ArticlePDF AvailableLiterature Review

Psilocybin occasioned mystical-type experiences



Objective Research into psychedelic therapy models has shown promise for the treatment of specific psychiatric conditions. Mystical‐type experiences occasioned by psilocybin have been correlated with therapeutic benefits and long‐term improvements in positive mental outlook and attitudes. This article aims to provide an overview of the topic, highlight strengths and weaknesses in current research, generate novel perspectives and discussion, and consider future avenues for research. Design This narrative review was designed to summarise and assess the state of research on psilocybin occasioned mystical‐type experiences and applications for the treatment of specific psychiatric conditions. Results Contemporary methods on the quantification of mystical‐type experiences and their acute subjective effects are discussed. Recent studies provide some understanding of the pharmacological actions of psychedelics although the neurological similarities and differences between spontaneous and psychedelic mystical‐type experiences are not well described. Applicability to modern clinical settings is assessed. Potential novel therapeutic applications include use in positive psychology interventions in healthy individuals. Conclusions Since 2006 significant advancements in understanding the therapeutic potential of psilocybin‐assisted psychotherapy have been made; however, more work is required to understand the neuromechanistic processes and applicability in modern clinical settings. Despite promising results in recent studies, funding issues for clinical trials, legal concerns and socio‐cultural resistance provide a counterpoint to experimental evidence.
Psilocybin occasioned mystical-type experiences
Edward James
| Thomas L Robertshaw
| Mathew Hoskins
| Ben Sessa
School of Pharmacy and Pharmaceutical
Sciences, Cardiff University, Cardiff, UK
Division of Psychological Medicine and
Clinical Neurosciences, School of Medicine,
Cardiff University, Cardiff, UK
Cardiff and Vale University Health Board,
Cardiff, UK
Neuropsychopharmacology Unit, Department
of Medicine, Imperial College London,
London, UK
Edward James, School of Pharmacy and
Pharmaceutical Sciences, Cardiff University,
King Edward VII Avenue, Cardiff, Wales CF10
3NB, UK.
Email: edward.james.correspondence@hotmail.
Ben Sessa, Neuropsychopharmacology Unit,
Department of Medicine, Imperial College
London, London W12 0NN, UK.
Objective: Research into psychedelic therapy models has shown promise for the
treatment of specific psychiatric conditions. Mystical-type experiences occasioned
by psilocybin have been correlated with therapeutic benefits and long-term improve-
ments in positive mental outlook and attitudes. This article aims to provide an over-
view of the topic, highlight strengths and weaknesses in current research, generate
novel perspectives and discussion, and consider future avenues for research.
Design: This narrative review was designed to summarise and assess the state of
research on psilocybin occasioned mystical-type experiences and applications for the
treatment of specific psychiatric conditions.
Results: Contemporary methods on the quantification of mystical-type experiences and
their acute subjective effects are discussed. Recent studies provide some understanding of
the pharmacological actions of psychedelics although the neurological similarities and dif-
ferences between spontaneous and psychedelic mystical-type experiences are not well
described. Applicability to modern clinical settings is assessed. Potential novel therapeutic
applications include use in positive psychology interventions in healthy individuals.
Conclusions: Since 2006 significant advancements in understanding the therapeutic
potential of psilocybin-assisted psychotherapy have been made; however, more work is
required to understand the neuromechanistic processes and applicability in modern clinical
settings. Despite promising results in recent studies, funding issues for clinical trials, legal
concerns and socio-cultural resistance provide a counterpoint to experimental evidence.
Psilocybin, mystical-type experiences, psychotherapy, clinical applications, quantum change,
current research
After 100 years of modern psychiatry, there remains a lack of consis-
tency in the provision of effective services for people with mental
health disorders. While the popular media often present a negative,
stigmatising picture of mental disorders and a lack of effectiveness of
treatments (Stuart, 2006), large meta-analyses have demonstrated
that in reality psychiatric treatmentswhen delivered appropriately
by well-resourced servicesare comparable in efficacy to general
medical interventions (Seemüller, Möller, Dittmann, & Musil, 2012).
The negative perception persists, nevertheless, with particular empha-
sis placed on the potential adverse impact of the pharmaceutical
industry, which has prompted significant criticism (Greenberg, 2010).
Polypharmacy (the use of two or more medications to treat the
same illness) is often observed and is frequently associated with a lack
of efficacy and increased harms from combining multiple drug
Received: 15 November 2019 Revised: 2 May 2020 Accepted: 11 May 2020
DOI: 10.1002/hup.2742
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited and is not used for commercial purposes.
Hum Psychopharmacol Clin Exp. 2020;e2742. © 2020 John Wiley & Sons Ltd 1of8
treatments (Kukreja, Kalra, Shah, & Shrivastava, 2013). Polypharmacy is
especially the case when lack of attention is paid to the provision of
non-drug, psychosocial interventionsespecially outpatient psychother-
apy (Mojtabai & Olfson, 2008). In this context, what has emerged in the
last 50 years of biological psychiatry is an urgent need to rationalise
pharmacological treatments and bolster the efficacy and efficiency of
psychotherapies. It is into this environment that psychedelic-assisted
psychotherapies are becoming increasingly explored as viable innovative
approaches for the future of psychiatry (Sessa, 2012).
The prodrug psilocybin, from Psilocybe mushrooms (Figure 1), is dem-
onstrating therapeutic potential for the treatment of psychiatric con-
ditions including alcohol use disorder (Bogenschutz et al., 2015),
tobacco addiction (Garcia-Romeu, Griffiths, & Johnson, 2014), depres-
sion (Carhart-Harris et al., 2016) and existential anxiety in palliative
care (Griffiths et al., 2016; Grob et al., 2011; Ross et al., 2016). In
many of these clinical studies, subjects' mystical-type experiences
have been correlated with therapeutic outcomes and improvements
in various aspects of mental well-being such as reductions in anxiety
and an increase in the personality domain of openness (Griffiths
et al., 2016; Johnson, Garcia-Romeu, & Griffiths, 2017; MacLean,
Johnson, & Griffiths, 2011).
In 2006 a Roland Griffiths publication reported that psilocybin
can occasion mystical-type experiences having substantial and
sustained personal meaning and spiritual significance(Griffiths,
Richards, McCann, & Jesse, 2006). Since then, a number of
psilocybin-assisted psychotherapy studies have been conducted
which employ experimental features such as randomisation and
double-blind crossover designs to mitigate the effects of expectation
in both participants and clinicians (Griffiths et al., 2016; Ross
et al., 2016). While double-blinding in a clinical trial for psychedelic
therapy presents inherent challenges the long-term enduring effects
have been recorded to discern the applicability of psychedelic expe-
riences as a form of psychiatric therapy (Barnby & Mehta, 2018).
Contemporary research indicates that if medical health care profes-
sionals could reliably induce psychedelic experiences of an insightful
and mystical-type nature eliciting sudden, dramatic and enduring
transformations that affect personal emotion, cognition and behav-
iour (a phenomenon referred to as quantum change) then there
could be improvements in public health and well-being (Griffiths
et al., 2018; Griffiths, Richards, Johnson, McCann, & Jesse, 2008;
Johnson, Hendricks, Barrett, & Griffiths, 2019; Miller, 2004).
