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Skip the Trip? Five Arguments on the Use of Nonhallucinogenic Psychedelics in Psychiatry

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Andrew Peterson at George Mason University
Andrew Peterson
Dominic A. Sisti at University of Pennsylvania
Dominic A. Sisti
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Abstract

This article examines five arguments on the use of non-hallucinogenic psychedelics in psychiatry. The authors argue that researchers and physicians should continue to use hallucinogenic psychedelics because current data support their therapeutic effect. If equally safe and efficacious non-hallucinogenic psychedelics were developed, these should also be an option offered to appropriate patients.
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COMMENTARY
Skip the Trip? Five Arguments on the Use of
Nonhallucinogenic Psychedelics in Psychiatry
Andrew Peterson
1,2
*and Dominic Sisti
3
1
Institute for Philosophy and Public Policy and Department of Philosophy, George Mason University, Fairfax, Virginia 22030,
USA
2
Penn Program on Precision Medicine for the Brain, University of Pennsylvania Memory Center, Philadelphia, Pennsylvania
19104, USA
3
Department of Medical Ethics and Health Policy, Perelman School of Medicine, University of Pennsylvania, Philadelphia,
Pennsylvania 19104, USA
*Corresponding author. Email: apeter31@gmu.edu
Introduction
Might there someday be psychedelic medicines that do not produce a subjective hallucinogenic
experience but still provide safe and effective treatment to people with mental illness? If so, which
modality would be preferable: nonsubjective or conventional hallucinogenic psychedelics? Should
hallucinogenic psychedelics be the “default”option, in part, because the subjective experience might
offer additional non-medical (i.e., spiritual or existential) benefits?
These questions capture the ethical challenges of using psychedelics in psychiatry that confer
therapeutic benefits without the hallucinogenic “high.”
1,2
We refer to these substances as “nonhallu-
cinogenic psychedelics.”For some people with mental illness, the hallucinogenic experience could
increase the risk of psychosis, often making them ineligible to participate in psychedelic research.
3
In
healthy individuals, there is also the risk of a disturbing adverse psychological event, or “bad trip.”
4
Nonetheless, according to some theorists, there are good reasons to provide patients with hallucino-
genic psychedelics even if nonhallucinogenic options are available.
We examine five arguments on the use of nonhallucinogenic psychedelics in psychiatry and
hypothesize about ethical trade-offs in a scenario in which the safety and efficacy profiles are equivalent
to traditional psychedelics. The first three arguments, advanced by David Olson, support the substitution
of hallucinogenic psychedelics with nonhallucinogenic alternatives.
5
In contrast, arguments developed
by David Yaden and Roland Griffiths favor the continued use of hallucinogenic psychedelics because
they might confer non-medical benefits.
6,7
We argue that researchers and physicians should continue to use hallucinogenic psychedelics because
current data support their therapeutic effect, not because of potential non-medical benefits. If equally
safe and efficacious nonhallucinogenic psychedelics were developed, these should also be an option
offered to appropriate patients.
Eliminating “Bad Trips”
The key presumption in support of using nonhallucinogenic psychedelics is that the hallucinogenic
experience plays little to no direct role in the therapeutic effect. Instead, in a small number of cases, the
experience might cause psychological distress. The possibility of adverse psychological events can be
mitigated by removing the hallucinogenic experience. Hence, the argument goes, nonhallucinogenic
psychedelics should replace hallucinogenic psychedelics, since they offer the same therapeutic benefit
with little to no safety risk.
8
If someday the evidence became clear that the hallucinogenic experience is unnecessary to therapeutic
effect, we would agree that researchers and physicians should consider nonhallucinogenic psychedelics
© The Author(s), 2022. Published by Cambridge University Press.
Cambridge Quarterly of Healthcare Ethics (2022), 31: 4, 472–476
doi:10.1017/S0963180122000081
https://doi.org/10.1017/S0963180122000081 Published online by Cambridge University Press
as a viable treatment option. However, the present evidence does not support this conclusion. Data from
psychedelic trials overwhelmingly suggest that the hallucinogenic experience is integral to the reduction
of psychiatric symptoms.
9,10,11,12
Subperceptual doses, or “micro-dosing,”of hallucinogenic psyche-
delics with or without guided psychotherapy appear to produce little to no similar effect.
