DMT Program for Stroke
A Natural Psychedelic that May Help the Brain Heal
N,N-Dimethyltryptamine, (DMT), is a naturally occurring hallucinogenic tryptamine producing effects similar to those of other psychedelics like LSD, ketamine, psilocybin and psilocin. DMT occurs naturally in many plant species and animals including humans and has been used in religious ceremonies as a traditional spiritual medicine by indigenous peoples in the Amazon basin. DMT can also be synthesized in a laboratory.
DMT has a rapid onset, intense psychedelic effects, and a relatively short duration of action at high doses. At sub-hallucinogenic doses, DMT has been shown to induce and improve structural and functional neuroplasticity both in vitro and in preclinical murine models.
DMT increases brain derived neurotropic factor (BDNF) which is a key mechanism involved in healing the brain after an injury like a stroke. DMT is believed to activate pathways involved in forming neuronal connections and has been shown to increase the number of dendritic spines on cortical neurons. Dendritic spines form synapses (connections) with other neurons and are a critical site of molecular activity in the brain.
A Phase 1 DMT trial is currently underway at the Centre for Human Drug Research in Leiden, The Netherlands. Following the completion of the study we will move forward and investigate an intravenous sub-hallucinogenic dose of DMT in acute ischemic stroke patients, in a planned Phase 2a DMT stroke study. A second Phase 2a study is being planned for traumatic brain injury (TBI).
Potential Treatment for Ischemic Stroke Patients
There are more than 12.2 million new strokes each year globally, with 7.6 million (62%) of these being ischemic, meaning a clot blocks blood flow to the brain. The balance are hemorrhagic strokes where there is bleeding in the brain. There are 6.5 million people who die from stroke annually, with one in four people over the age of 25 expected to have a stroke in their lifetime. Over 63 million years of healthy life is lost each year due to ischemic stroke-related death and disability.1
Blood thinners and clot removal can be employed in only 15-20% of ischemic stroke cases, and must be initiated within a short window following onset of symptoms. Further, these can only be administered once a CT scan has confirmed the type of stroke. The remainder of stroke patients are subject to ‘watchful waiting’ with the hope of a natural resolution to the blockage and limited attendant damage.
A preclinical study in an animal model for stroke, published in 20202, showed that rats treated with DMT recovered motor function more quickly and to a greater extent, and also exhibited lower lesion volumes when compared to control group animals that did not receive DMT. Key data from the study achieved statistical significance.
At Algernon, we plan to investigate whether DMT can be used to treat ischemic stroke to minimize its impact and trigger recovery. Such a drug could allow patients to begin treatment immediately, without a CT scan, and possibly while enroute to the hospital.
A Global Market for Stroke Treatment
The global stroke treatment market is forecast to reach USD $15 Billion by 2027.3 An aging population and a rapid rise in comorbidities like diabetes, hypertension, obesity, and atrial fibrillation are expected to contribute to a projected compound annual growth rate of approximately 7 percent in this disease indication.
North America is the leading regional market and will continue to have a significant share throughout the forecast period of 2019 to 2027.
Preclinical Data for DMT
Multiple independent preclinical studies demonstrate that DMT potentially helps promote neuritogenesis and structural and functional neuroplasticity: the brain’s ability to form and reorganize synaptic connections, which are essential for healing following a brain injury. The side chart shows the concentric measurement of cortical neuron growth in a murine model following exposure to DMT, as well as other psychedelic compounds, demonstrating how they promote neuritogenesis and synaptic growth – in vitro. The distinguishing value of DMT is its active life of only 8 minutes (as opposed to LSD’s half-life of 24 hrs.) and its ability to be effective at sub-psychedelic doses as well, which may be required in the cases of traumatized brain injury patients.
Data from our own preclinical study showed that a sub-hallucinogenic dose of DMT (30 nM) increased cortical neuron growth by 40 percent. In addition, significant neuron growth was also observed at concentrations as low as 100 pM. The dramatic neuron imagery displayed on the right from this study shows the comparative impact to a single cortical cell that was untreated against one that was treated with DMT. The resulting data generated will help the Company to plan its Phase 2 studies more effectively.