Effects of psilocybin on cognitive processes and mental function-
ing of a participant during a psilocybin trial are typically measured by
inviting the participant to complete validated questionnaires such as:
5-Dimension Altered States of Consciousness; the States of Con-
sciousness Questionnaire (SOCQ); and the Mystical Experience Ques-
tionnaire (Barrett, Johnson, & Griffiths, 2015; Griffiths et al., 2016;
MacLean, Leoutsakos, Johnson, & Griffiths, 2012; Maji
c, Schmidt, &
Gallinat, 2015). In order to determine whether a participant has had a
complete mystical-type experiencethe results of questionnaires are
totalled rendering a scoresuch as 60% on each subscale of the
SOCQ (MacLean et al., 2011). The core phenomenology of mystical
experiences, as described by previous work, include feelings of unity
and interconnectedness with all people and things, a sense of sacred-
ness, feelings of joy, peace and awe, a sense of transcending normal
time and space, ineffability and an intuitive belief that the experience
is a source of objective truth about the nature of reality (Griffiths
et al., 2006, 2018; James, 1902; Kundi, 2013; MacLean et al., 2011;
Roseman, Nutt, & Carhart-Harris, 2018; Stace, 1960).
The results of recent studies into both psychedelic-induced and non-
psychedelic-induced mystical experiences suggest that mystical expe-
riences are biologically normal(Griffiths et al., 2011) and can occur
in both religious and non-religious individuals (Yaden et al., 2017).
Studies suggest that mystical experiences and quantum change can
occur in non-drug conditions with reports of spontaneous occur-
rences in times of crisis or stagnation (Miller, 2004). While subjective
effects of psychedelic and non-psychedelic-induced mystical
FIGURE 1 Wild Psilocybe semilanceata
experiences differ, there are certain similarities such as the sense of
transcendence of time and space which imply there are continuities
between the psychological states (Yaden et al., 2017). In the case of
mystical experiences induced through disciplined contemplative prac-
tices an individual is typically required to spend months or years train-
ing their mind in order to reliably occasion meaningful mystical
experiences (Kundi, 2013). While in the case of psychedelic-induced
mystical-type experiences, research suggests that the quality of the
experience is improved while the probability of occurrence is also
increased enabling this generally rare state to become more readily
accessible (Winkelmann, 2017; Yaden et al., 2017).
3.1 |Cultural debate about the validity of
psychedelic-induced mystical-type experiences
The subject of psychedelics' place in the study of comparative reli-
gions has been well explored by the likes of Alan Watts (Watts, 1968)
and Aldous Huxley (Huxley, 1954). But from the beginning of dis-
course on the subject there were opposing viewpoints. Following
Huxley's widely read description of his mescaline experience in 1953
there came a rebuttal from other academics, notably Professor Robert
Zaehner, who warned of the dangers of conflating the transient, drug-
induced psychedelic state with attainment of mystical states through
non-drug religious experiences (Zaehner, 1957). The debate increased
as the 1960s progressed and whilst Zaehner later agreed that drug-
induced states could provide some useful guidance towards leading a
spiritual life he also highlighted examples of the misuse of psychedelic
spirituality and its capacity to do harm (Zaehner, 1974).
This article focuses on the capacity of psilocybin to induce acute
mystical-type and insight experiences which can mediate persisting
changes in perspective and psychological well-being. While mystical
experiences can occur spontaneously in non-drug conditions and the
reported subjective effects and long-term alterations of the two types
are comparable, the two experiences are not the same due to differing
neuropharmacological states.
Psilocin, the pharmacologically active dephosphorylated metabolite of
psilocybin, is highly structurally related to serotonin with a dimethyl
tertiary amine as opposed to a primary amine on the two carbon ali-
phatic chain and a hydroxyl group at the 40carbon as opposed to the
50carbon on the indole phenyl ring being the sole differences in the
chemical structures of psilocin and serotonin (Figure 2). Psilocin is a
functional agonist of the G protein-coupled 5-HT
serotonin recep-
tors and modulation of these receptors has been implicated in neuro-
plasticity, environmental sensitivity, learning and psychological
adaptability (Carhart-Harris et al., 2018b; Carhart-Harris &
Nutt, 2017; Erritzoe et al., 2019).
Research suggests that psychedelics mediate their subjective
effects partly by decreased connectivity within the default mode
network (DMN) (Johnson et al., 2019; Speth et al., 2016;
Winkelmann, 2017), modulation of the anterior and posterior cingu-
late cortex (Carhart-Harris, Leech, Williams, et al., 2012) and whole
brain integration (Hendricks, 2018). The subjective mystical-type
effects of psilocybin including ego dissolution have been at least par-
tially attributed to disruption of the DMN (Griffiths et al., 2006). Psy-
chedelics down-regulate expression of 5-HT
receptors in the
prefrontal cortex (Hendricks, 2018); and subjective effects of psyche-
delics may result from 5-HT
receptor-mediated excitation of deep
pyramidal cells leading to a desynchronization of oscillatory rhythms
in the cortex (Muthukumaraswamy et al., 2013). Disruption of the pre-
frontal cortex allows ancient brain systems such as the mirror neuron
system (Winkelmann, 2017), which is located in numerous cortical
regions, to occupy a more central role in subjective awareness
(Rizzolatti & Sinigaglia, 2016). Current research into the effects of psi-
locybin on brain function suggests an increase in communication
between brain networks accompanied by a decrease in communica-
tion within those networks (Hendricks, 2018).
The function of brain serotonin is reportedly an enigma
(Carhart-Harris & Nutt, 2017) and the exact role of 5-HT
nin receptor signalling and how it relates to both psilocybin
occasioned mystical-type experiences and naturally occurring
spontaneous mystical experiences is poorly understood (Barnby &
Mehta, 2018; Carhart-Harris & Nutt, 2017). Conducting controlled
experiments to elucidate the neuromechanistic similarities and dif-
ferences between the two types of experience presents significant
challenges due to the difficulty of eliciting spontaneous mystical
experiences in experimental settings.
4.1 |Sensitivity to meaning response
Psychotherapeutic benefits of psilocybin are not reportedly as depen-
dent on dose or intensity of drug effect as they are dependent on the
quality of the experience (Carhart-Harris, Roseman, et al., 2018;
Griffiths et al., 2006; Roseman et al., 2018). While expectation and
mood play a role in the therapeutic effects of all therapies, through
the innate placebo and nocebo effects universal to all forms of medi-
cal treatment, psychedelics render the participant especially sensitive
to the effects of set (the psychological mind-set in the build up to the
experience including expectations and intentions) and setting (the
FIGURE 2 The chemical structures of psilocin and serotonin
physical, social and political environment in which the experience
takes place) (Hartogsohn, 2016, 2017; Metzner, Litwin, & Weil, 1965).
It has been proposed that the effects of set and setting and the
placebo effect are not two differing extra-pharmacological compo-
nents which contribute to mediating effects of treatment but are both
expressions of meaning response. Meaning response is a broader con-
cept which includes the many ways in which extra-pharmacological
elements, including ritualistic and medical symbology, exert positive
and negative effects on health in a variety of contexts. Psychedelics
such as psilocybin are putative meaning response enhancers
suggesting that one of their modes of action is to directly enhance the
placebo effect itself. As potential magnifiers of the placebo response
patients' expectations of the outcome of treatment may be more fun-
damental to successful therapeutic outcomes than in other forms of
medical intervention (Hartogsohn, 2016). Furthermore, use of psilocy-
bin to induce psychological transformations may result in modification
of the epigenome via the enhanced placebo response (intent-oriented
gene expression modulation) (Carey, 2012; Martin & Nichols, 2017).
