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The Bliss Gene And The Burden Of Mood
00:32:45
Psychiatrist Richard A. Friedman explains how a rare genetic mutation affecting the enzyme FAAH, and a ubiquitous neurotransmitter called Anandamide may account for unusually low anxiety, reduced drug cravings, and an innate buoyancy, the type of...
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- [00:00]
Mike Pesca
Bradley Tusk is an interesting guy with a long political resume and also a venture capital resume. Why am I just talking about Bradley Tusk? Because he's interesting, but also because I'm doing a substack live with him at 6:30 on Wednesday that I'm inviting you to. But I want to point out that he did a TED Talk because his big project is to totally change the way we do primaries. He thinks this will be a massive overhaul of the political process. I tend to agree. And then he has this other project, solving hunger. He did campaigns in different state legislatures and he wants to in our substack live, just shame the members of the legislatures who got in the way of feeding kids. So if you want to check into our substack live doing some homework, the TED Talk is out there and we'll also be naming the names of those who just smacked food and out of the mouths of hungry kids. See at 6:30 on substack. Mike pesca.substack.com It's Tuesday, July 22, 2025 from Peach Fish Productions, it's the Gist. I'm Mike Pesca. Justice Department officials had wanted Brett Hankinson, a former Louisville police officer, to serve a day in prison. This was the only officer who was convicted in federal court of firing into the home of B.R. taylor. He did not strike Brianna Taylor, but he did stand outside the apartment and just pump shots into the side of it. I'm enough of a fan of law and order to think that the law should be more orderly. And so too did prosecutors before Donald Trump got into office, recommending a fairly lengthy sentence. The maximum for what he did was a lifetime in jail. The Trump administration, because his actions as irresponsible though they were and unlawful as found by a jury, his actions comported with their message of, I don't know, being against dei. Luckily, the judge in the case dismissed the federal prosecutor's recommendations and Rebecca Grady Jennings gave Hankinson 33 months. Grady Jennings, a Trump appointee, by the way, that low sentence of one day was just too stupid for her to to abide. This was an example of the Trump administration having no follow through and not accomplishing anything. But they're right there. On the front page of the Louisville Courier Journal was another story out of Louisville that shows the opposite. The Trump administration actually having some follow through and getting some results. They have been putting the pressure on local mayors whose cities are sanctuary cities. And in the case of Louisville, it worked. Their mayor, Craig Greenberg, said that he received a letter from the assistant attorney general of the Department of Justice's civil division. He said that he was contacted by the Justice Department who told him that the city needed to start issuing detainer requests. This is when someone is arrested. They are detained for up to 48 hours to allow ICE agents that to investigate and possibly deport them. 48 hour holds on inmates. Lots of places do this. In fact, every other place in the state of Kentucky does this. But the Justice Department was threatening Louisville with serious sanction violation penalties if they did not abide. Greenberg, pressured on all sides, looked at the actual effect of this law. About 100 people in Louisville each year, or in fact fewer than 100 inmates annually, are affected by immigration detainers at metro corrections in Louisville. And the mayor decided that the best policy for the city, the best tradeoff, would be to remove Louisville's sanctuary city designation. He cited concerns about increased ICE raids and loss of federal funding if he didn't do it. The ACLU decried this action, saying that by choosing to comply in the face of the Trump administration's threats, Louisville has aligned itself with policies that have led to increased fear, mass deportation and instability in cities across the country. Mayor Greenberg arguing that if he didn't comply, more instability would be visited upon his city. We should note that during the Biden administration, federally when he was in charge of such policies, 48 hour detainers were still in effect. And some cities, some states, like the entire state of California, did not comply. But others, like Texas, complied. Hundreds, if not thousands of detainers during the Biden administration were served. There are no good choices for the mayors or even the presidents who have to oversee such policies on the show today. Being a world leader is tough and full of conflict and border disputes. And