Clinical Trials for DMT
Phase 1: Intravenous Formulation Study
We have commenced treatment of subjects for our Phase 1 clinical study of an intravenous formulation of DMT in the Netherlands. The trial is being conducted at the Centre for Human Drug Research in Leiden.
The purpose of the study is to identify the safety, tolerability, and pharmacokinetics of DMT when administered as an intravenous bolus followed by prolonged infusion, for durations which have never been studied clinically. In addition, several pharmacodynamic measures believed to be associated with neuroplasticity, including both measurements of biochemical markers and electroencephalographic readings, will be recorded.
The first part of the study will use a single-escalating dose design aimed at identifying a safe and tolerable dose that will not produce psychedelic effects, while the second part will test the effects of repeated administrations of this same dose. There will be up to 60 healthy volunteers enrolled across the two parts of the study, which will include both psychedelic experienced and psychedelic naïve patients.
Since there have already been several Phase 1 studies successfully conducted on DMT, the Company is not anticipating any serious adverse events or safety issues arising from the study. The resulting data generated will help the Company to plan Phase 2 more effectively.
Phase 2a: Acute Ischemic Stroke and Rehabilitation
The Company has been working with top stroke experts to design planned Phase 2 studies in acute stroke and rehabilitation. The planned studies are expected to dose patients immediately following confirmation of their ischemic stroke diagnosis by imaging and will test the effects of DMT versus placebo on both the progress of the infarct and on patients’ recovery following the stroke as well.
Phase 2a: Traumatic Brain Injury (TBI)
We recently began consultation with global experts on traumatic brain injury to design a Phase 2a study. Established TBI databases will be used to determine the appropriate patient population for the trial.
The resulting data generated from our current Phase 1 clinical study will allow us to plan both our Phase 2 acute stroke and traumatic brain injury (TBI) studies more effectively, anticipated to take place in 2023.
- Phase 1 DMT study underway
- Phase 2a DMT human stroke study being planned
- Phase 2a DMT human traumatic brain injury (TBI) study being planned
We have engaged several global experts in the areas of DMT stroke and traumatic brain injury (TBI) and have retained the following medical and scientific advisors:
Dr. Rick Strassman, MD
Dr. Rick Strassman is a native of Los Angeles and obtained his undergraduate degree in Biological Sciences from Stanford University and his medical degree from Albert Einstein College of Medicine of Yeshiva University. His book DMT: The Spirit Molecule (2001) has sold 250,000 copies, been translated into 12 languages, and is the basis of a successful independent documentary that he co-produced. He is currently a Clinical Associate Professor of Psychiatry at the UNM School of Medicine. He trained in general psychiatry at UC Davis in Sacramento and took a clinical psychopharmacology research fellowship at UC San Diego. Joining the faculty at the University of New Mexico School of Medicine in 1984, his clinical research with melatonin discovered its first known function in humans.
Between 1990 to 1995, Dr. Strassman performed the first new US clinical research with psychedelic drugs in a generation. His studies involved DMT, and to lesser extent psilocybin, and received federal and private funding. From 1995 to 2008, he practiced general psychiatry in community mental health and the private sector. He has authored or co-authored nearly 50 peer-reviewed papers, has served as guest editor and reviewer for numerous scientific journals, and consulted for various government, non-profit, and for-profit entities.
Dr. David Nutt DM, FRCP, FRCPsych, FSB, FMedSci
Dr. David Nutt is currently the Edmund J. Safra Professor of Neuropsychopharmacology and Head of the Centre for Neuropsychopharmacology in the Division of Brain Science, Department of Medicine, Hammersmith Hospital, Imperial College London. He is also visiting professor at the Open University in the UK and Maastricht University in the Netherlands.
Dr. Nutt is also Chair of the charity DrugScience (formally the Independent Scientific Committee on Drugs (ISCD). He has been President of major national and international organizations: the British Neuroscience Association, the British Association for Psychopharmacology, the European Brain Council, and the European College of Neuropsychopharmacology. In recognition of his research success, he has been made a Fellow of the Royal Colleges of Physicians, of Psychiatrists, and of the Academy of Medical Sciences. He is also the UK Director of the European Certificate and Masters in Affective Disorders Courses and a member of the International Centre for Science in Drug Policy. He has edited the Journal of Psychopharmacology for over twenty-five years and acts as the psychiatry drugs advisor to the British National Formulary. He has published over 500 original research papers, a similar number of reviews and books chapters, eight government reports on drugs, and 31 books, including one for the general public–Drugs Without the Hot Air–which won the Transmission book prize in 2014.
