Ologies with Alie Ward

Cannabinology (MARIJUANA) Part 1 with Ziva Cooper and Caroline Melly

80 min
Apr 8, 202611 days ago
Listen to Episode
Summary

This episode explores the science, history, and current state of cannabis research with UCLA cannabinoid researcher Dr. Ziva Cooper and Smith College anthropologist Dr. Caroline Melly. The discussion covers cannabinoid chemistry, THC potency increases over decades, medical applications, legalization trends, and the gap between policy and scientific evidence.

Insights
  • Cannabis potency has increased dramatically from ~3-4% THC in the 1990s to 20-35% in modern dispensaries, creating a moving target for research and consumer safety
  • Policy legalization has consistently outpaced scientific evidence; states legalized medical cannabis before rigorous clinical trials were conducted
  • Strain names (indica/sativa/purple kush) are marketing constructs; actual cannabinoid and terpene profiles determine effects, not strain nomenclature
  • Minor cannabinoids (CBN, CBG, THCV) show therapeutic potential without intoxication, but research is still in early stages with limited human trials
  • Cannabis withdrawal is real and measurable; regular users experience anxiety, sleep disruption, and mood changes for days to weeks after cessation
Trends
Shift from flower to high-potency concentrates (dabs, wax, shatter) reaching 90% THC concentrationStandardization gap: edibles show 60% mislabeling rate; consumers need third-party lab verificationMedical cannabis driven by patient advocacy (epilepsy, cancer, AIDS, veteran communities) rather than top-down researchEmerging focus on minor cannabinoids as therapeutic alternatives with lower adverse effect profiles than THCRegulatory inconsistency: Schedule 1 federal status blocks research despite state-level legalization in 24 statesTolerance and titration behavior: users self-regulate doses based on potency, complicating dose-response researchCannabis as self-medication for neurodivergence and mental health conditions, despite limited clinical evidenceRacial justice and criminal reform movements accelerating legalization policy independent of pharmacological evidenceEdible market expansion with inconsistent labeling and unpredictable bioavailability based on fat contentCalifornia cannabis tax revenue ($7.8B in 8 years) creating economic incentive for continued legalization
Companies
UCLA
Dr. Ziva Cooper is director of the UCLA Center for Cannabis and Cannabinoids and professor at the Department of Psych...
Columbia University
Dr. Cooper conducted postdoctoral fellowship in human behavioral pharmacology studying psychoactive substance effects
Smith College
Dr. Caroline Melly is professor of anthropology studying social stigmas and legalization of cannabis
University of Michigan
Dr. Cooper earned graduate degree studying animal models of addiction and substance use disorders
DEA
Drug Enforcement Administration has seized and analyzed cannabis samples showing THC concentration increases over dec...
FDA
Food and Drug Administration approved synthetic THC (dronabinol) for appetite and nausea in cancer patients
Dadgrass
Company selling hemp cigarettes with <0.3% THC but higher minor cannabinoid concentrations
People
Dr. Ziva Cooper
Leading cannabis researcher studying potency effects, cannabinoid pharmacology, and therapeutic applications
Dr. Caroline Melly
Sociocultural anthropologist studying cannabis legalization, social stigma, and medical applications for pediatric ep...
Alie Ward
Podcast host conducting interviews and synthesizing cannabis research for general audience
Dr. Aaron Boster
Referenced as expert on cannabis efficacy for MS-related spasticity, sleep, and chronic pain
Dr. Crystal Dilworth
Referenced for previous Ologies episode on molecular neurobiology relevant to cannabinoid receptor function
Quotes
"The policies were not at all guided by science. So a decade ago, at least in the US, policy was like, yeah, man, do you go for it? But science was a little lacking in the time."
Dr. Ziva Cooper~20:00
"It's not the name of the cannabis that's going to impact how somebody's going to feel when they use it. What's going to impact somebody is the actual chemicals in that cannabis plant."
Dr. Ziva Cooper~65:00
"The cannabinoid receptor is the most prevalent receptor in the brain. There are more cannabinoid receptors than dopamine receptors or serotonin receptors."
Dr. Ziva Cooper~35:00
"People who are using cannabis for medical reasons, they're not using once a week. They're not using once a month. People who are using for medical reasons, for example, for chronic pain, they're using it every day typically."
Dr. Ziva Cooper~75:00
"Cannabis medicine really did grow in some ways out of people's desperate circumstances. Families were using it and had been using it for many decades, oftentimes very illicitly, buying it on the street and in their own kitchens."
Dr. Caroline Melly~45:00
Full Transcript
Oh hey, it's the lady at the diner weeping into her hash browns, Sally Ward. Pack in as much info right now and let's spark some discussion about weed, the psychology, the botany, the chemistry, the neurology, the legality, and the methodology. I.e. do you hold it in your lungs until you choke? Why do edibles sometimes feel like you will be high until you become dead? And are any of those tinctures at crystal shops worth it? I tracked down one of the world's best researchers on this. Oh, so excited. Studied biopsychology and anthropology. Got a PhD in psychology, went on to do a postdoc in human behavioral pharmacology at Columbia. They're now a professor and the vice chair for research in the Department of Psychiatry and Biobahavioral Sciences at UCLA. They're the director of the UCLA Center for Cannabis and Cannabinoids. I was so committed to interviewing this particular person that I waited three years until the scheduling worked out. Every week in an ology staff meeting, I would ask, have we heard back? When will my dreams come true? Finally, they did. And on a Friday afternoon a few weeks ago, I braved campus parking and a 90 degree February afternoon. And soon you will hear the result. And because we can't discuss the present without a little sprinkling of the past, I also tracked down a wonderful second expert, a sociocultural anthropologist and professor of anthropology at Smith College, and sat in a sunny conference room to ask about their experience, both personally and academically, researching the social stigmas and attitudes about this plant and how they've changed over time in regard to both recreational and medicinal marijuana. Now, I felt you bristle, some of you, even the word marijuana is contentious. Marijuana is a word that has blurry origins. It may have come from a Central American Indigenous term, although it wasn't widely grown or used in that part of the world until after Spanish colonization. Others say marijuana was coined by anti-drug propagandists who wanted to blame it as a plague to the moral fiber of the US by way of immigration from Mexico. But as it stands, it's the most common word for the psychoactive buds of the plant, cannabis sativa. Although cannabis is a term is edging that out and cannabis comes from this ancient, ancient Eastern, ironic people, meaning cannabis. Now the current legality, it gets very semantic, but hemp is different from marijuana, but both are cannabis sativa. Now hemp, it's the same species, but that has less than 0.3% THC, while marijuana refers to cultivars of cannabis with enough THC to be intoxicating when it's smoked or heated or refined. Federal law uses marijuana as a legal term to denote intoxicating plants. I'm already in the weeds with this, and we took two interviews. We folded them into a two-parter because this is such a huge, interesting, contentious topic socially and scientifically. Honestly, I'm going to cover as much as I can, and we've got a part two coming. But anyway, let's first say a quick thank you to patrons of oligies who make this show possible and submit questions to the guests ahead of time. Part two is entirely your questions, and they are sharp and smart and thoughtful, so stay tuned for that next week. Also, if you need oligies merch, and you do get yourself a shirt or a tote at oligiesmerch.com. Also, reminder, we have small oligies episodes that are shorter and kid-friendly. They're in their own feed wherever you get podcasts. Also, thank you to reviewers who, for no money, help us out so much by simply leaving a review, I read them all. And as proof, thank you this week too, sir, who wrote, when I was a little girl, there was a diagram of a beaver dam at our nature center, and I so badly wanted to live there. It just seems so safe and cozy. Listening to oligies gives me that same feeling. And sir, this honestly is one of the best compliments I've ever received. Also, Newt's in a human suit. Glad you liked the Newt Brink episode. Ready to review. Also, thank you to sponsors of the show who enable us to donate to a cause each week. Okay, my buds, prepare to understand the draw or the caution around a substance that has calmed the nerves, stimulated the mind, and boiled the blood of so many millions of people for millennia. We're going to chat about edibles versus pre-rolls, hash versus keef, CBD, CBN, CBG, THC, THCV, ADHD, psychosis, your dad's grass versus the modern stuff, inflammation over the counter cannabinoids, garden variety, chemovars, brain receptors, cancer therapeutics, addiction, withdrawal, the munchies, schedule one, incarceration, legalization, titration, addiction, medical uses, hash dabs, shatters, strains, so much more with scientists, scholars, and academics, cannabinologist, and Smith College anthropologist Dr. Caroline Melly and UCLA researcher and cannabinologist Dr. Ziva Cooper. My name is Ziva Cooper. She heard. So this is a dream come true. The fact that I'm sitting in a room with you, I have wanted to interview you for so many years. I woke up like it was Christmas morning. You're making me feel really