How Older Brains Could Benefit From Marijuana
A team of German and Israeli researchers working with mice have new data suggesting that while marijuana may affect cognition and memory, the results vary depending on age of the mouse. Writing for Nature Medicine this week, they describe how young mice fed low doses of THC (the main psychoactive component in marijuana) over a period of a month performed worse on cognitive and memory tests afterward. But they also found that the older mice—those over 12 and 18 months—performed better than they had before the trial. The old and young mice also showed different physical changes in their brains and gene expression after the treatment.
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Staci Gruber, an associate professor of psychiatry at Harvard University, directs programs investigating marijuana and the brain for the Harvard-affiliated McLean Hospital. She explains the findings (she was not involved in the study), and discusses the path ahead for further research into marijuana’s effects on the brain.
Staci Gruber is director of Marijuana Investigations for Neuroscientific Discovery at McLean Hospital, and an associate professor of Psychiatry at Harvard University in Cambridge, Massachusetts.
IRA FLATOW: I’m Ira Flatow. This is “Science Friday” from PRI, getting ready to finish up with the rest of the program. And I thought I’d read, there’s some tweets that came in about our last segment. Let’s read Pomeroy. He says, remember to keep door area clean with a damp cloth. Avoid the fiery merry-go-round.
And people really weren’t surprised. I think this was the most interesting comment we got about using that baked potato. And it’s a question of, is this a new meme? Instead of a dumpster fire, we have a microwave potato fire. So people are talking about that.
So let’s move on to some other interesting stuff. Because I think I have a story here that’s going to be as interesting, at least, about the fire in the microwave. And that is about marijuana, a new marijuana study that shows that in older people– marijuana, a study in mice, at least, in older mice– showed that when given to the mice, they had sharper memories by the end of the study. And in fact, they were on par with younger mice who hadn’t had any exposure to THC at all. And they published the research in the journal Nature Medicine last week.
So what does this mean for those of us with aging human brains, and how do we continue research with marijuana, which is, as you know, classified as a Schedule I drug? And that means federal regulations limit its use in actually conducting research on marijuana. My next guest, I think, has some insights on that.
Staci Gruber is Director of the Marijuana Investigations for a Neuroscientific Discovery and the Cognitive and Clinical Neuroimaging Core program at McLean Hospital. And she’s Associate Professor of Psychiatry at Harvard in Cambridge. Welcome to “Science Friday.”
STACI GRUBER: Oh, thanks so much. Thanks for having me.
IRA FLATOW: So this was done in mice, right? So let’s– we know how hard that is to move that into people studies. So are you saying we should start prescribing pot to everyone who’s starting to lose their car keys? Not yet, I’ll bet.
STACI GRUBER: Well, that would certainly be an interesting headline, wouldn’t it? I think people would be very interested in hearing that. So I think these types of pre-clinical or animal studies are always extraordinarily interesting and always very helpful in terms of areas like this, where we absolutely, positively need more research.
You know, these studies of mice, and in this case, three different groups of mice certainly give us some really interesting ideas about what might be happening. And it actually dovetails pretty nicely with what we see in recreational human marijuana users, in addition to more recent work in medical marijuana patients. So it’s interesting.
IRA FLATOW: These were not– in studies sometimes they give massive doses of things to lab animals. But this was not a massive dose. Give us a thumbnail of what happened here.
STACI GRUBER: So in this study, there were basically three groups of mice. And they had young mice that they termed young because they’re two months old, mature mice that are a whopping 12 months old, and old mice, which are, I guess, mice that are about 18 months old. And they basically fit– half the animals in each group are what we call vehicle or control. And the other half are given THC, tetrahydrocannabinol, the main psychoactive constituent of the plant, right?
And they did this using sort of a subcutaneous pump method. So it’s not like they’re– you know, somebody said to me, well, are they smoking little tiny joints? No, they’re not, not inhaling it. So it’s a low dose that’s administered sort of subcutaneously under the skin.
And what they did was, they tested the animals first and determined that, in fact, sort of consistent with what we know about aging, young mice not exposed to THC outperformed the mature and the old mice. Because, in fact, we get a little bit worse with regard to cognitive tasks as we get old. It’s very sad, but it’s true.
IRA FLATOW: What did you say? No. Just joking.
