Harms and benefits associated with psychoactive drugs: Findings of an international survey of active drug users

There have been several recent efforts in the UK and the Netherlands to describe the harms of psychoactive substances based on ratings of either experts or drug users. This study aimed to assess the perceived benefits as well as harms of widely used recreational drugs, both licit and illicit, in an international sample of drug users. The survey was hosted at https://www.internationaldrugsurvey.org/ and was available in three languages. Residents reported their experience of 15 commonly used drugs or drug classes; regular users then rated their harms and benefits. In all, 5791 individuals from over 40 countries completed the survey, although the majority were from English speaking countries. Rankings of drugs differed across 10 categories of perceived benefits. Skunk and herbal cannabis were ranked consistently beneficial, whilst alcohol and tobacco fell below many classified drugs. There was no correlation at all between users’ harm ranking of drugs and their classification in schedules of the USA or ABC system in the UK. Prescription analgesics, alcohol and tobacco were ranked within the top 10 most harmful drugs. These findings suggest that neither the UK nor US classification systems act to inform users of the harms of psychoactive substances. It is hoped the results might inform health professionals and educators of what are considered to be both the harms and benefits of psychoactive substances to young people

Acute effects of cannabis on speech illusions and psychotic-like symptoms:two studies testing the moderating effects of cannabidiol and adolescence

Background Acute cannabis administration can produce transient psychotic-like effects in healthy individuals. However, the mechanisms through which this occurs and which factors predict vulnerability remain unclear. We investigate whether cannabis inhalation leads to psychotic-like symptoms and speech illusion; and whether cannabidiol (CBD) blunts such effects (study 1) and adolescence heightens such effects (study 2). Methods Two double-blind placebo-controlled studies, assessing speech illusion in a white noise task, and psychotic-like symptoms on the Psychotomimetic States Inventory (PSI). Study 1 compared effects of Cann-CBD (cannabis containing Δ-9-tetrahydrocannabinol (THC) and negligible levels of CBD) with Cann+CBD (cannabis containing THC and CBD) in 17 adults. Study 2 compared effects of Cann-CBD in 20 adolescents and 20 adults. All participants were healthy individuals who currently used cannabis. Results In study 1, relative to placebo, both Cann-CBD and Cann+CBD increased PSI scores but not speech illusion. No differences between Cann-CBD and Cann+CBD emerged. In study 2, relative to placebo, Cann-CBD increased PSI scores and incidence of speech illusion, with the odds of experiencing speech illusion 3.1 (95% CIs 1.3–7.2) times higher after Cann-CBD. No age group differences were found for speech illusion, but adults showed heightened effects on the PSI. Conclusions Inhalation of cannabis reliably increases psychotic-like symptoms in healthy cannabis users and may increase the incidence of speech illusion. CBD did not influence psychotic-like effects of cannabis. Adolescents may be less vulnerable to acute psychotic-like effects of cannabis than adults

Defining appropriateness in coach-athlete sexual relationships: The voice of coaches

The sporting culture, with omnipotent coaches, fierce competition for recognition and funding, and ‘win at all cost’ ethos, creates an environment conducive to sexual exploitation of athletes. Recent increased public awareness and the development of child protection policies in sport have led to the questioning of previously accepted coach-athlete relationships. This study is an exploratory investigation into male swimming coaches’ perceptions of appropriateness of coach-athlete sexual relationships. Sexual relationships with athletes under the age of 16 were unanimously considered totally inappropriate. With regard to sexual relationships with athletes above the age of consent for heterosexual sex, opinions ranged from “totally inappropriate” to “it’s a question of civil liberties.” These results are discussed in relation to how coaches have adapted their own behaviours in the face of public scrutiny but are still reluctant to restrict the rights of their fellow coaches

“This Is Something That Changed My Life”: A Qualitative Study of Patients' Experiences in a Clinical Trial of Ketamine Treatment for Alcohol Use Disorders

