DMT's Clinical Path For Treating TBI And Stroke: Phase 1 Dosing Finished As Phase 2 Gears Up

Algernon Pharmaceuticals’ AGNPF wholly-owned Algernon NeuroScience (AGN Neuro) successfully completed dosing the third and final cohort of its Phase 1 clinical study assessing an intravenous (IV) formulation of the company’s DMT compound, AP-188, aiming to treat both stroke and Traumatic Brain Injury (TBI.)

The study, conducted at the CHDR in the Netherlands, is set to test DMT’s safety, tolerability and pharmacokinetics (PK) at single-escalating, sub-psychedelic concentrations through a 6-hour long IV infusion. 

The trial’s safety review committee confirmed there were no safety or tolerability issues with the highest dose, which was able to maintain plasma DMT concentrations at targeted levels while being below the established psychedelic dose, equivalent to 0.2 mg/kg according to Dr. Rick Strassman, DMT researcher and the company’s consultant. 

Based on the positive delivery of the highest dose tested, the next study will include dosing subjects for six hours with multiple administrations, over a two-week period. The company would use its new single-dose regimen in an upcoming Phase 2 study on patients with stroke and TBI.

DMT’s Relation To TBI And Stroke

DMT, an agonist of multiple receptors including serotonin and sigma-1 -a receptor that responds to stress and is responsible for promoting cell survival, neuroprotection, neuroplasticity and neuroimmunomodulation, would also promote the release of Brain-Derived Neurotrophic Factor (BDNF), a protein believed to help in recovery after a brain injury.

Algernon’s CEO Christopher Moreau explained that neuroplasticity’s role in healing the brain after an injury is “one of the most exciting areas of research going on globally in the pursuit of a treatment for stroke and TBI.”

At high doses, DMT shows a rapid onset, intense psychedelic effects and a relatively short action duration. 

At non-hallucinogenic doses, DMT has preclinically been shown to induce and improve structural and functional neuroplasticity by activating pathways involved in forming neuronal connections and increasing the number of dendritic spines, which in turn connect with other neurons and are a critical site of molecular brain activity.

“Now that we have established the safety of a single sub-psychedelic dose of DMT, we are planning to accelerate our DMT Phase 2 studies accordingly, for both stroke and TBI,” said Moreau.

Photo by Robina Weermeijer on Unsplash