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Another Psychedelic and Its Potential Psychiatric Promise

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Psychedelics’ potential is rivaled only by their power. They are extremely potent substances that have been used in various cultures dating back thousands of years, largely for ritualistic and spiritual purposes. In addition, they have traditionally been called upon to offer those who wish to gain insight into realms believed to be inaccessible to the conscious mind.

This is more or less the same reason why interest in psychedelics has skyrocketed among clinicians, researchers, and the general public. For clinicians, these drugs are being touted as potential groundbreaking treatment options for a host of psychiatric and inflammatory conditions as they can potentially treat symptoms that are extremely difficult to manage with conventional medicines. For researchers, studying psychedelics can help them understand how these substances can eliminate the interference of ego structures and conscious experiences in their subjects to unveil the most fundamental dynamics of the mind, thereby offering new insights into our understanding of neuroscience, consciousness, and how the two intersect. For the general public, they offer relief from symptoms of hobbling psychiatric conditions, fuel for philosophical musings, and the opportunity to take part in deeply meaningful experiences. As has been frequently reported in research dating back to at least 2006, psychedelic sessions are frequently ranked among the top five most meaningful experiences in individuals’ lives even more than a year later.1

Psychiatrists are very excited about the potential of psychedelics, particularly with respect to drugs like psilocybin, LSD (lysergic acid diethylamide), and MDMA (3,4-methylenedioxymethamphetamine). Despite the excitement about adding these substances to psychiatrists’ toolkits, one of the most potent psychedelic compounds available, DMT (N,N-dimethyltryptamine), has received very little attention from clinicians until recently.

While there is no question that DMT holds enormous potential, as clinicians we must first understand how to harness it.

What Is DMT?

DMT is a classic psychedelic that can induce profound changes in sensory perception (hallucinations), feelings of euphoria, and radical alterations in typical thought patterns. On the neurochemical level, DMT behaves similar to other psychedelics (e.g., LSD, psilocybin, mescalin) by not only binding to serotonin 2A (5-HT2A) receptors in the central nervous system, but also interacting with other serotonergic (5-HT1A, 5-HT2C, and 5-HT7) and glutaminergic receptors, sigma-1 receptors, and trace-amine associated receptors. DMT also interacts with acetylcholine and dopamine signaling.2 Interestingly, DMT exists naturally in the brains of mammals, including humans, though the reason is unclear. Some have speculated that it may play a role in altering consciousness to allow for dream states, spiritual or mystical experiences, or even passage from life onto death. Currently, there is no evidence to support these claims, and it is not even clear if DMT exists in concentrations high enough to produce measurable effect.3

DMT is the main ingredient in medicines that have traditionally been prepared and consumed as teas by indigenous peoples from throughout South America well before any European contact. The most well-known example is ayahuasca. In conjunction with DMT (from Psychotria viridis), ingredients in these teas include naturally occurring monoamine oxidase inhibitors, which delay onset and extend the duration of DMT’s effects for several hours. If one takes synthetic DMT, which is often inhaled using a vape pen, the effects may take a few minutes to manifest and may peak within five to ten minutes before beginning to wear off. The entire experience may only last 30 minutes or so.2

What Are the Effects of DMT?

One of the most promising areas of research for psychedelics in recent years has been its potential role in mitigating anxiety and depression among terminal cancer patients suffering with existential crisis. Unfortunately, there are few pharmacotherapies or interventions in the field of psychiatry that can be used to help patients as they struggle to come to terms with their own mortality. “The ego, faced with the prospect of its own extinction, turns inward and becomes hypervigilant, withdrawing its investment in the world and other people,” Michael Pollan wrote in his paean to psychedelics, How to Change Your Mind.4 Psychedelics offer the opportunity to suspend the ego temporarily, which can be experienced initially as terrifying, but it is followed by a gradual sense of surrender, acceptance, love, and a greater sense of unity with the universe as the ego dissolves and one experiences simulated death and rebirth. Psychedelics are not treating end-of-life anxiety and depression pharmacologically; rather, they are treating these conditions phenomenologically (i.e., through the subjective experience it induces).

