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Preparing for the Bursting of the Psychedelic Hype Bubble

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David Bryce Yaden at Johns Hopkins Medicine
David Bryce Yaden
James B. Potash
James B. Potash
James B. Potash
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Roland R Griffiths at Johns Hopkins Medicine
Roland R Griffiths
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Abstract

This Viewpoint presents impediments to the clinical application of psychedelics created by extreme shifts in public perception while advocating further study and encouraging the dispute of claims not supported by available evidence.
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Preparing for the Bursting of the Psychedelic Hype Bubble
Psychedelic research currently appears to be trapped
in a hype bubble driven largely by media and industry
interests. We believe that it wouldbenef it the field of psy-
chedelic research if this bubble were to be systemati-
cally deflated by researchers and clinicians using good
science communication practices.
The term bubble is often applied to something of
value that has become overvalued in popular percep-
tion. As a society, weare familiar with the term as it has
been applied to, for example, the internet (the dot-
com bubble of the 1990s) and the value of housing (the
housing bubble of the early 2000s). In terms of psyche-
delics, headlines have turned from presenting alarmist,
extremely negative views of the drugs (approximately
1960s to 2000s) to acknowledging their positive po-
tential (2006 to the present). However, in the past few
years, a disturbingly large number of articles have touted
psychedelics as a cure or miracle drug as well as men-
tioned the investment potential of psychedelics reach-
ing billions of dollars. These extreme shifts in percep-
tion can create impediments to rigorous science and
reasonable clinical applications.
State of the Evidence
The subject of treatments using psychedelics asks of our
society something that is difficult to do well: maintain a
degree of nuance, critical thinking, and grounding in the
scientific evidence. In our social media–influenced cul-
ture, it seems easy to fall into extreme views. However,
when it comes to psychedelics, the scientific data ap-
pear to prove wrong superenthusiasts and super-
skeptics alike.
The superenthusiasts are incorrect in believing that
psychedelics pose no risks because those risks are well
established.
1
Furthermore, the treatment potential of
psychedelics is real but is less impressive than ex-
pected, as shown in a recent trial comparing psilocybin
with a gold-standard treatment of depression.
2
On the
other hand, the skeptics are incorrect in thinking that the
short-term subjective effects of psychedelics consist of
a psychoticlike state of delirium; well-replicated find-
ings have shown these effects to be challenging yet posi-
tive and highly meaningful, with persisting favorableef-
fects for most people.
3,4
Finally, the therapeutic potential
of psychedelics is not merely hypothetical but has been
supported by the results of several clinical trials.
2,5-7
The Hype Cycle
Although the future is unknown, the Gartner Hype Cycle
provides an illustration of what we might reasonably
forecast about public perceptions of psychedelics
(Figure). The cycle begins with a novel and promising
technological trigger that attracts substantial attention—
examples from psychiatry include electroconvulsive
therapy and risk gene identification.
In such cases, the first step is a rapid increase in ex-
treme visibility and expectations. This peak of inflated
expectations can be considered a bubble, and we be-
lieve that psychedelics are currently cresting this peak.
After the peak comes an equally steep decline in which
highly inflated expectations are dashed. Formerly overly
positive press reports may become overly negative. Af-
ter the bottom of the trough, well-calibrated assess-
ments of the state of the evidence may begin to occur.
Finally, the process reaches the plateau of productivity,
which is where we hope the field of psychedelics settles
because it is the social context in which rigorous re-
search and responsible clinical applications flourish most
effectively.
If perceptions of psychedelic science shift accord-
ing to this process, then we are fast approaching a dan-
gerous moment for the research field. The potential for
blowback is real; we saw this shift in the 1960s for psy-
chedelics. Many people forget that there were years of
glowing reviews in the 1950s and 1960s before the press
turned alarmist and a government clampdown pre-
vented research progress for decades.
8
It is also worth remembering that psychedelic treat-
ments present real risks similar to virtually any effec-
tive treatment. These risks increase in recreational set-
tings and include confusional states, abuse potential, and
precipitation of enduring psychiatric conditions, par-
ticularly in persons with preexisting vulnerabilities (eg,
psychotic disorders). Unfortunately, it is a matter of
when, not if,a patient or par ticipant will be harmed, and
we need to do everything possible to prevent such trag-
edies. However, although some people are unfortu-
nately harmed by any number of effective treatments,
the visibility of psychedelic use means that such cases
will be widely reported, often without the context of how
clinical trials contribute to scientific progress.
