Compassionate use of psychedelics

This paper (2020) reviews the safety and efficacy of psilocybin- and MDMA-assisted therapies and argues that it can be rational for some patients to try compassionate psychedelic therapy, notwithstanding the uncertainty of outcomes, as the expected value of psychotherapy can outweigh the expected value of routine care, palliative care, or no care at all. They also address the epistemic risk carried by the notion that psychedelics are philosophically deceptive given that the subjective effects may often feel more real than normal consciousness, but the authors argue that it is not known how classical psychedelics influence one’s beliefs or whether they make one metaphysically irrational, and assert that metaphysics should be ignored in medicine as much as possible. While acknowledging that there are suboptimal uses of psychedelics, the authors see no ethical barriers for their compassionate use in palliative care.

Abstract

“In the present paper, we discuss the ethics of compassionate psychedelic psychotherapy and argue that it can be morally permissible. When talking about psychedelics, we mean specifically two substances: psilocybin and MDMA. When administered under supportive conditions and in conjunction with psychotherapy, therapies assisted by these substances show promising results. However, given the publicly controversial nature of psychedelics, compassionate psychedelic psychotherapy calls for ethical justification. We thus review the safety and efficacy of psilocybin- and MDMA-assisted therapies and claim that it can be rational for some patients to try psychedelic therapy. We think it can be rational despite the uncertainty of outcomes associated with compassionate use as an unproven treatment regime, as the expected value of psychedelic psychotherapy can be assessed and can outweigh the expected value of routine care, palliative care, or no care at all. Furthermore, we respond to the objection that psychedelic psychotherapy is morally impermissible because it is epistemically harmful. We argue that given the current level of understanding of psychedelics, this objection is unsubstantiated for a number of reasons, but mainly because there is no experimental evidence to suggest that epistemic harm actually takes place.”

Authors: Adam Greif & Martin Šurkala

Summary

In the present paper, we discuss the ethics of compassionate psychedelic psychotherapy and argue that it can be morally permissible. We also respond to the objection that psychedelic psychotherapy is epistemically harmful, and show that there is no experimental evidence to suggest that epistemic harm actually takes place.

Introduction

Psychedelics are psychoactive substances that induce profound changes in the perceptual, affective, and cognitive domains of subjective experience. They have been traditionally used by cultures around the world for centuries and millennia, but have only recently been re-schedule as controlled substances.

Two substances, psilocybin and MDMA, are at the forefront of this psychedelic revival. They are currently undergoing phases II and III of clinical trials and can be administered to patients with terminal, serious or chronic diseases on the basis of the institution of unproven treatment.

As requests for unproven treatment are on the rise, compassionate psychedelic psychotherapy may be in the interest of terminally ill, profoundly depressed, and incurably or chronically ill patients suffering from psychological distress. However, the therapy calls for ethical justification.

There are some concerns related to how to conduct psychedelic therapy ethically. In this paper, we argue that compassionate psychedelic therapy can be ethically permissible on the basis of beneficence, despite the uncertainty with regard to the side-effects and efficacy of psychedelics.

Psilocybin

Psilocybin has a similar pharmacodynamic profile to LSD, although its duration of effect is shorter. The phenomenology of the psychedelic state is identical for both substances.

Psilocybin and LSD increase global connectivity by interfering with cortical connectivity, which corrects dysfunctional neuronal circuits and has a rapid antidepressant effect.

Psilocybin and LSD show promise in the treatment of end-of-life psychological distress, addiction, and depressive symptomatology in general. A 2016 study found that high-dose psilocybin significantly reduced depression and anxiety in 51 cancer patients.

Studies suggest that psilocybin and LSD have a positive effect on depression and anxiety in cancer patients, and that these effects are also present in treatment-resistant patients.

Safety of psilocybin

Psilocybin is a substance of very low toxicity. It causes dilated pupils, slight change in blood pressure, vertigo, and nausea, as well as motor tension and a slight tremor.

