Psychedelics and potential benefits in “healthy normals”: A review of the literature

Abstract

We are in the midst of a psychedelic research renaissance. With research examining the efficacy of psychedelics as a treatment for a range of mental health indications still in its early stages, there is an increasing body of research to show that careful use of psychedelics can yield a variety of benefits in “healthy normals” and so lead to “the betterment of well people.” Psychedelics have been found to modulate neuroplasticity, and usage in a supportive setting can result in enduring increases in traits such as well-being, life satisfaction, life meaning, mindfulness, and a variety of measures associated with prosocial behaviors and healthy psychological functioning. The effect of psychedelic experience on measures of personality trait openness and is potential implications is examined, and the potential role of awe as a mediator of the benefits of the psychedelic experience is discussed. Special attention is given to the capacity of psychedelics to increase measures of nature relatedness in an enduring sense, which is being correlated with a broad range of measures of psychological well-being as well as a key predictor of pro-environmental awareness and behavior. The effects of particular classical psychedelic compounds on healthy people are discussed, with special attention given to the mystical-type experiences occasioned by high doses of psychedelics, which appear to be an important mediator of long-term benefits and psychotherapeutic gains. Research looking at the potential benefits of psychedelic microdosing is discussed. Potential future research avenues are explored, focusing on the potential development of psychedelics as agents of ecotherapy.

Full text

Psychedelics and potential benefits in “healthy normals”:
A review of the literature
SAM GANDY*
Independent Researcher, Leicestershire, UK
(Received: April 30, 2019; accepted: October 24, 2019)
We are in the midst of a psychedelic research renaissance. With research examining the efficacy of psychedelics as a
treatment for a range of mental health indications still in its early stages, there is an increasing body of research to
show that careful use of psychedelics can yield a variety of benefits in “healthy normals”and so lead to “the
betterment of well people.”Psychedelics have been found to modulate neuroplasticity, and usage in a supportive
setting can result in enduring increases in traits such as well-being, life satisfaction, life meaning, mindfulness, and a
variety of measures associated with prosocial behaviors and healthy psychological functioning. The effect of
psychedelic experience on measures of personality trait openness and is potential implications is examined, and the
potential role of awe as a mediator of the benefits of the psychedelic experience is discussed. Special attention is given
to the capacity of psychedelics to increase measures of nature relatedness in an enduring sense, which is being
correlated with a broad range of measures of psychological well-being as well as a key predictor of pro-environmental
awareness and behavior. The effects of particular classical psychedelic compounds on healthy people are discussed,
with special attention given to the mystical-type experiences occasioned by high doses of psychedelics, which appear
to be an important mediator of long-term benefits and psychotherapeutic gains. Research looking at the potential
benefits of psychedelic microdosing is discussed. Potential future research avenues are explored, focusing on the
potential development of psychedelics as agents of ecotherapy.
Keywords: psychedelics, benefits, nature, psilocybin, LSD, ayahuasca
INTRODUCTION
Classical or serotonergic psychedelic compounds are a
subclass of psychedelic compounds whose method of action
is strongly tied to the neurotransmitter serotonin, with the
compounds acting as partial agonists at the serotonin
5-HT
2A
receptor, which is widely distributed across numer-
ous cortical areas of the brain (Carhart-Harris et al., 2014;
Glennon, Titeler, & McKenney, 1984). They are known for
their very low physiological toxicity, being non-addictive,
and exerting profound effects on human consciousness.
Examples of classical psychedelics include DMT, LSD,
psilocybin, mescaline, and compounds of the 2C family.
The tryptamine psychedelics such as DMT and psilocybin
structurally resemble serotonin itself, whereas mescaline
and compounds of the 2C family resemble the neurotrans-
mitter dopamine in structure. Psychedelics, such as
psilocybin, mescaline, DMT, and lysergic acid compounds,
have been employed for purposes of healing and divination
by some cultures for centuries if not millennia (Nichols,
2016). We are in the midst of a psychedelic renaissance,
with scientific research into the properties of these
compounds expanding rapidly (Sessa, 2018). Although
much of this current research has been focused on their
medical potential, there is an increasing body of evidence on
the effect of psychedelics on “healthy normal”people
without a specific mental health diagnosis (a good propor-
tion of which may be psychedelic naive), and this research
suggests a number of potential benefits of controlled
psychedelic use among this population on cognition, aware-
ness, and well-being. A large-scale survey study found that
there were no significant associations between lifetime use
of classical psychedelics and rate of poor mental health
outcomes, and psychedelic usage may in fact confer mental
health benefits (Krebs & Johansen, 2013). A further popu-
lation study of 130,000 adults in the US failed to find any
evidence for a link between usage of classical psychedelics
and mental health problems (Johansen & Krebs, 2015).
