Ethics and ego dissolution: the case of psilocybin

Abstract

Despite the fact that psychedelics were proscribed from medical research half a century ago, recent, early-phase trials on psychedelics have suggested that they bring novel benefits to patients in the treatment of several mental and substance use disorders. When beneficial, the psychedelic experience typically includes features unlike those of other psychiatric and medical treatments. These include senses of losing self-importance, ineffable knowledge, feelings of unity and connection with others, and encountering “deep” reality or God. In addition to symptom relief, psychedelic experiences often lead to significant changes in a patient’s personality and worldview.

Focusing on the case of psilocybin, we argue that the peculiar features of psychedelics pose certain novel risks requiring an enhanced informed consent process, moving beyond what is typical for most psychiatric interventions. We highlight key issues that should be focused on during the consent process and suggest discussion prompts for enhanced consent in psychedelic psychiatry. Finally, we respond to potential objections before concluding with a discussion of ethical considerations that will arise as psychedelics proceed from highly-controlled research environments into mainstream clinical psychiatry.

Early-phase trials with psilocybin-assisted psychotherapy suggest it provides sustained symptom-reduction for treatment-resistant depression (TRD) as well as for cancer-related depression and anxiety.[1–5] Additionally, early studies with psilocybin for smoking and alcohol cessation have shown promising results.[6–8] Moreover, psilocybin appears to be safe, with very few adverse events.[9] Likewise, trials with MDMA for social anxiety in autistic patients[10] and for PTSD[11, 12] as well as those with LSD for anxiety[13] and ayahuasca for TRD[14] have also yielded promising results. Additional clinical trials are currently underway, aiming to replicate some of these findings[15, 16], and more are likely to follow. In short, psychedelics have returned to psychiatric research, despite having been banished half a century ago. Widespread clinical use may soon follow.

The therapeutic potential of psychedelics appears to be related to the peculiar, so-called “mind-manifesting,” experiences they tend to induce in the subjects that benefit. In the case of psilocybin, the characteristic experiences reported by subjects include a sense of new, ineffable knowledge, feelings of unity and connection, and encounters with “deep” reality or God. Subjects who benefit also tend to experience a sense of loss of self, or at least of self-importance, that researchers describe as “ego dissolution.” These effects are often characterized as ‘mystical’ and are associated with the therapeutic benefits of psilocybin[3] and changes to personality broadly understood.[17]

Yet, despite its recent renaissance, significant benefits, and potentially personality-changing mechanisms, psychedelic psychiatry has attracted very little attention among medical ethicists. Others have considered the possibility of psilocybin and MDMA for moral enhancement[18] and couple’s therapy.[19] Still others have considered the ethics of newly proposed, early research on psilocybin as a proposed aid recovery from disorders of consciousness.[20] In contrast, and notwithstanding insights by Johnson et al[9], we believe that the most pressing and underexplored questions regarding psychedelics concern the established and growing work in psychiatry pointing to the potential for widespread use and benefit.

In this paper we partially fill this gap in ethical analysis. We focus on the case of psilocybin as one of the most well-researched psychedelics. We argue that psilocybin’s properties may pose novel risks—such as potentially undesirable personality changes or trauma re-exposures—as well as novel benefits (Section I). We recommend guidance for informed consent in light of such risks in both research and clinical contexts. In particular, we believe that an enhanced consent process—beyond that of typical consent in medicine—is critical (Sections II–IV). After responding to potential objections (Section V–VI), we conclude by addressing ethical challenges that will arise as psilocybin moves from well-controlled clinical trials to clinical practice (Section VII).

