In its efforts to mainstream psychedelics, the biomedical model runs the risk of proclaiming and defending particular dogmas and orthodoxies. These raise the risk of stifling inquiry into the full psychedelic experience: its mechanisms, meaning, and optimal applications. In this week’s post, I discuss the state of this mainstreaming effort, and suggest how to prevent its successes from prematurely closing the psychedelic mind.

The biomedical research model has been extraordinarily successful in re-introducing psychedelic drugs to the larger scientific community and popular culture. Moderate doses, strict attention to non-drug factors, and a modest relationship with the media all have contributed to this success.

However, the biomedical research model has done less to mainstream the psychedelic experience. Rather, one reads about psychedelic drug effects on drug abuse or depression, or views images of functional brain scans demonstrating mathematically significant data. The actual experience, on the other hand, is transformed into relatively abstract categories; e.g., “bliss,” “highly significant,” or “openness.” Only short narrative excerpts by research subjects may appear in the welter of statistical analyses.

Part of this reluctance to describe and discuss in-depth unprocessed narratives of the full-blown psychedelic experience relates to how non-mainstream these effects are. They may be alarming and/or confusing to those reading about them—two reactions that the biomedical research community has worked hard to avoid. This restraint in discussing the full spectrum of the psychedelic experience is practical and successful. However, it should not at the same time constrict discussion of the psychedelic drug experience within the academic community, nor limit explanatory model-building. I encourage us to use the widest, not the narrowest, spectrum of disciplines’ models of the mind-brain complex for this project. By so doing, we’ll develop the most sophisticated models of the psychedelic drug effect.

The biomedical model mainstreaming psychedelics emphasizes biological mechanisms, and this is where we are seeing the most rapid advances. Psychopharmacology research has established that psychedelic drugs attach to and stimulate a type of serotonin receptor, the 5HT-2A site, in the brain. Animal behavioral models that are believed to reflect psychedelic effects in humans demonstrate blockade of these effects using 5HT-2A blocking drugs. Despite doses of, for example, LSD in animal studies that are 500-1000 times greater than a high dose in humans, this model has proven clinically relevant. For example, 5HT-2A blocking drugs reduce and may even completely abolish subjective effects of classical psychedelics—psilocybin, LSD, and ayahuasca—in humans.

However, the necessity of psychedelic drug activity at the 5HT-2A site does not mean that it is sufficient. Adding LSD to a test tube containing nerve cells whose 5HT-2A receptors are stimulated is not the occasion for a psychedelic experience. In humans, the rest of the brain as well as the mind are necessary. The “rest of the brain” is being investigated and we’re learning more about the interactions among various receptors in the brain circuits whose activities they modify. And, the importance of the mind is now clearly established as we see with the current attention and strict adherence to rigorous regulation of set, setting, and suggestion.

As I discussed in a previous post (, these biological effects may not be the ultimate cause of whatever outcomes we see. The notion of psychedelics as “super-placebos,” on the other hand, helps explain how one drug can have so many different effects depending on set, setting, and suggestion. That is, it may be that 5HT-2A receptor activation mediates the placebo response, rather than a set of brain circuits mediating mood elevation, spiritual experience, and so on—these are later downstream effects.

This conceptual blurring between the necessity and sufficiency of 5HT-2A receptor activation may be blinding us to even more fruitful ways of understanding how these drugs work. It is an example of how orthodoxy and dogma could interfere with valuable scientific research. There is a burgeoning field of biological research into the placebo effect, and nothing intrinsically should prevent the biomedical investigation of the placebo-enhancing effects of psychedelic drugs.

Psychological models formally adhere to the doctrine that subjective experience reflects the underlying biological mechanisms through which psychedelics act. However, the explanatory gap—between brain physiology and subjective experience—remains wide, and psychological models are still free to rely upon their own traditions, tools, and theories. Psychoanalytic psychology is one popular and powerful model. It also possesses a long and well-established tradition of in-depth descriptions of the psychological contents and processes involved in psychotherapy, as well as in altered states of consciousness like dreams, dissociation, and psychosis.

