FDA May Allow Trials for Algernon’s Psychedelic DMT

Canada-based Algernon announced its clinical program in January based in part on a preclinical study published last year in Experimental Neurology by researchers from Semmelweis University, which showed DMT can promote neurogenesis and neuroplasticity in a rat model of brain ischemia.

Drug repurposing company Algernon Pharmaceuticals has requested a pre-Investigational New Drug (IND) meeting with regulators in the hopes of launching a clinical trial in stroke patients for n,n-dimethyltryptamine (DMT), a naturally derived psychedelic compound. If approved, the trial could be the first psychedelic tested by a company in patients recovering from stroke.

Canada-based Algernon announced its clinical program in January based in part on a preclinical study published last year in Experimental Neurology by researchers from Semmelweis University, which showed DMT can promote neurogenesis and neuroplasticity in a rat model of brain ischemia.

The company’s compound, AP-188, is an intravenously delivered microdose of DMT that will not produced hallucinogenic effects, and it will seek a Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA).

The DMT program fits with Algernon’s approach to repurposing existing compounds. Its lead asset is NP-120 (ifenprodil), a decades-old N-methyl-d-aspartate (NDMA) receptor glutamate receptor antagonist that has been approved in some markets outside the U.S. for circulatory disorders.

The company is planning to release topline results from a Phase IIb study in patients with COVID-19 by the end of this month. Algernon is also planning a Phase II trial for NP-120 in patients with idiopathic pulmonary fibrosis.

In recent years, the FDA has approved a marijuana-derived drug, Epidiolex(cannabidiol), for rare forms of epilepsy, and ketamine a dissociative anesthetic often used as a party drug–for treatment-resistant depression.

Academics and nonprofits have launched dozens of trials in recent years for psychedelics like 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, and lysergic acid diethylamide (LSD), primarily in patients with psychiatric diseases including depression, post-traumatic stress disorder, eating disorders, or alcohol use disorder.

DMT, a serotonergic agonist derived from the Psychotria viridis plant and used to make a traditional psychedelic compound called Ayahuasca, is in the same tryptamine family as psilocybin, but has not received the same amount of attention. COMPASS Pathways received an FDA Breakthrough Therapy designation for psilocybin in 2018 for treatment resistant depression.

Still, interest is increasing: it has been tested in clinical trials by academics in patients with depression. The first company-backed Phase I DMT trial, by London-based Small Pharma Ltd., launched in January in patients with anxiety and depression. And earlier this week, psychedelic specialty companies PharmaDrug and MindSet Pharma announced progress on preclinical programs researching DMT. PharmaDrug is exploring DMT for ischemia reperfusion injury in patients undergoing kidney transplantation.

And in November, Dublin-based GH Research, announced its DMT had completed the Phase I safety trial in patients with treatment-resistant depression for a similar psychoactive compound, 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT), and was beginning a Phase II trial.