good today. I know, it's true. Can we keep this part in so I can listen to it on a rainy day? Yes. This is so nice of you. Thank you. Make it your ringtone. And this is obviously a very hot topic for so many people in so many states and countries, but can you walk me back a little bit about your history when you started studying cannabis? I know that's a broad question, but let's just start with the basic. No, I know specifically when I started studying cannabis, I was in undergraduate and graduate school at University of Michigan. And I was really interested in psychoactive substances, specifically ones that were are illicit, ones that people enjoyed using, right? So, you know, opioids, cocaine, those kinds of psychoactive substances. And so I got my graduate degree studying animal models of addiction or substance use disorders. And I was really focused on opioids because opioids are interesting. They can be a very effective therapy for pain, but we also know that they're very addictive. And so what are some of these variables that contribute to the therapeutic side or might push it to the harm addiction side? And so I spent a lot of time thinking about that. And totally serendipitously, I was thinking about where I was going to do my postdoctoral fellowship. And I ended up at Columbia University. And at Columbia, they were doing the human counterpart of what we do in animal studies, where they were trying to understand the effects of these psychoactive substances that people use and might develop addiction to. And they were answering questions that people really want to know, but are very rarely answerable. Because essentially we want to know what are the effects of these psychoactive drugs like cocaine and opioids. The real way to know is to actually give the substance to somebody and measure the effects and compare it to a placebo. Right? But Dr. Cooper says it's very difficult, because one might imagine, to just willy-nilly give people drugs with known and potentially deadly side effects in an ethical manner. Review boards are like, that's a no, I fear. But it got her so excited about applying some animal models to the human neuroscience that could lead to ethical trials to improve public health and impact policy in a helpful way. Since many laws are ideally based on solid peer reviewed studies, how does the research really reflect what is harmful and what's helpful? What an exciting dilemma thought the future Dr. Cooper? So around that time, I joined Columbia. It was a very hard transition moving from animal to human research. And during that time, states started legalizing cannabis for medical purposes. So California legalized cannabis for medical purposes back in 1996. And other states were pretty slow to come on board. But at that point in time in 2007, a couple of states had started legalizing cannabis for medical purposes. And this was really interesting to me because it's, pharmacology in action. And I was in a lab that was studying the negative effects of cannabis. And here we're having legislation being passed to allow people to use it for medical purposes. So I became interested in understanding where was the science that was leading this public policy? The implication to non-scientists is essentially, oh, cannabis is actually therapeutic for these indications. And so I started doing research and realizing very quickly that the policies were not at all guided by science. So a decade ago, at least in the US, policy was like, yeah, man, do you go for it? But science was a little lacking in the time. And again, back in 2007, a handful, just 12 states had legalized cannabis for medical use. And as a Los Angelino, where we have this thing called Cali sober, and it means you don't drink, but like weed, mushrooms, fine. This was news to me that currently weed is illegal in most of the world. I was like, what in Canada though, in Germany, South Africa, Luxembourg, a few other countries, and in 24 of the United States, you can get it for recreational use. In Amsterdam, they have cafes where one can blaze. But it was not always so. There have been various crackdowns and taxes, a lot of campaigns for prohibition based in really racist and xenophobic ideologies. And in 1970, cannabis was deemed a Schedule One drug, which is the highest level of restriction in this country. And it was seen as having no medicinal benefits and a high likelihood of addiction. So it is in the same class currently, Schedule One, as heroin, molly and coiloads. But in 1996, California enacted the Compassionate Use Act, and it allowed seriously ill patients to possess, grow and just use medical marijuana, if given the blessing of their doctor. And I know legally, according to the federal government here, it's still called marijuana, even though it seems like such a formal name and also antiquated and also rooted in racism. Pot seems like your grandma trying to have a serious talk with you. Weed also feels a little bit like, hello, fellow kids. These days, I guess people call cannabis trees, or they say that they garden. I mean, also a lot of humans just communicate by emojis in code to circumvent social media censorship. So the leaf emoji it is. But let's take a quick trip back to Massachusetts to chat with an anthropologist who literally studies the legalities and the social stigmas of cannabis for both medicinal and recreational use. And her name is Dr. Caroline Melly. And after her son was diagnosed as an infant with a rare neurological disease and severe epilepsy and other treatments failed, her family turned to cannabinoids for therapy. And I met up with her on the Smith College campus where she's a professor in Northampton, Massachusetts. I'm Caroline Melly, and I use she, her pronouns. Do your friends call you Dr. Weed or no? No, my friends, most of my friends are like astonished that this has become my field of research. When they hear this podcast, perhaps they will start doing that. But no, it's okay. And so how, okay, your friends and their astonishment. I want to talk about your backstory because it's so fascinating. Can you tell me a little bit about the backstory? Yeah, I would say if you had told me 12 years ago that this is where my scholarly future was headed, I don't think I would have imagined that that could be the case. I actually was trained as an urban anthropologist. I worked in West Africa, had every intention on continuing to pursue that research with a new project based in technology. When my infant son, who was five months old at the time, was diagnosed with a catastrophic form of epilepsy. So that form of epilepsy is notoriously quite difficult to treat. She said that she and her husband found themselves in this surprising company of many other parents who are chasing down studies and doctors who might implement cannabinoids as a type of therapy. And she was surprised that there was still such stigma. And again, this was over a decade ago before it was easy to buy wacky-to-backy, the devil's lettuce, and assorted other things by just strolling into a dispensary. What happened around 10 or so years ago where something snapped and the U.S. said, all right, let's go ahead and do this? This is a question that I'm constantly trying to puzzle out. And I think that there were a lot of entangled forces that made that even possible. Some of it is a kind of movement towards anti-racism that we see bubbling over the years in the United States and a reconsideration along the terms of prison reform, for instance. I do think a lot of the force in the country that has come around legalization in general has really come first through medical cannabis. And there are many different, perhaps unusual solidarities that have formed in order to make that happen. So some of it is veterans of wars, for instance, who are living with debilitating conditions that involve lots of bodily systems. And where they were put on high doses of medications that caused even more trouble. There is a pretty significant force of veteran folks who were part of the drive towards legalization in various states. Certainly in California, for instance, it was AIDS patients who were a large part of the catalyst there. And certainly across the country, I think epilepsy patients have been a huge part of this, and parents of children with epilepsy and cancer as well. But in order to advance the therapeutic options of cannabis, you need randomized controlled trials done by people like Dr. Cooper. It became apparent to me that there is a whole bunch of research that has to be done that can really only be done giving the drug to people to understand the potential therapeutic effects, potential medicinal effects and potential adverse effects, what might optimize the therapeutic effects, what might reduce the adverse effects. And the research became more and more relevant as more states started legalizing cannabis for medical purposes. Each state was legalizing cannabis for different reasons. California legalized it for 11 reasons. And the last reason was if your physician thought you might be able to benefit from it. Oh, that was the last one. Okay, so that was California's 2016 Proposition 64. And it passed with over 58% of the vote. Other reasons why it passed were decriminalization and saving money on law enforcement, making money for kids programs, making money, making money, making money. And you might be shocked to learn that a decade later now, in a state that feeds the world, cannabis is thought to be California's biggest cash crop. And according to a February 2026 release via ca.gov, in the last eight years, California's sticky icky sales have generated more than $7.8 billion in tax revenue. But the money train, it was moving faster than the scholastic bus. Way more research needed to happen. And so I became really drawn to cannabis, the plant, as well as cannabinoids, the chemicals in the cannabis plant, to understand, you know, what are the effects of these chemicals? And then, you know, as legalization continued, industry started ramping