it turns out it doesn't get much easier when you're dying or even dead. But first, a little about me. I'm generally positive I have a positive affect. Maybe that affects my judgment on the show. It certainly affects my judgment in life. Maybe you come around and hearken to my words because I am somewhat logical but certainly optimistic, assessor of the world situation, trousseau in my own life. And is this because I've studied? I think so. Is this because I understand big picture macroeconomics, political trends? Indeed, I think so. But it's also because of just my internal brain chemistry. In fact, I am blessed by bliss Anandamide. It is the bliss molecule. We all have some of it, but some people like me, I believe, have it more than others. For the first time on the show I talked to the medical professional who put this idea, this molecule on the map, if not in my mind. That was my creator. Richard A. Friedman is a professor of clinical psychiatry and the director of the psychopharmacology clinic at nyu. And he is here to discuss the bliss molecule, Anandamide Talk up next. So some interviews on the GIST are because I just needed to know, and some interviews are because you needed to know, and some interviews are because, I'll admit it, I owed someone a favor. But sometimes those wind up being really, really good interviews. This is a kind of interview and it's one that is designed to pretty much unlock the key to my existence, the core of my being, the mystery at the center of the soul. I'll take you back about 10 years and there in the New York Times was an article called the Feel Good Gene. It was written by Richard Friedman and it talks about what is called, and maybe this is his dubbing, the bliss molecule, anandamide. We'll get into it more. There are, we could get into the cannibal endocannabinoid system, system, why it works, how it works. But I have never in my life before read an article or a piece of literature where I said more that explains me. This is exactly what's going on with me. So Richard Friedman, the professor of clinical psychiatry and director of the psychopharmacology clinic at Weill Cornell Medical College, joins me now. Hi, welcome to the gist.
- [07:53]
Richard A. Friedman
Thank you. It's a pleasure to be here and.
- [07:55]
Mike Pesca
Welcome to the Bliss. Did you invent that? The bliss molecule, the bliss gene?
- [07:59]
Richard A. Friedman
Well, I mean that's, you know, anandamide means the bliss in Sanskrit, so I didn't invent it.
- [08:06]
Mike Pesca
You just translated it from the trans.
- [08:08]
Richard A. Friedman
Exact.
- [08:09]
Mike Pesca
But. Which is good of you. Yes. So explain what it is and how it works in that order. What is it? And then what's the effect?
- [08:17]
Richard A. Friedman
So anandamide is a naturally occurring, so called cannabinoid, nature's own cannabis, that exists in the brain of humans and also other, you know, non human primates. And it's very important in the brain in regulating mood and appetite and anxiety, all kinds of behaviors. And it's one of two endogenous, meaning natural to us, endogenous cannabinoids in the brain. That. The other is something called 2 AG, which is lesser known. But anandamide is, is the cannabinoid in the brain that stimulates the cannabinoid receptors, which is the target of cannabis that people, you know, smoke, eat, vape, et.
- [09:05]
Mike Pesca
Cetera and in fact, is that how they found it? They did a reverse engineer asking the question, wait, why does cannabis work?
- [09:15]
Richard A. Friedman
Well, that's a profound question. Because we have receptors in our brain for all kinds of consciousness altering states. And so the natural question always is when you find these receptors, and sometimes you find them because you're using your reverse engineering, you're using recreational drugs and then tagging them and studying where in the brain do they go? And then you find out where they go and you say, what is this receptor doing in the brain? And what is the natural, what is the natural molecule in the brain that operates at that receptor?
- [09:50]
Mike Pesca
Yeah. So every drug works in an analog to a chemical in the brain, otherwise it wouldn't have an effect on the brain.
- [10:01]
Richard A. Friedman
Exactly. I mean, we recognize these molecules because we evolved for, you know, millions of years surrounded by them, and we've been exposed to them. If they're truly foreign, it has no effect at all.
- [10:13]
Mike Pesca
And to be a bit more clear, it is not really the case that we have chemicals that are like marijuana and we're hitting ourselves with marijuana. It's more the case, I want you to describe it, that these chemicals bond to receptors that we have and either limit or increase the amount of naturally occurring substances or chemicals that affect our mood. Is that, is that a better way to think about it?
