The goal of this study is to assess the effects of LSD on neural synchrony, prosocial behavior, and relationship quality in healthy romantic couples.

Evidence is growing that psychedelic substances such as psilocybin, lysergic acid diethylamide (LSD) and ayahuasca could be a potential alternative treatment option for common and difficult to treat psychiatric conditions. One proposed mechanism that psychedelics target, which is a hallmark of seemingly all psychiatric disorders, are deficits in social cognitive abilities. However, the neural underpinnings of psychedelic induced alterations in prosocial behavior are currently unknown. The investigators hypothesize psychedelics increase such prosocial behaviors by increasing neural synchrony, which is the coupling of brain-to-brain activity across two or more people; it has been found to underlie social connection and various forms of shared prosocial behavior.

The current project will primarily assess whether LSD enhances neural synchrony between romantic partners. Second, the investigators will assess whether LSD enhances prosocial behavior between members of a dyad, thus replicating previous studies which assessed prosocial behavior within one individual at a time. The investigators will also assess the relationship between neural synchrony and outcome variables of the prosocial behaviour tasks. Lastly, it will be assessed whether LSD-induced changes in neural synchrony and/or prosocial behaviour affect persisting relationship quality. Oxytocin and cytokine concentrations, will also be quantified to investigate whether there is a relationship between these factors and changes in prosocial behaviour.

The study design will be conducted according to a double-blind, placebo-controlled, 2-way crossover design. Healthy participants (N=60) who are in a relationship (N=30 couples) will receive placebo and an oral dose of 50 µg of LSD. Between each condition, there will be a minimum of 14 days washout. This leads to a total study duration of minimally four weeks, for a participant to go through the medical examination and both drug conditions.

Inclusion Criteria:

• Written Informed Consent
• Understanding the procedures and the risks associated with the study.
• Age between 18 and 35 years old.
• Being in a steady relationship for at least 6 months.
• Proficient knowledge of the English language
• Previous experience with at least one psychedelic drug (psilocybin, LSD, mescaline, Ayahuasca, DMT, 5-MeO-DMT), but not within the past 3 months
• Absence of any major medical condition as determined by medical examination and laboratory analysis
• Absence of any major psychological condition as determined by medical examination
• Free from psychotropic medication
• Participants must be willing to refrain from taking illicit psychoactive substances during the study.
• Participants must be willing to drink only alcohol-free liquids and no coffee, black or green tea, or energy drink after midnight of the evening before the study session, as well as during the study day.
• Participants must be willing not to drive a traffic vehicle or to operate machines within 24 h after substance administration.
• Normal weight, body mass index (weight/height2) between 18 and 28 kg/m2

Exclusion Criteria:

• History of drug addiction (determined by the medical questionnaire, drug questionnaire and medical examination)
• Previous experience of serious side effects to psychedelic drugs (anxiety or panic attacks)
• Pregnancy or lactation
• Hypertension (diastolic > 90 mmHg; systolic > 140 mmHg)
• Current or history of psychiatric disorder (determined by the medical questionnaire and medical examination)
• Psychotic disorder in first-degree relatives
• Any chronic or acute medical condition
• History of cardiac dysfunctions (arrhythmia, ischemic heart disease,…)
• For women: no use of a reliable contraceptive
• Tobacco smoking (>20 per day)
• Excessive drinking (>20 alcoholic consumptions per week)
• Experience with a full dose of a psychedelic within the last three months
• Current use of SSRI medication

Random allocation of couples to a the treatment order will be done using Sealedenvelope software, by one experimenter who does not come in direct contact with the participants. The study will be double blind to the subject and the testing experimenter. One experimenter will be responsible for preparing the LSD. This experimenter will not be the one testing the participants. If a subject is withdrawn from the study they will be replaced, for a maximum of n=60 participants (n=30 couples). Following completion of all data collection the study will be fully unblinded.