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Psychedelics and music: neuroscience and therapeutic implications

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Abstract

From the beginning of therapeutic research with psychedelics, music listening has been consistently used as a method to guide or support therapeutic experiences during the acute effects of psychedelic drugs. Recent findings point to the potential of music to support meaning-making, emotionality, and mental imagery after the administration of psychedelics, and suggest that music plays an important role in facilitating positive clinical outcomes of psychedelic therapy. This review explores the history of, contemporary research on, and future directions regarding the use of music in psychedelic research and therapy, and argues for more detailed and rigorous investigation of the contribution of music to the treatment of psychiatric disorders within the novel framework of psychedelic therapy.
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Psychedelics and music: neuroscience and
therapeutic implications
Frederick S. Barrett, Katrin H. Preller & Mendel Kaelen
To cite this article: Frederick S. Barrett, Katrin H. Preller & Mendel Kaelen (2018): Psychedelics
and music: neuroscience and therapeutic implications, International Review of Psychiatry, DOI:
10.1080/09540261.2018.1484342
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REVIEW ARTICLE
Psychedelics and music: neuroscience and therapeutic implications
Frederick S. Barrett
a
, Katrin H. Preller
b,c
and Mendel Kaelen
d,e
a
Department of Psychiatry and Behavioral Sciences, Behavioral Pharmacology Research Unit, Johns Hopkins University School of
Medicine, Baltimore, MD, USA;
b
Neuropsychopharmacology and Brain Imaging, Department of Psychiatry Psychotherapy and
Psychosomatics, University Hospital for Psychiatry Zurich, Zurich, Switzerland;
c
Department of Psychiatry, Yale University School of
Medicine, New Haven, CT, USA;
d
Psychedelic Research Group, Department of Medicine, Imperial College London, London, UK;
e
Wavepaths Ltd, London, UK
ABSTRACT
From the beginning of therapeutic research with psychedelics, music listening has been consist-
ently used as a method to guide or support therapeutic experiences during the acute effects of
psychedelic drugs. Recent findings point to the potential of music to support meaning-making,
emotionality, and mental imagery after the administration of psychedelics, and suggest that
music plays an important role in facilitating positive clinical outcomes of psychedelic therapy.
This review explores the history of, contemporary research on, and future directions regarding
the use of music in psychedelic research and therapy, and argues for more detailed and rigor-
ous investigation of the contribution of music to the treatment of psychiatric disorders within
the novel framework of psychedelic therapy.
ARTICLE HISTORY
Received 11 February 2018
Accepted 30 May 2018
KEYWORDS
Psychedelic; hallucinogen;
LSD; psilocybin; music;
music therapy; music;
neuroscience
Introduction
Classic psychedelic drugs
1
are being investigated for
the treatment of psychiatric disorders, such as
addiction (Bogenschutz et al., 2015; Johnson, Garcia-
Romeu, Cosimano, & Griffiths, 2014), end-of-life
distress (Griffiths et al., 2016; Grob et al., 2011; Ross
et al., 2016), and depression (Carhart-Harris et al.,
2016a;Os
orio et al., 2015; Sanches et al., 2016).
Although mood and substance use disorders have a
long time-course and uncertain prognosis when
treated with currently available methods, psychedelic
therapies are showing great promise. Recent studies
demonstrate positive behavioural outcomes, including
clinically relevant reduction in self-report and clin-
ician-rated disorder severity (Bogenschutz et al., 2015;
Carhart-Harris et al., 2016a; Griffiths et al., 2016;
Os
orio et al., 2015; Ross et al., 2016; Sanches et al.,
2016), physiological outcomes, including breath car-
bon monoxide and urine cotinine (Johnson et al.,
2014), and, in one case, modulation of potential
neurobiological correlates of mood disorders
(Carhart-Harris et al., 2017; Roseman, Nutt, &
Carhart-Harris, 2018). Given that only one or a small
number (i.e. 2) of psychedelic therapy sessions can
bring acute and sustained symptom improvements,
psychedelic therapies represent a strong departure
from the common medical model of chronic, daily
pharmacotherapy and/or counselling as treatment.
A central principle in psychedelic therapy is that
the quality of subjective experiences during acute
drug effects predict (Roseman et al., 2018) and medi-
ate (Griffiths et al., 2016; Ross et al., 2016) clinical
outcomes. Music listening during acute drug effects
has been a consistent feature of both research and
therapeutic administration of psychedelics, as a
method to guide or support experiences (Eisner &
Cohen, 1958). Although music delivery during psy-
chedelic therapy is not standardized, and methods
used to select music for psychedelic therapy are
largely untested, there may be some consistency in
the features of music that are used to support
therapeutic experiences (Barrett, Robbins, Smooke,
Brown, & Griffiths, 2017b). Recent findings point to
the potential of psychedelics to support meaning-
making (Preller et al., 2017), emotion (Carbonaro,
Johnson, Hurwitz, & Griffiths, 2018; Kaelen et al.,
2015; Kaelen et al., 2017), and mental imagery (Kaelen
et al., 2016) during music listening, and suggest that
music plays an important role in facilitating positive
clinical outcomes of psychedelic therapy (Kaelen et al.,
CONTACT Frederick S. Barrett, PhD fbarret2@jhmi.edu Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of
Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224, USA
All authors contributed equally to this work.
ß2018 Institute of Psychiatry and Johns Hopkins University
INTERNATIONAL REVIEW OF PSYCHIATRY
https://doi.org/10.1080/09540261.2018.1484342
2018). In this review, we will explore the history of,
contemporary research on, and future directions
regarding the use of music in psychedelic research
and therapy, and argue for more detailed and rigor-
ous investigation of the contribution of music to the
treatment of psychiatric disorders within the novel
framework of psychedelic therapy.
