3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) releases serotonin and norepinephrine. MDMA is reported to produce empathogenic and prosocial feelings. It is unknown whether MDMA in fact alters empathic concern and prosocial behavior. We investigated the acute effects of MDMA using the Multifaceted Empathy Test (MET), dynamic Face Emotion Recognition Task (FERT) and Social Value Orientation (SVO) test. We also assessed effects of MDMA on plasma levels of hormones involved in social behavior using a placebo-controlled, double-blind, random-order, cross-over design in 32 healthy volunteers (16 women). MDMA enhanced explicit and implicit emotional empathy in the MET and increased prosocial behavior in the SVO test in men. MDMA did not alter cognitive empathy in the MET but impaired the identification of negative emotions, including fearful, angry and sad faces, in the FERT, particularly in women. MDMA increased plasma levels of cortisol and prolactin, which are markers of serotonergic and noradrenergic activity, and of oxytocin, which has been associated with prosocial behavior. In summary, MDMA sex-specifically altered the recognition of emotions, emotional empathy and prosociality. These effects likely enhance sociability when MDMA is used recreationally and may be useful when MDMA is administered in conjunction with psychotherapy in patients with social dysfunction or post-traumatic stress disorder.

Lysergic acid diethylamide (LSD) is used recreationally and has been evaluated as an adjunct to psychotherapy to treat anxiety in patients with life-threatening illness. LSD is well-known to induce perceptual alterations, but unknown is whether LSD alters emotional processing in ways that can support psychotherapy. We investigated the acute effects of LSD on emotional processing using the Face Emotion Recognition Task (FERT) and Multifaceted Empathy Test (MET). The effects of LSD on social behavior were tested using the Social Value Orientation (SVO) test. Two similar placebo-controlled, double-blind, random-order, crossover studies were conducted using 100 μg LSD in 24 subjects and 200 μg LSD in 16 subjects. All of the subjects were healthy and mostly hallucinogen-naive 25- to 65-year-old volunteers (20 men, 20 women). LSD produced feelings of happiness, trust, closeness to others, enhanced explicit and implicit emotional empathy on the MET, and impaired the recognition of sad and fearful faces on the FERT. LSD enhanced the participants’ desire to be with other people and increased their prosocial behavior on the SVO test. These effects of LSD on emotion processing and sociality may be useful for LSD-assisted psychotherapy.

Rationale Lysergic acid diethylamide (LSD) and other serotonergic hallucinogens can induce profound alterations of consciousness and mystical-type experiences, with reportedly long-lasting effects on subjective well-being and personality. Methods We investigated the lasting effects of a single dose of LSD (200 μg) that was administered in a laboratory setting in 16 healthy participants. The following outcome measures were assessed before and 1 and 12 months after LSD administration: Persisting Effects Questionnaire (PEQ), Mysticism Scale (MS), Death Transcendence Scale (DTS), NEO-Five Factor Inventory (NEO-FFI), and State-Trait Anxiety Inventory (STAI). Results On the PEQ, positive attitudes about life and/or self, positive mood changes, altruistic/positive social effects, positive behavioral changes, and well-being/life satisfaction significantly increased at 1 and 12 months and were subjectively attributed by the subjects to the LSD experience. Five-Dimensions of Altered States of Consciousness (5D-ASC) total scores, reflecting acutely induced alterations in consciousness, and Mystical Experience Questionnaire (MEQ30) total scores correlated with changes in well-being/life satisfaction 12 months after LSD administration. No changes in negative attitudes, negative mood, antisocial/negative social effects, or negative behavior were attributed to the LSD experience. After 12 months, 10 of 14 participants rated their LSD experience as among the top 10 most meaningful experiences in their lives. Five participants rated the LSD experience among the five most spiritually meaningful experiences in their lives. On the MS and DTS, ratings of mystical experiences significantly increased 1 and 12 months after LSD administration compared with the pre-LSD screening. No relevant changes in personality measures were found. Conclusions In healthy research subjects, the administration of a single dose of LSD (200 μg) in a safe setting was subjectively considered a personally meaningful experience that had long-lasting subjective positive effects. Trial registration Registration identification number: NCT01878942.

Rationale Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. Acute mystical-type experiences that are acutely induced by hallucinogens are thought to contribute to their potential therapeutic effects. However, no data have been reported on LSD-induced mystical experiences and their relationship to alterations of consciousness. Additionally, LSD dose- and concentration-response functions with regard to alterations of consciousness are lacking. Methods We conducted two placebo-controlled, double-blind, cross-over studies using oral administration of 100 and 200 μg LSD in 24 and 16 subjects, respectively. Acute effects of LSD were assessed using the 5 Dimensions of Altered States of Consciousness (5D-ASC) scale after both doses and the Mystical Experience Questionnaire (MEQ) after 200 μg. Results On the MEQ, 200 μg LSD induced mystical experiences that were comparable to those in patients who underwent LSD-assisted psychotherapy but were fewer than those reported for psilocybin in healthy subjects or patients. On the 5D-ASC scale, LSD produced higher ratings of blissful state, insightfulness, and changed meaning of percepts after 200 μg compared with 100 μg. Plasma levels of LSD were not positively correlated with its effects, with the exception of ego dissolution at 100 μg. Conclusions Mystical-type experiences were infrequent after LSD, possibly because of the set and setting used in the present study. LSD may produce greater or different alterations of consciousness at 200 μg (i.e., a dose that is currently used in psychotherapy in Switzerland) compared with 100 μg (i.e., a dose used in imaging studies). Ego dissolution may reflect plasma levels of LSD, whereas more robustly induced effects of LSD may not result in such associations.

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.