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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, we present a narrative overview and compare evidence for the prosocial effects of MDMA and serotonergic psychedelics to elucidate shared mechanisms that may underlie the therapeutic process. We discuss 4 categories of prosocial effects: altered self-image, responses to social reward, responses to negative social input, and social neuroplasticity. While both categories of drugs alter self-perception, MDMA may do so in a way that is less related to the experience of mystical-type states than serotonergic psychedelics. In the case of social reward, evidence supports the ability of MDMA to enhance responses and suggests that serotonergic psychedelics may also do so, but more research is needed in this area. Both drug classes consistently dampen reactivity to negative social stimuli. Finally, preclinical evidence supports the ability of both drug classes to induce social neuroplasticity, promoting adaptive rewiring of neural circuits, which may be helpful in trauma processing. While both MDMA and serotonergic psychedelics produce prosocial effects, they differ in the mechanisms through which they do this. These differences affect the types of psychosocial interventions that may work best with each compound.

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 3,4‐methylenedioxymethamphetamine (MDMA) (75 mg and 125 mg) described in previously published placebo‐controlled studies, which used identical outcome measures including Visual Analogue Scales (VAS), the Adjective Mood Rating Scale (AMRS), and the 5 Dimensions of Altered States of Consciousness (5D‐ASC) scale. MDAI was well tolerated and produced subjective effects comparable with those of 125 mg MDMA. MDAI increased blood pressure similar to 125 mg MDMA but did not increase heart rate or body temperature. MDAI increased cortisol and prolactin levels and could be detected in serum about 20 min post ingestion and remained detectable at least for 4 days. In urine, MDAI was detectable over a period of at least 6 days. Further clinical investigations are warranted to assess whether MDAI could serve as drug with medicinal properties. [ABSTRACT FROM AUTHOR]

To investigate if clinical features associated with acute cannabis intoxication in patients presenting to Emergency Departments for medical assistance differ according to patient age and sex. We analysed presentations in the Euro-DEN Plus dataset from 2014 to 2019 in which cannabis was the only drug involved (except for alcohol), and age, sex and alcohol co-ingestion had been recorded. Age was considered as categorical (five groups; <20, 20–29, 30–39, 40–49 and ≥50 years), and sex as binary variable (male/female). We evaluated 12 key clinical features recorded during emergency department (ED) care. Risks of presenting with each of these clinical features according to patient age and sex were calculated by logistic regression models, and adjusted for sex, age and alcohol co-ingestion. 4,268 of 43,633 Euro-DEN presentations (9.8%) fulfilled the inclusion criteria (median age: 26 years (IQR = 20–34), 70% male, 52% co-ingested alcohol). The frequency of clinical features was: anxiety 28%, vomiting 24%, agitation 23%, palpitations 14%, reduced consciousness 13%, acute psychosis 9%, hallucinations 9%, chest pain 7%, headache 6%, hypotension 4%, hypertension 3% and seizures 2%. Patients younger than 20 years more frequently had vomiting (34.7% of cases), reduced consciousness (21.5%), and headache (10.8%); and less frequently acute psychosis (5.5%). Patients older than 49 years more often had hypotension (6.5%) and less frequently vomiting (20%), anxiety (14%), agitation (14%) and reduced consciousness (10%). Males more frequently presented with hypertension (3.7 vs. 1.5%; OR = 2.311, 95%CI = 1.299–3.816), psychosis (10.4 vs 6.3%; 1.948, 1.432–2.430), chest pain (8.1 vs 4.5%; 1.838, 1.390–2.430) and seizures (2.5 vs 1.4%; 1.805, 1.065–3.060), and less frequently with vomiting (21.8 vs 28.2%; 0.793, 0.677–0.930), anxiety (25.4 vs 32.3%; 0.655, 0.561–0.766) and hypotension (2.9 vs 5.8%; 0.485, 0.350–0.671). The prevalence of some clinical features typically associated with acute cannabis intoxication differed according to age and sex. The causes for these differences should be further investigated in order to better understand the pathophysiology of cannabis-related acute toxicity, and they may be relevant particularly for developing prevention campaigns and for treatment in specific sex and/or age groups. [ABSTRACT FROM AUTHOR]

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 describe patient characteristics, treatment indications and acute alterations of mind in patients receiving LSD (100-200 µg) and/or MDMA (100-175 mg) within the Swiss compassionate use programme from 2014-2018. Acute effects were assessed using the 5 Dimensions of Altered States of Consciousness scale and the Mystical Experience Questionnaire, and compared with those in healthy volunteers administered with LSD or MDMA and patients treated alone with LSD in clinical trials.Results: Eighteen patients (including 12 women and six men, aged 29-77 years) were treated in group settings. Indications mostly included posttraumatic stress disorder and major depression. Generally, a drug-assisted session was conducted every 3.5 months after 3-10 psychotherapy sessions. LSD induced pronounced alterations of consciousness on the 5 Dimensions of Altered States of Consciousness scale, and mystical-type experiences with increases in all scales on the Mystical Experience Questionnaire. Effects were largely comparable between patients in the compassionate use programme and patients or healthy subjects treated alone in a research setting.Conclusion: LSD and MDMA are currently used medically in Switzerland mainly in patients with posttraumatic stress disorder and depression in group settings, producing similar acute responses as in research subjects. The data may serve as a basis for further controlled studies of substance-assisted psychotherapy. [ABSTRACT FROM AUTHOR]

Aims: We compared the phenotyping metrics of a combination capsule formulation to its individual components of the newly composed Basel phenotyping cocktail. Moreover, we investigated a reduced sampling regimen for clinical applications. Methods: We performed in vitro experiments and a crossover pharmacokinetic study in twelve healthy male subjects to compare the Basel phenotyping cocktail capsule containing 6 cytochrome P450 (CYP) probe drugs with individual administration of the same drugs. Parent compounds and selected metabolites were determined by liquid chromatography–tandem mass spectrometry. Metabolic ratios (MR) for are under the curve (AUC) and single time point measurements and their correlation were determined. Results: Experiments with human liver microsomes and primary human hepatocytes in 3D co‐culture confirmed that flurbiprofen is a suitable CYP2C9 substrate. Both cocktail formulations (capsule and individual probe drug administration) were well‐tolerated and yielded reproducible MRs, which were almost identical. Correlations between single time point ratios and the corresponding AUC ratios depended on the sampling time point and the concentration time curve of the probe drugs. The MR of the capsule (Spearman rank correlation coefficient, Rs: 0.77–0.97) as well as the individual components (Rs: 0.69–0.99) correlated best at 6 h post‐treatment considering all 6 CYPs. Moreover, the 2‐h time points of the capsule agreed suitably with the AUC; however, the MR of omeprazole could not be determined for 10 out of 12 subjects. Conclusion: The capsule is easy to swallow, well tolerated and provides reliable estimates for CYP activity. The optimal sampling point for the capsule formulation is 6 h after intake. [ABSTRACT FROM AUTHOR]