Ethical Obligation for Science Communications
Regardless of how public perceptions of psychedelics
change, researchers and clinicians have an obligation to
counter extreme statements when they spot them.
Headlines that fall into the category of superenthusiast
(eg, wonder drug) or superskeptic (eg, madness) should
be openly disputed.
Overly hyped claims fall into 2 main categories:
clinical and social. Clinically, psychedelics are not a
cure for mental disorders. We have not found evi-
dence for this claim, and it increases the risk of
inflated patient expectations. Socially, psychedelics
do not solve major issues such as racism and war. Such
claims risk trivializing the complexities of the issues
and resources needed to make real progress. That
said, we need to be on guard for equally extreme
negative claims that are likely just over the horizon.
After all, we have evidence-based reasons to believe
VIEWPOINT
David B. Yaden,PhD
Department of
Psychiatry and
Behavioral Sciences,
Johns Hopkins
University School of
Medicine, Baltimore,
Maryland; and Center
for Psychedelic and
Consciousness
Research, Johns
Hopkins University
School of Medicine,
Baltimore, Maryland.
James B. Potash, MD
Department of
Psychiatry and
Behavioral Sciences,
Johns Hopkins
University School of
Medicine, Baltimore,
Maryland.
Roland R. Griffiths,
PhD
Department of
Psychiatry and
Behavioral Sciences,
Johns Hopkins
University School of
Medicine, Baltimore,
Maryland; and Center
for Psychedelic and
Consciousness
Research, Johns
Hopkins University
School of Medicine,
Baltimore, Maryland.
Corresponding
Author: Roland R.
Griffiths, PhD, Center
for Psychedelic and
Consciousness
Research, Department
of Psychiatry and
Behavioral Sciences,
Johns Hopkins
University School of
Medicine, 5510 Nathan
Shock Dr, Baltimore,
MD 21224 (rgriff@
jhmi.edu).
Opinion
jamapsychiatry.com (Reprinted) JAMA Psychiatry Published online August 31, 2022 E1
© 2022 American Medical Association. All rights reserved.© 2022 American Medical Association. All rights reserved.
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that psychedelics show promise for treating mental disorders,
enhancing well-being, and advancing the study of psychological
and neurobiological processes.
2-7,9,10
Conclusions
Across the field of psychedelic research to date, promising data sug-
gest that further studies are needed. Researchers should pursue
mechanistic studies that may shed light on biological underpin-
nings and psychotherapeutic processes responsible for the thera-
peutic effects of psychedelics. Such studies can help to refine treat-
ment approaches and achieve better target engagement. As
scientists and clinicians, we have an ethical mandate to dispute claims
not supported by available evidence. We encourage our colleagues
to help deflate the psychedelic hype bubble in a measured way so
that we can get on with the hard work of more precisely determin-
ing the risks and benefits of psychedelics.
ARTICLE INFORMATION
Published Online: August 31, 2022.
doi:10.1001/jamapsychiatry.2022.2546
Conflict of Interest Disclosures: Drs Yaden and
Griffiths reported receiving support through the
Johns Hopkins Center for Psychedelic and
Consciousness Research (CPCR) provided by Tim
Ferriss, Matt Mullenweg, Blake Mycoskie, Craig
Nerenberg, and The Steven and Alexandra Cohen
Foundation. Dr Griffiths also reported receiving
grants for research support from the Riverstyx
Foundation, the National Institute on Drug Abuse,
and a crowd-sourced funding campaign organized
by Tim Ferriss; personal fees from and serving on
the board of directors of the Heffter Research
Institute outside the submitted work; and serving
as site principal investigator for a multisite trial of
psilocybin-facilitated treatment of major depressive
disorder sponsored by the Usona Institute.
No other disclosures were reported.
Additional Contributions: We thank Mary Yaden,
MD, chief resident in Psychiatry at the Perelman
School of Medicine, University of Pennsylvania, for
her feedback.
REFERENCES
1. Carbonaro TM, Bradstreet MP, Barrett FS, et al.
Survey study of challenging experiences after
ingesting psilocybin mushrooms: acute and
enduring positive and negative consequences.
