We met with Dr. Allyn Howlett to discuss neuropharmacology, how the brain reacts to different drugs, the effects of marijuana, and much more. Enjoy!
Dr. Allyn Howlett shares her journey into becoming a neuropharmacologist, a field that she believes allows her to best study how the brain works. Dr. Howlett uses cell cultures to study how brain cells react to various drugs, such as cannabis. These studies have allowed Dr. Howlett, working alongside chemists from Pfizer, to discover the CB1 receptor for cannabinoid agonists. Dr. Allyn Howlett also discusses the effects of marijuana and times when it can be especially harmful.
Researchers have just discovered that THC had some pain-killing responses, so the drug company, Pfizer, was very interested.” – Dr. Allyn Howlett
If you’re interested in becoming involved in the emerging cannabis industry, check out our article Majoring in Marijuana: Best Colleges for Studying Cannabis
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(Editor’s Note: The following transcript has been lightly edited to improve clarity.)
Karina Macosko: Hi, my name is Karina Macosko from Academic Influence, and I’m here with Dr. Howlett. And I just wanna know:
How did you get into your field? And what kind of influenced you to go into it?
Allyn Howlett: Well, when I was in high school, I was very interested in how the brain worked, and I read a lot of books. I went to college because I liked Biology and I liked Chemistry.
And so my uncle, who had been educated at Penn, told me that I should go to Penn State because they have a degree in Biochemistry. And at the time, it was one of the few degrees strictly in Biochemistry, and it originated from the Chemistry Department.
I had originally started thinking about being a Psychology major, and then as I read the kinds of things that psychology people were doing, I concluded that I could better understand how the brain worked by being a biochemist.
Karina: Wow, that is so interesting.
And why did you choose to do a PhD, rather than go to med school or something?
Allyn: Well, I wanted to do something that was biomedical, and I also liked music. And so I had Albert Schweitzer as my idol.
Albert Schweitzer was an MD who went to Africa, and he took his organ with him so he could play the organ. And then my dad took me to a movie about what life was really like for Albert Schweitzer, and I concluded that maybe that wasn’t the life for me.
And so I thought a little bit about being a pharmacist, and I got a job when I was 16 years old in the local pharmacy. And as I watched the pharmacists work, I concluded that it was a good deal of education for simply counting cells, putting them in a bottle, and typing the name on; and that really didn’t excite me either.
So when I really started doing some of the research that you can do in the chemistry and biology labs, I concluded that even though Penn State was an agricultural and engineering school, I could use that kind of knowledge and background to study things that are related to the brain.
So that’s, I would have to say I had to have those negative influences in order to let me know what I did not want to do, but I clearly did want to be in a medical school environment. So here I am.
Karina: Wow, yeah! And I’m seeing that, too, as I’m trying to decide what I wanna major in or what kind of school I wanna go to. It’s really a lot of checking off the list, being like, “No, that is not what I wanna do,” before you find something.
Karina: So what was it about psychology that really turned you off?
Because obviously, you wanted to just study the brain.
So what was it that made you decide psychology was not the best field to do that?
Allyn: Well, psychology has many different kinds of branches. Some of them were counseling, and some psychologists are involved in educational aspects of learning, and then there are some who do research.
And the kind of research they were doing, I really didn’t feel was getting down to the nitty-gritty of how neurons communicate with each other. So it’s just a different kind of level of understanding.
Clearly, right now, I’m in a department that has a lot of people who do animal behaviors, and they teach their animals how to press buttons so that they can communicate, and they teach them how to recognize symptoms of certain kinds of drugs so that they can recognize whether a drug they’ve been given is one kind versus another. That wasn’t the kind of thing I wanted to do. I wanted to look more at the level of the cells.
Karina: Wow, that is so interesting! And the next interview is gonna be very focused on marijuana and your study of that. So can you explain to us:
How did you get into that? How did you start studying how that can affect our brains?
Allyn: I was working in an undergraduate lab that was doing biochemistry using cell culture. And at the time, cell culture was really very new. I took that interest into graduate school, but in graduate school, I was doing much more brain-related work.
