The Viability of DMT in the Treatment of Major Depressive Disorder

In a recent groundbreaking study, researchers investigated the safety, tolerability, and effectiveness of dimethyltryptamine (DMT) administered to patients with treatment-resistant major depressive disorder (MDD).  Authors indicated that their study was the first of its kind to test the therapeutic effects of pure DMT in patients with depression. Their findings, including the rapid antidepressant effect of DMT in patients only one day following dosing, opened the gateway for future investigations that may unravel the full therapeutic potential of DMT.

The study, summarized:

  • Study participants were either patients with “treatment resistant” MDD, i.e., they had experienced a minimum of two prior treatment failures for MDD and at least one failed course of antidepressants in their current depressive state and those who were classified as “healthy controls,” i.e., those without MDD or any mood disorders.  Participants who regularly used psychedelics were excluded from the study.
  • Two dosing sessions were conducted in which both patient groups were given a small dose of DMT (0.1mg/kg) for the first session and a larger dose of DMT (0.3mg/kg) for the second session.
  • Blood pressure and heart rate significantly increased shortly after (intravenous) administration of DMT, though returned to baseline over periods spanning approximately 10-45 minutes
  • Participants tolerated both doses of DMT relatively well, experiencing relatively few and adverse effects of limited severity while reporting a marked reduction in depression severity only one day after receiving a dose of DMT.  The drop in depression severity was emphasized even more with the larger DMT dose, with significant improvements seen for those with chronic MDD (average duration of 27 years) who had failed several prior antidepressant trials.

Prompted by growing interest in the therapeutic potential of psychedelics, e.g., psilocybin and ketamine, researchers took the first steps towards exploring the viability of DMT within the realm of clinically treated MDD by conducting an exploratory clinical trial at the Neurobiological Studies Unit (Yale University School of Medicine, West Haven, CT).  Previous clinical trials exploring the usefulness of psychedelics as therapeutic modalities for depression have highlighted the utility of psilocybin-assisted therapy as a potential adjunct to established treatment methodology.  However, as orally-administered psilocybin typically has a very slow onset and long duration of action, researchers were intrigued by the almost instantaneous psychedelic effects of DMT in conjunction with their comparatively shorter duration and sought to determine if this trend was translatable to the rapid relief of depression symptoms. 

In contrast to other psychedelics used in medicinal and recreational forums, DMT is identified as innate, i.e., endogenous, to the composition of human and animal brains (in low concentrations) where it binds to several serotonin receptors including the  5-HT2A receptor targeted by a litany of pharmaceuticals employed in MDD treatment regimens.  Accordingly, DMT belongs to a class of “serotonergic” psychedelics including lysergic acid diethylamide (LSD) and psilocybin which act on the brain to produce a gamut of effects on perception, mood, and cognition.  Despite extensive research, the full role of endogenous DMT is still widely unknown.  Research has suggested DMT may act as a “protective” molecular compound that enhances survivability of cells under extreme stress and at risk of death, particularly in the brain, e.g., from conditions causing prolonged oxygen deprivation.  Other studies have alluded to the potential antidepressant effect of DMT.  However, these studies are rare and have involved the use of ayahuasca (an Amazonian botanical hallucinogenic brew that contains DMT in addition to a slew of other compounds) and rat-models.  With this in mind, researchers at the Neurobiological Studies Unit sought to elucidate the effects of pure DMT on human subjects.  Interestingly, study participants exhibited results similar to those seen in rats in an unrelated study whereby DMT administration initially provoked an anxiety response that was then rapidly extinguished through elimination of the rats’ cued fear memory in addition to eliciting behavioral responses characteristically induced by many antidepressants.

When taken recreationally, psychedelic effects of DMT are typically elicited at doses higher than 0.2mg/kg and include alterations in perceptions, emotion, and cognition that are intensified with increasing dosage.  Effects also include visual hallucinations and “spiritual insights.”  

In both MDD and healthy patient cohorts, DMT elicited transient alterations in perception without any evidence of serious adverse psychological effects.  Participants reported that the experience was intense yet meaningful and pleasurable, with all participants willing to return for the increased DMT dose.

The study model was etched from the same framework seen in studies examining the antidepressant effects of ketamine, i.e., participants were administered DMT within a hospital setting and given minimal supportive psychotherapy.  Although depression markedly decreased in patients following administration of the higher dose of DMT, no correlation was noted in regard to the psychedelic effects felt with either dose.

Traditional antidepressants often take weeks to months of consistent use before the first signs of positive mood changes may be seen and are ineffective in 30% or more of the population.   As this is the first study to produce data surrounding the safety and tolerability of DMT in patients with depression, future studies are warranted which entail trials of increased duration, larger and more diverse patient populations, assessment of a litany of psychedelic and other effects including the duration of the antidepressant effect achieved following DMT administration and any potential adverse symptoms that may arise afterward, changes in DMT dose concentration and speed of administration, e.g., slower IV infusion, alterations in setting where DMT is administered, and more.  The prospect of rapid antidepressant delivery for those who are otherwise treatment resistant casts a guiding light for those who may use this study as a platform from which to build upon, inform, and possibly establish a means for therapeutic DMT within the clinical sphere.