The history of music and
psychedelic therapies
Music is ubiquitous in society and throughout known
history. The earliest known musical instrument, a
sophisticated bone flute, dates back at least 35 000
years (Conard, Malina, & M
unzel, 2009), but recorded
music history begins much more recently (Burkholder,
Grout, & Palisca, 2010). The earliest records in
music history document the use of music in religious
worship, such as plainchant (including Gregorian
Chant), and later in maintaining local and cultural
histories, as in the medieval troubadours and
trouveres (Burkholder et al., 2010). Theories of the
origins of music suggest that music evolved to sup-
port emotional communication (Juslin & Vastfjall,
2008; Snowdon, Zimmermann, & Altenm
uller, 2015),
and may even have developed before more formal
spoken language (Brandt, Slevc, & Gebrian, 2012;
Panksepp, 2009). Theories that associate the co-evo-
lution of language and music gain traction when we
consider that the preponderance of brain regions
that track syntactic components (Koelsch, 2011) and
time-varying structures (Janata et al., 2002)inmusic
are also brain regions critical for language processing
(Levitin & Menon, 2003;Patel,2008;Sch
on
et al., 2010).
Alternative evolutionary theories focus on social
functions of music or view music as a product of sex-
ual selection (Hauser & McDermott, 2003). Although
a consensus on biological origins of music is yet to be
found, an increasing number of empirical studies
illustrate a diverse significance of music in human
development and culture. Research with infants indi-
cates biological predispositions for melody-perception
(Trehub, 2001), which likely serves an important
social function (Mehr, Song, & Spelke, 2016), and
cross-cultural studies show a universal singing of
lullabies by mothers (Trehub & Trainor, 1998). Cross-
cultural studies have also provided evidence that
emotional content can be universally perceived as being
associated with acoustic properties of music (Fritz
et al., 2009; Laukka, Eerola, Thingujam, Yamasaki, &
Beller, 2013). Emotional responses to music occur
reliably in young children (Dalla Bella, Peretz,
Rousseau, & Gosselin, 2001;Mote,2011) and occur
continuously in daily life (Juslin, Liljestrom, Vastfjall,
Barradas, & Silva, 2008). Across the globe, music is
an important element of diverse aspects of life, rang-
ing from work, entertainment, and social settings to
medicine and spirituality (Hargreaves & North, 1999;
Merriam, 1964;Nettl,1956).
For the present discussion, the medicinal and spir-
itual usage of music is particularly relevant. Although
the use of music may be diverse, traditionally cultures
often place a special emphasis on musics capacity to
facilitate altered states of consciousness, and historic-
ally music-making has been a respected role reserved
for priests or medicine-men (Nettl, 1956).
Contemporary research on music listening has begun
to address musics capacity to engender or support
altered states, including emotionally intense peak
experiences (Gabrielsson, 2011), absorption (Sandstrom &
Russo, 2013), groove and flow states (Cs
ıkszentmih
alyi,
1990; Janata, Tomic, & Haberman, 2012), trance (Hove
et al., 2016;Rouget,1985), and states of religious
ecstasy (Penman & Becker, 2009).
Similar to the use of music, archeology suggests
ancient roots for the use of psychedelics. Cave art
depicting mushrooms in Algeria (Lajoux, 1964;
Samorini, 1992) and Spain (Akers, Ruiz, Piper, &
Ruck, 2011) are dated to be 70009000 years old;
40005600 year old specimens of psychedelic plants
and seeds are found across North, Central, and South
America (Bruhn, De Smet, El-Seedi, & Beck, 2002; El-
Seedi, De Smet, Beck, Possnert, & Bruhn, 2005;
Torres, 1998), and 20003000 year old mushroom-
shaped stones were uncovered in Guatemala (de
Borhegyi, 1963; Guerra-Doce, 2015). Many traditional
societies preserved their use of psychedelics until
today in a medicinal and spiritual context (Schultes,
Hofmann, & R
atsch, 2001), and modern research has
demonstrated psychedelics can reliably facilitate spirit-
ual-type experiences (Bogenschutz & Johnson, 2016;
Carhart-Harris et al., 2017; Garcia-Romeu, Griffiths, &
Johnson, 2015; Griffiths, Richards, McCann, & Jesse,
2006; Griffiths et al., 2011,2016; Roseman et al., 2018;
Ross et al., 2016).
Traditional medicinal and spiritual practice with
psychedelics was most likely combined with music
(Nettl, 1956). Icaros, or ritual songs, are a universal
component of traditional ayahuasca ceremonies, and
are considered to be necessary to facilitate both phys-
ical and spiritual healing (Dobkin de Rios, 1984).
Music is also a central component within mushroom
ceremonies of the Mazatec Indians (Estrada, 1981),
2 F. S. BARRETT ET AL.
the peyote ceremonies of Native Americans
(Maroukis, 2005), and the ibogaine rituals of Bwiti in
west-central Africa (Fernandez, 1982; Schultes et al.,
2001). In Europes antiquity, music was also specu-
lated to play a critical role in the Rites of Eleusis,
which involved imbibing a psychedelic mixture
(Wasson, Hofmann, & Ruck, 1978).
The synthesis of LSD (Hofmann, 1983) spurred a
large wave of psychiatric and neuroscience research
with psychedelics in the 1950s and 1960s. The thera-
peutic potential of psychedelics was heavily explored
(Busch & Johnson, 1950), and music was early on iden-
tified as a factor that can potentiate and influence drug
experiences significantly (Eagle, 1972; Eisner & Cohen,
1958; Gaston & Eagle, 1970). Soon, music was recog-
nized as an important element of the setting to support
the therapeutic process (Chandler & Hartman, 1960;
Eisner, 1997; Eisner & Cohen, 1958; Hoffer, 1965;
Holzinger, 1964). Emphasis was given to view music as
a therapeutic aid (Hoffer, 1965), and that, due to musics
profoundinfluence (Bonny & Pahnke, 1972), great
care and responsibility must be practiced in selecting
the music for patients individual therapeutic needs
(Bonny & Pahnke, 1972; Hoffer, 1965).