The psychological construct awehas been proposed to be a key
feature of spontaneous and psychedelic occasioned mystical-type
experiences. The experience of awe can lead to the sensation of the
small self”—the feeling that one is small in comparison with the
cosmosand this has been proposed as being a psychological media-
tor of mystical experience (Piff, Dietze, Feinberg, Stancato, &
Keltner, 2015). Individuals with high personality trait openness report-
edly demonstrate a greater capacity to experience awe as participants
who are able to fully absorb themselves in an external stimulus such
as music are more likely to experience chills”—an indication of subjec-
tively experienced awe (Hendricks, 2018). Commonly reported elici-
tors of awe include the natural environment, art, music and religious/
spiritualistic imagery. Greater emotional sensitivity to the environ-
ment may facilitate enhanced feelings of connectedness (Carhart-
Harris et al., 2018a) and subjective effects of awe resulting in a psy-
chological mind-set more receptive to mystical-type experience.
4.2 |Improved psychological flexibility mediates
therapeutic outcomes
Recent studies have elucidated certain functional characteristics of a
model of psychedelic-induced quantum change. Mystical-type and
insight experiences as measured using validated questionnaires were
found to be highly correlated with one another while only indirectly
correlated with improved psychological well-being. Regression ana-
lyses showed mystical-type and insight experiences to be highly cor-
related with improved psychological flexibility and feelings of personal
meaningfulness which in turn were highly correlated with improved
psychological outlook (Davis, Barrett, & Griffiths, 2020; Garcia-Romeu
et al., 2019; Garcia-Romeu et al., 2020). Therefore, these studies sug-
gest that it is the improved psychological flexibility and personal
meaningfulness associated with mystical-type and insight experiences
which enables depressed and anxious individuals and people with sub-
stance use disorders to reframe how they view their medical
conditions, themselves, their lives and relationships with others
(Belser et al., 2017; Davis et al., 2020; Garcia-Romeu et al., 2019,
2020; Spiegel, 2016; Watts, Day, Krzanowski, Nutt, & Carhart-
Harris, 2017).
Siempre se tomaron para que los enfermos sanaran (They were
always taken to cure the sick)- Maria Sabina (Estrada, 1977)
As psilocybin is a putative meaning response enhancer, it is
important that the medical health care profession inspires confidence
that the treatment will be effective otherwise critical attitudes
towards psilocybin use and mystical-type experiences among the gen-
eral population may impair therapeutic efficacy (James et al., 2019).
Preconceptions in any treatment will impact its efficacy as demon-
strated by the fact that the placebo effect is different across cultures
and personality types (Hartogsohn, 2016). The attitudes of partici-
pants in psilocybin trials are key to successful therapeutic outcomes
as participants should reportedly have a desire to improve their condi-
tion, demonstrate a clear intention and an open, enquiring attitude
and be willing to surrenderto the experience (Carhart-Harris
et al., 2018b; Russ, Carhart-Harris, Maruyama, & Elliot, 2019). In addi-
tion, trait absorption which is correlated with openness to experience
has been indicated as being the second strongest predictor of
mystical-type experience after drug dose (Hendricks, 2018; Studerus,
Gamma, Kometer, & Vollenweider, 2012).
Consequently, inducing mystical-type experiences as a form of
treatment is primarily likely to apply to specific groups of patients
such as the types of patients who are currently included in psilocy-
bin studies. These patients seek psilocybin treatment because they
think it will help them and often on the basis of past experience.
Additionally, many of the participants in psilocybin trials who report-
edly meet the criteria for a complete mystical-type experience regu-
larly engage in some form of spiritual practice (MacLean
et al., 2011). Patients high in personality trait neuroticism may be
less likely to benefit from psilocybin (Studerus et al., 2012). Patients
currently taking medications prescribed to treat a range of psychiat-
ric conditions such as tricyclic antidepressants, lithium, selective
serotonin reuptake inhibitors, monoamine oxidase inhibitors and the
antipsychotic medication haloperidol are typically excluded from psi-
locybin trials due to impaired psychopharmacological effects of psi-
locybin (Johnson, Richards, & Griffiths, 2008). These patients would
likely need to go through a period of abstinence from their medica-
tions prior to psilocybin-assisted psychotherapy and such a require-
ment demands individual assessment to determine if the potential
risk to reward is acceptable.
Due to clinical literature and case reports of psychedelics (typi-
cally LSD) inducing prolonged psychoses, patients with psychotic dis-
orders and people with a family history of psychotic disorders or
bipolar disorder are currently excluded from psilocybin trials (Johnson
et al., 2008; Ross et al., 2016). Psilocybin can induce periods of anxi-
ety, fear, panic, paranoia, sadness, depressed mood, anger, loss of san-
ity, delusions, dysphoria, perceptual effects and physiological
symptoms (e.g., nausea and increased heart rate). Patients with disor-
ders on the psychotic spectrum may be at increased risk of suffering
paranoia whilst experiencing the effects of psilocybin (Johnson
et al., 2008). Overwhelmingly difficult challenging experiences while
under the influence of psychedelics can lead to dangerous behaviour
such as leaving the study site and patients attempting to cause physi-
cal harm to themselves or otherswith rare reports of attempted sui-
cides. Challenging experiences have also been associated with
apparent onset of psychotic symptoms although prolonged psychoses
are rare and typically dissipate within 48 hr (Carbonaro et al., 2016;
Johnson et al., 2008).
Groups of patients with psychotic illnesses such as schizophrenia,
schizoaffective disorder, bipolar affective disorder, delusional disorder
and severe depression with psychosis present significant complica-
tions to an already complex treatment model. Great care should be
taken when considering psychedelic treatment for individuals in these
groups to minimise the potential psychedelics have for exacerbating
psychotic symptoms (Barrett, Bradstreet, Leoutsakos, Johnson, &
Griffiths, 2016; Carbonaro et al., 2016). This risk may also translate to
populations who are at high risk for developing psychosis. While the
established wisdom is that psychedelics are contraindicated for indi-
viduals with a family history of psychosis; studies have suggested that
psychedelics are not demonstrated to cause lasting anxiety, depres-
sion or psychosis and are associated with reduced negative mental
health outcomes (Johnson et al., 2008; Krebs & Johansen, 2013). It
could be that some patients currently excluded from psilocybin trials
are not at significant risk from psilocybin use although there is no con-
sensus on the issue of psychedelic use and psychosis and further
research is warranted (Nesvag, Bramness, & Ystrom, 2015).
Investigations of challenging psychedelic experiences have shown
a majority of individuals attribute increased life satisfaction to the
event, and while the duration of the challenging experience has been
negatively correlated with enduring increased well-being, increased
life satisfaction is reportedly positively and significantly related to the
difficulty of a psychedelic experience. As such it has been suggested
that therapeutic interventions should focus on reducing the duration
of a challenging experience rather than reducing its peak difficulty
(Barrett et al., 2016; Carbonaro et al., 2016).
