The Symmetrical Global Mental Health (Sym-GMH) paradigm proposes a reciprocal integration between traditional and Western medical systems. This prospective, longitudinal study evaluates the psychological outcomes of 264 Western participants who engaged in Shipibo-led ayahuasca retreats at the Temple of the Way of Light in the Peruvian Amazon. Over a 12-month period, participants completed assessments of personality (NEO-FFI), quality of life (WHOQOL-BREF), decentering (EQ-Decentering), and psychiatric symptoms (SA-45). The results showed significant reductions in Neuroticism and Openness to Experience and increase in Extraversion, with no significant change in Agreeableness and Conscientiousness. Quality of life improved across all measured domains, and decentering capacities increased significantly with moderate to high effects size. Most participants (91.7%) reported long-term benefits, primarily in spiritual well-being, mental health, and personal growth. Adverse effects were minimal (2.3%). Despite higher frequency of last month substances use was observed, increase on the prevalence was only observed for tobacco. Extraversion at baseline predicted improvements across all quality-of-life domains. Notably, higher baseline psychological distress was associated with higher Neuroticism and lower decentering, suggesting that enhancing decentering may serve as a resilience factor. These findings suggest that Amazonian traditional practices, when contextually preserved and ethically applied, can offer meaningful contributions to mental health in Western populations. The study supports the integration of traditional systems within global mental health frameworks, advocating for a non-extractive, culturally respectful, and evidence-based exchange between healing paradigms.

BACKGROUND:The rise of nonfentanyl synthetic opioids such as brorphine highlights the dynamic evolution of illicit opioid markets and the persistent toxicological and public health risks they pose. METHODS:Studies reporting the pharmacology, toxicology, and analytical detection of brorphine and its analogues were identified through systematic searches of PubMed and Scopus databases. Additional data from official international organizations' early-warning platforms were also included. RESULTS:Brorphine acts as a potent μ-opioid receptor agonist with preclinical evidence of strong antinociceptive activity, respiratory depression, and abuse potential. Since 2019, it has been increasingly identified in forensic casework, frequently in combination with fentanyl or benzodiazepines, and implicated in multiple nonfatal and fatal intoxications. Structurally related analogues, including halogenated derivatives and "orphine-type" compounds, whose pharmacological properties and toxicological profiles are not well understood, have emerged. Although several liquid chromatography coupled with mass spectrometry-based methods exist for brorphine detection, no validated analytical workflows or certified reference materials are currently available for its analogues, limiting comprehensive monitoring and biomonitoring capacity. CONCLUSIONS:The rapid spread of brorphine and its analogues underscores the ongoing transition from fentanyl derivatives toward novel nonfentanyl μ-opioid receptor agonists. These substances pose significant analytical and toxicological challenges and require increased international surveillance, improved laboratory capabilities, and coordinated public health responses to reduce their impact.

The first high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed for enantioselective analysis of psychoactive compound N-ethylpentedrone. The method also enabled a detection of phase-1 metabolites of N-ethylpentedrone. Enantiomers some of the phase-1 metabolites were also separated. Application of this method to urine and oral fluid samples from the controlled naturalistic clinical study indicated to no enantioselective metabolism and elimination of N-ethylpentedrone. With the developed method a certain chemical and stereochemical instability of N-ethylpentedrone was also shown. Therefore, the observation about non-enantioselective pharmacokinetics of N-ethylpentedrone can be apparent and caused by post-collection racemization of this compound in the studied biological matrices.