Studies reported profound alterations in a patients
perception of and response to music, and suggested
this underlies the usefulness of music as an adjunct to
psychedelic therapy. For example, Hoffer
(1965) noted:
Very often, sounds which normally have no
particular aesthetic appeal, were heard in a most
unusual manner. Subjects who were indifferent to
music, were enthralled by it. [ ] This property of
the experience is very useful in bringing out the
psychedelic reaction. Carefully selected music can be
very powerful in altering the subjects mood and
associations. (p. 204)
Studies investigating the effect of psychedelics on
auditory processing reported altered sensitivity and
tolerance to sound after the intake of LSD (Silverman,
1971), and have shown that, after the administration
of psilocybin, participants listening to music described
an intensive, exhilarating sound experience (Weber,
1967). One participant reported that she was for the
first time able to fully surrender to the music, while
at the same time she could not capture the structure
of the piece (Weber, 1967).
Subsequent early research on the therapeutic effects
of psychedelics included music listening as a consist-
ent feature during acute drug effects (Grof, 1980;
Grof, Goodman, Richards, & Kurland, 1973; Kurland,
1985; Kurland, Unger, Shaffer, & Savage, 1967;
Pahnke, Kurland, Goodman, & Richards, 1969;
Richards, 1979; Richards, Rhead, DiLeo, Yensen, &
Kurland, 1977). Guidelines for the use of music in
clinical settings were developed (Bonny & Pahnke,
1972), and clinical opinion suggested the use of spe-
cific musical pieces (Eisner, 1997), or styles of music
(Bonny & Pahnke, 1972) to support specific phases of
psychedelic experience (e.g. onset of effects,peak
intensity of drug action, and return to normal con-
sciousness) (Bonny & Pahnke, 1972). Consequently,
modern guidelines for safe use of psychedelics in
research recommend the use of music listening as a
critical element of the therapeutic setting (Johnson,
Richards, & Griffiths, 2008). The use of music to sup-
port specific experiences during psychedelic therapy
has been typically framed and characterized in terms
of supporting specific emotional experiences, such as
peak or mystical experiences
2
or emotional catharsis
(Bonny & Pahnke, 1972).
Contemporary research on the
neuropsychobiology of music and
psychedelics
Music listening has been shown to engage a wide
range of domain-general brain areas, including those
associated with reward, emotion, and memory proc-
essing (Barrett & Janata, 2016; Blood & Zatorre, 2001;
Salimpoor, Benovoy, Larcher, Dagher, & Zatorre,
2011; Salimpoor et al., 2013). Brain regions recruited
during music listening overlap at least partially with
brain regions where activity and connectivity are
altered after the administration of psychedelics
(Carhart-Harris et al., 2012a; Carhart-Harris et al.,
2016b; Preller et al., 2017). Psychedelic drugs have
notable effects on auditory perception (Hoffer, 1965;
Silverman, 1971; Timmermann et al., 2017; Umbricht
et al., 2003; Weber, 1967). This follows from the
neurobiology of both psychedelic drugs (serotonin
2A, or 5-HT
2A
, receptor agonists) and the neurobiol-
ogy of auditory processing. Brainstem serotonergic
neurons have been implicated in selective neuronal
responses to auditory stimuli (Hall, Rebec, & Hurley,
2010; Hurley & Pollak, 1999), and 5-HT
2A
signaling
has specifically been shown to alter neuronal
responses to auditory stimuli from the cochlear
nucleus (Tang & Trussell, 2015), through the pre-cor-
tical primary auditory sensory pathway (Hurley, 2006;
Hurley & Sullivan, 2012), through to the primary
auditory cortex (Riga, Bortolozzi, Campa, Artigas, &
Celada, 2016) and auditory cortical neurons (Luo, Hu,
Liu, Guo, & Wang, 2016).
INTERNATIONAL REVIEW OF PSYCHIATRY 3
Investigating the neurobiological mechanisms
underlying psychedelic-induced alterations in auditory
processing, modern neuroimaging studies reported a
reduced N1 sensory EEG-ERP, suggesting reduced
processing of intensity of auditory stimuli under
psilocybin (Umbricht et al., 2003), and altered audi-
tory sensitivity measured with MEG under LSD
(Timmermann et al., 2017). Empirical studies further
investigated music processing after the administration
of LSD, while participants underwent functional mag-
netic resonance imaging (Barrett, Preller, Herdener,
Janata, & Vollenweider, 2017a; Kaelen et al., 2016,
2017; Preller et al., 2017). These studies revealed that
LSD alters the perception of the acoustic properties of
music. In particular, LSD increased the BOLD signal
in response to timbral complexityindicative of the
complexity of the musics spectral distributionin
brain networks associated with music perception and
emotion, i.e. the auditory cortices, inferior frontal
gyrus (IFG), insula, precuneus, striatum, and the sup-
plementary motor area (SMA; Kaelen et al., 2017).
Additionally, processing of high timbral complexity was
associated with increased coupling of the precuneus
with the right superior frontal gyrus and decreased cou-
pling of the precuneus with the right IFG and auditory
cortex after LSD administration (Kaelen et al., 2017).
LSD was further shown to influence the neural response
to the time-varying tonal structure of musican effect
that was predominantly attributable to LSDs agonist
activity on the 5-HT
2A
receptor (Barrett et al., 2017a).
LSD enhanced tonality tracking in areas that respond to
music and speech, as well as higher cognitive areas such
as the superior temporal cortex, the IFG, medial pre-
frontal brain regions, the angular gyrus, and the amyg-
dala (Barrett et al., 2017a).
