Cannabis, THC, and CBD

Ryan: And I think one of the big failures of this whole medical legalization process is that the states did not invest funding to do those clinical trials, to find out if what they did was a good idea or not. And so the argument for this state level legalization has been, look, it's been around forever. People have been using this.

Ryan: The whole reason we've stopped using it is for racist politics.

Brent: Welcome to The Life Lab by Death Clock. I'm your host, Brent Franson. The mission of Death Clock is to help 100 million people live ten years longer. Today, we speak with Doctor Ryan Vandrey about cannabis. The conversation focuses on the health impacts and the negative side effects of THC and CBD. Doctor Vandrey is a professor of psychiatry and behavioral sciences at Johns Hopkins, where he works in the Behavioral Pharmacology Research Unit and co-led the Cannabis Science Lab.

Brent: This is a topic that's followed a windy path. When it was illegal, we espoused the benefits of cannabis if it were legal. Now that it is legal, there's more questioning around what the benefits are and paying a bit more attention to the harm given its widespread availability. Doctor Vandrey does a really good job of cutting through the noise, helping us understand where it should be considered beneficial based on research, where the research is weaker, and where it's harmful.

Brent: He's about as good of a guest as you can get on this topic. He spent his entire career studying it. Hope you enjoy.

Brent: Doctor Ryan Vandrey, welcome to the show.

Ryan: Thanks for having me.

Brent: Today we're going to talk about marijuana, THC, and CBD. I used to be a very heavy marijuana smoker when I was in high school, and now I can't consume it at all because I get too anxious. I'm looking forward to learning about it from you. Before we dive in, give us a sense of your background and day job.

Ryan: Sure. I'm an experimental psychologist by training, specifically focused on behavioral pharmacology, which is the study of how drugs impact human behavior. I've been studying cannabis for over 26 years now. I do a lot of different things in the cannabis space. My bread and butter is running human laboratory studies, where we bring healthy volunteers from the Baltimore community into our lab and dose them with various cannabis products. We examine how differences in chemical composition, route of administration, and formulation impact drug absorption, drug testing outcomes, cognitive performance, and subjective drug effects.

Ryan: Another arm of my work focuses on understanding the health effects of medicinal cannabis use. Starting with California 30 years ago, states have been approving cannabis for medical use, but we still don't know a whole lot about how it impacts health, for good or for bad.

Ryan: We've built a large national project called the Cannabis and Health Research Initiative, where we enroll people who are newly starting medical cannabis use. We assess them before they start and follow them for a year to understand what products they use, at what doses, frequency, and for which health conditions. We track their journey to determine if medical cannabis is helpful, harmful, or somewhere in between for specific conditions based on the products they use.

Brent: I view you as a scientist at Johns Hopkins running the Behavioral Pharmacology Research Unit. You're running studies, analyzing data, and publishing findings. Did you originally get into this as an advocate?

Brent: It's been an interesting arc over the last 20 years. Twenty years ago, when it was illegal, the common refrain was that it shouldn't be criminalized because of its beneficial use cases. Then we legalized it in many places.

Brent: Now that it's legal for medical and recreational use, the narrative has shifted to questioning its effects. Did you start out on the advocate side saying it shouldn't be criminalized and that we need to understand the health benefits?

Brent: It shouldn't be. Let's understand, the health benefits.

Ryan: I came at it from a completely different perspective. Early in my career, I didn't study cannabis at all—I studied every drug except cannabis. I was interested in psychopharmacology and conducted research on alcohol, opioids, and stimulants.

Ryan: When getting my PhD, I trained under Alan Budney at the University of Vermont, who was starting a cannabis program. Our studies focused on characterizing cannabis withdrawal symptoms and treating individuals with cannabis use disorders.

Ryan: The focus of our research was helping people who struggled with heavy daily use quit. It wasn't about proving medical benefits or changing policy. For the first ten years of my career, I focused on helping people stop using cannabis.

Ryan: We aimed to identify their challenges to develop better treatments. Around that time, states like California, Colorado, Maine, and Michigan began legalizing medical cannabis.

Ryan: When the Cole Memorandum signaled a federal hands-off approach, new types of products flooded dispensaries. The scientific questions we could ask exploded overnight, moving beyond basic addiction research to a vast array of topics that will take decades to fully explore.

Brent: What's your view on addiction? This is close to my heart because I went to rehab at 21 when I couldn't stop smoking weed. As a teenager, I smoked constantly throughout the day.

Brent: There's that running joke in movies like *Half Baked*—"You went to rehab for weed?"

Ryan: Where Bob Saget's character jokes about what he did for cocaine, right?