Though DMT acts upon the same serotonin receptors as other classical psychedelics, the DMT experience is unique. With smoked DMT, the ego is not just dissolved in a transcendent experience; it is obliterated.

According to DMT users, the visible world is often replaced by extremely vivid kaleidoscopic patterns of color. Furthermore, users report being transported to what they describe as another plane of reality with the presence of godlike creatures, and many of those who have taken DMT have reportedly interacted with these creatures. An online survey conducted by researchers at Johns Hopkins School of Medicine involving 2,561 individuals (median age 32 years; 77% male) who reportedly had encounters with these ostensibly autonomous beings found that half of participants who considered themselves atheists before the experience no longer did afterwards, and more than half of total participants believed that these beings are conscious, intelligent, benevolent and continued to exist after the encounter in a real but different reality.2

Characterized by Davis as an “ontological shock,” over half of the participants claimed that the DMT experience was one of the most spiritually significant and meaningful moments in their lives. Many respondents also reported profound changes in outlook and positive changes in life satisfaction and subjective well-being.2

Potential Directions for DMT Research

Clinical trials of DMT are only now beginning, so it will likely be years before we even start to glean its full potential. However, years of research has shown us that the beneficial psychological effects of psychedelics appear to be tied to their long-term subjective effects and how they change patient perspective. The important question to ask is that if DMT imparts its effect through ego annihilation, wouldn’t it make sense that it could be even more effective than other psychedelics?

Theoretically, yes.

Like other psychedelics, it may prove capable of easing existential distress among terminally ill patients and promoting subjective well-being. It may even help individuals with substance use disorders overcome their dependence. A pharmaceutical company based in the United Kingdom, in conjunction with Imperial College London’s Centre for Psychedelic Research, initiated a phase I trial earlier this year to see if DMT could be used to treat major depressive disorder.

However, there are potential roadblocks to DMT’s use in a clinical setting, too—at least in its smoked or vaped form. As Stephen Ross, one of my colleagues at New York University who has studied psychedelics extensively, observed during a conversation we had about frontiers of psychedelic research, psychedelics are only part of the equation in a larger model of medication-assisted psychotherapy.  Patients should not simply be given these extremely potent drugs, and then left on their own to process the experience. They need guidance from people who have the tools and training to place it into a larger narrative.

To properly provide care, staff members need to be trained to be effective guides to patients who are experiencing the acute effects of the drugs and to help them contextualize and absorb the experience. Furthermore, patients need to be psychologically prepared for the experience and will likely require several sessions before and after the experience to effectively process it. Given the enormous difference between the acute effects of DMT and LSD or psilocybin, it stands to reason that protocols and models that provide the best therapeutic experience are not even remotely interchangeable.

To fully harness the therapeutic power of DMT, as well as psychedelics in general, research will need to focus not only on the potential conditions it can help treat or the neurophysiological effects of the drug, but how the drug is administered and how patients are guided through the experience. We will need to embrace the role of navigator, rather than simply impartial facilitator of awareness, growth, and psychological development of our patients.

About the author:

Samoon Ahmad, M.D., is Professor of Psychiatry at NYU Grossman School of Medicine.


1: Griffiths RR, Richards WA, Johnson MW, McCann UD, Jesse R. Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J Psychopharmacol. 2008;22(6):621-632. doi: 10.1177/0269881108094300.

2: Davis AK, Clifton JM, Weaver EG, Hurwitz ES, Johnson MW, Griffiths RR. Survey of entity encounter experiences occasioned by inhaled N,N-dimethyltryptamine. J Psychopharmacol. 2020;34(9):1008-1020. doi: 10.1177/0269881120916143.

3: Carbonaro TM, Gatch MB. Neuropharmacology of N,N-dimethyltryptamine. Brain Research Bulletin. 2016;126:74-88. doi: 10.1016/j.brainresbull.2016.04.016.  

4: Pollan M. How to change your mind: what the new science of psychedelics teaches us about consciousness, dying, addiction, depression, and transcendence. 2018.