A considerable amount of time is spent on the preparation and moni-
toring of the participants for psilocybin-assisted psychotherapy in
order to ensure an acceptable level of safety and efficacy of
Patients meet with monitors (also referred to as guides) on sev-
eral occasions and visit the site where the experience will take place
so that they are comfortable in that environment. Monitors are
typically a femalemale dyadic pair although malemale and female
female dyads have also been utilised (Eisner & Cohen, 1958; Johnson
et al., 2008). Participants are required to establish rapport with the
monitors and the monitors should demonstrate supportive clinical
sensitivity such as empathy and respect (Johnson et al., 2008). In
recent studies participants are encouraged to wear a mask over their
eyes, relax, listen to music and focus their attention inward while
being monitored throughout the usual 7- to 8-hr session (Belser
et al., 2017; Johnson et al., 2008; Kaelen et al., 2018). Due to the
afterglow effect and the potential long-term therapeutic window of
psilocybin it may be possible to enhance the benefits of mystical-type
experiences by preliminary and follow up activities. Meditation, mind-
fulness or other spiritual practices combined with exposure to stimuli
that maintain awe such as nature, art and music are potential
approaches to maintaining and enhancing the long-term benefits of
mystical-type experiences (Brewer et al., 2011; Griffiths et al., 2018;
Hendricks, 2018).
Some patients such as meditation and hallucinogen-naive individ-
uals are likely to require more extensive preparation than others
(Studerus et al., 2012). It will be challenging to adapt psychedelic ther-
apy to already overstretched public health care services and psyche-
delic therapy may initially be adopted as a form of private health care.
However, the psychedelic treatment model, while costlier in terms of
delivery in comparison with conventional therapies for mental illness,
may ultimately be cost-saving in certain situations where individuals
with severe and treatment-resistant anxiety, depression and trauma-
related conditions could be saved years of conventional treatment by
a course of controlled and supported psychedelic therapy sessions
(Carhart-Harris et al., 2018b).
7.1 |Alternative applications of mystical-type
Research has suggested that psilocybin use can lead to positive changes
in personality and increased altruism such as enhanced nature-
relatedness (Lyons & Carhart-Harris, 2018), pro-environmental behav-
iour (Forstmann & Sagioglou, 2017), decreased violent and criminal
behaviour (Hendricks et al., 2018; Walsh et al., 2016), reduced suicidal
ideation (Hendricks, Thorne, Clark, Coombs, & Johnson, 2015), tem-
pered politically authoritarian views (Lyons & Carhart-Harris, 2018) and
an increase in the personality domain of openness (MacLean
et al., 2011; Nour, Evans, & Carhart-Harris, 2017). In light of the previ-
ously highlighted research, it could be argued that use of psilocybin in
positive psychology interventions to induce changes in domains of per-
sonality could have benefits to society and the global environment
(Elsey, 2017; James, Robertshaw, & Westwell, 2019; Shelton &
Hendricks, 2016; Watts et al., 2017).
Psychedelics have been used to attempt to treat narcissistic per-
sonality disorder due to their effects on the ego (Maji
c et al., 2015).
Spontaneously occurring quantum change experiences have been
associated with reduced egotistical attitudes and greater prosocial dis-
position (Miller, 2004). Using psilocybin to induce mystical-type expe-
riences may be beneficial for individuals who excessively ruminate on
the self. With the continually rising prevalence of social media and the
reported crisis of meaning within society (Roberts, 2007), psilocybin's
effects on the ego and connectedness could be of use to the mental
healthcare profession (Carhart-Harris, 2018a).
7.2 |Clinical settings
The emergence of evidence-based psychedelic-assisted therapies will
present new opportunities and challenges for existing health care sys-
tems; many aspects of psychedelic-assisted therapies will look familiar
to doctors, nurses and therapists, with drug-free preparation sessions
and integration sessions requiring little change from the logistics of
usual practice. However, drug-assisted sessions are novel and will
require specially dressed and comfortable rooms, the use of music,
supportive and reassuring interaction, the presence of two therapists,
overnight stays with night sitters in most cases and intensive clinical
contact in between sessions. In some circumstances purpose-built
facilities may be more suitable than using existing infrastructure.
In the long-term, in order for psilocybin treatment to become
established practice, rescheduling from Schedule I needs to be
achieved and specific training for psychedelic therapy must be devel-
oped, standardised and licensed to maintain patient safety and effi-
cacy of treatment (Carhart-Harris et al., 2018b; Rucker, Iliff, &
Nutt, 2018). Despite the growing awareness of their potential thera-
peutic capabilities many regulatory authorities continue to consider
these compounds to be controversial (Nutt, 2014). Such opinions
threaten to hold back clinical research and deny patients the thera-
peutic potential of psychedelics. In addition, as psilocybin is a natural
product the issues surrounding intellectual property mean that the
investment route for progression through clinical trials and eventual
approval by the FDA and EMA is challenging. Therefore, the funding
for clinical trials will likely have to come via charitable or non-profit
Whilst this article has focused on mystical-type experiences and
applicability for the treatment of specific conditions, it is worth noting
that alternative treatment modalities such as microdosing may have
therapeutic value and the treatment of obsessive compulsive disorder
and cluster headaches are reported to be a result of pharmacological,
rather than psycho-spiritual, mechanisms (Cameron, Benson, DeFelice,
Fiehn, & Olson, 2019; Maji
c et al., 2015). Psilocybin occasioned
mystical-type experiences represent an intriguing novel form of treat-
ment; however, the cognitive and neural mechanistic processes are
not well understood (Barnby & Mehta, 2018; Lieberman &
Shalev, 2016). Correlation does famously not equal causality and
although current evidence suggests that inducing experiences of a
highly mysticalnature could lead to novel forms of psychiatric treat-
ment, more work is needed to inform the psychiatry profession on
how to reliably induce such experiences in clinical settings.
This research received no specific grant from any funding agency,
commercial or not-for-profit sectors.
Dr Hoskins has received MDMA-assisted therapy training and travel
expenses from the Multidisciplinary Association for Psychedelic Stud-
ies (MAPS), and is a principal investigator on a MAPS sponsored phase
II clinical trial of MDMA.
Dr Sessa is Managing Director of Mandala Therapy Ltd and has
authored and co-authored several books on psychedelics for which he
receives royalties.
Edward James
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How to cite this article: James E, Robertshaw TL, Hoskins M,
Sessa B. Psilocybin occasioned mystical-type experiences.
Hum Psychopharmacol Clin Exp. 2020;e2742.
... 6 of 35 -JAMES ET AL. Clifton et al., 2020;James et al., 2020;Strassman et al., 2001). DMT users frequently describe some form of acute psycho-spiritual changes during the subjective experience which they later incorporate into their long-term perception of the cosmos (Cott & Rock, 2008;Griffiths et al., 2019). ...
... Therefore, 5-HT2A receptor agonism alone is not sufficient to explain the entirety of DMT phenomenology (Barker, 2018a;Brito-da-Costa et al., 2020;Carbonaro & Gatch, 2016;Nichols, 2016;Valle et al., 2016;Vollenweider & Preller, 2020;Wallach, 2009). Finally, all classic psychedelics, including DMT, which act upon 5-HT2A receptors are understood to cause consumers to be sensitised to set and setting, however, the mechanism of this sensitisation and its link with 5-HT2A receptor binding is not clear (Carhart-Harris & Nutt, 2017;Hartogsohn, 2016;James et al., 2020). ...