- [10:44]
Richard A. Friedman
Yeah, it's more like we have these naturally occurring substances, but the ones that humans use are often either a little stronger than the ones in our brain or given at much higher concentrations than the ones that occur naturally in our brain. So, you know, for example, if you smoke a joint or you vape, you're delivering an amount of cannabinoid to your brain that's much higher concentration than what naturally occurs in your own brain. Meaning the anandamide is there at very low levels. And. But when you smoke marijuana, you, you basically flood the brain with, you know, thc, which is a cannabinoid that binds the receptor and you get a big effect.
- [11:37]
Mike Pesca
So someone self diagnosed, like me, who feels that the systems that you're talking about, who feels the effect of anandamide, and I again self diagnosed, how will such a person who has higher than normal levels feel? They won't feel loopy, right? They won't laugh at things like someone who's high, they won't speak slower like fish in the Grateful Dead. How will it show up? Typically, someone with perhaps elevated levels of anandamide.
- [12:12]
Richard A. Friedman
There's a variation in humans about the level of naturally occurring anandamide. And if you have a lot of it. Let's say you're above the mean. If you were first, you wouldn't want to use as much marijuana. You would be not so interested in using it. And if you did use it, it might actually not be so pleasant. You might have a negative reaction because you've got your own, you know, naturally occurring cannabinoid at a, at a level that's high enough. So your anxiety level is probably lower at baseline than average.
- [12:49]
Mike Pesca
Lower. Lower anxiety effects of marijuana doesn't work. What about the munchies and obesity?
- [12:58]
Richard A. Friedman
You probably still would have an appetite increase if any of you had elevated anandamide. If you smoked cannabis, it would still exert appetite.
- [13:09]
Mike Pesca
Oh, what I mean is I walking around again, self diagnosed with elevated anandamide. Am I hungrier than most?
- [13:17]
Richard A. Friedman
Oh, that's interesting. You know, not in, in, in the clinical studies of, you know, anandamide, they didn't notice that people who had higher levels of anandamide were either heavier or consumed more food.
- [13:36]
Mike Pesca
What are some other characteristics of the elevated anandamide community? So now it's a community.
- [13:42]
Richard A. Friedman
Yeah. So lower levels of anxiety, lower drug seeking, less likely to want to use cannabis and probably other drugs as well, maybe alcohol. And another thing that's very interesting about people who have higher levels of anandamide is they learn and can learn to be unafraid more easily than the rest of us.
- [14:08]
Mike Pesca
There's also something, and I want to get this, you know, I want to get this right. I'm speaking to a man of science. There is the faah, the fatty acid amide hydrolase. And then they actually have a number for the single nucleotide polymorphism. What's that, how's that apply to the anatomy? Anandamide that me and the anandamide community might have?
- [14:33]
Richard A. Friedman
Okay, so this is the key, that enzyme is the key to why some people have normal, Some people have low, Some people have high levels of anandamide. So fa fatty acid. It's a fatty acid hydroxylase. And basically it's an enzyme in the brain that degrades anandamide. It chews it up, degrades it. So if you have low levels of this enzyme, you have higher levels of anandamide. And if you have higher levels of this enzyme, which is chewing it up and degrading it, you have lower levels. If you have a mutation in your enzyme, in your gene that makes this enzyme and you lose function of the enzyme, you're walking around with higher levels of an. Antibodies. So it's a loss of function.
- [15:22]
Mike Pesca
Yeah, a Loss of function that results in you being quite happy about things.
- [15:26]
Richard A. Friedman
Exactly. On the other hand, if you had a gain of function mutation where your enzyme was more active than average, you would have lower levels of anandamide and have higher levels of, let's say, baseline anxiety potentially. And also you would, you would enjoy marijuana. You would want to use it.
