Is there a role for DMT in the body and brain beyond the deep psychedelic journeying it can elicit? Numerous studies have shown a neuroprotective and neurogenesis potential for DMT to assist recovery from stroke and to protect from crippling degenerative diseases like Parkinson’s and Alzheimers. What is the latest scientific overview for this fundamental neurotransmitter and how does it fit into the evolving model of consciousness itself?
The Plastic Brain
Comparing the body to a machine and the brain to a computer couldn’t be further from the truth. As opposed to mechanical objects, the body and brain are composed of living biology that harbours the ability to adapt and regenerate. Every time we learn a new skill, expose ourselves to a new language, or sit down to meditate, we effectively rewire our neurocircuitry and alter the shape of our brains. Much like plastic, our brains are malleable and mould around our experiences.
Science has come a long way in its understanding of the adult brain. At the beginning of the 20th century, Nobel Prize winner and “father of modern neuroscience” Santiago Cajal proposed the model of the “fixed” and “immutable brain”. This school of thought recognized that — while the child brain rapidly learns, adapts, and morphs — the adult brain simply stalls and consists of neurons that never divide or regenerate.
Since this time, animal and human studies have demonstrated that the brain churns out a consistent supply of new neurons. The work of neuroscientist Joseph Altman in 1965 played a particularly important role in challenging the dogma of the fixed brain.
Although some researchers contest this idea, others have gathered evidence that suggests the adult hippocampus produces new neurons and incorporates them into its circuitry — a process known as neurogenesis.
Neurogenesis might supply waves of new neurons, but many of these cells die shortly after differentiation. As an energetically expensive organ, the brain actively prunes and deletes idle cells and synapses; they aren’t contributing to its overall function.
However, by engaging in effortful learning and exposing our brains to something outside of our fixed routines, we can harness the power of neuroplasticity to make sure the brain integrates these new neurons into the cerebral network. Despite his metaphorical intent, Einstein might have hit the nail on the head when he stated, “once you stop learning you start dying”.
Neurogenesis and disease
Not only does neurogenesis most likely take place in the adult brain, but it also appears to play a key role in cognitive health and disease. Neurodegenerative diseases such as Parkinson’s and Alzheimer’s feature altered neurogenesis as a hallmark sign. Not only do existing neurons degenerate during maladies of the brain, but the organ loses its ability to generate new cells.
Logically, efforts to prompt the brain to create new neurons might counter these deleterious effects. Using animal models, researchers have demonstrated that stress and depression may contribute towards disease pathogenesis, whereas modalities such as exercise could help to reverse it.
Do psychedelics hold the key to neurogenic medicines?
In its search for catalysts of neurogenesis, science has examined the effects of certain psychedelic compounds on neuronal activity. Among these, DMT stands out as a particularly promising molecule.
DMT, or N,N-dimethyltryptamine, occurs as an endogenous neurotransmitter and indole alkaloid in various species of plants and animals. The hallucinogen also occurs in the human body, yet the exact source of the molecule remains unknown. The presence of enzymes involved with the metabolism of DMT suggest it might occur within lung, thyroid, adrenal, and pineal gland tissue.
Researchers have explored DMT, and the DMT-containing brew ayahuasca, for their potential in stoking neurogenesis. Whereas DMT represents a single molecule, ayahuasca consists of multiple species of plants and features a broad spectrum of phytochemicals.
While data surrounding DMT display promise in inducing neurogenesis, other components of ayahuasca might augment this effect. For example, a 2017 study published in the journal Scientific Reports tested alkaloids from Banisteriopsis caapi on adult mammalian brain cells. Also known as the ayahuasca vine, this plant species doesn’t contain DMT but produces molecules that enable the gut to uptake the molecule without destroying it.
Motivated by findings that detailed the antidepressive effects of B. caapi, the researchers decided to test and observe the effects of the alkaloids harmine, tetrahydroharmine, harmaline — as well as the harmine metabolite harmol — on adult mouse progenitor cells.
