ArticlePDF Available

Additive Effects of 3,4-Methylenedioxymethamphetamine (MDMA) and Compassionate Imagery on Self-Compassion in Recreational Users of Ecstasy

Abstract and Figures

3,4-Methylenedioxymethylamphetamine (MDMA;‘ecstasy’) produces prosocial subjective effects that may extend to affiliative feelings towards the self. Behavioural techniques can produce similar self-directed affiliation. For example, compassionate imagery (CI) and ecstasy reduce self-criticism and increase self-compassion to a similar extent, with the effects of CI enhanced in the presence of ecstasy. Here, we examine self-compassion and self-criticism in recreational users who consumed chemically verified MDMA in a within-subjects crossover study. In a naturalistic setting, polydrug-using participants performed a self-focused CI exercise on two occasions separated by ≥6 days: once having consumed self-sourced MDMA and once not. Effects on state self-criticism, self-compassion and emotional empathy were assessed before and after MDMA use (or over an extended baseline period on the occasion that MDMA was not consumed) and reassessed after CI. In participants (n = 20; 8 women) whose ecstasy contained MDMA and no other drug, CI and MDMA appeared to separately increase emotional empathy (to critical facial expressions) and self-compassion. The effects of CI and MDMA on self-compassion also appeared to be additive. Establishing the observed effects in controlled studies will be critical for determining the combined utility of these approaches in fostering adaptive self-attitudes in a therapeutic context.
This content is subject to copyright. Terms and conditions apply.
Additive Effects of 3,4-Methylenedioxymethamphetamine
(MDMA) and Compassionate Imagery on Self-Compassion
in Recreational Users of Ecstasy
Sunjeev K. Kamboj
&Ylva S. E. Walldén
&Caroline J. Falconer
Majdah Raji Alotaibi
&Ian S. Blagbrough
&Stephen M. Husbands
&Tom P. Fre em a n
Published online: 4 November 2017
#The Author(s) 2017. This article is an open access publication
Abstract 3,4-Methylenedioxymethylamphetamine
(MDMA;ecstasy) produces prosocial subjective effects that
may extend to affiliative feelings towards the self. Behavioural
techniques can produce similar self-directed affiliation. For
example, compassionate imagery (CI) and ecstasy reduce
self-criticism and increase self-compassion to a similar extent,
with the effects of CI enhanced in the presence of ecstasy.
Here, we examine self-compassion and self-criticism in recre-
ational users who consumed chemically verified MDMA in a
within-subjects crossover study. In a naturalistic setting,
polydrug-using participants performed a self-focused CI exer-
cise on two occasions separated by 6 days: once having
consumed self-sourced MDMA and once not. Effects on state
self-criticism, self-compassion and emotional empathy were
assessed before and after MDMA use (or over an extended
baseline period on the occasion that MDMA was not con-
sumed) and reassessed after CI. In participants (n= 20; 8
women) whose ecstasy contained MDMA and no other drug,
CI and MDMA appeared to separately increase emotional
empathy (to critical facial expressions) and self-compassion.
The effects of CI and MDMA on self-compassion also ap-
peared to be additive. Establishing the observed effects in
controlled studies will be critical for determining the com-
bined utility of these approaches in fostering adaptive self-
attitudes in a therapeutic context.
Keywords MDMA .Prosocial .Compassion .
Self-compassion .Self-criticism .Compassionate imagery .
Ecstasy is a popular recreational drug (European Monitoring
Centre for Drugs and Drug Addiction 2015). Its subjective
interpersonal effects are well documented in recreational users
(Sumnall et al. 2006), with reports of heightened interpersonal
understanding and compassion for others. Similar subjective
effects are seen in controlled laboratory experiments with 3,4-
methylenedioxymethamphetamine (MDMA; Kamilar-Britt
and Bedi 2015), the primary constituent of most street ecstasy
(Brunt et al. 2012).
MDMA may have unique potential as an adjunct to psy-
chotherapy for disorders characterised by heightened
(interpersonal) threat, concerns about social evaluation and
deficits in understanding of interpersonal communication
(Danforth et al. 2016; Mithoefer et al. 2016). A number of
biological and neuropsychological mechanisms have been
proposed to account for these potential therapeutic effects.
Behavioural studies, for example, indicate that MDMA in-
creases emotional empathy and reduces aspects of cognitive
empathy (Kamilar-Britt and Bedi 2015). In addition, evidence
from multiple experimental paradigms (e.g. Bershad et al.
2016) supports the idea that MDMAs subjective effects are
mediated by supranormal central oxytocin levels (Francis
et al. 2016). Since oxytocin is implicated in attachment behav-
iour, altruism and cooperation (Campbell 2010), its enhanced
*Sunjeev K. Kamboj
Clinical Psychopharmacology Unit, Research Department of
Clinical, Educational and Health Psychology, University College
London, Gower St., London WC1E 6BT, UK
Medicinal Chemistry, Department of Pharmacy and Pharmacology,
University of Bath, Bath BA2 7AY, UK
Present address: National Addiction Centre, Institute of Psychiatry,
Psychology and Neuroscience, Kings College London, 4 Windsor
Walk, London SE5 8BB, UK
Mindfulness (2018) 9:11341145
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
release could result in a strengthening of the therapeutic rela-
tionship and increase the willingness of patients to disclose
private and painful memories during MDMA-assisted psycho-
therapy. In addition, MDMA might promote changes in dys-
functional self-referential attitudes, especially when used in
conjunction with behavioural procedures that aim to modify
these attitudes (Kamboj et al. 2015).
The goal of changing dysfunctional self-attitudes and be-
liefs (e.g. I am worthless/unloveable) reflects a general chal-
lenge in psychotherapy, namely, to create conditions that en-
able patients to respond to their perceived personal shortcom-
ings in a less harsh and self-critical manner. In cognitive ther-
apy, for example, this involves encouraging patients to gener-
ate compassionate responses to self-attacking thoughts (Kelly
et al. 2009). These strategies have been refined into a system
of psychological treatment—‘compassion focused therapy’—
which integrates insights from Buddhist psychology with cog-
nitive therapy (Gilbert 2010).
The inwardly directed affiliation promoted by techniques
used in compassion-focused therapy, such as compassionate
imagery, may also be generated or augmented by oxytocin
release. In fact, intranasal oxytocin administration (Rockliff
et al. 2011) and a common variant of the oxytocin receptor
gene (Isgett et al. 2016) are associated with heightened self-
compassion or prosocial and positive emotions after behav-
ioural training intended to generate compassionate feelings.
These observations contribute to our understanding of neuro-
biological mechanisms for building resilience and improving
well-being, but also point to strategies for overcoming the
pernicious negative emotional/cognitive states that character-
ise a variety of psychopathologies (Mennin and Fresco 2013).
Such resilience can be inculcated through repeated and disci-
plined cognitive training regimes that enhance emotion regu-
lation and down-regulate stress. An example of such training
is mindfulness, although other approaches from Eastern med-
itative traditionsincluding compassion-oriented practices
have also been adopted in contemporary psychiatric and psy-
chotherapy practice (D'Silva et al. 2012).
Despite the potential benefits of using compassion-
oriented contemplative techniques as therapeutic strate-
gies, individuals vary in their trait capacity for compas-
sion and may find self-directed compassion-oriented strat-
egies challenging, despite training. This has been
conceptualised as a resistance to, or fear of, compassion
and can represent a risk factor for psychopathology, or a
barrier to successful treatment (Gilbert et al. 2012).
Neuropsychopharmacological augmentation (e.g. through
hyperstimulation of the oxytocinergic system) of psycho-
social compassion-oriented strategies might mitigate
against such barriers in those who are relatively insensi-
tive to self-compassion-enhancing strategies. Such aug-
mentation has been highlighted as an important area for
psychiatric treatment development, especially for patients
who are unresponsive to single-modality treatments, or for
those who have special risk factors (Moss et al. 2016).
In a recent preliminary study, we found that recreational
ecstasy usewhich increases circulating oxytocin levels
(Wolff et al. 2006)was associated with an acute enhance-
ment in self-compassion and reduction in self-criticism
(Kamboj et al. 2015). The size of these effects was similar to
those associated with use of a self-directed compassionate im-
agery (CI) task, and summation of the effects of MDMA and
CI appeared to depend on participantsadult attachment char-
acteristics. However, since street ecstasy is often composed of
various psychoactive substances other than MDMA, and the
presence of MDMA was not assessed in that study (Kamboj
et al. 2015), there are some justifiable concerns that psychoac-
tive adulterants influenced those initial findings. More gener-
ally, data obtained under naturalistic conditions are also more
likely to be influenced by drug, set and setting(Zinberg
1986). This necessarily imposes some limits on the strength
of conclusions that can be drawn from studies conducted in
such settings. However, while obviously lacking the high
levels of experimental control afforded by double-blind labo-
ratory studies, naturalistic studies(i.e. those conducted in
ecological settings and/or with participants who are under the
influence of a drug they have sourced themselves) are none-
theless potentially valuable in allowing efficient preliminary
hypothesis testing on, as yet, poorly characterised drug effects.
These canthen pave the way for more tightly controlled studies
if promising effects are observed. Previous naturalistic drug
studies (Freeman et al. 2012;Morganetal.2010) have yielded
novel findings that were subsequently independently replicated
in double-blind laboratory experiments (de Sousa Fernandes
Perna et al. 2016; Englund et al. 2013). Naturalistic studies of
MDMA, in particular, may also have direct relevance to the
reported self-experimental use of MDMA in those attempting
to achieve personal growth through spiritual/contemplative
practices (Watson and Beck 1991).
Here, we aimed to replicate previous findings on self-
compassion and self-criticism following ecstasy use and/or
CI (Kamboj et al. 2015), while also assessing the composition
of participantsself-administered ecstasy using high-precision
spectroscopy. By only using data from participants whose
ecstasy was confirmed to contain MDMA, and no other psy-
choactive compound, we aimed to demonstrate a clearer asso-
ciation between MDMA use and/or CI, and changes in self-
attitudes (increased self-compassion and/or reduced self-criti-
cism). On the basis of our previous findings (Kamboj et al.
2015), we hypothesised that recreational MDMA use and CI
would be associated with similar increases in self-compassion
and reductions in self-criticism. Furthermore, additive effects
on these self-attitudes were hypothesised when MDMA and
CI were combined. In addition, we examined the ostensibly
separate and combined effects of MDMA and CI on general
interpersonal processing of criticism and compassion using a
Mindfulness (2018) 9:11341145 1135
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
measure of emotional empathy that included critical and com-
passionate facial stimuli. Based on experimental studies of
MDMA showing that it enhances emotional empathy in re-
sponse to positive social stimuli (Kamilar-Britt and Bedi
2015), we predicted that it would enhance emotional arousal
in response to compassionate facial expressions in the current
Recreational ecstasy users were recruited by word-of-
mouth and snowballing from the local community (note
that we use the term ecstasywhen referring to the rec-
reational drug when its composition is unknown and
MDMAin situations in which this constituent is known
to be present). Interested participants were asked to con-
tact the research team for information about the study.
Those expressing an interest in participating were tele-
phone-screened. Those disclosing a history of serious
mental health problem or physical illness (i.e. requiring
ongoing medical/psychiatric treatment), as well as women
who were pregnant or likely to become pregnant or who
were breast-feeding, were excluded.