Preller et al. (2017) showed enhanced meaningful-
ness perceived in music under LSD, associated with
greater BOLD activations in regions previously linked
to music-listening, emotion, and autobiographical
memory, including the SMA, putamen, insula, and the
PCC. Kaelen et al. (2016) demonstrated that an inter-
action between LSD and music lead to increased infor-
mation flow (effective connectivity) from the
parahippocampus towards the visual cortex, and this
effect correlated with enhanced mental visual imagery
and seeing autobiographical scenes (Kaelen et al., 2016).
Together, these results indicate that psychedelics signifi-
cantly modulate the brains processing of music, and
these effects may explain the altered subjective experi-
ence of music under psychedelics (Barrett et al., 2017a;
Kaelen et al., 2016,2017; Preller et al., 2017).
How do music and psychedelics interact to
promote healing?
Music supports emotional experiences
A prime motivation for many people to listen to
music is to modulate emotion (Berlyne, 1971; Sch
afer,
Sedlmeier, St
adtler, & Huron, 2013), and the emo-
tion-arousing properties of music arguably comprise
one important motivation for the application of music
therapy in the treatment of various psychiatric
(Castillo-P
erez, G
omez-P
erez, Velasco, P
erez-Campos, &
Mayoral, 2010; Erkkil
aetal.,2011; Zhao, Bai, Bo, &
Chi, 2016) and neurological diseases (Fakhoury,
Wilhelm, Sobota, & Kroustos, 2017; Hohmann, Bradt,
Stegemann, & Koelsch, 2017; Leubner & Hinterberger,
2017). Emotionally intense chill-inducingeffects of
music are common (Panksepp, 1995) and empirically
studied (Grewe, Nagel, Kopiez, & Altenm
uller, 2005;
Harrison & Loui, 2014;Mori&Iwanaga,2014;
Salimpoor, Benovoy, Longo, Cooperstock, & Zatorre,
2009). However, the mechanisms through which music
can modulate emotional experience are many
and varied.
Different classes of determinants, from acoustic
and musical features of individual stimuli (Coutinho &
Cangelosi, 2009;Hevner,1937; Leman, Vermeulen,
De Voogdt, Moelants, & Lesaffre, 2005; Maher, 1980),
to personal associations people have made with music
(Barrett et al., 2010; Janata, Tomic, & Rakowski,
2007), to more abstract concepts such as preference
traits and personality (Dollinger, 1993; Rawlings &
Ciancarelli, 1997; Rentfrow & Gosling, 2003;
Rentfrow, Goldberg, & Levitin, 2011; Zweigenhaft,
2008), have been shown to influence the emotions
that are experienced during music listening (see also
Juslin & Vastfjall, 2008). Liking, in particular (e.g. a
persons affinity for a particular piece of music), is
shown to influence the emotions experienced with
music significantly (Juslin, 2013; Juslin & Vastfjall,
2008; North & Hargreaves, 1997), and it may be the
case that liking moderates the effect of musical fea-
tures and familiarity on music-evoked emotions
(North & Hargreaves, 1995). Consistent with previous
theoretical perspectives (Berlyne, 1971), liking may act
as an index for the emotional utility of a musical
stimulus, thus functioning as a gatekeeperor filter
for the subsequent effects of the music on the
listeners emotional state.
The effects of psychedelics, however, are concep-
tualized as a relinquishment of the normal filters the
selfutilizes to regulate its internal milieu (Barrett &
Griffiths, 2018; Carhart-Harris et al., 2014). Thereby,
4 F. S. BARRETT ET AL.
psychedelics may diminish the usual regulatory proc-
esses of music-evoked emotion and allow a fuller
processing of music and the features of the music
that evoke emotion. Support for this hypothesis can
be found in both psychopharmacological and neuroi-
maging investigations. In a comparative psycho-
pharmacology study, volunteers reported far greater
absorption in music, as well as greater perceived
beauty and significance of music, during the acute
effects of psilocybin than during placebo or the
acute effects of dextromethorphan (an NMDA antag-
onist and dissociative hallucinogen) (Carbonaro
et al., 2018). Kaelen et al. (2017) demonstrated an
association between intensified music-evoked emo-
tion and enhanced BOLD activation to musics tim-
bral complexitytimbre (tone colour) being
associated with conveying emotional information in
music (Eerola, Ferrer, & Alluri, 2012; Hailstone
et al., 2009).
Psychedelics indeed have been shown to not only
alter the processing of acoustic properties of music,
but also the psychological and emotional reaction to
it (Kaelen et al., 2015,2017; Preller et al., 2017).
Intensification of emotion and mental imagery by
music was a primary motivation for the use of music
in psychedelic therapy in the 1950s and 1960s (Bonny
& Pahnke, 1972), and has been most frequently
reported by patients undergoing psychedelic therapy
(Kaelen et al., 2018). To illustrate, one patient from
Kaelen et al. (2018) reported:
Under the influence of psilocybin the music
absolutely takes over. Normally when I hear a piece
of sad music, or happy music, I respond through
choice, but under psilocybin I felt almost that I had
no choice but to go with the music. (p. 10)
(For more insight in patients experiences of music,
see Supplementary materials in Kaelen et al., 2018).
One way the intensifying effects of psychedelics
on music-evoked emotion may support the therapy
is by contributing to the occurrence of mystical
experiences during psychedelic therapy sessions
(Barrett & Griffiths, 2018; Kaelen et al., 2018), which
have been associated with positive therapeutic out-
comes (Barrett & Griffiths, 2018; Johnson &
Griffiths, 2017). LSD has been shown to enhance
emotional features of mystical-experiences (Kaelen
et al., 2015,2017), and psilocybin has been shown
to enhance absorption in and the beauty and signifi-
cance of music (Carbonaro et al., 2018), and the
music-experience of patients in psychedelic therapy
has been associated with the occurrence of mystical-
experiences (Kaelen et al., 2018). Furthermore,
Lebedev et al. (2016) showed that LSD-induced
increases in entropic brain dynamics were related
with subsequent increases in personality trait open-
ness, only during the music-listening condition, indi-
cating that music may drive brain dynamics
important for the occurrence of experiences that
have long-lasting beneficial effects (Lebedev
et al., 2016).
