows potential in neuropsychiatric disorders but has a complex relationship with epilepsy and seizures. We reviewed literature up to November 2025 to identify studies relevant to psilocybin's effects on seizures and epilepsy, including our research on serotonergic modulation. Core studies addressing the research question and supplementary mechanistic evidence were included for...
Recreational nitrous oxide (N2O) misuse is an increasing public health problem associated with functional cobalamin (B12) deficiency and severe neurological complications. Despite growing recognition of its harms, the dose-response relationship and clinical value of biomarkers remain unclear. This study aimed to characterize the demographics, patterns of use, outcomes, and biomarker utility in...
Oral administration of (S)-ketamine for treatment-resistant depression (TRD), as alternative to the registered intranasal or off-label intravenous administrations, has high potential. However, it is characterized by an extensive first-pass metabolism, resulting in low (S)-ketamine exposure and high levels of active metabolites, including (S)-norketamine and (S)-hydroxynorketamine. The relative...
This study aimed to investigate a set of pharmacodynamic biomarkers reflecting acute, delayed and sustained central nervous system effects of S-ketamine, used as a tool compound for rapid-acting antidepressant activity, with the goal of informing biomarker strategies for delayed antidepressant effects. In this randomized, double-blind, double-dummy, placebo-controlled, 4-way crossover study in...
Rates of mental illness in young people are increasing, whereas the development of novel mental health treatments has not significantly progressed. Psychedelic-assisted therapy, using substances such as psilocybin and 3,4-methylenedioxymethamphetamine (MDMA), has shown potential in the treatment of mental illnesses in the adult population, including depression, anxiety and post-traumatic stress...
The aim of this study was to develop a novel workflow to identify human urine biomarkers for drugs of abuse and new psychoactive substances. Metabolites of amphetamine, cocaine, LSD, MDMA, methamphetamine, THC, MDMB-CHMICA, and MDPPP were first identified in a zebrafish embryo (ZE) metabolism study followed by comparison to most abundant human metabolites in literature. Finally, metabolites...
The rise of psychedelics in contemporary medicine has sparked interest in their potential therapeutic applications. While traditionally associated with countercultural movements and recreational use, recent research has shed light on the potential benefits of psychedelics in various mental health conditions. In this review, we explore the possible role of psychedelics in the management of...
Recent years have witnessed an unprecedented increase in the search for the use of psychedelics in improving physical and mental health. Anaesthesia has evolved since very early times, born from the need to eliminate pain and reduce suffering and there are reports of the use of anaesthetics to achieve mystical states since the nineteenth century. Nowadays, the renaissance of psychedelics in...
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...
Esketamine may reduce acute postoperative pain in several settings. However, the effects of low-dose esketamine on postoperative pain after vestibular schwannoma (VS) resection with propofol/remifentanil total intravenous anaesthesia (TIVA) are unclear. The aim of this study is to observe the effects of intraoperative low-dose esketamine on postoperative pain after vestibular schwannoma...
The opioid crisis emerged in part due to the overprescribing of opioid analgesics for chronic pain. Although not the only source of the current epidemic of opioid use disorder (OUD), the prescription of opioids for chronic pain remains one vector for the development of opioid misuse and OUD. However, opioid tapering is not appropriate for all patients, and some patients may need to remain on...
Aims: To conduct a single-arm open-label feasibility trial of the safety and tolerability of a full-spectrum cannabidiol (CBD)-dominant cannabis-based medicinal product for treating the symptoms of long COVID. Methods: The treatment phase ran for a total of 21 weeks, followed by ~3 weeks without the study drug. Participants received up to 3 mL of MediCabilis 5% CBD Oil (50 mg CBD/mL, <2 mg...
Lysergic acid diethylamide (LSD) is currently investigated for several neurological and psychiatric illnesses. Various studies have investigated the pharmacokinetics and the pharmacokinetic-pharmacodynamic relationship of LSD in healthy participants, but data on urinary recovery and confirmatory studies are missing. The present study characterized the pharmacokinetics,...
AIMS: To characterise the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of oxathridine, a first-in-class histamine-3 receptor partialagonist, in healthy male volunteers. METHODS: A randomised, double-blind, placebo-controlled study including the NeuroCart, consisting of a battery of drug sensitive neurophysiological tests, was performed....
The two pillars of modern medical research are where in most randomized controlled trials (RCTs), the active treatment is compared with placebo. A recent expert consensus survey endorsed the statement that 'Results from placebo-controlled trials are more reliable than results from any other study design',1 reflecting that placebo controlled RCTs are considered to be the gold standard.
Ketamine and dextromethorphan are widely abused psychoactive substances. Inhibition of N-methyl-d-aspartate receptors (NMDARs) results in neurobehavioural effects including hallucinations, "out of body" sensations and dissociative effects. However, little is known about a possible extended addictive class effect linked to pharmacologically-related amino-adamantane derivatives (e.g., amantadine...
The urgent need for appropriate treatment for suicide, the tenth leading cause of death, has led to numerous studies. This study aims to systematically identify and appraise systematic reviews with or without meta-analyses investigating ketamine in suicidal ideation and behaviours. Scopus, ISI, Embase, PubMed, CINAHL, PsycINFO, Cochrane Library, Google Scholar and two registries were searched...
Aims: We aimed to incorporate a pharmacologically inactive midazolam microdose into early clinical studies for the assessment of CYP3A drug–drug interaction liability. Methods: Three early clinical studies were conducted with substances (Compounds A, B and C) which gave positive CYP3A perpetrator signals in vitro. A 75 μg dose of midazolam was administered alone (baseline CYP3A activity)...
AIMS To explore the feasibility of delivering community-based drug safety testing ('drug checking'), to trial service design characteristics and to compare with festival-based testing. METHODS 171 substances of concern were submitted on five dates at three venues in two UK cities and tested using up to six analytical techniques. Test results and harm reduction advice were distributed directly...
Aims The aim of the present study was to characterize the pharmacokinetics and exposure–subjective response relationship of a novel oral solution of lysergic acid diethylamide (LSD) that was developed for clinical use in research and patients. Method LSD (100 μg) was administered in 27 healthy subjects using a placebo‐controlled, double‐blind, cross‐over design. Plasma levels of LSD, nor‐LSD,...
AIMS: γ-Hydroxybutyrate (GHB) is used as a treatment for narcolepsy and alcohol withdrawal and as a recreational substance. Nevertheless, there are limited data on the pharmacokinetics and pharmacokinetic-pharmacodynamic relationships of GHB in humans. We characterized the pharmacokinetic profile and exposure-psychotropic effect relationship of GHB in humans. METHODS: Two oral doses of GHB (25...
Olfactory loss impairs the patient's quality of life. In individualized therapies, olfactory drug effects gain clinical importance. Molecular evidence suggests that among drugs with potential olfactory effects is Δ(9) -tetrahydrocannabinol (THC), which is approved for several indications, including neuropathic pain or analgesia in cancer patients. The present study aimed at assessing the...