So when I left graduate school, I went to a postdoc in which I could do some cell culture work. So I was able to work with neurons in cell culture so that I could give them drugs and understand a little bit about how their biochemistry worked, and not be looking at it at the level of animal behaviors, such as the one we just witnessed, but more at the level of how the cells change their behaviors in order to adapt to new environments such as drugs of abuse.
And so how did you go from that to specifically studying marijuana?
Allyn: I really wasn’t so very interested in drug abuse at the time. I didn’t really know very much about it, and I was more interested in some of the new hormones that were being discovered like the prostaglandins.
And a Nobel Prize had just been won for learning about prostaglandins, and my cells responded to them. Most people studying prostaglandins were studying immune responses, and I saw that there was a response that the brain cells were having.
So I thought that was interesting. And in the process of looking at that, and I should tell you, prostaglandins were hard to really think about as a drug because they didn’t have any blockers that could block their activities.
Instead, the only thing we had was aspirin-like compounds. So there’s a whole series of compounds now like ibuprofen and acetaminophen. The brand names are things like Advil and Tylenol.
So these kinds of drugs blocked the synthesis of prostaglandins. So in the process of these studies, I came across some papers by chemists from Pfizer. Pfizer had been studying compounds that came from cannabis, the active compound, THC, and researchers had just discovered that THC had some pain-killing responses.
So the drug company, Pfizer, was very interested because the only painkillers that we had at the time, and in fact, even now, were either these nonsteroidal anti-inflammatory aspirin-like compounds or opioid compounds. And as we all know now, those opioid compounds do have some pretty bad side effects.
Allyn: So we had a situation where the drug company thought that the compounds they were working with might be blocking prostaglandins. And the chemist put a small communication in the research literature, and as researchers, we all read what other people are doing in their labs so that we can go a little bit further in our own labs.
So I was watching to see what they were doing, and they suggested that these compounds that they were making that were very much like THC, the active compound in cannabis, they proposed that they were working by blocking prostaglandins.
So there I was with my cell culture that responded to the prostaglandins, I could test their hypothesis. So I wrote to the chemist at Pfizer and I said, “I think I can test how your compounds work,” and they not only gave me what I asked for, but they gave me some additional compounds as well. So I tested that hypothesis, and there was no support for it at all.
Now, what I don’t mean is I do not mean the experiment didn’t work. What I mean is I got a result that indicated that their compounds had an effect, but it was not the effect through the prostaglandins.
So now, I had to devise an alternative hypothesis, and my alternative hypothesis was that the compounds like THC had a receptor of their own. And up until that time, I didn’t know very much about cannabis, even though the 60s were over, the 70s were over, now, we’re in the 1980s, lots of people had been using pot for a long time, and I just made the assumption that scientists knew exactly how that worked, until I started reading the research literature.
And then the best explanation I could find was that some researchers thought that cannabis worked by the same way that some analgesics and anesthetics work by getting into the cell membranes and perturbing the cell membranes; that would be very non-specific. But my hypothesis was that they had a very specific receptor.
So that’s how I got into this. I stopped what I had been studying and I moved completely into trying to answer that question.
And why was it that a lot of scientists weren’t studying this? Why hadn’t anybody figured out exactly how it worked before this?
Allyn: I think it was because people in science work with different kinds of methods and different kinds of techniques. And when the active compound in cannabis was first discovered and identified by a synthetic organic chemist, he was able to make that compound and demonstrate that it had the same effects that extracts from cannabis had in animal models.
So he engaged a number of researchers throughout the whole world who had different kinds of animal models and gave them his purified drugs and asked them, asked him to test them.
So we had people working from that point of view on animal models, and then there were people that were studying what we call pharmacokinetics, and that’s how a drug gets into the body and is absorbed into the tissues and is distributed to the tissues that it needs to go to and then how it’s eliminated.
So there were a lot of chemists and biochemists studying that aspect, but there weren’t any cell biologists studying this. And at that point, I was a biochemist moving into cell biology. So I think it was just that people were asking different kinds of questions, and the answers that I could give were based on my training in my field.