up as well. And we started to see that cannabis itself was becoming a very different type of plant than it was like in the 90s or, you know, 80s, 60s. And also products were being made that were quite different, right? People weren't just like making their own pot brownies at home. There were actually these like artisanal gourmet food products that were being prepared with cannabis infused and other products like now we have the vape pens, right? And so very little work had been done in this area. So the genie was out of the bottle. The smoke had curled out of the bank. The business commerce aspect was picking up and it still is picking up. People are using at much higher rates than they were before, but our science is still, you know, it's kind of in its infancy still. I think it's interesting because I feel like if you're studying opioids, people are like, that's amazing. You must be wanting to end the opioid epidemic. If you're studying weed, people are probably like, okay, like, do you find that the opinions on cannabis are really polarized like pro or con? Do you find that in your research or who you present to or your study subjects at all? It is a really polarizing topic. And I can say that some of the work that I've generated with the help of colleagues has spurred advocacy from both groups as well as have been demonized by both groups, right? And actually, if you think about it, that science should be that way, right? So we're trying to figure out really, what is the evidence? What are the effects so that we can better inform people, which is really important in this day and age? Yeah. Well, I'm wondering, because you mentioned opioids too and other addictive substances. And from what I understand, I'm not you, but from what I understand, there are receptors in our brain that say yum, yum, yum opioids. And there are also endo cannabinoids that we create. So the way that certain chemicals land in our system is there just like an open basket in our brain been like, this is so much like the thing that I make. I want this. Is that what happens? How does it work in the brain? So such an interesting perspective. Did I fuck that up? Let's find out. So it is true that the drugs that people use, generally, they are acting on certain receptors or certain targets in the brain. And generally speaking, the drugs that have greater addictive potential are either indirectly or directly impacting certain neurotransmitters, for example, like dopamine, which I'm sure you and your listeners have heard about. Some drugs of abuse or some drugs of misuse, I should say, act at very specific receptors. So for example, opioids, such as morphine and heroin, they act specifically at opioid receptors. And those opioid receptors didn't evolve to receive the compounds from the poppy plant. They evolved alongside our endogenous opioid system. So our body naturally produces substances that are similar to those opioids that the poppy plant produces. So yes, our endogenous opioids and endo cannabinoids came first. They are tasty little compounds that our body makes, our brains use them to stay alive. And it's not like we just evolved these empty baskets waiting for the arrival of fun, sparkly drugs. And according to the National Institute of Health's article, Drugs, Brains, and Behavior, some drugs such as marijuana and heroin can activate neurons because of their chemical structure. And it mimics that of natural neurotransmitters in the body. And this allows, it says, the drugs to attach onto and activate the neurons. And it says that although these drugs mimic the brain's own chemicals, they don't activate neurons in the same way as a natural neurotransmitter. And they can lead to some funky, abnormal messages being sent through the network. And it continues that it was once thought that surges of the neurotransmitter dopamine produced by the drugs directly caused the euphoria. But scientists now think that dopamine has more to do with getting us to repeat pleasurable activities than with producing the pleasure directly. So you're like, that felt good. Let's do that again. Similarly, cannabinoids, specifically, Delta 9-tetrahydrocanabinol THC, that primary intoxicating component of the cannabis plant, also binds to receptors that we have in our brain and our body. They're called cannabinoid receptors. And just like with the opioids, the cannabinoid receptors didn't evolve with the cannabis plant so that we would have receptors that would be available for THC. They evolved alongside our endocannabinoid system, which is not only comprised of the receptors, but also our body's own cannabinoid ligands. You're not alone. Earthworms, leeches, all kinds of critters have the same endocannabinoid systems, just maybe a little less extensive. And also, they don't have access to dispensaries because weed stores usually don't take cash. But yeah, according to the 2013 Veritable Textbook Smoke Signals, a social history of marijuana, medical, recreational, and scientific, we started to discover our own endocannabinoid system after first discovering the close to it chemical nature of cannabinoids. So we noticed it in the plant first and then backtracked and was like, oh, we make these two. And one of the first endocannabinoids to be identified is called anondamide. And the name comes from the Sanskrit, meaning bliss. It's called the bliss molecule, hell yeah man. But for more on molecular neurobiology, we have an episode titled just that with Dr. Brain from CBS, aka Dr. Crystal Dilworth. But onward. So they're lipids that bind to those receptors. And those receptors and those endocannabinoids are critical in homeostasis and how we manage the stimuli that we interact with in our everyday life. In fact, the cannabinoid receptor is the most prevalent receptor in the brain. There are more cannabinoid receptors than dopamine receptors or serotonin receptors. Yeah. And they're located in all these different regions of the brain and they really play an instrumental role in a whole host of behaviors, you know, executive function, hunger, as you can imagine. Yes, I can't. I love snacks. And so they're really important in our overall homeostasis. And so yeah, the cannabis plant has chemicals that act at those receptors. Oh boy. This episode, it's a beast, but real quick, some botanical and cultural history, shall we? So according to the University of Sydney's article, The History of Cannabis, the plant cannabis sativa has been used by humans since at least 2800 BCE. And Indian Hindus, Greeks, Romans, more cultures have relied on it as a remedy for, quote, a vast array of different health problems, including arthritis, depression, menstrual issues, inflammation, pain, lack of appetite, and asthma. And the word ganja, by the way, I thought that was just a catch all, but it refers to the female flowers of the plant or most of the cannabinoids hang out. What about all those floppy leaves? You ask, well, you can't eat them and become stony. It's not like catnip. THC needs heating and that's called decarboxylation to convert it from something called THCA, which doesn't do much for you, to just THC, which does a lot for you. So let's chat with Caroline again to get more history of humans and hashish. It passed even through the Silk Road, both the plant itself and the expertise around it passed from your Asia into the Middle East, India and Africa as well. So it has a really storied history as a treatment. And then there have been many surges of trying to kind of suffocate it to, right, and to ban it across time and space as well. It's really a medicine that in, especially during its prohibition for so long, was really shaped in kind of interstitial spaces outside legality, never through randomized controlled trials, right? I think that what comes about is a kind of folk knowledge. We might call them folk healers, right, who have shaped cannabis medicine over time. And so let's get back to how these things are just doing their thing. What do those receptors normally do? Or where do we make those cannabinoids in our body? Those come from like exercise or eating or let's say that you don't live in a place where it's legal or you just don't like getting high. How do we make those usually? So generally speaking, we think that these endocannabinoids are usually made on demand. So for example, they are made in the cells in your brain and your body, they're synthesized in a way to be able to regulate the body's response to external or internal stimuli. Okay, so for example, if you're in a particularly anxious situation or anxiety provoking situation, then your body might produce or synthesize those endocannabinoids. But it's really happening all the time, given how critical those endocannabinoids are to our everyday functioning. And according to a 2021 Harvard Health article titled, The Endocannabinoid System, Essential and Mysterious, the cannabinoid receptors in our brain, one of them is a CB1 receptor, they act like it says traffic cops to control the levels and activity of most of the other neurotransmitters. And that is how they're regulating things. They're giving immediate feedback, they're turning up, they're turning down the activity of whichever system needs to be adjusted. It says whether that's hunger or temperature or alertness. And our body's own endocannabinoid stimulate those receptors. And there are ways that we can increase our own endocannabinoids, which you'd never guess this, but exercise, sleeping better, who knew. But there's another receptor called CB2, and it helps modulate our immune system and things like inflammation. But there are so many endocannabinoids we make and so many cannabis derived cannabinoids. It's so hard to keep track. It's like a Willy Wonka tunnel of just letters. And then what about CBN, CBDs? I feel like there's so many. We've heard of THC, which is psychoactive, but what are those other guys doing? All right. So the cannabis plant is really amazing because it has over 500 different chemicals. Now, about 120 of