Before proceeding two clarifications about terms are necessary. First, there is debate about the use of term psychedelic. Some prefer to restrict it to the “classic” or serotonergic psychedelics, such as psilocybin, LSD, ayahuasca, and ibogaine, which are thought to share a mechanism of action.[21, 22] Yet, others would understand the term “psychedelic” more broadly to include any substances with “mind-manifesting” properties.[23] While we focus on psilocybin, we believe that our analysis generally applies to other interventions with serotonergic psychedelics. Thus, for ease of reference, we will use the term psychedelic to refer to this class in the following. Some of our points below may further generalize to interventions with non-serotonergic substances that might be called psychedelics, such as MDMA, but a full discussion of these issues is beyond our scope here.ⁱ

Second, as noted above, personality change will be central to our discussion here, but the notion of personality is vague. Here we will use the term broadly to refer to, roughly, the narrative features and values of an agent that make them a distinctive (type of) person. Our choice is supported in part because the term personality groups together a variety of changes that psilocybin affects. This broad sense of personality is common in lay English discourse—even if less specific than some usage in the psychology literature. When asked to describe a friend’s personality, we might appeal to their love of certain activities and the importance they place on certain relationships or organizations. For instance, we might contrast a person’s personality by appeal to her care for her family, her love of wine, and her concerns for the world and her country with that of another who is happily single, more individualist, and prefers soft drinks. This broad usage admittedly compromises specificity that comes with the notion employed by the psychology literature, but as we will see below, psilocybin-assisted psychotherapy is associated these kinds of ethically important changes.

I. Personality Change and Neurobiology of Psilocybin-Assisted Psychotherapy

Psilocybin’s therapeutic benefits have been best studied in the cases of anxiety and depression in terminal illness as well as TRD. Hence, we will focus on these cases, noting that not all changes may generalize to other therapeutic targets or other dosing strategies, such as “mico-dosing.” In these studies, therapeutic benefit is associated with the mystical features of the psychedelic experience. These are assessed as a function of several features, including feelings of internal and external unity, sacredness, positive mood, transcendence, and ineffability.[3] Similar associations have been found between the therapeutic benefit and feelings of “oceanic boundlessness,” including “experience of unity, spiritual experience, blissful state, insightfulness, and disembodiment.”[24] Notably, not all subjects achieve these states. Yet, doing so is correlated with the therapeutic benefits of psychedelics.[3, 24]ⁱⁱ

Further, in several studies, most subjects have ranked the psychedelic treatment with psilocybin as one of the most meaningful events of their lives.[1, 3, 17] They report experiences like encountering “a great plane of consciousness” and being able to “reach out to anybody and connect with them.”[25] Subjects also report the “realization that life and death are part of one circle.”[25]

Using validated instruments, such as the NEO Personality Inventory-Revised (NEO PI-R), researchers have characterized psilocybin’s effects on personality according to the Five-Factor Model of personality, which describes personality in terms of openness, conscientiousness, extraversion, agreeableness, and neuroticism.[26–28] (See Box 1). Psilocybin decreases neuroticism and increases conscientiousness, extraversion, and openness, which may be unsurprising given the profound feelings of connection during the experience.[25, 26]

Box 1. Defining Features of the Factors in the Five-Factor Model. (Adapted from [28]).ⁱⁱⁱ Higher scores on a given factor are associated with the relevant defining features, whereas lower scores are associated with opposing features.

Extraversion	Agreeableness	Conscientiousness	Neuroticism	Openness
Talkative Assertive Rapid Personal Tempo Gregarious Enthusiastic Warm	Appreciative Not critical Giving Generous Altruistic Trusting Straightforward	Efficient Reliable Productive Not Self-Indulgent Dutiful Aspiring Disciplined	Anxious Thin-Skinned Worrying Tense Vulnerable Tense Self-Pitying	Artistic Introspective Curious Insightful Original Judges in Unconventional Terms

However, therapeutic psilocybin appears to induce personality changes, in our broad sense, beyond those clearly measured by the NEO PI-R. For instance, psilocybin augments participants’ sense of spirituality.[3] Subjects report feeling deeper spirituality and being “reborn in a way.”[25] Even participants without prior feelings of spirituality sometimes report such feelings during treatment.[29] Similarly, psilocybin appears to induce feelings of transcendence over death in patients with life-threatening cancer.[1, 3]

Finally, psilocybin increases subjects’ sense of connection.[29, 30] Participants note profound senses of “a greater understanding of global connectedness” and feelings that “people, … animals, [and] … trees” are all connected. They also note deeper connections to family members—including feeling “more emotionally open” to significant others. They feel more in touch with themselves.[25] Participants with TRD contrast this sense of connection with “disconnection and tendency to avoid painful emotions” that they associate with previous treatments.[29]