13
Whether the
hallucinogenic experience is causally related or epiphenomenal to neurobiological changes, such as
neuroplasticity, is presently unknown. It is therefore premature to use nonhallucinogenic psychedelics as
therapeutic options in research and treatment.
Inclusion of Vulnerable Persons
The second argument on the use of nonhallucinogenic psychedelics is that the hallucinogenic
experience could harm persons with serious mental illness who might otherwise benefit from psyche-
delic therapy.
14
In most psychedelic trials, individuals with a history of serious mental illness and
suicidal ideation or behavior are excluded from participation.
15
The concern is that the hallucinogenic
experience could trigger a decompensatory, psychotic, or suicidal episode. This is a common worry in
clinical psychiatry research, which often unnecessarily leads to participant exclusion.
16
Still, persons
with serious mental illness might derive the most benefit from psychedelic research and eventual
psychedelic-assisted therapy. Anything researchers can do to minimize risk and broaden inclusion
should be a priority.
As a matter of justice, promoting inclusion in research and treatment is praiseworthy. Moreover, the
inclusion of clinically diverse populations improves the science. Illness-specific dosing regimens, for
instance, might be developed, which offer an ideal benefit-to-risk profile. Nevertheless, it is far from clear
whether nonhallucinogenic psychedelics are therapeutically equivalent to conventional psychedelics.
Although maximizing participant inclusion and safety are strong reasons in favor of using nonhallu-
cinogenic psychedelics, this argument fails for the same reason as the first: it is currently unsupported by
the evidence.
Cost Savings
The third argument in favor of nonhallucinogenic psychedelics is that they would substantially reduce
treatment costs.
17
Current models of psychedelic-aided psychotherapy involve a psychotherapist or
other trained counselor to guide patients through the experience and manage distress. If the hallucino-
genic experience is unnecessary and eliminated, then, it is argued, there is no need for time-intensive
clinical supervision or integration sessions. Health systems and patients could save money, time, and
other resources. Patients might also safely self-administer treatments at home, perhaps at bedtime to
receive therapeutic benefits as they sleep.
Current evidence, again, does not support this argument. Moreover, the proposal ignores the critically
important roles of psychotherapy and the therapeutic milieu in bringing about a therapeutic effect.
18
We
find instances in the popular press and scientific literature of an overly reductive account of mental
health, leading to a narrow focus on the interaction of psychedelic chemical properties and brain
function. But this framing overlooks the important—and likely essential—role of psychotherapy in
conferring a clinical benefit.
The hallucinogenic experience, as well as psychotherapy and setting, form a potent therapeutic
ensemble that brings about therapeutic change. The use of SSRIs and psychotherapy is an analogy. In
other contexts, psychotherapy is an important complement to medication. Combination therapy with
psychotherapy and an SSRI provides benefits beyond what either intervention offers alone.
We also know that psychotherapy is already undervalued—insurers do not cover psychotherapy and
there is a dearth of well-trained psychotherapists across the United States. The decades-long reductionist
turn in psychiatry has deprioritized research into psychotherapy in favor of neurological and pharma-
cological interventions. Altering neurochemistry is surely critical to relieving debilitating symptoms, but
it is also important to provide patients the phenomenological tools to process, frame, and attribute
Five Arguments on the Use of Nonhallucinogenic Psychedelics in Psychiatry 473
https://doi.org/10.1017/S0963180122000081 Published online by Cambridge University Press
meaning to their emotions. Psychotherapy should therefore be regarded as integral to psychedelic
medicine, and efforts to devalue it should be met with skepticism.
Non-Medical Benefits
The above-reviewed arguments offer reasons in favor of replacing hallucinogenic psychedelics with
nonhallucinogenic alternatives. These arguments are valid but not sound since the key premise about
therapeutic equivalence is currently unsupported by evidence–indeed the opposite premise is likely true.
Additionally, one might be suspicious about the underlying motivation. Mitigating harm, promoting
inclusion, and stewarding resources are all noble efforts on their face. Yet, it is plausible that these reasons
are mere window dressing for less virtuous agendas. Eliminating the “high”would make psychedelics
morally acceptable among those who negatively stereotype drug culture and addiction. Manufacturing
novel compounds would allow drug companies to profit from substances that have long been used in
indigenous communities. We have charitably interpreted these arguments, but one might also reason-
ably reject them as attempts to obfuscate stigma and commodification.
