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How Weed Works: A Conversation With Margaret Haney

Vital City

December 13, 2023

The science on cannabis — including some big questions still unanswered

The science on cannabis — including some big questions still unanswered

Vital City · Meg Haney on Cannabis

Everywhere they look these days, New Yorkers see and smell cannabis, most of it bought and sold at unlicensed pot shops. Other pieces in this issue consider what to do about that phenomenon and other unintended consequences of pot legalization. This one asks a more basic question: What do we know about marijuana and what the chemicals in it do to us, good and bad?

Margaret Haney knows as much about the effects of cannabis on the human brain as anyone in America. She’s a neurobiology professor at the Columbia University Irving Medical Center, where she directs the Cannabis Research Laboratory and co-directs the Substance Use Research Center. Her work investigates the effects of and treatment for cannabis use disorder, as well as the potential therapeutic use of cannabis and its constituent chemicals for appetite enhancement, pain relief and more. Years ago, she conducted extensive research on cocaine, especially smokable (crack) cocaine

Vital City spoke with her in November. The following conversation has been edited for length and clarity.

Credit: Arthur Mount. Portrait of Margaret Haney.

Vital City: What do the active substances in cannabis do to the human brain?

Margaret Haney: There are over a hundred active components, at least, in the plant. There are two that we know the most about, and that’s Delta-9 Tetrahydrocannabinol, which is usually called THC, and cannabidiol, or CBD. 

THC we know quite well. We’ve studied it for the past 30, 40 years or so. And we have a very good sense of how it acts on the brain. It binds to these proteins in the brain called CB1 receptors, and that’s how it produces the myriad of effects we associate with cannabis: all the intoxicating effects, changes in food intake, cognition, sleeping. 

Cannabidiol is a really complex chemical that we’re still really sorting out, but we know it’s not acting on the same receptor. It seems to have more anti-inflammatory effects. It seems to have promising effects on pain, but it’s a complicated one. 

The other important thing I think a lot of people don’t know is that there are terpenes and flavonoids, components of the plant that are not cannabinoids yet seem to have effects in addition. This adds to the complexity of this plant.

VC: What do you see as the biggest benefits?

MH: THC can be beneficial for appetite enhancement for people who have trouble maintaining their weight, who have a lot of stomach distress, including people with HIV. It’s actually FDA-approved for that, Delta-9 THC. It has analgesic effects — meaning it helps with pain management — and we can demonstrate that in the lab as well. It’s not fentanyl, but it is maybe more like codeine and it can help with certain pain conditions.

Something I’m excited about is really studying the components of the plant for a type of pain that isn’t well treated and yet for which there is no really robust medication and that’s neuropathic pain. There’s evidence in animals showing that components of the cannabis plant can be helpful for that. 

Now, none of these studies are enough to satisfy the Food and Drug Administration, because, again, we’re talking about a plant with a myriad of chemicals. There are so many steps one has to take to demonstrate to the FDA in a carefully controlled way that this is an effective medicine. The circular problem is that we can’t study it very well in large groups and do randomized controlled clinical trials easily when something is a Schedule I drug.

‘The federal approach and our current drug policy with cannabis is insanity.'

VC: What would you consider the biggest risks of cannabis?

MH: I study cannabis use disorder. I study people who are smoking, “wake and bake.” They smoke every day, never miss a day, and smoke from morning to night. I have a lab, an inpatient setting where I bring heavy cannabis smokers in and I have them smoke cannabis. And then I study their behavior 24 hours a day: sleep, food intake, mood intoxication and so forth. 

My claim to fame back in the late 1990s was documenting a time-dependent cannabis withdrawal syndrome. When these heavy cannabis smokers stop abruptly, they go through a series of withdrawal symptoms. 

A big focus of my work has been looking for treatments for cannabis use disorder, pharmacological treatments. 

VC: What percentage of people who use cannabis have cannabis use disorder, and how does that compare with other drugs?

MH: These numbers get a little bit complicated because cannabis use disorder can be mild, moderate or severe. To meet any of those criteria, it can be quite high, like 30% to 40% of people who smoke one cannabis cigarette go on to develop some type of cannabis use disorder.

I am more interested in perhaps the 10% who go on to reach a truly problematic level of use, which would be considered moderate to severe cannabis use disorder. But again, the numbers shift depending on the way you’re defining cannabis use disorder.

