title Cannabinology (MARIJUANA) Part 2 with Ziva Cooper and Caroline Melly

description Neurodivergence and weed. Munchie remedies. Long term toking. The Entourage Effect. Drag a bean bag into the circle and kick back for Part 2 of Cannabinology with UCLA’s Center for Cannabis and Cannabinoids director Dr. Ziva Cooper and Smith College cannabis anthropologist Dr. Caroline Melly. We’ll probe the great mystery and misfortune of hyperemesis, the effect of THC on memory and neuroplasticity, why edibles sometimes send you to a distant galaxy, CBD and inflammation, the risks of psychosis, older vs. younger brains and cannabis, a guy named Rick Simpson, how much weed is the right amount of weed, and if any studies warrant further research. Heads up: they do.

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Other episodes you may enjoy: Psychedeliology (HALLUCINOGENS), Dolorology (PAIN), Molecular Neurobiology (BRAIN CHEMICALS), Mnemonology (MEMORY), Attention-Deficit Neuropsychology (ADHD), Obsessive-Compulsive Neurobiology (OCD), Traumatology (PTSD), Somnology (SLEEP), Eudemonology (HAPPINESS), Neuropathology (CONCUSSIONS), Neuropathoimmunology (MULTIPLE SCLEROSIS), Sports & Performance Psychology (ANXIETY & CONFIDENCE), Addictionology (ADDICTION), Salugenology (WHY HUMANS REQUIRE HOBBIES), Quasithanatology (NEAR-DEATH EXPERIENCES), Oneirology (DREAMS), Surgical Angiology (VEINS & ARTERIES), Cardiology (THE HEART)

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pubDate Wed, 15 Apr 2026 09:00:00 GMT

author Alie Ward

duration 5585000

transcript

Speaker 1:
[00:00] Oh, hey, it's still the lady weeping into hash browns at the diner. Alie Ward, this is part two of Cannabinology, part two, weed. If you're starting here for all of the supple, juicy answers to ADHD and THC and Alzheimer's and smoking and vaping, don't start here. Start at episode one. We made you a whole part one. I promise you will love it. And it's fun, all the basics. And then come back for this wall to wall questions from listeners via patreon.com who submit them before we record. You too can join that for a mere dollar a month. Thank you also to all the folks out there in the world wearing Ologies merch from ologiesmerch.com. And thank you to sponsors of the show who make it possible for us to donate to a cause each week. And as always, thanks to those of you leaving reviews for the show which help us get discovered by others. Also, I read them all. I promise that I do. And thank you, Jules, who wrote that Ologies is truly inspirational in lighting a fire of hope and immense joy in us all. Speaking of lighting a fire, Jules, you're right on time with that one because we are blazing toward 420. And for the few of you who listened to this last week and told me that I should have waited to release this on 420, we've planned this for like a year. I'm one step ahead because now you're going to know your weed better if you do celebrate. And also, you can send this pair of episodes around to educate the masses on 420 on matters such as Dab vs. Shatter, Indica vs. Sativa, the legal semantics of hemp vs. marijuana, pre-rolls, gummies, the endocannabinoid system, the bliss molecule, and a bunch more. You can also let people know that 420 was never a police code for public grief or smoking. Rather, it was just an inside joke that got out of hand between a group of Marin County high school stoners in the 1970s who would meet up after school at 420 to go treasure hunting for this rumored forgotten weed patch. They just drove around smoking weed, looking for a big field of weed. They never found it. But one of them ended up working for a Grateful Dead member. Now the rest is history because at 40 minutes to five, it's always 420 somewhere. Drag up a bean bag into the circle, kick back for neurodivergence and cannabis, the great mystery and misfortune of hyperemesis, munchy remedies, the entourage effect, THC and memory and neuroplasticity. Why edibles sometimes send you to a distant galaxy? CBD and inflammation, the risks for psychosis, older versus younger brains and cannabis, and if any studies warrant further research. With UCLA, Center for Cannabis and Cannabinoids Director, Dr. Ziva Cooper and Smith College Cannabis Anthropologist, Dr. Caroline Melly, both cannabinologists. So if you recall, last week, we left off with a question from a patron, which was shared by Sydney Van Fleet, Gordo, HR. Puff and Stuff, Chely Bean, Cool Next Door Annie, and Rachel.

Speaker 2:
[03:29] Hi, this is Rachel calling from La Pine, Oregon.

Speaker 1:
[03:32] And I wanted to know if there's any truth to the idea that there are long-term side effects from cannabis usage, especially smokers. I've read some articles that suggest that it can affect your brain in bad ways over time. And then I read some articles that say that that's total bunk. And I have read some articles that say that it's only for people whose brains aren't fully developed. So I'm curious if there has been any new research on that and if there are any new conclusions. Thank you. And I've interviewed a vascular surgeon who's like, yes, you're smoking, you're vaping, you're putting things into your veins. But I also have heard people say, no, it's really not that bad to smoke it, but maybe that was just a lack of data. So yeah, when it comes to the method of administration, what do we know about danger?

Speaker 2:
[04:20] So we have method of administration with respect to cardiovascular outcomes that you specified here, but also effects from long-term use in general. So there's questions about if you start using when you're younger, is it going to impact your IQ, or are you gonna be at greater risk for developing psychosis or mood disorders, and cannabis use disorder, for example, which is essentially addiction to cannabis, right? We know that that is one effect from long-term frequent use that occurs, and it does impact a segment of the population, and it's hard to treat because we don't have any therapeutics right now to be able to treat people. So we do know for sure that that is a causal effect in certain populations who are using for long periods of time at very frequent intervals. With respect to cardiovascular outcomes and how mode of use is going to impact those. So this is actually an area of study that I am about to embark on with an awesome collaborator, Holly Medelkoff, who's an amazing cardiologist here at UCLA. And it hasn't necessarily been, it hasn't been answered. If you smoke, if you're inhaling cannabis with some percent of THC versus if you're having it orally, does that impact cardiovascular outcomes in a way that will steer you to some type of risk down the road? Okay, so that hasn't been researched yet. And it's really important given the past year where there's been alarm bells being sounded from large studies that have looked at people who have used cannabis once in their life or once per year versus those who haven't and those people who have used cannabis show increased risk for stroke and myocardial infarction, so heart attack, right? So there have been those larger studies. There's a lot of questions related to those studies, like other variables that might have also increased risk for those factors.

Speaker 1:
[06:30] And so let's take a trip back to our excellent 2024 Surgical Angiology episode about veins and arteries with NYU vascular surgeon and general medical hero, Dr. Sheila Blomberg. You mentioned smoking too. And I have been in New York for just this past week and I'm from California, and I have walked through absolute fogs of weed. And I feel like more people smoke not just cigarettes, but just in general, people who don't smoke cigarettes or maybe smoking more weed. And vaping, do those have any impact on your venous health? You ready for this?

Speaker 3:
[07:03] Yeah, I think the data on vaping is that it's pretty much as bad as tobacco. And also the particulates in vaping may actually be worse, at least for lungs in general, but that's a different ball game altogether. The marijuana smoke and the legalization of marijuana has actually opened up a huge kind of worms, I think, for people regarding public health, because you'll have conversations where people think it's natural. Me and Mother Nature. And therefore, it's not going to harm them. But we don't have enough data on long-term use of marijuana and how that affects the RTL system. I can say our suspicions from the early reports now are that it's quite damaging to your circulatory system. And unfortunately, with the widespread use, I think we're going to start seeing that in younger people who are consuming it at these high rates. And that's a big concern to me because I think this concept of it's a plant, and if I smoke it, it's not tobacco, so it's not going to hurt me, is a problem. There's other things that are natural, that occur in a plant, most just heroin comes from a flower. It's not necessarily good for you. Now that it's legal, it can actually be studied, right? And the natural population, natural studies will start to come out. And I'm not optimistic that it's going to be good news.

Speaker 1:
[08:32] So stick to gummies maybe.

Speaker 3:
[08:34] Yeah, if you need it.