Psilocybin can cause mood lability and altered self-perception, as well as panic reactions and prolonged unpleasant experiences (so-called difficult or bad trips). Under improperly supervised conditions, these experiences can lead to risky and dangerous behaviour, namely aggression against self or others, and on rare occasions, self-harm.

Perhaps the most serious side-effect of LSD is prolonged psychosis. In psychiatric patients, a psychotic reaction is expected in 4 cases out of 1000 administrations, or one for every 1338th administration.

Psilocybin may cause lasting changes in personality and values. Some studies have shown an increase in openness, a decrease in neuroticism, and other effects after an experience with psilocybin.

MDMA

MDMA is a member of the phenylethylamine family, and increases empathy towards others as well as oneself. It does not induce a full psychedelic state, but increases serotonin, noradrenaline, and dopamine into the synaptic cleft.

Several studies have been conducted to examine the effect of MDMA-assisted psychotherapy on various psychiatric diagnoses, including post-traumatic stress disorder. The results show that MDMA-assisted psychotherapy is superior to classical psychotherapy for treating depression, anxiety disorders, obsessive – compulsive disorders, suicidality, eating disorders, and addictions.

MDMA-assisted therapy is expected to be effective in addiction treatment because of its proven effect on psychological trauma.

Safety of MDMA

MDMA was safely given to thousands of patients in the late 1980s and afterwards, and is relatively safe even in recreational setting.

Participants in phase II clinical trials often spontaneously described adverse effects related to slight discomfort. These symptoms included insomnia, nausea, bruxism, impaired concentration or balance, dry mouth, and thirst.

Candidates with hypertension or cardiovascular diseases were excluded from this study. Blood pressure and body temperature were regularly measured during treatment sessions.

Mild episodes of anxiety or depression were occasionally reported, but were reduced with proper preparation for treatment sessions.

MDMA has moderate abuse potential, but no unexpected side-effects were observed during clinical trials. It is considered minimal in medical setting, and participation in MDMA-assisted trials was not linked to subsequent MDMA abuse.

Beneficence defence of PT

The cardinal reasons for determining the moral status of any therapy are related to facts about its safety and efficacy. If the expected benefits outweigh the expected harms, then the therapy is in the patient’s interest.

If the conception of compassionate psychedelic use is correct, then the expected benefits of compassionate psychedelic use can well outweigh its risks. The main dangers of compassionate psychedelic use seem to be of psychological nature, revolving around the risks of having a difficult trip and psychotic reactions.

We claim that for some patients, the expected value of undergoing unproven PT can be significantly higher than the expected value of not undergoing unproven PT. If this is true, then a physician providing compassionate PT would not violate their duty to not harm patients.

Some people think that unproven treatments are either too risky to try or useless and therefore psychologically and financially detrimental. However, formally approved drugs are not perfectly safe and efficacious either.

Several authors have called attention to the concerning success rates of investigational drugs, with only 11.83% of them being approved. In addition, 54% of drugs in late-stage clinical trials fail.

The majority of drugs in clinical testing will not be fit for approval, and the risk of unexpected harmful side-effects or frustrated hopes is relatively high. Therefore, unproven PT is morally impermissible.

Uncertainty makes decisions about unproven treatments more difficult than decisions about proven ones, especially in less severe and borderline cases. However, uncertainty can be accounted for in mathematical models of decision-making.

We think that unproven PT will be rational for some patients because the condition is so poor that even highly risky interventions may be expectedly beneficial.

Psilocybin, other classical psychedelics, and MDMA have a favourable track record without any serious adverse events documented, and are well-tolerated according to research and therapeutic sessions done so far.

For some patients, PT is well worth the risk despite its uncertain outcomes, because the alternatives available to them are expectedly worse, including long-term disability or death. This is especially true for profoundly depressed patients, the severely addicted, the terminally ill, and people wishing to end their lives.

There are reasons to reject the argument that unproven psychedelic treatments are not rational to try, because they are conducted with investigational drugs with the same success rates.

If trying unproven treatments is irrational because they are conducted with investigational drugs, then participating in clinical trials may also be irrational. However, to say that clinical trial participation is not rational for participants would put the moral permissibility of clinical trials in serious doubt.