Since our aim was to only include participants con-
firmed to have consumed MDMA, we over-recruited rel-
ative to our previous study (Kamboj et al. 2015), antici-
pating the exclusion of some volunteers. Twenty-five par-
ticipants began and completed the study (14 men; 11
women). Data from 20 participants (12 men; 8 women)
was retained as their ecstasy contained only MDMA
(n= 18) or MDMA plus 33% glucose (n=2).These
participants had previous regular experience with MDMA
(median length of experience, 4 years; median regularity
of use, 1/month). Excluded participantsecstasy contained
50% MDMA plus 50% cocaine (n= 1), 67% MDMA plus
33% mephedrone/sucrose (n= 1), > 99% glucose plus
undetermined impurities (n=1),and<50%MDMAplus
> 50% sucrose plus solvent plus undetermined impurities
(n= 2). The majority (n= 15) of participants used
MDMA < 2 times/month (n=5usedit2 times/month).
All participants also regularly (twice/month) consumed
other drugs or alcohol: alcohol (n= 20), cocaine (n=9),
cannabis (n= 14), mephedrone (n= 6), amphetamine
(n= 1), or other illicit drug (n= 3) and hence, are best
characterised as polydrug users. Sixteen were smokers. Of
the women participants, five used hormone-based contra-
ception, and three were regularly cycling.Themajority
of participants (n= 17) did not practice any form of med-
itation. Participants received £30 for participating.
The procedure closely followed that used in Kamboj et al.
(2015; see Fig. 1). A naturalistic (non-laboratory), within-
subjects design was used, with all participants completing
one session in which they took their usual dose of self-
sourced ecstasy 1 h before a compassionate imagery (CI) task
(the MDMA + CI session) and a second session (the CI-only
session) in which they took no drug prior to CI. Testing ses-
sions took place 614 days apart and were conducted in a
quiet space in participantshomes. Of the 20 participants
whose ecstasy contained MDMA and no other drug (and
whose data were therefore retained for analysis), 9 completed
the MDMA + CI session first, followed by the CI-only ses-
sion, meaning that session order was largely balanced across
the participants.
The participants were asked to refrain from any drugs
(except caffeine and nicotine) for 24 h prior to the testing
session. A urine sample was provided at the start of each of
the two sessions. ECG electrodes were attached and a pe-
riod of stabilisation allowed. Affect state measures and a
scenario-based measure of self-compassion/self-criticism
(Subjectivein Fig. 1) were taken at T1 (baseline), T2
(1 h after T1) and a third time point (T3; ~ 20 min after
T2). After the subjective measures were completed at T2
and T3, an additional brief task was performed to assess
emotional empathy (the Empathy Assessment Task using
the Self-Assessment Manikin (EAT-SAM); see below).
Since MDMA effects are close to peak levels after 1 h
(Tancer and Johanson 2003), this was the fixed time inter-
val used between T1 and T2 assessments, regardless of the
route of administration. Between T1 and T2, the partici-
pants read or listened to music. A 1-h interval also sepa-
rated T1 and T2 on the CI-only session. As such, T2 as-
sessments served as an additional baseline in the CI-only
session (see Fig. 1, top panel).
On the MDMA + CI session, participants provided the
experimenter with the amount of drug they intended to
consume to allow a small amount to be retained for testing,
and the remainder was weighed prior to consumption. All
MDMA was in powdered form and was consumed by in-
sufflation (n=3)ororally(n= 17), immediately after
completing T1 assessments. The mean weight of consumed
MDMA was 0.12 ± 0.03 g, with the following individually
consumed amounts: 0.10 g (n=5),0.12g(n= 8), 0.13 g
(n=5),0.14g(n=1),and0.25g(n= 1). Note, the latter
amount was an outlier (see below).
After repeating the state affect assessments at T2, the
participants listened to guided CI instructions and then
completed the state affect measures again at T3. The aim
of the assessments at T1 and T2 was to assess state affect,
self-compassion and self-criticism following MDMA use
alone (i.e. prior to CI; MDMA + CI session), compared to
1136 Mindfulness (2018) 9:11341145
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
thesameT1T2 period when MDMA was not consumed
(CI-only session). At T3, we aimed to compare the com-
bined effect of MDMA and CI (MDMI + CI session) with
those of CI alone.
Ecstasy-Related Mood States and Symptoms Aseriesof
visual analogue scales assessed ecstasy-related mood and
symptoms. Items included energetic,anxiety,thirsty,
muscle tension,hungry,jaw clenching,blurred vi-
sion,trust,empathy,sensitivity to colour,high,
alert,andhappy. The anchors not at alland very
(or severeor strong) were used at the extremes of the
scales (0 and 10).
State Self-Compassion and Self-Criticism The Self-
Compassion and Criticism Scale (SCCS; Falconer et al.
2015) is a scenario-based state measure of self-
compassion and self-criticism. It consists of five scenarios
designed to induce negative self-referential thinking.
Participants imagined the scenarios and immediately rated
their current reaction towards themselves in terms of self-
reassurance, self-soothing, self-compassion (self-compas-
sion subscale), self-contempt, self-criticism and self-
harshness (self-criticism subscale) on a 1 (Not at all)to
7(Highly)scale. This yields maximum subscale scores of
105 for self-criticism and 105 for self-compassion. The
SCCS has been validated and demonstrates good psycho-
metric properties (Cronbachsalphasof0.87and0.91re-
spectively for self-criticism and self-compassion subscales;
Falconer et al. 2015) and is sensitive to change in response
to compassion-oriented treatment strategies (Falconer et al.
Positive Affect TheTypesofPositiveAffectScale(TPAS;
Gilbertetal.2008) assesses the extent to which people
experience different types of positive affect using 18 ad-
jective descriptors rated on a 5-point scale to indicate their
current state (0 = Not characteristic of me,4=Ve ry
characteristic of me). Based on factor analysis, there are
three subscales for the different types of positive affect:
active (energetic, lively, adventurous, active, enthusiastic,
dynamic, excited, eager; maximum score = 32), relaxed
(peaceful, relaxed, calm, tranquil, laid back, serene; maxi-
mum = 24) and content/warm (safe, content, secure, warm;
maximum = 16). The participants responded to items in
relation to how they currently felt. Reported Cronbachs
alphas were 0.83 for active and relaxed affect and 0.73
for safe affect (Gilbert et al. 2008).
Depression The 21-item Beck Depression Inventory-II (BDI-
II; Beck et al. 1996) provided an assessment of severity of
symptoms of depression. It is scored on a 03 scale, with
- Subjective
- HR
- Subjective
- HR
Compassionate Imagery
MDMA self-administration
MDMA + CI session
Extended baseline
Post CI
Compassionate Imagery (CI-) only session
- Subjective
- HR
- Subjective
- HR
- Subjective
- HR
Compassionate Imagery
No drug-use
1 hr
1 hr - Subjective
- HR
Trait and drug-
use measures
Urine sample
Urine sample
~10 m
retained for NMR anal
Post CI
Fig. 1 Protocol outline. All the participants completed both sessions.
Subjective state measures (Subjectivein the boxes under T1, T2 and
T3) and heart rate (HR) were assessed at the three time points (T1, T2, T3)
and emotional empathy (EAT-SAM empathy assessment task using the
Self-Assessment Manikin) at T2 and T3. T1 corresponds to baseline,
before MDMA use (on the MDMA + CI session). T2 was post-MDMA
(on the MDMA + CI session) or served as a second, extended baseline
measure (on the CI-only session). T3 was post-CI (both sessions).
Procedure and assessment time points were the same on both sessions
with the exception that no MDMA was self-administered and additional
trait and drug-use history measures were completed (from T1 to T2) on
the CI-only session
Mindfulness (2018) 9:11341145 1137
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
higher values indicating higher levels of depressive symptoms
Adult Attachment The close relationshipsversion of the
Revised Adult Attachment Scale was used (Collins 1996),
which has three subscales (close,dependand anxi-
ety; six items each). The closesubscale assesses the
degree to which an individual is comfortable in close re-
lationships and taps an aspect of attachment avoidance
(e.g. People often want me to be emotionally closer than
I feel comfortable being). The dependsubscale assesses
a different aspect of attachment avoidance, namely,
comfort/discomfort in depending on others and the extent
to which participants believe others can be relied upon
(e.g. I know people will be there when I need them).
Higher scores are indicative of higher levels of comfort in
depending on others (an analogue of secure attachment)
and lower scores, greater discomfort (an analogue of in-
secure attachment). The anxietysubscale taps a
completely separate dimension of attachment that relates
to concerns about being abandoned or rejected (e.g. I
want to get close to people, but I worry about being
hurt), with higher scores indicating higher levels of at-
tachment anxiety. Items are rated on a 5-point Likert scale
(0 = Not at all characteristic of me; 5 = Very characteristic
of me). Cronbachs alphas were reported as 0.77, 0.78 and
0.85, respectively for close, dependent and anxiety sub-
scales (Collins 1996).
As previously described (Collins 1996), the closeand
dependsubscales were strongly correlated in the current
sample (r=0.709,p< 0.001), whereas their correlation with
attachment anxietywas small (r=0.284 and 0.273 re-
spectively; pvalues 0.224). These subscale scores were
entered as separate covariates to examine moderation of ef-
fects on self-compassion by individual differences in adult
Drug Use Participants indicated whether they had consumed
alcohol, tobacco, ecstasy, cannabis, cocaine, ketamine, hallu-
cinogens, mephedrone or amphetamine in the past 24 h and
previous 2 weeks. Urine samples were tested for the presence
of these common recreational drugs (Alere, Abingdon,
Oxfordshire, UK). Recent alcohol use was assessed using a
breathalyser (Lion Instruments, UK) at the start of both
Physiological Assessment An ambulatory ECG device
(Firstbeat Bodyguard 2, Jyväskylä, Finland) was used to re-
cord heart rate (beats per minute derived from the recorded
inter-beat intervals). One Ag/AgCl electrode was attached be-
low the right clavicle and the other, below the left ribcage.
Empathy Assessment Task Using the Self-Assessment
Manikin We adapted this task from the one originally de-
scribed by Ali et al. (2009); see also Seara-Cardoso et al.
2012). The Empathy Assessment Task using the Self-
Assessment Manikin (EAT-SAM) was programmed in
PsychoPy (Peirce 2007) and involved presenting and record-
ing subjective arousal and valence responses evoked by facial
affect stimuli comprising photographic images of basic (anger
and happiness) and complex interpersonal (criticism and com-
passion) emotions (see Ali et al. 2009 for further details).
Anger and happiness stimuli were drawn from the NimStim
series (Tottenham et al. 2009) and consisted of nine different
female actors. Since there are currently no similar standard
stimuli of critical and compassionate faces, we used a new
stimulus set consisting of nine facial expression of each, de-
veloped as part of a different project (Falconer et al., under
review). The approach we used in generating these stimuli is
outlined in detail in Tiddeman et al. (2001). Briefly, we first
created neutral facial stimuli of nine different female identi-
ties, each of which was itself generated by averaging the
photographed faces of three female actors using the image
averaging software, PsychoMorph (Tiddeman et al. 2001).