Still, for the sake of discussion, consider that nonhallucinogenic psychedelics will, in the future, confer
the same therapeutic benefit as hallucinogenic psychedelics. Might there be ethical reasons for physicians
to continue using hallucinogenic psychedelics for some patients?
The fourth argument, as described by Yaden and Griffiths, is that physicians have a positive obligation
to use hallucinogenic psychedelics as the “default”option, since the hallucinogenic experience itself could
confer non-medical benefits, such as meaningful or transformative experiences.
19
This positive obligation
hinges on physicians’duties to promote health, rather than narrowly preventing disease and death.
We disagree with this view. Physicians do indeed have positive obligations to promote patient health,
but those obligations do not require them to provide non-medically relevant experiences on the grounds
that they could be meaningful or existentially transformative.
Medicine is not in the business of self-transformation. This is the purview of the arts, scholarly
pursuits, world travel, or spiritual practices, where participants play an active role in meaning making.
Psychedelics, due in part to their cultural history and psychoactive properties, have an “uncanny alure”
among those seeking relief from any number of maladies.
20
Without temper, this can devolve into
unbridled enthusiasm in their transformative potential.
Research in psychedelic medicine should be guided by evidence about safety and efficacy, not
speculation about non-medical benefits. Identifying hallucinogenic psychedelics as a “default”option
based on extra-medical values is inappropriate.
Autonomy
A final argument suggests that, if nonhallucinogenic and hallucinogenic psychedelics confer the same
therapeutic benefit, then a patient should be allowed to choose between the two.
21
This argument turns
on the principle of autonomy, according to which the self-determination of competent patients ought to
be protected, enhanced, and respected. If, after consideration of risks and benefits, a patient decides she
wants to have a clinically supervised hallucinogenic experience, then physicians should provide her the
resources to participate in this therapy safely. In high-risk patients, a short-term safety plan should be in
place and long-term follow-up plans should be established.
This is a strong argument in favor of the continued use of hallucinogenic psychedelics, as it places
patient values at the center of the decision-making process. Consider an analogy: when patients are
diagnosed with a cancerous tumor, they might have the option of chemotherapy, surgery, or both. Each
treatment option confers the same therapeutic benefit for some tumors; each can forestall the spread of
cancer and preserve the same amount of quality life years. Still, for personal values, some patients might
prefer chemotherapy over surgery, or vice-versa. Surgery can involve general anesthetic, acute discom-
fort, and potential scarring or disfigurement. In contrast, chemotherapy might last several months and
results in nausea, weight loss, and hair loss.
474 Andrew Peterson and Dominic Sisti
https://doi.org/10.1017/S0963180122000081 Published online by Cambridge University Press
Trade-offs in benefits and risks of therapeutically equivalent treatments are common in medicine. A
patient’s values balance these trade-offs, often in concert with a physician’s counsel. If nonhallucinogenic
and hallucinogenic psychedelics were shown to confer the same benefit, and physicians have the option
of offering both, then a patient should be helped to choose the better option. This respects patient self-
determination, while also providing a clinically supervised environment to protect well-being.
Conclusion
Arguments favoring nonhallucinogenic psychedelics hinge on the assumption that they are therapeu-
tically equivalent to hallucinogenic psychedelics. Current data do not support this assumption, and so
conventional psychedelics should still be used in psychiatry research and treatment.
Still, even if nonhallucinogenic psychedelics were to be found to confer equivalent benefits, several
considerations might favor the continued use of hallucinogenic psychedelics. Although there is no
positive obligation to use them as a “default option,”physicians might appropriately offer patients the
choice between hallucinogenic and nonhallucinogenic psychedelics. Moreover, as psychedelic medicine
evolves, we may find that nonhallucinogenic psychedelics are ideal for certain clinical contexts, for
particular patients, or indications, while hallucinogenic compounds are appropriate for others.
Funding. A.P. is funded by R21AG069805 and the Greenwall Faculty Scholars Program. The content of this article does not
necessarily represent the official views of the NIH or private foundations. The funders played no role in the preparation, review,
approval, or decision to submit this manuscript for publication.
Conflict of Interest. D.S. reports paid consultation for Compass Pathways. A.P. has no conflict of interest to disclose.
Notes
1. DARPA. Structure-guided drug design could yield fast-acting remedies for complex neuropsychi-
atric conditions. DARPA 2011 Sept; available at https://www.darpa.mil/news-events/2019-09-11
(last accessed 17 Feb 2022).
