Psychedelic therapies may foster the emergence of a novel paradigm in psychiatry

Acknowledging methodological limitations of extant studies, including small sample sizes, expectancy bias and difficulties with blinding, the promising results being obtained, with large effects sizes for benefit and a very low signal for adverse outcomes, make a strong case for further high-quality controlled studies.

collection of extra-pharmacological parameters that impact clinical outcomes. These include the patient’s mental state and psychological preparation prior to administration; the experience and context of consumption during the acute (dosing) phase; and quality of psychological support and integration post consumption

gaining insights (into self, their disorder/s and its origin), altered self-perception, increased feelings of connectedness and an expanded emotional spectrum, in addition to ‘mystical’ aspects of healing

Many studies remain limited by highly selected cohorts, small sample sizes and lack of controls, while in those that are controlled, adequate blinding is difficult to achieve due to the obvious subjective and objective effects of the drug, further complicated by high expectation of benefit (introducing expectancy bias)

personally meaningful outcomes beyond symptom reduction

Thematic analysis of patient experiences

short- and long-term benefits relating to mood, depression, anxiety, PTSD and substance use

further research required to assess efficacy, effectiveness

If we do not take stock of the important lessons that can be learned from psychedelic sciences related to meaning and mysticism, set and setting, and care and compassion, we risk creating another psychiatric science that unhappily fits a mold constructed for biomedical research. If, on the other hand, we listen to the ways in which experiences of psychedelics and psychosis refuse to fit this mold, we might end up with a much greater understanding of these curious, and challenging, states of consciousness.

structures of EBM and capitalism influence seemingly minor decisions in research protocols, path dependencies are inevitably being created. Down the line, will experiences of mysticism, bliss, or ego-dissolution be forgotten, as psychedelics are increasingly seen as medical treatments?

some forms of knowledge are being prioritized over others (e.g., documenting meaningful experiences becomes less important than documenting a reduction in symptoms) and particular causal factors inevitably dominate (e.g., the influence of music and nature are sidelined in favor of information related to appropriate doses).

In efforts to meet regulatory requirements and fit within the paradigm of EBM, psychedelic-assisted therapy is increasingly being looked to as a “magic bullet” that can cure a variety of psychological or psychiatric conditions

Psychiatry has long grappled with the challenge of fitting its treatment modalities into the RCT framework, given the obvious importance of contextual, individual, and interpersonal factors

the structures of Evidence Based Medicine (EBM) are shaped in such a way that factors related to set and setting are often explicitly excluded from investigation. The randomized controlled trial, the pinnacle of EBM, requires that all factors be held steady across trial arms, so that the specific effects of the active intervention being examined can be captured. While this is an effective and productive form of measurement, it leads to a lack of investigation, and therefore a lack of interest, in the role that other factors related to set and setting might play in influencing clinical outcomes.

there is a wide spectrum of factors thatmake up the content and outcomes of an individual psychedelicexperience (see: Aday et al., 2021, for review), all of which mightalso influence the adequacy and efficacy of a particular psychedelicintegration practice applie

Challenges

Both quantitative (e.g., online surveys or pre–post questionnaires) and qualitative (e.g., interviews, focusgroups) measurements might be used

Exploratory qualitative studies (e.g., in-depth interviewsor focus groups) among various population

specificaspects of the debriefing sessions after the psychedelicexperience

consensus definition andoperationalization of psychedelic integration, for example,based on surveys and/or qualitative studies

At the moment, noneof the existing models or methods of psychedelic integration canbe described as evidence based

Validation of claimsabout understandings of human experience requires evidence in the form ofpersonally reflective descriptions in ordinary language and analyses usinginductive processes that capture commonalities across individual experi-ences.

what counts as evidence and what is acceptable as reasoned argumentneeds to be expanded so that knowledge claims about the understandings ofhuman experiences can be included

The community differences are about what counts asacceptable evidence and reasoned argument

in the actual performance ofvalidity judgments, the background beliefs and assumptions of differentcommunities affect what they accept as legitimating evidence and soundreasoning. For example, a community that believes that only directlyobservable facts are adequate to support the validity of a claim would holdthat no claim about people’s mental lives could be justified or valid

a statement or knowledge claim is not intrinsically valid; rather, itsvalidity is a function of intersubjective judgment. A statement’s validity restson a consensus within a community of speakers

