5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) is a psychoactive indolealkylamine derivative of tryptamine and binds to a variety of serotonergic (5-hydroxytryptamine) receptors1. The agonist activity at 5-HT receptors, particularly at 5-HT1A and 5-HT2A receptors is considered to be the mechanism for its psychoactive effects and are considered to be the most important for the majority of its reported activities2.
Archaeological evidence shows that 5-MeO-DMT containing plants have been used for thousands of years, and many indigenous societies in South America still use them for religious and medicinal purposes3. 5-MeO-DMT undergoes extensive first-pass metabolism and is not orally available. In non-therapeutic and ritual contexts, it is usually administered parenterally through inhalation of vapor, as a sublingual paste, or insufflated through the nose4.
Epidemiological surveys and observational studies have reported that 5-MeO-DMT is associated with improvements in mood, anxiety, reduced stress, increased life satisfaction and mindfulness5. These therapeutic effects are thought to be mediated via reaching mystical-type experiences3. 5-MeO-DMT has been reported to produce mystical experiences with comparative intensity as seen with high doses of psilocybin but has a significantly shorter duration of effect3.
About psilocybin and psilocin
Psilocybin (3-[2-(dimethylamino)ethyl]-1H-indol-4-yl] dihydrogen phosphate) is naturally produced by numerous species of Psilocybe mushrooms and some other fungi species. It was originally isolated and synthesised by Albert Hoffman in 19586.
In the body, psilocybin is rapidly transformed into psilocin, which produces psychoactive effects. As such psilocybin is often considered a prodrug, as it is essentially psilocin that is responsible for the serotonergic effects7. Psilocin is a partial agonist at a variety of serotonin receptors, the most important of which in this setting is the 5-HT2A receptor8.
A number of controlled, randomised research studies as well as anecdotal reports and surveys suggests a broad therapeutic potential for psilocybin/psilocin in multiple neuropsychiatric conditions including somatic and neuropathic pain and primary headache states9, 10.
Psilocin has about a 50% bioavailability when given orally and is detectable in plasma within 20-30 minutes of administration of the parent compound. The half-life of psilocin in blood is around 180 minutes11. Onset of noticeable psychoactive effects occurs within 20-40 mins, peaks at about 60-90 mins after a dose, and tapers off typically around 6 hours after the dose12, 13. In contrast, when given intravenously, the onset is almost immediate, and the duration of effects is much shorter14, 15.
ELE-101’s formulation is designed to be administered via infusion. This method of administration can potentially produce more consistent and controllable responses than those observed in clinical studies of oral psilocybin. Additional advantage is that ELE-101 can be delivered in less time thus reducing the cost of healthcare delivery.