2. Shayla L. Can a trip-free psychedelic still help people with depression? Vice Magazine 2019 Nov;
available at https://www.vice.com/en/article/pa748k/psilocybin-for-depression-and-the-world-of-
non-hallucinogenic-psychedelics (last accessed 17 Feb 2022).
3. Johnson MW, Richards WA, Griffiths RR. Human hallucinogen research: Guidelines for safety.
Journal of Psychopharmacology 2008;22(6):603–20.
4. Carbonaro TM, Bradstreet MP, Barrett FS, MacLean KA, Jesse R, Johnson MW, et al. Survey study of
challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and
negative consequences. Journal of Psychopharmacology 2016;30(12):1268–78.
5. Olson DE. The subjective effects of psychedelics may not be necessary for their enduring therapeutic
effects. ACS Pharmacology & Translational Science 2020;4(2):563–7.
6. Yaden DB, Griffiths RR. Ethical issues regarding non-subjective psychedelics as standard of care.
Cambridge Quarterly of Healthcare Ethics 2022; 31(4):464–71.
7. Yaden DB, Griffiths RR. The subjective effects of psychedelics are necessary for their enduring
therapeutic effects. ACS Pharmacology & Translational Science 2020;4(2):568–72.
8. See note 5, Olson 2020.
9. Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, et al. Rapid and sustained symptom
reduction following psilocybin treatment for anxiety and depression in patients with life-threatening
cancer: A randomized controlled trial. Journal of Psychopharmacology 2016;30(12):1165–80.
10. Carhart-Harris RL, Bolstridge M, Day CM, Rucker J, Watts R, Erritzoe DE, et al. Psilocybin with
psychological support for treatment-resistant depression: Six-month follow-up. Psychopharmacol-
ogy 2018;235(2):399–408.
Five Arguments on the Use of Nonhallucinogenic Psychedelics in Psychiatry 475
https://doi.org/10.1017/S0963180122000081 Published online by Cambridge University Press
11. Carhart-Harris R, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Murphy R, et al. Trial
of psilocybin versus escitalopram for depression. New England Journal of Medicine 2021;384
(15):1402–11.
12. Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa PC, Strassman RJ. Psilocybin-
assisted treatment for alcohol dependence: A proof-of-concept study. Journal of Psychopharmacol-
ogy 2015;29(3):289–99.
13. Marschall J, Fejer G, Lempe P, Prochazkova L, Kuchar M, Hajkova K, van Elk M. Psilocybin
microdosing does not affect emotion-related symptoms and processing: A preregistered field and
lab-based study. Journal of Psychopharmacology 2022;36(1):97–113.
14. See note 5, Olson 2020.
15. See note 3, Johnson et al. 2008.
16. Iltis AS, Misra S, Dunn LB, Brown GK, Campbell A, Earll SA, et al. Addressing risks to advance
mental health research. JAMA 2013;70(12):1363–71.
17. See note 5, Olson. 2020.
18. Golden TL, Magsamen S, Sandu CC, Lin S, Roebuck GM, Shi KM, Barrett FS. Effects of setting on
psychedelic experiences, therapies, and outcomes: A rapid scoping review of the literature.
In: Current Topics in Behavioral Neurosciences. Berlin, Heidelberg: Springer; 2022. doi:10.1007/
7854_2021_298. Published online ahead of print 10 Feb 2020.
19. See note 6, Yaden DB, Griffiths RR. 2022.
20. Anderson BT, Danforth A, Grob C. Psychedelic medicine: Safety and ethical concerns. Lancet
Psychiatry 2020;7(10):829–30.