Humanistic-transpersonal psychological models are also popular within the biomedical setting. It is important to remember that a, if not the, major influence on these schools’ development was the wish to incorporate the notion of a “universal spirituality” or “core mystical experience underlying all religions” into contemporary psychology. They thereby provide a psychological rationale for the unitive-mystical spiritual effects believed to mediate much of these drugs’ benefits. This they do by borrowing heavily from Eastern religious psychologies. Shamanic models also are gaining currency, but less explicitly, within the biomedical model.

Spiritual models, incorporating theology, philosophy, and metaphysics, are in their infancy. The doctrine of a universal core mystical-unitive experience now predominates discussions and runs the risk of becoming another dogma of psychedelic orthodoxy, brooking little dissent ( Political correctness—and conscious or unconscious hostility toward biblical religion—may be driving this as much as empirical reality. Models which rely upon traditions whose paradigmatic spiritual experience is interactive and relational may also be relevant. There is no scientific reason why this type of spiritual experience will not prove as amenable to current research methodologies as the mystical experience paradigm.

I believe that the rush to establish a biomedical research orthodoxy of psychedelics’ spiritual effects reflects uneasiness in its relationship with non-mainstream effects of these drugs. This is not necessarily a result of the biomedical model’s inability to examine these effects—ones that might be described as religious, supernatural, or particularistic—but by the wish to avoid them and potential religious controversy.

This is where I see value in non-biomedical disciplines, and biomedical discussions and studies of non-mainstream effects. It is also where I see danger in the tendency to denigrate the value of non-biomedical approaches to psychedelics and/or biomedical approaches to non-mainstream effects. Last week’s post ( discussed this at some length with respect to the non-mainstream effects of DMT, and how discussing them within the biomedical model has drawn such ire from segments of the research community.

The lack of mathematical certainty in the non-biomedical disciplines does not negate their value. And there are several reasons why they posses unique value. One is that these disciplines will keep alive interest in non-mainstream effects, effects which are the true hallmark of the fully psychedelic drug state. They will also apply their methodologies and tools in developing theoretical and practical models of the psychedelic experience. Above, I mentioned how traditional psychoanalytic research provides a useful example of this approach. Anthropological approaches to shamanic models is another useful example. And as biomedical research extends its interest in and ability to study non-mainstream effects objectively, significant groundwork will have already been laid and provide directions for this future research.

One of my favorite examples of how non-mainstream notions might one day yield to mainstream biomedical investigation relates to the Aristotelian psychological notion of the “rational faculty” (the intellect) and the “imaginative faculty” (everything else). This model led to the development of an extraordinarily sophisticated metaphysics (theology + physics) of spiritual experience in the Middle Ages. This was the golden age of fruitful dialogue and exchange of information and theories between the worlds of scripture-based faith and deductive scientific inquiry. Future biomedical research might identify and characterize the rational and imaginative faculties. These data would most likely prove similarly cross-fertilizing between science and religion. Once these faculties in the mind-brain complex are identified and characterized, higher-order hypotheses can be tested.

For example, how are these faculties influenced? How are they affected by psychedelic drugs, one’s biological constitution, personality, education, and training? The medieval metaphysical models suggested that these faculties are influenced via “emanation” and “invisible intermediaries.” Could we design experiments testing such hypotheses?  Not now, of course, but non-biomedical disciplines—like philosophy, theology, metaphysics, anthropology—should not shy away from remaining engaged in enlarging any discussion of the psychedelic drug effect.

Psychedelics never had a chance to become mainstream after their placement into Schedule I. With the renewal of clinical research, a new opportunity exists to place them relatively comfortably within the biomedical mainstream: safe, effective, and reliable. While a truly welcome development, I also hope that this successful transformation is accompanied by a comparable interest in their non-mainstream effects as well as by non-biomedical disciplines.

To paraphrase Spinoza’s portrayal of the ideal society, those interested in psychedelics should be free to think what they want, and to say (or write) what they think. With this in mind, I believe it is far too early in the development of our understanding of the psychedelic state to close off any potentially fruitful investigations and model-building.

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