Introduction:Alpha-pyrrolidinoisohexanophenone (α-PHiP) is a synthetic cathinone structurally related to alpha-pyrrolidinopentiophenone (α-PVP) and other pyrrolidinophenones, acting as a potent monoamine transporter inhibitor. Despite its raising prevalence on the recreational drug market, limited data exist about its human pharmacology. This study aimed to assess its concentrations in different matrices and characterize its acute effects in humans in comparison with cocaine when administered by intranasal route. Methods:A non-controlled observational study was conducted under naturalistic conditions in seventeen healthy adults (nine men, eight women) with prior experience using psychostimulants. Participants self-administered intranasal doses of 15-25 mg α-PHiP or 75-90 mg cocaine in two separate sessions. Physiological parameters and subjective effects (VAS, ARCI, and VESSPA-SSE questionnaires) were assessed repeatedly at baseline and up to 5 h post-administration. Biological samples (oral fluid, urine, sweat), were collected to evaluate concentration-time profiles, including a time point of dried blood spot. Results:α-PHiP was rapidly absorbed, reaching maximum concentrations in oral fluid at 20 min and showed a short half-life (1.1 h). The amount excreted unchanged in urine or present in sweat was less than 1%. Dried blood spot levels showed high interindividual variability in the range of intoxication cases. Both α-PHiP and cocaine increased heart rate while the increase in blood pressure was more sustained for α-PHiP. Subjective effects of α-PHiP peaked within the first hour and were very similar to those of cocaine, being the feelings of high and intensity reported lower. Conclusion:This study provides novel insights into the effects and distribution of α-PHiP across various biological matrices. α-PHiP elicited prototypical subjective effects characteristic of psychostimulants, confirming its potential for abuse. Compared to cocaine, α-PHiP produced similar subjective effects. Future research should further investigate the detection of its metabolites to improve monitoring and understanding of its pharmacokinetics.

In 2024, 3-Chloromethcathinone (3-CMC) accounted for over 63

Introduction Genetic variations impact drug response, driving the need for personalised medicine through pre-emptive pharmacogenetic testing. However, the adoption of pre-emptive pharmacogenetic testing for commonly prescribed drugs, such as tacrolimus, outside of tertiary hospitals is limited due to a lack of pharmacoeconomic evidence to support widespread implementation by healthcare policymakers. The iPHARMGx Consortium addresses this by developing the TRANSPGx clinical trial to assess the hypothesis that widespread adoption of a pre-emptive genotyping scheme in populations susceptible to receiving tacrolimus as immunosuppressive therapy following a kidney transplant is effective, cost-effective and feasible within the Spanish National Health System (SNHS) when compared to the standard of care tacrolimus dosing. Methods and analysis The TRANSPGx trial is a multicentre, adaptive, randomised, controlled, pragmatic phase IV clinical trial nested within the iPHARMGx master protocol, with two parallel arms, aiming for superiority. Randomisation will be conducted on an individual basis with a centralised approach, with stratification by centre. After inclusion in the trial and completion of genotyping, subjects will be randomly allocated to either the experimental group (pharmacogenetic genotype-guided tacrolimus prescription) or the standard of care tacrolimus prescription (as deemed by the attending physician). The primary objective is to assess the effectiveness of a tacrolimus pre-emptive genotyping strategy in reaching tacrolimus target plasma concentrations after renal transplant. A total of 114 subjects will be recruited among the different participating centres, provided that no futility/efficacy boundary is reached in the prespecified interim analyses. Recruitment will be carried out during a 12-month period, and subjects will be followed for a 6-month period. Ethics and dissemination The TRANSPGx trial received ethical approval on 16 January 2025 (La Paz University Hospital 2024.740). Results will be disseminated via publication in peer-reviewed journals as well as presentation at international conferences. Trial results will be submitted for publication in an open access peer-reviewed medical speciality-specific publication. Trial registration of this study can be located at both the EU Clinical Trials Register, available from https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en and https://clinicaltrials.gov . Registration on both websites was done before the enrolment of the first patient complying with European regulations. The EU Clinical Trials Register is a primary registry according to the WHO. Trial registration number EU CT number: 2024–5 16 596-32−00/Clinical trial Identifier (ClinicalTrials.gov): NCT06701825 . Protocol V. 1.2, 8 January 2025.

The enantioselective bioanalysis of synthetic cathinones and their metabolites remains analytically challenging. Due to the basic nature of these compounds, mobile phases with elevated pH are preferable for their analysis in high-performance liquid chromatography (HPLC). On the other hand, as it has been recently reported, cathinone derivatives are chemically and stereochemically instable, especially at high pH. As the alternative to HPLC, a supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) approach was developed in this study, to enable the chiral separation and detection of N-ethylpentedrone (NEP) and its major phase-1 metabolites. Careful selection of the chiral column and mobile phase compositions provided efficient retention and stereoselective resolution of both the parent compound and its polar metabolites. The applicability of the method was confirmed through the analysis of authentic human oral fluid (OF) and urine samples. The results of this study underscore the expanded analytical potential of SFC-MS/MS for chiral metabolite profiling and demonstrate its value as a complementary analytical tool to HPLC in forensic toxicology, particularly for new psychoactive substances.