Speaker 1:
[08:36] Okay, smoking weed. Definitely not without its bodily consequences from a vascular biology standpoint. Sorry to say. And for more on this, you can see the 2019 paper, Harmful Effects of Smoking Cannabis, A Cerebrovascular and Neurological Perspective. And also news came out in 2022 that if you're an adult who has a bleeding stroke and you have enjoyed the ganja in the last month, you're twice as likely to die or have serious injury from that stroke. But it's really hard to determine what's caused by the smoking or the vaping factor, right? So I did this deep dive on edibles. And you don't want to hear this, neither do I. But I have a responsibility to tell us that a 2019 Annals of Internal Medicine paper, acute illness associated with cannabis use by route of exposure, did find that according to the Colorado Behavioral Risk Factor Surveillance System, about half of THC users just smoke, and about four percent just do edibles, and the rest are kind of a combo of both. But edible cannabis did account for more ER visits for acute psychiatric symptoms, so don't let your mom eat the whole brownie, and visits for cardiovascular symptoms. So that's concerning. Does it have to do with all the snacks you like to eat when you're cooked? Jury is still very much out, and more research needs to be done, and doctors and scientists still need more questions answered, as do you. Hence, here we are. Again, more on those psychiatric symptoms, and also some additional context on the rates of them later in the episode, I promise. But those studies that Dr. Cooper mentioned were the 2024 paper in the Journal of the American Heart Association titled, Association of Cannabis Use with Cardiovascular Outcomes Among US Adults, which found that cannabis use is associated with adverse cardiovascular outcomes with heavier use associated with higher odds of adverse outcomes. So more smoking is worse for you? Who could have predicted that? But a subsequent 2025 study that compiled a bunch of other studies titled, Cardiovascular Risk Associated with the Use of Cannabis and Cannabinoids, a systematic review and meta-analyses in the journal Heart, said that findings reveal positive associations between cannabis use and cardiovascular death, as well as non-fatal acute coronary syndrome, including heart attacks or non-fatal strokes. These findings, they say, should encourage investigating cannabis use in all patients presenting with serious cardiovascular disorders. The American Academy of Cardiology also published a 2025 article titled, Cannabis Users Face Substantially Higher Risk of Heart Attack, which blessedly is the opposite of clickbait as the headline reveals that yes, cannabis users face substantially higher risks of heart attack. Now, if you have your heart set on more info, you may have an excellent cardiology episode with Dr. Herman Taylor, and we're going to link that in the show notes. But to my gummy comrades, I'm sorry, but the news gets worse. We had the 2025 Journal of the American Medical Association's Cardiology Report titled, Association of Endothelial Dysfunction with Chronic Marijuana Smoking and THC Edible Use, which looked at 55 San Francisco marijuana partakers, and they found that the arteries' ability to open up to accommodate more blood flow was hampered in weed smokers the most as well as, to a degree, edible users as compared to non-THC using controls. So, smoking anything, definitely not loved by cardiologists and vascular surgeons and people whose job it is to keep you alive longer.

Speaker 2:
[12:09] But it's really important to study, especially because one of the fastest growing demographic groups of cannabis users are people who are 55 and older, people who are already at a higher risk for cardiovascular disease. And so, this is a really important thing to look at. Now, whether or not inhaling it is going to be different than orally administering it, like the vascular expert that you were talking to said, it's not good to inhale anything, right? Especially when you think about combustion, what we know about combustion and the toxins that can be produced from combustion. We know that those can't be good for you. There is tar that is present in combusted cannabis. With respect to the vaping, the vapes that are available now, that people are using, those cartridges, we have very little information about the acute or the long-term effects, about what the different solvents, the different chemicals that are in those cartridges, what are the effects of those on lung health, that itself, forgetting about the cannabinoids, that itself. We don't really know. And so I think that for me, that seems like a very scary area because we know that people are increasing their use of vapes at a population level. People tend to think of vapes as being safer, right? So there's this kind of harm reduction approach to them, but we really don't know what the effects are on cardiovascular health.

Speaker 1:
[13:34] I can tell you that there's a condition called EVALI. It stands for e-cigarette or vaping product use associated lung injury. And it can put up to 50% of people who have it in the ICU. And it includes diseases like acute respiratory distress syndrome and hypersensitivity, pneumonitis, and bronchiolitis obliterans, which is a terrifying name for something that's also whimsically referred to as popcorn lung. Because factory workers who inhaled artificial butter flavorings came down with the same thing. It's damaged to the tiniest crevices of the lungs. And it's not good. So if you are a smoker too who turns to vaping thinking it's healthier, without the actual visual measure of like how many centimeters of this roach are left, it can be easier to overconsume THC because a vape is much more portable and more discreet than blazing up a bowl of skunk, according to first-person anecdotal reports from me.

Speaker 2:
[14:37] Now with respect to oral cannabis, in the past, I've always said, if somebody is thinking about or we're talking about using cannabis for medical purposes, of course, you wouldn't tell somebody to like pick up a joint and smoke it. Who smokes their medicine? Using it orally seems to make most sense. But at the same time, what we saw when Canada started legalizing cannabis at the national level, and as different states have started legalizing cannabis, the research has shown that people who are showing up in the EDs for acute intoxication from cannabis, I'm freaking out. They're usually showing up because they've used an edible or an oral product, not because they're inhaling it. Now, if you think about it, anybody who's used cannabis or knows something about pharmacology and pharmacokinetics, one of the reasons why is probably because if you're inhaling cannabis and you're uncomfortable, or you're paranoid, or you're very, very anxious, by the time you get to the ED, those effects are going to have dissipated. It's very short acting when you inhale it. But when you use a oral cannabis product, and in some cases, you don't feel the effects for the first 45 minutes, so you take some more, right? You eat another gummy or another chocolate bar, another brownie because you don't feel the effects. You keep on exposing yourself to more and more THC, and oral THC lasts a long time, much longer than inhaled cannabis. And so what ends up happening is that people mistakenly, unintentionally expose themselves to more THC than probably what's on the label. So they get to the ED, they are experiencing those effects, and they last for a while. So that's all to say that there is some words of caution that should be expressed when talking about modes of administration. There are risks to both, and the aspect of the mode of inhalation is that you feel the effects, people can titrate it more easily, and even if somebody is feeling uncomfortable, it will dissipate more quickly than with oral administration. Yeah. And whether or not it's going to have the same effect on cardiovascular endpoints, hopefully if you come back in a couple of years, we'll be able to answer that question.

Speaker 1:
[16:57] Smoking versus an edible feels really like trying to get off a subway versus trying to get off an airplane. Like you're in it, dude, and you're just like, I don't know where this is going.

Speaker 2:
[17:06] Right. You're stuck. Yeah.

Speaker 1:
[17:09] Which, yeah, we did have people that are like, why when I have an edible, do I go to outer space? Yeah. Izzy wanted to know what science says about metabolism and absorption. Becca, first time question asked her, why the hell do gummies blast me into another dimension every time and immediately regret my decision to take it? This was also on the minds of Erin Dewberry, Ali V, Addie Capello, Melenka K, Julia Abbott, Bobbins, Anna Wolf and Goblin Prince. Is it a higher concentration of THC in the blood or is it just because you're able to get more from it in your intestines and your lungs?

Speaker 2:
[17:47] Interesting because THC is metabolized in very different ways, whether you're inhaling it or whether you're taking it orally. When you're taking THC orally, it's going to go through the liver, it's going to go through the natural metabolic pathway that most therapeutics that you take orally goes through.

Speaker 1:
[18:04] Down the hatch.

Speaker 2:
[18:06] What's interesting with inhalation versus oral is that if you look at people's blood after they smoke a joint or a pre-roll or eat a brownie, is that you can have two people that are very intoxicated and maybe even impaired. When you draw the blood from the person who smoked, you're going to see high levels of THC. When you draw blood from the person that used it orally, they ate a gummy or something like that, the blood levels of THC are actually surprisingly low. What's high though is the active metabolite of THC, which is actually thought to be what's called more efficacious. It acts at that cannabinoid receptor in a more powerful way than THC itself.

Speaker 1:
[18:54] This whole thing had me gagged.

Speaker 2:
[18:57] What you'll see is that if you were to draw blood from somebody who just had a brownie and looked at THC, you'd be like, oh, this person didn't have much at all. Why are they so intoxicated? But when you look at that metabolite, you'll see that the metabolite levels are actually quite high. The body processes cannabis and cannabinoids in very different ways depending on how people are taking it in, which is understandable. That's just how drugs work. So to the audience members' question about why when she has a cannabis gummy she's blasted off into outer space and she always regrets it. Well, I mean, that's probably because the amount of THC in that gummy is very high, and so it's going to have that impact. Although if somebody were to take her blood, they probably wouldn't see very high levels of THC. They would see high levels of that metabolite.

Speaker 1:
[19:41] Wow. It's so interesting to stigma wise. It's like, yeah, I just smoked a joint before going into dinner with my friends. And you're like, okay, Stoner. But if you're like, I had a gummy before it came out. It's like, oh, fun.

Speaker 2:
[19:53] So interesting. You know, the idea of stigma and being in Los Angeles and the fact that stigma is still a part of the conversation around cannabis is really interesting. Because again, I mean, you walk down the street and you see the billboards, right? Or you see the dispensaries or you see the delivery carts. And it's all in our face. But interesting that you mentioned how like the gummies is not stigmatized. And I do wonder, you know, Alie, is that because you're like part of a certain, you know, demographic group? Yeah, you know, you think about like, oh, the soccer moms, they're all like having gummies and glasses of wine versus like other populations. They're not into the gummies, right? And so I think it has to do with the communities in which we're seated, right?

Speaker 1:
[20:39] So I'll break that down for you in less formal terms. But what Dr. Cooper is saying is that white ladies get away with a lot of shit that other people don't, both culturally and from the law. So let's check in again with part one cannabinologist and Smith College weed anthropologist, Dr. Caroline Melly. Can we talk a little bit about xenophobia and racism in cannabis? I'm curious like what crackdowns were had and what those were a red herring for if that occurred, or what was the stigma is attached to, people call them jazz cigarettes. Was that tied to like underground cultures or certain types of musical cultures, or where does racism factor in?

