Andrew R. Gallimore is a neurobiologist, chemist, and pharmacologist interested in the relationship between psychedelic drugs, the brain, consciousness and the structure of reality. Here he chats with Reset.me about the role of DMT in neurogenesis, neuroprotectivity and, quite possibly, neuroevolution itself.
Reset: So there’s been a couple of studies that have come out recently adding to the literature on the role of N,N-DMT in the brain. I wondered if you could just maybe share some brief explanations or thoughts on the role or potential role of neurogenesis with tryptamines.
Andrew Gallimore: So there are two different, quite distinct but potentially related facets of the DMT effect. You have the acute effect, which is the psychedelic effect, and which is what most people are interested in — the short term temporary disruption of cortical network activity.
So you get the emergence of new patterns of activity, which can be helpful in treating neuropsychiatric conditions where there are ingrained negative patterns of activity, cyclic negative thought patterns that lead to depression and anxiety or post traumatic stress disorder.
So that’s one aspect, where you basically plasticize the brain temporarily, you liquefy it in a sense, kind of like heating a metal so you can move it into a more desirable shape or geometry.
What is Brain Plasticity?
Reset: Just on that level of the plasticity of the brain: It seems to be that’s what the brain is designed to do, to have an imprint and then it has this plastic state, and then to certain degrees, as people age, the degree of their plasticity of the brain, their ability to learn new things, hold information might degrade. But it seems that what these studies are showing is that DMT has an active role in that process. Is that new understanding?
Andrew Gallimore: Yeah. You have to be very careful about use of the word plasticity and what it means. Plasticity in neuroscientific terms has a very specific meaning… when I’m saying plasticization of the brain, I’m talking about a temporary loosening of these networks and allowing new patterns of activity to emerge temporarily, which then become fixed in a more positive pattern as the brain “cools” after the psychedelic wears off.
But when academic papers discuss plasticity, what they’re talking about is connections between neurons. Neurons, as you know, connect mainly using synapses, the synaptic connections, which are these chemical connections between neurons. And plasticity is about changing either the strength of these connections –making them stronger or weaker — but also about forming new connections or getting rid of old or no longer needed ones.
Rewiring the Brain
Plasticity is about the brain being able to rewire itself by changing its connections. This is a slower process and is not something that occurs instantaneously when you take a psychedelic drug. It is something that takes a longer period of time to emerge because it involves both chemical and structural changes in the synapses.
So there are a number of ways that the brain can rewire itself. The cheapest way or the simplest way is to strengthen or weaken the wiring that it already has. You make the synaptic connections stronger, or you make them weaker. That’s one way to do it.
And the brain can do that in a matter of minutes. And it’s doing it all the time, every time you learn something, if you learn a new language, you learn a new piece of vocabulary, there are these kinds of changes that are taking place throughout different parts of the brain.
The brain can also form new connections, which are between these thin tendrils that come off neurons, axons and dendrites. The axons are what carry the information away from a neuron and the dendrites receive information from other neurons. And you can change the branching of these. Like a tree, these long membrane processes that come off these neurons, you can prune them, you can make them less branched, or you can increase the branching.
But it’s a little bit more complex than that — if you read a paper about neurogenesis, which means neuron generation, you’ll see that there are number of stages in the process. The first stage is the creation of new neurons, which must be then converted into the correct type of neuron, which is called differentiation. Then the neuron has to move, literally, physically has to move into the right place. Once it’s in position, then the connections begin to form. The neuron has to be wired up to the already existing neurons in the brain.
Then you can start tuning the actual strength of those connections. So you’ve got a number of stages in neurogenesis and they’re all controlled by different genes, different proteins, different small molecules. And all of these stages can be potential targets for manipulation by drugs.
The Role of the Sigma-1 Receptor
Reset: It seems like the studies mention ayahuasca, which contains DMT, and there’s a separate study on harmine and harmaline’s ability for neurogenesis as well, same with psilocybin, but it seems those specific, almost neurotransmitters seem to trigger this neurogenesis. That’s what the studies seem to be saying. Yeah?