This is the final version. Available on open access from Frontiers Media via the DOI in this recordData Availability Statement: Due to ethical concerns, the research data supporting this publication are not publicly available.Background: The therapeutic benefits of ketamine have been demonstrated for a variety of psychiatric disorders. However, the role of ketamine induced psychoactive experiences in mediating the therapeutic effects is unclear. Despite the growing quantitative research on the efficacy of ketamine treatment, very few studies examined participant experiences of ketamine infusions in a treatment setting. Aims: The current study aimed to examine participant experiences of ketamine infusions and how these relate to therapeutic mechanisms in a clinical trial setting. Methods: We conducted semi-structured interviews with 12 participants who received up to three ketamine infusions (0.8 mg/kg) as part of a Phase II double blind, randomised controlled trial. The interviews explored participants' acute experiences of ketamine infusions, experiences of psychotherapy/education, and the lasting effects of the trial. The interviews were transcribed verbatim and analysed using thematic analysis. Results: Six key themes were identified. (1) Participants reported multifaceted motivations for trial participation. (2) The set and setting was found to be influential in determining acute ketamine experiences. The acute ketamine experiences included: (3) the inherent contradictions of the experience (e.g., dissociation vs feelings of connection), (4) rapidly fluctuating and changing experiences, (5) meaningful, mystical and spiritual experiences. Finally, the final theme (6) relates to the transformational effects of the infusions and the trial. Conclusion: Provided in a supportive and professional environment, ketamine treatment led to a significant change in relationship with alcohol. Ketamine induced ego dissolution and dissociation were reported to be related to the transformational effects on relationship with alcohol. The extent to which the acute psychoactive effects of ketamine mediate therapeutic effects on drinking outcomes remain to be investigated in the trial data. The acute effects of ketamine reported by our participants transcend its traditional conceptualisation as a “dissociative anaesthetic”; therefore, we suggest the development or use of new measures alongside ketamine infusions to fully capture the spectrum of these effects which may be crucial in its therapeutic and transformative effects.Medical Research Council (MRC)Society for the Study of AddictionUniversity of Exete

A multiorganism pipeline for antiseizure drug discovery:Identification of chlorothymol as a novel γ-aminobutyric acidergic anticonvulsant

OBJECTIVE:Current medicines are ineffective in approximately one-third of people with epilepsy. Therefore, new antiseizure drugs are urgently needed to address this problem of pharmacoresistance. However, traditional rodent seizure and epilepsy models are poorly suited to high-throughput compound screening. Furthermore, testing in a single species increases the chance that therapeutic compounds act on molecular targets that may not be conserved in humans. To address these issues, we developed a pipeline approach using four different organisms. METHODS:We sequentially employed compound library screening in the zebrafish, Danio rerio, chemical genetics in the worm, Caenorhabditis elegans, electrophysiological analysis in mouse and human brain slices, and preclinical validation in mouse seizure models to identify novel antiseizure drugs and their molecular mechanism of action. RESULTS:Initially, a library of 1690 compounds was screened in an acute pentylenetetrazol seizure model using D rerio. From this screen, the compound chlorothymol was identified as an effective anticonvulsant not only in fish, but also in worms. A subsequent genetic screen in C elegans revealed the molecular target of chlorothymol to be LGC-37, a worm γ-aminobutyric acid type A (GABAA ) receptor subunit. This GABAergic effect was confirmed using in vitro brain slice preparations from both mice and humans, as chlorothymol was shown to enhance tonic and phasic inhibition and this action was reversed by the GABAA receptor antagonist, bicuculline. Finally, chlorothymol exhibited in vivo anticonvulsant efficacy in several mouse seizure assays, including the 6-Hz 44-mA model of pharmacoresistant seizures. SIGNIFICANCE:These findings establish a multiorganism approach that can identify compounds with evolutionarily conserved molecular targets and translational potential, and so may be useful in drug discovery for epilepsy and possibly other conditions

Determination of herbicides in human urine by liquid chromatography-mass spectrometry with electrospray ionization.

Aims: To determine the degree to which cigarette smoking predicts levels of cannabis dependence above and beyond cannabis use itself, concurrently and in an exploratory four-year follow-up, and to investigate whether cigarette smoking mediates the relationship between cannabis use and cannabis dependence. Methods: The study was cross sectional with an exploratory follow-up in the participants’ own homes or via telephone interviews in the United Kingdom. Participants were 298 cannabis and tobacco users aged between 16 and 23; follow-up consisted of 65 cannabis and tobacco users. The primary outcome variable was cannabis dependence as measured by the Severity of Dependence Scale (SDS). Cannabis and tobacco smoking were assessed through a self-reported drug history. Results: Regression analyses at baseline showed cigarette smoking (frequency of cigarette smoking: B = 0.029, 95% CI = 0.01, 0.05; years of cigarette smoking: B = 0.159, 95% CI = 0.05, 0.27) accounted for 29% of the variance in cannabis dependence when controlling for frequency of cannabis use. At follow-up, only baseline cannabis dependence predicted follow-up cannabis dependence (B = 0.274, 95% CI = 0.05, 0.53). At baseline, cigarette smoking mediated the relationship between frequency of cannabis use and dependence (B = 0.0168, 95% CI = 0.008, 0.288) even when controlling for possible confounding variables (B = 0.0153, 95% CI = 0.007, 0.027). Conclusions: Cigarette smoking is related to concurrent cannabis dependence independently of cannabis use frequency. Cigarette smoking also mediates the relationship between cannabis use and cannabis dependence suggesting tobacco is a partial driver of cannabis dependence in young people who use cannabis and tobacco

