Every forty seconds in the United States, someone experiences a stroke. Strokes represent the third leading cause of death and disability globally, with billions of dollars funneled into long-term health care services, rehabilitation and support to individuals for stroke survivors. Conventional stroke treatments often fail and long-term rehabilitation can be lengthy and intensive. In other words, a novel approach to stroke treatment and recovery is timely.
Enter Algernon Pharmaceuticals. In September, 2022, the company announced that they would be carrying out a Phase 1 clinical study investigating the use of slow-release intravenous DMT infusions for stroke patients.
“Hundreds of drugs have failed in the stroke treatment space, and nearly all of them have focused on the same strategy: a delayed attempt at neuroprotection,” explained Dr. David Nutt, Professor of Neuropsychopharmacology at Imperial College London and Algernon consultant.
“Algernon’s approach with DMT is to bolster the brain’s natural recovery by enhancing neuroplasticity to facilitate the creation of new neural networks. This is something completely different than what has been tried before.”
The rationale for using DMT for stroke patients
N,N-dimethyltryptamine, or DMT, is a psychedelic compound that produces similar effects to LSD and psilocybin. However, DMT differs from other psychedelics in the rapidity and intensity of its onset and effects, delivering a near instantaneous, visually intense trip that can last from 30 to 45 minutes. This potent psychedelic is produced by diverse plant and animal species and is also an endogenous hallucinogen found in the human body.
Evidence suggests that DMT may offer unique therapeutic benefits as a stroke treatment. Strokes represent a form of brain injury. The most common type of stroke, ischemic strokes, are often caused by clots that block critical blood flow to the brain. Brain cells can become damaged or can even die if blood flow is inhibited for a long time. However, strokes can also injure the brain in other ways. Neuroinflammation occurs following a stroke, largely due to reperfusion injury. Reperfusion takes place when the blood supply returns to the oxygen-deprived brain tissue, paradoxically causing tissue damage.
DMT has been well-studied with respect to its effects on neuroinflammation and reperfusion injury. The potential that DMT holds in this space is promising, particularly because there are currently no conventional, highly effective medical therapies for strokes that address reperfusion. DMT can offer protective effects after reperfusion injury and also stimulate cell growth and enhance neuroplasticity. Neuroplasticity is the process by which the brain forms new synaptic connections in response to learning, experience or injury. This combination of tissue protection, cellular growth and enhanced neuroplasticity may therefore be a game changer for stroke patients.
“In a rat stroke occlusion study, rats given DMT showed reduction in the area of brain damage from the stroke and had almost a full recovery of motor function when compared to control,” said Christopher Moreau, CEO of Algernon. “In a preclinical research study at UC Davis, DMT increased neuroplasticity in a cortical neuron growth assay.”
Moreau believes that DMT represents a novel way to promote healing and recovery after an ischemic stroke.
“For 85% of patients suffering an ischemic stroke, which constitute 85% of all strokes, there are no treatment options,” reflected Moreau. “Hundreds of stroke drugs have failed in the clinic but have been focused on neuroprotective measures, whereas DMT represents a different approach to stroke treatment, helping with healing after the injury occurs.”
Algernon has also been exploring the viability of DMT as a treatment for stroke for over a year. The company’s earlier preclinical research found that sub-hallucinogenic doses of DMT stimulated neuron cell growth by 40%. Their upcoming clinical research will be focused on studying the effects on sub-hallucinogenic doses on human participants.
“My work with DMT in the 1990s demonstrated that psychedelic drugs can be safely studied in humans and established a framework for investigations into the therapeutic benefits of the entire class,” said Rick Strassman MD, Algernon consultant, psychiatrist, psychopharmacologist, and author of DMT: The Spirit Molecule.
“Groups testing these agents in psychiatric disorders are manifold, but Algernon’s decision to explore the potential benefits of DMT’s neuroplastogenic effects in stroke is a unique and especially exciting strategy.”
Algernon’s landmark stroke study
Algernon’s Phase I stroke study will kick off in the last few months of 2022 in the Netherlands, testing the safety, tolerability and pharmacokinetics of DMT on up to 60 volunteers. What makes the study particularly unique is that DMT will be administered as a prolonged infusion for durations that have never before been clinically studied. For stroke patients, treatment is a race against the clock. Brain cells can begin to die within five minutes of blood supply being shut off. Prolonged intravenous infusion allows DMT to enter the bloodstream immediately and remain circulating in the body.
“The fastest way to deliver a drug and maximize the dose is through either a bolus dose or long duration intravenous delivery method because it bypasses the stomach and liver,” explained Moreau.
“Algernon will be delivering a sub-psychedelic dose to patients over a range of multiple time periods. This approach has never been done before in a Phase I trial.”
The administration of sub-hallucinogenic doses to human participants is also noteworthy. According to some experts, hallucinogenic effects are necessary for some or all of psychedelics’ therapeutic effects. To date, there have been few human trials exploring the therapeutic impact of psychedelics at sub-hallucinogenic levels. Algernon’s research will provide valuable insights into the specific therapeutic actions of sub-hallucinogenic doses of DMT on people –albeit using novel forms of DMT.
The brand has filed patent applications for novel salt forms of DMT, along with dosing, formulation and method of use applications. A novel salt form of DMT is considered a separate structure from the original compound, and can therefore be patented. Salts can be used to improve the core drug rendering it more stable, tolerable, safer, or even more effective.
The first part of the study will use a single-escalating dose design to determine a safe, tolerable dose that will not produce psychedelic effects. The second part of the study will test the effects of repeated, prolonged administrations at this dose. The sixty participants will be a mixture of psychedelic-naive and psychedelic-experienced healthy volunteers. Algernon plans to use data generated by the study to provide information about dosage and duration for the Phase II study, when the DMT IVF formula will be tested on acute and recovering stroke patients. Watch this space.