STACI GRUBER: Yeah, what was that? Say it again? There are things we can do. But that’s generally the sort of pattern that things tend to follow. Interestingly, the young mice, after being exposed to THC for 28 days, performed significantly worse than the mature or old mice, who actually performed better than the young mice.
So a little bit of THC to the young mice made them perform significantly worse, that is they looked like old mice who hadn’t been treated. While the mature and old mice who were treated with THC, looked like the young untreated mice. Now that’s very interesting and very similar to what we see in what we call early onset exposed individuals who use marijuana or cannabis at an early age, in our studies, prior to the age of 16.
Those folks tend to look worse than individuals who began using later. That’s because the brain is still absolutely, positively immature. It’s what we call a period of neurodevelopmental immaturity. It’s vulnerable. So exposure during this early period really renders them less able to do these tasks relative to the mature and older mice.
The really interesting take home, though, is what’s happening in the mature and old mice who are doing better than the young mice after being given a little THC. And that’s something that we’re starting to see emerge from, at least, our ongoing longitudinal study of patients certified for medical marijuana use who look as if they get better on cognitive tasks after only three months. We follow them for two years. But the first set of data comes after only three months. They look like they’re performing better. That’s very interesting.
IRA FLATOW: Well, does it make a difference that the rats were given, as you say, pure investigational THC? It comes from a lab, absolutely pure, as opposed to people who might buy marijuana on the street.
STACI GRUBER: So a good question that really speaks to what is it that they’re being exposed to. And this is, again, yeah, purified THC. Very different from what folks on the street, so to speak, recreational users might be getting.
But I will say, while there’s other cannabinoids present in recreational cannabis, we’ve seen the levels of THC, that is the potency of products, increase pretty sharply over the last two decades, and that’s also important. It’s certainly something to keep in mind as we think about the role of THC and other cannabinoids. But in the human subjects, studies of the medical marijuana patients, those folks are on products that are high in THC.
But we also have folks who are using products high in cannabidial, a main nonpsychoactive or nonintoxicating constituent. So it’s a good question. It may be that a little bit of THC helps sort of up regulate the endocannabinoid system in these aging animals. That is a real possibility.
IRA FLATOW: Is it difficult to investigate marijuana and THC because of the regulatory landscape, the classification that it’s in?
STACI GRUBER: Well, it’s certainly not the easiest area of investigation to embark upon, that’s for sure. The very best thing to do with studies like this is to replicate clinical trials in human subjects. And in fact, currently, there’s only really one source from which you can obtain product to administer to human subjects.
And we certainly wouldn’t ever be in a position to be able to administer products like that to, let’s say, our youngest consumers, our adolescents. That’s probably not going to happen, for all sorts of ethical reasons. But yes, it’s an area that’s difficult given the current restrictions. We aren’t able to use products that patients and consumers are actually using, from dispensaries or their local dealer. We can’t assess the impact of those products, which is a real limitation.
IRA FLATOW: So there’s good news and bad news about the study.
STACI GRUBER: Good news and bad news, but yeah. I mean, I think this is certainly the kind of thing that absolutely demands more research. And you know, chronic low dose treatment with THC or perhaps other cannabinoids may, I think the authors say, be a strategy to help slow down a reverse potential age-related deficit. We’ll have to see how that plays out in humans, but it’s certainly promising. And again, I wasn’t necessarily expecting what we’ve seen in our first studies of medical marijuana patients, very exciting.
IRA FLATOW: Could it be could be another reason to have medical marijuana, for prescribing it?
STACI GRUBER: You know, there are so many different indications. And there’s always a caveat in many states. You can use it for this indication, this indication, or anything your doctor feels is necessary. So to improve or increase cognitive performance– typically, what we see in the THC-related literature, or studies of recreational marijuana, really have been reports that THC is detrimental to the brain.
But again, mostly those studies focused on individuals who are young. We don’t necessarily know about the impact on older folks. And when you’re beyond the level, or beyond the period of vulnerability, could it potentially be facilitative? We don’t know.
IRA FLATOW: We’ll have you back, Dr. Gruber.
STACI GRUBER: We’re happy to come back.
IRA FLATOW: Staci Gruber, Marijuana Investigations for Neuroscientific Discovery Program at McLean Hospital, and Associate Professor of Psychiatry at Harvard.
Christie Taylor was a producer for Science Friday. Her days involved diligent research, too many phone calls for an introvert, and asking scientists if they have any audio of that narwhal heartbeat.