Finally, music in therapy is effective in reducing
stress and anxiety (Chanda & Levitin, 2013), and,
consistent with earlier reports (Bonny & Pahnke,
1972), music is reported to provide a sensation of
calm, safety, and support for patients in psychedelic
therapy (Kaelen et al., 2018). Hence, in addition to
evoking strong emotionality, music may play an
important role in reducing emotional arousal too,
helping the patient to find meaningful resolutions to
transient psychological struggles that are not uncom-
mon in psychedelic therapy (Barrett, Bradstreet,
Leoutsakos, Johnson, & Griffiths, 2016; Belser et al.,
2017;Swiftetal.,2017;Watts,Day,Krzanowski,Nutt,&
Carhart-Harris, 2017).
Music supports autobiographical meaning-making
Another potential effect through which psychedelics
and music interact on the therapeutic process was
described by Preller et al. (2017). This study showed
that LSD increases the attribution of personal mean-
ing to music, in particular to music pieces which
were not particularly meaningful to participants in
the placebo condition. This effect was associated with
an increased BOLD signal in the cortical midline
structures, brain areas which are associated with self-
referential processing (Northoff & Bermpohl, 2004;
Preller et al., 2017), and was dependent on 5-HT
2A
receptor stimulation (Preller et al., 2017). These brain
regions have been shown to be clinically relevant in
psychiatric disorders and might also be involved in
the therapeutic response to LSD (Moeller &
Goldstein, 2014; Northoff & Bermpohl, 2004). The
ability of LSD to increase perceived meaningfulness
can contribute to mystical experiences which have
been shown to be related to beneficial therapeutic
outcome. Furthermore, by altering brain activity in
regions important for self-referential processing, as
well as at the same time increasing the meaningful-
ness of the environment, patients may become more
accepting and open to changes (Halberstadt, 2017).
Therefore, the potential of psychedelics to enhance
perceived meaningfulness could contribute to benefi-
cial therapeutic outcomes, particularly in disorders
INTERNATIONAL REVIEW OF PSYCHIATRY 5
with altered self-referential processing such as depres-
sion (Halberstadt, 2017).
A further study by Kaelen et al. (2016) showed
that LSD and music interact to increase effective con-
nectivity from the parahippocampal cortex to the vis-
ual cortex, and the magnitude of this effect correlated
with increased visual mental imagery and ratings for
seeing autobiographical scenes from the past (Kaelen
et al., 2016). LSD-induced enhancement of autobio-
graphical memories, and associated with this the
potential reversal of negative cognitive biases, might
be associated with beneficial therapy outcome
(Carhart-Harris et al., 2012b; Kraehenmann et al.,
2015; Vollenweider & Kometer, 2010). Together, these
studies offer a mechanistic explanation on how LSD
together with music stimulates autobiographically
meaningful processes, and suggests that music could
be a tool to facilitate this process during psyche-
delic therapy.
Implications for psychedelic therapy
The capacity of psychedelic therapy to facilitate acute
and sustained therapeutic changes represents a prom-
ising direction in mental healthcare, and a significant
deviation from conventional treatments, both in terms
of administration of the drug and in the underlying
theoretical frameworks. Hence, an empirical under-
standing of the different components of this new
paradigm of therapy is critical to offer evidence-based
guidelines for researchers and therapists. The present
paper focuses on music, as this is one dominant com-
ponent in the therapeutic model, and this section will
discuss how the previously reviewed research on psy-
chedelics and music begins to inform an evidence-
based use of music in psychedelic therapies.
Studies reviewed previously indicate an enhanced
emotional and psychological responsivity to music
under psychedelics. While evidence exists for poten-
tial therapeutic effects of psychedelic drugs absent of
music listening (Sanches et al., 2016), patients often
emphasize the significant influence of music on their
experience in psychedelic therapy (Belser et al., 2017;
Swift et al., 2017; Watts et al., 2017). It has been dem-
onstrated that the music-experience during psyche-
delic therapy correlates with the occurrence of
mystical experiences and insightfulness during psy-
chedelic therapy, and with reductions in clinical
symptoms 1 week after the session, and that calming
effects of music are welcome and potentially beneficial
during onset, ascent, and return phases of the psyche-
delic experience (Kaelen et al., 2018). Together, these
findings provide a body of evidence that music can be
a potent medium to modulate emotion and meaning-
making, to facilitate experiences that have strong
therapeutic significance.
As the quality of the music experience has been
associated with therapy outcomes, and, more specific-
ally, a music-experience characterized by personal
resonance(Kaelen et al., 2018), the music-selection
requires a thoughtful optimization to the individual
patient. Although tailoring the music to the dynamic
needs of the individual patient is standard practice in
MDMA-assisted psychotherapy (Mithoefer, Wagner,
Mithoefer, Jerome, & Doblin, 2011), most studies
with classic psychedelics have prioritized a standar-
dized approach, where all patients listen to the same
music playlist. Although from a research perspective
this may be desirable, this can jeopardize the thera-
peutic experience of some patients significantly
(Kaelen et al., 2018). Standardization of the process
that generates patient-specific music, rather than sim-
ply standardizing the mere presence of the music,
may harmonize research-standards with the human-
centred practice inherent in the therapy model, and is
likely to optimize patient-experiences and ther-
apy outcomes.