Typically, the issue of validity is approached by applying one’s owncommunity’s protocols about what, in its view, is acceptable evidence andappropriate analysis to the other community’s research. In these cases, theusual conclusion is that the other community’s research is lacking

this cross-community approach is unpro-ductive and leads to a dead end because each community is making differ-ent kinds of knowledge claims

alue on the kind ofresearch that produces claims about cause-and-effect relationships that aregeneralizable to populations. It recommended that funding focus on pro-ducing the kind of knowledge claims that answers questions about “whatworks

the literature on narrative research appears to be rather vague about concrete inquiry procedures

problem of how to understand complex wholes. A major approach has been to break the complex whole down to its constituent parts, which are supposedly easier to grasp. The nature of the complex whole is then explained on the basis of an understanding of these parts

a kind of evidence that is most fraught with subjectivity – that found in narratives or accounts of first-person experience. I shall argue that even this kind of evidence ought to have a place in a properly conceived EBM

for those areas of medicine that are particularly amenableto producing evidence high on the hierarchy, this is an excellent way to procee

here is a convenient compromise here between the desire to be guided by the evidence and thedesire to acknowledge both clinical judgment and patient self-determination. Quanstrum and Hayward givean example of endorsement of this strategy when they write of “a gray area of indeterminate net benet, inwhich clinicians should defer to an individual patient’s preferences”

The proper response to scientic disagreement is to take all the scientic positionsseriously, and, if you are a scientist, support further development for each of them

Much of narrative medicine is politically disengaged.

pistemic and moral weaknesses of autobiography are obvious and commonly recognized. . . .One interesting question, then, is why narrative bioethics has not already recognized them”

think that the belief that narratives are singular gets in the way of discovering and acknowledging thatnarratives often have structural similarities with one another, and prevents us from seeing that thestructural similarities can serve various purpose

grim conclusion that pharmaceutical companies andgovernmental agencies have embraced and repeated the personal breast cancer narrative because it servestheir interests by distracting people from paying attention to the environmental causes of breast cancer

each story is a member of a class of stories that is essentially thesame, with dierences in identifying details. I

thereal target of this criticism is bureaucratic medicine, not consensus conferences or evidence-basedmedicine

impersonality of contemporary health care may have a number of sources, but it is typically blamed onthe “biomedical model” which treats diseases as kinds of biological dysfunction or on “evidence-basedmedicine” which reports statistical results. This is then contrasted with “humanistic” medicine, whosemethods come from the humanities,

Making meaning contributes to intimacy. Intimacy in turn produces aliation (and vice versa). A strongphysician–patient relationship is often essential to patient care, since it can contribute to nding adiagnosis, choice of treatment, compliance and eectiveness of treatment.

it is theresponsibility of the physician to address the emotional and existential suering

details of the narrative matter onlyin so far as they led the physician to seek further information; diagnosis is not available with narrativeanalysis alone

e eorts to test our attempts to empathize (by asking,“Is this how you feel?” or “Is this what you want?”) we often discover that our attempts are awed

Thomas Nagel’s “What is it like to be a bat?” paper(1974), which is well known to philosophers. In this paper, Nagel argues that there is no scientic evidencerelevant to the question of what it is like to be a bat. Bat experience is inaccessible to us, even if we knowmuch about bat behavior and bat neurons. This argument can be extended to what it is like to be a particularhuman, but with a crucial dierence. Humans can describe what it is like to be themselves.

hindsight manipulation ofendpoints

studies funded by pharmaceutical companies have three or four times the probability of studies notfunded by pharmaceutical companies of showing eectiveness of an intervention

There is a danger in departing from established guidelines: some studies have shown that physicians nd“exceptions to the rule” more often than appropriate,

epistemic gap . . . between the results of clinical research andthe care of individual patients”

“Is my patientsuciently similar to the trial subjects for the results of the trial to apply to her?” The patient might befrailer than the trial patients, and/or much older, or be of a dierent gender, or have signicantcomorbidities, or lack the requisite social support. Part of clinical expertise is having the ability to answerthis question, perhaps drawing on general pathophysiological and psychosocial knowledge as well asknowledge of the particular patient.

This statement is a carefully crafted backtracking from the 1992 original statement of evidence-basedmedicine, which explicitly advocated “de-emphasizing” what it called “unsystematic clinical experience”(Evidence-Based Medicine Working Group 1992). Now the individual clinical expertise of the physician isrecognized, indeed respected, as an important part of the process.

ealist synthesis uses a context-sensitive mechanistic account of the intervention tosupplement traditional evidence-based reviews

patient variability (age, sex, severity of disease, riskfactors, comorbidities, ethnicity, socioeconomic status), treatment variability (dose, timing ofadministration, duration of therapy, other medications taken), and setting (quality of care). In order toaddress these issues, knowledge of their importance in particular cases is needed.

standardize the evaluation of randomized controlled trials,

What happens to the process of systematic review if we allow the evidence hierarchy to be more nuanced?One consequence is that we may not be able to do a systematic review at all, because of the diculty ofdevising a nuanced and also impartial hierarchy of evidence. There is a shaky line between contextual andbiased determinations. The danger is that departure from a rigid standard “for good reasons” may open thedoor to any number of rationalized (rather than “rational”) departures from that standard. We may lose theactual and/or the perceived object-ivity of systematic review, both of which are necessary. We may also losethe perceived analytic rigor of systematic review, which contributes to its perceived objectivity

the likelihood of bias isdetermined by both trial methodology and the particular study details