21. See note 6, Yaden DB, Griffiths RR. 2022.
Cite this article: Peterson A and Sisti D (2022). Skip the Trip? Five Arguments on the Use of Nonhallucinogenic Psychedelics in
Psychiatry. Cambridge Quarterly of Healthcare Ethics 31: 472–476, doi:10.1017/S0963180122000081
476 Andrew Peterson and Dominic Sisti
https://doi.org/10.1017/S0963180122000081 Published online by Cambridge University Press
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Full-text available
  • Feb 2022
The health and well-being impacts of art and aesthetic experiences have been rigorously studied by a range of disciplines, including cognitive neuroscience, psychiatry, public health, and translational clinical research. These experiences, encompassed in the concepts of set and setting, have long been claimed to be pivotal in determining the acute and enduring effects of psychedelic experiences. Responding to the field’s longstanding emphasis on the role and value of setting, a rapid scoping review was undertaken to identify the extent to which effects of setting and aesthetics on psychedelic experiences and therapies have been explicitly studied. It offers an analysis of the strengths and limitations of the extant literature and discusses evidentiary gaps as well as evidentiary opportunities for the field. The 43 included studies indicate apparent consensus regarding the importance of setting in psychedelic therapies, as well as consistent interest in theorizing about these effects. However, this consensus has yet to generate consistent, prospective, rigorous tests of setting and its complexities. As a result, the field continues to lack understanding or agreement regarding the effects of various specific elements of setting, the mechanisms by which they affect outcomes, for whom these effects occur, under what circumstances, given what conditions, and other critical factors. Further studies of setting and aesthetics in the context of psychedelic therapies are likely to not only improve these therapies and their delivery, but also inform considerations of setting and aesthetics for non-psychedelic interventions.
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Psilocybin microdosing does not affect emotion-related symptoms and processing: A preregistered field and lab-based study
Article
Full-text available
  • Dec 2021
  • J PSYCHOPHARMACOL
Background Microdoses of psychedelics (i.e. a sub-hallucinogenic dose taken every third day) can reduce symptoms of depression, anxiety and stress according to anecdotal reports and observational studies. Research with medium to high doses of psilocybin points towards potential underlying mechanisms, including the modulation of emotion and interoceptive processing. Aims In this preregistered study, we investigated whether psilocybin microdoses alter self-reported interoceptive awareness and whether repeated microdosing over 3 weeks modulates emotion processing and reduces symptoms of anxiety and depression. Methods We used a double-blind, placebo-controlled, within-subject crossover design. Participants completed the Multidimensional Assessment of Interoceptive Awareness Questionnaire 1½ h after self-administering their second dose (or placebo), and the emotional go/no-go task and the shortened Depression Anxiety Stress Scale 1½ h after self-administering their seventh dose. Results Our confirmatory analyses revealed that psilocybin microdosing did not affect emotion processing or symptoms of anxiety and depression compared with placebo. Our exploratory analyses revealed that psilocybin microdosing did not affect self-reported interoceptive awareness, that symptoms of depression and stress were significantly reduced in the first block compared with baseline, that participants broke blind in the second block and that there was no effect of expectations. Further research in a substance-naïve population with clinical range anxiety and depressive symptoms is needed to substantiate the potential beneficial effects of microdosing.
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The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects
Article
Full-text available
  • Dec 2020
Classic psychedelics produce altered states of consciousness that individuals often interpret as meaningful experiences. Across a number of human studies, when the participant-rated intensity of the overall drug effects are statistically controlled for, certain subjective effects predict therapeutic and other desirable outcomes. Underlying neurobiological mechanisms are likely necessary but not sufficient to confer full and enduring beneficial effects. We propose that the subjective effects of psychedelics are necessary for their enduring beneficial effects and that these subjective effects account for the majority of their benefit.
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Psychedelic medicine: safety and ethical concerns
Article
Full-text available
  • Oct 2020
https://escholarship.org/uc/item/6jh50435
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Psilocybin with psychological support for treatment-resistant depression: six-month follow-up
Article
Full-text available
  • Feb 2018
  • PSYCHOPHARMACOLOGY
Rationale: Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy. Objectives: Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression. Methods: Twenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure. Results: Treatment was generally well tolerated. Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen's d = 2.2 at week 1 and 2.3 at week 5, both p < 0.001); nine and four patients met the criteria for response and remission at week 5. Results remained positive at 3 and 6 months (Cohen's d = 1.5 and 1.4, respectively, both p < 0.001). No patients sought conventional antidepressant treatment within 5 weeks of psilocybin. Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience. Conclusions: Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort. Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomised control trials.
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Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: A randomized controlled trial
Article
Full-text available
  • Dec 2016
  • J PSYCHOPHARMACOL
Background: Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. Methods: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks. Results: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60-80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. Conclusions: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress. Trial registration: ClinicalTrials.gov Identifier: NCT00957359.