This software allows facial features from photographs to be
registered with markers and then averaged into a composite of
those features captured as a new image (and therefore new
identity). The second stage involved morphing the facial fea-
tures of the new (averaged) identities towards a composite
prototype image of a face expressing either compassion or
criticism (Perrett et al. 1994,1998; Sprengelmeyer et al.
2009). These compassionate and critical facial stimulus com-
posites were generated from 10 photographic images (out of
an initial set of 128 different images) of different actors ex-
pressing compassion and criticism following an emotion-
induction task relevant to generating these states. The selected
photographs were those rated (by 70 raters) as most represen-
tative of compassionate and critical expressions (representa-
tive images available upon request from author CJF).
Immediately before the task, the participants were
instructed on the meaning of the Self-Assessment Manikin
(SAM) pictograms in terms of rating their current feelings
on dimensions of arousal and valence, based on standard in-
structions for the SAM (Bradley and Lang 1994). The task
was deployed on a PC when the participant indicated they
understood the instructions. There were no practice trials.
Individual facial expression images were preceded by a cen-
tral fixation cross (1 s) and presented in randomised order on a
17-in. monitor until the participant responded to indicate their
current arousal/valence in response to the facial expression.
The next trial then began. Each scale was displayed below
each affect image and consisted of nine radio buttons along
with manikin-form anchors (Bradley and Lang 1994). Using a
mouse, the participants selected one of the radio buttons for
each scale to indicate their current emotional state in response
1138 Mindfulness (2018) 9:11341145
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
to the images (1 = negative/low to 9 = positive/high) for each
stimulus trial (each stimulus was presented once to assess
valence, and once to assess arousal; 72 trials in total consisting
of 9 different stimuli for each of four basic/complex expres-
sions). The subjective arousal response to the affective dis-
plays of other people is considered an implicit measure of
emotional empathy (Ali et al. 2009; Dziobek et al. 2008).
Compassionate Imagery Task
Participants completed a guided CI exercise, as previously
described (Kamboj et al. 2015). Briefly, the participants lis-
tened to standardised audio-recorded instructions presented
through headphones describing the nature of compassion
and the qualities of an ideal compassionate being. They then
performed a guided rhythmic breathingrelaxation exercise
and were guided on how to generate an image of an ideal
compassionate being. The participants were told that this com-
passionate being could take any form they wished and that it
would emanate compassion, directed at them.
Analysis of Ecstasy Samples
Prior to consumption, a small amount of each participants
ecstasy (~ 10 mg) was retained for subsequent analysis using
H nuclear magnetic resonance spectroscopy. A pure sample
of MDMA was used as the reference material (99% pure by
NMR). One- and two-dimensional NMR data were collected
on a Bruker (500-MHz NMR) spectrometer. Mass spectra
were recorded on a Bruker Daltonics micrOTOF
electrospray ionization mass spectrometer (ESI-MS). Each
sample was weighed, labelled and dissolved in deuterated
methanol (0.05% TMS) before analysis. Samples that were
found to be impure by
H NMR, or that lacked MDMA, were
further analysed using
spectroscopy in order to determine the identity of the other
Data Analyses
The Statistical Package for Social Sciences (SPSS, version 24,
IBM) was used to perform all statistical analyses. Data was
examined graphically and statistically for normality and out-
liers. Shapiro-Wilk tests were non-significant (all pvalues
> 0.1) and no studentised residuals exceeded ± 3 on the out-
comes. Parametric statistical analyses were therefore applied.
Two-way Time × Session repeated measures ANOVAs, with
Session (CI-only or MDMA + CI) and Time (T1, T2 and T3)
as within-subject factors, were used to analyse positive/
negative mood states and state self-compassion and self-criti-
cism. Three-way (Time × Session × Emotion) ANOVAs were
used to analyse the EAT-SAM arousal responses. For the lat-
ter, the Time factor had only two levels (T2, T3) and separate
analyses were conducted for basic (angry; happy) and com-
plex emotions (critical; compassionate) because these pairs of
stimuli were drawn from different sources. As such, the
Emotion factor also had two levels (angry and happy or crit-
ical and compassionate). Additional ANCOVAs were used to
assess moderation by attachment security of the effects of
MDMA and CI on self-compassion. Specifically, indices of
dispositional avoidant attachment (closeness and dependence
scores on the AAS) were entered as covariates.
Planned comparisons were used to follow up the main
analyses on self-compassion and self-criticism. All other
post-hoc analyses of significant ANOVA effects were
Bonferroni-corrected. Pearsons correlations were used to
explore association between variables. All reported statis-
tics are two-tailed and values are presented as means ±
standard deviations unless otherwise indicated (in fig-
ures). As reflected in the reported dfs, the analyses were
based on complete data, except for heart rate, which, due
to technical difficulties, was missing at one or more time
points for two participants. ANOVA effect sizes (η
were calculated in SPSS, and individual effect sizes
(Cohensd) included an adjustment for the correlation
between paired observations where appropriate (Lenhard
and Lenhard 2015).
Key analyses were repeated excluding the participant
with the outlying MDMA dose (0.25 g). Similarly, re-
analyses was conducted by excluding the three partici-
pants who insufflated their MDMA. The patterns of
means, effect sizes and statistical significance (i.e.
< 0.05) were retained despite data removal, and as such,
all the 20 cases were retained in the analyses.
The mean age of the participants (12 men, 8 women) was
28.45 ± 6.16 years. They had 15.05 ± 2.35 years of edu-
cation and BDI scores of 9.50 ± 6.53. All the participants
provided 0.00% readings on the alcometer on both ses-
sions. All participants reported abstinence from drugs (in-
cluding alcohol) in the 24 h prior to both testing sessions,
but all also reported use of some illicit substance in the
2 weeks preceding one or both sessions. Urine tests on the
CI-only session were either negative for all drugs (n=7),
positive for THC (n= 6), cocaine (n= 5), MDMA (n=1),
opioids (n= 1) or benzodiazepines (n=3).Onthe
MDMA + CI session, urine tests were negative for all
drugs (n= 10) or positive for amphetamine (n=2),
THC (n=6;n= 5 of whom tested positive for THC on
the CI-only session), opioids (n= 1; who also tested pos-
itive on CI-only session) and benzodiazepines (n=3;
n= 1 of whom tested positive on CI-only session).
Mindfulness (2018) 9:11341145 1139
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Subjective Effects of MDMA: Visual Analogue Scales
There were significant Time × Session interactions for thirst,
energetic, muscle tension, jaw clenching, blurred vision, sen-
sitivity to colour, hunger, high and alertness. These interac-
tions reflected a general pattern of increases (or a decrease, in
the case of hunger) from T1 to T2/T3, only on the MDMA +
CI session. Main effects of Session on anxiety, trust and happy
reflected higher levels of these states on the MDMA + CI
session and main effects of Time on trust, empathy and happy
reflected lower levels of these states at T1. The pattern of
effects is not consistent with increasing MDMA effects be-
tween T2 and T3 on the MDMA + CI session. In fact, when
the above analyses were repeated with only two levels of the
Time factor (T2, T3), three of the ANOVAs showed a Time ×
Session interaction, with muscle tension (p= 0.011) and jaw
clenching (p= 0.002), evidencing an increase between T2 and
T3 on the MDMA + CI session, whereas highshowed a
decrease on the MDMA + CI session (p=0.004).Theremain-
ing 2 × 2 interactions were non-significant (pvalues > 0.1). As
such, it is unlikely that differential effects (reported below)
across sessions and between T2 and T3 (the period when the
CI task was performed) can simply be attributed to continued
increases in response to MDMA between T2 and T3, rather
than to the additional effects of CI.
Physiological Effects
An expected Session × Time interaction was found (F(1.4,
23.5) = 9.034, p= 0.003, ɳ
= 0.347) for heart rate. This
reflected a sustained increase in heart rate in the MDMA +
CI session. Specifically, compared to T1, heart rate was
14.15 ± 18.93 beats/min higher at T2 (t(17) = 3.171,
p= 0.006) and 14.63 ± 19.39 beats/min higher at T3
(t(17) = 3.200, p= 0.005) on the MDMA + CI session relative
to the CI-only session.
Effects on Self-Criticism and Self-Compassion
On the state self-criticism subscale of the SCCS, there were
main effects of Time (F(2,38) = 26.745, p< 0.001,
= 0.585) and Session (F(1,19) = 6.881, p= 0.017,
= 0.266), but the Time × Session interaction was not sig-
nificant (F(2,38) = 2.584, p=0.089,ɳ
=0.120;Fig.2a). The
state compassion subscale of the SCCS also showed main
effects of Time (F(1.5,28.1) = 10.285, p=0.001,
= 0.351) and Session (F(1,19) = 6.592, p= 0.019,
= 0.258). However, these were subsumed by a Time ×
Session interaction (F(2,38) = 5.794, p=0.006;ɳ
Fig. 2b). Follow-up analyses showed that on the CI-only ses-
sion, there was no change in self-compassion during the ex-
tended baseline (T1T2; p= 1.00; Fig. 2b), but there was an
expected increase between T2 and T3, after CI (p=0.023,
d= 0.355). On the MDMA + CI session, there was a signifi-
cant increase in self-compassion between T1 and T2
(p= 0.008, d= 0.396), ostensibly reflecting the effect of
MDMA alone. There was an additional, albeit small, increase
between T2 and T3 (p=0.015,d= 0.191) on the MDMA + CI
session, putatively reflecting the combined effects of MDMA
and CI on self-compassion. SCCS self-compassion scores
were not different at T1 on the two sessions (Fig. 2b)
(p> 0.1, d= 0.03), but diverged significantly at T3, with
higher state self-compassion on the MDMA + CI session
(p=0.003,d= 0.301). Overall, this pattern of effects is con-
sistent with enhancement of the effects of CI on self-
compassion in the presence of MDMA.
To determine whether these subjective effects of CI ±
MDMA on self-compassion were specific, or reflected a more
general pattern of effects on positive affective states, we ex-
amined the effects of CI ± MDMA on the TPAS active, re-
laxed and content/warm subscales (Table 1). However, we
found no Session × Time interactions on any of the TPAS
subscales (Fvalues 2.1, pvalues > 0.1). Even when consid-
ering only the first two time points (i.e. comparing the effects
of MDMA self-administration with the extended baseline on
T1 T2 T3
T1 T2 T3
MDMA + CIsession
Fig. 2 a Mean (± SEM) SCCS self-criticism scores at three time points:
T1 (baseline), T2 (the extended baseline/post-MDMA time point) and T3
(post-CI on both sessions). bMean (± SEM) SCCS self-compassion
scores recorded at the same time points (T1T3). The dashed line
represents results from the CI-only session, and the solid line, the
MDMA + CI session. One asterisk indicates p< 0.05; two asterisks
indicate p< 0.01 in post-hoc tests
1140 Mindfulness (2018) 9:11341145
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
the CI session), only the active subscale showed signs of a
potential interaction (F(1,19) = 3.252, p= 0.087), with higher
levels of active positive affect post-MDMA (at T2). The other
two subscales showed no interaction (Fvalues < 1).
