Why cannabis’s health effects are so hard to study

[MUSIC PLAYING] FLORA LICHTMAN: Hey, it’s Flora, and you’re listening to Science Friday. When states first began legalizing recreational cannabis a couple decades ago, 25 million Americans said they used the drug, according to the National Survey on Drug Use and Health. That number nearly tripled to 70 million in 2023. And there are a lot of open questions. Why do some people find more pain relief from THC than traditional painkillers? Does it really help your sleep? What are the effects of long-term use?

We have two scientists here with us who are on the forefront of that research. Dr. Ryan Vandrey is an experimental psychologist at the Johns Hopkins Cannabis Science Laboratory. He’s studied the health effects of cannabis for 26 years. And Dr. Natasha Wade, a neuropsychologist who studies the effects of substance abuse on adolescent brains. She recently analyzed data from 11,000 teens about how cannabis is affecting their development. Welcome to you both to Science Friday.

RYAN VANDREY: Thanks for having us, Flora.

NATASHA WADE: Thanks for having us.

IRA FLATOW: Thank you both for being here. Ryan, you’ve said that the cannabis market has been allowed to run rampant. Tell me more about that and what it means for you studying it.

RYAN VANDREY: Yeah, so when I started, we were just looking about cannabis as a drug of abuse. And people were smoking flower, and that was it. And so the kinds of questions that we’re concerned with now have changed dramatically, because now we have medical markets, we have adult-use markets, and we have hundreds of different products.

And so we have to understand what kinds of products are potentially helpful or harmful for the medical application for dozens of different health conditions. We need to understand how the route of administration, the formulation, and the dose affect different people. And we have to go back to our “is it a drug of abuse” kind of questions, and revisit that in this novel marketplace.

So we’re trying to look at this from a lot of different perspectives. And there’s been very few guardrails put up with regards to what kinds of cannabis products the industry can put out and the claims they can make about it. So as scientists, we’re constantly playing catch-up to this, to try to understand, OK, well, there’s this new kind of product. What does that mean? How does it compare to the more traditional forms of cannabis that we tend to come across?

FLORA LICHTMAN: Yeah, that’s interesting. I mean, it sounds like it’s different than alcohol, because there are actually different compounds. So it sounds like a lot more variables than other drugs.

RYAN VANDREY: It’s different compounds, and it’s different ways in which it’s being used and purposes for which it’s being used. And so alcohol is a fairly standard beverage. You drink it. And there’s a couple different variants there. You’ve got beer and wine. And then you have spirits. With cannabis, you’ve got oral dosing. You’ve got inhaled dosing with different kinds of devices. You have topicals. You have suppositories, and so many different– each one of those variants changes the experience of the user.

And then you throw on top of that a whole range of chemical entities. Alcohol is a single molecule. In cannabis, you’ve got THC and CBD and CBN and CBG and a whole alphabet soup of different kinds of chemicals that make up these products.

FLORA LICHTMAN: Tasha, you study teens. Are teens using cannabis differently than they used to?

NATASHA WADE: Absolutely. I think that with all these different products, like Ryan was just saying, there’s a lot more accessible to them. We’re seeing that there’s a lot more co-use of cannabis, especially with nicotine products, which also might even change the experience and the downstream effects of use, and perhaps, will make it worse, perhaps might mitigate some of the effects. But the jury’s still out. We still have a lot more to do to actually figure it out because everything is changing so rapidly right now.

FLORA LICHTMAN: Well, tell me about this recent study where you looked at neurological development in teens who use cannabis. What did you find, top level?

NATASHA WADE: Yeah, so we’ve been following about 11,000 kids across the country for almost a decade now. And we have about seven years of data that we used here. We started when they were 9 or 10 years old before they started using. And by the time they’re 16 or 17 years old, over 2,000 of those kids we’ve identified as using cannabis now and have started using cannabis.

And the big takehome is that the kids who started using cannabis, the teenagers were not showing the same gains in thinking abilities as their peers who were not using. And this was even after we control for whether they’re using alcohol or nicotine or any other substances, prenatal exposure, early childhood mental health concerns, family factors, sociodemographic factors. And so we see that there’s some link between cannabis and perhaps reducing cognitive trajectories over time. Not necessarily directly– we can’t say it’s causal. But there is a relationship between cognition and teens.

FLORA LICHTMAN: And what do you mean exactly by cognitive gains?

NATASHA WADE: Yeah, so we give the same test over and over again every couple of years. And naturally, when they’re teenagers, we expect them to improve, to grow, to learn. And so we expect them to do better when we’re giving them the same test. And almost across the board, everybody is showing improvement. But those who are using cannabis are not showing the same level of improvement, and in some cases, actually plateau and don’t show improvement at all.