those chemicals are what we call phytocannabinoids, but those are chemicals that are really unique to the cannabis plant. And so those are the chemicals that you're referring to now. So we have THC, Delta 9 tetrahydrocanabinol, and that is the chemical that is responsible for the intoxicating effect that people feel when they use cannabis. It's responsible for the memory impairing effects. It's responsible for how much people like the cannabis. It's also responsible probably for how much people dislike cannabis. It has a whole bunch of effects that are attributed to it, most of which I just talked about are the negative effects of cannabis, including the fact that if people use cannabis at very high frequency and then stop abruptly, a portion of the population might experience withdrawal symptoms. And so we know that's because of the THC in the plant and the body withdrawing from that THC. You can have cannabis withdrawal. You can. So regular use of THC means that your CB1 receptors get a little desensitized. And for a few days up to like three weeks, depending on your usage, you might experience anxiety, a bummer mood, problems sleeping, some weird freaky dreams, got tummy ache, nausea headaches, generally just feeling like a bitch. And if your roommate does not believe that you can have cannabis withdrawal, you can break the news via the 2017 paper, The Cannabis Withdrawal Syndrome, Current Insights. And if you've been indulging in a little too much weed and you're thinking maybe this is a coping mechanism for the horrors of the world, you can de-influence yourself with the 2025 Journal of the American Medical Association study, Brain Function Outcomes of Recent and Lifetime Cannabis Use, which concluded that in this study of young adults, lifetime history of heavy cannabis use was associated with lower brain activation during a working memory task. Or to scare you real straight, you can enjoy the 2025 paper, Convergence of Cannabis and Psychosis on the Dopamine System, which revealed that elevated dopamine function in some critical brain regions may be associated with psychosis risk in people with heavy cannabis use. But researchers noted in the methodology that those effects were following THC administration. And more garden variety drawbacks, again, as Dr. Cooper mentioned, might be anxiety, increased risk of mental health episodes, particularly for people who have bipolar disorder, or some people have a rare condition that causes them to violently barf. It's called cannabinoid hyper-emesis syndrome. And it can cause nausea, cramping, and vomiting, a lot of it after using cannabis. Or you might have it and feel happier and gigglier than ever in your life. It may be the best feeling you've ever had, smoking a J on the porch in the sunset, laughing with your friends. It's really obviously a mixed dime bag here. Maybe you're an occasional partaker. Or maybe you're more of a CBD babe than a several times every day, all day, high potency, THC baddie. Alongside these kind of negative effects, we also know that THC is therapeutic for some indications. We know that because a lot of studies were done back in the 80s and are still being done that actually led to the approval by the Food and Drug Administration, the FDA, of THC for a couple of different indications, such as improved appetite. So any of your listeners here who know that when they use cannabis or with THC in it, they get the quote-unquote munchies, that might resonate with them. So improved appetite also reduced nausea and vomiting in certain indications. For example, with cancer patients, synthetically derived. So made in the laboratory, it was actually approved by the FDA. And this is all pharmacologically produced and made into pills with standardized formulations and dosages. It's not like when you go down to the dispensary that like, you know, you can see outside the window from my lab here. It wasn't that, you know, that the FDA was approving. So we know that THC is therapeutic for certain indications. And there's been a lot of other studies looking at if THC can be helpful for sleep, if it can be helpful for certain types of pain, can it actually be helpful for certain substance use disorders for addiction? And so a lot of studies are coming out now that are looking at that. Finding this research is not always easy. One thing that drove me absolutely bad shit about this episode is the first several pages of a Google search about anything we'd related are garbage. It's like cannabis-like health products, a bunch of weird fringe, holistic homeopathy blogs written by AI, just a lot of weird web pages with pop-up ads. And you're like, where is the research? So you can go to your news app and you can type in cannabis research, or you can just head straight to heaven for information, ResearchGate or Google Scholar, and you can type in cannabinoids and THC or whatever, and you can sort for the most recent and then just dive the fuck in nerds. So that's THC. And then we have another cannabinoid THC is considered to be a quote unquote primary cannabinoid. And another one is cannabidiol CBD, which I'm sure you saw as you were like at the grocery store, you know, picking up your beverage or a chummas or, you know, your Erwan. Am I allowed to say that on this part? Yeah, yeah, definitely. Yeah, you're smoothie of choice with your shot of CBD, right? So CBD is everywhere, it's hard to escape it. CBD is very different from THC, even though the molecular structure is actually quite similar, it has a very different effect. And even though it's called a cannabinoid because it's found in the cannabis plant and it's unique to the cannabis plant, it actually doesn't really have an impact on those cannabinoid receptors that I was telling you about that THC has a strong effect on. Oh, okay. So CBD, it's also confusingly called cannabidiol, which is one of hundreds of cannabinoids hitting your endo cannabinoid receptors. But in the 2023 paper published in molecules titled Molecular and Cellular Mechanisms of Action for Cannabidiol, CBD isn't a big magnet to those CB1 and CB2 receptors, though it can have some influence. But rather, CBD can target a lot of different pathways and have farther reaching, like anti-inflammatory effects. And as this paper encouraged, research on CBD and its effects continues to expand and its therapeutic potential and utility in various medical contexts are becoming increasingly evident, thank you very much. And there was just a frontiers and psychiatry paper titled Cannabidiol and Brain Function, Current Knowledge and Future Perspectives, and it confirmed that, yes, CBD has reported anti-convulsant, anti-psychotic, anxiolytic, so anti-anxiety, anti-inflammatory and anti-craving properties, and that CBD's influence on brain function has also peaked the interest of researchers and people seeking to enhance cognitive performance. How does this work? We don't know. It continues, the molecular pathways and mechanisms through which CBD acts have not been fully established yet, but the hype is well established. And there was this Harvard Health article, it just cut to the chase with the headline, CBD products are everywhere. But did they work? Anyone's guess. It says that when it comes to CBD products, the marketing of an enthusiasm for them has gone way ahead of the science. And it continues, there's no evidence, for example, that CBD cures cancer, as some proponents claim. There is moderate evidence that CBD can improve sleep disorders, fibromyalgia pain, muscle spasticity related to multiple sclerosis and anxiety. And there's increasing data that CBD may help people overcome various addictions. But, yeah, CBD, it's not hanging out in the same watering hole that THC is, so it's not making you high and enraptured with a screensaver or having the best sandwich of your life. But it can potentially help out behind the scenes. Which is really interesting. CBD, though, however, has many different targets, tens of different targets. And it's thought that CBD, based off of a lot of animal studies, that CBD might actually be therapeutic for a wide range of indications without those side effects or adverse effects that come along with THC. So you can take CBD until the cows come home, thousands of milligrams, and you will not feel intoxicated. You can take a boatload of CBD and you will not experience memory impairment. That is, if the CBD has no THC in it. So CBD is very different than THC because people don't immediately feel the effect. And as far as we know, there's no withdrawal from the effects of CBD. So it's fairly benign in that respect. We can talk about some other studies showing that there are other areas where CBD might produce adverse effects, but relative to THC, it's fairly tame. We do know that CBD is a therapeutic for certain indications. In 2018, it was approved by the Food and Drug Administration for certain seizure disorders. And again, back to Caroline Melly, who steered her research into the anthropology of cannabis and has been uncovering the racial biases and xenophobia behind certain criminalization and prohibition movements and the policies and the blocks that researchers still face with this Schedule 1 drug. And this is also obviously spurred by and having impacts close to home for her. And she shared more of her son's story. We were eventually able to gain control using sort of typical pharmaceuticals, but the pharmaceuticals themselves have really catastrophic side effects. I think this is one of the really important things to understand about contemporary cannabis medicine, that it really did grow in some ways out of people's desperate circumstances. So in no way was this a movement where I think families were just sitting around thinking, we'd really like something plant-based or holistic. I think it's easy to assume in this era, in which there are such controversies around what we put into our mouths and our bodies, that it really must be natural parents who are looking for a more natural remedy. I think