Andrew Gallimore: Yeah, exactly. So this particular Nature Translational Psychiatry paper basically demonstrated that DMT acts via this Sigma-1 receptor to stimulate neurogenesis. The Sigma-1 receptor has something of a history in DMT research in that it binds strongly to and activates this Sigma-1 receptor, which is a mysterious receptor because no one is really 100% sure what its primary function is. And you can tell that by the name, Sigma-1. Normally receptors are given a name based on the molecule that naturally binds to it, like the serotonin receptors or glutamate receptors. You know the molecule produced by the body that’s actually activating it.
The Sigma-1 receptor is present in throughout the brain, but its endogenous activating molecule is unknown. Now, when people are given DMT, what this paper shows is that DMT activates neurogenesis in the hippocampus, which is involved in memory formation. The hippocampus is very important in memory. And it’s also highly sensitive to neuro-atrophy, since it’s a relatively small structure. Think of Alzheimer’s disease — when you start losing cells in the hippocampus, you get quite dramatic effects on memory across the brain.
What DMT seems to do is actually activate neurogenesis in the brain. As I said before, there are a number of stages of neurogenesis from the actual production of new cells, all the way through to their migration and wiring. DMT activates neurogenesis at this early stage, stimulating the production of new neurons.
And what this study showed is that this positive effect on the production of new neurons in the hippocampus was controlled by this Sigma-1 receptor. They demonstrated this using a Sigma-1 antagonist, a molecule that blocks the Sigma-1 receptor and stops DMT from binding. So not only did they observe this proliferation of new cells in the hippocampus, but they were able to pinpoint the key receptor that’s involved, which is the Sigma-1 receptor.
DMT for Treatment of Neurogenerative Diseases
Reset: So that sounds significant. So what’s the outcome here with the medical Psychedelic Renaissance for DMT, therapy and its healing mechanism? Is it something that for people with conditions like Alzheimer’s and things like that, would low-level doses… There was a recent study or came out saying they’re thinking of using it for stroke victims in sub-threshold doses and as psychedelics coming back into the medical fold at lower doses, micro doses, they’re seeming to find a lot of therapeutic applications or potential for that.
Andrew Gallimore: Yes. So it’s possible, and I would say it’s not demonstrated, but yes, I think the therapeutic aspect of something like DMT or psilocybin are likely to be manifold. There is the psychedelic effect, the temporary change in network activity, disrupting these negative network patterns. Then you’ve also got this neurogenesis effect as well. So potentially, you’re actually allowing the brain to form new connections, to actually rewire itself.
These obviously are not independent necessarily. You can envisage that part of recovery might be actual changes in the wiring of the brain with DMT facilitating the brain being able to rewire itself. So I think it’s highly likely in my opinion that they are related, in that you get this almost synergistic benefit of these psychedelic drugs. They’re generating both this temporary liquefaction of network activity. But then there is also this more prolonged effect where the neurons can actually start to rewire themselves.
These obviously are not independent necessarily. You can envisage that part of recovery might be actual changes in the wiring of the brain, and more permanent changes in the wiring, and allowing the brain to rewire itself, or at least facilitating the rewiring.
So I think it’s highly likely in my opinion, that they are related in that you get this almost synergistic benefit of these drugs, in that they’re doing both. They’re doing both this temporary liquefaction or plastification, whatever you want to call it, of network activity. But also then this is more prolonged effect where the neurons can actually start to rewire themselves.
DMT as a Neuroprotective
Now, there’s another effect as well, which is slightly different when it comes to DMT, in that DMT seems to protect neurons. So this is completely different to neurogenesis, in that it actually protects neurons against hypoxic stress. So when your brain is starved of oxygen, cells start dying. Brain cells cannot live for very long in the absence of oxygen.
DMT seems to protect cells. So if you give DMT to a stroke patient, for example, the hypothesis is that it’s going to protect cells by protecting against this hypoxic stress, so stop cells from dying in the first place. And then it may also have the effect of facilitating recovery by allowing the cells that do survive to actually rewire themselves and to maybe even reproduce themselves, to proliferate. So it’s producing new cells to replace the cells that died because of the stroke and naturally allowing those to rewire.
Reset: Yeah, that makes sense, because there’s a hypothesis that DMT is released in the brain potentially at death or near death experiences. And then if it has this direct complimentary activity, if we can see that it maybe adds a bit of credence to that theory as well, probably Strassman’s too.
Andrew Gallimore: Strassman and Ede Frecska worked on this a lot and he proposes this, that close to death when the respiratory system, the cardiovascular system is collapsing, the brain is being starved of oxygen, that the release of large amounts of DMT, not via the pineal, but probably the lungs or other structures, large structures will release large amounts of DMT.