The mechanisms and biological correlates of these experiences and changes to personality remain under investigation. Neuroimaging suggests they may involve acute decreases in functional connectivity of meta-cognitive centers, such as the default-mode network. These findings are associated with “disintegration”, the loss of a sense of self, and an increased global connectivity that may explain reported enhanced sensory experience.[22, 31, 32] Notably, the meta-cognitive circuits reintegrate shortly after the psychedelic state—perhaps suggesting that psilocybin works in part through restructuring pathways of depression.[22, 33]

Such a cognitive reset may also relate to subjects’ sense of openness and connection, as might be explained by a psychodynamic interpretation, on which its benefit is mediated by enabling better access to latent thoughts. This sort of interpretation has been offered for LSD’s mechanism.[34] Given the pharmacological similarities between LSD and psilocybin, the same theory might apply to psilocybin. Relatedly, interviews with LSD[34] and psilocybin patients[29] suggest that part of the mechanism may involve altering the cognitive schema with which patients approach challenging predicaments—similar to cognitive restructuring of more traditional psychotherapies such as cognitive behavioral therapy (CBT). Other emerging evidence with ayahuasca users has suggested that psychedelics improve skills traditionally associated with other therapeutic modalities, such as cognitive flexibility and mindfulness-related capacities like decentering.[35, 36] Another hypothesis is that the therapeutic effects are mediated by making subjects more suggestible and open to therapeutic changes.[9] It is likely that psilocybin’s mechanism of action is manifold and includes several of the above possibilities and others yet to be identified.

II. Why Enhanced Consent?

Some of psilocybin’s effects are likely to be difficult for patients to appreciate beforehand, and in turn, require enhanced consent processes beyond those typical of many informed consent discussions. Importantly, the process we envision is enhanced relative to that of informed consent procedures used to prescribe other psychotropics. Nevertheless, it is based on established principles of informed consent.

There is a shared consensus among ethicists and legal scholars that providers are obligated to disclose the information that a reasonable patient would want to know about the treatment in question.[37, 38]^iv In general, the fundamental elements of disclosure are the nature of the procedure, the risks and potential benefits, and what alternatives may be available.[38] While debate continues about the specificity regarding these elements in various contexts, there is consensus that the standards vary according to context and the intervention in question. For instance, standards for invasive surgery are higher than those for blood draw.[39]

Clinically, disclosure of the critical elements for most psychiatric interventions can be covered in a few minutes. For instance, disclosure for consent to use of selective serotonin reuptake inhibitors (such as escitalopram) can cover the common side effects, including gastrointestinal distress and sexual difficulties, and severe ones, such as serotonin syndrome. Similarly, for second generation antipsychotics, such disclosure can cover common side effects of weight gain, dizziness, and orthostatic hypotension as well as more severe, but rare, side effects like dystonic reactions and neuroleptic malignant syndrome relatively quickly. After introducing these elements, the provider can then invite any questions and direct patients to informational handouts if the patient finds these helpful. Finally, while consent to research is more rigorously regulated and monitored than in medical practice, generally, the chief concern about these particular agents that is different in research will be about understanding the fact that a patient is enrolled in research and, for randomized trials, may not receive the agent under investigation. Thus, in keeping with significant efforts to simplify consent forms and discussion[39, 40], many consent interactions in psychotropic research can be relatively straightforward.

The rationale for such simplicity in informed consent for these psychotropics stems in large part from the fact that a reasonable person can be expected to care about the most common and most severe effects. For SSRIs and antipsychotics, patients are unlikely to care mostly about the details of mechanism and side effects on their personality—which, at least in the case of SSRIs for which there is more compelling data, are limited relative to those of psychedelics.^v Hence, relatively little attention is paid to complex scientific information about underlying pharmacological mechanisms or to personal preferences, values, and deeper concerns of participants. This contrasts with the case of psilocybin, where talking about relieving depression, or even further, the general possibility of hallucination during the psychedelic experience and the risks of anxiety during it, may not make clear to patients the profound effects reviewed above, which may be critical to their decision-making about the intervention.