perhaps there's to some degree that is there too. But I think for many of us, especially in an era in which it was still pretty difficult to introduce to your child, with neurologists being on board about it, I think that... Sorry. No worries. It's a lot harder than I thought it was going to be. No, and I know this is such a personally charged story, which is really hard to talk about. And it's a very obviously emotional story that motivates you. And that decision is apparent and trying to parse out what will be effective on the person that you care about the most. So for us, at least, I was part of many different Facebook groups at the time of other parents who had children with the same kind of epilepsy and who were similarly moving from treatment to treatment and trying to figure things out. This is where I first was hearing whispers of cannabis being used. And when I began to dig deeper, I began to realize that in fact, there were quite a few families that were using that. There were a lot of people that were using it and had been using it for many decades, oftentimes very illicitly, oftentimes buying it on the street and in their own kitchens, boiling different concoctions that they would try to extract for their children. So there was actually quite a long history of doing this long before 2016. So she says that the loosening of stigmas is finally freeing up researchers to better understand the applications and the potential therapeutics of cannabinoids. But because CBD is thought to be a lot less risky than THC, it has been and it continues to be extensively studied for a range of indications, such as anxiety and sleep and pain as well, a multitude of indications. So that's THC and CBD. And then we have all these other cannabinoids that are referred to as minor cannabinoids. And they're called minor cannabinoids because they appear in very small concentrations in a standard plant. Cannabis can be grown and cultivated to have higher concentrations of certain cannabinoids, right, depending on the genetics of that cannabis plant. But generally speaking, the other cannabinoids, you mentioned CBN, which we can talk about in a second, CBN, CBG, which we're studying in our labs, CBC, which we're also going to be studying in our lab. A lot of these cannabinoids have been overlooked because the plant naturally produces very low levels of it. But if you look in some of the animal literature, there's some compelling, intriguing data that suggests that these minor cannabinoids might actually be therapeutic for certain outcomes without, again, without that intoxicating component of THC. Okay, those letters, we're going to plow through them so fast. So CBD, cannabidiol, we just talked about it. CBG, it forms in the stems and the stalks of the plant and kind of like a stem cell, in that all cannabinoids start off as CBG. People claim CBG is helpful for pain and anti-inflammatory and is a nice focus enhancer for creative tasks. CBN, it's supposed to feel like THC, but much milder. People say it gives some pain relief and kind of a cozy body high. CBN, people also like it as a sleep aid. Now, for more on this, there's a company called Dadgrass and they did not sponsor this. They gave me no money, but they sell technically hemp cigarettes and they're less than 0.3% THC, that's the legality, but they're higher in all those other cannabinoids. We just mentioned, they have a lot of info on their website and they're usually sold just legally at boutiques and stuff. So if you really want to inhale combustibles, but only get the non-THC effects, that's one way to do it or you can research some tinctures or gummies with non-THC cannabinoids. Another term to toss into your now crowded brain is THCV and I was like, this is too many terms. And then curiosity got the better of me and now you. So I checked out the 2025 paper in the journal Cannabis and Cannabinoid Research titled with, I swear I read into it like a sigh of exasperation, tetrohydro cannabavarin is not tetrohydro cannabinole. So THCV is not THC, it says people. I could tell, I wanted to scream. So out of the gate, this paper is like hell bent on destroying flimflam saying that because THCV has shown evidence to lower blood sugar and suppress hunger, it's earned this nickname of diet weed. It says, despite few human studies and it kind of continues in a huff. Additionally, THCV is usually an incorrectly categorized as an intoxicating analog of THC, which causes confusion among both consumers and regulators. And the paper continues that while they're often confused, THCV has a very faint THC like effects and usually only in high doses like 200 milligrams. And there's only been two human studies that have shown that 10 milligrams might be enough to suppress appetite and regulate blood sugar. And it calls out when taken in two five milligram doses, it's no better than a placebo and that most products contain five milligrams or less. So THCV to get remotely stoned, you'd need so much of it, but to possibly help metabolically, you'd need at least 10 milligrams at a time. But the study concludes additional literature on the effects of THCV in humans is scarce. Although there was a 2025 article in the Cannabis Journal titled Weight Loss and Therapeutic Metabolical Effects of Tetrohydrocanabinverine Infused Mucoh Adhesive Strips and it found that a 20 milligram daily dose of THCV was superior for weight loss compared to the 10 milligram and that both sets of results did differ from placebo in a way that was statistically significant. So that's what's going on with THCV. Will not get you high might make you feel a little more focused and is said to be an appetite suppressant and a blood sugar regulator. Again, jury's out. Also, let's get one more definition down and that's a terpene or a terp if you're nasty. A terpene is a compound that lends flavor and smell to the weed. Kind of like tasting notes. And if you're like, why so skunky? You can think some sulfur compounds for making your neighbors think that there's just a stinky critter on the loose and not grandpa token on the porch. But if you are headed to the dispensary to pick up a pre rolled joint of psychotropic THC or some very mildly high inducing THCV gummies, some CBD oil or some tinctures of CBN or CBG, your bud tender may or may not be up on these studies of what does what and what concentrations. Or then again, they might be on Google Scholar pouring through all of it or they might be listening to this. So how cool is that that the plant might be producing these chemicals that could potentially be therapeutic and have lower potential for adverse effects than let's say THC. And so when you go into health food stores or dispensaries, sometimes you can find that there are certain products specialty products that have these minor cannabinoids. For example, CBN, you might be able to find products where there's high concentrations of CBN and the product says that this could be helpful for sleep. Right now, whether or not it is helpful for sleep, I think that the jury is still out on that for sure. But there are thoughts about some of these minor cannabinoids and how they can be utilized to improve health. And also, you know, the whole well-being space and supplement space, which is becoming expensive, right? But also, you know, the supplement space is looking towards cannabis and cannabinoids as potential compounds that could be helpful for, you know, well-being in general. And again, whether or not, you know, those minor cannabinoids are helpful, the jury's out. I asked Dr. Melly, who studies a lot of cannabinoid therapeutics for medical purposes, especially in children, and she told me, at least if you're buying from a reputable company that provides those third-party labs, you usually get a report that tells you exactly in terms of the cannabinoids and other components, exactly what's in there. I mean, if you're just going to buy it from a gas station or from Whole Foods or something like that, you will not be getting that kind of knowledge, right? So I think many families that are using it, at least the ones that I've worked with over time, are using companies that they've known to be reputable by word of mouth and that provide all of those third-party labs. They're not going to target and getting CBD cream or oil, right? Like, that's not the good shit, right? No, definitely not. I mean, it would have marginal benefit, if any, I think, yeah. I talked to someone recently who told me that there are stem cell creams you can get for your face, and they don't mention that it's Apple stem cells. Can you believe that? So I can only guess. The marketing scheme. It's extraordinary, for sure. But there are plenty that work great. There are way too many studies to dive into, but we'll link some on our website at alleyward.com. For example, papers like minor cannabinoids as an emerging frontier for pain relief or anti-inflammatory and analgesic potential of minor cannabinoids in Vivo. Therapeutic potential of minor cannabinoids in psychiatric disorders, a systematic review. They're all there for you to see what doses were administered and the particulars look in the methodology section of the papers. Just a little hot tip from Dad Ward. So those are the cannabinoids. There are also hundreds of other chemicals, terpenes, flavonoids, and it's thought that some of these other chemicals might also have biological activity that could help to either improve the therapeutic index of cannabis itself or be therapeutic on their own. And we're going to continue to explore those in just a moment, as well as learn how scientists even study being high. But first, let's take a quick break. We're going to take a sip of water or whatever as we donate to a related cause. And this week, it's going to the last prisoner project, which is a nonprofit organization dedicated to cannabis criminal justice reform. And as the United States moves away from the criminalization of cannabis, they say, 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. Through