Speaker 4:
[21:30] Yeah, there are some really great historians who are actually writing extensively on the history of it, especially around say 1900 to 1970. There are lots of stigmatized groups that were sort of caught up, I think, in the larger mythology about what cannabis was and what it would do to society's like fabric, right? So some of it was about Mexican farm workers who were arriving and purported to be using it. Some of it has to do with black and brown urban folks who were using it, right, in the 1920s, even though, of course, we know it was used much more widespread than that, right? But it became associated with particular social groups that, at the time, were seen to be degrading society in some kind of way. Even within Nixon's announcements in the 1970s, it was embedded within there as well, right? Historians have argued, at least, that it was carrying forth these ideas about a kind of underclass that was ready and poised to kind of take the world over.

Speaker 1:
[22:32] The public enemy, number one, fundamentally, it is essential for the American people to be alerted to this danger, to recognize that it is a danger that will not pass with the passing of the war in Vietnam, which has brought to our attention the fact that a number of young Americans have become addicts as they serve abroad, whether in Vietnam or Europe or other places, and as we talked about in the intro of part one, the term marijuana is now a bit contentious because it's a throwback to this villainization of Mexican migrant workers who were blamed for bringing into the country, and all the racism folded into the scare tactics of the war on drugs. Privately, side note, Nixon later admitted that he didn't think cannabis was the biggest threat even as far as street drugs go and that heroin was a greater concern. But as John Hudak wrote in his book, Marijuana, A Short History, quote, For decades, the war on drugs has been a tool to target black and brown Americans and change life trajectories in those communities for millions of people. And Hudak echoes anthropologists and political analysts who for years pointed out that smoking a plant was a red herring to cause divides and fears among classes and races. But as it's become legal in several countries and many US states, weed culture has sprouted from the underground and into shiny dispensaries that look like apple stores and amber bottles of these high-end tinctures that are promising a cure for anything that ails you.

Speaker 2:
[24:07] I think that some people, you know, we ask in our particular laboratory where we recruit people who use cannabis, we'll have people who are using cannabis many times a day, every single day, and we ask them questions related to is it impacting their daily lives, is it impairing in any kind of way? And they'll frequently say, you know, no, it's like, it's just part of my daily life. And you think about, okay, well, there's social circle that's probably with other people who are similarly using cannabis at the same rate. Just like, you know, some people go to the bar every night or some people have a glass of wine with dinner every night. Right? So I think it matters about like social norms. Where I think this matters the most is when we think about patient care and we think about how people interface with their physicians in the health care system. And I think that this is a really important area where stigma definitely has to be addressed. It is absolutely critical if somebody is thinking about using cannabis and they're a patient, they're thinking about using cannabis for any one of their disorders or some symptoms, having that conversation with their physician is so important so that the physician can be informed, so that the physician can share with them information about how to reduce risk. Or if that patient is taking other medications, how will their cannabis use impact their other medications? Having that conversation is so important and the thought that stigma might impact the ability of the patient to be candid and open and feel comfortable talking to their physician is not beneficial in this day and age when cannabis is all over the place.

Speaker 1:
[25:43] And this is solid advice. It's backed by science like the 2023 paper, The Highs and Lows of Cannabis Stigma, a vignette study of factors that influence stigma toward cannabis consumers. It's in the journal Drugs, Education, Prevention and Policy. And it concluded that the stigma toward cannabis consumption increased when cannabis was used recreationally or by smoking joints or was purchased locally in the neighborhood. And that yeah, the impact of that stigma may be a barrier to help seeking for people who use what's seen as riskier methods of administration. And this is especially important, not seeking help when it comes to your psychiatrist, folks. Sarah King asked, what are the effects on underdeveloped brains? And Mental Health and Cannabis was also on the brains of Donnie Needham, Sarah King, Paul S. Kisholm, and Erica Gormley, whose name I'm about to mispronounce because Gormley is what I call my dog. Sorry. Oh, and Becca, first time question asker, wanted to know, is it true that marijuana can put you in psychosis? Now, I myself have many friends who have bipolar disorder, and a few will not touch cannabis because of the risk of psychosis, but not all of them. I have other friends who don't disclose to their psychiatrist that they are using it to self-regulate, and I wanted to ask about that. Maggie wrote in to say, I was in the hospital a few weeks ago for paranoia and mild psychosis related to stress and increased marijuana use. Erica Gomley wanted to know, what do they think is behind the increase in marijuana-induced psychosis? And now I'm like 30 percent free rolls. Howdy, Crabbe. Marisa asked about, Marisa asked, my brother smoked a lot of weed in his late teens and early 20s and developed schizophrenia. To this day, 50 years later, he's had a lot of difficulty giving it up because it doesn't interact well with his meds. But when it comes to psychosis and other mental health disorders, I've seen that smoking under a certain age can put you at risk for others. I myself am very glad I didn't ever really try it until it was in my late 30s. But I'm also like, what does that say that I'm engaged in it here and there? But yeah, what are the risks long term to mental health?

Speaker 2:
[27:55] So with respect to psychosis, we can say that using cannabis at a younger age especially can increase the risk of developing a psychotic disorder. Now, that's in a small percent of the population. This is not causal. We think that there are underlying factors that might predispose people to being nudged in that direction. So you mentioned how you have friends who are bipolar and they stay away from cannabis. So generally speaking, people who have, let's say, family risk of psychosis, of schizophrenia, it's generally advised, especially at a younger age, to stay away from cannabis, especially during this like sensitive developmental period. There have been studies demonstrating that there's an association between cannabis use and other mental health issues such as suicidal ideation, anxiety, depression, and there seems to be a period during late adolescence where this association is stronger. It's kind of hard to tease out what's happening there because we see that a lot of youth or adolescents are using cannabis. They might have had anxiety or depression beforehand and they start using cannabis. Is it that the increased use of cannabis is causing a increased severity of depression or anxiety? Or is it that they're using cannabis to help alleviate some of the symptomology around that? We know that there are associations there. We know there are studies that have looked at cannabinoids for some of these mental illnesses. For example, for schizophrenia, there have been placebo-controlled studies, rigorous studies looking at, let's say, cannabidiol in people with schizophrenia and demonstrating that cannabidiol might actually be helpful for some symptoms of schizophrenia. How interesting is that? Very interesting. There have been other studies, again, an association study that people with schizophrenia who use cannabis have improved cognition.

Speaker 1:
[30:04] If you're like, what was the last part? Seymour in the 2024 paper, which is inquisitively titled, Does Cannabis Affect Cognitive Functioning in Patients with Schizophrenia in the Journal Schizophrenia Research. The intro notes that while cannabis impairs cognitive performance in healthy subjects, several studies have shown improved cognitive outcomes in schizophrenic patients using cannabis. They recruited around 100 participants. They found that patients with schizophrenia who did not use cannabis performed better in certain tests like psychomotor function and attention and verbal memory, while cannabis using schizophrenia patients performed better in tests on working memory and visual memory and emotional regulation. But this study is not an invitation to just spark it up. Rather, it's a jumping off point for researchers to figure out parts of the brain are affected by which molecules. Speaking of molecular structures, just a reminder because I know it gets very confusing. Part 1, we talk a lot about the definitions of THC versus CBD, CBN, CBG, THCV, etc. But the non-high causing cannabinoid CBD is also known as cannabidiol. But a cannabinoid can be any of those various compounds. Also, THC is known as Delta-9 is sometimes referred to. And of course, Delta-9, highly regulated in most of the world, THC. Now Delta-8, however, you may have heard of, that's a compound similar to THC. It produces a milder high, but it's found in way smaller quantities in the cannabis plant. But because of the US Farm Bill from 2018, Delta-8 is more loosely regulated, kind of lumped in with hemp. And Delta-8 can be synthesized from CBD, although sometimes it's done with really dodgy backyard chemistry. And there was a 2024 Journal of Cannabis and Cannabinoids research paper titled Delta-8 THC Retail Availability, Price and Minimum Purchase Age. And it noted that Delta-8 THC retail outlets were disproportionately located in areas with more socioeconomic deprivation, which is a risk to those communities because this stuff can be formulated using what they called unsafe household chemicals. So TLDR on that is do not buy gas station knockoff weed. Good. Also, if your country doesn't even allow THC sales, does your CBD even do anything or does it need to be paired with THC to even work? So pairing THC with CBD is called, alluringly, the entourage effect. According to the 2024 paper, the entourage effect in cannabis medicinal products, a comprehensive review. The concept of CBD and THC working better together is plausible. It says current research suggests a potential overlap in the therapeutic benefits between the cannabinoids and turf beans. But the hypothesis that these effects are additive or better together remains unproven. And they say further research is expected to understand which factors are enhancing cannabinoid efficacy. So for the handful of people who told me that I didn't address that CBD only works in the presence of THC, sorry babes, but that's not true. You're bullying the wrong bitch here. Now this aside is already too long, but I'm going to loop back really quick to Bipolar Disorder and Weed and a 2023 Industrial Psychology Journal paper titled Cannabis Use and Its Relationship with Bipolar Disorder, a systematic review and meta-analysis says that yeah, cannabis has been stated as a causal risk factor for schizophrenia and other psychotic disorders. And it says that there's a dearth of literature stating the association of cannabis with bipolar disorder. And I was like, great, there's a dearth of research. I'm going to dive into it. And then I remembered that dearth means not a lot. It means it's the opposite of a glut. So there's not a lot of research on it. But the study did propose that cannabis use may worsen or precipitate bipolar disorder, which means we got to look at it more. So please be honest with your doctors and be good to your brains.