III. Disclosure Topics in Enhanced Consent

More specifically, we believe that, in particular, three components of the therapeutic process, mechanism, and side effect profile of psilocybin will be novel and potentially unexpected for patients. These are shifts in values and personality, rare mental health side effects, and the possible use of therapeutic touch during therapy. They thus require special attention in enhanced consent.

Shifts in values and personality

Two risks regarding change in values and personality are worth note. First, some of the personality changes reviewed above may be unwelcome to subjects if their newfound values are antithetical to their former ones. For example, nonspiritual, agnostic, or atheist patients may take the development of a newfound sense of spirituality or belief in God to be a loss if it is incongruent with their prior values or if it is disruptive to relationships with others. Similarly, religious patients who believe a mystical experience requires intensive spiritual work or a divine gift could be troubled if through treatment, they come to see it reduced to a biochemical cause.

Second, if psychedelic experiences are truly ineffable, their intensity as well as the possibility of changes to personality may be difficult to convey in consent conversations. For example, before the experience, atheist patients might not appreciate that they too could have intense spiritual experiences. Instead, they might acknowledge that others have deep encounters as if connecting to God or “deep” reality, but assume that they themselves would not take such encounters as real—even if therapeutically beneficial. Enhanced consent may increase the probability of patients’ appreciating the possibility of personality change.

Mental health risks

The second component is that of rare mental health risks—particularly those of severe anxiety of the experience, psychosis, and trauma re-exposure. First, while “transient anxiety” (frequently considered “mild” or “moderate”) is described as one of the chief risk factors in the literature[4], 39% of those surveyed about negative consequences of (mostly recreational) psilocybin use reported their worst “trip” to be one of the five most challenging experiences of their life.[41] Thus, while such experiences are likely different from those in controlled settings[41], we should take the possibility of severe anxiety seriously, and note that it could become more common with clinical psilocybin use outside of the tightly-controlled experimental environment.

The second mental health risk is that of psychosis. Here, it is noteworthy that clinical trials have reported no episodes of psychosis in participants. This may be due to careful screening of patients to minimize risk of psychosis and substance use.[9] Yet, such screening may relax as psilocybin transitions to clinical psychiatry given that, as a rule, the fidelity of safety monitoring, treatment protocols, and other standards is far higher in research practice than in clinical practice where oversight is often looser and time demands are often higher.

Some authors suggest that concerns about the negative, “long-term” psychological effects of psychedelics—and in particular of psychosis—are “largely unfounded.”[20] They point to cross-sectional interviews that find no association between mental health symptoms, including psychotic symptoms, within the past year and lifetime psychedelic use.[42] However, the survey about negative consequences of psilocybin use noted above found 3 self-reports consistent with enduring psychosis after psilocybin usage.[43] Alone these few self-reports may not be grounds to infer causation and may not be statistically significant.

Nevertheless, other considerations should give further pause to the conclusion that concern about psychosis is “unfounded.” For one, a hallmark of substance-induced psychosis is that symptoms remit shortly after the event. Indeed, the Diagnostic and Statistical Manual of Mental Disorders takes the persistence of symptoms for greater than a month after cessation of the substance to be one of the paradigmatic examples of evidence that a primary psychotic disorder should be diagnosed despite active substance use.[44]^vi Hence, a lifetime history of use, complicated by substance-induced psychosis, would not necessarily correlate with recent symptoms—mitigating the implications of the otherwise reassuring cross-sectional interviews.

Another consideration that gives pause to the conclusion that the concern about psychosis is unfounded, there may be psychosis-related risk other than that of acutely inducing psychosis. Hallucinogen abuse is a risk factor for developing schizophrenia, and hallucinogen use by individuals with schizophrenia is a risk factor for violent behavior.[45, 46]^vii Hence, while the risk of psychosis for any individual is likely low, it does appear sufficient for clinical attention, both for safety and for obtaining consent. Enhanced consent should call attention to these risks—though it should, of course, contain reassurance that in controlled settings the risk is exceptionally low.

