LSD Acutely Impairs Fear Recognition and Enhances Emotional Empathy and Sociality

Abstract

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.

Alcohol acutely enhances decoding of positive emotions and emotional concern for positive stimuli and facilitates the viewing of sexual images

“…Specifically, MDMA mainly induces the transporter-mediated release of serotonin (Hysek et al 2012) and stimulates oxytocin secretion Ramos et al 2013), which has been implicated in the prosocial effects of MDMA (Ramos et al 2013). Additionally, the serotonin receptor agonist LSD (Rickli et al 2016) stimulated oxytocin secretion (Schmid et al 2015a), produced prosocial effects, and enhanced emotional empathy in the MET (Dolder et al 2016). In contrast to MDMA and LSD and our prediction, the present study found that alcohol did not change oxytocin levels in 30 female and 30 male participants at a low dose (0.27 g/kg) as similarly shown for a high dose of alcohol (0.8 g/kg) in seven male subjects (Bershad et al 2015).…”

“…The three aspects of empathy were each tested with 20 stimuli with positive valence and 20 stimuli with negative valence. Explicit emotional empathy was the primary predefined outcome measure because it is most robustly altered in acute pharmacological challenge studies (Dolder et al 2016;Hurlemann et al 2010;Hysek et al 2014;Schmid et al 2014).…”

Development and validation of an ultra‐fast and sensitive microflow liquid chromatography‐tandem mass spectrometry (MFLC‐MS/MS) method for quantification of LSD and its metabolites in plasma and application to a controlled LSD administration study in humans

“…[1,[4][5][6] Additionally, LSD has been shown to acutely alter emotion processing in ways that may be useful for LSD-assisted psychotherapy. [6] However, under uncontrolled conditions, adverse psychological reactions including panic are common effects of LSD use. [7,8] LSD consists of an ergoline skeleton in which the (5R,8R)-configuration confers psychoactive properties.…”

d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology

“…Clinical research with LSD, psilocybin, and other phenethylamine derivatives is currently undergoing a major revival, and current studies are exploring the potential role of hallucinogens in the treatment of alcohol dependence [158] as well as mood disorders [159] and anxiety [160]. In particular, a recent study carried out by Dolder et al has demonstrated that the administration of 100 µg of LSD enhances emotional empathy in healthy volunteers [161] However, more research needs to be performed on the differential effects of LSD and other hallucinogenic drugs at low and high doses: while at lower doses they activate 5-HT system, likely producing therapeutic effects for depression, drug dependence [159], and anxiety [160], it is clear that at high doses they activate the dopaminergic system, producing psychosis and similar effects [115]. …”