Speaker 2:
[34:27] The point being is that it's a very complex relationship between mental health and cannabis use, especially now that people are using cannabis for a variety of mental health indications. In general, it's thought that waiting to use cannabis until brain maturation, and so people say, oh, this is not until you're 25, right? Waiting to use cannabis till a later age is definitely preferable because there is less risk for developing cannabis use disorder. There's less risk with respect to schizophrenia, less risk for a whole bunch of other mental health conditions. So there is some evidence and some words of caution around that. Not using the high potency cannabis products, right? And so we think that there is evidence suggesting that there's an association between psychotic like disorders or psychotic like experiences and that very high potency cannabis products. So we know that those are associations. Whether they're causal, we don't know that yet. I don't know if we'll ever know that necessarily. And keep in mind that cannabis isn't special in this respect. I mean, there are other substances that people use that carry the same type of risks. The tricky thing about cannabis, as you mentioned before, Alie, is that people are using cannabis as medicine, as therapeutics, right? And so what does that mean that makes the picture much more complicated? Yeah.

Speaker 1:
[35:48] It really does blur the line between recreational and medicinal because self-medicating not under a doctor's supervision to alleviate symptoms of something is still medicating. It's just perhaps not in the right dosage. So it's interesting what is recreation and what is trying to alleviate symptoms that either haven't been addressed or haven't been successful at being addressed otherwise. But I wanted to ask, when you're talking about psychosis, I don't know if this applies to paranoia as well. Is there a button kind of getting jammed, you know, like at a crosswalk, like ding, ding, ding, ding, ding, with the THC in a certain part of our brains that causes that paranoia, that intense anxiety or that psychosis in extreme cases? This was also bouncing around the minds of possibly anxious patrons. Cool next door, Janet R., Matt Thompson, Madeline Fox, Claire and Mariel, who asked, how do you measure or explain that threshold where a relaxed high turns into an anxious panic attack?

Speaker 2:
[36:47] Well, so it's interesting because what we see with THC is that some people will say that it helps with their anxiety. Other people say, oh, it makes them anxious. And usually, if people have a bad experience with cannabis, they're usually not going back to it, right? Until maybe they're at a later age, and they're trying it out again. But in the same human being, we know that THC can have a very different effect on this endpoint. It could reduce anxiety, and it could make that person anxious. It all depends on dose and probably also route of administration, how they're using it. And so what happens as a function of the THC concentration in the brain? It's a complicated story with respect to which neurotransmitters are being activated or being tamped down. I mean, similar to, let's say, alcohol where some people, as you say, they'll feel very stimulated when they have lower doses, but then when they drink too much, oh my gosh, you know, they can't stay awake, right? So it's a very similar type of thing where you have certain neurotransmitters that play a role in this anxiety-like response or calming-like response, but then when there's more THC on board, there's a complicated relationship between how different neurotransmitters are being released and activated in certain parts of the brain that are really important for anxiety relief or anxiety provocation.

Speaker 1:
[38:15] So different levels of cannabis can stop and start signals in the brain, and it can be dose dependent. It might be timing or every individual may be different because of brain chemistry. It's funny, a little bit of THC, and I'm like, I've never felt less anxious, and then a little bit more, and I'm making out with a grim reaper, and I'm like, I can see my own death. What's going to happen to my bones?

Speaker 2:
[38:38] It's so interesting. The window is very small.

Speaker 1:
[38:42] It's so narrow.

Speaker 2:
[38:43] So you can imagine that if you're taking a product and it hasn't been labeled correctly, or if you're taking a product and it's been labeled correctly, but let's say it's been not refrigerated or sitting out for too long, all of a sudden it's a very different type of experience. Yeah. And that's really tricky.

Speaker 1:
[38:59] It can feel like the scariest nightmare. And it's so interesting too that the doses can be so high. And to know like, why didn't that affect me so much? And then take a drag off a completely different, you know, and then again, your whole world is collapsing. A lot of people, Shelley Bean, Melenca Kay, Vanchelle Amphus, anonymous. Ellie Dix, first time question asker, wanted to know about, and Melenca Kay asked, are all those calming CBD products actually doing anything or is it a placebo? Like $72 CBD shampoo sold on goop.com. Like, does it do anything?

Speaker 2:
[39:38] I guess the question is, I mean, for me, I'm always like, if it is placebo, does it matter? Like, if people are feeling more calm, you know, does it matter? And probably the more expensive it is, if it is a placebo response, then you're going to have more of a response to it, right? Cause you're like investing into it. The only time that I think a placebo response is not beneficial is when there are the risks associated with it, right? And so you don't really see so many risks with CBD. There are issues with like liver enzymes and some gastrointestinal distress, but in general with CBD, you don't really see the adverse effects. And so what is the evidence that the CBD product that your listener is using is actually helping with anxiety or with sleep? Probably pretty minimal. The evidence that we have that CBD is actually helpful for anxiety is with mega doses, I'm talking like 300 milligrams, 600 milligrams far higher than what people are generally getting from dispensaries. That being said, a lot of CBD products also have some THC in it. And so the question is, is the calming effect actually coming from the CBD, the little bit of THC, which we know, you can have five milligrams of THC and it produces an effect versus like five milligrams of CBD doesn't really do anything. Or like you said, could it possibly be a placebo? So it could be any one of those things. But with respect to anxiety, again, like I said, we know that in certain situations, THC can help to alleviate anxiety. Although when you get too high of a dose, it can actually be quite anxiogenic.

Speaker 1:
[41:16] Meaning you'll freak out.

Speaker 2:
[41:17] With CBD, very high doses have been shown in certain situations to help alleviate anxiety in different populations, in people who are healthy, who are put in situations where they're meant to feel anxious. It's been found in people who have an opioid addiction and are presented with stimuli that remind them of the opioids that they use, and they find to have reduced anxiety around those types of cues, reduced craving. So it seems like CBD, at certain doses, high doses could actually be helpful for anxiety.

Speaker 1:
[41:50] If you are currently white-knuckle gripping a stress ball and asking, how much, why, where do I get it? I see you and I am you. So I looked at the 2020 paper, Use of Cannabidiol for the Treatment of Anxiety, which blasts right out of the gate with the statement, anxiety disorders have the highest lifetime prevalence of any mental illness worldwide leading to high societal costs and economic burden, which, okay, well, sorry, fuck me, I guess. But it continues that current pharmacotherapies for anxiety disorders are associated with adverse effects and low efficacy, which is a conclusion I like to call no shit, Sherlock. But the paper reports that for people with social anxiety disorder and PTSD, doses of 400 to 600 milligrams of cannabidiol or CBD significantly reduced subjective symptoms of anxiety and decreased the cognitive impairment and speech performance discomfort. So that's amazing. The paper continues that the majority of pre-clinical and clinical research has been conducted using males only. Thus, future research should focus on this area due to the lack of research in females in the effectiveness of CBD as a potential treatment for anxiety. So I wonder if being excluded from major medical studies of disorders that affect your gender more is causal to why we are so anxious. We'll never know because maybe no one will ever fund that study. Flames, flames on the side of my face. Speaking of inflammation, Alice Rubin, Lillian Rolfe, Bonnie M. Rutherford, Dawn Smolchek and Dr. Lena Carpenter wanted to know about conditions ranging from Crohn's to Hashimoto's to rheumatoid arthritis and getting relief from Kenos products where other pharmaceuticals just stay doing the trick. What about many people, Janet Hubbard and a ton of people wanted to know about the immune system and the autoimmune system and the effect on inflammation in general?

Speaker 2:
[43:53] This is so complicated. When we think about the immune system and inflammation, and this is not my area of expertise for one reason in that I've tried. I've tried to look at inflammation and inflammatory markers, and we actually do that in our lab to some degree, but it is extremely complicated. When we think about inflammation or immune response, is that a good thing or a bad thing? Immune response is actually really important. It's your body's natural defense. So you want to have an immune response if there's a foreign virus or if there's a bacteria. You really want that. And so I know people were really interested if CBD could be helpful for COVID. And I think that there was one study that actually found, it was like an analysis of people who were using CBD for those seizure disorders, and they found that fewer people actually got the COVID infection. This was a long time ago.

Speaker 1:
[44:49] Listen, global quarantine was an era of dark, lonely, weird, scary couch lock in and of itself. But add legal recreational weed to it, and no reason not to wear elastic wasted pants and order desserts, and you have got yourself plenty of time for some scientific speculation. One of them was touted by an anonymous source, I'm going to call my spouse, who asserted that our very stony binges of TV and pie were why we never caught COVID. But he got it in 2024. I am still a novice, haven't gotten it yet. I'm knocking on wood. But headlines were made with one 2022 study titled Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants. It did find that certain cannabinoids helped prevent the infection of human epithelial cells by the SARS-CoV-2 spike proteins, and it prevented entry of live virus into the cells. Oh my God, Jarrett was right. However, it's not the THC. The compounds in cannabis that were actually preventing entry of the live virus via those spike proteins into cells, were something called CBGA and a precursor to CBD, and both of those you can put in your body legally without getting toasted. Now, if you are smoking weed to prevent getting COVID, I'm sorry, but I must dig up a weedy study. Cannabis use is associated with lower COVID-19 susceptibility, but poorer survival, which looked at 13,000 cases, and it held our hand to tell us that regular cannabis users who smoked more than once per month had significantly poorer COVID-19-related survival after adjusting for other risk factors and comorbidities. So if you're looking toward cannabis to help with other health risks or issues, again, smoking is bad. Consider alternate methods of administration, just PSA.