... In addition, under the influence of DMT and ayahuasca, profound spiritual (also referred to as peak, unitive, mystical, mystical-type and, as is highlighted in this article, henosis 3 ) experiences can emerge, hallmarked by an altered perception of space and time, disassociation from the body, ego dissolution, a sense of entering into pure awareness and unity with the cosmos James, 1902;James et al., 2020;Pallavicini et al., 2021;Stace, 1960;Strassman, 2001). In the light of the zero-point field hypothesis, this suggests that DMT and ayahuasca modify the receiving characteristics of the brain, allowing the receiving unit to resonate with a larger set of ZPF modes and to tap into a wider spectrum of the phenomenal colour palette furnished by the ZPF (Figure 9). ...
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Objective: Reports have indicated possible uses of ayahuasca for the treatment of conditions including depression, addictions, post-traumatic stress disorder, anxiety and specific psychoneuroendocrine immune system pathologies. The article assesses potential ayahuasca and N,N-dimethyltryptamine (DMT) integration with contemporary healthcare. The review also seeks to provide a summary of selected literature regarding the mechanisms of action of DMT and ayahuasca; and assess to what extent the state of research can explain reports of unusual phenomenology. Design: A narrative review. Results: Compounds in ayahuasca have been found to bind to serotonergic receptors , glutaminergic receptors, sigma-1 receptors, trace amine-associated receptors , and modulate BDNF expression and the dopaminergic system. Subjective effects are associated with increased delta and theta oscillations in amygdala and hippocampal regions, decreased alpha wave activity in the default mode network, and stimulations of vision-related brain regions particularly in the visual association cortex. Both biological processes and field of consciousness models have been proposed to explain subjective effects of DMT and ayahuasca, however, the evidence supporting the proposed models is not sufficient to make confident conclusions. Ayahuasca plant medicine and DMT represent potentially novel treatment modalities. Conclusions: Further research is required to clarify the mechanisms of action and develop treatments which can be made available to the general public. Integration between healthcare research institutions and reputable practitioners in the Amazon is recommended.
... This may, in turn, have wider benefits to society and the global environment. [192][193][194][195][196] 2. ...
... Enhanced feelings of connectedness [192] 3. ...
... Enhanced-nature relatedness [40,192] ...
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The psychedelic effects of some plants and fungi have been known and deliberately exploited by humans for thousands of years. Fungi, particularly mushrooms, are the principal source of naturally occurring psychedelics. The mushroom extract, psilocybin has historically been used as a psychedelic agent for religious and spiritual ceremonies, as well as a therapeutic option for neuropsychiatric conditions. Psychedelic use was largely associated with the “hippie” counterculture movement, which, in turn, resulted in a growing, and still lingering, negative stigmatization for psychedelics. As a result, in 1970, the U.S. government rescheduled psychedelics as Schedule 1 drugs, ultimately ending scientific research on psychedelics. This prohibition on psychedelic drug research significantly delayed advances in medical knowledge on the therapeutic uses of agents such as psilocybin. A 2004 pilot study from the University of California, Los Angeles, exploring the potential of psilocybin treatment in patients with advanced-stage cancer managed to reignite interest and significantly renewed efforts in psilocybin research, heralding a new age in exploration for psychedelic therapy. Since then, significant advances have been made in characterizing the chemical properties of psilocybin as well as its therapeutic uses. This review will explore the potential of psilocybin in the treatment of neuropsychiatry-related conditions, examining recent advances as well as current research. This is not a systematic review.
... Consequently, those engaging in entheogenic-assisted religious rituals within the sacramental imaginary need to create and use their own religiously inflected vocabulary and not assimilate notions from other socio-psychedelic imaginaries to gain exemption. The way the system is currently structured necessitates a strict separation of the medical and spiritual, while at the same time clinical research of PAT demonstrates that the strongest healing effects in secular, biomedicalized settings tend to correlate with the appearance of mystical experiences [32,33,46], which are also considered to be the experiential basis of religion [47]. In addition to ad hoc beliefs, lack of ceremony and ritual, quantity of the controlled substance used, and the use of other controlled substances, the government also looks at evidence of commerce to demonstrate insincerity. ...
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After decades of criminalization, psychedelic substances such as psilocybin and LSD are experiencing their comeback in science and Western culture more broadly. While psychedelic plants and fungi have a long history of use in Indigenous cultures, the Western prohibitionist reality instantiated around 1970 has stigmatized psychedelics as medically useless and a threat to society. Yet studies are increasingly demonstrating their potential to treat widespread mental health conditions such as PTSD, depression, or anxiety in combination with psychotherapy. Most of this research is currently taking place in the US, where additionally decriminalization and legalization efforts and religious exemptions have paved the way to make psychedelics legally accessible. Based on 3 years of ethnographic research in the US (both in-person and virtual), this article explores contemporary US-American socio-psychedelic imaginaries, i.e., collective visions articulated and enacted to reintegrate psychedelics legally and responsibly into society. Four socio-psychedelic imaginaries are identified, described, and interpreted: the biomedicalization imaginary, decriminalization imaginary, legalization imaginary, and sacramental imaginary. These imaginaries diverge and converge around several politics: politics of access, politics of responsibility, politics of naming, politics of assimilation and social change, and politics of epistemic credibility. Contemporary socio-psychedelic imaginaries are co-evolving, mutually shaping, and amplifying each other. Together they function as societal corrective to the politically motivated prohibition of psychedelics. Although enacted by humans, the radical imagination expressed in socio-psychedelic imaginaries has its roots in human-psychedelics entanglements.
... Under sufficiently high-doses, psychedelics tend to be accompanied by transformative 'mystical-type' experiences, which may include content of a transcendent nature, such as experiencing a cosmic consciousness, or encountering interdimensional beings or Godly entities. The induction of mystical-type experiences during a psychedelic session has been found to be an important predictor of improvements in mental health (James et al., 2020;Roseman et al., 2018). Based on these findings, some researchers have cautioned that while psychedelics may be beneficial for psychological wellbeing, they may only do so through mediating the occurrence of metaphysical beliefs in 'non-natural' entities (Lavazza, 2017). ...
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In Philosophy of Psychedelics, Letheby provides a convincing basis for the idea that psychedelics primarily derive their therapeutic potential through mediating favourable changes to self-related belief systems. In this commentary, we take a closer look at the role that contextual factors (‘set’ and ‘setting’) play in Letheby’s two-factor account of psychedelic therapy. While Letheby acknowledges that psychedelic effects are highly context-dependent, the exact role that context plays in self-modelling during the acute experience is not entirely clear. We argue that context plays an essential role in shaping the ‘discovery’ of alternate self-conceptions during the acute experience. Specifically, users are more likely to experience alterations in self-conception that are consistent with context-dependent features, such as one’s prior mindset (‘set’) and aspects of the external environment (‘setting’). This is consistent with a REBUS model of psychedelic effects, where a corollary effect of relaxing high-level prior beliefs is that the system becomes increasingly sensitised to bottom-up information (‘prediction errors’) from lower-level intrinsic sources and the sensory periphery. Furthermore, it may explain why a positive well-intentioned state of mind and a supportive therapeutic environment are more likely to result in positive acute experiences and long-term improvements in mental wellbeing. We see this position as being largely compatible with Letheby’s proposal, but may shift some aspects of its emphasis and framing. In particular, it may conflict with Letheby’s notion that psychedelics lead to a ‘level cognitive playing field’, where self-related hypotheses are thought to be assigned more or less equal probability.
... However, the exact mechanisms and the reasons for psychedelic-induced mystical-type experiences and their long-lasting effects remain unknown (James et al., 2020). A recent proposal for a psychological framework suggests that the principal catalyst for the change may be the distinct emotion of profound awe experienced during those states. ...
