In the last years, psychedelic science has regained relevance in the field of psychiatric treatments with a radical idea. Research is showing that altered states of mind induced by psychoactive substances can in fact be healing for those suffering from mental health disorders. But what if it is not about the subjective experience? What if we could produce versions of these psychedelic substances with the same medicinal properties, yet without any psychoactive effects? Some researchers and pharmaceutical developers are putting their bets on this possibility. The case of non-hallucinogenic analogs illustrates the scientific and economic logics of an expanding field increasingly populated by investors and experts with diverse agendas. As psychedelics are integrated in the medical system and the pharmaceutical market, do they become less… psychedelic?
The development of new non-hallucinogenic psychedelic analogs has reopened an old debate around the mechanisms of action of these substances. Researchers have conflicting views about the importance of the subjective experience in mediating the therapeutic effects of psychedelic therapy (See here and here). A biotech company led by chemist David Olson has synthesized a new analog of the ibogaine molecule which seems to mimic its therapeutic effects on addiction without inducing any hallucinatory experience. This is not news for the psychedelic community though. In the 90s, neuropharmacologist Stanley Glick had already developed a similar analog (18-MC) which thanks to the investments of private sponsors is currently being tested in clinical trials. Another example, E2-Bromo-LSD, first synthesized by Albert Hoffman, has also been used as a non-hallucinogenic alternative to treat cluster headaches. Despite these developments, much of the psychedelic research until now has been rather eager to study the altered states of consciousness induced with psychedelics and their potential applications in psychotherapy. Chemically erasing the subjective effects of the substances has not been on the agenda of psychedelic psychiatrists. Why would they do that? It was precisely the so-called mystical-type experience and its transformative potential that appeared as a breakthrough. Today, the calls for a paradigm shift in psychiatric treatments lose momentum as the stigma around psychedelic science recedes and new actors with different backgrounds and goals have come to populate the field. But what is the logic behind these efforts to create non-psychedelic versions of these molecules?
The scientific rationale of these pharmaceutical ventures rests on a particular neurological model of psychedelic effects. Their hypothesis is that the brain mechanisms responsible for the therapeutic action of psychedelics can be disentangled and isolated from those inducing subjective effects. Therefore, through chemical engineering, it is theoretically possible to design a molecule which targets the neurological substrates involved in therapeutic outcomes, without acting upon those that produce alterations in perception and cognitive function. The neuroscientific ideal of specific molecules with specific targets responsible for specific effects resonates with the emphasis on customization and optimization that fuels pharmaceutical development. If this principle of specificity holds, then it should be possible to tinker molecular structures to fine-tune their target selectivity and chemically parse out side-effects from desired effects. In other words, it should be possible for pharmaceutical developers to improve psychedelic therapy at the molecular level. But what are the side effects that psychiatrists and bioengineers are trying to get rid of?
“…However, many psychoplastogens alter perception or produce other undesired effects. A better mechanistic understanding of mTOR signaling in the brain could lead to the development of compounds with psychoplastogenic properties but better safety profiles. A number of companies and academic scientists are currently pursuing this strategy”.
Major voices in the psychedelic renaissance have promoted “experience as medicine”, a notion that invites psychiatrists to reconsider the value of altered states of consciousness in mental health. In contrast, the work of David Olson has focused on neuroplasticity alone as the underlying factor causing therapeutic outcomes in addiction or depression. The psychedelic trip is therefore seen as an unnecessary epiphenomenon that can be dispensed with in therapy. Even more so, it is rejected as an adverse effect which may increase the patient’s levels of anxiety and potentially lead to complications in the therapeutic process. Olson’s conclusion mirrors the way in which altered states of consciousness have been historically regarded in psychiatry. In conventional psychiatric treatment, an implicit notion of mental health as self-mastery has prevailed; a rationalist fixation with maintaining an ordinary state of mind which privileges control and sobriety as signs of sanity and virtue. Altered states have thus been othered as irrational, hedonistic and pathological, along with the people who experience or cultivate them. The study of psychedelic experiences as models of psychosis in the early times of psychedelic research is illustrative of this bias. It comes as no surprise that orthodox psychiatrists have remained skeptical about treating mental disorders by inducing what is considered as a psychotic-like state. In a move that consolidates these strong feelings of doctors and the general public against “intoxication”, Olson concludes that the psychedelic experience itself is the main obstacle for these treatments to ever become widespread.
Another case that illustrates how various concerns and interests are built into the distinction between therapeutic effects and side effects is the proposal of “bad trip”-free psychedelics. Here, the value of the subjective experience is not completely discarded, but only the more pleasant or euphoric effects are thought to contribute to the success of the therapy. In contrast, many therapists agree that the more challenging parts of psychedelic trips can actually be the source of important therapeutic insights. What appears as an adverse side effect for some, constitutes the core of therapeutic efficacy for others. Moreover, therapists have developed a number of successful techniques to manage and process difficult experiences under psychedelics without the need to alter the chemistry of the substance. The propensity to solve problems at the pharmacological level can be traced back to a particular style of thinking in neuroscience; a logic which is promoted by the economic incentives that drive the pharmaceutical market.
“We want to put medicines on the market through the traditional pharmaceutical pipeline and distribution model because we think we can do a really good business out of it”
– CEO of a major psychedelic biotech company
A quick look at any of the new psychedelic investment conferences mushrooming online makes clear how important it is for the industry to build value through intellectual property. In the capitalist pharmaceutical market, innovation can only occur where economic incentives through exclusivity rights are possible. In the case of psychedelics, many of the available molecules and synthesis procedures are public domain knowledge and therefore not subject to patents. Economic opportunities in psychedelic pharma are restricted to the development of patentable products, including novel molecules, synthesis protocols, microdosing regimes and psychedelic formulations. Although there is still much to be researched about classical and naturally-occurring psychedelic substances and the factors mediating their therapeutic efficacy, we see how the agenda is shifted towards whatever is marketable, scalable and profitable. In this regard, non-hallucinogenic or short-acting versions of psychedelics appear to be an attractive strategy to reduce the costs of care. Without intense subjective effects, the supervision of a professional during drug administration is no longer required, getting psychedelics closer to the ultimate ideal of a cheap treatment delivery that does not rely on any psychotherapeutic support adjunct to drug prescription. This would amount to the integration of psychedelic treatments into a model that has been often criticized by psychedelic therapists, namely the out-patient paradigm of one-pill-a-day typical of conventional psychiatry.
The psychedelic renaissance has been a project built up on the shoulders of researchers and activists whose arduous advocacy efforts finally succeeded at reintroducing psychedelics into the scientific and public arenas. In the last decades, organizations like MAPS and Usona have proved that it is possible to develop new psychiatric treatments and overcome the hurdles of regulatory approval while staying committed to non-profit approaches, open science and public benefit. Today, we witness a new phase in the history of psychedelic research. Psychedelics are flowing into the mainstream and becoming the interest of biotech companies and pharmaceutical investors. As the field expands, new and diverse actors join the project of psychedelic medicalization, although perhaps with different motivations to those of the psychedelic pioneers who brought these substances from the underground. The broader goals of de-stigmatizing both psychedelics in particular and altered states of consciousness in general are abandoned as corporate psychedelia steps in. Profit-oriented approaches not only boost but also shift the research agenda of psychedelic scientists and, as the history of psychiatry has shown over and over again, profitability often becomes the worst enemy of good care.