J Psychopharmacol. 2016;30(12):1268-1278.
doi:10.1177/0269881116662634
2. Carhart-Harris R, Giribaldi B, Watts R, et al. Trial
of psilocybin versus escitalopram for depression.
N Engl J Med. 2021;384(15):1402-1411. doi:10.1056/
NEJMoa2032994
3. Griffiths RR, Richards WA, McCann U, Jesse R.
Psilocybin can occasion mystical-type experiences
having substantial and sustained personal meaning
and spiritual significance. Psychopharmacology (Berl).
2006;187(3):268-283.doi:10.1007/s00213-006-
0457-5
4. Griffiths RR, Johnson MW, Richards WA,
Richards BD, McCann U, Jesse R. Psilocybin
occasioned mystical-type experiences: immediate
and persisting dose-related effects.
Psychopharmacology (Berl). 2011;218(4):649-665.
doi:10.1007/s00213-011-2358-5
5. Davis AK, Barrett FS, May DG, et al. Effects of
psilocybin-assisted therapy on major depressive
disorder: a randomized clinical trial. JAMA Psychiatry.
2021;78(5):481-489. doi:10.1001/jamapsychiatry.
2020.3285
6. Griffiths RR, Johnson MW, Carducci MA, et al.
Psilocybin produces substantial and sustained
decreases in depression and anxiety in patients
with life-threatening cancer: a randomized
double-blind trial. J Psychopharmacol. 2016;30(12):
1181-1197. doi:10.1177/0269881116675513
7. Johnson MW, Garcia-Romeu A, Cosimano MP,
Griffiths RR. Pilot study of the 5-HT2AR agonist
psilocybin in the treatment of tobacco addiction.
J Psychopharmacol. 2014;28(11):983-992. doi:10.1177/
0269881114548296
8. Siff S. Acid Hype: American News Media and the
Psychedelic Experience. University of Illinois Press;
2015. doi:10.5406/illinois/9780252039195.001.0001
9. Reiff CM, Richman EE, Nemeroff CB, et al; Work
Group on Biomarkers and Novel Treatments,a
Division of the American Psychiatric Association
Council of Research. Psychedelics and
psychedelic-assisted psychotherapy. Am J Psychiatry.
2020;177(5):391-410. doi:10.1176/appi.ajp.2019.
19010035
10. Smigielski L, Kometer M, Scheidegger M,
Krähenmann R, Huber T, Vollenweider FX.
Characterization and prediction of acute and
sustained response to psychedelic psilocybin in a
mindfulness group retreat. Sci Rep. 2019;9(1):14914.
doi:10.1038/s41598-019-50612-3
Figure. The Hype Cycle
Peak of inflated expectations
Plateau of productivity
Slope of enlightenment
Trough of disillusionment
Technology trigger Time
Visibility
Therapeutic applications of
psychedelics appear to follow the
general trajectory of other highly
visible technologies. Concept from
Gartner, Inc. Image is licensed under
Creative Commons. Courtesy of
Jeremy Kemp.
Opinion Viewpoint
E2 JAMA Psychiatry Published online August 31, 2022 (Reprinted) jamapsychiatry.com
© 2022 American Medical Association. All rights reserved.
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Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial
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Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences
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  • 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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Pilot Study of the 5-HT2AR Agonist Psilocybin in the Treatment of Tobacco Addiction
Article
Full-text available
  • Sep 2014
  • J PSYCHOPHARMACOL
Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-week smoking cessation treatment protocol. Participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. Biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up. The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies (typically <35%). Although the open-label design does not allow for definitive conclusions regarding the efficacy of psilocybin, these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models. The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction.
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Psilocybin Can Occasion Mystical-Type Experiences Having Substantial and Sustained Personal Meaning and Spiritual Significance
Article
Full-text available
  • Aug 2006
Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects. This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable, supportive conditions. The participants were hallucinogen-naïve adults reporting regular participation in religious or spiritual activities. Two or three sessions were conducted at 2-month intervals. Thirty volunteers received orally administered psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) in counterbalanced order. To obscure the study design, six additional volunteers received methylphenidate in the first two sessions and unblinded psilocybin in a third session. The 8-h sessions were conducted individually. Volunteers were encouraged to close their eyes and direct their attention inward. Study monitors rated volunteers' behavior during sessions. Volunteers completed questionnaires assessing drug effects and mystical experience immediately after and 2 months after sessions. Community observers rated changes in the volunteer's attitudes and behavior. Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 months, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers. When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences. The ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.