Moderating Role of Attachment on Self-Compassion
We did not observe a moderating role for the Closeness aspect
of attachment avoidance in the Time × Session interaction on
self-compassion (F< 1; cf. Kamboj et al. 2015). The Time ×
Session × Attachment analysis with AASdependence
scores as a covariate did not reach statistical significance
(F(2,36) = 3.039, p=0.06,ɳ
= 0.144), although descriptive-
ly/graphically, it appeared that those with higher AASde-
pendence scores showed larger increases in self-compassion
in response to CI or MDMA whereas low scorers were rela-
tively insensitive to both CI and MDMA.
Emotional Empathy
On the arousal measure of the EAT-SAM, there were no ef-
fects of Session or Time (Fvalues 2.753, pvalues > 0.1) for
basic emotions, although there was a main effect of Emotion
(anger > happiness; F(1,19) = 11.756, p= 0.003). Similarly
for valence, there was only a main effect of Emotion (happi-
ness > anger; F(1,19) = 26.893, p< 0.001), but no effects of
Session or Time (Fvalues 3.047, pvalues 0.097). For the
complex emotion duo (critical and compassionate faces), there
was a significant Time × Session × Emotion interaction on the
arousal measure of the EAT-SAM (F(1,19) = 5.155, p=0.035,
= 0.213; Fig. 3), which was investigated further with sep-
arate Time × Session ANOVAs for compassionate and critical
facial stimuli.
Critical faces showed a significant Time × Session interac-
tion (F(1, 19) = 16.429, p= 0.001 η
= 0.464). Pairwise
comparisons across levels of Session and Time showed that
at T2 (which assesses the effect of MDMA relative to extend-
ed baseline, prior to CI), arousal in response to critical faces
was higher on the MDMA + CI session (p<0.001,d=0.768).
In addition, there was an increase in arousal in response to
critical faces between T2 and T3 on the CI-only session
(p= 0.019, d= 0.391), reflecting the effects of CI alone.
This suggests an increase in arousal in response to critical
faces after either intervention separately, although the effect
of CI alone was substantially smaller than that of MDMA.
There was no evidence of an additive response to MDMA
and CI on EAT-SAM arousal (between T2 and T3 on the
MDMA + CI session). In addition, there was only a main
effect of Emotion for the complex emotions on the valence
measure of the EAT-SAM (compassionate > critical;
F(1,19) = 28.466, p< 0.001; other effects: Fvalues 1).
Possible associations were examined between EAT-SAM
arousal and valence ratings to critical faces at T2 and T3, with
Self-Compassion and Self-Criticism scores at the same time
points but no significant correlations emerged.
In this report, we extend previous findings on the effects of
recreational ecstasy and compassionate imagery (CI) on self-
attitudes. The broad qualitative pattern of individual effects of
MDMA and CI reported previously(Kamboj et al. 2015)were
also found here, although the statistical pattern of interactions
diverged. In particular, in our previous study, we found clearer
evidence of additive effects of MDMA and CI on self-
criticism (here, the Time × Session interaction was suggestive
but not statistically significant). Critically, in the current study,
we only used data from participants whose ecstasy was con-
firmed to contain only MDMA (plus 33% glucose in two
samples). The broadly similar pattern of effects across both
studies supports the validity of those previous findings, al-
though the confirmed sole presence of MDMA in participants
ecstasy in this study lends it more weight.
The primary findings in the current study were that MDMA
and CI appeared to produce similar (small to medium) in-
creases in self-compassion when administered separately.
Note however that these effects were not based on placebo-
controlled comparisons and must therefore be considered pro-
visional. When the CI instructions occurred in the presence of
Tabl e 1 Three types of positive affect (TPAS; active, relaxed and warm/content) at three time points (T1, T2 and T3) by session (mean ± SD)
CI session MDMA + CI session Fvalue
T1 T2 T3 T1 T2 T3 Session Time Session × Time
TPASactive 16.10 (6.04) 15.40 (5.85) 11.80 (5.31) 18.80 (5.07) 22.05 (5.81) 17.55 (6.07) 27.808*** 12.00*** 2.056
TPASrelax 15.15 (4.61) 16.05 (4.14) 18.50 (5.10) 14.75 (5.31) 15.40 (4.60) 20.35 (4.18) 0.110 16.056*** 1.770
TPASwarm 11.10 (2.65) 12.05 (2.24) 12.80 (2.55) 12.35 (2.28) 12.80 (2.91) 14.15 (1.90) 5.652* 8.591** 0.450
Mindfulness (2018) 9:11341145 1141
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
MDMA, there was a small but significant further increase in
self-compassion, suggesting that the effects of CI can be po-
tentiated in the presence of MDMA. In addition, emotional
empathy in response to critical faces appeared to increase
following CI (the small within-session increase in EAT-SAM
arousal between T2 and T3 on the CI-only session) and fol-
lowing MDMA (the medium to large between-session differ-
ence in EAT-SAM arousal at T2).
The effects on self-compassion were found in the absence
of interactions on three relevant and psychometrically distinct
types of positive affect (relaxation, contentment/warmth and
activation). It has been suggested that arousal ratings in tasks
such as the EAT-SAM represent an implicit index of emotional
empathy (Dziobek et al. 2008). As such, our main findings are
not entirely consistent with a simple generalised enhancement
of positive affect or demand characteristics. In contrast to
these effects on self-compassion, the effects of CI ± MDMA
were less clear-cut for self-criticism. Examination of Figure 2a
shows that there was an unexpected reduction in self-criticism
in the absence of MDMA and before CI (i.e. between T1 and
T2), which may explain the lack of a Time × Session interac-
tion (p= 0.089; cf. Kamboj et al. 2015).
Although previous studies have also examined the effects
of MDMA on emotional empathy, these have tended to use
situational rather than facial stimuli (reviewed by Kamilar-
Britt and Bedi 2015) and have not specifically examined com-
passion and criticism. Unlike these previous studies, we did
not find a generalised increase in emotional empathy or the
more specific hypothesised increase in response to compas-
sionate expressions in the presence of MDMA (cf Kamilar-
Britt and Bedi 2015). Instead, while there was no effect on
EAT-SAM arousal to basic emotion or compassionate facial
expressions in response to CI ± MDMA, critical faces elicited
enhanced arousal following MDMA at T2 relative to the ex-
tended baseline time point (T2) on the CI-only session. In
addition, CI also appeared to increase arousal to critical faces
(from T2 to T3 on the CI-only session). The specific effects of
MDMA on critical (i.e. negative) expressions diverged from
previous studies, which have not tended to show such en-
hancement of emotional empathy in response to negatively
valenced stimuli. This divergence may relate to our use of
facial (rather than situational) affective stimuli generally or
critical facial expressions in particular, which have not been
used in previous studies.
The apparently similar effects of CI and MDMA (on state
self-compassion rather than positive affect more generally,
and on arousal to critical facial stimuli, rather than other emo-
tion expressions) might suggest a common biopsychological
mechanism through which some behavioural and pharmaco-
logical strategies increase aspects of self-affiliation and emo-
tional empathy. However, given the distinct effects of MDMA
on the sympathetic system (Clark et al. 2015)and
compassion-oriented practices on the parasympathetic system
(Stellar et al. 2015), it seems unlikely that the qualitatively
similar effects of CI and MDMA observed here are due to
common effects on the autonomic nervous system.
Alternatively, given its ostensible role in (self-) affiliation
(Rockliff et al. 2011) and its hyperstimulation by MDMA
(Bershad et al. 2016), the oxytocinergic system seems to be
a mechanistically plausible substrate for the common effects
observed here, at least for self-compassion.
Our current and previous (Kamboj et al. 2015) findings
complement the existing biobehavioural methods used in the
neuroscientific study of contemplative practices (Ricard et al.
2014). MDMAs effects are particularly relevant to contem-
plative neuroscience in terms of mimicking or augmenting the
effects of compassion-oriented practices (e.g. loving kindness
meditation or compassion-focused therapy) through a biolog-
ically plausible (oxytocinergic) pathway. Whether the obser-
vations reported here have therapeutic relevance, however,
remains an open question and would need to be the subject
of separate careful study. A primary concern in such studies
would be to determine if lasting beneficial effects (on self-
attitudes) would be observed after a small number of doses
of MDMA in combination with a compassion-oriented psy-
chosocial strategy (such as CI). If so, this would be in line with
T2 T3
Compassionate faces
MDMA + CI session
CI-onlys ession
T2 T3
Critical faces
Fig. 3 Mean (± SEM) arousal
ratings (indexing emotional
empathy) in response to critical
and compassionate faces on the
empathy assessment task using
the Self-Assessment Manikin
(EAT-SAM). Two asterisks
indicate p< 0.01 for MDMA
versus drug-free performance on
critical faces at T2; one asterisk
indicates p< 0.05 for the T2
versus T3 effect of CI only on
critical faces
1142 Mindfulness (2018) 9:11341145
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
the existing model of MDMA-assisted psychotherapy for
posttraumatic stress disorder (Mithoefer et al. 2013).
Moreover, it may be that such combination treatments would
be applicable in those with specific vulnerabilities (e.g. inse-
cure attachment or fear of/resistance to compassion) who
might otherwise fail to benefit from compassion-oriented psy-
chosocial treatments (e.g. compassion-focused therapy).
While our assessment of MDMA composition represents a
methodological improvement to our previous study design,
naturalistic studies have some clear limitations and can only
be considered to be a starting point, paving the way for inves-
tigating the relevant phenomena in tightly controlled experi-
mental contexts. The setting within which this study was con-
ducted and critically, the participant group in whom it was
conducted are important considerations. As a result, we cannot
know, for example, the degree to which the findings would
generalise to MDMA-naive participants or to those with
whom compassion-oriented strategies are typically used in
the context of psychopathology (Gilbert 2010). Moreover,
while highly controlled laboratory settings are clearly the pre-
ferred context within which to test drug effects, when subjec-
tive (rather than implicit behavioural) effects are the primary
outcome, concerns about expectancy are not eliminated. In
particular, it is not possible to retain blinding of participants
once they become aware of the drugssubjectiveeffects,es-
pecially if they have previous experience with MDMA (which
is commonly the case in related studies; Kamilar-Britt and
Bedi 2015).
In addition, since participants chose the amount of MDMA
they consumed (presumably based in their previous experi-
ence with the drug, and expectations about its likely effects
on them), this inevitably introduced some variability in the
effects of the drug. On the other hand, except for one outlier,
the absolute weight of participantsMDMA fell within a rath-
er narrow band (0.10.14 g). However, another potential lim-
itation was that, while the participants indicated verbally that
they had not consumed any drugs in the 24 h prior to testing, a
sizeable proportion provided positive urine screens for illicit
drugs. However, the slow clearance of some drugs means that
their presence in urine does not necessarily imply non-
compliance with abstinence instructions in the preceding
24 h. THC and benzodiazepines in particular have prolonged
elimination kinetics (Moeller et al. 2008). However, apart
from alcohol (which all the participants provided negative
readings for), a more fine-grained quantitative analysis of re-
cent drug use was not employed here. The absence of confir-
matory chromatographic/spectrometric analysis of positive
drug screens leaves some uncertainty about the role other
drugs might have played in the effects reported here.