Preliminary evidence suggests that ayahuasca may alleviate severe grief symptoms. This three-arm, sequentially allocated, open-label study examines the therapeutic changes associated with ayahuasca-assisted meaning reconstruction therapy (A-MR) compared to meaning reconstruction therapy alone (MR) and a no-treatment control (NT). A total of 84 adults experiencing severe grief within 12 months of losing a first-degree relative were allocated to A-MR (n = 28), MR (n = 28), or NT (n = 28). Grief severity, prolonged grief disorder symptoms, post-traumatic growth, and quality of life were assessed at baseline, after the intervention, and 3 months post-intervention. Ayahuasca was well tolerated, with no serious adverse events reported. All groups showed significant grief severity reduction (A-MR: p < .0001, d = 2.44; MR: p < .0001, d = 1.84; NT: p < .002, d = 0.74). Greater reductions were observed in the A-MR compared to MR (p = .012, d = 0.86) and NT (p = .0008, d = 1.07). A-MR was also associated with significant improvements in prolonged grief symptomatology, post-traumatic growth, and quality of life, with medium-to-large effect sizes. This is the first controlled prospective study to provide preliminary support for A-MR as a safe and potentially effective intervention for severe grief, though replication in larger randomized trials is required.

BackgroundPsychotherapy for Prolonged Grief Disorder (PGD), a condition characterized by an intense and persistent grief response, has received increased attention over the past decades. Evidence-based approaches to prevent PGD are currently scarce, and not always effective. This paper introduces a protocol for a clinical trial exploring the effectiveness of a Meaning Reconstruction psychotherapy approach (MR) assisted with ayahuasca, a traditional indigenous medicine.MethodThe outlined protocol is a three-arm, non-randomized controlled trial focused on reducing normal and pathological grief symptoms, comparing the effectiveness of Ayahuasca-assisted MR therapy (A-MR), MR therapy alone (MR) and No Treatment (NT). At least 69 people who lost a first-degree relative during the prior year, and with a Texas Revised Inventory of Grief score up 39 (TRIG ≥ 40), will participate in the trial. Participants will be allocated to an A-MR (n ≥ 23), MR (n ≥ 23) or NT (n ≥ 23) group. Those from the A-MR and MR therapy groups will undergo a therapeutic process involving 9 sessions of online psychotherapy. In addition, the A-MR condition involves 2 group sessions of ayahuasca. The primary outcomes will be normal and pathological grief severity as measured by the TRIG and Traumatic Grief Inventory Self-Report (TGI-SR), administered at baseline, post-treatment, and 3-month follow up. Measures of quality of life, post-traumatic growth, meaning-made, psychological flexibility, and self-belief consistency will be also included. In addition, subjective effects of ayahuasca and acceptance-avoidance promoting effects will be assessed following ayahuasca administration. Finally, we will analyze the potential mediating effect of meaning-made, psychological flexibility and self-belief consistency in grief symptoms (as measured by the TRIG and TGI).DiscussionThis trial is the first to empirically examinate the potential of psychedelic-assisted psychotherapy for grief, as well as the potential processes of change that may account for it.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT06150859.

