The effect of LSD on neural synchrony, prosocial behavior, and relationship quality

Psychedelic research has seen a revival in the past decades, leading to a wave
of new studies investigating the effects of these substances in both clinical
populations and in healthy volunteers. In regard to clinical studies, 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, such as
depression, anxiety, addiction, and post-traumatic stress disorder (PTSD). One
proposed mechanism that psychedelics target, which is a hallmark of seemingly
all psychiatric disorders, are deficits in social cognitive abilities. It has
been repeatedly found that a single ingestion of a psychedelic drug increases
prosocial behavior such as enhanced empathy, willingness to disclose sensitive
information about a person*s life, and (emotional) connectivity with others.
That said, the neural underpinnings of psychedelic-induced alterations in
prosocial behavior are currently unknown. We 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.
Hyperscanning allows for the measurement of electroencephalography (EEG)
activity of multiple brains simultaneously, and thus assessment of neural
synchrony in dyads.

To assess this, the effect of a single administration of LSD (50 µg) on neural
synchrony, prosocial behaviour, and relationship quality, and the relationship
between these variables, will be assessed between healthy, romantic partners,
when given the substance simultaneously.



Primary Objectives:

Primary objectives are to investigate the effects of one dose of LSD (50 µg) on
neural synchrony, as assessed via EEG hyperscanning, between members of a
romantic couple.



Secondary Objectives:

Secondary objectives are to investigate whether LSD (50 µg) enhances
(pro)social behaviour, defined by changes in empathy, self-other distinction,
altruism, social influence processing, social rejection processing, creativity,
sociality, and conflict resolution, between the members of the romantic couple
(assessed via task batteries and questionnaires), and whether outcome measures
of prosocial behaviour correlate with neural synchrony.



Tertiary Objectives:

Tertiary objectives are to investigate the effects of LSD (50 µg) on
relationship quality, as assessed via subjective questionnaires measuring
relationship and sexual satisfaction, at set time points after the acute dosing
day. The outcome variables of relationship quality will be correlated with the
outcome variables of neural synchrony and prosocial behaviour, to assess
whether there is a relationship. Additionally, tertiary objectives include
assessment of LSD, metabolomics, oxytocin, and cytokine concentrations in
blood.

The study design will be conducted according to a double-blind,
placebo-controlled, 2 way crossover design. Healthy subjects who are in a
relationship will receive placebo and an oral dose of 50 µg of LSD, with both
subjects receiving the same treatment on the same test day. After the initial
dosing day, participants will return 2 days later to complete follow-up
measures. Up to four days after the dosing day, they will complete short
questionnaires asking about how they feel and about their perceived
relationship quality. Between each dosing condition, there will be a minimum of
14 days washout.

50 micrograms LSD dissolved in ethanol, resulting in a 1 mL solution, placebo
(1mL of ethanol) per oral

Volunteers will be enrolled for minimally four weeks, which will include five
lab visits, and undergoing two drug conditions in total. During the first lab
visit, participants will independently undergo a full medical screening
(medical history review, laboratory exam, electrocardiogram, and blood and
urine samples will be taken) by a licensed physician ensuring their safety. The
following four lab visits consist of the official testing days, two acute
testing days in which participants are given the drug treatment, and two short
follow-up visits which take place 2 days after each drug treatment.
Furthermore, participants will be asked to respond to short questionnaires up
to 4 days post treatment administration, from home. Each testing day will be
conducted with both partners simultaneously.

The acute testing day consists of both partners taking the treatment (50 mcg
LSD or placebo). Safety concerns regarding LSD are primarily psychological,
i.e. transient anxiety, which is common at the beginning of the onset of the
drug effect. At the doses of LSD used in the present study, subjects are
expected to retain most of their thought control and in contrast to psychotic
patients, subjects will remain aware of the transient state of the drug-induced
experience. Negative experiences (bad trips) and flashback phenomena may occur
under LSD, generally in uncontrolled conditions, and at much higher doses than
used in this study. In the case of any psychiatric complications after the
study session and also if the participants want to discuss negative experiences
in association with the study they can contact the study physician who will
offer further assistance beyond the testing days. Physiological effects are
limited and include sympathomimetic effects such as an increase in systolic
blood pressure, body temperature and pupil size when under the influence of the
drug.

During the acute testing day, blood samples, urine sample, an EEG scan,
computer tasks, a video recorded talking task, and questionnaires will also be
completed. The urine sample and the first blood sample shall be taken before
treatment administration. The remaining five blood samples will be used to
determine LSD, metabolomics, oxytocin, and cytokine concentrations at set
time-points after drug administration. Two days after the drug treatment,
participants will return to give a follow-up blood sample for cytokine
assessment, and complete short tasks assessing prosocial behaviour, and
complete a video recorded talking task. Up to four days after the drug
treatments, participants will be asked to answer short questionnaires about
relationship quality and sexual functioning. The acute drug testing days will
be interspersed by 14 days, to allow for a washout period. Over the course of
the medical examination and the lab visits, participants will give a total of
203 ml of blood. In case they experience complaints, the medical supervisor
will be contacted. The total discomfort experienced by the volunteer is minimal
when all precautions are taken into account.