Ceremonial Ayahuasca in Amazonian Retreats—Mental Health and Epigenetic Outcomes From a Six-Month Naturalistic Study

Ayahuasca is a natural psychoactive brew, used in traditional ceremonies in the Amazon basin. Recent research has indicated that ayahuasca is pharmacologically safe and its use may be positively associated with improvements in psychiatric symptoms. The mechanistic effects of ayahuasca are yet to be fully established. In this prospective naturalistic study, 63 self-selected participants took part in ayahuasca ceremonies at a retreat centre in the Peruvian Amazon. Participants undertook the Beck Depression Inventory (BDI-II), State-Trait Anxiety Inventory (STAI), Self-compassion Scale (SCS), Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM), as well as secondary measures, pre- and post-retreat and at 6-months. Participants also provided saliva samples for pre/post epigenetic analysis. Overall, a statistically significant decrease in BDI-II (13.9 vs. 6.1, p < 0.001), STAI (44.4 vs. 34.3 p < 0.001) scores, and CORE-OM scores were observed (37.3 vs. 22.3 p < 0.001) at post-retreat, as well as a concurrent increase in SCS (3.1 vs. 3.6, p < 0.001). Psychometric improvements were sustained, and on some measures values further decreased at 6-month follow-up, suggesting a potential for lasting therapeutic effects. Changes in memory valence were linked to the observed psychometric improvements. Epigenetic findings were equivocal, but indicated that further research in candidate genes, such as sigma non-opioid intracellular receptor 1 (SIGMAR1), is warranted. This data adds to the literature supporting ayahuasca's possible positive impact on mental health when conducted in a ceremonial context. Further investigation into clinical samples, as well as greater analyses into the mechanistic action of ayahuasca is advised

The incidence of unpleasant dreams after sub-anaesthetic ketamine

Ketamine is an N-methyl-D-aspartate (NMDA)receptor antagonist with psychotogenic effects and for whichthere are diverse reports of whether pleasant or unpleasantdreams result during anaesthesia, post-operatively or aftersub-anaesthetic use. The aim was to assess in healthy volunteers the incidence ofunpleasant dreams over the three nights after receiving asub-anaesthetic dose of ketamine, in comparison to placebo,and with retrospective home nightmare frequency as acovariate.Thirty healthy volunteers completed questionnairesabout retrospective home dream recall and were then giveneither ketamine or placebo. Ketamine resulted in significantly more meandream unpleasantness relative to placebo and caused athreefold increase in the odds ratio for the incidence of anunpleasant dream. The number of dreams reported over thethree nights did not differ between the groups. Theincidence of unpleasant dreams after ketamine use waspredicted by retrospectively assessed nightmare frequencyat home.Ketamine causes unpleasant dreams over thethree post-administration nights. This may be evidence of aresidual psychotogenic effect that is not found on standardself-report symptomatology measures or a result of disturbedsleep electrophysiology. The results have theoretical implications for the relationship between nightmares and schizotypy

A framework to assess the quality and impact of bioinformatics training across ELIXIR.

ELIXIR is a pan-European intergovernmental organisation for life science that aims to coordinate bioinformatics resources in a single infrastructure across Europe; bioinformatics training is central to its strategy, which aims to develop a training community that spans all ELIXIR member states. In an evidence-based approach for strengthening bioinformatics training programmes across Europe, the ELIXIR Training Platform, led by the ELIXIR EXCELERATE Quality and Impact Assessment Subtask in collaboration with the ELIXIR Training Coordinators Group, has implemented an assessment strategy to measure quality and impact of its entire training portfolio. Here, we present ELIXIR's framework for assessing training quality and impact, which includes the following: specifying assessment aims, determining what data to collect in order to address these aims, and our strategy for centralised data collection to allow for ELIXIR-wide analyses. In addition, we present an overview of the ELIXIR training data collected over the past 4 years. We highlight the importance of a coordinated and consistent data collection approach and the relevance of defining specific metrics and answer scales for consortium-wide analyses as well as for comparison of data across iterations of the same course