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Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences
Article
Full-text available
  • Aug 2016
  • J PSYCHOPHARMACOL
Acute and enduring adverse effects of psilocybin have been reported anecdotally, but have not been well characterized. For this study, 1993 individuals (mean age 30 yrs; 78% male) completed an online survey about their single most psychologically difficult or challenging experience (worst “bad trip”) after consuming psilocybin mushrooms. Thirty-nine percent rated it among the top five most challenging experiences of his/her lifetime. Eleven percent put self or others at risk of physical harm; factors increasing the likelihood of risk included estimated dose, duration and difficulty of the experience, and absence of physical comfort and social support. Of the respondents, 2.6% behaved in a physically aggressive or violent manner and 2.7% received medical help. Of those whose experience occurred >1 year before, 7.6% sought treatment for enduring psychological symptoms. Three cases appeared associated with onset of enduring psychotic symptoms and three cases with attempted suicide. Multiple regression analysis showed degree of difficulty was positively associated, and duration was negatively associated, with enduring increases in well-being. Difficulty of experience was positively associated with dose. Despite difficulties, 84% endorsed benefiting from the experience. The incidence of risky behavior or enduring psychological distress is extremely low when psilocybin is given in laboratory studies to screened, prepared, and supported participants.
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Trial of Psilocybin versus Escitalopram for Depression
Article
  • Apr 2021
Background Psilocybin may have antidepressant properties, but direct comparisons between psilocybin and established treatments for depression are lacking. Methods In a phase 2, double-blind, randomized, controlled trial involving patients with long-standing, moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, a selective serotonin-reuptake inhibitor, over a 6-week period. Patients were assigned in a 1:1 ratio to receive two separate doses of 25 mg of psilocybin 3 weeks apart plus 6 weeks of daily placebo (psilocybin group) or two separate doses of 1 mg of psilocybin 3 weeks apart plus 6 weeks of daily oral escitalopram (escitalopram group); all the patients received psychological support. The primary outcome was the change from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16; scores range from 0 to 27, with higher scores indicating greater depression) at week 6. There were 16 secondary outcomes, including QIDS-SR-16 response (defined as a reduction in score of >50%) and QIDS-SR-16 remission (defined as a score of ≤5) at week 6. Results A total of 59 patients were enrolled; 30 were assigned to the psilocybin group and 29 to the escitalopram group. The mean scores on the QIDS-SR-16 at baseline were 14.5 in the psilocybin group and 16.4 in the escitalopram group. The mean (±SE) changes in the scores from baseline to week 6 were −8.0±1.0 points in the psilocybin group and −6.0±1.0 in the escitalopram group, for a between-group difference of 2.0 points (95% confidence interval [CI], −5.0 to 0.9) (P=0.17). A QIDS-SR-16 response occurred in 70% of the patients in the psilocybin group and in 48% of those in the escitalopram group, for a between-group difference of 22 percentage points (95% CI, −3 to 48); QIDS-SR-16 remission occurred in 57% and 28%, respectively, for a between-group difference of 28 percentage points (95% CI, 2 to 54). Other secondary outcomes generally favored psilocybin over escitalopram, but the analyses were not corrected for multiple comparisons. The incidence of adverse events was similar in the trial groups. Conclusions On the basis of the change in depression scores on the QIDS-SR-16 at week 6, this trial did not show a significant difference in antidepressant effects between psilocybin and escitalopram in a selected group of patients. Secondary outcomes generally favored psilocybin over escitalopram, but the analyses of these outcomes lacked correction for multiple comparisons. Larger and longer trials are required to compare psilocybin with established antidepressants. (Funded by the Alexander Mosley Charitable Trust and Imperial College London’s Centre for Psychedelic Research; ClinicalTrials.gov number, NCT03429075.) VISUAL ABSTRACT Psilocybin versus Escitalopram for Depression
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The Subjective Effects of Psychedelics May Not Be Necessary for Their Enduring Therapeutic Effects
Article
  • Dec 2020
Psychedelics represent one of the most promising classes of experimental medicines for the treatment of neuropsychiatric disorders due to their ability to promote neural plasticity and produce both rapid and sustained therapeutic effects following a single administration. Conventional wisdom holds that peak mystical experiences induced by psychedelics are a critical component of their therapeutic mechanisms of action, though evidence supporting that claim is largely correlational. Here, I present data suggesting that the subjective effects induced by psychedelics may not be necessary to produce long-lasting changes in mood and behavior. Understanding the role of subjective effects in the therapeutic mechanisms of psychedelics will have important implications for both basic neuroscience and for increasing patient access to the next generation of medicines developed as a result of psychedelic research.
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