We aimed to use the most efficient design possible to pre-
liminarily test our hypotheses. As such, additional control
conditions (e.g. an MDMA-only condition, and a control be-
havioural strategy for CI) were not employed. Future tests of
these ideas in laboratory-controlled experiments would need
to carefully consider the issue of the number of control con-
ditions and experimental sessions, as it is unclear whether the
outcome measures used here would retain sensitivity to
change within a more intensive testing schedule.
Alternatively, less efficient between-subjects designs would
be required.
Overall, our findings suggest that further research on adap-
tive modification of intrapersonal attitudes following MDMA
(and its combined use with compassion-oriented behavioural
strategies) is warranted. Future related studies should employ
randomised, double-blind controlled designs. Rigorous tests
of the suggestive findings reported here could eventually in-
form the way in which MDMA (or similar entactogensthat
might be developed in the future) is used in combination with
psychotherapeutic strategies. Clearly, future work in this area
requires continued efforts by researchers and advocates of
psychedelicresearch to persuade regulators and funders that
this is a legitimate area of research, with potentially important
implications for the treatment of psychological disorders (Nutt
et al. 2013).
Author Contributions SKK designed the study, performed data anal-
yses and wrote the paper. YSEW designed the study, executed the study
and collaborated on writing and editing the final manuscript. CJF de-
signed the study, executed the study, collaborated on writing and edited
the final manuscript. MRA collaborated on the design, analysed the data
(medicinal chemistry) and wrote part of the results. ISB collaborated on
the design, analysed the data (medicinal chemistry) and wrote part of the
results. SMH collaborated on the design, analysed the data (medicinal
chemistry), wrote part of the results and edited the final manuscript.
TPF designed the study, executed the study and collaborated on writing
and editing the final manuscript.
Funding The study was partially funded by the UCL and a scholarship
awarded to Majdah Raji Alotaibi by the government of Saudi Arabia.
Compliance with Ethical Standards
Conflict of Interest The authors declare that they have no conflicts of
Ethics Statement All procedures were performed in accordance with
the ethical standards of the institutional and were in line with the
Declaration of Helsinki. The study received ethical approval by the
University College London Research Ethics Committee and was con-
ducted under a UK Home Office license for controlled drugs.
Informed Consent All the participants gave written informed consent
at the start of the first session; all were made aware that they could
withdraw from the study at any time without needing to give a reason.
Mindfulness (2018) 9:11341145 1143
Open Access This article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://, which permits unrestricted use,
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Falconer, C. J., King, J. A., & Brewin, C. R. (2015). Demonstrating mood
repair with a situation-based measure of self-compassion and self-
criticism. Psychology and Psychothotherapy, 88,351365.
Francis, S. M., Kirkpatrick, M. G., de Wit, H., & Jacob, S. (2016).
Urinary and plasma oxytocin changes in response to MDMA or
intranasal oxytocin administration. Psychoneuroendocrinology, 74,
Freeman, T. P., Morgan, C. J., Vaughn-Jones, J., Hussain, N., Karimi, K.,
& Curran, H. V. (2012). Cognitive and subjective effects of
mephedrone and factors influencing use of a new legal high.
Addiction, 107,792800.
Gilbert, P. (2010). An introduction to compassion focused therapy in
cognitive behavior therapy. International Journal of Cognitive
Therapy, 3,9711 2.
Gilbert, P., McEwan, K., Mitra, R., Franks,L., Richter, A., & Rockliff, H.
(2008). Feeling safe and content: a specific affect regulation system?
Relationship to depression, anxiety, stress, and self-criticism.
Journal of Positive Psychology, 3,182191.
Gilbert, P., McEwan, K., Gibbons, L., Chotai, S., Duarte, J., & Matos, M.
(2012). Fears of compassion and happiness in relation to
alexithymia, mindfulness, and self-criticism. Psychology and
Psychotherapy, 85,374390.
Isgett, S. F., Algoe, S. B., Boulton, A. J., Way, B. M., & Fredrickson, B.
L. (2016). Common variant in OXTR predicts growth in positive
emotions from loving-kindness training.
Psychoneuroendocrinology, 73,244251.
Kamboj, S. K., Kilford, E. J., Minchin, S., Moss, A., Lawn, W., Das, R.
K., Falconer, C. J., Gilbert, P., Curran, H. V., & Freeman, T. P.
(2015). Recreational 3, 4-methylenedioxy-N-methylamphetamine
(MDMA) or ecstasyand self-focused compassion: preliminary
steps in the development of a therapeutic psychopharmacology of
contemplative practices. Journal of Psychopharmacology, 29,961
Kamilar-Britt, P., & Bedi, G. (2015). The prosocial effects of 3, 4-
methylenedioxymethamphetamine (MDMA): controlled studies in
humans and laboratory animals. Neuroscience and Biobehavioral
Reviews, 57,433446.
Kelly, A. C., Zuroff, D. C., & Shapira, L. B. (2009). Soothing oneself and
resisting self-attacks: the treatment of two intrapersonal deficits in
depression vulnerability. Cognitive Therapy and Research, 33,301.
Lenhard, W., Lenhard, A. (2015). Calculation of effect sizes.
Psychometrica: Institut fur psychologische Diagnostik. Website:
Mennin, D. S., & Fresco, D. M. (2013). What, me worry and ruminate
about DSM-5 and RDoC? The importance of targeting negative self-
referential processing. Clinical Psychology Science and Practice,
Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T., Jerome, L., Martin, S.
F., Yazar-Klosinski, B., et al. (2013). Durability of improvement in
post-traumatic stress disorder symptoms and absence of harmful
effects or drug dependency after 3, 4-
methylenedioxymethamphetamine-assisted psychotherapy: a pro-
spective long-term follow-up study. Journal of
Psychopharmacology, 27,2839.
Mithoefer, M. C., Grob, C. S., & Brewerton, T. D. (2016). Novel psy-
chopharmacological therapies for psychiatric disorders: psilocybin
and MDMA. Lancet Psychiatry, 3,481488.
Moeller, K. E., Lee, K. C., & Kissack, J. C. (2008). Urine drug screening:
practical guide for clinicians. Mayo Clinic Proceedings, 83,6676.
Morgan, C. J., Schafer, G., Freeman, T. P., & Curran, H. V. (2010). Impact
of cannabidiol on the acute memory and psychotomimetic effects of
smoked cannabis: naturalistic study. British Journal of Psychiatry,
Moss, A., Curran, H. V., Bloomfield, M. A., Kamboj, S. K., Blackwell, S.
E., & Freeman, T. P. (2016). Bringing together pharmacological and
1144 Mindfulness (2018) 9:11341145
distribution, and reproduction in any medium, provided you give appro-
priate credit to the original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were made.
Ali, F., Amorim, I. S., & Chamorro-Premuzic, T. (2009). Empathy defi-
cits and trait emotional intelligence in psychopathy and
Machiavellianism. Personality and Individual Differences, 47,
Beck, A. T., Steer, R. A., & Brown, G. K. (1996). Manual for the Beck
Depression Inventory-II. San Antonio: Psychological Corporation.
Bershad, A. K., Weafer, J. J., Kirkpatrick, M. G., Wardle, M. C., Miller,
M. A., & de Wit, H. (2016). Oxytocin receptor gene variation pre-
dicts subjective responses to MDMA. Social Neuroscience, 11,592
Bradley, M. M., & Lang, P. J. (1994). Measuring emotion: the Self-
Assessment Manikin and the semantic differential. Journal of
Behavior Therapy and Experimental Psychiatry, 25,4959.
Brunt, T. M., Koeter, M. W., Niesink, R. J., & van den Brink, W. (2012).
Linking the pharmacological content of ecstasy tablets to the sub-
jective experiences of drug users. Psychopharmacology, 220,751
Campbell, A. (2010). Oxytocin and human social behavior. Personality
and Social Psychology Review, 14,281295.
Clark, C. M., Frye, C. G., Wardle, M. C., Norman, G. J., & Wit, H.
(2015). Acute effects of MDMA on autonomic cardiac activity
and their relation to subjective prosocial and stimulant effects.
Psychophysiology, 52(3), 429435.
Collins, N. L. (1996). Working models of attachment: implications for
explanation, emotion, and behavior. Journal of Personality and
Social Psychology, 71,810832.
Danforth, A. L., Struble, C. M., Yazar-Klosinski, B., & Grob, C. S.
(2016). MDMA-assisted therapy: a new treatment model for social
anxiety in autistic adults. Progress in Neuropsychopharmacology
and Biological Psychiatry, 64,237249.
de Sousa Fernandes Perna, E., Papaseit, E., Pérez-Mañá, C., Mateus, J.,
Theunissen, E., Kuypers, K., de la Torre, R., Farré, M., &
Ramaekers, J. (2016). Neurocognitive performance following acute
mephedrone administration, with and without alcohol. Journal of
Psychopharmacology, 30,13051312.
D'Silva, S., Poscablo,C., Habousha, R., Kogan, M., & Kligler, B. (2012).
Mind-body medicine therapies for a range of depression severity: a
systematic review. Psychosomatics, 53,407423.
Dziobek, I., Rogers, K., Fleck, S., Bahnemann, M., Heekeren, H. R.,
Wolf, O. T., & Convit, A. (2008). Dissociation of cognitive and
emotional empathy in adults with Asperger syndrome using the
Multifaceted Empathy Test (MET). Journal of Autism and
Developmental Disorders, 38,464473.
Englund, A., Morrison, P. D., Nottage, J., Hague, D., Kane, F.,
Bonaccorso, S., Stone, J. M., Reichenberg, A., Brenneisen, R., &
Holt, D. (2013). Cannabidiol inhibits THC-elicited paranoid symp-
toms and hippocampal-dependent memory impairment. Journal of
Psychopharmacology, 27,1927.
European Monitoring Centre for Drugs and Drug Addiction (2015)
European Drug Report 2015: trends and developments.
Publications Office of the European Union, Luxembourg.
Retrieved from EMCDDA website:
Falconer, C. J., Slater, M., Rovira, A., King, J. A., Gilbert, P., Antley, A.,
& Brewin, C. R. (2014). Embodying compassion: a virtual reality
paradigm for overcoming excessive self-criticism. PLoS One, 9,
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
psychological approaches to mental health research. The Lancet
Psychiatry, 3,700702.
Nutt, D. J., King, L. A., & Nichols, D. E. (2013). Effects of Schedule I
drug laws on neuroscience research and treatment innovation.
Nature Reviews Neuroscience, 14,577585.
Peirce, J. W. (2007). PsychoPypsychophysics software in Python.
Journal of Neuroscience Methods, 162,813.
Perrett, D., May, K. A., & Yoshikawa, S. (1994). Facial shape and judge-
ments of female attractiveness. Nature, 368,239242.
Perrett, D., Lee, K., Penton-Voak, I., Rowland, D., Yoshikawa, S., Burt,
D., Henzi, S., Castles, D., & Akamatsu, S. (1998). Effects of sexual
dimorphism on facial attractiveness. Nature, 394,884887.
Ricard, M., Lutz, A., & Davidson, R. J. (2014). Mind of the meditator.
Scientific American, 311,3845.
Richter, P., Werner, J., et al. (1998). On the validity of the Beck
Depression Inventory. A review. Psychopathology, 31,160168.
Rockliff, H., Karl, A., McEwan, K., Gilbert, J., Matos, M., & Gilbert, P.