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Psilocybin Occasioned Mystical-Type Experiences: Immediate and Persisting Dose-Related Effects
Article
Full-text available
  • Jun 2011
  • PSYCHOPHARMACOLOGY
This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions. Participants were 18 adults (17 hallucinogen-naïve). Five 8-h sessions were conducted individually for each participant at 1-month intervals. Participants were randomized to receive the four active doses in either ascending or descending order (nine participants each). Placebo was scheduled quasi-randomly. During sessions, volunteers used eyeshades and were instructed to direct their attention inward. Volunteers completed questionnaires assessing effects immediately after and 1 month after each session, and at 14 months follow-up. Psilocybin produced acute perceptual and subjective effects including, at 20 and/or 30 mg/70 kg, extreme anxiety/fear (39% of volunteers) and/or mystical-type experience (72% of volunteers). One month after sessions at the two highest doses, volunteers rated the psilocybin experience as having substantial personal and spiritual significance, and attributed to the experience sustained positive changes in attitudes, mood, and behavior, with the ascending dose sequence showing greater positive effects. At 14 months, ratings were undiminished and were consistent with changes rated by community observers. Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose, with the lowest dose showing significant effects. Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. Implications for therapeutic trials are discussed.
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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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Acid Hype: American News Media and the Psychedelic ExperienceAmerican News Media and the Psychedelic Experience
Book
  • May 2015
Now synonymous with Sixties counterculture, LSD actually entered the American consciousness via the mainstream. Time and Life , messengers of American respectability, trumpeted its grand arrival in a postwar landscape scoured of alluring descriptions of drug use while lesser outlets piggybacked on their coverage with stories by turns sensationalized and glowing. This book offers the untold tale of LSD's wild journey from Brylcreem and Ivory soap to incense and peppermints. As the book shows, the early attention lavished on the drug by the news media glorified its use in treatments for mental illness but also its status as a mystical—yet legitimate—gateway to exploring the unconscious mind. The book's history takes readers to the center of how popular media hyped psychedelic drugs in a constantly shifting legal and social environment, producing an intricate relationship between drugs and media experience that came to define contemporary pop culture. It also traces how the breathless coverage of LSD gave way to a textbook moral panic, transforming yesterday's refined seeker of truths into an acid casualty splayed out beyond the fringe of polite society.
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Psychedelics and Psychedelic-Assisted Psychotherapy
Article
  • Feb 2020
Objective: The authors provide an evidenced-based summary of the literature on the clinical application of psychedelic drugs in psychiatric disorders. Methods: Searches of PubMed and PsycINFO via Ovid were conducted for articles in English, in peer-reviewed journals, reporting on "psilocybin," "lysergic acid diethylamide," "LSD," "ayahuasca," "3,4-methylenedioxymethamphetamine," and "MDMA," in human subjects, published between 2007 and July 1, 2019. A total of 1,603 articles were identified and screened. Articles that did not contain the terms "clinical trial," "therapy," or "imaging" in the title or abstract were filtered out. The 161 remaining articles were reviewed by two or more authors. The authors identified 14 articles reporting on well-designed clinical trials investigating the efficacy of lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, and ayahuasca for the treatment of mood and anxiety disorders, trauma and stress-related disorders, and substance-related and addictive disorders as well as in end-of-life care. Results: The most significant database exists for MDMA and psilocybin, which have been designated by the U.S. Food and Drug Administration (FDA) as "breakthrough therapies" for posttraumatic stress disorder (PTSD) and treatment-resistant depression, respectively. The research on LSD and ayahuasca is observational, but available evidence suggests that these agents may have therapeutic effects in specific psychiatric disorders. Conclusions: Randomized clinical trials support the efficacy of MDMA in the treatment of PTSD and psilocybin in the treatment of depression and cancer-related anxiety. The research to support the use of LSD and ayahuasca in the treatment of psychiatric disorders is preliminary, although promising. Overall, the database is insufficient for FDA approval of any psychedelic compound for routine clinical use in psychiatric disorders at this time, but continued research on the efficacy of psychedelics for the treatment of psychiatric disorders is warranted.
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