Speaker 2:
[46:56] So it was thought, okay, well, maybe it protects people, but it is really complicated and I am not convinced, probably because of the complexity, that we know for sure if CBD or THC has a positive effect on the immune system, meaning like it's maximizing our immune system so that it's protecting ourselves in the maximum way while reducing the unnecessary inflammation. I haven't seen data on that. There's a lot of signals in the animal literature showing that multiple cannabinoids can have an impact on inflammation. But what situation are we talking about? There's really a lot more work that has to be done in this area.

Speaker 1:
[47:38] I did an episode on concussions the week that I fell down the stairs at my in-law's house. It was Christmas Eve. We flew in early to surprise them. I was like, surprise. Just ate shit down a flight of stairs and socks and I lived. But a neuroscientist friend was like, you should get some CBD, like high concentrations of CBD for your brain inflammation. I think my sister-in-law happened to have some. Is there actually any research? This is a long story to get to it. But I was like, if it can't hurt, fine. But do they use it for neurological inflammation for accidents or anything?

Speaker 2:
[48:14] They know. They don't. If you go to UCLA Health, they're not going to be telling you to go out and get CBD. I think that there is suggestion that cannabinoids might be actually helpful for traumatic brain injury, right after the insult, in fact. But the data in humans is far behind animals. Maybe it could have a negative effect. What's in the product that you're using? I mean, it seems like a no-brainer. Like, why not just try it? But what's in the product? What are the potential downstream effects? I couldn't mess things up. If your brain is supposed to have a certain response to an insult, do you want to interrupt that effect, right?

Speaker 1:
[48:55] Yeah. So patrons with neuro questions, Elise, Susie Q, Beth, and first-time question asker Maddox, who asked specifically about concussions, I hope out of pure curiosity and not concussiosity. But in the TBI episode I made while recovering from a TBI episode, I found a study called Review of the Neurological Benefits of Phyto-Cannabinoids, Neuroprotective, Anti-Inflammatory, and Immunomodular Benefits. I was like, okay. But then all the way at the bottom in the Conflicts of Intrasection, there was a disclosure that the leading researcher was a shareholder in a CBD gummy startup. But maybe he just really believes in it, which is totally fine too. But in a 2023 Journal of Neuroinflammation paper, Cannabinoids in Traumatic Brain Injury and Related Neuropathologies, scientists note that the only cannabinoid-based synthetic pharmaceutical that's undergone the right kind of control trials in TBI was found non-effective. And it also states that cannabinoids that target the CB2 receptor we talked about last week show the strongest evidence for neuroprotection. But plant extracts with a variety of phyto-cannabinoids may be the most helpful. Like every other cannabis study I seem to look at in the last several weeks, it just says more research is warranted. But at least there wasn't a conflict of interest on that one. At the bottom, it declares that the study was funded by a company that sells cannabis nutraceuticals, foods and other hemp-based wellness products. But none of them are Rick Simpson. Remind me to talk about a guy named Rick Simpson in a minute. But once again, a lot of the research is emerging, a lot of it has merit, a lot of non-industry funded research remains unfunded and undone. Last I checked, I'm just a lady recording a podcast decides in a rented house for her mother-in-law's birthday, and I'm not your doctor. What about Dylan V. Chloe, Marsha Lewitz, Ricky G wanted to know, Dylan said, I've heard from unreputable sources that cannabis can treat any type of cancer. Chloe said, my grandma claims it cured her breast cancer. She's been in remission for six years, obviously very dodgy and prone to misinformation in general. But yeah, anything on that?

Speaker 2:
[51:14] Right, so in general, the idea that cannabis can cure cancer, I think is dangerous, primarily because people might think that they can forego the evidence-based approaches that we have right now, that if you can think about what has been accomplished over the last 60 years in cancer therapeutics, I mean, it is astounding. And so the idea that cannabis can cure cancer, there is a danger to that. We know that certain cannabinoids might be helpful for some symptoms in cancer patients. For example, improving appetite, reducing nausea and vomiting, the FDA approved THC for those indications. But with respect to how it impacts tumor growth, again, we are in the infancy stages of this type of research. And another really important aspect to this that patients should feel very comfortable talking to their physicians about is the fact that, is it possible that the cannabinoids that people are taking, especially if they're taking it orally, because it goes through first-pass metabolism, all those kinds of things, could it actually have a indirect negative impact on the chemotherapeutics that they're using? And so that's really important. Again, those chemotherapeutics, the anti-cancer agents have been studied through rigorous FDA authorized trials. I'm not an oncologist, but I think that the adverse effects are fairly well known. The therapeutic profile is fairly well known. Pairing that up with cannabinoid products, where we know very little, and also the integrity, the labeling, the manufacturing of those cannabinoid products is dodgy. So you look in California or Los Angeles, where only 20% of the dispensaries are regulated. Those other dispensaries, what do those products look like? What types of mold or pesticides or other types of chemicals are present in those products that if you're a cancer patient, if you're any type of patient, you don't want to be exposed to. So there's a lot of things to consider here.

Speaker 1:
[53:17] Oh, yes. Rick Simpson, thank you. So this is a guy who in the 1990s was living in Nova Scotia and working as an engineer. When he fell, he bonked his head, had lasting headaches and tinnitus, and ended up making a highly concentrated rocket fuel cannabis extract oil that is almost 90% THC. It has a bunch of other terpenes and cannabinoids in it too. He felt much better taking it, and when some basal cell carcinoma popped up on his skin, he had seen a study about cannabis slowing tumor growth in mice. So we put some of that magic oil on it and a bandage, and claimed that the tumors disappeared. So he has become a legendary folk hero on the cannabis scene, like a bearded Paul Bunyan on the horizon of, this stuff cures everything, man, kind of remedy. Little dab will absolutely do you, because in every millimeter of this dark, goopy stuff, you're looking at up to 600 milligrams of THC. I can't fathom that. That's five of those cookies I told you about in Last Week's Secret, or eating 120 moderate dosage weed gummies at once. The recommended starting dosage of this RSO, Rick Simpson Oil, is half the size of a grain of rice. Does this stuff cure cancer though? Guess what? Not a lot of studies on it, folks. But there are a lot of studies on chemotherapy and radiation and immuno-oncology. So see a real doctor and not a guy named Rick first. But there was a 2015 Journal of Investigative Dermatology study exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death, which injected sweet little mice with melanoma and then injected that injection with cannabinoids or fed the mice a tincture of them, and found that THC activates non-canonical autophagy-mediated apoptosis of melanoma cells. Gobbledygook to most of us, I get that, but it means that THC kind of helped the body gobble up and destroy tumor cells, at least on small studies involving mice. But if you're facing a life or death health crisis, and you find yourself deep into message boards for Rick Simpson oil, you might be convinced to use it on everything from zits to those orange stains that lasagna leaves on top of where. So take this all with one half of a grain of rice of salt, and please don't use hemp oil instead of an oncologist. But what about an emergency medical team? Well, if you ever find yourself dialing an ambulance or wishing for the sweet breath of death to take you, let's chat about CHS, shall we? Honeydew, Elvreev, Christian Demarquez, Soapy in honor of their groovy grandfather, first time question askers Izzy, Abby Taylor, Olivia Sukup and patron Jaydeen Lannan, who wrote in Cannabis Hyper-Emesis Syndrome. My friend got this and he really suffers. What causes it? Is it more common in some people than others? What are the risk factors? Let's see. Well, you mentioned cancer patients though, and helping with appetite, which brings me to the munchies. Many people wanted to know, as a researcher, as a scientist, what is the munchies and why do some people run through their cabinet like a locust and others have cannabinoid hyper-emesis syndrome, which a lot of people asked about, which news to me, some people can have a gummy or smoke a joint and they cannot stop barfing.

Speaker 2:
[56:53] Right, right, right.

Speaker 1:
[56:55] So why these munchies are barfing?

Speaker 2:
[56:57] Right, so it's funny because I was just talking about how cannabis can help improve appetite. And we know this has been an effect that we've known about for decades and decades and decades, probably before Angelino entrepreneurs were cultivating cannabis. So one of the profound effects of cannabis is that it increases appetite. We know that this could be a therapeutic endpoint and we know that people who use for non-medical reasons probably also it helps, you know, they enjoy their food more for people who don't necessarily have an appetite but are healthy, you know, it helps them eat more.

Speaker 1:
[57:27] This is the best thing I've ever had.