It is widely acknowledged that an open character or attitude is vital for having a meaningful and transformative psychedelic experience. Studies further indicate that a mindful and open state of mind paves way for so-called mystical experiences which in turn are predicting positive outcomes regarding mental health. This study further examined the role of openness as a state and trait variable in predicting the degree of experienced mystical states and the levels of acute well-being, using pooled data from 3 trials studying the acute effects of the substances lysergic acid diethylamide (LSD) and psilocybin in two distinct doses each (n = 60). Correlational and regression analyses have shown that the personality trait of openness (NEO-FFI) and its subscales or facets were significantly associated with experienced openness during the psychedelic peak phases in all examined substances and doses (r = 0.35 − 0.62). They also show that an early state of openness between ingestion and onset of substance effects leads to higher levels of mystical states (r = 0.37 − 0.54). Multiple regression analyses show that these mystical experiences have a significant effect on well-being 24 hours after ingestion, in all but the high-dose psilocybin condition. Also, the personality trait of openness to experience has been identified to moderate this relationship significantly and positively (p = 0.034 − 0.025). Further coincidental findings revolve around the timepoint and amplitude of the peak psychedelic phase, which both seem to correlate with certain personality facets of openness to experience. Findings from this thesis can provide information that may have implications for the integration of mindfulness-based therapy models, such as the psychological flexibility model, into psychedelic experiences and their research. Future use cases may also include the prediction of the course and nature of acute psychedelic experiences by means of personality screening.
... Several studies have found that psilocybin occasioned mystical experiences are related to long term beneficial outcomes (e.g., Doblin, 1991;Griffiths et al., 2018;Russ, Carhart-Harris, Maruyama, & Elliott, 2019). Possible mediators of this effect include ego dissolution experiences (e.g., Carhart-Harris et al., 2018), feelings of "awe" (James, Robertshaw, Hoskins, & Sessa, 2020), post-experience behavioral changes such as engagement with meditation and other spiritual practices (Griffiths et al., 2018), and significant changes to beliefs and worldviews such as decreased self-identified atheism (Davis et al., 2020;Griffiths et al., 2019) and increased nature-relatedness (Lyons & Carhart-Harris, 2018). Additionally, Hartogsohn (2018) has argued that psychedelics have a meaningenhancing effect, so that under the influence of psychedelics, things appear to be profoundly more meaningful than usual. ...
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This article reports on the experiences of four healthy individuals who attended a legal psilocybin truffle retreat in the Netherlands. The study employed a qualitative phenomenological approach, using semi-structured interviews to gain an understanding of participants' psilocybin experiences and their after-effects. The experiential themes that emerged from these case studies closely match themes that have been identified in previous studies of psilocybin, including variability of the experience, the presence of mystical-type features, significant changes to subjective sense of self, and a generalized sense of connectedness. Participants framed their narrative accounts around moments of key insight, and these insights were related to a sense of connection: to self, others, and to a broader relational ontology. Embodiment, currently an understudied topic in psychedelic research, also emerged as a theme. The case studies presented here provide preliminary evidence to suggest that for healthy individuals in a well-controlled and supportive retreat setting, a high dose of psilocybin can lead to enduring positive after-effects that last up to twelve months.
... 2 At higher doses, classic psychedelics drugs also produce profound alterations of consciousness, including changes in one's sense of self 3 and relationship to others, 4 as well as peak or mystical-type experiences. 5 Over the past two decades, a growing body of research has begun to evaluate the mental health effects, including the effects on suicidality, associated with both non-clinical classic psychedelic use (i.e., recreational and ritualistic use outside the context of a clinical intervention) and psychedelic therapy (i.e., administration of a classic psychedelic in a supportive, legally sanctioned clinical environment and often in combination with psychological preparation and integration). 6,7 Accordingly, there remains a need for a synthesis of the literature on the effects of classic psychedelic use and psychedelic therapy on suicidality. ...
Full-text available
Use of classic psychedelics (e.g., psilocybin, ayahuasca, and lysergic acid diethylamide) is increasing, and psychedelic therapy is receiving growing attention as a novel mental health intervention. Suicidality remains a potential safety concern associated with classic psychedelics and is, concurrently, a mental health concern that psychedelic therapy may show promise in targeting. Accordingly, further understanding of the relationship between classic psychedelics and suicidality is needed. Therefore, we conducted a systematic review of the relationship between classic psychedelics (both non-clinical psychedelic use and psychedelic therapy) and suicidality. We identified a total of 64 articles, including 41 articles on the association between non-clinical classic psychedelic use and suicidality and 23 articles on the effects of psychedelic therapy on suicidality. Findings on the association between lifetime classic psychedelic use and suicidality were mixed, with studies finding positive, negative, and no significant association. A small number of reports of suicide and decreased suicidality following non-clinical classic psychedelic use were identified. Several cases of suicide in early psychedelic therapy were identified; however, it was unclear whether this was due to psychedelic therapy itself. In recent psychedelic therapy clinical trials, we found no reports of increased suicidality and preliminary evidence for acute and sustained decreases in suicidality following treatment. We identify some remaining questions and provide suggestions for future research on the association between classic psychedelics and suicidality.
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When the link between psychedelic drugs and mystical states of experience was first discovered in the 1960s, Huston Smith challenged scholars in religion and philosophy to consider the implications. Very few took up his challenge. Beginning in 2006, hundreds of studies have linked psychedelics not just to mystical states of experience but to potential treatments for many mental health disorders. Regulatory approval for therapies is on the horizon, and hundreds of millions of people worldwide could be treated. Research findings challenge the underlying rationale of the War on Drugs, leading to decriminalization of specific psychedelic drugs or to authorization of their use in mental health contexts. Religious institutions are slowly adapting, with some referring to psychedelics as sacraments or as pathways to deeper spirituality. Religious leaders are also beginning to speak out publicly in support of careful use of these drugs, and some are training to become “psychedelic chaplains” to work alongside mental health professionals administering these drugs. Scholars in theology and religion are encouraged to engage these trends, to explore challenging philosophical and theological issues surrounding mystical states of experience in general, and to consider the long-term cultural impact of the most recent psychedelic research.