The third mental health risk is that of trauma re-exposure. Subjects have noted that they relived traumatic experiences during the psychedelic experience or even experienced completely new, putative “memories” of trauma.[4, 29] Indeed, sometimes therapists cannot assess the accuracy of such new memories.[4] Clinicians will have to both inform subjects about such a possibility as well as be prepared to address it. The possibility of reliving traumatic experiences merits careful discussion in the informed consent process.

Therapeutic Touch

Finally, the use of physical touch, such as patting a shoulder to offer support for a grieving or suffering patient in acute dysphoria, for therapeutic support of patients while in the psychedelic state is of significant ethical concern for psychedelic psychotherapists. The use of such touch has long been of significant controversy in psychotherapy—particularly in the psychodynamic context[47, 48]—and surveys show varying percentages of providers who employ it in various ways.[49, 50] Given that some psychedelic psychotherapists practice such touch[51], we wish to consider special complexities particular to consent for such touch in psychedelic psychotherapy as many psychedelic psychotherapists employ such touch and consent to it is an active point of discussion in psychedelic psychotherapy community.

One might think there are no such distinctive issues. Presumably, if therapists are to employ touch at all, they should do so only if it is therapeutic and acceptable to the patient.[51] Further, while there might be concerns about the possibility of exploitation of a vulnerable patient, these are at least partially mitigated in part by the fact that current protocols often require therapists to work in pairs—ensuring the presence of a chaperone.

However, the possibility of patients’ changing preferences about touch may be more ethically challenging. For instance, patients may anticipate that they would be receptive to this ahead of time, but in the state may have new feelings about such therapeutic support—especially if encountering severe anxiety or trauma. This raises a challenge from the standpoint of consent as patients may not anticipate that such a change in preference should be expected, and therapists may not know which preference to respect.

One might assume that patients should have the ability to change their preferences and that that change should be honored as long as patients have capacity to make this decision. Yet, patients’ decision-making capacity may be in doubt (and hard to assess) at various points during psychedelic use. The standard way of assessing capacity is to determine whether patients have the abilities to express a stable preference, to understand the information relevant to the decision, to appreciate the impact of the decision, and to rationally manipulate the information in making a decision (at least to some degree).[52] However, it is unclear that this standard can be easily applied in challenging cases of psychedelic psychotherapy.

In particular, two problems might arise with this standard’s implementation while patients are in the psychedelic state. First, given that decision-making capacity requires the ability to express a stable preference over time, if the patient’s preference is changing, this ability is immediately called into question. This makes it difficult for therapists to assess decision-making capacity—particularly if the patient is in severe anxiety and thus unlikely to be able to answer the many questions that may be involved in capacity assessment. Second, the possibility of assessing the understanding and appreciation of patients and participants as well as their rationality in manipulating the information could be severely limited if they are in the midst of an extremely distressing psychedelic experience.

Given the challenges of treating changes in preferences about therapeutic touch as a simple case of capacity assessment, we would suggest two further points to address consent to therapeutic touch. First, unless demands of patient safety arise—such as that of a patient falling[51] or becoming agitated to the point of needing forcible restraint—patients’ refusals to be touched at any moment are inviolable. Such patients should not be touched even if they had requested therapeutic touch before.

Second, the psychedelic psychotherapy community should develop shared standards of how to respond to cases where patients change their minds about therapeutic touch. The Multidisciplinary Association for Psychedelic Studies—a leader in psychedelic psychotherapy—has emphasized that consent must be obtained before and during therapy sessions to ensure that patients not be touched against their will. They further suggest that “simple and specific words and gestures” that the patient feels comfortable with in communicating their preferences during the experience will be identified before the psychedelic therapy.[51] However, development of such standards will be needed as research progresses, and in particular, guidance should be developed for how to respond to cases where patients change their minds about therapeutic touch. Legal and ethical scholars should help in development of such standards—both in providing expertise about similar cases from other medical specialties and in assessing how the law might respond to standards under consideration.