Introduction:Alpha-pyrrolidinopentiophenone (α-PVP) is a commonly consumed analogue of pyrovalerone, a synthetic cathinone with psychostimulant properties similar to those of 3,4-Methylenedioxypyrovalerone (MDPV) and cocaine. Since the pharmacology of α-PVP remains scarcely studied, we aimed to evaluate the acute pharmacological effects and its abuse potential in humans after intranasal administration. Methods:We carried out a non-controlled observational study in a naturalistic environment in nine participants (3 women and six men) with a previous history of psychostimulant use. Participants self-administered a single intranasal dose of 10mg or 20mg of α-PVP. The outcomes included physiological effects (systolic and diastolic blood pressure, heart rate, and temperature) and subjective effects (Evaluation of Subjective Effects of Substances with Abuse Potential questionnaire_VESSPA-SSE, the short form of the Addiction Research Center Inventory questionnaire_ARCI and visual analog scales_VASs) and were measured at different time points (0, 20 and 40 minutes and 1, 1.5, 2, 2.5, 3, 4 and 5 hours). Results:An acute increase in blood pressure and heart rate was observed that peaked 40 minutes after administration. Subjective effects also showed a rapid onset and disappeared 3 to 5 hours after administration. Discussion:α-PVP showed psychostimulant properties similar to those displayed by cocaine and empathogenic effects commonly associated with MDMA and other cathinones (eg. methylone) consumption.

Nowadays, synthetic cathinones (SCs) is the second more representative subclass of New Psychoactive Substances, accounting for 104 analogues in the illegal market. Since its first report in 2011, α-pyrrolidinovalerophenone (α-PVP) gained popularity among drug users, provoking an increased number of intoxications. Nonetheless, pharmacokinetics data is still limited in the literature. An observational non-controlled naturalistic study on 8 healthy volunteers was conducted to assess the α-PVP and β-OH-α-PVP concentrations in OF and urine, after snorting 10 mg or 20 mg of α-PVP. A multi-analytical approach based on GC-EI-MS/MS and LC-HESI-HRMS/MS was developed and fully validated for the analytes quantification, while four untargeted LC-HESI-HRMS/MS methods in full-MS and ddMS2 were set up for unknown metabolites characterization in urine samples assisted by a dedicated data mining software. In OF, α-PVP reached a mean Cmax of 762 ± 323 ng/mL at 1 h after 10 mg administration, while a Cmax of 2,900 ± 1,373 ng/mL at 47 min after 20 mg dose. In urine, a total α-PVP mean amount of 179.2 ± 94.9 µg was accumulated after 10 mg dose, (27.2 ± 9.8 µg between 0-2 h and 152.0 ± 98.2 µg between 2-5 h), while a total amount of 122.9 ± 44.0 µg, of (36.2 ± 16.5 and 86.7 ± 28.3 µg between 0–2 and 2-5 h, respectively) was detected after 20 mg dose. Among the 10 identified metabolites, β-OH-α-PVP was a minor metabolite (total amount: 56.4 ± 27.1 and 69.1 ± 38.1 µg after 10 mg and 20 mg). The N-butanoic acid metabolite was the most abundant, detected also as glucuronide. In conclusion, α-PVP showed a later time peak than non-pyrrolidine SCs, with comparable Cmax. The pyrrolidine ring oxidative opening produced the most abundant urinary metabolite, independently from the dose.

Cannabis is the most commonly used illicit substance worldwide. Recent years have seen an increase in cannabis consumption, and with new approvals and therapeutic indications, there are challenges in minimizing the risks and interactions between cannabis-based products, cannabis prescription drugs, other approved prescription drugs, and other substances of abuse. Thus, identifying the enzymes metabolizing cannabinoid drugs and their relationship with other prescription drugs is crucial for understanding the potential interactions and effects of their simultaneous use. This article offers a comprehensive review of cannabis and the pharmacokinetic interactions between cannabis products, cannabis prescription drugs, and other approved prescription drugs, as well as other substances of abuse. It also compiles existing evidence of these interactions and describes the clinical outcomes associated with the inhibition or induction of various enzymes.