- [15:49]
Mike Pesca
Yeah, yeah. You would seek it out. And in fact, at least in the anecdote that starts off your story, either that's how you got into it, literally, that's how you found out about it, or that's what sparked your curiosity about this, a very heavy cannabis user.
- [16:05]
Richard A. Friedman
Yeah. And why some people have no interest at all.
- [16:08]
Mike Pesca
Yeah. So let's talk about the implications of what you're saying. I guess a decade or so ago, the concept of, well, you know, what is personality or what is depression? Something like the wiring of your head. And then if you get a little more complex, something like your, the, the genetic or chemical makeup of your brain and someone like you would know that, know about that a little more in depth. But this was the lay understanding of how brain worked and it was usually used to express some sentiment like we shouldn't stigmatize people who suffer depression, let's say, or we should think about them in a way analogous to someone who's suffering some physical malady, like a broken bone. There's physical components, it's about chemicals. Then when I started reading your story, or maybe even before it, sort of like a receptor looking, or sort of like a gene looking for a receptor, I did say to myself, well, might it not be the case that even positive affect or even a buoyant personality is not just that you have the right outlook on life, it's the same thing. It's just another side of the chemical wiring in your head. If you want to think about it that way. I mean, have you considered that perhaps all of the human experience, human cognition and mood is just some positive or negative aspect to what I'm talking about?
- [17:45]
Richard A. Friedman
Right. So it's an appealing idea. And I, and I think there's definitely a biological contribution to mental states. You know, happiness, the tendency to be happy or buoyant and the mirror image, you know, the tendency to be gloomy and given to negative outlooks at the same time? Psychology, you know, non biological factors, they do have a big effect. You know, just think of your own emotional responses to stresses or sad things. You know, we're, we're very easily influenced by the environment and by, you know, those, those around us. It's just that some of us have a genetic loading and there's an interaction between our genes and our biology and, and the environment. So there are some people who, let's say in response to stress, they don't get that anxious and even when they're heavily stressed, they barely get anxious. And on the, on the other side, there are people who have the best environment, most protected environment, they've got everything, they're financially secure, people who love them and they have desperate depression and they're addicted to drugs. So it's, it's, it what we call gene environment interaction is a, is a way to think about the outcome between, you know, what you've got genetically and biologically and what kind of environment you find yourself in.
- [19:13]
Mike Pesca
Right. Nature determines the range and nurture hones you in on that range. Nature determines, that's the genetic range of possible reactions, outcomes, affects, as I said before, and then you know, your environment and maybe if someone like you is good enough, your reactions to the environment, your ability to use techniques to not be overwhelmed by the environment, that determines, that determines a lot about your personality and your mood.
- [19:46]
Richard A. Friedman
Yeah. And also it's, it's not fair in a way because people inherit certain genetic variants that have, you know, that either increase or decrease their burden. So it might be, you know, for some people to maintain a good mood or be less anxious in the world, they have to work much harder than others and not because they're weaker, but because, you know, genetic variants that they have give them an advantage or a disadvantage. Life is unfair that way.
- [20:19]
Mike Pesca
Well, it's unfair in the way that someone could be a two pack a day smoker and not die of lung cancer and then someone who never smoked can die of lung cancer. I mean, there's all this variation. It's not, I think with physical things. Yes, we know it's not fair. We know some people are taller and some people get diseases or some people are a bit healthier. We probably don't say it's not fair about that. Maybe we need to totally reconstruct our concept of what fairness is. I don't know what the baseline of mental health fairness should be assumed to be.
- [20:46]
Richard A. Friedman
Yeah, right, but, but also the attitude that we take toward people who are ill, especially with psychiatric illness or drug abuse is usually moralistic. You know, you, you just need to suck it up and be, be stronger. It's, it's a weakness as opposed to actually these are real illnesses, diseases, and it's not entirely in your control at all.