Dr. Nutt was the clinical scientific lead on the 2004/5 UK Government Foresight initiative “Brain science, addiction and drugs” that provided a 25-year vision for this area of science and public policy.
Dr. Ede Frecska, MD
Dr. Ede Frecska is the Chairman of Psychiatry at the Faculty of Medicine of the University of Debrecen. He received his medical degree in 1977 from the Semmelweis University in Hungary. He then earned qualifications as a certified psychologist from the Department of Psychology at Lorand Eotvos University in Budapest. Dr. Frecska completed his residency training in Psychiatry both in Hungary (1986), and in the United States (1992). He is a qualified psychopharmacologist (1987) of international merit with 17 years of clinical and research experience in the United States, where he reached the rank of Associate Professorship.
During his academic years, Dr. Frecska’s studies were devoted to research on schizophrenia and affective illness. In his recent research he is engaged in studies on psychointegrator drugs, especially on the physiological effects of DMT in acute and chronic cellular stress like hypoxia. His theoretical work focuses on the interface between cognitive neuroscience and quantum brain dynamics. He is specifically interested in the mechanism of initiation ceremonies and healing rituals. He published more than 100 peer reviewed scientific papers and book chapters on these topics. Dr. Frecska is a member of several professional organizations (APA, ECNP, CINP), and has received grants and awards from a variety of sources (NARSAD, NIAA). Together with Slawek Wojtowicz, Luis Eduardo Luna, and fellow Algernon Medical & Scientific Advisor Dr. Rick Strassman, Dr. Frecska is the co-author of “Inner Paths to Outer Space”. He has also contributed chapters in Ervin Laszlo’s books “The New Science and Spirituality Reader” and “A New Map of Reality”.
Dr. Steven L. Wolf, PT, PhD, FAPTA
Dr. Steven Wolf is a professor in the Department of Rehabilitation Medicine, Emory University School of Medicine, where he explores novel interventions to improve extremity use in patients with stroke as well as mechanisms of cortical reorganization and inter-joint coordination associated with such changes. He is a world expert in physical therapy, a prolific and innovative researcher and leader who has made seminal contributions to patient care, and a highly sought-after lecturer and teacher who has been a valued mentor to students, residents and faculty. Dr. Wolf’s research has been widely disseminated via more than 300 publications. He has also authored or co-authored nine books that have become major pillars in the fields of physical therapy and rehabilitation medicine. Dr. Wolf has additionally made numerous appearances on National Public Radio and CNN, as well as multiple other media outlets as a subject expert commentator.
Dr. Anthony Rudd, MB, BChir, FRCP, CBE
Anthony Rudd, MB, BChir, FRCP, CBE is an emeritus professor of Stroke Medicine at Kings College London and recently retired as a consultant stroke physician at Guy’s and St Thomas’ Hospital. He was the London Stroke Clinical Director from 2010-2019 and the National Clinical Director for Stroke for NHS England from 2013-2019, where he oversaw dramatic improvements in the paradigm of NHS stroke treatment.
For over 20 years he chaired the Intercollegiate Stroke Working Party at the Royal College of Physicians which was responsible for developing the National Clinical Guidelines for Stroke and running the National Sentinel Stroke Audit program. He chaired the National Institute for Health and Care Excellence (NICE) Guidelines Group for Acute stroke and TIA and the NICE Stroke Quality Standards Development Group. He is also past president of the British Association of Stroke Physicians and is Honorary Vice President of the Stroke Association.
Dr. Rudd was educated at Cambridge and King’s College London, receiving his medical degree in 1978. His research interests are stroke rehabilitation, organization of care and quality improvement. He has published over 300 peer reviewed publications and supervised fourteen higher degrees. He was made a CBE (Commander of the British Empire) in 2013 in recognition of his services to stroke medicine.