Background: Synthetic cathinones (SCs) are the second most representative class of New Psychoactive Substances, with more than 100 analogues identified in the illicit drug market up to 2024. According to the United Nations Office on Drugs and Crimes, N-ethylhexedrone (NEH) and N-ethyl-nor-pentedrone (NEP) were identified among the most frequently seized SCs worldwide. However, still, little is known with regard to their pharmacological effects in humans. Methods: For the first time, we conducted a naturalistic, prospective observational study in 16 participants (7 women and 9 men) with a previous history of psychostimulant recreational use. They intranasally self-administered a single dose of NEP (n = 8, 20-40 mg) or NEH (n = 8, 20-40 mg). The physiological effects (systolic and diastolic blood pressure, heart rate, and temperature) and subjective effects (visual analogue scales, Addiction Research Center Inventory questionnaire and Evaluation of Subjective Effects of Substances with Abuse Potential questionnaire) were assessed up to 4 h after the self-administration at different time points (0, 20 and 40 min and 1, 1.5, 2, 3 and 4 h). Results: Despite several differences, both NEP and NEH produced significant effects within 20 min, with a return to baseline 3-4 h after self-administration. In general, NEP showed a faster onset and a more rapid disappearance of subjective effects than NEH. Moreover, intranasal self-administration of NEH and NEP in experienced recreational drug users, within a non-controlled setting, induces a constellation of psychostimulant-like effects. Conclusion: NEH and NEP showed similar pharmacological properties after insufflation, with typical effects of SCs.

Introduction:Consumption of alcohol mixed with energy drinks (AmEDs) is trendy among young people. It has been related to risk-taking behaviors like binge drinking and driving under the influence of alcohol. Previous data suggest that women are more sensitive to alcohol-induced impairment. The aim of the study was to assess whether women experience greater acute effects (on driving-related skills and subjective and physiological responses) after the controlled administration of alcohol and energy drinks in an experimental binge-drinking episode. Methods:A randomized, crossover, double-blind clinical trial was conducted with 28 healthy volunteers (14 men and 14 women) across four treatment conditions, namely, alcohol + energy drink (A/ED), alcohol + placebo of ED (A), placebo of alcohol + ED (ED), and both placebos (P). Men received 70 g of alcohol and women received 55 g, combined with 750 mL and 589 mL of ED, respectively; these were administered over 80 min, mimicking a binge-drinking episode. Driving-related skills (measured by a tracking test and the psychomotor vigilance task), subjective effects (using the visual analog scales (VASs, Biphasic Alcohol Effects Scale (BAES), and Addiction Research Center Inventory (ARCI)), vital signs, and alcohol and caffeine concentrations were measured over an 8-h period. Results:Peak alcohol concentrations in breath air were 0.46 mg/L in both genders, despite the alcohol dose being 21% lower in women. Similar peak blood caffeine concentrations were observed in men and women (4,500 ng/mL vs. 4,635 ng/mL with A/ED, higher than those with ED). Women reported greater drunkenness (effect size: 45 mm; 95% CI: 5-85 mm) and more alcohol-induced sedation than men (ARCI sedative subscale effect size: 12; 95% CI: 2-22), but no significant gender differences were found in driving-related skills. AmEDs slightly reduced alcohol's effects on most subjective and psychomotor outcomes, but ED did not entirely offset alcohol's effects, and no interaction between the two beverages was found for either gender. Conclusion:After a binge-drinking episode, women reported greater drunkenness and more sedation than men. Our results support that women are more sensitive to several subjective effects of alcohol, but further studies should be conducted to better elucidate gender differences in the effects of AmEDs on driving performance. ClinicalTrials.gov NCT04616859.

Synthetic cathinones represent the second most frequently reported group of new psychoactive substances identified annually, according to the United Nations. It remains unknown whether specific derivatives differ in the onset of effects related to absorption kinetics. Clephedrone (4-chloromethcathinone, 4-CMC) has been among the most frequently seized cathinones in recent years; however, available data on its pharmacology and abuse potential remain scarce. A non-controlled, prospective, observational study was conducted involving eight healthy volunteers (six women) who self-administered a single oral dose of clephedrone (100 or 150 mg). Study variables were assessed at baseline and over a 5-h period following administration, including vital signs and subjective effects. Oral fluid concentrations of clephedrone and cortisol were determined. For comparison, this article also presents previously unpublished data from a pilot study in which 12 healthy male participants received 150 or 200 mg of methylone under comparable conditions to evaluate effects. Results indicated that both clephedrone and methylone produced stimulant-like subjective effects. However, clephedrone exhibited a delayed onset and peak of effects compared with methylone, indicating a clinically relevant pharmacokinetic difference. Both substances were detected in oral fluid, with peak concentrations occurring later following clephedrone administration, consistent with its delayed pharmacodynamic profile.