Limitations
While we have attempted to present a thorough
review of studies that inform our understanding of
the interaction between music and psychedelic experi-
ences, there are several limitations to our review.
First, many of the earlier reports of the relationship
between psychedelics and music listening lacked the
rigour of modern experimental controls (e.g. reviewed
in Eisner & Cohen, 1958 and Richards, 1979) or were
largely based on observation and clinical opinion (e.g.
Bonny & Pahnke, 1972). In addition, many recent
reports, especially those involving clinical outcomes,
were open-label studies (e.g. Bogenschutz et al., 2015;
Carhart-Harris et al., 2016a; Johnson et al., 2014;
Os
orio et al., 2015; Sanches et al., 2016). While a
number of recent reports did involve placebo or
active control as well as single-blind (e.g. Kaelen
et al., 2015,2017) or double-blind randomized condi-
tions (e.g. Barrett et al., 2017a; Carbonaro et al., 2018;
Griffiths et al., 2016; Preller et al., 2017; Ross et al.,
2016), some of the reports cited in this review
involved multiple analyses of data from the same
sample (e.g. Barrett et al., 2017a; Carhart-Harris et al.,
2016a,2017; Preller et al., 2017; Roseman et al.,
2018). While we have reviewed the nascent literature
6 F. S. BARRETT ET AL.
on the interaction between music and psychedelic
experiences, which is growing, the field has yet to
develop a literature sufficient to support a meaningful
systematic review, but we hope that this review will
stimulate further structured research in this field.
Future directions
The current state of research regarding psychedelics
and music presents several limitations and necessities
for future research. The studies reviewed were the first
to assess the combined effects of music and psyche-
delics on subjective experience and brain function, and
these findings, therefore, implicate the need of their
replication and expansion in independent future stud-
ies. Future studies that enable a better separation
between music- and drug-conditions are also necessary
to deepen our understanding of their interactive effects
on subjective experience and therapy outcomes. In
therapeutic contexts, studies involving one group of
patients undergoing psychedelic therapy with music,
and one group without any music, will be needed to
reveal both the magnitude and the nature of the thera-
peutic effects of music. With respect to the latter, stud-
ies on the nature of the therapeutic effects of music
can provide important insights into key therapeutic
processes at play, and the different ways these can be
best supported, with and without music.
Furthermore, studies are needed that compare the
relative contribution of music to the therapeutic
experience and outcome to other factors present
during therapy sessions, such as interpersonal factors
and physical environment. Future studies can help
us to better understand the interactions between the
psychological context of the patient (mood, attitudes,
expectations, personality-traits) and the patients sub-
jective experience of music, both with and without
psychedelics. Future studies must also address how
music can be tailored to the time-phase within the
drug-experience, and assess whether any music gen-
res, composition features, or acoustic features in par-
ticular are suitable for the facilitation of therapeutic
experiences. Related to this, the role of an individu-
alsmusic-listening history and its relationship to the
music-experience under a psychedelic remains to
be clarified, and, together with the above, will
aid the construction of empirical guidelines for
music-selection and playlist design during psyche-
delic therapy sessions. The choice of music in the
reviewed neuroimaging studies may have signifi-
cantly influenced their findings, and future studies
that use different genres or a multitude of musical
genres may be positioned to test hypotheses regard-
ing the effects of and appropriateness of different
styles of music in the context of psychedelic therapy.
Although individual variation in patientsmusic-
experience has been related to therapy outcomes,
there is little experimental insight into how music
can be adapted to optimize therapy outcomes.
Studying this is crucial to help define music-selection
protocols that are empirical and scalable, which
must include an accurate mapping of music with its
experience, given the psychological context of
the patient.
Finally, the subjectiveexperiences of music-listening
under a psychedelic can be remarkably profound,
indicating that their combined study may significantly
advance our understanding of human brain mecha-
nisms of music-perception and subjective experiences
of music, as well as the neural correlates of subjective
experiences that are normally difficult to access under
experimental conditions (for example, emotionally
intense peak experiences).
Conclusion
Psychedelics and music listening interact to produce
profound alterations in emotion, mental imagery, and
personal meaning. Research is beginning to unveil
underlying brain mechanisms, and to support a cen-
tral role of music in psychedelic therapy. Music
appears to influence the efficacy of therapy signifi-
cantly, through modulating emotion, including the
facilitating of mystical experiences, and through sup-
porting autobiographical processes. Acknowledging
the significance of music and the importance of rigor-
ous future empirical investigations in this young field
of research is key to improving our understanding of
psychedelic therapies, and key to improving the effi-
cacy of psychedelic therapies.
Disclosure statement
MK is a founder and shareholder in Wavepath Ltd. FSB
and KHP report no conflicts of interest. The authors alone
are responsible for the content and writing of the paper.
FSB was supported in part by NIH grants R03DA042336
and a grant from the Heffter Research Institute. KHP was
supported by the SNSF grant P2ZHP1_161626.
Notes
1. Classicpsychedelics produce a range of idiosyncratic
and often profound subjective effects via agonist
actions on the serotonin 2A receptor. Examples of
classic psychedelics include lysergic acid diethylamide
INTERNATIONAL REVIEW OF PSYCHIATRY 7
or LSD, psilocybin, found in hundreds of species of
psychoactive mushrooms, dimethyltryptamine or
DMT, found in the Psychotria viridis and Diplopterys
cabrerana plants used to brew ayahuasca, and
mescaline, found in some psychoactive cacti. The term
psychedelic is derived from merging the Greek word
psyche, meaning mind or soul, with delos, meaning to
unveil or make visible effects.
