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.”Footnote
1
, Footnote
2 We refer to these substances as “nonhallucinogenic 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.Footnote
3 In healthy individuals, there is also the risk of a disturbing adverse psychological event, or “bad trip.”Footnote
4 Nonetheless, according to some theorists, there are good reasons to provide patients with hallucinogenic 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.Footnote
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.Footnote
6
, Footnote
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.Footnote
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 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.Footnote
9
, Footnote
10
, Footnote
11
, Footnote
12 Subperceptual doses, or “micro-dosing,” of hallucinogenic psychedelics with or without guided psychotherapy appear to produce little to no similar effect.Footnote
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 psychedelic therapy.Footnote
14 In most psychedelic trials, individuals with a history of serious mental illness and suicidal ideation or behavior are excluded from participation.Footnote
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.Footnote
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 nonhallucinogenic 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.Footnote
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 hallucinogenic 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.Footnote
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 pharmacological 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 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 reasonably 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.Footnote
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.Footnote
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.Footnote
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 discomfort, and potential scarring or disfigurement. In contrast, chemotherapy might last several months and results in nausea, weight loss, and hair loss.
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 therapeutically 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.
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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.”Footnote 1 , Footnote 2 We refer to these substances as “nonhallucinogenic 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.Footnote 3 In healthy individuals, there is also the risk of a disturbing adverse psychological event, or “bad trip.”Footnote 4 Nonetheless, according to some theorists, there are good reasons to provide patients with hallucinogenic 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.Footnote 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.Footnote 6 , Footnote 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.Footnote 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 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.Footnote 9 , Footnote 10 , Footnote 11 , Footnote 12 Subperceptual doses, or “micro-dosing,” of hallucinogenic psychedelics with or without guided psychotherapy appear to produce little to no similar effect.Footnote 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 psychedelic therapy.Footnote 14 In most psychedelic trials, individuals with a history of serious mental illness and suicidal ideation or behavior are excluded from participation.Footnote 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.Footnote 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 nonhallucinogenic 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.Footnote 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 hallucinogenic 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.Footnote 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 pharmacological 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 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 reasonably 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.Footnote 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.Footnote 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.Footnote 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 discomfort, and potential scarring or disfigurement. In contrast, chemotherapy might last several months and results in nausea, weight loss, and hair loss.
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 therapeutically 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.