Speaker 2:
[57:29] So we know it acts in certain areas of the brain that control hunger and food regulation. I mean, it's been studied time and time again. The weird thing that has happened, you know, and I think that this is probably not going to be the last that we see of this type of thing, unexpected, where we have cannabis legalization, more people are using it, cannabis products have higher amounts of THC in it, people are using it in a multitude of different ways. We're starting to see this adverse effect of cannabinoid hyperemesis syndrome, where people have very painful vomiting, gastrointestinal distress, some people call it scrommeting because it hurts so much, they're screaming while they're vomiting, they go to the ER, there's really no remedy except abstaining from cannabis. Some people report that they feel better when they take hot showers for some weird reason, and I think that some physicians usually use that as a marker to indicate that that person has cannabinoid hyperemesis syndrome rather than like cyclical vomiting syndrome or something like that. So this is something that I don't think anybody would have predicted. And we don't necessarily know the mechanism. Research is just starting to touch on who's at risk or what factors might predict that this happens, and we're still not clear on that, except for the fact that we know that it usually happens in people who are using cannabis at very high frequencies. So it's not necessarily going to happen for people who are using it once a month or once a week. Although, you know, one of the effects of high doses of THC, even in somebody who doesn't use it regularly, is nausea and vomiting. I mean, that's at pretty high doses. Generally, at lower doses, you have the munchies or you have increased hunger, increased appetite. But so how we have these very opposite things, you know, the increased hunger and then the cannabinoid hyperemesis syndrome, it's not similar to what we see with anxiety, where low doses of THC can help anxiety, higher doses can make people more anxious. But it's a pattern that we see emerge with drugs in general, is that no drug does one thing, right? You know, you're always going to have the yin and the yang. There's no therapeutic that is all good. And this is an indication, this is the case where we see this very unusual, unexpected outcome that people can develop, this cannabinoid hyperemesis syndrome. Generally speaking, people have an episode and they'll abstain from using cannabis for a while because it is very disruptive. And those people can report being very sensitive, even just to the smell of cannabis. And it could actually be upsetting because if somebody was in a community or a circle that was very much involved in cannabis, instead of going out to the bar, they're sharing pre-rolls or something like that, well, then now they can't be part of that anymore. So in that respect, there's also that type of factor that isn't usually thought about in this case. But with respect to cannabinoid hyperemesis syndrome, I think over time, we're going to figure out who is at risk, what is the mechanism, like why is this happening, and also what can we do to help treat these people, because it's not pleasant.

Speaker 1:
[60:45] Oh, I can't even, it's scrumming. Oh, that's not a word I ever needed to know. Now I just feel so bad, but they need a telethon. I had this tug of empathy and like a dark curiosity. It was so strong that I found myself reading through first-person accounts of this herbal horror. And on message boards, sufferers of Cannabis Hyperemesis Syndrome, AKA weed scrumming, found solace in each other's company and wrote things like, every morning I would wake up, take my dog outside, and puke basically just bile into the grass. I essentially didn't eat for the 30 days it took to get out of my system. I had to carry a trash bag around with me at all times to puke into. My wife got so used to it, we'd have full conversations with just little pauses for me to puke. A guy named CFO Charles said, nearly two weeks of the most intense pain I've ever had, unable to eat most of that time, barely able to keep fluids down, couldn't sleep for days on end, the pain was so intense, basically just lived in the bathroom for 10 days and did nothing but shower. Someone calling themselves your mom's pimp wrote, anyone who denies this is real is a fool. It's definitely real and it's absolutely horrible. It's what I imagine torture to be like all consuming. Okay, Evidence wrote, I thought I was dying or had rabies. Did anything bite me? No. One patron, Jennifer Douglas, asked us if we could please talk about cannabinoid hyperemesis syndrome, adding that they're a nurse and that they see it a lot. One University of Colorado-based toxicologist and emergency medicine professor, Dr. Kennan Hurd, said that when patients present with CHS, which is usually worse in the morning and can last for weeks on end, the ER will give them emergency fluids due to the extreme dehydration it causes. Doctors have seen patients go into kidney failure or need surgery for a torn esophagus. But can't you just give them an anti-nausea med? Dr. Hurd says those don't even work, but the staff has tried some older nausea meds and off-label psychiatric drugs to help. But often the patients come back a few days or even hours later. And yes, emergency departments are seeing far more cases of this, especially where recreational cannabis is legal and people don't realize how much THC is in their usual pre-roll or edible. And one Ologies patron identifying themselves as Dr. Primo Delicata, retired organ grinder, asked, any thoughts on the treatment of a hot shower or topical capsaicin? Doctor, I gotcha. I spent several hours on a train from Madrid to Sevilla, Spain, as my in-laws napped, and I dug into a pot of vomit info on my laptop. And there was one 2021 study, efficacy of topical capsaicin for cannabinoid hyperemesis syndrome in a pediatric and adult emergency department. And doctors tried applying a 0.025 capsaicin cream, like a hot pepper cream, topically to patients presenting with CHS and found that significantly more patients in the capsaicin group experienced relief compared to patients who did not get the hot pepper capsaicin cream. But future research is needed to determine capsaicin's efficacy when utilized earlier in therapy, ideally upon diagnosis. And the study also gives a heads up to others looking to try it. It says, quote, wear gloves and apply to an area specified by the ordering clinician, usually the abdomen, wash hands after applying, and avoid contact with eyes or other sensitive areas of the body. Now, how is this even working? How is hot chili pepper cream working on intractable vomiting? Well, I found a 2020 Journal of Neuroscience paper, THC and cannabinol activate capsaicin-sensitive sensory nerves via the CB1 and CB2 cannabinoid receptor independent mechanism. And it explains that THC and other cannabinoids cause a release of these sensory neuropeptides and open up blood vessels. And they don't act on the same molecular target as capsaicin, but they have an effect on some sensory nerves similar to those of capsaicin. And there's also some calcitronin-gene related peptide from capsaicin-sensitive pervascular set. Don't worry about that. Don't worry about all those words when your face is in a spattered trash bag. Also, if you smell rank, don't worry about it. The Mayo Clinic study cannabinoid hyperemesis relieved by compulsive bathing explained that type 1 cannabinoid receptors in your intestines can inhibit the motility of your intestines, which may lead to the hyperemesis or lots of barfing in marijuana users. But they say that the thermoregulatory role of endocannabinoids, stuff you already make, may be responsible for the patients need to take these hot showers that help. In this paper, the doctors wrote, in a tone, honestly, it's a little like lunch break gossip. They described one patient, a daily weed smoker who spent much of her hospitalization in the shower, noting that this was the only thing that controlled her symptoms. They say she showered as much as four hours at a time, and even left her room to use her neighbor shower when her shower stall broke. They described another patient, they said, he noted having similar symptoms several times during the past two years. And on these occasions, he would come to the emergency department only after exhausting all the hot water in his showered home. So see that paper for more of the gossip. But some folks say that temperatures between like 105, 110 Fahrenheit or around 43 degrees Celsius may provide relief. So you could also hang out in Arizona if you have one handy or better for the planet. And for your pruney hag fingers is a simple heating pad on your tummy. That may help. Now, what if your belly is fine? No barfing, but you have foolishly followed up with a second edible, and now you are high and everything gives you the Ick and you think people hate you. Dadward, you ask me. Your literal father, just tell me how to get less high right now. So some old nice hippies say that you should try chewing a few black peppercorns. If they didn't also tell me that my moon sign mattered, I would believe them. So I consulted literature instead, and it turns out boy howdy, there is something to that. A 2011 British Journal of Pharmacology paper, Taming THC Potential Cannabis Synergy and Phytocannabinoid Turpenoid Entourage Effects, takes us on a tour of too much THC through the ages, and it explains that other terpenes like ones in black pepper can complement or inhibit THC intoxication because it helps your brain lean into the anti-anxiety effects of the CBD enough to calm the paranoia of the THC for a few minutes and help ground yourself through a wave of the scaries. And it explains that the black pepper may offer mental clarity from something called pining, which is a terpene. It's also found in pistachio nuts and pine nuts, pine tar, and it can help clear your mind enough to get through it. Also, eating a mango, which has mersene, might help dial up the couchlock sedation and sleepiness if you need to sleep it off. Now, another helpful remedy if you have a case of the Oh Nose is a lemon wedge. So says generations of our ancestors who have your back. And also the 2024 Journal of Drug and Alcohol Dependence paper, which found that when subjects were given a pretty big dose of 30 milligrams of THC together with 15 milligrams of limonene, they had significantly reduced ratings of anxious and nervous and paranoid symptoms compared to people who just were given the 30 milligrams of THC alone. The paper ends with a familiar refrain, future research is needed. But yes, if you're needing to dial up the chill effects, you can drink some water, you can recline somewhere comfy, maybe order a black peppercorn lemon chicken dish, and have a pistachio baklava dessert. It'll pass, kiddo. Patron Bobbins, I hope these ones work out for you. Now, one listener wanted to let me know after listening to last week's part one that quote, I've been a hospital doctor for decades and never have I admitted a patient because of cannabis intoxication or withdrawal, only for vomiting. And those people shouldn't use it or use it too much. On the other hand, they say, I've admitted thousands of patients with alcohol-related, life-threatening medical conditions from severe detoxes, which goes straight to the ICU, or liver failure, or GI bleeding, liver cancer, severe anemia, etc. But alcohol, they write, is sold at grocery stores when cannabis puts you in jail. Political hypocrisy, they say. Doctor, thank you for those words and your service. On that note, let's donate to a relevant cause. This week, we're giving again to The Last Prisoner Project, a nonprofit organization dedicated to cannabis criminal justice reform. They say, as the United States moves away from the criminalization of cannabis, giving rise to a major new industry, there remains the fundamental injustice inflicted upon those who have suffered criminal convictions and the consequences of those convictions. And through legal intervention, education and legislative advocacy, The Last Prisoner Project works to redress past and continuing harms of our country's unjust and ineffective approach to drug policy. So thank you to sponsors of the show for making that donation possible. After the break, we will address the munchies. Okay. Patron Ricky G noted that when their bro-in-law got cancer, weed was the only thing that could help him eat and stay healthy. But Lauren Harder and Erika Gormley asked, how do people mitigate munchies? For munchies, anything that can be done for munchies?