VC: Do we see similar rates of moderate to severe use disorder as we do with, say, alcohol or cigarettes? 

MH: No, no. I think there’s pretty good evidence that cannabis has less of an addictive liability than those other drugs of abuse. So these are very rough estimates, but I think it’s like one in five who drink go on to develop an alcohol use disorder. And cigarette smoking, it’s quite high as well. With cannabis, it would be more along the lines of one in 10. 

But the tricky thing is with cannabis, so many more people are using cannabis than are using cocaine, for example — which means the end result is going to be a decent number who will go on to develop a cannabis use disorder. 

VC: The U.S. Drug Enforcement Administration breaks drugs into different schedules based on their acceptable medical use and potential for abuse. Though the federal government is considering moving cannabis to Schedule III, which would loosen restrictions, as of now it is a Schedule I drug, which to the DEA means it has “no currently accepted medical use and a high potential for abuse.” Is “no currently accepted medical use” a defensible statement given that we’ve got 38 states with medical cannabis?

MH: I’m not swayed by the states passing the laws because those were all done for political reasons, in my opinion, more than scientific reasons. So we may say that there’s plenty of promising evidence with cannabis, but to the level of meeting DEA criteria for a medicine, they could always snap back and say, “We don’t have large randomized controlled clinical trials.” Because we’re talking about a plant as opposed to a discrete chemical, it gets a lot trickier. 

We’re trapped in this loop that we can’t do the studies for which we think there’s promise that need to be done to satisfy the FDA to determine it as a medicine. So the federal approach and our current drug policy with cannabis is insanity.

VC: Explain what it’s like to research a Schedule I substance.

MH: I give people cannabis in the laboratory. So I get a set amount from a source approved for federally funded researchers; for many years there was only one such source. I put it in a gun safe in a locked refrigerator and safe in a door I get into with my fingerprint. When I give people an 800-milligram cannabis cigarette, I then take the butt and I save that for the DEA to someday take away because you’d have to imagine if I was giving someone heroin and I gave them a gram and I had two grams, I would have to report what happened to that other gram. 

VC: You did research in the past on cocaine. Can you compare and contrast?

‘There’s a great deal of incentive to make more and more and more potent cannabis for recreational reasons.'

MH: Because cocaine’s Schedule II, funny enough, it wasn’t quite as rigorous. There’s a documented medical use for cocaine. 

VC: That brings us back to the second part of the Schedule I definition, which is “high potential for abuse.” Do you think that cannabis stands out?

MH: Well, it certainly doesn’t have as high abuse liability as heroin. And LSD, funny enough, I don’t think it has a great deal of abuse liability. It certainly is used recreationally, but it’s not like there’s a swarm of people with an LSD addiction. So that’s another funny one. Obviously these were all put on there for political reasons, really not scientific reasons.

VC: How about cocaine?

MH: Smoke cocaine or crack cocaine has a very, very, very high abuse liability, far higher than cannabis.

VC: The cannabis people smoke: Has it gotten more potent over time? One credible source says the THC content has increased tenfold over the last 50 years.

MH: Yeah. There’s financial incentive, if you’re looking at a recreational market, to really boost the THC levels. Then you can extract THC and make oils that can then be put into vape pens and then you can extract it further and put it into a wax that’s like 90% THC. So there’s a great deal of incentive to make more and more and more potent cannabis for recreational reasons. And then you can also vary the THC to CBD concentrations because it seems like most people using cannabis therapeutically like the combination. I don’t know if that’s based on marketing or real scientific evidence or experience, but many want that combination. 

VC: What can you say about the public health consequences of broader cannabis use — both people who use and don’t have use disorder, and people who use and do?

MH: There are public health consequences to cannabis use, I think, in terms of cognition, for example. I raised two sons, and cannabis use I think is riskier during periods of rapid brain development. In utero and then in adolescence, the brain really develops at a rapid pace. And your body’s own THC, these endocannabinoids play a critical role in brain development. So I am concerned about heavy, heavy use of highly potent cannabis at these vulnerable periods. There’s plenty of 14-year-olds using it daily and that could have consequences.