Having reviewed several features that are critical to discussion in enhanced consent, we offer discussion prompts for the enhanced consent process in Table 1.

Table 1.

Suggested Disclosure Information and Questions for Consent to Psilocybin

Information about the Experience	“You may think you are communicating with higher powers or understanding “deeper” realities. This happens to people who have spiritual and religious beliefs, but also to those who do not have such beliefs. Those who have experienced this often find it difficult to convey to others exactly what they experienced. Hence, we cannot tell you exactly what this is like, and you may have trouble understanding it before you experience it yourself.”
	“You may feel profound connections that would have seemed odd to you prior to this experience. These may include connections with various people (perhaps all of humanity) as well as animals and nature generally.”
	“You may feel a sense that you have lost yourself, that everything is somehow connected, or that all is one.”
Information about Potential Long-Term Changes	“You may become more open to new experiences and different points of view.”
	“You may become more spiritual—whether or not you currently consider yourself spiritual.”
	“You may feel a deeper connection with nature.”
	“You may feel a greater sense of extroversion and openness to new experiences and ideas.”
	“These changes may lead you or your family to perceive you as different in various ways.”
Information about Mechanism	“The benefits of this intervention may be related to or depend on these effects of the experience and these changes to your personality. We have found that encouraging participants to embrace the experience is important to achieving the benefits. In fact, trying to resist aspects of the experience can lead to more anxiety provoking and less beneficial outcomes.”
	“The benefits may also be related to the power of suggestion that the drug enables. For instance, patients with cancer have seen decreased in their depression with the experience. This might be, in part, because it helps them to accept the idea that their cancer lacks power over their mood and meaning in life.”
Therapeutic Touch	“We can use our clinical discretion to support you during intense moments in the psychedelic experience, for instance by holding your hand if you become distressed. However, we would never do this unless you wished. Would you like us to? If so, we should talk about how to communicate about this during the experience.”
Questions for Subjects’ Reflection	“Would any of these changes be difficult for you?”
	“Do you have any further questions about this experience, its risks, or its benefits?”

IV. Enhanced Consent and Current Practice

Do current research practices meet the demands of enhanced consent? Perhaps so—particularly during the sessions designed to prepare research participants for psychedelic psychotherapy. The state of the art for such sessions was described early in the psychedelic renaissance through a set of safety guidelines for psychedelic research by Johnson, Richards, and Griffiths (2008). Regarding informed consent, those guidelines note that the psychedelic experience may be difficult for psychedelic-naïve participants to understand and that, hence, more time may be required to discuss such effects than would otherwise be the case. They also emphasize that participants should be told about a number of the possible effects of psilocybin use, including many that we discuss above,^ix and particularly psychedelic-induced disorders in the consent process.

Perhaps more interestingly, they then detail preparatory sessions, which many might take as a separate step from the informed consent process. These sessions are not only designed to introduce subjects to logistics of treatment sessions and build a therapeutic relationship with participants, but also to provide “a detailed discussion of the possible range of [psychedelic] experiences” as well as guidance on how to address challenging experiences. However, we believe that such discussions should be considered not only as preparatory for therapy, but as part of informed consent. We would urge that such sessions be thought of as part of the extended process of consent, offering recurrent opportunity to improve subject understanding and achieve enhanced consent.

Nevertheless, we know of no detailed reviews that have surveyed the exact protocols of preparatory sessions across different psychedelic studies, nor any describing details of informed consent processes across various psychedelic studies. Hence, we cannot assess the degree to which our standards are met in current research practice with certainty, but we hope, that in providing them, we can aid in their being regularly realized in both research and future practice.

V. Is Psilocybin Relevantly Different?

The chief concern about our argument may be that psilocybin is not as different from standard psychotropics, like SSRIs, as we have suggested. Indeed, psychedelics are not the first psychotropic to raise concerns about changes to patients’ personalities. Similar concerns were raised about SSRIs over 20 years ago.[53] SSRIs appear to decrease neuroticism and increase conscientiousness.[26, 54–56] Similarly, psychotherapy in various forms, including CBT, supportive, psychodynamic, hospital-based, and mixed therapy modalities, appears to change personality as well—perhaps more than conventional antidepressants.[57] Thus, some might ask: “Is psilocybin really different?”—at least regarding one of the most significant novel risks—that of personality change. The answer is yes.