(2011). Effects of intranasal oxytocin on compassion focused im-
agery.Emotion, 11, 1388.
Seara-Cardoso, A., Neumann, C., Roiser, J., McCrory, E., & Viding, E.
(2012). Investigating associations between empathy, morality and
psychopathic personality traits in the general population.
Personality and Individual Differences, 52,6771.
Sprengelmeyer, R., Perrett, D. I., Fagan, E. C., Cornwell, R. E., Lobmaier,
J. S., Sprengelmeyer, A., Aasheim, H. B. M., Black, I. M., Cameron,
L. M., Crow, S., Milne, N., Rhodes, E. C., & Young, A. W. (2009).
The cutest little baby face: a hormonal link to sensitivity to cuteness
in infant faces. Psychological Science, 20,149154.
Stellar, J. E., Cohen, A., Oveis, C., & Keltner, D. (2015). Affective and
physiological responses to the suffering of others: Compassion and
vagal activity. Journal of Personality and Social Psychology,
108(4), 572.
Sumnall, H. R., Cole, J. C., & Jerome, L. (2006). The varieties of ecstatic
experience: an exploration of the subjective experiences of ecstasy.
Journal of Psychopharmacology, 20,670682.
Tancer, M., & Johanson, C.-E. (2003). Reinforcing, subjective, and phys-
iological effects of MDMA in humans: a comparison with d-
amphetamine and mCPP. Drug and Alcohol Dependence, 72,33
Tiddeman, B., Burt, M., & Perrett, D. (2001). Prototyping and
transforming facial textures for perception research. IEEE
Computer Graphics and Applications, 21,4250.
Tottenham, N., Tanaka, J. W., Leon, A. C., McCarry, T., Nurse, M., Hare,
T. A., Marcus, D. J., Westerlund, A., Casey, B., & Nelson, C. (2009).
The NimStim set of facial expressions: judgments from untrained
research participants. Psychiatry Research, 168,242249.
Watson, L., & Beck, J. (1991). New age seekers: MDMA use as an
adjunct to spiritual pursuit. Journal of Psychoactive Drugs, 23,
Wolff, K., Tsapakis, E. M., Winstock, A. R., Hartley, D., Holt, D.,
Forsling,M. L., & Aitchison, K. J. (2006). Vasopressin and oxytocin
secretion in response to the consumption of ecstasy in a clubbing
population. Journal of Psychopharmacology, 20,400410.
Zinberg, N. E. (1986). Drug, set, and setting: the basis for controlled
intoxicant use. New Haven: Yale University Press.
Mindfulness (2018) 9:11341145 1145
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Terms and Conditions
Springer Nature journal content, brought to you courtesy of Springer Nature Customer Service Center GmbH (“Springer Nature”).
Springer Nature supports a reasonable amount of sharing of research papers by authors, subscribers and authorised users (“Users”), for small-
scale personal, non-commercial use provided that all copyright, trade and service marks and other proprietary notices are maintained. By
accessing, sharing, receiving or otherwise using the Springer Nature journal content you agree to these terms of use (“Terms”). For these
purposes, Springer Nature considers academic use (by researchers and students) to be non-commercial.
These Terms are supplementary and will apply in addition to any applicable website terms and conditions, a relevant site licence or a personal
subscription. These Terms will prevail over any conflict or ambiguity with regards to the relevant terms, a site licence or a personal subscription
(to the extent of the conflict or ambiguity only). For Creative Commons-licensed articles, the terms of the Creative Commons license used will
We collect and use personal data to provide access to the Springer Nature journal content. We may also use these personal data internally within
ResearchGate and Springer Nature and as agreed share it, in an anonymised way, for purposes of tracking, analysis and reporting. We will not
otherwise disclose your personal data outside the ResearchGate or the Springer Nature group of companies unless we have your permission as
detailed in the Privacy Policy.
While Users may use the Springer Nature journal content for small scale, personal non-commercial use, it is important to note that Users may
use such content for the purpose of providing other users with access on a regular or large scale basis or as a means to circumvent access
use such content where to do so would be considered a criminal or statutory offence in any jurisdiction, or gives rise to civil liability, or is
otherwise unlawful;
falsely or misleadingly imply or suggest endorsement, approval , sponsorship, or association unless explicitly agreed to by Springer Nature in
use bots or other automated methods to access the content or redirect messages
override any security feature or exclusionary protocol; or
share the content in order to create substitute for Springer Nature products or services or a systematic database of Springer Nature journal
In line with the restriction against commercial use, Springer Nature does not permit the creation of a product or service that creates revenue,
royalties, rent or income from our content or its inclusion as part of a paid for service or for other commercial gain. Springer Nature journal
content cannot be used for inter-library loans and librarians may not upload Springer Nature journal content on a large scale into their, or any
other, institutional repository.
These terms of use are reviewed regularly and may be amended at any time. Springer Nature is not obligated to publish any information or
content on this website and may remove it or features or functionality at our sole discretion, at any time with or without notice. Springer Nature
may revoke this licence to you at any time and remove access to any copies of the Springer Nature journal content which have been saved.
To the fullest extent permitted by law, Springer Nature makes no warranties, representations or guarantees to Users, either express or implied
with respect to the Springer nature journal content and all parties disclaim and waive any implied warranties or warranties imposed by law,
including merchantability or fitness for any particular purpose.
Please note that these rights do not automatically extend to content, data or other material published by Springer Nature that may be licensed
from third parties.
If you would like to use or distribute our Springer Nature journal content to a wider audience or on a regular basis or in any other manner not
expressly permitted by these Terms, please contact Springer Nature at
... These compounds also demonstrate potential for therapeutic application due to their empathogenic and dissociative effects, respectively. For example, experimental trails indicate that MDMA may enhance the effects of self-compassion practice (Kamboj et al., 2018), and in a psychotherapeutic setting, has passed preliminary trials for safe and effective treatment of post-traumatic stress disorder (PTSD) (Mithoefer et al., 2018). Experimental trials have also provided preliminary evidence that ketamine may help treat harmful drinking behaviours (Das et al., 2019). ...
... Griffiths and colleagues (2018) found that those receiving spiritual support alongside the psychedelic had significantly more acute and enduring benefits in terms of affect, attitudes, and meaning in life at six-month follow-up. Observational studies have demonstrated that compassion-based meditation may be enhanced after consumption of MDMA, pointing to a potentially synergistic effect (Kamboj et al., 2018). Recent investigations have also demonstrated increases in mindfulness capacities after ayahuasca consumption, alongside evidence of neuroplastic changes associated with such enhancements (Sampedro et al., 2017;Soler et al., 2018Soler et al., , 2016. ...
... This was achieved by employing a parsimonious mixed within-between subjects design (e.g. Kamboj et al., 2015;Kamboj et al, 2018) in which assessment of a pharmacological effect is separated from that of a behavioural manipulation, while also allowing their combined effects to be tested. We assessed state mindfulness, positive and negative affect, and autonomic activity (indirectly), to determine the extent to which modafinil's effects paralleled those of mindfulness meditation, and whether modafinil and mindfulness interact additively or synergistically (Moss et al., 2016). ...
Background: Mindfulness protocols, though beneficial for a range of indications, often involve long-term commitment and may not be accessible for those naturally low in trait mindfulness (e.g. attention-/ anxiety-related disorders). It remains unclear which ‘dose’ of mindfulness is necessary to produce beneficial effects, and broadly, how drugs such as nootropics and psychedelics may interact with mindfulness meditation. / Aims: The aims of this thesis are (1) to explore what dose of mindfulness is necessary to enhance state mindfulness (among other outcomes) and whether a drug can modulate, or add to the effects of a mindfulness strategy, (2) to explore how psychedelics may affect a meditation experience, and (3) to examine what role changes in mindfulness play in regards to beneficial psychological health outcomes shown after ceremonial psychedelic use. / Methods: A mixture of methodologies were applied to answer the above questions. Specifically, single-session mindfulness literature was systematically reviewed, and a double-placebo controlled study was designed and conducted to explore the potential for pharmacological enhancement of a single mindfulness strategy. A thematic analysis was conducted to explore user accounts of combined psychedelic and meditation experiences. Finally, linear multilevel models and longitudinal mediation models were used to explore the associations between changes in mindfulness capacity and psychological health over the course of a naturalistic ayahuasca study. / Results: Single-session mindfulness studies are capable of producing a variety of beneficial effects, and adjunctive modafinil appears to enhance some effects of behavioural strategies as well as participant engagement in subsequent practice. Psychedelics may also prove to be useful counterparts to meditations, and conversely, while psychedelics appear to enhance mindfulness, meditation practice can assist also in the navigation of, and potentially enhance effects of the psychedelic process.
... One study of people in treatment for SAD found that people who reported seeing themselves as closer to others had better treatment outcomes, suggesting that shifts toward a greater sense of closeness and similarity to others may improve outcomes (Meuret et al., 2016) Some of the self-transcendent emotions and experiences in MDMA-AT may occur in the form of self-compassion, which is likely to be particularly helpful in relation to the high levels of shame experienced by people with SAD. Experimental research has shown that self-compassion increases when people take MDMA/ecstasy (Kamboj et al., 2015(Kamboj et al., , 2018 and experiences with self-compassion are commonly reported in MDMA-AT as shown in qualitative reports like, "It was really that first MDMA session that we had…where I was able to clearly see that I had a big disconnect in compassion that I had for myself. In fact, I didn't have, really, any compassion for myself, other than maybe enough just to want to try to get help," (Barone et al., 2019). ...
Full-text available
Objective Researchers have suggested that psychotherapy may be enhanced by the addition of 3,4-methylenedioxymethamphetamine (MDMA), particularly in the treatment of disorders wherein interpersonal dysfunction is central, such as social anxiety disorder. We review literature pertaining to three potential processes of change that may be instigated during sessions involving MDMA administration in the treatment of social anxiety disorder. Design This is a narrative review that integrates research on the etiology and maintenance of social anxiety disorder and mechanisms of action of MDMA to examine how MDMA may enhance psychotherapy outcomes. Results We first outline how MDMA may enhance memory reconsolidation in social anxiety disorder. We then discuss how MDMA may induce experiences of self-transcendence and self-transcendent emotions such as compassion, love, and awe; and how these experiences may be therapeutic in the context of social anxiety disorder. We subsequently discuss the possibility that MDMA may enhance the strength and effectiveness of the therapeutic relationship which is a robust predictor of outcomes across many disorders as well as a potential key ingredient in treating disorders where shame and social disconnection are central factors. Conclusion We discuss how processes of change may extend beyond the MDMA dosing sessions themselves.
... MDMA-AT may help individuals with SAD reduce shame by facilitating experiences of compassion or kindness toward the self through neurochemical changes, as well as through modeling from the therapist in the dosing session. With respect to the former, two experimental studies with ecstasy (presumably containing MDMA in one study and tested to confirm MDMA in the other) demonstrated that ecstasy increases feelings of selfcompassion and reduces self-criticism (108,109). In addition, anecdotal reports of MDMA-AT sessions suggest that MDMA increases self-compassion and self-acceptance (28,110). ...