Karina: Wow, that is so interesting! And you’ll cover this more in the next interview, I’m guessing, but just for people watching, I’m sure everybody is very curious…
could you give us just a brief rundown of the question: Is cannabis good for us?
Obviously, there’s probably pros and cons, but just give us a brief rundown of what’s good and what is not so good.
Allyn: Well, I think the situation is that the THC interacts with a receptor that is found on all cells in the body, almost all cells.
And at first, people thought, “Oh, it’s just a brain compound.” But as we went into more detail and people from other fields, gastrointestinal people, metabolism people, people studying bone, people studying the liver, all began looking, it’s got effects on many different cells.
And what it’s doing is working through a receptor that is there for feedback to tell cells how to get back to the state that they were in the first place. So you know when cells respond to hormones, or brain cells respond to neurotransmitters, that changes the way they behave. And that’s what you would need because that’s how you can signal from one cell to another.
But sometimes, that causes changes in those cells in the process of their continuing their communication.
And so these receptors that are therefore feedback mechanisms are responding to small molecules that the neighboring cells have made called endocannabinoids, and we call them that because its endogenous, meaning, your cells in your body make them, endogenous cannabinoids.
Those endogenous cannabinoids are what is meant to be part of a signalling system, and that helps the cell to get back to the way it was before.
We call that homeostasis.
So now, if you introduce a drug that’s exogenous, that means coming from someplace else, so this is the plant product, it comes from some place else, it hits these cells at a point where they should have been responding, if they wanted to, to feedback mechanisms, but now, they’ve got THC hitting them instead. And so that perturbs them.
Now, in the brain, there are lots of different neurotransmitters that are under this kind of regulation, and many of them are involved in important functions like memory and keeping people awake and responding to other stimulus that are gonna be important in telling the brain whether you should start eating or whether you should stop eating, these kinds of things.
So you can just imagine that there’s some perturbation to have a compound coming in from a plant, that doesn’t belong there, now trying to signal through these receptors.
…that's where I think we have to start to think about: Is this good or is this bad?” – Dr. Allyn Howlett
So I would say that that’s really how a lot of compounds work, is we use them because they come from some kind of a natural product like a plant or a snake venom or spider toxins, or something, and drug companies have modified those active compounds, and then you can use them either to mimic the effects of the hormones in your body or to block the effects of the hormones in your body.
And that’s not an unusual thing, but here, we’ve got it going on in your brain. And that’s where I think we have to start to think about: Is this good or is this bad?
Now, one of the things that it’s doing is during development and synapse-formation, if now, you’re perturbing the way the cell responds to its neurotransmitters, that’s not a good thing. [chuckle]
Karina: Right. [chuckle]
Allyn: So it can change the way your brain develops. And there are two times in your lifetime that that’s gonna be particularly important.
One is when your brain is developing in the first place, that’s in-utero in a pregnant mother while the baby’s brain is developing. And then subsequent to that, in early development, when the baby is drinking the milk from the mother that contains things that are in the mother’s body.
The second place is people that are your age because after you leave childhood and you begin going into adulthood, your brain goes into a tremendous pattern of eliminating childhood synapses and building new adulthood synapses.
And that’s the time of brain development that you don’t want to be interfering with that by smoking pot. So I would say that’s the bad part.
The good part might be that if you need to use them as drugs that are going to be similar to something that’s not really working so well in the brain like response to pain, that’s a good thing.
So I would not say there's good drugs or bad drugs; what there are good uses or bad uses.” – Dr. Allyn Howlett
But the bad thing is taking something when your brain is developing and interfering with those processes. So I would not say there’s good drugs or bad drugs; what there are good uses or bad uses.
Karina: Right, right. I think that is a great point. And thank you so much for taking the time to talk with me. I cannot wait for people to watch this video and watch the next interview after because I think it’s just so interesting, and something that a lot of people have been talking about lately. So thank you so much for taking the time to talk with me.
Allyn: Well, thank you very much.
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