2. Peak experiences with psychedelic drugs were first
defined by Pahnke et al. (Pahnke, 1963; Pahnke et al.,
1969) as sharing common features with non-drug
mystical experiences. Peak/mystical experiences are
characterized by an experience of unity (with ones
self, ones surroundings, some or all people, or all that
exists), loss of ones usual sense of space and time,
deeply felt positive mood, the felt sense that the
experience involves some fundamental truth (noetic
quality), difficulty putting the experience into words
(ineffability), a felt sense of sacredness, transiency, and
paradoxicality (simultaneously containing contradictory
feelings, thoughts, experiences, or characteristics).
ORCID
Frederick S. Barrett http://orcid.org/0000-0001-
7443-3237
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INTERNATIONAL REVIEW OF PSYCHIATRY 13
... Substances administered in (psycho-)therapeutic contexts include serotonergic psychedelics (e.g., LSD and psilocybin) sharing a primary mechanism of action at the 5-HT2A receptor (Geyer and Vollenweider, 2008;Nichols, 2016;Preller et al., 2018), NMDA antagonists with dissociative properties like ketamine (Krupitsky and Grinenko, 1997;Serafini et al., 2014), serotonergic entactogens like MDMA (Thal and Lommen, 2018), and atypical and pharmacologically complex psychedelics like ibogaine (Alper, 2001). ...
... Musicmost often delivered through headphoneshas been a consistent feature (Barrett, Preller and Kaelen, 2018) and method for guidance and support (Bonny and Pahnke, 1972;Eisner and Cohen, 1958) across different models of SAPT with potential influences on the psychoactive experience itself and the therapeutic outcome (Kaelen et al., 2015;Kaelen et al., 2016Kaelen et al., , 2018Preller et al., 2017;Swift et al., 2017;Watts et al., 2017). It was suggested by Kaelen et al. (2018) that optimal music may personalize the experience and foster the expression of meaningful therapeutic content. ...
... Musicmost often delivered through headphoneshas been a consistent feature (Barrett, Preller and Kaelen, 2018) and method for guidance and support (Bonny and Pahnke, 1972;Eisner and Cohen, 1958) across different models of SAPT with potential influences on the psychoactive experience itself and the therapeutic outcome (Kaelen et al., 2015;Kaelen et al., 2016Kaelen et al., , 2018Preller et al., 2017;Swift et al., 2017;Watts et al., 2017). It was suggested by Kaelen et al. (2018) that optimal music may personalize the experience and foster the expression of meaningful therapeutic content. ...
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Drawing on perspectives from music psychology, cognitive neuroscience, philosophy, musicology, clinical psychology, and music education, Music and Mental Imagery provides a critical overview of cutting-edge research on the various types of mental imagery associated with music. The four main parts cover an introduction to the different types of mental imagery associated with music such as auditory/musical, visual, kinaesthetic, and multimodal mental imagery; a critical assessment of established and novel ways to measure mental imagery in various musical contexts; coverage of different states of consciousness, all of which are relevant for, and often associated with, mental imagery in music, and a critical overview of applications of mental imagery in health, educational, and performance settings. By both critically reviewing up-to-date scientific research and offering new empirical results, this book provides a unique overview of the different types and origins of mental imagery in musical contexts, various ways to measure them, and intriguing insights into related mental phenomena such as mind-wandering and synaesthesia. This will be of particular interest for scholars and researchers of music psychology and music education. It will also be useful for practitioners working with music in applied health and educational contexts.
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Music is a highly dynamic stimulus, and consists of distinct acoustic features, such as pitch, rhythm and timbre. Neuroimaging studies highlight a hierarchy of brain networks involved in music perception. Psychedelic drugs such as lysergic acid diethylamide (LSD) temporary disintegrate the normal hierarchy of brain functioning, and produce profound subjective effects, including enhanced music-evoked emotion. The primary objective of this study was to investigate the acute effects of LSD on music-evoked brain-activity under naturalistic music listening conditions. 16 healthy participants were enrolled in magnetic resonance imaging (fMRI) while listening to a 7-minute music piece under eyes-closed conditions on two separate visits (LSD (75 mcg) and placebo). Dynamic time courses for acoustic features were extracted from the music excerpts, and were entered into subject-level fMRI analyses as regressors of interest. Differences between conditions were assessed at group level subsequently, and were related to changes in music-evoked emotions via correlation analyses. Psycho-physiological interactions (PPIs) were carried out to further interrogate underlying music-specific changes in functional connectivity under LSD. Results showed pronounced cortical and subcortical changes in music-evoked brain activity under LSD. Most notable changes in brain activity and connectivity were associated with the component timbral complexity, representing the complexity of the music’s spectral distribution, and these occurred in brain networks previously identified for music-perception and music-evoked emotion, and showed an association with enhanced music-evoked feelings of wonder under LSD. The findings shed light on how the brain processes music under LSD, and provide a neurobiological basis for the usefulness of music in psychedelic therapy.
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Rationale: Recent studies have supported the safety and efficacy of psychedelic therapy for mood disorders and addiction. Music is considered an important component in the treatment model, but little empirical research has been done to examine the magnitude and nature of its therapeutic role. Objectives: The present study assessed the influence of music on the acute experience and clinical outcomes of psychedelic therapy. Methods: Semi-structured interviews inquired about the different ways in which music influenced the experience of 19 patients undergoing psychedelic therapy with psilocybin for treatment-resistant depression. Interpretative phenomenological analysis was applied to the interview data to identify salient themes. In addition, ratings were given for each patient for the extent to which they expressed "liking," "resonance" (the music being experienced as "harmonious" with the emotional state of the listener), and "openness" (acceptance of the music-evoked experience). Results: Analyses of the interviews revealed that the music had both "welcome" and "unwelcome" influences on patients' subjective experiences. Welcome influences included the evocation of personally meaningful and therapeutically useful emotion and mental imagery, a sense of guidance, openness, and the promotion of calm and a sense of safety. Conversely, unwelcome influences included the evocation of unpleasant emotion and imagery, a sense of being misguided and resistance. Correlation analyses showed that patients' experience of the music was associated with the occurrence of "mystical experiences" and "insightfulness." Crucially, the nature of the music experience was significantly predictive of reductions in depression 1 week after psilocybin, whereas general drug intensity was not. Conclusions: This study indicates that music plays a central therapeutic function in psychedelic therapy.
