Even mild head impacts that don't count as concussions can raise the risk of neurodegenerative disorders such as chronic traumatic encephalopathy (CTE), so finding an effective treatment for these blows could be useful for warding off debilitating conditions down the line.
Live Science spoke with study co-author Argel Aguilar-Valles, an associate professor of neuroscience at Carleton University in Ontario, about the new study and how the research might eventually translate to treatments for repetitive head injuries.
Argel Aguilar-Valles: This work was spearheaded by our collaborator, Dr. Craig Ferris at Northeastern University in Boston. The idea was to focus on the cumulative effect of those milder head hits, or injuries, that happen quite commonly; a lot of children and older adults can have repeated instances of these events of head trauma, and it doesn't necessarily lead to any immediate treatment or hospitalizations because they are considered fairly mild.
So it's repeated — it's three hits — they're controlled, they're fairly mild. And they produce some alterations in the brain networks that are evident in using either MRI [which looks at the brain's structure] or functional MRI [which analyzes brain activity] analysis.
AAV: It's always difficult to compare [what a rat is experiencing] to what a human might experience, especially here. One good way to put it is that there's no loss of consciousness — so in those instances where the hits happen but you don't black out.
Mild head injuries can cause cumulative harm if a person experiences multiple over time, evidence suggests. (Image credit: Shutterstock)AAV: Well, as far as I'm aware, there's not really an intervention. I've experienced this secondhand with my children. Sometimes, they will come back from school and then they [the teachers] say, "OK, they had a hit on the head; there's a bump, but they didn't lose consciousness or anything."
There is no intervention — for instance, if we do this [treatment], it's going to prevent you from developing dementia 50 years down the line. There's obviously nothing like that, particularly when you have repeated instances and the effects are cumulative.
AAV: My group specifically has had an interest in testing the ability of molecules collectively known as psychoplastogens. We didn't coin the term, but it basically refers to all of these drugs that produce these brain-plasticity effects [changes in the brain's structure and activity]. These include serotonergic psychedelics [such as psilocybin and LSD, which affect serotonin receptors], and also things like ketamine or even MDMA.
There are deficits in this plasticity in psychiatric illnesses, but also, obviously, in neurological disorders and even neurodegenerative disorders, where these plasticity mechanisms are completely nonfunctional.
It's still unclear if they're disease-modifying, in the sense they could provide lasting changes that can modify the course of the disorder. But so far, the evidence indicates that they can at least help to ameliorate some of the negative consequences of either neurodegeneration models or physical trauma, like in this case.
NL: Psychedelics have been more thoroughly studied for conditions like depression. In both depression and head trauma, could similar mechanisms explain the drug's potential benefits?
We don't know the limits of these drugs yet. I'm not trying to imply that they don't have limits; what I'm trying to say is that our knowledge is incomplete. We don't know when they will work better than other potential treatment options.
NL: Is there reason to think that psilocybin would be more promising than other psychoplastogens?
I'm not a clinician, but one of the reasons why psilocybin is favored over others is the length of the psychedelic trip. It's a few hours. If you go with something like LSD, it will last much longer. While the person is under the influence of the drug and undergoing the trip, there needs to be clinical supervision, so it becomes really challenging logistically to arrange sessions with psychedelics that last a long time.
NL: In clinical trials of psychedelics, scientists often use a very small dose to try to avoid triggering strong hallucinogenic effects. Was that a goal with the rats?
One measure we use is the "head twitch response," which is a behavioral measure that we commonly use in rodent work to test the hallucinogenic potential of a drug. This is a very rapid head movement that occurs in response to the serotonergic psychedelics. It's a behavioral response that correlates with hallucinogenic potential, and not perfectly.
The new study that Aguilar-Valles co-authored looked only at rats. More work is needed to understand if psilocybin could be useful for humans with head injuries. (Image credit: dra_schwartz via Getty Images)
NL: What notable changes did you see in the rats in this study?
But also the hyperconnectivity — the brain's functional connectivity was really dramatically affected in the treated rodents with the head hits. They not only recovered but went to higher levels than the control-group animals.
NL: And these effects were seen throughout the brain?
These modulatory regions, the dopaminergic regions, are concentrated in one part of the brain, but they affect overall brain function because they have these widespread connections. So they're really crucial for a lot of functions, and we're seeing effects in these regions — that's really intriguing.
AAV: It is currently a hotly debated topic in the psychedelic field, whether the intensity of the psychedelic experience has anything to do with the beneficial effects or not. You can envision situations like psychological trauma, as opposed to physical trauma, where that trip might be part of the therapeutic mechanisms. It becomes evident in the debriefing sessions after psychedelic treatment, where it seems like in some cases, the psychedelic experience is fundamental.
I don't think we've had the first clinical trial with these drugs yet. Some of them may have undergone Phase I clinical trials just for safety, but I believe none of them have been tested in Phase II trials yet [in which their effectiveness is explored for specific conditions].
AAV: Extending the observations, like other groups have done — looking at what happens if you do give this treatment months after the events. It's still unclear to me if, with this model we have, you will have effects months later.
And obviously, the psychedelic trip is still a potential issue. But testing whether these non-hallucinogenic derivatives have the same lasting effects as their hallucinogenic counterparts do — that will be crucial and that can, in some cases, potentially facilitate the translation [into treatments]. Because not every person reacts the same way to these hallucinogenic compounds, and not everybody has the same risks.
AAV: We don't know what the consequences [of psychedelic use] are in a developing brain. There's not enough data. That will be obviously a big thing to sort out before recommending the use of these drugs, and maybe some of those non-hallucinogenic derivatives may hold the answer for that — for those cases where you really don't want to induce a full-on psychedelic experience.
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AAV: There's a lot of enthusiasm in the field and a lot of push to try to characterize and understand better these drugs, from a basic perspective or a cellular level up to a brain wave level and then also the psychological effects. So there are a lot of different disciplines implicated in studying these drugs, and I think that's really exciting. That will hopefully lead to a wealth of knowledge about these drugs — not only their effects but also their limitations and their potential risks.
There's a lot of potential there, but we should proceed with caution.
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