Full-text available
Social anxiety disorder (SAD) is a prevalent and often debilitating psychiatric disorder that can assume a chronic course even when treated. Despite the identification of evidence-based pharmacological and behavioral treatments for SAD, much room for improved outcomes exists and 3,4-methylenedioxymethamphetamine (MDMA) has been proposed as a promising adjunctive treatment to psychological interventions for disorders characterized by social dysfunction. A small randomized, placebo-controlled trial of MDMA-assisted therapy (MDMA-AT) for social anxiety in autistic adults offered encouraging results, but more research is sorely needed to explore the potential for MDMA-AT in treating SAD. This review aims to stimulate future study by summarizing research on disruptions in neurological, perceptual, receptive, and expressive systems regulating social behavior in SAD and proposing how MDMA-AT may alter these systems across four domains. First, we review research highlighting the roles of social anhedonia and reduced social reward sensitivity in maintaining SAD, with specific attention to the reduction in positive affect in social situations, infrequent social approach behaviors, and related social skills deficits. We posit that MDMA-AT may enhance motivation to connect with others and alter perceptions of social reward for an extended period following administration, thereby potentiating extinction processes, and increasing the reinforcement value of social interactions. Second, we review evidence for the central role of heightened social evaluative threat perception in the development and maintenance of SAD and consider how MDMA-AT may enhance experiences of affiliation and safety when interacting with others. Third, we consider the influence of shame and the rigid application of shame regulation strategies as important intrapersonal processes maintaining SAD and propose the generation of self-transcendent emotions during MDMA sessions as a mechanism of shame reduction that may result in corrective emotional experiences and boost memory reconsolidation. Finally, we review research on the role of dysfunctional interpersonal behaviors in SAD that interfere with social functioning and, in particular, the development and maintenance of close and secure relationships. We discuss the hypothesized role of MDMA-AT in improving social skills to elicit positive interpersonal responses from others, creating a greater sense of belonging, acceptance, and social efficacy.
... MDMA augments the response to reactivating positive autobiographical memories, diminishes the response to negative autobiographical memories, and promotes self-compassion. 3,4 Perhaps consistent with these effects, MDMA attenuates fear reconsolidation 5 and produces prosocial effects in animals. 6 In humans, MDMA increases trust, increases responsiveness to positive stimuli and social cues, diminishes responses to negative stimuli and social cues, enhances empathy, facilitates the sharing of sensitive personal information with others, and enhances the response to social touch, among other effects. ...
Full-text available
A promising new Phase III study of MDMA plus psychotherapy for PTSD treatment by Mitchell and colleagues that appeared in Nature Medicine raises important new questions about the biology and optimal treatment of this disorder.
... Because the study was naturalistic and exploratory, and polytoxicomania was a common phenomenon among respondents, it cannot be assumed that MDMA users perform better than those who do not use MDMA, as these results may be associated with reduced criticism of their own health condition, or other distortions of self-esteem [18]. Conducting personal, long-term observations of MDMA users to verify this result can be difficult in the face of penalizing the possession of psychoactive substances, including MDMA, which may lead users to avoid telling the truth in contact with their physician. ...
Full-text available
MDMA is one of the most commonly used drugs in the world. Clinical studies are currently being conducted around the world on the use of this substance in the treatment of PTSD and alcoholism. However, little demographic information is available on users who use the substance for non-medical purposes. The aim of the study was to determine basic demographic and health characteristics with validated tools. The authors prepared an original questionnaire on the demography of MDMA users and combined it with the General Health Questionnaire-28 (GHQ-28) and the Hospital Anxiety and Depression Scale (HADS). The survey was sent to Polish MDMA users via the Internet. 304 responses were received from people over 18 years of age. MDMA is wide- spread among young adults, in many different places of residence and regardless of gender. The users take MDMA in both pill and crystal form and very rarely test drugs bought from a dealer. Most users feel that MDMA has had a good impact on their lives. MDMA is rarely used as the only psychoactive substance. MDMA users rate their health higher than people using other psychoactive substances.
... We employed a parsimonious mixed within-between subjects design in which assessment of pharmacological effects were separated from those of a behavioural manipulation, while also allowing their combined effects to be tested (e.g. Kamboj et al., 2015Kamboj et al., , 2018. Our pre-registered hypotheses were that, compared to an active relaxation control, brief mindfulness training would increase state mindfulness, improve sustained attention and decrease mind wandering. ...
Background: Mindfulness-meditation has a variety of benefits on well-being. However, individuals with primary attentional impairments (e.g. attention deficit disorder) or attentional symptoms secondary to anxiety, depression or addiction, may be less likely to benefit, and require additional mindfulness-augmenting strategies. / Aims: To determine whether a single dose of the cognitive enhancer, modafinil, acutely increases subjective and behavioural indices of mindfulness, and augments brief mindfulness training. / Methods: A randomised, double-blind, placebo-controlled, 2 (drug: placebo, modafinil) × 2 (strategy: mindfulness, relaxation control) experiment was conducted. Seventy-nine meditation-naïve participants were assigned to: placebo–relaxation, placebo–mindfulness, modafinil–relaxation or modafinil–mindfulness. Pre-drug, post-drug and post-strategy state mindfulness, affect and autonomic activity, along with post-strategy sustained attention and mind-wandering were assessed within a single lab session. After the session, participants were instructed to practice their assigned behavioural strategy daily for one week, with no further drug administration, after which, follow-up measures were taken. / Results: As predicted, modafinil acutely increased state mindfulness and improved sustained attention. Differential acute strategy effects were found following mindfulness on autonomic activity but not state mindfulness. There were no strategy or drug effects on mind-wandering. However, exploratory analyses indicated that participants receiving modafinil engaged in more strategy practice across strategy conditions during follow-up. / Conclusions: Modafinil acutely mimicked the effects of brief mindfulness training on state mindfulness but did not enhance the effects of this training. Limitations of the current study, and recommendations for future research examining modafinil as an adjunct to mindfulness- (or relaxation-) based treatments are discussed.
... We employed a parsimonious mixed within-between subjects design in which assessment of pharmacological effects were separated from those of a behavioural manipulation, while also allowing their combined effects to be tested (e.g. Kamboj et al., 2015Kamboj et al., , 2018. Our pre-registered hypotheses were that, compared to an active relaxation control, brief mindfulness training would increase state mindfulness, improve sustained attention and decrease mind wandering. ...
Full-text available
Background: Mindfulness-meditation has a variety of benefits on well-being. However, individuals with primary attentional impairments (e.g. attention deficit disorder) or attentional symptoms secondary to anxiety, depression or addiction, may be less likely to benefit, and require additional mindfulness-augmenting strategies. Aims: To determine whether a single dose of the cognitive enhancer, modafinil, acutely increases subjective and behavioural indices of mindfulness, and augments brief mindfulness training. Methods: A randomised, double-blind, placebo-controlled, 2 (drug: placebo, modafinil) × 2 (strategy: mindfulness, relaxation control) experiment was conducted. Seventy-nine meditation-naïve participants were assigned to: placebo–relaxation, placebo–mindfulness, modafinil–relaxation or modafinil–mindfulness. Pre-drug, post-drug and post-strategy state mindfulness, affect and autonomic activity, along with post-strategy sustained attention and mind-wandering were assessed within a single lab session. After the session, participants were instructed to practice their assigned behavioural strategy daily for one week, with no further drug administration, after which, follow-up measures were taken. Results: As predicted, modafinil acutely increased state mindfulness and improved sustained attention. Differential acute strategy effects were found following mindfulness on autonomic activity but not state mindfulness. There were no strategy or drug effects on mind-wandering. However, exploratory analyses indicated that participants receiving modafinil engaged in more strategy practice across strategy conditions during follow-up. Conclusions: Modafinil acutely mimicked the effects of brief mindfulness training on state mindfulness but did not enhance the effects of this training. Limitations of the current study, and recommendations for future research examining modafinil as an adjunct to mindfulness- (or relaxation-) based treatments are discussed.
... The last three emotional states are more typical of entactogenic effects, which seem to have a pronounced social and empathy-enhancing component (Greer and Tolbert 1986;Hysek et al., 2013;Kirkpatrick and de Wit, 2015), as well as increasing the perceived pleasantness of affective touch (Bershad et al., 2019). Perhaps most relevant for its therapeutic potential, it was found that while MDMA increased self-report anxiety, it decreases social anxiety, increased sociability, openness and authenticity Dolder et al., 2018a;Kamboj et al., 2018;Wagner et al., 2017). These results are consistent with previous findings that MDMA decreases the perceived intensity of social rejection (Bedi et al., 2010;Frye et al., 2014). ...
Full-text available
The last two decades have seen a revival of interest in the entactogen 3,4-methylenedioxy-N-methylamphetamine (MDMA) as an adjunct to psychotherapy, particularly for the treatment of post-traumatic stress disorder. While clinical results are highly promising, and MDMA is expected to be approved as a treatment in the near future, it is currently the only compound in its class of action that is being actively investigated as a medicine. This lack of alternatives to MDMA may prove detrimental to patients who do not respond well to the particular mechanism of action of MDMA or whose treatment calls for a modification of MDMA's effects. For instance, patients with existing cardiovascular conditions or with a prolonged history of stimulant drug use may not fit into the current model of MDMA-assisted psychotherapy, and could benefit from alternative drugs. This review examines the existing literature on a host of entactogenic drugs, which may prove to be useful alternatives in the future, paying particularly close attention to any neurotoxic risks, neuropharmacological mechanism of action and entactogenic commonalities with MDMA. The substances examined derive from the 1,3-benzodioxole, cathinone, benzofuran, aminoindane, indole and amphetamine classes. Several compounds from these classes are identified as potential alternatives to MDMA.
Conference Paper
This clinical psychology doctoral thesis is structured into three chapters. The first chapter presents a systematic review of the cognitive and emotional domains affected by transcutaneous vagus nerve stimulation (tVNS). It also aims to present an overview of the experimental designs, psychological tasks, outcome measures, participant groups and stimulation parameters used in the field of tVNS. The second chapter is an empirical paper investigating the potential facilitatory effects of tVNS as an adjunct to compassionate mind training (CMT). The study investigates the effect of tVNS and CMT on state affect, self-compassion/criticism, vagally mediated heart rate variability and emotional face processing in healthy participants. The third chapter is a critical appraisal of the research process of chapter 1 and 2.
Full-text available
The success of modern medicine creates a growing population of those suffering from life-threatening illnesses (LTI) who often experience anxiety, depression, and existential distress. We present a novel approach; investigating MDMA-assisted psychotherapy for the treatment of anxiety in people with an LTI. Participants with anxiety from an LTI were randomized in a double-blind study to receive MDMA (125 mg, n = 13) or placebo (n = 5) in combination with two 8-h psychotherapy sessions. The primary outcome was change in State-Trait Anxiety Inventory (STAI) Trait scores from baseline to one month post the second experimental session. After unblinding, participants in the MDMA group had one open-label MDMA session and placebo participants crossed over to receive three open-label MDMA sessions. Additional follow-up assessments occurred six and twelve months after a participant’s last experimental session. At the primary endpoint, the MDMA group had a greater mean (SD) reduction in STAI-Trait scores, − 23.5 (13.2), indicating less anxiety, compared to placebo group, − 8.8 (14.7); results did not reach a significant group difference (p = .056). Hedges’ g between-group effect size was 1.03 (95% CI: − 5.25, 7.31). Overall, MDMA was well-tolerated in this sample. These preliminary findings can inform development of larger clinical trials to further examine MDMA-assisted psychotherapy as a novel approach to treat individuals with LTI-related anxiety. Trial Registration: Identifier: NCT02427568, first registered April 28, 2015.