legal intervention, public education, and legislative advocacy, they work to redress the past and continuing harms of our country's unjust and ineffective approach to drug policy. So that is the last prisoner project. And thank you to the sponsors of the show for enabling us to support that justice work. Get the Google Pixel 10 Pro XL on the UK's best network. Press to talk out live with Gemini, your AI assistant from Google, and find out how to revive that plant. Yep, we've all been there. Plus, you'll stay connected even when you run out of data. Get yours on EE Today. Results for illustrative purposes and may vary. Check responses for accuracy, eligibility, credit check and terms of apply, credit by EE Limited. Verify best network at EE.cadk.claims. The weather's warmer, the days are longer, and the savings are even better in the Hillary's Spring Sale. Right now, there's up to 40% off hundreds of made-to-measure styles. Plus, get an extra 10% off everything in our flash event, including our total black outlines for complete darkness and a good night's sleep. And don't forget, with Hillary's, measuring and fitting is always included. So get window-wise and book your free in-home appointment today at hillarys.co.uk. But hurry, an extra 10% off everything ends the 13th of April. Conditions apply. Okay, let's get back into the methodology of cannabinology. The house of highs in a lab. What about the studies? Do you like hot box a mouse or do you have to get an undergrad who's like, I will absolutely go in an MRI, which is baked? Like, how do you study this? So people in our field, and I don't think cannabis is unique, generally people either are doing studies with animals or with humans. And you gave the hot boxing example on the animals, which is appropriate since there are researchers who actually do that. They fill the cages with vapor or aerosol, cannabis smoke, and they look to see what happens to the animal. Does the animal display signs of intoxication? Or like with respect to the potential therapeutic effects, if you expose animals to that type of inhalation of THC, will they show pain relief or reduced anxiety, all those types of things? In our specific lab, we are interested in some very basic questions. Okay, so for example, basic questions like people are using cannabis now that has higher THC content than we've ever seen before. Yeah, I can only imagine. So I didn't smoke weed or I was like a straight edge goth, but I lived with a bunch of drug dealers who were constantly stoned. We had like a six foot bong in the garage and like every single cross punk in the neighborhood would sleep on our couches. It was disgusting. I can't believe I didn't get skabies. A six foot bong. We need a ladder for that. It was ridiculous. I was always like, you guys, can you clean up your nitrous containers? But I love them and I talk to them still and now most are sober and have adorable children. But I didn't smoke. I didn't do any. And so until it was legal here and then I'm like, well, okay, I'll have some gummies or whatever. By the way, PS, isn't that interesting how the public policy impacted your decision and your perception? For sure. I wasn't about to meet a guy in the parking lot of Denny's to exchange, you know, whatever for an eighth. I don't even know what an eighth is. But the difference between like what they call dad grass and like what my cousin Rusty would call reefer, you know, in the nineties or whatever, how is that different from, you know, if you get like a Durban poison or like a purple kush or whatever. Wow, you know all the different types that are available now. That's because I smoke weed. Although I think that purple kush might be a little bit from 2001. Yeah. Just a disclaimer, smoking, even the occasional joint is so bad for you. And it's been a really weird year. And yeah, sometimes I'm like, you know what sounds good? Do not do what I do. I should be better at edibles. We're going to talk about that more later in this episode and next week. But all he knows it, we call Durban poison, derpy poi poi, because I'm like, I was like, I'm having an out of body experience. I can't ever touch that again. But these strains, is it the concentration of THC in the particular weed? What are we talking? Was it 5% and now it's like 30 or what? Okay. So I'm a scientist. So I love data. So if we're trying to figure out like how cannabis has changed over time, one way that we can do it is we can look at the cannabis that's been seized by the Drug Enforcement Administration, right? So the DEA, they're going around, they're seizing cannabis because it's federally illegal. They've been doing it for years and years and years and there's a lab that has been analyzing it, right? So what you can see is that back in the early 90s, the THC concentration was about like 3%, 4%. Back in the 70s, it was a lot lower. Okay. And so if you track it over time, now the DEA has been seizing cannabis and the concentrations of THC is more like 17% or 18%. And this isn't a US phenomenon either. It's been shown across the globe as well. Now that's what the DEA is seizing. So that's like unregulated cannabis. Now people who are listening to this podcast, who are in Los Angeles and who frequent dispensaries are going to be like 18%. Like that is, you can't even find 18% THC cannabis and dispensaries right now. Like good luck finding anything less than 20% THC cannabis. When you go into dispensaries now, generally speaking, 20% is the lowest strength. It'll usually go up to 30, 35%. And then so that's just the plant matter. So when you buy a pre-roll, right, if it's a regulated dispensary, it should have on the label how much THC is in it. And so you can see, you know, how much THC, how much CBD, if there is CBD in it at all. And so that, those are like characteristic of the pre-rolls or of the, you know, loose flower. Pre-rolls, side note are joints that are already rolled into these tiny little cigarettes. And flower, like blooming flower or a bud, not like wheat flower, is a lump of green that you then grind up to roll yourself. Keef, it's this powdery sticky kind of fairy dust containing dreams and wonders, maybe panic attacks. And when the loose stuff of Keef is compacted into a cake, it can be called hashish or hash. There is also naturally occurring resin on cannabis, and that can be processed into concentrates called dabs or wax, aka, shatter, butter, crumble, among others, which those can be up to 90% THC, just in case you've ever been to a dispensary and been like, what the hell is this stuff? Now, also, you can get what's called infused pre-rolls now. And so what that means is that those pre-rolls are infused with even more THC. So think like, you know, Keef or things like that. And so you can get a cannabis pre-roll that has much higher levels of THC. So you think about the difference between like the 1990s and what's available today. And you also just think about like the cost per milligram of THC, you know, back in the 90s where like an eighth would be like $60. Yeah. And so that's like three and a half grams. Now you go into dispensary, you get a pre-roll, which is a half a gram or a gram for $5 or $10. And it has 35% THC. You just think about the price per THC milligram and how, you know, the economics of it is that, you know, the price has definitely gone down. The price has gone down and the effects most certainly have amplified. Yeah. Right. And the question is, Allie, is how much have the effects been amplified by this change in THC concentration? The great news for chronic or casual stoners, you get so much bang for your buck. The not great news is you get too much bang for your brain potentially. How much, you ask? And the answer is, is that we're just starting to get information on this right now. Because up until recently, the cannabis that was available to be, that was available to be studied, did not reach 20% THC. It was, you know, 3% THC, maybe 7% THC if you were lucky. Oh my God. Right. So does the dose make the poison or the remedy then? Can you extrapolate it like one for one? Are you trying to figure out the data if it's exponential effects, good or bad, down to the chemistry of it? How do you start to try to figure that out? It's a good question because you're not just dealing with chemistry. You're dealing with human behavior. Right. And so frequently people will say, Oh, well, cannabis strength is increasing. That just means that people will use less. Right. So instead of smoking a whole, you know, the zigzag joints back in the 90s, which might have had like a third of a gram of cannabis in it, you know, people might smoke that whole joint in one sitting. Now, when you go and get a pre-roll, some people might just smoke one puff and be okay for a little while. Right. And so that is, was like a general idea that people titrate to get to a point of where they want to go to. Right. And if you think about it that way, maybe the actual THC that they're being exposed to from the 90s to today, maybe it's like equivalent, but there are two factors here. That's here. One factor is, you know, back in the 90s, when people smoked a whole joint, it would take a while for them to smoke that joint, be exposed to X number of milligrams of THC versus today, if they were to just take one puff and get the same accumulated THC exposure from that one puff as they would in the 90s from a whole joint. A, they're getting the THC in like a bolus inhalation. Right. So it's hitting the brain. It's hitting the body all at once. And so we think that that's probably having a different effect on physiology, different effect on neurobiology, probably a different effect on the overall feeling. Right. And then also, if you think about it over time, when somebody is using that high strength cannabis and they're starting off with taking one puff at a time, then the next time they might take two puffs. So they start using more and more over time. And this is what we see in our laboratory, where people