At Clínica Synaptica, we continually rethink what mental health means in a society where our basic needs are often neglected. That is why we are committed to disseminating the latest scientific advances in innovative, evidence-based treatments, bringing research closer to society. Our goal is to ensure that as many healthcare professionals and interested parties as possible are aware of developments that could open up new possibilities in mental health and social well-being.
What is 5-MeO-DMT and where does it come from?
5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) is a psychedelic substance that differs from the classic pharmacological profile of other better-known psychedelic substances. This tryptamine is found naturally in both the plant and animal kingdoms. Some of the best-known Amazonian plants include Virola, Anadenanthera peregrina (yopo or cohobo), and Dictyoloma incanescens, found in their seeds, bark, and leaves (Agurell et al., 1969; Pachter et al., 1959). It also attracted the attention of 20th-century anthropologists because it is present in the venom of the Sonoran desert toad (Incilius alvarius), where it constitutes a significant proportion of its chemical composition (Uthaug et al., 2019).
Phenomenology and pharmacology of 5-MeO-DMT
While most classic psychedelics exert their effects primarily through activation of the serotonergic 5-HT2A receptor, 5-MeO-DMT acts on 5-HT1A receptors (Halberstadt et al., 2012), which are involved in mood regulation (DeLorenzo et al., 2016) and control of the autonomic nervous system (Youn et al., 2013), lowering blood pressure and heart rate.
Its subjective effects are also unique in that, rather than causing vivid and complex visual images, they are characterized by ego dissolution and a sense of oneness with Everything (Barker, 2018). However, it is difficult to predict a generalized effect, with reports of nausea, distress, confusion, and flashbacks of memories that are subsequently difficult to recall (Davis et al., 2018).
5-MeO-DMT is orally inactive (Shulgin & Shulgin, 1997a) and is frequently administered intranasally or by inhaling vapor extracted with a controlled heat source. The use of these routes of administration causes its acute effects to last for 15–20 min (Weil & Davis, 1994). Learning to navigate the subjective effects of this substance is difficult due to the speed and intensity of its effects, as well as the brief duration of the altered state of consciousness it evokes.
Evidence of its therapeutic potential in observational studies
The first data we have on the therapeutic potential of 5-MeO-DMT comes from observational, prospective studies in natural settings.
Davis et al. (2018) conducted a cross-sectional survey of more than 500 people to characterize patterns of use in the general population and assess the potential risks and benefits associated with its use. Of the proportion of participants who reported having been previously diagnosed with a psychiatric disorder, significant improvements were reported in the following conditions: post-traumatic stress disorder (79%), depression (77%), anxiety (69%), substance use problems (63%), and obsessive-compulsive disorder (53%). Only 2–10% reported a worsening of these conditions.
In another subsequent survey, led by the same research group (Davis et al., 2019), specific improvements in symptoms of depression and anxiety were observed after the use of 5-MeO-DMT in a group setting. Specifically, among the 149 participants who reported symptoms of depression, 80% said they felt an improvement in their condition, 17% experienced no change, and 3% reported a worsening of their depressive symptoms.
Evidence of its effectiveness in depression in clinical trials
However, it has been in recent years that the therapeutic potential of 5-MeO-DMT has been systematically studied in clinical trials.
In a Phase 1/2 clinical trial involving 16 patients diagnosed with treatment-resistant depression, a potent and rapid antidepressant effect was observed with a vaporized formulation of 5-MeO-DMT (Reckweg et al., 2023). The study compared the effect of a 12 mg dose and an 18 mg dose, with a personalized dosing schedule that included up to three dose increases in a single day (from 6 mg, 12 mg, and 18 mg). The results showed that, after 7 days, 50% of patients in the 12 mg group and 25% in the 18 mg group were in remission, while in the personalized dose group, remission reached 87.5%. In the latter group, seven out of eight patients reached a peak level of mystical experience during the subjective effects. All remissions from depression were observed from the first day, and 60% were detected just 2 hours after treatment.
On the other hand, in an even more recent Phase I study, participants received a weekly sublingual dose of 5-MeO-DMT (6 mg, 9 mg, or 12 mg) or placebo for a period of four weeks (Bistue et al., 2025). Participants did not experience any subjective effects from this route of administration, maintaining stable cognitive and behavioral functions and continuing their daily activities and usual social interactions. The results of this study showed that 5-MeO-DMT is a safe, fast-acting compound with good tolerability, emerging as a promising candidate for future therapeutic applications, minimizing or eliminating subjective psychedelic effects. However, there is still no specific evidence on its efficacy in depression via the sublingual route.
Mechanisms underlying the depressive effect.
However, the reasons for the antidepressant properties of this particular psychedelic appear to be similar to the neurobiological and phenomenological mechanisms that are triggered by other psychedelics:
- In animal studies, 5-MeO-DMT has been shown to promote neuroplasticity in the medial frontal cortex by increasing dendritic spine density (Jefferson et al., 2023). These changes correlate with a decrease in ruminative processes that are present in various mental illnesses.
- In addition, it has shown a formidable ability to regulate the immune system and inflammation (Uthaug et al., 2020), which alters the flow of neurotransmitters and activates the stress system, keeping the body in threat mode.
- Finally, mystical experiences characterized by ego dissolution and union with the Whole have also been associated with a therapeutic response. The intensity of such an experience promotes psychological changes of openness and psychological flexibility (Carhart-Harris & Nutt, 2017).
Final Considerations
Research on 5-MeO-DMT is still in its early stages, but the available data points to an emerging field with enormous therapeutic potential. The short duration of its subjective effects makes its administration in clinical settings more feasible and economical than other psychedelic substances. However, the intensity of its subjective effects and the disruption of the ego structure may require more clinical sessions to integrate the experience.
At Clinica Synaptica, we are closely following these advances with an attitude of scientific prudence and critical openness. Our commitment is not to promote quick fixes, but to contribute to therapeutic changes that are profound and can stabilize over time.
In the coming years, we will likely see a transformation of the therapeutic landscape in mental health. Staying up to date, promoting critical thinking, and continuing to conduct rigorous research will be key to integrating these new tools safely, ethically, and responsibly into clinical practice.
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