Speaker 2:
[71:04] Oh, you mean for people who don't want the munchies?

Speaker 1:
[71:06] Yeah. For people who are like, you know what I mean? Like they're like, my door dash bill for Haagen-Dazs is too high.

Speaker 2:
[71:18] Anything that can be done. It's interesting because I usually think of, I guess probably because we do these studies in our lab, we're actually looking at how improvements in appetite and hunger and food intake is actually a good outcome for cannabis. But I guess that isn't the case for everybody. So what can be done? Gosh, that is a good question. What can't, I guess, be prepared and understand that even if you're hungry, it depends on the person if they get enjoyment out of eating the food. That's part of the experience. Yeah.

Speaker 1:
[71:52] Maybe they need to stem a different way, like knitting or something, you know? So yeah, sometimes try another activity that gives you a physical or a tactile sensation, like play with some slime or one of those neato squishy cubes that are sold out everywhere, but you can steal one from your grade school niece, or lie down and do a body scan meditation. Feel your toes, feel the air on your face, how the blanket feels on your arms. And if you're like, this isn't helping, and your version of the Buddha is less mindfulness and more just smiling, happy belly man, try to look for strains of weed that are maybe lower in that myrcine terpene and higher in one called humuline. There are strains like sour diesel or Atlantis or one called gelato, which isn't helping. But as for the munchies, another thing that works for me is I tell myself, Ward, you can either be a little stoned or you can snack. You pick one. So yeah, try that. Or physically distract yourself, like make a rag rug or sculpt something or hit a rock with a stick. On the topic of stimming, a lot of people wanted to know about ADHD and weed. Eli Dick said, can you speak on the beneficial effects of cannabis on ADHD symptom? A few people said, my husband sometimes calls it nighttime adderall. He has ADHD and he's like sometimes do a little bit and then boom, he's got an editing project he's got to get through or he can focus more.

Speaker 2:
[73:27] But specifically in the nighttime.

Speaker 1:
[73:29] Yeah, because he takes adderall during the daytime, but sometimes if he's got to get through a project, he's like, had a little nighttime adderall.

Speaker 2:
[73:36] Because it doesn't keep him up?

Speaker 1:
[73:38] Yeah, it doesn't keep him up. But a lot of people asked about ADHD and why it can help their focus sometimes. Baz Pugmeier, Anna, Kate, Ellie Dix, Boppy, Alison Clark, and Yulia Rayhelt, and a patron by the name of Poo Poo Fart Goblin, who asked, why do all my neurodiversion friends and I basically rely on weed to get by?

Speaker 2:
[73:59] So why it can help their focus is a big question in part because even though we hear these reports, that people who have ADHD, a lot of them don't want to take the stimulants for whatever reason, stimulants don't help them, they make them feel jittery, and people do turn to cannabis for ADHD. Some people say that it does help them focus. Probably it's dependent on the dose and dependent on how people are taking it.

Speaker 1:
[74:25] Yeah, exactly.

Speaker 2:
[74:26] But there have been a couple of studies that have really probed this and those particular studies, just a couple, those placebo-controlled trials haven't really panned out to demonstrate that it is very helpful. So it's hard to know what the mechanism might be. But it's not unusual to hear that it does help certain people. And specifically in people who don't react well with stimulants either. You know, they're opting for cannabis because for whatever reason, it's helpful, it doesn't have the same type of side effect profile as the stimulants do.

Speaker 1:
[74:58] Patron Jen Amina, first time question asker, mentioned that they use regularly and intentionally as part of my mental health self-care plan. It's not prescribed, but it's definitely medicine, they say. In a 2017 study, Cannabinoids in Attention Deficit Hyperactivity Disorder, a randomized controlled trial in the journal European Neuropsychopharmacology, gave some weed nasal spray to volunteers with ADHD during a six-week double-blind randomized placebo-controlled experimental trial. Pretty legit. Each participant got a one-to-one THC CBD squirt a day of about 2.5 milligrams each, so a low dose. And the researchers checked cognitive performance and activity level and behavioral symptoms of ADHD and behavioral and emotional symptoms of ADHD. And in the active group, they found improvements for hyperactivity, impulsivity, and more trends toward improvements for inattention and emotional mobility. And they concluded that yes, quote, adults with ADHD may represent a subgroup of individuals who experience a reduction of symptoms and no cognitive impairments following cannabinoid use. And it says, well, not definitive, this study provides preliminary evidence supporting the self-medication theory of cannabis use in ADHD and the need for further studies of the endocannabinoid system in ADHD. Now, patron Madison Hartman asked, THC and autism? Why do so many autistic baddies love weed? Let's ask the 2021 paper Cannabis and Cannabinoid Use in Autism Spectrum Disorder in the journal Trends Psychiatry Psychotherapy. And it told me that cannabis and cannabinoids may have promising effects in the treatment of symptoms related to autism spectrum disorder. And it can be used as a therapeutic alternative in the relief of those symptoms. And it told me that cannabis may have promising effects in the treatment of symptoms related to autism spectrum disorder, like including hyperactivity, attacks of self-mutilation and anger, sleep problems, anxiety, restlessness, psychomotor agitation, irritability and depression. And moreover, the researchers found an improvement in cognition, sensory sensitivity, attention, social interaction and language. But they said that the most common adverse effects were sleep disorders, stresslessness, nervousness and a change, probably an increase in appetite. But of course, the paper warned that more randomized blind placebo-controlled clinical trials are necessary to clarify findings on the effects of cannabis and its cannabinoids in individuals with ASD. No surprise there. There was another 2025 Nature article which used surveys from self-identified and diagnosed autistic adults. That found that cannabis provided temporary relief from symptoms associated with ASD. But there are other studies suggesting that autistic folks or people with ADHD are way more likely to have cannabis use disorder, where the frequency or the consequences of THC use impair aspects of life like work and self-care or relationships. But as we discussed in our three-part ADHD episode, and as many studies already recognize, are these neurodivergent people turning to cannabis to relieve symptoms of ADHD or ASD or does the impulsivity seen in ADHD folks keep them from resisting it? You can ask your neighborhood neurodivergent how they feel about it. But if you are trying to resist the cannabis that's calling to you from an old lunchbox under your bed, what is the best method? Patron D asked, I'm curious to know how long it actually stays in your system, which is a great question knowing how strong some oils and strains can be. Will we ever not be a little high? Who knows? Maybe Dr. Cooper. Well, I'm wondering too, I mean, with it being so prevalent, so available, so strong, so widely used, so much research still jury out on just because of time. What do you see is most effective for titrating off of it or recognizing when it is addictive or you mentioned the withdrawal symptoms earlier, but for someone who is like, I think I'm done, any good way to get your brain off on the off ramp?

Speaker 2:
[79:26] Right. This is an area that I think has been an important one to tackle and will continue to be an important one to tackle with increased legalization across the United States. We're seeing more states become legal, and that's generally been associated with greater frequency of use, is what can we do for people who do have a use disorder? Where their use is impairing socially, professionally, physically, and they want to stop using. So we don't have a therapeutic like we do for, let's say, people who have opioid use disorder, for people who are trying to quit tobacco, we don't have one of those. There are some behavioral treatments that have been employed, that have been shown to be successful. We do know that people are starting to take what's called tolerance breaks, where they don't necessarily want to stop completely, but they feel like their tolerance has just gotten out of control, and so they'll wean themselves off a little bit at a time, be abstinent for a period, and then maybe start up again. But those are people who don't necessarily find that the cannabis use is disruptive to their life, they just feel like they've become tolerant to the effects. So, generally speaking, if people want to stop using, they should very much be aware of the fact that there are withdrawal symptoms that do occur, again, in a subset of the population. These withdrawal symptoms are not easily recognizable. It's not like, you know, if you drink coffee every day, 8 a.m., you have your morning cup of coffee, you know that at 9 a.m., the next day, if you don't have your cup of coffee, you're grouchy, nobody wants to be around you, you don't feel well, you know that it's because you haven't had the coffee. With cannabis withdrawal, it's much more subtle. Generally speaking, the symptoms, which include increased anxiety, increased irritability, reduced sleep, reduced appetite, those don't necessarily start even happening until 24 hours after somebody stopped using and they generally don't peak until three days after. And so it's hard for people to recognize that they're feeling crappy and oh yeah, it might be because they haven't had cannabis. And so without knowing that and acknowledging that, it could make the path to continued abstinence or being able to cut down much more difficult. Understanding that there is that connection there and being prepared for it could be helpful in achieving either reduced use or no use at all. And so that's an important factor.