Lifetime use of classical psychedelics has been associated
with significantly reduced odds of past-month psychological
distress, past-year suicidal planning, and past-year suicide
attempt likelihood, unlike lifetime illicit use of other drugs,
which was largely associated with increased likelihood of
these outcomes, suggesting psychedelics may hold promise
in the prevention of suicide (Hendricks, Thorne, & Clark,
2015). Lifetime use of classical psychedelics has also been
associated with reduced odds of antisocial criminal behavior
(Hendricks et al., 2018). Long-term regular ritualistic use of
peyote among Native Americans has not been associated
with any psychological or cognitive deficits (Halpern,
Sherwood, Hudson, Yurgelun-Todd, & Pope, 2005).
* Corresponding address: Dr. Sam Gandy; Independent Researcher,
Farndon Grange, Marston Lane, Market Harborough, Leicestershire
LE16 9SL, UK; Phone: +44 7971 894 662; E-mail: greensam2512@
hotmail.com
This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License,
which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and
source are credited, a link to the CC License is provided, and changes –if any –are indicated.
© 2019 The Author(s)
ORIGINAL ARTICLE Journal of Psychedelic Studies 3(3), pp. 280–287 (2019)
DOI: 10.1556/2054.2019.029

Psychedelics have been implicated in promoting struc-
tural neural plasticity, by robustly increasing the formation
of new synapses and dendrites between neurons, facilitating
the formation of new synapses and dendrites between
neurons. These neuroplastic properties could at least partly
explain their long-term therapeutic potency, with the label
“psychoplastogen”being applied to them (Ly et al., 2018),
with neuroplasticity believed to be a key mechanism in
learning and adaptation, and the brain’s ability to modify
and change both structure and function throughout life in
response to experience (Voss, Thomas, Cisneros-Franco, &
de Villers-Sidani, 2017).
A correlative study assessing the values, beliefs, and
emotional empathy of psychedelic users found increased
values of spirituality and concern for others and lower
appreciation of financial prosperity, although it is hard to
say whether these values preceded psychedelic usage or
resulted from it (Lerner & Lyvers, 2006). Other studies have
found psychedelic users to show greater creativity than
non-users (Sweat, Bates, & Hendricks, 2016), and lifetime
use of psychedelics to positively predicts liberal political
views, openness, and nature relatedness, while negatively
predicting authoritarian political views (Nour, Evans, &
Carhart-Harris, 2017).
Psychedelic usage may help facilitate creative pursuits
(Sessa, 2008) and both artists and scientists have reported
valuable insights as a result of psychedelic experiences
(Narby, 2002;Sessa, 2008). One study using mescaline
with scientists and engineers working on creative problems
found that the engineers reported an enduring positive
impact on their creative process (Harman, McKim, &
Mogar, 1966). One study reported that lifetime use of
classical psychedelics (but not that of other substances
examined) was found to predict pro-environmental behavior
through an increase in nature relatedness, or connectedness,
which can be viewed as one’s self identification with nature
(Forstmann & Sagioglou, 2017).
There is a substantial body of literature reporting a
positive correlation between nature relatedness and a broad
range of measures of psychological well-being. Nature
relatedness has been found to correlate with lower levels
of anxiety (Capaldi, Dopko, & Zelenksi, 2014;Martyn &
Brymer, 2016); greater happiness and positive affect
(Capaldi et al., 2014;Nisbet, Zelenksi, & Murphy, 2011;
Pritchard, Richardson, Sheffield, & McEwan 2019;Zelenski
& Nisbet, 2014); life meaning and vitality (Cervinka,
Röderer, & Hefler, 2012), and improved psychological
well-being at the state and trait level (Capaldi et al.,
2014;Capaldi, Passmore, Nisbet, Zelenksi, & Dopko,
2015;Cervinka et al., 2012;Dean et al., 2018;Howell,
Dopko, Passmore, & Buro, 2011;Kamitsis & Francis, 2013;
Mayer & Frantz, 2004;Mayer, Frantz, Bruehlman-Senecal,
& Dolliver 2008;Nisbet & Zelenski, 2014;Van Gordon,
Shonin, & Richardson, 2018;Zelenski & Nisbet, 2014).