Brent: Yeah. But I genuinely couldn't quit until I spent 30 days in treatment in Arizona. How addictive is cannabis in reality?

Ryan: It's important to distinguish nuance: THC is the addictive compound, not the cannabis plant itself. People often argue that because it's natural, it isn't addictive, but opioids come from poppy plants and are clearly addictive.

Ryan: Drugs of abuse share a common mechanism: they increase dopamine in the reward centers of the brain. THC does this, just like cocaine, caffeine, nicotine, and morphine.

Ryan: Relative addictiveness depends on neurobiology and route of administration. Inhalation delivers a large spike of the drug followed by a rapid decline, which prompts repeat use—a classic recipe for addiction.

Ryan: When a heavy daily user abruptly stops, neurobiological adaptations in the brain trigger a withdrawal syndrome in the absence of the drug.

Ryan: Withdrawal symptoms are typically the opposite of the drug's effects. While cannabis relaxes you, aids sleep, and stimulates appetite, stopping abruptly causes insomnia, irritability, appetite loss, and mood changes.

Ryan: Withdrawal symptoms can last two to three weeks. Knowing that smoking a joint will immediately relieve them makes breaking the cycle difficult. Our early research showed that THC withdrawal looks very similar to nicotine withdrawal.

Ryan: Controlled studies demonstrated that cannabis withdrawal severity and difficulty in quitting match those of tobacco.

Brent: I also quit cigarettes in my twenties and actually found that easier because I could use a nicotine patch without feeling intoxication. With THC, quitting felt binary—you had to stop completely rather than tapering off easily.

Brent: There wasn't an obvious gradual path like there is with nicotine replacement options.

Ryan: People usually have a primary drug of choice that they gravitate toward, whether it's alcohol, nicotine, cannabis, or cocaine, and that one is always the hardest to quit. Among dual users of tobacco and cannabis, half find tobacco harder to quit, while the other half find cannabis harder.

Ryan: Treatment success rates for cannabis use disorder sit at best around 20% for long-term abstinence among people seeking treatment.

Brent: How do psychedelics fit into addiction research? Can one substance help address addiction to another?

Ryan: Colleagues at Johns Hopkins are studying psilocybin alongside behavioral therapy to assist people in quitting smoking, cannabis, and opioids. This builds on research dating back to the 1950s that evaluated LSD for treating alcoholism.

Ryan: This approach isn't simply substituting one drug for another. In clinical trials, therapy prepares patients for one or two controlled psychedelic sessions, where they are guided to reflect deeply on their lives and habits.

Ryan: That profound experience often leads to valuable insights regarding their substance use. However, it doesn't work for everyone, and taking unsanctioned substances outside a clinical setting does not produce the same structured therapeutic results.

Ryan: It's a very structured format in which they do those kinds of clinical testing.

Brent: My experience with ketamine in relation to alcohol felt almost spiritual. I visualized opening my skull and pouring beer directly onto my brain, realizing I was putting cheap poison into a remarkable organ.

Brent: That memory permanently altered my relationship with alcohol.

Ryan: That aligns with experiences others describe, such as visualizing internal organ damage from smoking. Mystical experiences during psychedelic sessions are a recognized area of study.

Ryan: We're still researching whether behavioral change is driven by the psychological epiphany, underlying neurobiological rewiring, or both, but clinical trial results are promising.

Brent: It's fascinating that early AA founders experimented with LSD in the 1950s before stepping away from it prior to its criminalization.

Brent: The early history connecting psychedelics and alcohol treatment is well documented.

Brent: And kind of the rest is history. But I think there is some truth to the origin story of AA actually is psychedelics. It got covered up very quickly.

Ryan: Yes, there are several documentaries covering Bill W.'s work with psychedelics in AA's early days.

Brent: Let's define THC and CBD. Could you break down the basics of the cannabis plant and these two compounds?

Ryan: Cannabis is a plant genus with complex chemistry. Through selective breeding, growers upregulate or downregulate specific plant features.

Ryan: Delta-9-THC is the primary psychoactive constituent responsible for the intoxication or high. Over recent decades, selective breeding significantly increased THC concentrations in plants.

Ryan: THC effects depend heavily on dose and individual factors. For example, low doses can relieve nausea or anxiety, while high doses can induce them.

Ryan: Genetics, biological sex, age, metabolism, and user experience all shape the response to THC.

Ryan: The endocannabinoid system helps regulate physiological homeostasis across various pathways, and its activity changes across a lifespan.

Ryan: As neurobiology adapts over time, a dose that felt enjoyable at age 18 might trigger anxiety or panic at age 60. Generalizations don't capture this nuance.