There are critical differences between psilocybin and conventional psychiatric treatments. First, while data are preliminary, the personality changes effected by psilocybin are different in both kind and degree from those of traditional psychiatric intervention. While they share alterations in neuroticism and conscientiousness with conventional antidepressants, evidence suggests that psilocybin induces significant changes in extraversion and openness compared to conventional antidepressants.[26]^x As noted above, the effect on openness may be critical to the mechanism of psilocybin; hence, this difference in effect size is crucial.

Second, patients may incorporate evidence from their experience of conventional psychopharmacological and psychotherapeutic interventions to their decision-making about continuing with such interventions. Having experienced part of a therapeutic process, they can decide whether to continue it. This allows for longitudinal processes of revisiting the disclosure process to informed consent. In contrast, they may lack the time to do so with psychedelic interventions because the psychedelics’ effects appear to happen quickly with single doses. Therefore, the ethical importance of patients’ understanding information about personality changes before engaging in psilocybin treatment may be much greater than that of their understanding of such change in conventional therapy, which they may terminate at any time.

Finally, not all of the personality changes elicited by psilocybin seem to be explained by changes that are well-measured by the Five-Factor Model. Many of psilocybin’s effects reviewed in Section I, such as its ability to induce new ineffable realizations of the deep connections between all things or of truth or of God, appear to affect personality without obviously affecting any of the five factors. Such changes are not typical of conventional antidepressants. Moreover, they are not paradigmatic features of conventional psychotherapy as such—though undoubtedly existential subjects may sometimes be a feature of such therapy. Even when this occurs in conventional therapy, the process through which it happens is generally not ineffable, mystical, or rapid, so subjects may have more control over whether and how they wish to accept such changes as part of themselves.

VI. Suggestibility and Capacity to Consent

Two other objections must be addressed. First, one might object that enhanced consent might limit psilocybin’s power to induce suggestibility, potentially affecting its therapeutic effects given that this may be part of its mechanism.[5, 9] Perhaps hearing about personality changes or the potential role of suggestibility in psilocybin’s mechanism may render subjects less open to suggestion, reducing effect size and therapeutic power. Further, this might raise research concerns about difficulties in controlling for this disclosure-related effect.[17]

Yet, given the discussion above, failure to discuss this may be withholding material information from patients. Hence, the standard requirement of informed consent to discuss information that can be expected to be material to decision-making[37] (unless waived by the patient) implies one ought not withhold this information. Additionally, the considerations raised by this objection point to further reasons for enhanced consent. First, patients may not be as interested in a form of pharmacology that makes them more suggestible to certain beliefs that they would not otherwise endorse. Second, if new trials with enhanced consent result in a smaller effect size for psilocybin, we would gain valuable knowledge about suggestibility and psilocybin’s mechanism. While such a finding might limit some of the current enthusiasm about psilocybin, it might also suggest a mechanism that other novel therapies could be developed to target.

The final objection charges that patients cannot consent to psilocybin—even under the conditions of enhanced consent—if psilocybin-assisted psychotherapy involves experiences that are inarticulable. When we attempt to assess the subjective value of some event, we often do so by imagining what it—and its results—would be like to experience.[58] Unfortunately, if the event or results are not possible to appreciate before having the experience, we lack the information to do so. Indeed, some bioethicists have claimed that similar imaginative exercises are necessary for one to have a rational desire—one that is an expression of one’s autonomy.[59] In turn, if psilocybin induces truly ineffable experience (or changes that are too difficult to appreciate), one might question whether one can give informed consent to psilocybin-assisted psychotherapy.

Yet, we doubt that being unable to fully imagine^xi the experience or outcomes undermines one’s ability to give consent. After all, we regularly accept consent to various activities that cannot be fully imagined—including beginning new relationships, getting married, starting a job, and moving. Likewise, we take consent to traditional psychotherapy as authoritative despite effects on personality and worldview that subjects cannot fully appreciate before therapy.

