The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects

This perspective paper (2020) argues that the subjective experience of psychedelics is necessary for enduring therapeutic outcomes.

Abstract

“Classic psychedelics produce altered states of consciousness that individuals often interpret as meaningful experiences. Across a number of human studies, when the participant-rated intensity of the overall drug effects are statistically controlled for, certain subjective effects predict therapeutic and other desirable outcomes. Underlying neurobiological mechanisms are likely necessary but not sufficient to confer full and enduring beneficial effects. We propose that the subjective effects of psychedelics are necessary for their enduring beneficial effects and that these subjective effects account for the majority of their benefit.“

Authors: David B. Yaden & Roland R. Griffiths

Notes

This paper was published at the same time, and argues (partly) against ‘The Subjective Effects of Psychedelics May Not Be Necessary for Their Enduring Therapeutic Effects‘.

This paper argues that the subjective experience is necessary for (lasting) therapeutic effects. A thought experiment is proposed where one imagines having a psychedelic administrated when someone is sedated, would the effects still (partially) be there?

The authors do note that part of the effects of psychedelics can be found in their neurological effects, the reorganisation (increased plasticity) through 5-HT2a receptor mechanisms.

One argument put forth is the correlation between mystical experiences (MEQ) and the therapeutic outcomes. What is (possibly) missed here is that the MEQ can also be an outcome measure of ‘intensity’ of the experience. Or in other words, that the neurological changes both predict the MEQ and therapeutic outcomes. Do see the paper for more discussion of this aspect of the argument.

The paper concludes with stating that the subjective experience is necessary for the lasting therapeutic outcome, something that we will better understand in the coming years (i.e. by doing experiments where people don’t remember the psychedelic experience).

Summary

Classic psychedelics produce altered states of consciousness that individuals often interpret as meaningful experiences. These subjective effects are likely necessary but not sufficient to confer full and enduring beneficial effects.

■ INTRODUCTION

Psychedelics are compounds that are partial agonists at 5-HT2A serotonin receptors and produce a unique profile of subjective effects. Pharmacological blocking of the 5-HT2A receptor blocks many subjective and other major effects of psychedelics.

Psychedelics have been shown to have therapeutic effects when taken under supportive conditions, but questions remain regarding their mechanisms of action. We argue that some subjective effects are necessary for the full and enduring therapeutic and otherwise beneficial outcomes of psychedelics.

Although there is some evidence that psychedelics have positive effects in a rodent model of depression, it seems unlikely that rodents would have experiences similar to those to which humans attribute deep personal meaning and positive, therapeutically relevant mood and behavioral change after taking a psychedelic.

■ SUBJECTIVE EFFECTS OF PSYCHEDELICS

Naturally occurring psychedelics have been used for millennia in religious and healing rituals, and they have been shown to produce profound subjective experiences. These experiences have been documented in qualitative interview studies of patients treated with psychedelics in contemporary settings.

Several subjective features of psychedelic experiences are measurable through psychometric survey instruments, such as the Mystical Experience Questionnaire, which includes four subscales: unity, love, peace, and difficulty putting the experience into words.

Psychedelic naive participants who reported a mystical experience had greater positive changes in attitudes about life and self, positive mood, positive behaviors, and positive social effects two months after the sessions than methylphenidate naive participants. A study showed that mystical experience on session days and positive ratings on follow-up increased as an orderly function of psilocybin dose. A further study showed that mystical experience in combination with meditation contributed significantly to enduring changes in trait measures of prosocial attitudes and behaviors.

Mystical-type experience scores on psilocybin session days are predictive of treatment success at long-term follow-up in clinical studies. These scores are higher immediately after a moderate psilocybin dose than after a low placebo-like dose, and are also correlated with most enduring changes in therapeutic outcome measured 5 weeks later. In open-label pilot studies of psilocybin in the treatment of substance dependence and depression, participants who reported mystical experiences were more likely to be successful in biologically assessed smoking abstinence, and mystical experience ratings were a better predictor of decreases in depression than subjective measures assessing visual or auditory alterations.

The experience of psychological insight is frequently cited as fundamentally important to enduring positive outcomes in anecdotal descriptions of psychedelic treatments. Although experiences of insight may sometimes overlap with mystical-type experiences, they independently mediate positive therapeutic outcomes on depression, anxiety, and substance use after psychedelics.

RELEVANCE OF SUBJECTIVE EFFECTS

Although preliminary, the experimental observations make a case that some subjective effects occasioned by moderate to high doses of psychedelics play a key role in their enduring beneficial effects.

■ CONCLUSION

Based on the results from experimental studies of moderate to high dose psychedelics, we believe that subjective effects play a major role in enduring beneficial effects.

Notes

Dr. Griffiths reports grants from the Riverstyx Foundation, the National Institute on Drug Abuse, and the Heffter Research Institute, and declares no competing financial interest(s).