Nature relatedness has also been found to mediate the effect
of nature exposure or immersion on affect, with more
positive outcomes of nature exposure observed in those
who rate high in nature relatedness (McMahan, Estes,
Murfin, & Bryan, 2018) while also acting as a mediator of
the perceived restorativeness of natural settings (Berto,
Barbiero, Barbiero, & Senes, 2018). Measures of well-being
were also found to be partially mediated by degree of nature
relatedness in response to perceiving natural beauty (Zhang,
Howell, & Iyer, 2014), and nature relatedness may also elicit
higher valuating of intrinsic aspirations following exposure
to nature (Weinstein, Przybylski, & Ryan, 2009).
Nature relatedness has also been found to strongly
predict pro-environmental awareness (Dutcher, Finley,
Lulogg, & Johnson, 2007;Mackay & Schmitt, 2019;Mayer
& Frantz, 2004;Restall & Conrad, 2015;Whitburn,
Linklater, & Abrahamse, 2019) being perhaps the single
strongest psychological predictor of pro-environmental
behavior (Otto & Pensini, 2017). This is an important
finding given that it is widely considered we are experienc-
ing the sixth mass extinction of life on this planet due to
human actions on the biosphere (Barnosky et al., 2011;
Ceballos, Ehrlich, & Dirzo 2017;Dirzo et al., 2014;
McCallum, 2015). Pro-environmental behavior appears
strongly linked to prosocial behavior, sharing a mutually
enhancing relationship, with an increase in one fostering an
increase in the other (Neaman, Otto, & Vinokur, 2018).
Psilocybin has been found to result in increases in nature
relatedness in patients with treatment-resistant depression
up to 7–12 months post-experience (Lyons & Carhart-
Harris, 2018). A study pooling data from eight different
trials administering psilocybin to healthy volunteers found
that 38% of people reported enduring positive changes in
their relations to nature and the environment (Studerus,
Kometer, Hasler, & Vollenweider, 2011)8–16 months
post-experience. This occurred in spite of the clinical,
nature-deprived settings the trials were conducted in, which
included a PET scanner, suggesting that such enduring
changes to one’s relationship with nature are not entirely
dependent on the setting in which the experience occurs. In a
classic study known as “The Good Friday Experiment,”
high-dose psilocybin was administered to divinity students,
with the majority reporting a complete mystical experience
(Pahnke, 1963). A follow-up interview survey conducted
between 24 and 27 years after the original study revealed
that study participants felt strongly that they had continued
to benefit from their experience, reporting a deepened
appreciation of life and nature, as well as enhanced joy, a
deepened sense of spirituality, and appreciation for unusual
experiences and emotions (Doblin, 1991). Numerous mod-
ern research studies in both healthy (Griffiths et al., 2011;
Griffiths, Richards, McCann, & Jesse, 2006;MacLean,
Johnson, & Griffiths, 2011) and patient (Carhart-Harris
et al., 2018;Garcia-Romeu, Griffiths, & Johnson, 2016;
Griffiths et al., 2016;Ross et al., 2016) populations have
found that the occurrence of a mystical-type experience
during a psychedelic session is a key mediator of long-term
therapeutic gains and benefits post-session. Psychedelic
usage has been implicated to evoke experiences of “God”
or “Ultimate Reality,”with a study on psychedelic users and
people who have had such experiences while sober report-
ing that two thirds of both groups stated they no longer
identified as atheists following their experience. Such
experiences were associated with long-term increases in
life satisfaction, purpose and meaning, and a decreased fear
of death (Griffiths, Hurwitz, Davis, Johnson, & Jesse, 2019).