Dr. Robert Simister, MA, MB, BS, PhD, FRCP
Robert Simister MA MB BS PhD FRCP is a consultant neurologist and stroke physician as well as an honorary senior lecturer at University College London, where he also serves as the Clinical Lead for the Comprehensive Stroke Service and the Clinical Director of Stroke Medicine and Acute Neurology. Since 2019, he has been the Joint Clinical Director for the London Stroke Clinical Network.
Dr. Simister received his medical degree from the Charing Cross and Westminster Medical School, now part of Imperial College London, and was awarded his PhD in Neuroscience from University College London in 2012. In addition to his consulting and directorial responsibilities, he maintains an active research program directed towards improving outcomes for stroke patients.
Dr. Zoltán Nagy (Neurologist)
Dr. Zoltán Nagy is a neurologist and a research doctor with a focus on brain damage, neuron destruction and apoptosis research, and running clinical studies dealing with post-stroke plasticity and bioelectric imaging. In 1966, Dr. Nagy graduated summa cum laude from the Faculty of General Medicine of the Budapest University of Medicine. In 1969, he obtained his professional qualification as a pathologist at the Institute of Pathology. In 1971, he was admitted to the Neurological and Psychiatric Clinic and in 1980 obtained a neuropathology qualification. In 1981, he became the head of the Cerebrovascular Department of the clinic and the consultant of the Vascular and Cardiovascular Surgery Clinic.
In 1991 he was appointed university professor. In 1994, he was appointed to the administration of the National Center for Brain Diseases, and after the National Psychiatry and Neurology Clinic placement of the Center, he was transferred to this institute as department head and stroke director. He is the founding president of the Hungarian Stroke Society and from 2002-07 was the director of the National Institute of Psychiatry and Neurology (OPNI) and the National Institute of Clinical Neuroscience (2012-18). He is currently (2019) professor emeritus of Semmelweis University and Pannon University in Hungary, head of the OKITI neuro-epidemiology working group, member of ETT-TUKEB (since 2010), president of the Semmelweis University Consistory, and member of the MAB Review Committee.
Traumatic Brain Injury (TBI) Advisors
Dr. Andrew Maas, MD, PhD
Dr. Andrew I. R. Maas is Emeritus Professor of Neurosurgery at the Antwerp University Hospital and University of Antwerp. He holds positions as past Chairman of the Neurotraumatology Committee of the World Federation of Neurosurgical Societies (WFNS) and the International Neurotrauma Society, and is Co-Chairman of the European Brain Injury Consortium. He has a vast experience as a general neurosurgeon and has specific research interests in Traumatic Brain Injury and neuro-intensive care.
Dr. Maas was the Principal Investigator of the IMPACT study group (International Mission on Prognosis and Clinical Trial design in TBI), that was awarded an NIH grant (2003-2011) and resulted in over 55 publications and recommendations for improved trial design. Currently, together with Prof David Menon, University of Cambridge, he coordinates the large-scale collaborative project CENTER-TBI: Collaborative European NeuroTrauma Effectiveness Research in TBI (www.center-tbi.eu), supported by the FP7 program of the European Union (Grant no: 602150; duration:2013-2020). He received an Honorary doctoral degree at the Burdenko Institute of Neurosurgery in Moscow in 2013 and Lifetime Achievement Award for his work on traumatic brain injury from the International Brain Injury Association in 2016.
Dr. Maas is member of various editorial boards, review committees and is a reviewer for over 35 international journals. In total he has authored over 250 publications in peer reviewed international journ
Dr. David L. Brody, MD, PhD
Dr. Brody, MD, PhD is a board-certified neurologist with both a research and a clinical specialization in TBI and neurodegenerative diseases. Dr. Brody was the Norman J. Stupp Professor of Neurology at the Washington University School of Medicine in St. Louis. Dr. Brody was also the Washington University site director for the National Football League (NFL) Neurological player care program. His research focuses on accelerating implications for better diagnosis, treatment and outcomes of traumatic brain injury.
Dr. Brody’s achievements have been recognized with several awards, including a Career Development Award from the National Institute of Neurological Disorders and Stroke (NINDS) and a Burroughs Wellcome Career Award in the Biomedical Sciences. His clinical monograph entitled Concussion Care Manual: A Practical Guide was published by Oxford University Press in 2014. Dr. Brody is the editor in chief of the journal of Neurotrauma and a member of the Editorial Board of Acta Neuropathologica.