Intravenous DMT shows promise in reducing depression symptoms, study reveals

A recent Scientific Reports study focussed on evaluating the effect of intravenous (IV) N, N-Dimethyltryptamine (DMT), a psychedelic intervention, on the mental health of healthy volunteers.

Study: Effects of DMT on mental health outcomes in healthy volunteers. Image Credit: Astafjeva / ShutterstockStudy: Effects of DMT on mental health outcomes in healthy volunteers. Image Credit: Astafjeva / Shutterstock


The prevalence of mental health disorders, particularly depression and anxiety, has significantly increased globally. At present, not many treatments are available to treat these conditions. However, psychedelic therapy, such as serotonin 2A receptor [5-HT2AR] agonist, has been shown to bring about considerable improvements in mental health disorders.

The majority of studies have examined the efficacy of classic psychedelics, such as lysergic acid diethylamide (LSD), psilocybin, and ayahuasca. Open-label and controlled trials have shown that psilocybin can effectively reduce symptoms of anxiety and depression. The effectiveness of this compound lasted for up to six months. 

A placebo-controlled trial also revealed that LSD was able to reduce symptoms of depression and anxiety. Similarly, the DMT-containing brew ayahuasca effectively alleviated the symptoms of depression. Interestingly, a study based on a limited number of individuals observed that DMT could effectively reduce depression symptoms after a day of administration. There is a need for a large-scale study to analyze the effects of DMT as monotherapy.

In comparison to classic psychedelics, DMT exhibits a distinct profile that includes a lack of tachyphylaxis or desensitization with use and a short acute manifestation when introduced via inhalation or injection. Owing to a lack of tachyphylaxis, DMT offers flexible administrations. More studies must be conducted to analyze IV DMT, particularly concerning its brief effect duration. Such an effect could be beneficial for patients who experience recurrent symptoms manifestation after psilocybin therapy.

About the Study

The current recruited a total of 30 psychedelic-experienced healthy individuals. These participants were subjected to IV DMT fumarate in two separate studies, i.e., a placebo-controlled study and a DMT arm. Participants with a history of psychedelic drug use, psychiatric illness, alcohol abuse, blood or needle phobia, diabetes, and heart ailment were excluded.

Two studies were conducted to investigate the positive and negative effects of IV DMT on psychological factors. In the case of negative manifestation, the association of IV DMT and the occurrence of severe depression, anxiety, and neuroticism in psychedelic-experienced healthy volunteers was studied. The role of IV DMT on optimism, gratitude, well-being, and meaning in life was explored to assess the positive effect.

Study Findings

The current study indicated that IV DMT administration significantly reduced depression severity. Furthermore, a decrease in neuroticism was observed in the placebo-controlled sample. In line with previous research, this study highlighted a significant association between DMT-induced acute experiences of ‘Oceanic Boundlessness’ and improvements in depression and anxiety. This finding supports the therapeutic potential of DMT for the treatment of psychiatric disorders.

Recent clinical trials on psychedelics indicated an association between psychedelics and depression symptomatology. Consistent with the findings documented here, previous studies have also revealed that psychedelic therapy causes a significant reduction in symptoms of depression in psychiatric patient populations and healthy populations. 

In contrast to previous clinical trials, this study did not note any decrease in neuroticism or an increase in positive psychological factors, such as optimism, well-being, nature-relatedness, and gratitude, after being exposed to intravenous DMT. This contradictory result could be due to the lack of long-term experiments and insufficient clinical data for neuroscience experiments, such as magnetic resonance imaging data and echocardiographs. Furthermore, there is a possibility that the effects of DMT on mental health outcomes could be compromised due to the ceiling effects of the healthy cohort.

Notably, a decrease in the symptoms of anxiety and depression was significantly correlated with the quality of the acute experiences triggered by DMT. In this study, the acute experiences were measured by the 5D-ASC subscale Oceanic Boundlessness. In the future, researchers must focus on investigating whether other variables are responsible for inducing positive emotional health.

Similar to the mechanism of action of other psychedelics, the effect of DMT on mental health is also based on neurobiology. Mechanistically, DMT stimulates 5-HT2A receptors, which help alleviate symptoms of depression and anxiety.


The present study has some limitations that include the use of different dosages of DMT in the placebo-controlled sample, which may generate variability in study outcomes. Another limitation of this study is the different times of assessment of mental health outcomes. Since the datasets of both studies were pooled, the study outcomes may be affected due to variable methodology. There is a possibility of underestimation of the true psychological improvements induced by IV DMT.

Despite the limitations, this study indicated the positive effect of IV DMT in improving mild symptoms of depression in a healthy population. In the future, more research is required to assess the safety and effectiveness of DMT for clinical application.

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