Basically this is the brain’s last stand against this hypoxic stress. So should you actually recover from the collapse of your cardiovascular and respiratory system, that you might stand a better chance of coming out of it intact, neurologically intact. So that makes sense.
And that would link into, of course, the NDE in that your brain would be full of DMT. And of course, assuming you were conscious, it would have the usual psychedelic effects that would be separate from its intended effect, perhaps, by the body, which would be to protect the brain from cell death caused by lack of oxygen.
Functioning in Hyperspace
Reset: So if we look at the full dose psychedelic DMT experience, there’s often that information density, there’s that speed, there’s that everything at once-ness and connection. It feels like a lubricant, or what we’re seeing here is that it’s protecting the brain structure, but also it has the potential to increase, as you said, the dendrites and the synaptic pathways. It’s like part of the process of building the ability to function in hyperspace. Do you think there’s any credence or could you conjugate that a bit further?
Andrew Gallimore: Yeah. These are the kind of ideas I’ve thought about as well. So when people normally take DMT, it’s over within a few minutes. So you give them 50 milligrams or whatever by injection or smoke it, and it floods the brain and then it’s gone again rather quickly. Now, the question is, if you bring someone into the space and keep them there over an extended period of time, over hours or even days, then perhaps this kind of rewiring effect could be absolutely important, as you say, in that the DMT might actually cause the brain to rewire and resculpt itself and allow it to adapt to and learn to construct this hyper-dimensional environment experienced during a DMT trip.
The secondary effect of DMT, which is this effect on the Sigma-1 receptor, which is promoting plasticity, promoting neurogenesis, might allow the brain to actually restructure itself to more efficiently build that hyper-dimensional structure, the DMT space. So, beyond its acute psychedelic effect, DMT is also priming the brain to construct the DMT space, which is wild.
Of course, that wouldn’t necessarily be the orthodox explanation for DMT. The orthodox explanation is the facile one, just to say, well, it’s just a hallucination, but I think we both think that it’s more than that. There is something about the DMT space that appears to be well beyond the geometric constraints of this universe, of this reality, of consensus reality.
So the brain does appear to be able to reach into these spaces, or even has a tendency or propensity to reach into these high dimensional spaces, given the right stimulation. DMT seems to provide just the right stimulation. Why is that the case? Why is it that DMT in particular allows this? What’s the historical relationship between the human brain and DMT?
In my opinion it’s not a coincidence that one of the most common naturally occurring plant alkaloids in the world, or certainly the most common and simplest naturally occurring psychedelic plant alkaloid, also happens to be the most effective in transporting you to this high dimensional, crystalline, alien reality.
A Neuroevolutionary Catalyst?
I don’t think that’s a coincidence. I think there is a long standing relationship between DMT and the human brain. We just don’t know what it is. And that also would explain why the brain is able to switch from constructing normal waking reality to constructing this extremely complex high dimensional space.
The brain has learned to construct this reality, the normal waking world as a model of the environment, in our normal low dimensional, three-dimensional space that we exist within. But it also seems capable of constructing these high dimensional realities. I’ve always maintained that to be utterly confounding, that the brain is able to do that.
And it might suggest that the brain has somehow at some point, and it still is, learning to construct this high dimensional space. And to what end? Why did the brain do this? What’s the purpose of this? Biology is functional. Evolution is functional. So why can the brain construct these bizarre and complex spaces filled with intelligent beings so effortlessly?
Reset: Well, Andrew. We came out of the ocean somehow and we went onto the land, and now there’s another step perhaps, that we just have to grasp. We have to grasp the dimensionality of that new space.
Andrew Gallimore: Right. Exactly. And that remains something of a mystery as to what’s actually going on in the DMT space and how it relates to our world and whether we are on some kind of trajectory into this hyper-dimensional space. And that DMT is the gateway into that space.
Andrew Gallimore is a Neurobiologist, chemist, and pharmacologist interested in the relationship between psychedelic drugs, the brain, consciousness and the structure of reality. Currently based at the Okinawa Institute of Science and Technology, Japan. His book, Building Alien Worlds: DMT, the Brain, and Structure of Reality is available through his website: http://www.buildingalienworlds.com