Full-text available
Recreational use of mephedrone, alone and in combination with alcohol, has increased over the past years. Pharmacological properties of mephedrone share similarities with methylenedioxymethamphetamine (MDMA), but its effect on neurocognitive function has not been well established in humans. The present study assessed the effect of mephedrone alone and after co-administration with alcohol on neurocognitive function. It was hypothesised that mephedrone would improve psychomotor performance but impair memory performance, when administered alone. Neurocognitive performance was expected to be impaired following mephedrone when combined with alcohol. Eleven participants received single doses of 200 mg mephedrone or placebo combined with 0.8 g/kg alcohol or placebo. Neurocognitive performance was assessed at baseline (T0), at one hour (T1) and four hours after (T2) mephedrone administration, by means of the Divided Attention Task (DAT), Critical Tracking Task (CTT), and the Spatial Memory Test (SMT). Mephedrone intoxication impaired short-term spatial memory at T1 and improved critical tracking performance at T2. Mephedrone alone did not affect divided attention, but did show an interaction with alcohol on reaction time at T2. Reaction time decreased when mephedrone was combined with alcohol as compared to alcohol alone. Alcohol intoxication impaired both short- and long-term spatial memory at T1 and divided attention at T1 and T2. Critical tracking performance was not affected by alcohol intoxication. The current findings support the hypothesis that mephedrone improves psychomotor performance, impairs spatial memory and does not affect divided attention performance. Stimulatory effects of mephedrone were not sufficient to compensate for the impairing effects of alcohol on most performance parameters.
Full-text available
3,4-methylenedioxy-N-methylamphetamine (MDMA) produces diverse pro-social effects. Cognitive training methods rooted in Eastern contemplative practices also produce these effects through the development of a compassionate mindset. Given this similarity, we propose that one potential mechanism of action of MDMA in psychotherapy is through enhancing effects on intrapersonal attitudes (i.e. pro-social attitudes towards the self). We provide a preliminary test of this idea. Recreational MDMA (ecstasy) users were tested on two occasions, having consumed or not consumed ecstasy. Self-critical and self-compassionate responses to self-threatening scenarios were assessed before (T1) and after (T2) ecstasy use (or non-use), and then after compassionate imagery (T3). Moderating roles of dispositional self-criticism and avoidant attachment were examined. Separately, compassionate imagery and ecstasy produced similar sociotropic effects, as well as increases in self-compassion and reductions in self-criticism. Higher attachment-related avoidance was associated with additive effects of compassionate imagery and ecstasy on self-compassion. Findings were in line with MDMA's neuropharmacological profile, its phenomenological effects and its proposed adjunctive use in psychotherapy. However, although conditions were balanced, the experiment was non-blind and MDMA dose/purity was not determined. Controlled studies with pharmaceutically pure MDMA are still needed to test these effects rigorously. © The Author(s) 2015.
Full-text available
The first study of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of social anxiety in autistic adults commenced in the spring of 2014. The search for psychotherapeutic options for autistic individuals is imperative considering the lack of effective conventional treatments for mental health diagnoses that are common in this population. Serious Adverse Events (SAEs) involving administration of MDMA in clinical trials have been rare and non-life threatening. To date, MDMA has been administered to over 1133 individuals for research purposes without the occurrence of unexpected drug-related SAEs that require expedited reporting per FDA regulations. Now that safety parameters for limited use of MDMA in clinical settings have been established, a case can be made to further develop MDMA-assisted therapeutic interventions that could support autistic adults in increasing social adaptability among the typically developing population. As in the case with classic hallucinogens and other psychedelic drugs, MDMA catalyzes shifts towards openness and introspection that do not require ongoing administration to achieve lasting benefits. This infrequent dosing mitigates adverse event frequency and improves the risk/benefit ratio of MDMA, which may provide a significant advantage over medications that require daily dosing. Consequently, clinicians could employ new treatment models for social anxiety or similar types of distress administering MDMA on one to several occasions within the context of a supportive and integrative psychotherapy protocol. Identifier: NCT02008396. Copyright © 2015. Published by Elsevier Inc.
Background: The neuropeptide oxytocin (OT) has received increased experimental attention for its putative role in both normal social functioning and several psychiatric disorders that are partially characterized by social dysfunction (e.g., autism spectrum disorders: ASD). Many human experimental studies measure circulating plasma levels of OT in order to examine the relationship between the hormone and behavior. Urinary OT (uOT) assays offer a simple, easy, and non-invasive method to measure peripheral hormone levels, but the correspondence between uOT and plasma OT (pOT) levels is unclear. Here, we conducted two within-subjects, double-blind studies exploring changes in uOT and pOT levels following administration of two drugs: MDMA, an oxytocin-releasing drug (Study 1), and intranasal oxytocin (INOT: Study 1 and 2). Methods: In Study 1, 14 adult participants (2 females) were each administered either oral 1.5mg/kg MDMA or 40IU INOT across two different study sessions. In Study 2, 10 male participants (adolescents and young adults) diagnosed with ASD received either 40IU INOT or placebo across two different sessions. In both studies, blood and urine samples were collected before and after drug administration at each study session. For Study 1, 10 participants provided valid plasma and urine samples for the MDMA session, and 8 provided valid samples for the INOT session. For Study 2, all 10 participants provided valid samples for both INOT and placebo sessions. Pre- and post-administration levels of pOT and uOT were compared. Additionally, correlations between percent change from baseline uOT and pOT levels were examined. Results: Study 1: Plasma OT and uOT levels significantly increased after administration of MDMA and INOT. Furthermore, uOT levels were positively correlated with pOT levels following administration of MDMA (r=0.57, p=0.042) but not INOT (r=0.51, p=0.097). Study 2: There was a significant increase in uOT levels after administration of INOT, but not after administration of placebo. Under both conditions, INOT and placebo, significant increases in pOT levels were not observed. Additionally, change from baseline uOT and pOT levels were positively correlated (r=0.57, p=0.021). There was no significant correlation between uOT and pOT levels following placebo administration. Conclusion: Our results show a measurable and significant increase in pOT and uOT levels after the administration of MDMA (Study 1) and INOT (Study 1 and Study 2). Additionally, a positive correlation between uOT and pOT levels was observed in both samples (healthy adults and ASD patients) in at least one condition. However, uOT and pOT levels were not correlated under all conditions, suggesting that uOT levels do not fully correspond to pOT levels in the time windows we measured. Future studies should further examine the relationship between levels of pOT and uOT in healthy and clinical populations on measures of social behavior because uOT may serve as an additional non-invasive method to measure peripheral OT changes.
Ample research suggests that social connection reliably generates positive emotions. Oxytocin, a neuropeptide implicated in social cognition and behavior, is one biological mechanism that may influence an individual's capacity to extract positive emotions from social contexts. Because variation in certain genes may indicate underlying neurobiological differences, we tested whether several SNPs in two genes related to oxytocin signaling would show effects on positive emotions that were context-specific, depending on sociality. For six weeks, a sample of mid-life adults (N=122) participated in either socially-focused loving-kindness training or mindfulness training. During this timespan they reported their positive emotions daily. Five SNPs within OXTR and CD38 were assayed, and each was tested for its individual effect on daily emotions. The hypothesized three-way interaction between time, training type, and genetic variability emerged: Individuals homozygous for the G allele of OXTR rs1042778 experienced gains in daily positive emotions from loving-kindness training, whereas individuals with the T allele did not experience gains in positive emotions with either training. These findings are among the first to show how genetic differences in oxytocin signaling may influence an individual's capacity to experience positive emotions as a result of a socially-focused intervention.
Pharmacotherapy and psychotherapy are crucial and often complementary tools in mental health care. However, efficacy studies have been heavily dominated by pharmacotherapy. Given that both approaches are comparably effective for treating a range of disorders,1 there is an urgent need to promote investment in psychotherapy research. Furthermore, combining these two approaches typically outperforms either treatment alone, but these studies are rarely conducted.1 Since combined approaches have the potential to be optimal, we make recommendations for promoting this largely neglected area of research, including study methodology, funding, and training.
4-phosphorloxy-N,N-dimethyltryptamine (psilocybin) and methylenedioxymethamfetamine (MDMA), best known for their illegal use as psychedelic drugs, are showing promise as therapeutics in a resurgence of clinical research during the past 10 years. Psilocybin is being tested for alcoholism, smoking cessation, and in patients with advanced cancer with anxiety. MDMA is showing encouraging results as a treatment for refractory post-traumatic stress disorder, social anxiety in autistic adults, and anxiety associated with a life-threatening illness. Both drugs are studied as adjuncts or catalysts to psychotherapy, rather than as stand-alone drug treatments. This model of drug-assisted psychotherapy is a possible alternative to existing pharmacological and psychological treatments in psychiatry. Further research is needed to fully assess the potential of these compounds in the management of these common disorders that are difficult to treat with existing methods.
3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") enhances desire to socialize and feelings of empathy, which are thought to be related to increased oxytocin levels. Thus, variation in the oxytocin receptor gene (OXTR) may influence responses to the drug. Here we examined the influence of a single OXTR nucleotide polymorphism (SNP) on responses to MDMA in humans. Based on findings that carriers of the A allele at rs53576 exhibit reduced sensitivity to oxytocin-induced social behavior, we hypothesized that these individuals would show reduced subjective responses to MDMA, including sociability. In this 3-session, double blind, within-subjects study, healthy volunteers with past MDMA experience (N = 68) received a MDMA (0, 0.75 mg/kg and 1.5 mg/kg) and provided self-report ratings of sociability, anxiety, and drug effects. These responses were examined in relation to rs53576. MDMA (1.5 mg/kg) did not increase sociability in individuals with the A/A genotype as it did in G allele carriers. The genotypic groups did not differ in responses at the lower MDMA dose, or in cardiovascular or other subjective responses. These findings are consistent with the idea that MDMA-induced sociability is mediated by oxytocin, and that variation in the oxytocin receptor gene may influence responses to the drug.
Users of ±3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') report prosocial effects such as sociability and empathy. Supporting these apparently unique social effects, data from controlled laboratory studies indicate that MDMA alters social feelings, information processing, and behavior in humans, and social behavior in rodents. Here, we review this growing body of evidence. In rodents, MDMA increases passive prosocial behavior (adjacent lying) and social reward while decreasing aggression, effects that may involve serotonin 1A receptor mediated oxytocin release interacting with vasopressin receptor 1A. In humans, MDMA increases plasma oxytocin and produces feelings of social affiliation. It decreases identification of negative facial expressions (cognitive empathy) and blunts responses to social rejection, while enhancing responses to others' positive emotions (emotional empathy) and increasing social approach. Thus, consistent with drug folklore, laboratory administration of MDMA robustly alters social processing in humans and increases social approach in humans and animals. Effects are consistent with increased sociability, with mixed evidence about enhanced empathy. These neurobiologically-complex prosocial effects likely motivate recreational ecstasy use.