VII. The Ethics of Going Mainstream

To conclude, we review the cautionary history of previous (ultimately unfounded) concerns about personality-altering therapies. This should remind us that the data on psilocybin are still largely preliminary. We then turn to four issues beyond those of consent that are critical as psilocybin transitions to mainstream psychiatry.

There is a long history of concerns about personality-changing interventions beyond the concerns about SSRIs’ effects on personality noted above. Many lay people have raised concerns about such changes from organ transplants, particularly heart transplants—though many such concerns rely on implausible beliefs about the physiological process through which the organ itself might induce such change.[60] Perhaps more plausibly, ethicists have historically been concerned about personality change from deep brain stimulation. Yet, systematic review has found that evidence of personality change from deep brain stimulation is from only 8 of 150 studies. All 8 were uncontrolled, and several noted potentially better explanations for the observed behavioral changes than changes to personality.[61] Additionally, ethicists have worried that face transplants were ethically problematic given the importance of facial features in social identity. Yet, when transplants proved successful without evidence of such problems, commentary became much more favorable.[62] Many now believe that those initial concerns about face transplantation rested on little more than poorly founded speculation.[63]

This history reminds us of the importance of caution in drawing conclusions from initial research. In the case of psilocybin, we must remember that the initial data reviewed above on psilocybin’s effects generally—and on personality in particular—is still preliminary. Thus, we must emphasize that more research is required and that ethical conclusions must be tentative. Nevertheless, we believe the above arguments support enhanced consent for psilocybin—at least precautionarily until further evidence suggests otherwise.

We now note four ethical issues that will be critical as the use of psilocybin transitions from a limited research setting to psychiatric practice. First, if we are right that psilocybin induces personality changes that are not well-accounted for on the Five-Factor Model, further research is needed to understand this personality change. Indeed, we may even need new instruments to assess how participants understand changes to personality—given that the Five-Factor Model (the dominant model of personality in psychology) does not appear to do so.^xii Given the importance of personality in mental health, a model that accommodates these other types of personality change may offer contributions far beyond the realm of psychedelic psychiatry.

Second, psilocybin is like other novel therapeutic modalities in that ethical challenges arise because knowledge of mechanisms, safety, and further benefits is limited and norms about standard practice outside of the research context have yet to emerge. Thus, it is important to develop careful policy safeguards for the most obvious risks, including anxiety, psychosis, and trauma exposure. In particular, these risks could be exacerbated if clinical psilocybin use evolves as ketamine use did, where robust (or even overzealous) enthusiasm emerged. If so, clinics could begin to use non-standard dosing or minimize safeguards.[66, 67] Others have proposed a Risk Evaluation and Mitigation Strategies (REMS) through the Food and Drug Administration[68]; this could be one way of maintaining safety (potentially combinable with others) as psilocybin transitions to clinical use.

Third, it is standard practice for intense psychotherapy to be conducted in the research setting with psychedelics including psilocybin. While there is no evidence to show that such psychotherapy is necessary (or to assess how much is necessary) for benefit or safety, anecdotally, experienced therapists believe it is critical. Yet, therapy can be expensive and time-consuming; hence, eliminating a requirement for psychotherapy may be a tempting means of increasing access. Undoubtedly, research should begin to address the question of how much—if any—therapy is necessary. Yet, in the meantime, the precautionary principle would suggest that clinical psilocybin therapy should always involve supportive psychotherapy as well as integration therapy (or some therapeutic equivalent) to address the experiences that arise while using psilocybin. Such therapy may help in monitoring and addressing both psychosis and trauma exposure.

Finally, it must be emphasized that participants appear to have profoundly positive feelings about the experience. Hence, the risk-benefit analysis of psychedelic intervention seems favorable for those who are screened as having low-risk for psychosis—even more so when we note the potentially profound effects on illness. Despite the ethical considerations presented here, if the initial benefits of psilocybin can be replicated in Phase III trials, there will be an ethical imperative to proceed with a transition of psilocybin to mainstream psychiatry.