Amphibious anti-depressants and other wonders

This article refers to:

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety

The last two decades have been remarkable for the level of scientific and now popular interest in hallucinogenic compounds. It is inevitable that this interest would come to extend beyond the current darling of such research – the classical hallucinogen, psilocybin, which is found in a variety of mushrooms. In this month’s issue, Davis, et al. report on data from a survey provided to individuals who were administered vaporized 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), another classical hallucinogen, in a group, ceremonial setting. Their findings suggest that inhaling 5-MeO-DMT in these ceremonies was not associated with any adverse effects or persistent problems, and that it may have led to improvements in depression and anxiety. Though the authors are careful to not draw any conclusions given the naturalistic, questionnaire-based, and cross-sectional nature of these findings, they suggest that 5-MeO-DMT may represent a novel anxiolytic and anti-depressant pharmacotherapy, and that it deserves further study.

5-MeO-DMT comes from many organic sources, ranging from plants, such as the ayahuasca admixture diplopterys cabrerena, to more exotic sources, such as the Sonoran Desert toad, whose parotid glands produce an exudate that may be dried, pyrolysed, and inhaled. The ceremonial use of 5-MeO-DMT likely dates back millennia, and it continues to be used in communities – both indigenous and syncretic – centered around the consumption of “plant medicines” and other “entheogens.” As reported by the authors, inhaling 5-MeO-DMT leads to profound psychoactive effects lasting about an hour, and characterized by all the hallmarks of a “psychedelic” or mystical-type state: transformations in the sense of self and of reality, and an experience of communion with a higher consciousness. The apparent lack of adverse effects is reassuring and consistent with what we know about these compounds more generally – that when administered in a responsible manner, to suitable and prepared individuals, they are almost invariably well-tolerated.

Any conclusions pertaining to the anti-depressant efficacy of 5-MeO-DMT must wait until the appropriate clinical trials are conducted. There are some features of this administration paradigm, however, that suggest new directions for hallucinogen-based treatment, and that merit some exploration. Since the 1950s until today, researchers and clinicians exploring the therapeutic potential of hallucinogens have administered them almost entirely in individual psychotherapy settings, often with more than one therapist present. Drug effects, meanwhile, can last several hours. No research has examined how the apparent benefits of hallucinogen-based treatment models might be preserved, and their risks managed, while also rendering them less labor- and time-intensive. A group-based framework, involving the administration of a relatively short-acting agent that may be just as effective, represents a more practicable approach that is better suited to widespread clinical dissemination.

It is an important question, of course, whether this unconventional strategy for entering into non-ordinary states – namely, smoking toad venom, or a synthetic analogue, in a group ritual – might find acceptance and appeal beyond the communities of enthusiasts and seekers currently engaged in such practices. Yoga, other mind/body practices, chanting, and meditation, for example, may also have comparable effects, are less forbidding, and are more likely, with regular practice, to lend themselves to sustained benefits. Additionally, there are various hurdles, the most onerous of which being that 5-MeO-DMT is illegal, Schedule 1, and beset by stigma and misperception. Currently, Compass Pathways and Usona Institute are each poised to independently begin an ambitious research program to investigate the anti-depressant efficacy of psilocybin, when administered orally in an individual psychotherapy setting. Though there is no guarantee that any of these efforts will result in FDA approval, the ground-work is being set for rescheduling and commercializing a paradigmatic classical hallucinogen, with implications for sister compounds, perhaps, such as 5-MeO-DMT. It is important to emphasize here that research concerning psilocybin is still in its infancy, and it is far too early to draw any conclusions regarding its anxiolytic and antidepressant benefits.

Toad drool, mushroom caps, and communion with a higher consciousness: the eldritch and eerie associations are inevitable. All that’s missing is a bubbling cauldron and some eye of newt. One might worry that, frustrated with the modest effects of SSRIs, we risk regressing to some twilight past of sorcery and witchcraft. It is precisely in reports such as this, however, that we might take a more dispassionate and scholarly perspective on such matters. As the research continues, we may even go on to dispel our prejudices entirely, irrespective of whether our reflex is yay or nay, and come to an entirely empirical view of what these compounds actually do, and how they might be responsibly approached.