- [21:13]
Mike Pesca
It's not entirely in your control But I'm sure because you've done, you've advised many people over the years to get not just psychopharmacology but some form of therapy that it's somewhat in your control, which doesn't take off the. Because if it's not in your control, then why even work on it? Then why even use techniques like biofeedback or techniques that work? Right. So, you know, I'm not, I'm not one to stigmatize or I'm not one to blame. Blame is not useful. But within the range of the genetically and environmentally determined, there are some interactions, some interdictions that we could do that maybe moves the needle a little bit and think and just know that it's determined by forces outside ourself or maybe literally inside ourselves, inside our brains.
- [22:04]
Richard A. Friedman
Yeah, I think there's actually a lot that people can do with their own biological genetic constraints.
- [22:11]
Mike Pesca
Yeah. Or their predispositions. Now, I want to ask you, if you were a different kind of medical doctor and people came to you and they were showing effects of a malady, you might reach for genetic testing as the first thing. But that, from what I understand, that is not usually done. Psychiatrists don't know the baseline of anandamide within their patients or far should they? Wouldn't it help them?
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Richard A. Friedman
It's interesting question. It might help them understand a little more why somebody likes to use cannabis. But often the kinds of information you get from genetic testing, you know, you can infer clinically by observing someone's behavior. It can cut both ways. I mean, let's say you do the genetic testing, you find out that someone's got a variant that, you know, predisposes to low levels of anandamide, then what would you do? You could. That information could be useful and cut both ways. The person could say, you see, I. I just was born this way. And so I'm simply doing what nature's demanded of me. I'm supplementing my low Anandabod. So.
- [23:24]
Mike Pesca
Right.
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Richard A. Friedman
You know, I have no control over this. But actually you do. You can decide there are other things to do. So I don't think it would be so useful. It's useful in understanding the biology behind the behavior that leads us more or less prone to wanting to do this. But at the moment, the actual clinical usefulness is limited.
- [23:57]
Mike Pesca
Yeah, I don't know. I think maybe that could change. I understand what you're saying, but the first you said that clinically you could get to the same conclusion as one may be able to do with genetic testing, but that's probably true with jaundice. Right? That's probably. If you ask a liver specialist, I'm sure they would say, and they, if they're very good, nine times out of ten I could figure out exactly what's going on just based on external observation. But then again, they might get the test and it might help them. And the other thing I would say is, yeah, it could. If the doctor said, the genetics said you're at a low level of anandamide, that's why you're doing it, it could help you rule it out. If the test comes back and says, actually you're not at low levels of anandamide, there's something else going on here, it might be useful to try to get to that something else.
- [24:50]
Richard A. Friedman
Yeah, but, but you would go after that something else even if you didn't have the test. Because let's say, you know, somebody is abusing a drug or using a lot of it, it leads you to think, okay, they may be self medicating for an untreated anxiety or depressive disorder or any number of those things. But I mean, there aren't that many tests that we do in psychiatry looking at genes mainly because a single mutation only contributes a tiny amount to the overall behaviors that humans have. It's not like in, let's say a classic genetic disorder that is like a Mendelian dominant like hair color or eye color or sickle cell anemia. If I, if I do a gene test on you in any of those issues, I'll get an answer determinant and I can say to you, right, exactly. I will know from the gene what the phenotype is, what the, what the physical trait is going to be. In behavior genes, you need hundreds, if not more than hundreds of genes to give you to account for a lot of the behavior. It's polygenic, it's many, many, many variants.
- [26:06]
Mike Pesca
There are so many books and self help programs and podcasts. Oh, the podcast doctor about happiness and this quest for happiness and how, you know, the number one class at Yale is about happiness. What if it were the case that, okay, we could cut through this and there is still a lot to be gleaned, but you should just know that the people who are doing it right, a vast majority of them or some huge disproportion of them, just are genetically wired that way. Wouldn't that be useful in terms of all the people who are downloading all those podcasts?
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Richard A. Friedman
Yes, it would be useful. It would be helpful especially for people who have a hard time being happy, they might not blame themselves, but then they're still going to want to know what do I do to be happy? Okay, I've got this genetic marker that puts me at a risk for being anxious. So I just have to accept this, but then try to incorporate all these behaviors and practices to be happy. So we all, we all have all, all kinds of unknown genetic, you know, variants that probably contribute to things like this.