FLORA LICHTMAN: What about on the medical side? Are there health conditions that cannabis is showing promise for?

RYAN VANDREY: Yeah, so there’s a long history of cannabis being used and prescribed as a therapeutic. And we’re uncovering even more. So the endocannabinoid system, which cannabis modulates directly, is a homeostatic controller for a lot of different physiological systems in our bodies. And we’ve seen tremendous promise for treatment of pain conditions. It’s used to help treat the adverse effects of chemotherapy, if you’re going through cancer treatment, as well as CBD reducing seizures in rare forms of epilepsy.

Aside from that, there’s a lot of promising data emerging that shows that cannabis or other cannabinoids might be helpful for a variety of health conditions, a lot of which really have a huge unmet clinical need. PTSD is one. Another is autism, Parkinson’s disease, agitation in people with dementia. But again, the science to find the right product and to determine which patients it’s most likely to be effective for is still evolving as we speak.

FLORA LICHTMAN: I wanted to ask you about dose. Do we have a sense of how much THC you need for a medical benefit for some of these conditions?

RYAN VANDREY: There’s a company based in Israel that’s been developing a metered dose inhaler to help treat patients with chronic low back pain. And they have found efficacy for doses as low as a half a milligram of THC. So that’s a dose that is imperceptible to the patient in terms of cognitive impairment or intoxication, anything like that. But it’s effective on the clinical outcome.

So the dose of THC needed to induce an effect is going to vary based on what that effect is that you’re looking for. And also, it’s going to depend on the age of the person, sometimes the sex of the person, and also, the experience that person has with using THC or other forms of cannabis.

FLORA LICHTMAN: So it sounds like you might be able to get a health benefit without the high, in some cases.

RYAN VANDREY: Correct. And honestly, that’s where I see the future of cannabinoid medicine going. Cannabis is a very blunt tool in that it’s very chemically complex. It has a number of different chemicals in it that hit a number of different receptors in our brains. It’s a sledgehammer approach to medicine. Ideally, what we want to do is we want to utilize what we can learn about the cannabis plant as a whole, identify the chemical constituents that drive very specific effects, and then develop novel therapeutics that really narrow down and can achieve target therapeutic effects without side effects and adverse consequences.

FLORA LICHTMAN: We got to go to break. But when we come back, I want to ask you if recent policy changes is making cannabis easier to study or not. Does that sound OK?

NATASHA WADE: Great.

RYAN VANDREY: Of course.

FLORA LICHTMAN: Stay with us.

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FLORA LICHTMAN: President Trump is trying to reschedule some medical cannabis products from Schedule I, which includes heroin, to Schedule III, which includes ketamine and steroids. If it goes through, what would that rescheduling actually mean for your work? Would it make it easier to research cannabis?

RYAN VANDREY: On my side, I do two main lines of research. One is human laboratory studies where people come in, and we give them the drug in the laboratory. And the value in that is we can understand differences in the different kinds of products. And we can also understand how receiving that drug can impact performance, drug testing outcomes, and a variety of other things. So legalization would help us in terms of being able to purchase products that people can buy in dispensaries and bring those into our laboratory and study them.

But perhaps, probably the biggest impact on my side is that the other line of research that we engage in quite a bit is trying to understand, again, the health effects of medicinal cannabis use. And right now, with it being federally illegal, a lot of patients don’t have access to regulated products. A lot of patients don’t tell their doctors about what they’re using. And the doctors can’t prescribe them any cannabis product.

And so the exact product that people are using is relatively unknown. It’s not usually captured in their electronic health records. And so when we’re trying to follow cohorts of people or trying to look at a health systems level, if people at Johns Hopkins Hospital have epilepsy or autism or Parkinson’s or insomnia, we have very little understanding of how many people are using cannabis, what kinds of cannabis products they’re using, and what dose, or for how long. And that’s really limiting what we can say about the overall health effects of medical cannabis use for those health conditions.

FLORA LICHTMAN: As you both have noted, cannabis falls into this muddy territory of medical and recreational. How are dispensaries navigating that?

NATASHA WADE: I mean, there’s a coffee shop down the road from my house that has a list of CBD benefits. And you can get a bump of CBD for $2.50 added to any coffee product. And some of them might be conditions that have already been named. And some of them are definitely things that are not. And so I think it’s not a dispensary, but going into dispensary–

FLORA LICHTMAN: It’s not even a dispensary.

NATASHA WADE: Yeah. It’s just out there, and it’s a very large sign. And so I think, at least in California, there’s a lot of information that’s being put out there. You go and talk to bud tenders, and I have seen online you can do different trainings as a budtender, so that you can better advise your consumers who come in to buy certain products. So I think, likely, you’re going to get very different experiences, depending on what shop you go into. But they, I think, are feeling confident, in some way, of providing some advice, based on wherever they’re finding their information from.