The experience of ego dissolution, which can occur to
people under high dosages of psychedelics, appears to be
Journal of Psychedelic Studies 3(3), pp. 280–287 (2019) |281
Psychedelics and potential benefits in “healthy normals”

tied to the experience of awe, which may be a mediator of
their beneficial effect (Hendricks, 2018), with the experi-
ence of awe being linked to both enhanced well-being
(Rudd, Vohs, & Aaker, 2012) and prosociality (Piff, Dietze,
Feinberg, Stancato, & Keltner, 2015), two aftereffects com-
monly noted following psychedelic experiences, and par-
ticularly the mystical-type experiences they can occasion
(Griffiths et al., 2006,2011,2018;Hendricks, 2018).
PSILOCYBIN
The psychedelic research renaissance was largely reignited
by the publication of Roland Griffiths and the Johns
Hopkins team’s seminal paper on psilocybin and mystical
experiences in 2006. The study participants were well-
educated, healthy people with an interest in spiritual or
religious practices. The study used a rigorous double-blind
design and used community observer ratings to gain a more
objective measure of post-psilocybin changes. At 2 months
after the session, 67% of study participants rated the high-
dose psilocybin experience to be either the single most
meaningful experience of their lives, or among the top five
most meaningful experiences, with 33% of people rating it
as the single most spiritually significant event of their lives
(Griffiths et al., 2006). In another study conducted on
healthy, psychedelic-naive subjects by the Johns Hopkins
team, high-dose psilocybin sessions evoked mystical-type
experiences in 72% of volunteers and resulted in sustained
positive changes in attitudes, mood, and behavior, with
ascending dosage correlated with greater positive effects.
At 14 months after dosing, ratings were undiminished and
were consistent with changes rated by community obser-
vers, with 94% of study volunteers stating that their well-
being or life satisfaction had been increased moderately or
very much by their psilocybin experiences, with 89%
reporting moderate or higher changes in positive behavior.
Persistent positive changes in attitude, mood, and life
satisfaction catalyzed by psilocybin-induced mystical
experiences appear similar to those following spontaneous
mystical experiences (Griffiths et al., 2011).
The mystical-type experiences associated with psilocy-
bin have also been implicated with leading to long-term
increases in personality trait openness, and at 14 months
following dosing in the aforementioned study participant
group, openness remains significantly elevated (MacLean
et al., 2011). This is significant, as openness was believed to
be fixed by the age of 30 years and to decline with age.
Openness is correlated with a number of cognitive abilities,
and appreciation for new experiences and aesthetics,
creativity, imagination, hunger for knowledge, broad-
minded tolerance of the viewpoints, and values of others
(MacLean et al., 2011) and increased cognitive reserve in
the older people (Franchow, Suchy, Thorgusen, & Williams,
2013). In addition, it correlates with nature connection
and pro-environmental behavior (Lee, Ashton, Choi, &
Zachariassen, 2015;Richardson & Sheffield, 2015;Tam,
2013). A recent double-blind study with healthy participants
explored the effect of a number of meditation or spiritual
practices in combination with psilocybin sessions (Griffiths
et al., 2018). Participants embarked upon a given spiritual
practice 1–2 months prior to their psilocybin (or placebo)
sessions. High-dose psilocybin was found to produce great-
er persisting effects, and at 6-months follow-up of dosing,
high-dose groups showed significant large positive changes
in prosocial attitudes and behaviors and healthy psycholog-
ical functioning, including in measures of interpersonal
closeness, gratitude, life meaning/purpose, forgiveness,
death transcendence, daily spiritual experiences, and reli-
gious faith and coping, with changes validated further by
external community observer ratings. Determinants of
enduring positive effects were the psilocybin-occasioned
mystical-type experience and rates of meditation/spiritual
practices. Other research has found a synergy between
psilocybin and meditation practice, with psilocybin
increasing meditation depth, incidence of positive
experienced ego-dissolution and enhancing mindfulness
and psychosocial functioning (Smigielski, Kometer, et al.,
2019), extent of ego dissolution and brain connectivity
predicting positive changes in psycho-social functioning
of participants 4 months post-session (Smigielski,
Scheiddegger, Kometer, & Vollenweider, 2019). Previous
research suggests that psychedelics can help foster psy-
chological growth when used in the context of an ongoing
discipline (Walsh, 1982).