who are using much more regularly are usually exposed to much higher doses of THC relative to people who are using infrequently. So you have this human behavior aspect. And it kind of plays out in our laboratory, where we're looking at people who do use infrequently, let's say once a week versus people who are using every single day, several times a day, we would give them the same strength of cannabis. They would have to smoke the same amount of that cigarette, of that cannabis cigarette or cannabis pre-roll. And you would see that the people who are occasional users, again, they're being exposed to the same amount of plant material, but they take a lot longer to smoke it. So if you're sipping in these bigger puffs of smoke and in more frequent bursts, it's more of a gonga slam than having the very same joint, but taking fewer hits, holding it, waving it around, just sort of smoking into the air. So you're going to become less high and it's paced out too. It's literally like a slower burn. Their plasma levels of THC. So when we draw their blood, their THC levels are a lot lower because it's taking them a lot longer to smoke it. And some of that THC is being lost to sidestream smoke. And then we have our people who are using it daily and they can suck down that pre-roll and, a couple of puffs. And so their THC levels are much higher. Now, the question is, how does that impact behavior? What happens? We find that the occasional users feel much higher than the daily. The daily users, even though their blood levels are really high, they're not going to be as intoxicated. So there is a tolerance. Like someone who rarely drinks, just getting shithammered off an apparel spritz, as opposed to a daily drinker who might feel disappointedly clearheaded after half a bottle of pino. And so maybe if they were at home, they would use more in order to reach that level of intoxication. With our lighter users, they are feeling really high, even though they have low blood levels. Sometimes we see the adverse effects the most in those occasional users. They're going to feel a little more anxious. They're going to report a bad effect. They're not going to like it as much. This is something that we do study in our laboratory, which is an example of what is the impact when you start increasing the strength of the cannabis. How does that play out in the person with the adverse effects? And to your point also, I think you said, is it the poison or the... Yeah, the dose makes the poison or the remedy. Or the remedy. Right. And so it's interesting, the remedy aspect to that, because that applies... You probably didn't mean it this way, but that really applies also to people who are using cannabis for medical reasons. We know that people who use cannabis for medical reasons, like if you look on a population-based level, people are using cannabis for medical reasons, they're not using once a week. They're not using once a month. People who are using for medical reasons, for example, for chronic pain, they're using it every day typically. The frequency of use is much higher. But this daily frequency for medical use can come in the form of a low but effective dose of THC, CBD gummies, or it may look like rip and bongs with gnarly shatter. Effects are going to vary according to dose, of course. And so what does it mean if they're using higher strength products to help with them medically? Does it mean that they're going to get more relief? Right? Does it mean that if they get more relief in the beginning, if you see them a year later, that they've become tolerant because they need higher and higher doses? These are really important questions that we're starting to answer in our lab and certainly other labs are also starting to try and get at that specific question because a third of people with chronic pain are using cannabis to help with their pain. Yeah, I had an MS episode and the doctor is an expert in MS. My mom also has MS. But my mom and dad are, despite living in San Francisco in the 60s, my dad even in hospice wouldn't take a prescribed pill for his appetite. I'm like, dad, the feds are not going to arrest you. It's prescribed by your oncologist. But our MS episode, Dr. Aaron Boster, was like, it's the most effective remedy for things like spasticity of the muscles and sleep and chronic pain. But the uses recreationally and medically, I imagine the doses are so much different. The habits are so much different. The effects are probably much different. But I'm wondering, going back to how much of a dose and a pre-roll and stuff, buss and flam flam or not for me. But if you're holding it in your lungs, like my roommate's donors, is that staying in the lungs longer if you're smoking? Does that really have an effect? So evidence doesn't suggest that the longer that you hold it in the lungs, like the more high you're going to get. In our own laboratory, we do have people hold it in their lungs for a specific period of time. But at a certain point, you get maxed out. But what matters though, probably more, although I don't know what the data are, is the depth of inhalation. So the volume of smoke you intake. You can imagine that somebody who's never used before, they're going to take little sips. They're going to figure out, oh, how does this feel? Versus somebody who's very experienced, they're going to inhale quite deeply. And when you inhale quite deeply, you're burning that cigarette faster indicates you're getting a lot more THC into your body than if you're taking little sips. So it's really, I think, the depth of inhalation that probably matters the most. What about indica versus sativa? Because you mentioned anxiety. And I know a lot of listeners, a lot of friends I have, to manage maybe being neurodivergent or to manage mental health symptoms that are probably becoming more and more prevalent with like our culture at large and social media and COVID having really disrupted a lot of our support system socially. So a lot of people are using this to manage certain conditions that they might already walk into. But indica versus sativa, do those affect us really differently? I've been self-medicating. So I want to approach this for two different reasons. One reason is to acknowledge the science behind these chemicals in the plant. And another one is to address, I think, some of the policies and regulation of these plants. So the first area is addressing the science of the chemicals and these quote unquote strain names. So it's long been thought that indica and sativa as like different quote unquote strains have different effects, right? Like sativa is stimulating, indica can produce couch lock. And so there's been this kind of lore around it. We know now that when you walk into dispensaries and you see the strain names and it's no longer indica and sativa necessarily, but let's say it's like purple kush or Girl Scout Cookie or things like that. So yes, while sativa and indica are both the same species, it's kind of like breeds of dogs. So the psychoactives like THC and then the flavor and smell profile of compounds called terpenes in sativa have the reputation of like an Australian shepherd, just hyperactive, brain high, they can induce creative thought or spine stiffening anxiety in some folks called me. Now the indica strains are said to be more like a basset hound, just a body high, keeps one cuddled on a soft surface, watching the world go by, making your brain more molassesy and perhaps hungry for things like molasses cookies. Because while it has elements of this low-riding, sleepy hound, users report that indica keeps you hungry like the wolf, stimulating appetite for better or for worse. So this is what a lot of people think and a lot of dispensaries sell hybrid strains too of sativas and indicas and they name them things like white widow, super boof, pineapple express, soap, AK-47, chem dog, glitter bomb, train wreck and cheetah piss. Now some strains are well known such as the pure sativa, Maui-Waui, you may have heard about, Durban Poison, I call it Durby Poipoi and Purple Haze. Now there are some well known indica dominant strains that are called like rainbow lights and Donnie Boy or Kush varieties generally and the chemical variations in strains are called chemovars. It's like a pino versus a shard and for more on all of this confusion you can get a gander at the 2020 paper. Cannabis chemovar nomenclature misrepresents chemical and genetic diversity, survey of variations of chemical profiles and genetic markers in Nevada medical cannabis samples from the Journal of Cannabis and Cannabinoid Research. Let's hear more. People have a sense that they are getting a cannabis type that is consistent from one purple Kush to another purple Kush. A, this is not the case and B, it's not the name of the cannabis that's going to impact how somebody's going to feel when they use it. What's going to impact somebody is the actual chemicals in that cannabis plant. We know that from seed to harvest to being put on the shelves there's a lot of steps there that will directly impact the cannabinoid concentrations in the cannabis plant. This blew my mind. For example, if a plant got too much sunlight or was exposed to too much heat at certain points of the growth process, that's going to impact how that plant expresses certain cannabinoids. You can have two seeds and two chemovars that are starting off in the same way, but they can diverge completely with respect to their chemical profile based off of a number of things. When people are going to look at different cannabis types and the dispensary, it's not the name that's really important. It's what are the chemicals in that cannabis plant. If you look at regulated cannabis, you'll find that either there will be some indication of the different cannabinoid concentrations in that particular cannabis. There might be a QR code where you can click on it and you can get actually a certificate of analysis and it can tell you even how the terpene concentrations in there that people think