- [27:24]
Mike Pesca
How likely is it that from the rough checklist that you provided, how likely is it just from my reading of it and descriptions that I'm right, since I've never had an actual test that I'm right, that I have this mutation that gives me elevated levels of anandamide?
- [27:42]
Richard A. Friedman
There's a good chance you're right. But because there are other variants that relate to happy temperament, you, you may have other protective genetic variants that, let's say are producing the same result, but it's not an andamide. There's, there are many. You could be, you could be genotyped. People could find out if you're, if you have the feel good gene or not.
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Mike Pesca
I'd like that. I think I'd like that. It would explain a lot of things. Richard Allen Friedman is an MD professor of clinical psychiatry and director of the psychopharmacology clinic at the Weill Cornell Medical College. Thank you.
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Richard A. Friedman
My pleasure.
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Mike Pesca
And now the spiel. Internal strife in Zambia has spilled over the border to South Africa. The dispute between the two generally aligned countries is sure to have a loss of life. And that is because the dispute is about a guy who's already dead and has been for a month and a half. Edgar Lungo was president of Zambia from 2015 to 2021. But he did not like the current president, Hakatan Day, he Chelema and Hakan Day He Chelema did not like Lungo. Lungo gave word that he Chellima was not to attend his funeral. Thus, the Lemola very much wanted to give his predecessor a state funeral, arguing that Lungo's body belonged to the state. And since he shellma was the state, of course he'd have to go to the funeral. No way, Hakan Day said the Luongo kids, we'll just bury him in South Africa. And so the funeral was held and so Lungo was to be laid to rest thereafter. But then a South African court ruled the burial would not proceed due to what the court described as an agreement between the parties perhaps agreeing. We're both looking pretty bad in all of this, but not coming to a resolution Neither the hatchet nor the Zambian ex president would be buried on that day or any day since.
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Richard A. Friedman
Several of Edgar Lungu's family members alongside the funeral service company holding his remains are named in the lawsuit filed by Zambia's Attorney General Molilo Kabesha. He says the former president should be buried in Zambia with full military honors in line with Zambian law and traditions.
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Mike Pesca
The Zambian attorney general, fresh out of things to do other than play Fisher and Sons funeral directors is now arguing that his government has the right to include H. Lama in a short church service at the airport when Lungo's body is returned to Zambia. The Lungo family objects to this as well. I understand their disquiet. When Edgar was alive, Chilema put him under house arrest and wouldn't let him travel to South Africa for medical treatment. Had he shell him, I might not be in this position because Lungo might not be in this position, which is to say dead. It should be noted that when Lungo was president he once locked up Hachellema for 100 days in what Zambian media flimsy charges. This is something short of a full blown international incident, but it is a mortuary one. The funeral home in South Africa, as you heard, is part of the suit. This is a little bit of a South African tradition, by the way. Robert Mugabe was all set for a fancy state funeral to be laid to rest in the Zimbabwean national heroes acre. That was what the Zimbabwean government wanted. His family was having none of that. He was buried privately. Same with Angola's president Jose Eduardo dos Santos. His fourth wife second, depending on how you count. It's complicated. Arranged for him to be buried in Spain, not the country that he presided over for 35 years. Not a democracy, Angola. You know, funerals are never fun. They're always tense. And when you add past indignities or snubs, like who didn't get a wedding invite or who got grandma's china or how flimsy was or wasn't the 100 days of arrest. It is really hard for all parties to maintain being disinterested and for the deceased to avoid being disinterred. Whatever funeral arrangements do occur, they are not expected to take place until August in a country to be named later. And that's it for today's show. Cory Ward is the producer of the Gist. Astric Green runs our social. Our primary production coordinator is Ashley Khan. And Michelle Pesca oversees all of this happy family because no one has been arrested on flimsy 100 day charges. G per Duparu. Thanks for listening.