Résumé Objectif Cet article propose une revue de littérature concernant les psychédéliques dits classiques (LSD, psilocybine, DMT et mescaline) et, plus précisément, leur utilisation en psychothérapie dans le champ de la dépression, du point de vue des processus de symbolisation. Méthode Après quelques éléments introductifs portant sur la dépression, nous décrivons les principales caractéristiques des psychothérapies assistées par psychédélique et les résultats des essais cliniques modernes. Nous en présentons ensuite la phénoménologie et en proposons un éclairage théorique au croisement des neurosciences et de la psychanalyse, avant de conclure sur les perspectives ouvertes par cette thérapie. Résultats Les résultats déjà obtenus suggèrent qu’une seule dose, prise dans un environnement étayant, peut être suffisante pour produire des effets thérapeutiques significatifs et objectivables dès la prise de psychédéliques et au moins six mois après celle-ci. La réponse clinique dépend de l’intensité phénoménologique initiale de l’expérience et de la capacité du sujet à laisser advenir des reviviscences traumatiques. Elle dépend également de la présence et de l’intensité de vécus de nature mystique caractérisés par un sentiment de dissolution du moi et d’unité avec le monde. Discussion La thérapie assistée par psychédéliques semble favoriser l’émergence des processus primaires et la levée des mécanismes de défense. Les psychédéliques catalyseraient ainsi la relance des processus de symbolisation, favorisant notamment l’intégration de certains conflits psychiques ainsi que le remaniement de relations d’objets pathogènes. Sur le plan neurobiologique, ces processus seraient sous-tendus par une diminution de l’activité du réseau du mode par défaut – parfois considéré comme lié à certaines fonctions du Moi – associée à une dimension entropique du fonctionnement cérébral. Ces différents éléments participeront d’une diminution de la symptomatologie dépressive, en particulier des ruminations. Ces effets thérapeutiques nécessitent néanmoins un cadre clinique particulièrement contenant et un positionnement clinique plus engagé qu’à l’accoutumée afin d’accompagner dans les meilleures conditions ces potentiels effets de transformation psychique. Conclusions Les études déjà menées sur cette thématique soulignent le caractère très prometteur des psychédéliques dans la prise en charge de la dépression et de ses formes résistantes. Ces substances semblent opérer comme un catalyseur des processus de symbolisation qui nécessite néanmoins, pour se déployer pleinement, un accompagnement psychothérapique plus global à la croisée de la psychiatrie, la psychologie clinique, des neurosciences et de la psychanalyse.
Psychedelic drugs are increasingly being incorporated into therapeutic contexts for the purposes of promoting mental health. Yet, they can also induce adverse reactions in some individuals, and it is difficult to predict pre-treatment who is likely to experience positive or adverse acute effects. Although consideration of setting, dosage, and excluding individuals with psychotic predispositions has thus far led to a high degree of safety, it is imperative researchers develop a more nuanced understanding of how to predict individual reactions. To this end, the current systematic review coalesced the results of 14 studies that included baseline states or traits predictive of the acute effects of psychedelics. Individuals high in the traits of absorption, openness, and acceptance as well as a state of surrender were more likely to have positive and mystical-type experiences, whereas those low in openness and surrender, or in preoccupied, apprehensive, or confused psychological states were more likely to experience acute adverse reactions. Participant sex was not a robust predictor of drug effects, but 5-HT2AR binding potential, executive network node diversity, and rACC volume may be potential baseline biomarkers related to acute reactions. Lastly, increased age and experience with psychedelics were individual differences related to generally less intense effects, indicating users may become slightly less sensitive to the effects of the drugs after repeated usage. Although future well-powered, placebo-controlled trials directly comparing the relative importance of these predictors is needed, this review synthesizes the field's current understanding of how to predict acute reactions to psychedelic drugs.
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Background Observational data and preliminary studies suggest serotonin 2A agonist psychedelics may hold potential in treating a variety of substance use disorders (SUDs), including opioid use disorder (OUD).AimsThe study aim was to describe and analyze self-reported cases in which naturalistic psychedelic use was followed by cessation or reduction in other substance use.Methods An anonymous online survey of individuals reporting cessation or reduction in cannabis, opioid, or stimulant use following psychedelic use in non-clinical settings.ResultsFour hundred forty-four respondents, mostly in the USA (67%) completed the survey. Participants reported 4.5 years of problematic substance use on average before the psychedelic experience to which they attributed a reduction in drug consumption, with 79% meeting retrospective criteria for severe SUD. Most reported taking a moderate or high dose of LSD (43%) or psilocybin-containing mushrooms (29%), followed by significant reduction in drug consumption. Before the psychedelic experience 96% met SUD criteria, whereas only 27% met SUD criteria afterward. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced substance misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with greater reduction in drug consumption.Conclusions While these cross-sectional and self-report methods cannot determine whether psychedelics caused changes in drug use, results suggest the potential that psychedelics cause reductions in problematic substance use, and support additional clinical research on psychedelic-assisted treatment for SUD.
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Background Contemporary research indicates that the legal classifications of cannabis (Schedule 2, Class B), 3,4-methylenedioxymethamphetamine (MDMA) (Schedule 1, Class A) and psilocybin (Schedule 1, Class A) in the United Kingdom are not entirely based on considerations of harm and therapeutic utility. The legal classifications of the substances discussed are typically determined by legislators such as Parliament and, therefore, may be a reflection of the views or perceived views of the general public. Objective The aim of the study was to provide an indication of the underlying psychology regarding the legislated sale of alcohol, tobacco, cannabis, MDMA and psilocybin in pharmacies according to a UK general population sample. Methods A sample of 105 UK nationals was selected for the survey. Participants were asked questions on perceived relative harm of the five substances. After viewing contemporary information on reported relative harm and therapeutic applications, the participants were asked questions related to using the pharmacy retail model for the sale of the substances discussed. Participants who opposed the substances being sold primarily in pharmacies were asked to explain their rationale according to a predetermined list of options for each of the five drugs. Participants were also asked whether they consider it a human right to be legally permitted to consume the substances. Results The participants' perceptions of relative harm (tobacco > MDMA > psilocybin > alcohol > cannabis) were not in agreement with the relative harm reported in the literature (alcohol > tobacco > cannabis > MDMA > psilocybin). Principal objections to the currently illicit substances being legally available in pharmacies include it sending the wrong message; it feels wrong; it is too dangerous; disliking the smell of cannabis; disapproval of the people; and not liking the idea of people using psychoactive drugs for entertainment or to have mystical/religious experiences. Overall, the participants determined that being legally permitted to consume the substances discussed is an issue of relevance to human rights. A majority of the male participants concluded that being legally permitted to consume alcohol, tobacco, cannabis and Psilocybe mushrooms is a human right in contrast to the majority of female participants who solely considered alcohol consumption to be a human right. Conclusions The data suggest that the legal classifications may not simply be based on considerations of harm. Misperceptions of the dangers, biases and non-health-related aversions likely contribute to the continuation of policies that do not reflect the state of scientific research.
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Background Recent research demonstrated the potential of psychedelic drugs as treatment for depression and death-related anxiety and as an enhancement for well-being. While generally positive, responses to psychedelic drugs can vary according to traits, setting, and mental state (set) before and during ingestion. Most earlier models explain minimal response variation, primarily related to dosage and trust, but a recent study found that states of surrender and preoccupation at the time of ingestion explained substantial variance in mystical and adverse psilocybin experiences. Objectives The current study sought to replicate the previous model, extend the model with additional predictors, and examine the role of mystical experience on positive change. Method A hierarchical regression model was created with crowdsourced retrospective data from 183 individuals who had self-administered psilocybin in the past year. Scales explored mental states before, during, and after psilocybin ingestion, relying on open-ended memory prompts at each juncture to trigger recollections. Controlled drug administration was not employed. Results This study replicated the previous model, finding a state of surrender before ingestion a key predictor of optimal experience and preoccupation a key predictor of adverse experience. Additional predictors added to the explanatory power for optimal and adverse experience. The model supported the importance of mystical experiences to long-term change. Conclusion Mental states of surrender or preoccupation at the time of ingestion explain variance in mystical or adverse psilocybin experiences, and mystical experiences relate to long-term positive change. The capacity to recognize this optimal preparatory mental state may benefit therapeutic use of psilocybin in clinical settings.