Neural progenitor cells are a form of stem cell found throughout the central nervous system. These precursor cells have the ability to differentiate into several types of brain cells. Progenitor cells reside in two primary areas within the brain of adult mammals.
First, they’re found within the subgranular zone of the dentate gyrus — an area of the hippocampus that plays a critical role in learning and memory. Secondly, these neural stem cells are located within the subventricular zone. Also positioned in the hippocampus, this region harbours the highest quantity of proliferating brain cells.
When genes call for it, stem cells transform into early progenitor cells. From here, they differentiate into one of three brain cells types: oligodendrocytes, astrocytes, or neurons. When the latter occurs, the brain undergoes neurogenesis — “neuro” relates to the cell type, and “genesis” refers to their generation in the brain.
After applying these alkaloids to progenitor cells within a Petri dish, the research team discovered that all four molecules successfully prompted the cells to divide and proliferate. Not only this, but the phytochemicals also caused them to differentiate into neurons and migrate. Neuronal migration plays an important part in neurogenesis and involves neurons moving to areas of the brain where their signal-transmitting abilities are required.
Although promising, an obvious gap exists between the action of molecules on cells within a Petri dish and those within the complex network of the brain. To get a clearer picture of the effects of ayahuasca constituents on the adult brain, researchers from the University of Madrid, Spain, tested DMT on both cell cultures and living animals.
First things first, the team isolated progenitor cells from the subgranular zone of the hippocampus of adult mice. They then administered DMT to some cells, while adding a combination of DMT and a molecule that blocks its action to other cell cultures. The cells that received DMT alone demonstrated increased neurogenesis. The researchers determined that DMT achieved this outcome by binding to a receptor site known as sigma-1.
Next up, they tested the neurogenic effects of DMT on living mice. One group received the psychedelic, while the second group served as a control. Both groups underwent a battery of learning and memory tests. The DMT-treated mice outscored their counterparts, signalling the new production of neurons within the hippocampus.
The researchers stated, “Taken together, our results demonstrate that DMT treatment activates the subgranular neurogenic niche regulating the proliferation of neural stem cells, the migration of neuroblasts, and promoting the generation of new neurons in the hippocampus, therefore enhancing adult neurogenesis and improving spatial learning and memory tasks.”
It appears that both DMT and the group of B. caapi alkaloids all contribute to the neurogenic effects of ayahuasca, and most likely contribute to the improvements experienced by depressed, addicted, and traumatized individuals.
The University of Madrid team concluded, “The versatility and complete neurogenic capacity of the DMT guarantee future research regarding this compound. In addition, its ability to modulate brain plasticity indicates its therapeutic potential for a wide range of psychiatric and neurological disorders, among which are neurodegenerative diseases.”
The role of DMT in emergency stroke treatment
As well as displaying promise in the domain of chronic cognitive disease, DMT might also play a future role in more acute settings. Almost 800,000 Americans experience a stroke every year, a medical emergency that damages neurons and reduces their ability to communicate with each other. For every minute a stroke patient remains untreated, they lose almost 2 million neurons and 12km worth of axonal fibres.
A study to be conducted by Algernon Pharmaceuticals aims to administer DMT to stroke patients. Driven by evidence of the molecule’s ability to induce neurogenesis, researchers hope that DMT will ramp up neuronal production and exert positive neuroplastic effects. As opposed to catapulting patients into alternate dimensions, they’ll receive sub-threshold microdoses. If successful, this research could lay the groundwork for the use of DMT at the hands of first responders to preserve neurons during the acute stage of a stroke.
This study follows previous research that administered DMT in an animal model of stroke. Rats that received DMT exhibited lower lesion volume. Researchers also identified lower levels of proteins involved in cellular death and inflammatory processes.
Luke Sumpter is a freelance journalist that specializes in health, wellness, and alternative therapies. Currently, he’s working on a dissertation exploring the emerging role of the endocannabinoid system in orthopaedic medicine.
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