Ryan: Product categories matter tremendously. Referring broadly to "cannabis" is uninformative because chemical compositions and administration routes vary wildly—from high-THC smoked flower to topical CBD lotions.

Ryan: Legally, hemp and marijuana are distinguished by Delta-9-THC content: hemp contains 0.3% THC or less by dry weight and higher concentrations of cannabidiol (CBD).

Ryan: Beyond THC and CBD, the plant contains hundreds of other phytocannabinoids with distinct pharmacology.

Ryan: Delta-9-THC is a cannabinoid receptor agonist that directly activates the system, whereas CBD interacts with multiple neurotransmitter systems without binding directly to cannabinoid receptors in the same way.

Ryan: Consequently, THC produces intoxicating effects, while CBD does not.

Ryan: And so when you think about intoxicating effects, THC does that CBD does not.

Brent: How strong is the medical evidence for THC?

Ryan: It's solid. The FDA approved synthetic THC (Marinol) 40 years ago for chemotherapy-induced nausea and appetite stimulation in AIDS patients.

Ryan: Research also supports THC for treating chronic neuropathic pain and anxiety, though administration route and dosage remain critical to avoid adverse effects.

Ryan: CBD (Epidiolex) earned FDA approval in 2018 for rare pediatric seizure disorders, dramatically reducing seizure frequency in many patients.

Ryan: We need greater clinical precision rather than relying on broad claims or leaving patients to experiment without evidence-based guidance on product type and dosage.

Ryan: What I think we need to do is we need to get more precision in that. We need to say, well, what kind of cannabis product at what dose is good for which health condition? Because the current approach is like a sledgehammer approach. It's like, oh, you have any of these three dozen health conditions? Try cannabis. Will try what?

Ryan: And so our current process is to send a patient to a dispensary or to the internet to buy something without a ton of guidance and without a lot of evidence and say, try whatever you think might work. If that doesn't work, try another one and figure out the dose on your own. And so I think we really can do a lot better than that.

Brent: How do you distinguish formal medical applications from broader wellness uses, such as managing mild anxiety or sleep?

Brent: Is the research behind THC or CBD for general well-being robust?

Ryan: It requires nuance. Mild occasional anxiety differs from debilitating anxiety disorders. I advise treating cannabinoids as active drugs rather than harmless supplements simply because they derive from plants.

Ryan: Even non-intoxicating CBD can cause adverse effects or interact with other medications. In severe cases, improved sleep or reduced anxiety through CBD significantly enhances quality of life, but controlled evidence varies.

Ryan: Right. And so it these are drugs and CBD, you know, even though it doesn't cause intoxication, it's not necessarily totally inert. Right. And that's why people take it so it can have beneficial effects. It can also have adverse effects. And you have to understand what those are and understand the risks. So right now if we're talking about, you know, benefits of CBD, again people will say lots of stuff.

Ryan: I mean, again, on the hardcore science and medicine side, treating seizure disorders in the absence of benefit and other for other anti-epileptic medications. I mean, that's huge. And we've seen over and over again amazing cases of kids having hundreds of seizures a day, taking a CBD oil and being seizure free for years. That's amazing. Then you go into, you know, I've got someone's got an anxiety disorder.

Ryan: And we see taking this thing really helps them and not only helps their anxiety, but it helps their quality of life. It helps their functioning. It can translate to improved sleep, which improves a number of other kind of facets of health. So I don't want to discount that too much.

Brent: Where do randomized controlled trials (RCTs) stand for anxiety or wellness applications versus individual case evidence?

Brent: Right. So the carnivore diet would be a good example of this. That's never across a large population. That's never going to rise to the top in terms of being the best and healthiest diet. Now, that's not to say that there aren't some individuals where that might be a really great diet for them. And if we look at that individual and we study that individual, say, hey, that is the best diet for you.

Brent: And so where does this fall like THC for anxiety? Is that a hey, we've done the placebo controlled randomized trials and the evidence is really strong at the population level. Or is it? We see it in individuals, but we don't have the we don't have the, you know, the CT data.

Ryan: The primary critique of the cannabis space is the shortage of large, population-level randomized controlled trials. State and national legalizations occurred legislatively rather than through traditional pharmaceutical development paths.

Ryan: Without legislative mandates requiring companies to fund multi-million dollar Phase 3 trials for existing commercial products, standard clinical trial data remains limited.

Ryan: State-funded research initiatives in California, Colorado, and Michigan have shown positive indications, but comprehensive multi-center RCTs are still needed.

