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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.

Social cognition is important in everyday-life social interactions. The social cognitive effects of 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) and methylphenidate (both used for neuroenhancement and as party drugs) are largely unknown. We investigated the acute effects of MDMA (75 mg), methylphenidate (40 mg) and placebo using the Facial Emotion Recognition Task, Multifaceted Empathy Test, Movie for the Assessment of Social Cognition, Social Value Orientation Test and the Moral Judgment Task in a cross-over study in 30 healthy subjects. Additionally, subjective, autonomic, pharmacokinetic, endocrine and adverse drug effects were measured. MDMA enhanced emotional empathy for positive emotionally charged situations in the MET and tended to reduce the recognition of sad faces in the Facial Emotion Recognition Task. MDMA had no effects on cognitive empathy in the Multifaceted Empathy Test or social cognitive inferences in the Movie for the Assessment of Social Cognition. MDMA produced subjective ‘empathogenic’ effects, such as drug liking, closeness to others, openness and trust. In contrast, methylphenidate lacked such subjective effects and did not alter emotional processing, empathy or mental perspective-taking. MDMA but not methylphenidate increased the plasma levels of oxytocin and prolactin. None of the drugs influenced moral judgment. Effects on emotion recognition and emotional empathy were evident at a low dose of MDMA and likely contribute to the popularity of the drug.