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Introduction: It is a basic principle of the “psychedelic” treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would have negligible predictive value. Materials and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10 and 25 mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25 mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-Time and DED-by-Time interactions were the primary outcomes of interest. Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson's correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC (p < 0.05). Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety. Trial Registration: ISRCTN, number ISRCTN14426797, http://www.isrctn.com/ISRCTN14426797
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Music therapy (MT) and music-based interventions (MBIs) are increasingly used for the treatment of substance use disorders (SUD). Previous reviews on the efficacy of MT emphasized the dearth of research evidence for this topic, although various positive effects were identified. Therefore, we conducted a systematic search on published articles examining effects of music, MT and MBIs and found 34 quantitative and six qualitative studies. There was a clear increase in the number of randomized controlled trials (RCTs) during the past few years. We had planned for a meta-analysis, but due to the diversity of the quantitative studies, effect sizes were not computed. Beneficial effects of MT/ MBI on emotional and motivational outcomes, participation, locus of control, and perceived helpfulness were reported, but results were inconsistent across studies. Furthermore, many RCTs focused on effects of single sessions. No published longitudinal trials could be found. The analysis of the qualitative studies revealed four themes: emotional expression, group interaction, development of skills, and improvement of quality of life. Considering these issues for quantitative research, there is a need to examine social and health variables in future studies. In conclusion, due to the heterogeneity of the studies, the efficacy of MT/ MBI in SUD treatment still remains unclear.
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Rationale: Although psilocybin and dextromethorphan (DXM) are hallucinogens, they have different receptor mechanisms of action and have not been directly compared. Objective: This study compared subjective, behavioral, and physiological effects of psilocybin and dextromethorphan under conditions that minimized expectancy effects. Methods: Single, acute oral doses of psilocybin (10, 20, 30 mg/70 kg), DXM (400 mg/70 kg), and placebo were administered under double-blind conditions to 20 healthy participants with histories of hallucinogen use. Instructions to participants and staff minimized expectancy effects. Various subjective, behavioral, and physiological effects were assessed after drug administration. Results: High doses of both drugs produced similar increases in participant ratings of peak overall drug effect strength, with similar times to maximal effect and time-course. Psilocybin produced orderly dose-related increases on most participant-rated subjective measures previously shown sensitive to hallucinogens. DXM produced increases on most of these same measures. However, the high dose of psilocybin produced significantly greater and more diverse visual effects than DXM including greater movement and more frequent, brighter, distinctive, and complex (including textured and kaleidoscopic) images and visions. Compared to DXM, psilocybin also produced significantly greater mystical-type and psychologically insightful experiences and greater absorption in music. In contrast, DXM produced larger effects than psilocybin on measures of disembodiment, nausea/emesis, and light-headedness. Both drugs increased systolic blood pressure, heart rate, and pupil dilation and decreased psychomotor performance and balance. Conclusions: Psilocybin and DXM produced similar profiles of subjective experiences, with psilocybin producing relatively greater visual, mystical-type, insightful, and musical experiences, and DXM producing greater disembodiment.
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Under the predictive coding framework, perceptual learning and inference are dependent on the interaction between top-down predictions and bottom-up sensory signals both between and within regions in a network. However, how such feedback and feedforward connections are modulated in the state induced by lysergic acid diethylamide (LSD) is poorly understood. In this study, an auditory oddball paradigm was presented to healthy participants (16 males, 4 female) under LSD and placebo, and brain activity was recorded using magnetoencephalography (MEG). Scalp level Event Related Fields (ERF) revealed reduced neural adaptation to familiar stimuli, and a blunted neural 'surprise' response to novel stimuli in the LSD condition. Dynamic causal modelling revealed that both the presentation of novel stimuli and LSD modulate backward extrinsic connectivity within a task-activated fronto-temporal network, as well as intrinsic connectivity in the primary auditory cortex. These findings show consistencies with those of previous studies of schizophrenia and ketamine but also studies of reduced consciousness - suggesting that rather than being a marker of conscious level per se, backward connectivity may index modulations of perceptual learning common to a variety of altered states of consciousness, perhaps united by a shared altered sensitivity to environmental stimuli. Since recent evidence suggests that the psychedelic state may correspond to a heightened 'level' of consciousness with respect to the normal waking state, our data warrant a re-examination of the top-down hypotheses of conscious level and suggest that several altered states may feature this specific biophysical effector.
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Classic psychedelic drugs (serotonin 2A, or 5HT2A, receptor agonists) have notable effects on music listening. In the current report, blood oxygen level-dependent (BOLD) signal was collected during music listening in 25 healthy adults after administration of placebo, lysergic acid diethylamide (LSD), and LSD pretreated with the 5HT2A antagonist ketanserin, to investigate the role of 5HT2A receptor signaling in the neural response to the time-varying tonal structure of music. Tonality-tracking analysis of BOLD data revealed that 5HT2A receptor signaling alters the neural response to music in brain regions supporting basic and higher-level musical and auditory processing, and areas involved in memory, emotion, and self-referential processing. This suggests a critical role of 5HT2A receptor signaling in supporting the neural tracking of dynamic tonal structure in music, as well as in supporting the associated increases in emotionality, connectedness, and meaningfulness in response to music that are commonly observed after the administration of LSD and other psychedelics. Together, these findings inform the neuropsychopharmacology of music perception and cognition, meaningful music listening experiences, and altered perception of music during psychedelic experiences.