Last updated: March 4, 2025
Psychedelic substances are gaining increasing scientific attention worldwide, both among researchers and in clinical settings. A study from the University of California draws striking conclusions about microdosing DMT: even a dose too small to cause hallucinations appears to have measurable effects on depression and anxiety in rats. Below, you can read exactly what the study did, what it found, and what its limitations are.
The therapeutic effects of psychedelics: the current state of affairs
Research into psychedelics as therapeutic agents has gained significant momentum over the past decade. Clinical studies on psilocybin (Johns Hopkins, Imperial College London), MDMA (MAPS), and ketamine show promising results for treatment-resistant depression, PTSD, and anxiety disorders. At the same time, the data base for virtually all of this research is still limited, and larger randomized trials are needed to draw definitive conclusions.
DMT, short for dimethyltryptamine, is one of the most extensively studied classic psychedelics. It is also the active ingredient in ayahuasca, the traditional South American beverage that has been the subject of both anthropological and pharmacological research for decades. Psychiatrist and researcher Rick Strassman conducted the first controlled clinical study of DMT in humans at the University of New Mexico in the 1990s; his findings are documented in the book DMT: The Spirit Molecule, which remains a standard work to this day for anyone delving into the psychopharmacology of psychedelics.
Neural plasticity: what ketamine revealed
The starting point for the research by David Olson, professor of chemistry and neuroscience at the University of California, Davis, was an observation in rats under the influence of ketamine. Ketamine was found to be able to reconstruct damaged connections between neurons in the networks that regulate emotions and mood—an effect known as neural plasticity or neuroplasticity.
Neuroplasticity refers to the brain’s ability to reshape synaptic connections. In depression and chronic stress, certain neural networks, particularly in the prefrontal cortex, become damaged or depleted. Substances that promote neuroplasticity can potentially restore these connections. Olson suspected that this mechanism was not unique to ketamine but was also driven by other psychedelics.
His suspicion proved correct. In a follow-up publication, his team demonstrated that LSD, DMT, and MDMA had similar neuroplastic effects in rats asketamine.² Olson called this group of substances “psychoplastogens”—substances that promote neuroplasticity via psychedelic mechanisms.
The problem: anxiety at higher doses
However, there was a complication. The doses required to measure clear neuroplastic effects also caused pronounced anxiety reactions in the rats. Therapeutic effect and unwanted side effect went hand in hand. This led Olson to a central research question: can the therapeutic effects be achieved without the hallucinogenic effects, and thus also without the accompanying anxiety?
“I really wanted to answer the question of whether the hallucinogenic effects of these compounds were necessary for the therapeutic effects,” said Olson.
DMT microdosing: the experiment
Olson and his team calculated a dose of DMT that would be comparable in potency to microdoses of LSD or psilocybin. The rats were administered a microdose of DMT every three days, an amount too small to induce hallucinatory behavior. On rest days, the animals underwent standardized tests that serve as proxies for anxiety and depression in humans: the forced swim test protocol and the open-field model.³
After seven weeks, the researchers measured a significant reduction in anxiety- and depression-related behavior in the rats that had received the microdose. The increase in anxiety observed with higher doses did not occur with the microdose. At the same time, brain samples from the animals did show signs of improved synaptic density in relevant brain regions; the neuroplastic effects were thus present, even without a hallucinogenic stimulus.
What does this mean, and what does it not mean?
Olson’s conclusion is cautious but relevant: in rats, the therapeutic effects of DMT can, at least in part, be achieved without the hallucinogenic component. This is scientifically interesting because it challenges the common assumption that the psychedelic experience itself is necessary for the therapeutic effect.
However, there are two important caveats. First, these are rat studies. The physiology of the rat brain differs from that of humans in crucial ways, and behavioral models for anxiety and depression in rats are only an indirect approximation of how these conditions manifest in humans. Second, DMT had a neurotoxic effect in some of the rats: in some cases, damage to brain cells was observed. Olson explicitly acknowledges this and emphasizes that further research, including human studies, is necessary before conclusions about safety and efficacy in humans can be drawn.
DMT, ayahuasca, and related substances
DMT occurs naturally in a large number of plants and is produced in trace amounts by the body itself. In the context of ayahuasca, it is combined with MAO-inhibiting plants (such as Banisteriopsis caapi), which makes it orally active; when taken orally on its own, DMT is rapidly broken down by the MAO enzyme in the intestinal wall. When administered intravenously or via inhalation, however, it is immediately active, which forms the basis of clinical research protocols.
A chemically related substance is 5-MeO-DMT, a stronger and shorter-acting psychedelic found, among other places, in the venom of the Bufo alvarius toad. 5-MeO-DMT is also being studied in early clinical trials as a potential treatment for treatment-resistant depression, but is separate from Olson’s DMT microdosing research.
Microdosing in a Broader Context
Olson’s research aligns with the broader discussion on microdosing, in which users take sub-perceptual doses of psychedelics—typically one-tenth to one-twentieth of an experiential dose—with the aim of achieving subtle improvements in mood, focus, or well-being. Anecdotal reports are numerous, but controlled scientific evidence in humans remains scarce. Ongoing research at institutions including Imperial College London and the University of Toronto is attempting to fill this gap.
For those who want to learn more about the scientific background of DMT and psychedelics in a broader sense, Rick Strassman ’s work is a good starting point, particularly his book *DMT: The Spirit Molecule*. Questions about products in our range or the content of this article? Contact us via customer service or read more about Dutch-Smart on our About Us page.
Sources
Castrén, E. & Antila, H. (2017) - Neuronal plasticity and antidepressant drugs, Nature Neuroscience
Ly, C. et al. (2018) - Psychedelics Promote Structural and Functional Neural Plasticity, Cell Reports
Kuypers, K.P.C. et al. - Microdosing psychedelics: More questions than answers? PLOS ONE
About the author
Editor
Derek writes for Dutch Smart about smart shop products, cultivation techniques, and harm reduction. He combines practical experience with factual, substantiated information, without hype or vague promises.