LSD
A study on healthy people who had complained of a lack of
purpose or meaning in their lives found that a supervised
LSD session resulted in higher self-reported measures of
self-actualization and creativity, with participants reporting
a greater sense of meaning and purpose in their lives,
oneness with humanity, decreased valuation of superficial
pursuits such as material gains and social status, and an
increase in confidence and assertiveness, with many of these
changes still apparent months later (Savage, Fadiman, &
Mogar, 1966).
Modern research has found that an LSD experience in a
controlled setting can result in elevated levels of optimism
and trait openness 2 weeks post-experience (Carhart-Harris
et al., 2016). The administration of a single large (200 μg)
dose of LSD in a supportive setting to 16 healthy partici-
pants was found to lead to increases in positive attitudes
about life and/or self, positive mood changes, altruistic/
positive social effects, positive behavioral changes, and
well-being/life satisfaction at 1 and 12 months following
dosing, with no negative effects on attitudes or behavior
attributed to the LSD experience. After 12 months, 10 of 14
participants rated their LSD experience as among the top 10
most meaningful experiences of their lives, with five rating
the experience as among the most meaningful
experiences of their lives (Schmid & Liechti, 2018).
AYAHUASCA
Ayahuasca use in a ritual setting is considered safe and may
confer benefits (Barbosa, Mizumoto, Bogenschutz, &
Strassman 2012), with lower rates of alcoholism and addic-
tion observed among ritualistic users (Fábregas et al., 2010).
282 |Journal of Psychedelic Studies 3(3), pp. 280–287 (2019)
Gandy

Its use has been associated with long-term beneficial
changes such as lower ratings on all psychopathology
measures, with higher ratings of life purpose, well-being,
and prosocial behavior as compared to non-ayahuasca-
using controls (Bouso et al., 2012). Additional research has
found long-term ayahuasca use to be associated with higher
positive perception of health and healthy life style, and
reduced intake of prescription drugs (Ona et al., 2019).
Ayahuasca usage has also been found to increase measures
of “acceptance”(associated with a more detached and less
judgmental stance toward potentially distressing thoughts
and emotions) as effectively as an 8-week mindfulness
course, a more lengthy and costly intervention (Soler
et al., 2016). Ayahuasca usage has been linked to reductions
in stress and improvements in convergent thinking 4 weeks
post experience (Uthuag et al., 2019). Repeated ingestion of
ayahuasca in a ritual setting has been found to increase
visual creativity (Frecska, M´oré, & Vargha, 2012). Ayahua-
sca users have been found to rate more highly in
self-transcendence (Bouso et al., 2012), which has been
found to be a significant positive predictor for nature
relatedness and environmental concern (Dornhoff,
Sothmann, Fiebelkorn, & Menzel, 2019).
Anthropologist Jeremy Narby accompanied three molec-
ular biologists to the Amazon rainforest where they partook
of an ayahuasca ceremony. While all three found the
experience to be personally meaningful, two of the three
gained perspectives on their research they considered
valuable following the session (Grant, 2006).
5-MEO-DMT
An online survey study reported that the psychedelic
compound 5-MeO-DMT was commonly used infrequently
and primarily for spiritual exploration, and was well-
tolerated with very few problems associated with usage
(Davis, Barsuglia, Lancelotta, Grant, & Renn, 2018). The
use of 5-MeO-DMT (in the form of vaped Incilius alvarius
toad secretion) in a naturalistic setting has been implicated
in unintended but substantial reductions in measures of
depression (80%) and anxiety (79%). Its usage in naturalis-
tic settings has also been implicated in increasing measures
of well-being and mindfulness long term (with the latter
measure gaining statistical significance a month after dos-
ing), with long-term benefits correlating with a greater
intensity of mystical experiences and higher ratings of
spiritual significance and personal meaning (Davis, So,
Lancelotta, Barsuglia, & Griffiths, 2019). A single inhala-
tion of 5-MeO-DMT (again in the form of vaped I. alvarius
toad secretion) resulted in a significant increase in ratings of
life satisfaction and convergent thinking immediately after
intake, and was sustained at follow-up 4 weeks later.
