Once considered fringe medicine and the domain of maverick clinical researchers, innovators in the psychedelics field are now poised to make a significant contribution to the mental health landscape worldwide. Leading the way are companies now investing their energies in therapies using N,N-Dimethyltryptamine (DMT), a powerful entheogen existing in many plants and animals, as well as present exogenously in human beings. DMT’s extremely rapid onset and short duration of action are making it a frontrunner in the competitive field of medical therapies, where quicker patient turnarounds will mean financially viable models.
While DMT was first synthesized in 1931 by Canadian chemist Richard Manske, for thousands of years prior to that the substance has been used in the Amazonian Basin for ritualistic purposes in the form of ayahuasca brews to heal users and provide roadmaps for living. It wasn’t until 1956 that DMT’s psychoactive qualities were first clinically discovered by a Hungarian chemist and psychiatrist named Stephen Szara, after he extracted DMT from the Mimosa hostilis plant and administered it to himself intramuscularly.
DMT got a boost in the 1990s when researcher Dr. Rick Strassman, author of the iconic book “DMT: The Spirit Molecule,” conducted U.S. government-approved and funded clinical research at the University of New Mexico from 1990 to 1995, where he injected sixty volunteers with DMT. The book details the medical doctor’s groundbreaking research into the biology of near-death and mystical experiences. Many of the participants said the sessions with DMT ranked among the most profound experiences of their lives.
Today, clinicians are again revisiting the drug that promotes neuroplasticity, increased synaptic connectivity, and is showing promise for decreasing depressive symptoms and addictive urges. The following are a few of the frontrunners looking to be the first ones to bring new DMT therapies to market, and in the process ease a significant amount of human suffering.
ATAI Life Sciences
The biopharmaceutical conglomerate ATAI Life Sciences — a startup that currently has in the works 10 psychedelic programs and counts PayPal billionaire Peter Thiel as one of its primary investors — is currently involved in preclinical studies using DMT for treatment-resistant depression. Acting as a research incubator for the development of effective mental health treatments, one of ATAI’s subsidiaries, Viridia Life Sciences, is creating DMT treatments that will be paired with digital therapeutic integration developed by Introspect Digital Therapeutics (another ATAI-company) with the aim of streamlining preparation, integration, and continued patient engagement. The idea is to eventually make psychedelic treatments available for patients who live far away from treatment centers. ATAI’s website notes that while DMT for clinical trials is commonly administered intravenously by medical professionals, Viridia Life Sciences is utilizing ATAI’s drug development know-how to generate multiple DMT products based on alternative routes of administration. Delivery methods will likely use more simplified devices like mucosal delivery through the nose or mouth. Atai’s website states that studies are underway with clinical trials expected to begin early next year.
Earlier this month, Algernon Pharmaceuticals confirmed in a pre-clinical study that DMT increased growth of neurons in the brain when using “sub-hallucinogenic” doses. Part of their stroke treatment program, researchers conducted in vitro trials (performed in a controlled environments, typically in a test tube or petri dish) using their proprietary version of DMT called AP-188. They found that the compound increased the growth of neurons by 40 percent when compared to a control assay using ketamine. The aim of the study was to identify blood concentration and exposure time to target in Algernon’s eventual Phase 1 trial to optimize the neuroplastic effects of DMT without causing hallucinations. Prominent DMT researcher Dr. Rick Strassman, who is a consultant with Algernon’s stroke program, weighed in on the study results, saying, “These exciting in vitro data provide further evidence supporting the use of DMT in stroke, and strongly suggest that low doses and short exposure times are feasible.”
MindMed is exploring a number of psychedelic compounds as part of their mission to “discover, develop and deploy psychedelic-inspired medicines and therapies to address mental illness and addiction.” In addition to psilocybin-assisted therapy for alcohol use disorder and the ibogaine-derived molecule 18-MC for opioid addiction, this summer MindMed announced the initiation of a Phase 1 clinical trial of intravenous DMT therapy intended to produce a stable and prolonged DMT experience. Because DMT has a rapid onset and offset compared to the longer-acting psychedelic substances like psilocybin, the company believes their study will show that intravenous administration may allow greater control of the patient experience by enabling an acute termination of the psychoactive effects of DMT in the event of an excessively challenging event.
A biotech company specializing in the clinical development of psychedelics and analogues to target mental health disorders, Psilera’s current preclinical studies are focused particularly on alcohol use disorder. Their psychedelic-inspired new chemical entities are based on the DMT molecule and meant to affect the brain’s 5-HT2A receptors and other neurologically relevant proteins. Co-Founder and CSO of Psilera Dr. Jackie von Salm said in a release, “The growing prevalence of alcohol use disorder, especially in conjunction with the Covid-19 pandemic, needs to be addressed as the current methods of treatment are outdated and insufficient.”
Focusing primarily on DMT for addiction recovery, Entheon’s therapies are intended to treat the underlying causes of substance use disorder. Developing a combination of genetic and predictive data analysis through its genetic testing subsidiary HaluGen Life Sciences, the company’s intention is to ensure the safest possible DMT treatments. To that end, Entheon employs genetic testing using a saliva sample to help determine the risk probability of different compounds prior to treatment, in the hopes of mitigating risk factors like serotonergic toxicity and other adverse outcomes. Entheon’s biomarker platform is powered by artificial intelligence and machine learning with the intent to understand individual biological traits and align suitable treatments, as well as establish patient-specific support post DMT experience. Entheon’s website notes that a proof of concept human study (Phase 1/2a equivalent) is estimated to begin in Q4 2021 at the Centre for Human Drug Research in Leiden, Netherlands, to assess the effect of DMT in otherwise healthy adult nicotine users.
Creating a treatment strategy aimed at the psychedelic naïve, Small Pharma is exploring DMT therapy as a rapid-acting treatment for major depressive disorder and beginning clinical trials early in 2021 in collaboration with Imperial College London. In an announcement last week, Small Pharma says their study is “the world’s first regulated clinical trial for DMT-assisted therapy in major depressive disorder.” They note that their “proprietary intravenous formulation of DMT was very well tolerated in individuals with no previous experience of psychedelics.” The Phase I study of their DMT formulation, called SPL026, was administered in combination with psychotherapy to 32 healthy volunteers and showed a favorable safety profile with no serious adverse effects. Small Pharma is now in the process of a Phase IIa study of SPL026 in combination with psychotherapy in 42 patients with major depressive disorder. The study, being held at two UK clinical trial sites — Hammersmith Medicines Research and MAC Clinical Research — will assess the efficacy of one versus two doses of SPL026 in combination with psychotherapy.
Image: Nicki Adams with adapted graphic by Sbrools