We know it impairs cognition. Now, I’m not saying permanently, but there are short-term acute effects on cognition, and there’s some indication for adolescents that the effects might be both more severe and potentially longer lasting. Memory and learning are affected. 

VC: Anyone who walks around the city a lot sees a good deal of cannabis use. Is there any consequence to that that we should be concerned about? If you smoke weed on a break, does it impair your ability to do your work when you go back to the job?

MH: It’s pretty safe to say it’s not going to help. It doesn’t help cognition. It depends on what your job is. I guess maybe if you’re working at a factory and are bored out of your mind, it could, doing something incredibly rote. It’s not good for driving. Now, again, it pales in comparison to alcohol, but that is another risk. I ride my bike in this city and smoke is pouring out of 10% of the cars I bike past and that doesn’t make me happy. So maybe it doubles your risk of an accident versus 25 times your risk of an accident with alcohol. 

There are many ways in which cannabis is a more benign drug, but as opposed to nothing, it’s not often good. This isn’t “Reefer Madness;” I understand that many people enjoy it and use it sensibly and so forth, and that’s totally fine. But the risks are important to consider. 

‘We know it impairs cognition. Now I’m not saying permanently, but there are short-term acute effects on cognition, and there’s some indication for adolescents that the effects might be both more severe and potentially longer lasting.'

I also do worry a bit about the unregulated basis of cannabis. There was a recent article from Columbia, not from my lab, showing this plant apparently is incredibly effective at picking up heavy metals. It soaks them all up. So cannabis users do have higher levels of lead in their blood. Regular cannabis users. That’s certainly not great for the growing brain either. 

And then, if people who are immunocompromised are forgoing approved medications for a cannabis plant, that comes with problems of its own. I had a friend who had cancer, was hoping to use a particular product to help with neuropathic pain. Neither one of us could find a product that we were comfortable with because nobody was regulating it. So we don’t know if there are things in there that could harm an immunocompromised person.

VC: Some people smoke weed to help with anxiety. Is it good for anxiety?

MH: Actually, many people get more anxious with cannabis, but for some people — the participants in my study, it is the balm for their reality. It’s so soothing. It has a great effect that you could say reduces anxiety. 

Importantly, though, that doesn’t mean it’s an anxiety medication. I drink a glass of wine after a hard day. Nobody’s telling me alcohol is an anxiety medication. The fact that it acutely is going to have an effect doesn’t mean it’s helping with your issue long-term. In fact, there’s no evidence cannabis helps with anxiety or depression, even though when you smoke, when you’re intoxicated, maybe you feel those effects like I do with a glass of wine. That’s not a medicine. 

VC: In New York, the rollout has been messy, with illegal shops everywhere. The state clearly wants the taxed, regulated legal market to take off. The state also has some incentive to not encourage use. Have policymakers struck the right balance in your view?

MH: This is the area that I pay the least attention to, I have to confess. I do know that Canada has some restrictions in place that I think are essential for cannabis, if we think about legalizing this federally — about advertising and about warning labels and approaches for different vulnerable populations. 

VC: You referred to different types of cannabis. Are there meaningfully different types from the perspective of a scientist?

MH: There’s, of course, a ton of nonsense marketing about indica and sativa cannabis plants — that doesn’t matter — but yes, there are different chemovars, different types of plants grown differently that have different behavioral effects. We have no idea why. We don’t know what the ratios of the different cannabinoids are doing or why they’re producing effects. But clearly some are more sedating and some are a little bit more of a stimulant. For reasons we don’t know, there are strains that produce different effects.

VC: What haven’t I asked that you want to say?

MH: Well, something that I’m most passionate about and I tend to say to anybody who will listen to me is: The reason why we have these very strict definitions for defining something as a medicine and have placebo control when we do experiments is because we as human beings are incredibly susceptible to the placebo effect and the expectancy effect. Add to that, that this is an intoxicant. 

The most common reasons people are using medical cannabis for are pain, anxiety and sleep. And those three things have the highest placebo response of many, many endpoints.

The placebo response has a great neurobiology. Your pain signal literally shuts down if you think you’re taking an active compound. 

So just have a little skepticism. Buyer beware. Don’t swallow this billion-dollar industry’s marketing wholesale. There’s a lot we have to learn and we can’t just let marketers tell us what it’s a medicine for and what it’s not.