There are no shortage of ethical objections against unproven treatments, including the possibility that widespread use of compassionate PT could hamper enrolment in clinical trials, which would undermine the generation of new medical knowledge and drugs that benefit the population at large.

This particular objection to unproven treatment is regulation-dependent. In the European Union, compassionate use is allowed only on the condition that the patient is not eligible to participate in a suitable clinical trial.

There are several traditional moral arguments against psychoactive drug use, but these are hard to apply to psilocybin and MDMA when used as medicines.

Epistemic harm

Psychedelics are classified as hallucinogens, and if one takes this classification seriously, one could question the authenticity of personal insights PT seems to provide.

Some wonder if psychedelics involve deception as well, albeit in a new guise. They believe that psychedelics lead to beliefs in afterlife and god, which seem inconsistent with physicalism and naturalism.

Letheby points out that studies show a correlation between the therapeutic effect of psilocybin and the occurrence of mystical experiences, which seem to invoke supernaturalistic, or at least non-naturalistic, metaphysics. If naturalism is true, then psychedelic therapy is foisting a comforting delusion on the sick and dying.

The objection is that PT causes metaphysical delusions via compelling hallucinations, and that these delusions are harmful to one’s knowledge because they can function as a psychological defence mechanism.

Letheby’s argument from epistemic harm is relevant to policy debates and ethics, but the ethical implications of his conclusion need to be fleshed out.

If PT is based on mystical experience and philosophical naturalism, then PT is foisting comforting delusions and is therefore morally impermissible.

One could take a pragmatic approach to the problem of delusions and claim that a man’s delusion that he is married to Jane saved him from the devastating truth.

Although we sympathise with the pragmatic approach, we do not think that PT is epistemically harmful. Therefore, we think that PT is morally permissible in less severe cases or as a proven treatment.

The most problematic premise in Pollan’s argument is that mystical experience compels one to accept non-naturalistic beliefs. However, Letheby acknowledges that it is possible for psychedelic users to form beliefs consistent with naturalism.

If classical psychedelics had the power to compel one to accept non-naturalistic beliefs, it would not follow that they foisted delusions.

The second premise of PT, that mystical beliefs are the therapeutic mechanism, deserves two remarks: first, we do not doubt that mystical-type experience is a strong predictive factor of positive outcomes in depressive symptomatology, but it does occur only occasionally.

Psychedelic mystical experiences are identical to naturally occurring mystical and religious experiences, and may lead to metaphysical delusions.

The third premise of the epistemic harm argument seems questionable because metaphysics is a controversial discipline even for philosophy’s standards, and delusion can be described as metaphysical knowledge.

Delusion is a belief that is demonstrably untrue or not shared by others, usually based on incorrect inference about external reality.

If we accept this description of delusion, how should one diagnose metaphysical delusion? The description excludes metaphysics ad hoc, because metaphysical beliefs are not susceptible to modification by experience or evidence that contradicts them.

We are inclined to think that PT compels one to accept non-naturalistic beliefs, and we should care about philosophical naturalism in psychiatry. Therefore, therapists should steer patients’ understanding away from non-naturalism and towards naturalism.

If it is possible to reason PT patients out of their non-naturalistic beliefs, then PT patients could subsequently undergo “philosophical therapy”.

We are not refuting naturalism, we are showing that it is hard to believe that it would be appropriate to steer patients towards any metaphysical conception.

Imagine naturedelic therapy, which is identical to PT with one difference: naturedelics compel one to believe in philosophical naturalism. Would it be permissible to subject a deeply religious patient to naturedelic therapy?

The argument that philosophical naturalism is true is not the kind of thing we generally think we know, so we suggest that we should ignore metaphysics in medicine as much as possible and accept that we do not know.

Conclusion

We responded to two regulation-independent objections against moral permissibility of compassionate PT. We claimed that compassionate PT can be rational for patients despite the uncertainty of outcomes, and that compassionate PT can be morally permissible despite its potential epistemic risks.

There will be problematic uses of psychedelics, regardless of the context of their use, and we hope that scientific understanding will shed more light on the issue.