Are the Subjective Effects of Psychedelics Necessary for Their Therapeutic Benefits?

Researchers at the forefront of psychedelic science put forth their arguments in this important debate.


It is generally believed that peak mystical experiences induced by psychedelic compounds are necessary for their remedial advantages. Historically speaking, the cultural and religious use of naturally occurring psychedelics was centered around their subjective effects.1 However, as scientific study continues to reveal the clinical applications of these compounds, it is worth asking: are the subjective effects essential to their therapeutic properties? 

It is likely that the availability of these therapies would increase if the subjective effects were not required to treat depression, anxiety, and addiction. Two prominent researchers in psychedelic science, Dr. Roland Griffiths and Dr. David Olson, are currently debating if the therapeutic benefits produced by psychedelic compounds are dependent on their subjective effects.

Griffiths’s Argument

David Yaden and Roland Griffiths of Johns Hopkins University School of Medicine make the case that the subjective effects produced by psychedelics impart their full and enduring beneficial effects.2 Their argument relies primarily on self-report data provided by the Mystical Experience Questionnaire (MEQ), which allows for the empirical measurement of the first-person experience. Fundamentally, the scores derived from the MEQ can predict beneficial outcomes from experiments where psychedelics were administered. Subsequent statistical analyses of these data have suggested that mystical-type experience is a mediator in positive therapeutic response (anti-depressive, anxiolytic, and anti-addictive).3,4

It is worth noting that the participants in these studies commonly rate their psychedelic experiences among the most meaningful experiences of their lives. Interestingly, the statistical analyses carried out revealed that the high ratings of personal meaning assessed at 14 months after the study could be predicted by the occurrence of a mystical experience on session day.5 The authors suggest that the subjective effects experienced under psychedelics may provide the impetus for modifying pathological thoughts and behaviors.

Olson’s Argument

While it is appealing to attribute the therapeutic benefits of psychedelics to their subjective effects, one researcher is suggesting that a specific pharmacological mechanism is responsible. David Olson from the University of California Davis makes the point that the evidence supporting the necessity of subjective effects is largely correlational.6 And, of course, it is imperative for scientists to adhere to the perennial scientific axiom “correlation does not imply causation.” Olson maintains that enhanced neural plasticity in key circuits is the root of psychedelic-induced changes in behavior. Therefore, a mystical experience, per se, may not be required to produce the anti-depressive, anxiolytic, and anti-addictive effects that have brought these compounds to clinical attention.

To his point, Olson emphasizes that the psychedelic compounds are psychoplastogens, compounds with the capacity to engage neural plasticity mechanisms in the brain and therefore rewire neural circuitry.7 He claims that the relevant pharmacological feature of psychedelics is their psychoplastogenic capacity. Olson goes on to point out that the antidepressant response of ketamine increases for several days following treatment despite the subjective effects vanishing after a few hours.8 Mechanistically, this is due to the fact that psychoplastogens only require a short stimulation period (<1 hr) to initiate a neuronal growth response that can last for several days.9  Additionally, Olson mentions that MDMA, another psychoplastogen, has mild subjective effects relative to classical psychedelics, but still shows tremendous clinical potential for treating neuropsychiatric diseases such as PTSD.10

Future Directions

Both Griffiths and Olson recognize that neither view can be established as the paradigm without further studies. Each group has suggested a study that would provide useful information regarding the necessity of subjective effects. This hypothetical study would involve psychedelics being administered to individuals who were rendered fully unconscious under anesthesia. It would be crucial that the participants in the study report no recollection of a psychedelic-like experience. Such a study would help sort out some of the psychological and neurobiological effects of psychedelic compounds.

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Journey Man
3 months ago

Trying to extrapolate a personal psychedelic experience from a questionnaire on a piece of paper or similar method. You should immediately understand the limited ability to express the un-expressible. I’ve had many of these experiences and have filled out several questionnaires. But even a decade after a mind blowing experience I’m still learning from the experience. Most experiences are compared to a NDE I had in my late teens. To try to even express from my own thought onto paper the experience is like trying to describe a sunset to a blind person. And you want to think you have… Read more »

Rose Jade, LCSW
3 months ago

I am not confident that the proposed study would answer the question. Forcing someone to become “unconscious” (however one defines that — and good luck with that –, let alone the variety of ways unconsciousness might be achieved) is quite the additional variable. This is a very exciting field and, thanks to MAPS et al, currently somewhat open to scientific exploration in the U.S. But behavior-changing felt-“epiphanies” occur under a wide spectrum of subjectively-reported circumstances. I’m just grateful that we are making strides towards getting these compounds out of Schedule I and available for safe(r) human consumption.

Neal M. Goldsmith, Ph.D.
3 months ago

The foundation of the subjective effects is neurochemistry. This is a heuristic duality, not whole knowledge. Neurochemistry and subjective effects are the same phenomenon observed at the neuronal and behavioral levels, respectively. It will be interesting to see if researchers can find benefit in the part of the neurochemistry that doesn’t include the subjective effects, but even if that benefit is significant, it certainly won’t be the exact same benefit.

Cindy Carrington
2 months ago

I have tried to complete MEQ recently and nothing there described my experience with psychedelics so I didn’t complete it. I have tried Mushrooms and Ayahuasca neither gave me the expected mystical experience often described and what I was looking for. I have upped the dosage on Mushrooms and still no. Before I traveled all the way to Peru from Australia in search of the enlightened “experience” I asked the Sharman if Ayahuasca works for everyone as I felt like psychedelics didn’t work on me properly. He said doesn’t matter if you trip or not the medicine always works. It’s… Read more »

2 months ago

Hello everyone! Well, I think the main question is not adequate nor well-formed in its aim to produce a superficial-scientific-promoting debate. It kind of sounds like referring to psychedelic compounds as if they would inherently have or produce subjective effects, like if those effects would be part of such compounds. This is not the case. I think it would be clearer to say that psychedelics do not have nor produce any subjective effects per se, though they do produce effects, biochemical, neurological, etc, such effects might not always be translated into a subjective effect. It is something else that makes… Read more »