Even among psychedelics, DMT is extraordinary. Sometimes called the “spirit molecule”, this endogenous psychoactive compound occurs naturally in many plants and animals, and has been implicated in everything from dreaming to religious experiences. However, unlike most psychedelics, for example psilocybin, DMT exhibits extremely rapid onset and short duration of action.
Now, in light of research showing its positive effects on neuroplasticity and EEG-observed brainwave activity, this may mean DMT is the key to reaching the hundreds of millions of people who stand to benefit from psychedelics-assisted psychotherapy.
It’s everywhere – but still a mystery
N,N-dimethyltryptamine (DMT), is a psychoactive indole alkaloid present in the South American beverage Ayahuasca, an entheogenic brew that often contains Banisteriopsis caapi vine, the Psychotria viridis shrub, as well as a variety of other ingredients. Critically, in this form, DMT’s effects can persist for up to 3-6 hours, due to the presence of monoamine oxidase inhibitors (MAOIs), which prevent oxidization of DMT in the digestive tract and allows it to be absorbed in the stomach and small intestine; without this, the body metabolizes orally ingested DMT too quickly to allow it to have any effect.
Structurally, DMT is an analog of tryptamine and archetypical for most classical psychedelics (e.g. psilocybin), closely resembling the neurotransmitter serotonin and the hormone melatonin, associated with feelings of calm and sleep, respectively. Additionally, though DMT is endogenously produced by some mammalian tissues, including the human lungs and brain, its function continues to be debated.
Like many psychedelic compounds, DMT acts on a variety of 5-HT receptors: In particular, it is a partial agonist of the 5-HT1A/2A/2C receptors, primarily in cortical neurons and the limbic system, where it is believed to increase neuroplasticity and decrease functional connectivity, respectively. This is critical, since neural plasticity in is especially important for exerting the anti-depressant effects of serotoninergic psychedelics.
An express lane to psychedelia?
While there have been few well-controlled clinical studies exploring isolated DMT as a treatment for depression, several recent studies have demonstrated the utility of Ayahuasca in the treatment of major depression. In rat cells, in vitro assays have shown DMT to promote neuroplasticity, as assessed by neuronal growth and increased synaptic connections, both processes correlated with improvements in depressive symptoms. Moreover, EEG observations of DMT’s effects on brainwaves have shown changes hypothesized to be beneficial for depression.
Despite similarity to other psychedelics, however, DMT exhibits comparatively more rapid onset and shorter duration of action when not administered alongside the MAOIs present in ayahuasca brew. For example, unlike a psilocybin experience, which can last upwards of 6-hours, DMT’s hallucinogenic effects can pass in just 15 minutes. Indeed, in 60s popular culture, recreational use of DMT was sometimes referred to as going on a “business trip”, due to the fact that a user could achieve a full psychedelic experience so rapidly.
The experiences reported by both recreational users and clinical trial participants include an altered reality, visualization of geometric patterns with closed eyes, altered sense of time and space, unusual somatic sensations, perception of dream-like situations and presence of external sentient forms, among others. There has been particular fascination with the lattermost of these, with researchers like Terence McKenna and Rick Strassman reporting “encounters” with remarkably consistent themes across settings and users, putatively due to top down neurological processing of some types of psychedelic experiences.
While DMT is commonly administered intravenously, Viridia Life Sciences is leveraging atai’s drug development expertise to generate multiple DMT products based on alternative routes of administration. Importantly, Viridia’s DMT product will be paired with a digital therapeutic being developed by atai-company Introspect Digital Therapeutics, with the aim of streamlining preparation, integration, and continued patient engagement.
Development is underway with clinical trials expected to begin early next year.