Forensic laboratories are constantly required to identify new drugs and their metabolites. N-ethylhexedrone (NEH, HEXEN), N-Ethylpentedrone (NEP), and 4-Chloromethcathinone (4-CMC, clephedrone) are synthetic substances structurally related to natural cathinone, alkaloid present in the leaves of the Catha edulis (Khat) plant. These synthetic cathinones (SC) are members of the heterogenous family of new psychoactive substances (NPS) that raised major concerns in scientific and forensic communities over the past years due to their widespread consumption. In this context, we investigated their metabolic profile using of UHPLC-QTOF-HRMS to elucidate the distribution of the parent drug and its metabolites in urine samples over time. Initially, both male and female volunteers were divided into three groups and eight subjects of each group were administered intranasally or orally with one SC (20-40mg of NEH or NEP intranasal, 100-150mg of 4-CMC oral). Urine samples were collected at 0-2 and 2-4 or 2-5hours. Urine (50µL) was diluted 1:2 with acetonitrile/methanol (95:5) and injected into the UHPLC-QTOF-HRMS. Phase-I and phase-II metabolites were identified on the basis of fragmentation patterns and exact masses. Several phase-I and glucuronide-phase-II metabolites were identified in urine samples. Keto group reduction, hydroxylation and dealkylation were the common metabolic pathways identified for all cathinones and the presence of NEH-glucuronide, NEP-glucuronide and 4-CMC-glucuronide was also relevant. Significant is the slower metabolite formation for 4-CMC, which was detected at high concentrations in its original form even 5hours after administration, due to its long half-life and low intrinsic clearance compared to the other SCs. UHPLC-QTOF-HRMS demonstrated a considerable capability to semi-quantify the three synthetic cathinones and identify the target metabolites with high reliability. The introduction of new target compounds improves the efficiency of toxicological screening analysis on real samples and extends the window of detection of the SCs in biological matrices.

BACKGROUND:Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG). METHODS:We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than -10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis. FINDINGS:Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference -29·6, 95% CI -50·5 to -8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up. INTERPRETATION:The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis. FUNDING:European Research Council and Fondo de Investigaciones Sanitarias.

Substance use disorders (SUD), also named addiction when it is severe, is a chronic brain disorder with serious impact on individual who suffer, the public health and with high burden of disease. They are multitude of mechanisms/factors involved in addiction: from individual characteristics of the person (from genetic to impacts of stress, sex, and age) to social and environmental situation (availability and accessibility of substances, cultural and legal aspects, socio-economical situation) and type of substance of use (pharmacological characteristics) Then, research on Addiction must include different, complementary, and translational perspectives.In this review, we explore the neurobiological, psychosocial, and epidemiological knowledge of substance addiction, and the main role played by pharmacology in the research in this field.In Spain, since 2002, collaborative networks have emerged for comprehensive research on addictions, with the creation of the Addictive Disorders Network (RTA), currently redefined as the Research Network for Primary Care in Addictions (RIAPAd) with the support of the Carlos III Health Institute (Instituto de Salud Carlos III). Basic (including neuropharmacology and behavioral pharmacology), clinical and epidemiological research groups stand out, combining efforts to address prevention, early detection and treatment through interdisciplinary cooperation and the subsequent dissemination of results.

This paper focuses on a single case of ayahuasca-assisted grief therapy for the prevention of complicated grief, conducted within a clinical trial. The participant, a woman in her thirties who lost her father to cancer, completed a 9-session process of Meaning Reconstruction Therapy (MRT) organised around two ayahuasca sessions. Following each psychedelic experience, she also completed a psychedelic integration session. The case study investigates the effect of the intervention, the observed changes in the participant, and the potential processes of change which may account for this improvement. The analysis relies on a qualitative narrative approach to examine the content of each therapy session, as well as on the psychometric measures completed at baseline, post-treatment, and at the three-month follow-up. These results are linked to emerging theories in the field, with a particular focus on the role of meaning reconstruction, psychological flexibility, and a continuing bond with the deceased.