Speaker 1:
[81:51] Patrons Crouton, Zoe Bookbinder, Sam DeHollander asked about neuroplasticity. And among the research is a 2023 Frontier study, effects of inhaled cannabis high in the Delta 9 THC or CBD on the aging brain. And it said that chronic inhaled CBD resulted in enhanced global network connectivity that persisted after drug cessation, but that the behavioral consequences of this change in brain connectivity remain to be determined. So more neuroplasticity, but what does that actually mean? We're not sure yet. Now, stoners are usually known for their hacky sack skills or their creativity when it comes to microwave nachos. But Quincy Robuchau asked, can it actually make you dumber? Serena Palmer, Mitchell L., Elahoma and Goblin Prince also pondered this. Peyton Nill took us back writing, the frying egg in a pan imagery of the 70s and 80s seems like a gross oversimplification to the point of bald faced inaccuracy when it comes to cannabis. But it's apparently a core memory for my mom, and she still takes it as gospel. And Lauren Reed wanted to know, does it really fry your brain? If your memory is not so good, or you're feeling like, is weed making me not so sharp? Are those reversible? If you're like, I feel like I'm getting more stupid. Does your brain bounce back, or have you just torched certain neurons?

Speaker 2:
[83:19] So it is reversible. But I do want to say that there's an interesting phenomenon where for somebody who doesn't use cannabis regularly, if they use cannabis, you see those cognitive deficits, those memory deficits very clearly. For somebody who's using cannabis every day, you might not see those deficits, in part because they might be tolerant to those effects. And what might happen is that when they're going through withdrawal, then you might actually see some cognitive impairing effects because they're going through withdrawal. And that's been shown before that there's actually some decline in cognitive capabilities. There hasn't been a whole bunch of research in that area, but that has been shown to resolve over time.

Speaker 1:
[83:59] And for patrons Crouton, Amelia Diaz-Edinger and Penelope McCavitt, yes, cannabinoids do show promise for potential protective effects against Alzheimer's. There was a 2025 six-month Brazilian study, a randomized clinical trial of low dose cannabis extract in Alzheimer's disease, and it gave participants 0.35 milligrams, tiny low dose of THC and CBD daily. And it found that it can be an effective and safe therapeutic option for Alzheimer's-related dementia. Guess what? Though it continues, nonetheless, larger and longer trials are necessary to confirm this finding. But those benefits may come later in life, offering the protective benefits while starting on cannabis at a younger, more tender age can come with some lasting cognitive risks. So says the 2025 JAMA piece, Brain Function Outcomes of Recent and Lifetime Cannabis Use, which found that heavy lifetime cannabis use was associated with lower brain activation during a working memory task. But I don't know, maybe more research is needed. Why aren't there more studies? What's the hardest thing about what you do? Is it getting funding?

Speaker 2:
[85:11] Is it stigma? The hardest thing. I love science. I love what we do. I think it's so important because it's developing the evidence that can potentially help guide public policy on the one hand, but also just telling people. They have these questions. All of your listeners, they have these questions. I really love what we do. Now, I do call myself a scientist, but I have to say that a small percentage of my time is actually doing science. A large part of what I do is dealing with funding, trying to get funding for the work. The work is not cheap. It's really important. The work that we do, we want to keep the participants healthy. We want to keep it risk free. So there's a lot of resource that goes into screening participants to make sure they're healthy, to getting the appropriate drug that we want to give them, the appropriate cannabis that's clean, pesticide-free, et cetera, et cetera. So we need to apply for the funding, which actually I love. I mean, I love thinking about what are the most important areas that we should be tackling right now. But it's also the regulatory aspect. And so part of ensuring the safety and the ethics of these studies, and rightly so, we have to get approval from a lot of different boards. If you're going to study a cancer therapeutic, you have to get approval from the IRB, the Institutional Review Board of your university, and they check out on the ethics of the actual study. And you also have to get approval from the Food and Drug Administration. The Food and Drug Administration is very interested in making sure that the drug you're giving is safe and that you're doing it in a safe way. For cannabis, it's a whole nother level because we also have to bring in the Drug Enforcement Administration. Okay, so the DEA has to say, okay, yes, you are legally able to have in your possession an illegal substance and the place that you're getting it is also approved to give it to you, right? I can't go down to the dispensary and pick up cannabis down there, right? And then in California and in many other states, there's an additional level of approval. So in California, we have four boards that have to be able to approve our work. That can take months, that can take years. And then we also have to get the product. Oh my gosh, can you imagine how frustrating it is? You are a whole beautiful grant that really tackles a critical public health issue, and then you find out that the company that was going to make you the product or that had the product all of a sudden, it dissolved or they're not able to make it anymore, or all these other things can happen. So getting products, whether it's cannabis or whether it's oral formulations, is really hard. I mean, it's fun in a way because you get to meet people and collaborate with people, and there's no better joy of doing science other than meeting people and talking to them and brainstorming, but it is really hard.

Speaker 1:
[88:05] I can't even imagine. Because if you were studying sunflower seeds or something, like not a problem, you know? But yeah, the effects of almonds, really different. What about the thing that just lights you up? What do you love about this work?

Speaker 2:
[88:18] I mean, so much of it, and I think that that's what keeps me going is I love teaching. I love mentoring students. We have so many students that volunteer in the lab, that are really excited about the work, and it's so fun to teach them and hear about what they're interested in, what they think are the most pressing issues. I love being with other scientists and collaborating with people who have never even thought about studying cannabis or any drugs itself. There's so many ways that you can connect with people over this one topic. So I love that. And then at the end of the day, I also really love the fact that we are able to generate, even though it takes a very long time, we are able to generate evidence that is important, that can potentially help guide policy or at least consumer knowledge. So I love that. And of course, I love speaking to people like you. It's so fun. So there's a lot of really great aspects of this.

Speaker 1:
[89:17] This is a dream episode. I cannot thank you enough. Honestly, we've talked about you every single week for years. Can we get Dr. Cooper? So this is a big day for me and the Ologies team. Thank you so much for everything you do. It's just such a wild west right now, and it's good and bad. So thank you for doing the work to understand it.

Speaker 2:
[89:35] And I feel so honored that I've been top of mind. This has been really a pleasure. Thank you.

Speaker 1:
[89:42] What a way to have a Friday. So ask smart people, not smart questions, because your brain is hungry for answers. And thank you so much to UCLA's Dr. Ziva Cooper for letting me hang out in her office and peppering her with so much well-intentioned absurdity. She's a real one. Also thank you to Dr. Caroline Melly for sharing historical knowledge about cannabis. You can find out more about them and their work, as well as the nonprofit, The Last Prisoner Project at the links in the show notes. I have never in over 500 episodes of Ologies compiled as much research as we did for these episodes. So please delight yourself with honestly like 11 pages worth of links we posted at alieword.com/ologies/cannabinology. Part of the reason I did that also is because if I didn't cite studies, some of you may not have believed the research. So studies are all cited, bibliographies up. We are at Ologies on Instagram and Blue Sky. I'm at Alie Ward on both. Alie has just one L. You can join our Patreon at patreon.com/ologies, and merch is available at ologiesmerch.com. We have shorter kid-friendly episodes called Smology is available. Where are you at podcasts? That's S-M-O-L-O-G-I-E-S. Thank you so much to Erin Talbert, Adminz, The Ologies Podcast Facebook group. Aveline Malik makes our professional transcripts. Kelly Ardwyer does the website. Noelle Dilworth keeps an eye on the clock as scheduling producer. Huge research assistance from our queen, Susan Hale, who's also our managing director and keeps the hot peppers out of our eyes every week. Once again, the CBD THC duo who edit this all together are Jake Chafee and lead editor, Mercedes Maitland of Maitland Audio, Nick Thorburn, Jam Bandit, the theme music. If you stick around till the very end, you know I may tell you a secret. This week it's that, yeah, I'm in Spain for a family trip with my husband and his family. And everyone s'mores like they eat really late there. And I was like, well, okay. Honestly, it'll be 10.30 on a weeknight, restaurants packed. It makes no sense to me. It's great, but I've become nocturnal. I keep going to bed at like two and three in the morning. It's so weird. And then I sleep late. Right now as I'm recording this, it's 6.15 in the morning, local time in Spain. This episode is going up in a few hours. I am whisper recording it from a bedroom in a rented home. Everyone is asleep. I do not know what I'm doing, but I know I'm on the other side of the world, and this episode is going out. So I'll nap, and then I'll eat some cheese, probably, and then maybe I'll nap again. Who's to say? Not me. I'm along for the ride. I hope you enjoyed this. Happy 420, everyone. I'm trying to think of a better closer out. Good night. Bye bye. Oh yes, dooby-dooby-doo!