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Background: Meta-analysis of randomized studies using lysergic acid diethylamide (LSD) for alcohol use disorder (AUD) showed large, significant effects for LSD efficacy compared to control conditions. Clinical studies suggest potential anti-addiction effects of LSD and mechanistically-related classic psychedelics for alcohol and other substance use disorders. Aims: To supplement clinical studies, reports of psychedelic use in naturalistic settings can provide further data regarding potential effects of psychedelics on alcohol use. Methods: An anonymous online survey of individuals with prior AUD reporting cessation or reduction in alcohol use following psychedelic use in nonclinical settings. Results: 343 respondents, mostly White (89%), males (78%), in the USA (60%) completed the survey. Participants reported seven years of problematic alcohol use on average before the psychedelic experience to which they attributed reduced alcohol consumption, with 72% meeting retrospective criteria for severe AUD. Most reported taking a moderate or high dose of LSD (38%) or psilocybin (36%), followed by significant reduction in alcohol consumption. After the psychedelic experience 83% no longer met AUD criteria. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced alcohol misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with a greater reduction in alcohol consumption, controlling for prior alcohol consumption and related distress. Conclusions: Although results cannot demonstrate causality, they suggest that naturalistic psychedelic use may lead to cessation or reduction in problematic alcohol use, supporting further investigation of psychedelic-assisted treatment for AUD.
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Drugs capable of ameliorating symptoms of depression and anxiety while also improving cognitive function and sociability are highly desirable. Anecdotal reports have suggested that serotonergic psychedelics administered in low doses on a chronic, intermittent schedule, so-called "microdosing", might produce beneficial effects on mood, anxiety, cognition, and social interaction. Here, we test this hypothesis by subjecting male and female Sprague Dawley rats to behavioral testing following the chronic, intermittent administration of low doses of the psychedelic N, N-dimethyltryptamine (DMT). The behavioral and cellular effects of this dosing regimen were distinct from those induced following a single high dose of the drug. We found that chronic, intermittent, low doses of DMT produced an antidepressant-like phenotype and enhanced fear extinction learning without impacting working memory or social interaction. Additionally, male rats treated with DMT on this schedule gained a significant amount of body weight during the course of the study. Taken together, our results suggest that psychedelic microdosing may alleviate symptoms of mood and anxiety disorders, though the potential hazards of this practice warrant further investigation.
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A psychological model of classic psychedelic-assisted psychotherapy informed by contemporary scientific data is presented in this paper. It is suggested that classic psychedelic-occasioned mystical experience is characterized by profound awe, a discrete emotion experienced in the presence of a vast stimulus requiring accommodation of mental structures. Awe, in turn, promotes the small self, a construct that, in the extreme, is analogous to those of unitive experience and ego dissolution. The small self is conceptualized as key to understanding the downstream effects of mystical experience occasioned in the context of classic psychedelic-assisted psychotherapy. With this novel theoretical framework in mind, a number of clinical implications and recommendations are provided so as to advance this incipient field of study.
Prior research has shown that acute subjective psychedelic effects are associated with both spontaneous and intended changes in depression and anxiety. Psychedelics are also theorized to produce increases in psychological flexibility, which could explain decreases in depression and anxiety following a psychedelic experience. Therefore, the present cross-sectional survey study sought to examine whether psychological flexibility mediated the relationship between acute psychedelic experiences and spontaneous or intended changes in depression and anxiety among a large international sample of people who reported having used a psychedelic (n=985; male=71.6%; Caucasian/white=84.1%; Mage=32.2, SD=12.6). A regression analysis showed that acute effects (i.e., mystical and insightful effects) were significantly associated with decreases in depression/anxiety following a psychedelic experience. A path analysis revealed that, while controlling for age and sex, increases in psychological flexibility fully mediated the effect of mystical and insightful experiences on decreases in depression and anxiety following a psychedelic experience. This suggests that psychological flexibility may be an important mediator of the therapeutic effects of psychedelic drugs. Future prospective experimental studies should examine the effect of psychedelic drug administration on psychological flexibility in order to gain a better understanding of the psychological processes that predict therapeutic effects of psychedelics.
Background:: Recent studies have suggested therapeutic benefits of psychedelics for a variety of mental health conditions. The understanding of how single psychedelic administrations can induce long-lasting effects are, in large, still lacking. However, recent studies in both healthy and clinical populations suggest a role for personality changes. Aim:: To test support for some of these plausible mechanisms we evaluated (cross-sectional) associations between recreational use of psychedelics and 3,4-methylene-dioxymethamphetamine (MDMA) and (a) personality measures and (b) key markers of cerebral serotonergic signalling (serotonin transporter and serotonin-2A-receptor binding). Methods:: In 10 psychedelic-preferring recreational users, 14 MDMA-preferring users and 21 non-using controls, personality was assessed using the 'big five' instrument Revised NEO Personality Inventory (NEO-PI-R). Frontal serotonin transporter and serotonin-2A-receptor binding potentials were quantified using [11C]DASB and [18F]altanserin positron emission tomography, respectively. Results:: Of the five NEO-PI-R traits, only openness to experience scores differed between the three groups; psychedelic-preferring recreational users showing higher openness to experience scores when compared with both MDMA-preferring users and controls. Openness to experience scores were positively associated with lifetime number of psychedelic exposures, and among all MDMA-preferring user/psychedelic-preferring recreational user individuals, frontal serotonin transporter binding - but not frontal serotonin-2A-receptor binding - was positively associated with openness to experience. Conclusion:: Our findings from this cross-sectional study support increasing evidence of a positive association between psychedelic experiences and openness to experience, and (a) expands this to the context of 'recreational' psychedelics use, and (b) links serotonergic neurotransmission to openness to experience. A modulation of personality induced by psychedelic experiences may have important therapeutic implications via its impact on peoples' value systems, cognitive flexibility, and individual and social behaviour.
The purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are serotonin 2A receptor (5-HT2AR) agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been administered as sacraments since ancient times. They were of prominent interest within psychiatry and neuroscience in the 1950s to 1960s, and during this time contributed to the emergence of the field of molecular neuroscience. Promising results were reported for treatment of both end-of-life psychological distress and addiction, and classic psychedelics served as tools for studying the neurobiological bases of psychological disorders. Moreover, classic psychedelics were shown to occasion mystical experiences, which are subjective experiences reported throughout different cultures and religions involving a strong sense of unity, among other characteristics. However, the recreational use of classic psychedelics and their association with the counterculture prompted an end to human research with classic psychedelics in the early 1970s. We provide the most comprehensive review of epidemiological studies of classic psychedelics to date. Notable among these are a number of studies that have suggested the possibility that nonmedical naturalistic (non-laboratory) use of classic psychedelics is associated with positive mental health and prosocial outcomes, although it is clear that some individuals are harmed by classic psychedelics in non-supervised settings. We then review recent therapeutic studies suggesting efficacy in treating psychological distress associated with life-threatening diseases, treating depression, and treating nicotine and alcohol addictions. We also describe the construct of mystical experience, and provide a comprehensive review of modern studies investigating classic psychedelic-occasioned mystical experiences and their consequences. These studies have shown classic psychedelics to fairly reliably occasion mystical experiences. Moreover, classic-psychedelic-occasioned mystical experiences are associated with improved psychological outcomes in both healthy volunteer and patient populations. Finally, we review neuroimaging studies that suggest neurobiological mechanisms of classic psychedelics. These studies have also broadened our understanding of the brain, the serotonin system, and the neurobiological basis of consciousness. Overall, these various lines of research suggest that classic psychedelics might hold strong potential as therapeutics, and as tools for experimentally investigating mystical experiences and behavioral-brain function more generally.