RYAN VANDREY: Yeah, and that’s going to depend a little bit on which state you live in. So, for example, some states require that a pharmacist be available for consultation who’s had some kind of training versus the budtender, who’s really just a retail employee and no different than the person who’s checking you out at the grocery store, and asking them for nutrition advice. They’ll tell you something, but whether it’s evidence-backed or not remains to be seen.

FLORA LICHTMAN: I mean, what advice would you give people who are shopping for these products?

RYAN VANDREY: That’s a loaded question. That’s way too broad to answer.

[LAUGHTER]

So again, my whole thing is the dispensary model removes the health care provider from the conversation with the patients, especially in states that have legalized adult use, because the adult-use market has rolled the medical market in there. There’s usually no provider on site there to provide guidance. And we still don’t have the quality of data that we would want to have, even if we could make good recommendations.

So I tell people all the time, even if we had a large phase III clinical trial of some cannabis for a given health condition, the effect in that trial for that product wouldn’t necessarily generalize to all the other products out there. And so, the advice right now is for people to educate themselves on what different types of cannabis products there are, how route of administration impacts it. And unfortunately, we’re still in an age where “start low and go slow” is the best advice you can give to anybody.

But in addition to that, on the therapeutic side, it’s you don’t have to necessarily feel high to get a therapeutic effect. And so you want to gather as much information as you can from the internet. Talk to your doctor, because your doctor should know if you’re taking any kind of cannabis-related drug, especially for health purposes. And then it’s a lot of trial and error from there.

FLORA LICHTMAN: Tasha, I know you talk to teens, and you go to high schools. What do you tell them?

NATASHA WADE: I mean, I try to be as honest with them as possible. They are going to be making their own decisions in life very soon. It may not be legal for them to buy, but there’s ways they find. And so I try to lay out for them where it’s the riskiest, what is perhaps less risky, like some of the things Ryan just said, and then, ultimately, especially while their brain is still developing, the message is wait. Wait as long as you can, because it’s still going to be there. Cannabis is not about to disappear.

But if they have big life things going on right now and they just want to feel high, go on a run. There’s good runner’s highs. There’s other things you can do. But if they have big goals right now in their lives, I have not seen evidence in generally healthy teens that it’s going to benefit them in clear ways. And I do see that there’s some evidence that it could harm them. And so they might as well wait in this very vulnerable life stage.

FLORA LICHTMAN: OK, last question– is it frustrating to work in a field where there are so many unknowns, and it’s changing so rapidly? Or is it fun? What’s it like for you two?

NATASHA WADE: I mean, it’s why I’m in it. I started in alcohol. And like you talked about, I think there’s a lot of great research in alcohol, but it is, to some extent, simpler because it’s alcohol, and we can translate it in so many different ways. Cannabis, we have to be on your toes constantly. And again, going into high schools, they push back on everything. They ask a lot of really great questions. And they’re trying to figure out, well, if I just use once, just one time at a party, or something like that– they’re really asking hard questions and trying to think it through for themselves.

And at least, when talking about alcohol– because I give similar talks on alcohol– you don’t get the same kind of back-and-forth. And so, to me, it makes it a lot more fun. There’s a lot of potential good, there’s a lot of potential harm here. And so it keeps me very interested in it.

RYAN VANDREY: Yeah, I’m right there with you, Tasha. It’s fascinating. I think we’ve got 10 lifetimes’ worth of work that all need to be done next week. And the other part of this is that not only does cannabis research keep giving us new things to study and new directions to go, but really, everything we’re doing right now has direct policy implications, which is rare in science, that you can honestly say, the work we’re doing should and could inform the next policy decisions at the federal, state, or local level.

And I really enjoy the fact that, hopefully, this impacts the betterment of public health, because as Tasha mentioned, cannabis has tremendous potential as a therapeutic and could help a lot of people, but it also has that dark side where it can cause a lot of harm. And I think if we use research and science to maximize the benefit while minimizing the harms, we’ll all be better off.

NATASHA WADE: Agreed.

FLORA LICHTMAN: Well said. Dr. Ryan Vandrey is a professor of psychiatry at Johns Hopkins. And Dr. Natasha Wade is an associate professor of psychiatry at UCSD. Thank you both for taking the time to talk to us today.

NATASHA WADE: Thanks, Flora.

RYAN VANDREY: Thank you very much.

FLORA LICHTMAN: This episode was produced by Dee Peterschmidt. If you have a question for us, we always want to hear it. Give us a call, 8774-SCIFRI is our number. That’s 8774-SCIFRI. Thank you for listening. I’m Flora Lichtman.

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