might impact the effects. It's important for people to realize that these names aren't necessarily all that meaningful. It's really the chemical constituents. Also, for people who are specifically using cannabis and cannabis based products for therapeutic purposes, if they find relief with a certain type of product, it doesn't necessarily mean that they are going to get the same exact product every time they go to the dispensary. At least with flower and pre-rolls. Now, what about edibles? It's a great question. A 2016 JAMA article, cannabinoid dose and label accuracy in edible medical cannabis byproducts allotted people's with a doctor's note to spend 400 bucks each to buy some weed at dispensaries in a few different cities. They're like secret shoppers or narcs, but just really nice scientists looking out for you. They found after all this analysis that of 75 products purchased, 17% were accurately labeled for THC content, 23% were under labeled, meaning there was more THC than it said, and 60% were over labeled and people were getting a little ripped off. But if you say had the same bag of edibles and you swear it hits different, what is up with that? So conversely to what might happen with a martini on an empty stomach, fatty foods actually increase the high with edibles because THC and other cannabinoids are fat soluble. Like when you use an oil-based makeup remover to just dissolve off your mascara, it's like that, or like goo gone on some sticky stuff. So that's what fat in your stomach does to those compounds. So if you're not looking to go for that higher ride with an edible, do not eat it right before a fatty snack, like cheese or butter or else that's going to turn up the volume on that stuff. And we're going to talk more about why you launch into space after a gummy in part two. It's not like when you go to CVS and you get Advil or you get, you know, Benadryl, whether it's liquid form or oil form, where you kind of know that there's standards of quality and testing that are put in place, primarily through the FDA, so that those products are consistent time and time again. This is not the case with cannabis products and it is a real issue, right? Because there isn't that type of oversight and that type of regulation that we have with other types of medicines. And so what it means is that people have to be more sophisticated consumers. They have to understand what it is they're buying, what's in that product, if their product is going to change a little bit, you know, can they find a similar product that has a similar cannabinoid profile as the product that they used before. So it's really, we're moving away from the Indica-Sativa categorization and trying to improve the recognition that it's the cannabinoids in the cannabis plant that is going to have the outcome, the impact. Do you ever have to get high to test things? I mean, I know people must ask you this all that time, but it is legal here in California. Do you have to remain very agnostic? Like I do not divulge whether I partake or do you have to be like, yeah, I have to understand what it's like to feel high or scared. It's an interesting question. I think like as a scientist, you know, coming at this from a scientific perspective, I don't think it really matters, you know, whether or not I use it, have used it, will use it to be able to be a good scientist. Back in the day, psychopharmacologists, you know, they did try out the different compounds, you know, you read these stories about pharmacologists trying to understand the effects of drugs and, you know, they did experiment. I don't think that's necessarily the case here. You don't have to try to fit in all the study yet. Right, yes. Case in point. And, you know, now something like cannabis is used by so many different demographics and people are using it for so many different reasons that my experience that I have with it is, can't be mapped on to somebody who's necessarily using it because they have insomnia or they have chronic pain. I do not have insomnia, you know, when I, as soon as, although I, you know, when my head hits the pillow at like 2am, I am out, right? So, you know, I wouldn't be able to use my experience to inform my research in that respect. Yeah, it's so interesting because of the legality. There is still such a stigma, but it's interesting that like I can go to a bar and order enough shots where that's up to me until I get 86. But I think maybe because THC can affect people so differently and because there are so many compounds that might just be like CBD or CBN that might be so beneficial. It feels like if someone has smoked weed, you don't know what they're going through because it can affect people so differently. But whereas if you've had a drink, you're like, okay, after a drink, you're probably a little bit more chatty. And after, you know, three, you're probably going to belt out karaoke or something, you know, right? It's more, feels more predictable. I wanted to, well, actually, can I ask you some questions from listeners? Is that okay? Yeah, absolutely. Just one point about that as well is that it's not only, you know, kind of unpredictable because we don't know, you know, some people might not know how it might impact them or there's so many different types of cannabis varieties and cannabis, you know, ways of using cannabis and people just might not be as familiar. When people start drinking alcohol at a younger age, they kind of get the hang of, okay, one beer will have an impact on me in this way. I will never touch tequila again. Oh, vodka is my spirit of choice. Right. So there's like this self-knowledge that I think comes along with it. I mean, I think that's certainly with cannabis that is definitely growing as well. But there's still a group of people that are fairly inexperienced and don't necessarily have a full understanding of how it will impact them. It's wild to think of like people in the 90s were drinking like 2% beer and now people are just drinking a pint of 60-proof alcohol. That would be like... Right, exactly. That's a good analogy right there. Yeah. And studying that with the data changing so much has got to be such a moving target. I can't even, I can't even imagine. But, well, I wanted to ask you some questions. Rachel Olesner asked, if there's any truth to the idea that there are long-term side effects from cannabis usage, especially smokers, 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, how, what do we know about danger? So ask higher education experts, half-baked questions, because there's so much to learn. They're worth the wait, and you're going to have to wait a week for part two, but you will be rewarded with more doctors, Cooper and Melly, and we'll be covering smoking, vaping, gummies, brownies, neurodivergence and cannabinoids, mental health conditions that may not mix, trials on inflammation, what to do about the munchies, long-term side effects of lots of weed, more flim flam busted, and what to do if you'd like to have a little less in your system and how to make sure that your gummy doesn't lead you into a realm you never asked to be in. Meanwhile, find links to both of ourologists in the show notes, as well as a trove of links to studies that we mentioned at alleyward.com slash ology slash cannabinolegy. We are at ologies on Blue Sky and Instagram, where we just posted some dazzling fashion roundups of sea slugs and some leopard videos, and I'm at alleyward with 1L on both. We have small ologies episodes at the links in the show notes, and thank you to patrons at patreon.com slash ologies for the wall to wall questions episode next week. Erin Talbert, Admin Z Eologies podcast Facebook group, Aveline Malik makes our professional transcripts. Kelly R Dwyer does the website, scheduling producer and Noel Dilworth pesters our guests until they are friends with us. Seeing us through our weekly haze is the potent managing director Susan Hale, and the hybrid Indica Sativa of dreamy but alert and focused our editors Jake Chaffee and lead editor Mercedes Maitland of Maitland Audio. Nick Thorburn exhaled the theme music, and if you stick around to the very end, you know, I may tell you a secret. This week, it's, of course, it will be gonja related. I once went to a street fair and with my friend Catherine and they won there was a stand that was selling cookies and they were fancy funky cookies and I said I'll take one of those and had had a little bite and it was pretty good. And then I was putting together some IKEA furniture. I just moved into my house and I was so confused by the directions and I thought par for the course. And then I was very confused by the directions. I was also a little hungry. I had a little pile of snack and then I began to not understand what being alive was and I should mention that the snack I had was the rest of the cookie and I was so high. I call I could do was go to bed. Jared was like, you got to sleep this off. And I was like, I don't think this is gonna this can't end well. And his mom knocked on the door at seven in the morning. We had plans to go to the Rose Bowl flea market, which is best when you're an early bird. And I was like, I cannot. I'm still high. I can't go and she, his mom is so wonderful and so understanding and she just came and sat on the bed and touched my hair and said, yeah, it happened sometimes. And they went to the flea market and they bought me a crystal, which I still have on the coffee table. But the point of this very long aside was there was no label on the cookie. It was homemade. And I went back the next day. The fair was a two day affair. And I said, just curious, how much was in that cookie? Because I ate the whole thing and it was 125 milligrams. It's like taking a dozen hardcore gummies. That is so much. It was like a shortbread though. So good. Anyway, check your labels kids. Thank you for listening. Get all right. Next week. Bye bye. Hi, Bubba Kush, chocolate thunder, Barbara Bush, Barbara Streisand, Barbara Bush Jr. Yeah, this is plenty.