Ratings of mindfulness increased over time and attained
statistical significance at 4 weeks. Ratings of depression,
anxiety, and stress decreased after the sessions and reached
significance at 4 weeks. High levels of ego dissolution and
oceanic boundlessness during the experience were correlat-
ed with higher ratings for life satisfaction and lower ratings
of depression and stress (Uthaug et al., 2019). The short
lasting effects of 5-MeO-DMT and its consistency in
inducing mystical-type experiences, which have been im-
plicated in long-term benefits and therapeutic gains, are
notable (Barsuglia et al., 2018).
PSYCHEDELIC MICRODOSING
Research on psychedelic microdosing is still in its prelimi-
nary stages, but studies conducted to date warrant further
research. Surveys of psychedelic microdosers have yielded
reported benefits of improved mood, cognition, and creativ-
ity, which in some cases help counteract symptoms of
depression and anxiety, although various challenges were
also associated with the practice (Anderson, Petranker,
Christopher, et al., 2019;Johnstad, 2018). One observation-
al study found that microdosing was associated with a
general increase in reported psychological functioning on
dosing days, but little evidence of residual effects on
following days. Analyses of pre- and post-study measures
showed reduced levels of depression and stress, lower levels
of distractibility, increased absorption, and increased neu-
roticism. Effects that were believed likely to manifest were
also unrelated to the observed patterns of reported effects
(Polito & Stevenson, 2019). In an additional observational
study, former and current microdosers scored lower on
measures of dysfunctional attitudes and negative emotion-
ality and higher on measures of wisdom, open-mindedness,
and creativity compared to non-microdosing controls
(Anderson, Petranker, Rosenbaum, et al., 2019). Microdos-
ing may lead to improvements in convergent and divergent
thinking, although further research is warranted using rig-
orous placebo-controlled study findings to investigate this
further (Prochazkova et al., 2018).
FUTURE RESEARCH AVENUES
There are a number of interesting studies currently
underway exploring the effects of psychedelics (psilocybin
especially) in healthy people. At present, there is still a lack
of knowledge of the prospective, causative role of psyche-
delics and their effects on cognition, well-being and per-
sonality in healthy psychedelic naive people, particularly
their longer-term effects. Longer-term qualitative assess-
ments and MRI brain scans comparing psychedelic naive
people pre- and post-psychedelic experiences (both short-
term and long-term assessments) would help elucidate the
longer-term effects of psychedelics. At present, despite its
vast importance for individual well-being and in facilitating
pro-environmental awareness, the capacity of psychedelic to
enhance nature relatedness in the long term remains under
explored. Although there are a number of correlative studies
linking psychedelic use to increased nature relatedness,
there is only one small study (n=7) that shows a causative,
prospective role of psychedelics in increasing nature relat-
edness, and further prospective research is warranted to
explore this in greater detail. Such data could be obtained
via online prospective surveys, or via prospective clinical
trials, comparing measures of nature relatedness in psyche-
delic naive people, pre- and post-psychedelic experiences,
including longer-term measures. Due to strict regulations
Journal of Psychedelic Studies 3(3), pp. 280–287 (2019) |283
Psychedelics and potential benefits in “healthy normals”

governing clinical trials of psychedelics at the present time,
psychedelic trials are conducted in clinical nature-deprived
environments. In the future, it will be interesting to investi-
gate the influence of nature-based settings, and how these
may influence measures of nature relatedness and associated
well-being. It would also be interesting to conduct a com-
parative study to see whether ingestion of organic or
synthetic psychedelics influences subsequent measures of
nature relatedness. Further research is warranted to explore
the potential of psychedelics to act as agents of ecotherapy.
Given promising past pioneering research findings on
psychedelics and creativity among scientists and engineers
in the 1960s, modern rigorous research on the potential
effect of psychedelics on creativity and divergent thinking is
warranted. Research on psychedelic microdosing is still in
its preliminary stages, and it would be useful for future
clinical studies to investigate the effects of microdosing on
biological and cognitive parameters to better evaluate po-
tential beneficial and negative effects, and assess the poten-
tial risks of repeated administrations of psychedelics in low
doses, using rigorous placebo-controlled study designs.
Conflict of interest: The author declares no conflict of interest.
Acknowledgements: The author has no financial assistance
to acknowledge but would like to thank Dr. Rosalind Watts
for the inspiration to write the paper.
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