Ryan: What company that is given legislative permission to grow and sell a drug is going to then invest $50 million into large phase three clinical trials to demonstrate that what it can already do as a good thing. And I think one of the big failures of this whole medical legalization process is that the states did not invest funding to do those clinical trials, to find out if what they did was a good idea or not.

Ryan: Now, some states have California. Michigan in particular, have put millions of dollars up. Colorado has put millions of dollars up to fund clinical studies. And by and large, those clinical studies have shown benefit. But again, it's not a phase three, placebo controlled, multinational 52 site thing that you would normally see if you're bringing a new analgesic on the market.

Brent: By passing standard FDA approval processes through state legislation, the commercial incentive to invest in rigorous clinical trials evaporated.

Brent: It becomes approved. And in this case, we said, hey, everybody's doing it, and there's this black market for it. So we're just going to approve it at the state level. And so all right, now I don't need to go through that rigorous process. I can just say that this is good for whatever. And I can and I can start selling it.

Brent: And so there's a negative byproduct actually of the intention is is good I think in legalizing it. But there's a negative byproduct there, which is, all right, why am I going to spend the money to do all of those rigorous studies? I don't need to. I can just sell it. I can basically sell it for that indication without the study.

Ryan: Standard drug development evaluates safety for single novel molecules targeted at specific conditions. In contrast, botanical cannabis has a long history of traditional use across diverse applications.

Ryan: State legalizations bridged herbal history and modern pharmaceuticals, but rapid product diversification—including semi-synthetics and concentrates—outpaced regulatory oversight.

Ryan: Layering adult recreational access on top of medical frameworks without clinical guardrails leaves medical patients navigating consumer markets largely separated from clinical guidance.

Ryan: And so it's stuck because you have this historical use. We know it's good for a lot of certain things, in certain cases for certain people, but then we've kind of blown it up to be instead of just this raw botanical. Now it's like there's synthetic cannabinoids, semi-synthetic cannabinoids. You eat it, you rub it on your skin, you do all of this stuff that wasn't normal ten, 15, 20 years ago.

Ryan: And how do you reconcile all of that? And so that's where things get really sticky, is we legalize things, didn't put any guardrails on what could be done or what kinds of products could be made. And then now we've doubled down on the silliness of the policy, and we've thrown adult use on top of the medical use at the state level.

Ryan: And the patients who are looking to use it for medical purposes are going to the same stores as the person who just wants to get high after a long day's work. And the products are geared more towards that latter person. And so it's a it's a just a mess. We've taken the medical providers almost completely out of the equation in most states now.

Brent: On balance, has recreational legalization been net positive or negative?

Ryan: Policy evaluation falls outside my primary focus in pharmacology. Assessing overall impact involves balancing usage rates, criminal justice reform, and public health metrics, which different groups interpret in contrasting ways.

Ryan: It's understanding rates of use and misuse. Now the statistics there can be cooked to really kind of deliver whatever message you want. And that's why we see the same data being used by the two different camps to argue. It's been great. It's been terrible. You know, you see increased rates of use, but youth use has stayed the same if not started to go down.

Ryan: The rate of problematic use among users is going up. But treatment seeking has gone down like it's really complicated, right? But all of that stuff has to be factored in on the on the good or bad thing. And then you have to again, outside of the health of the user, you have to factor in, okay, at the societal level, the criminal justice piece.

Ryan: Right. So there are a lot of people were getting arrested, thrown in jail, losing scholarships, losing federal funding for college, losing jobs because they wanted to smoke a joint in their house on the weekend. Right. And so there's a lot of that stuff that goes into this and that historical, again, racist politics stuff that has to be reconciled with all of this stuff as well.

Ryan: So the impact on society, I think David Nutt, this British scientist, did a really fascinating review of all the kind of scheduled drugs and kind of put all of those factors into a, into an equation and said, all right, from rank order worst to least harmful to society. Cannabis was kind of toward the bottom. And so if you factor all of that stuff in there, making it a little more available, tightening up regulations on quality control and cultivating and minimizing contaminants, and you can pull education in and say, all right, listen guys, we're going to make this available similar to alcohol.

Ryan: But here's what you should know about it. And know if you're going to the store and you're buying it it's going to be regulated product. It's not going to be laced with anything. You're not going to an illegal drug dealer who's also selling all this other stuff, probably a net positive on the legalization. But again, not it's not something that I've extensively studied and that I'm expert in.

Ryan: I'm more expert in the pharmacology.

Brent: Well, maybe maybe I'll ask the question from that perspective then. And I'll give an opinion of my own. And I know I'm going to be more comfortable giving opinions than the guests on the show, typically, who are who are much more rigorous in their approach to science and what's in their domain and what's outside of their domain. But okay, so my opinion would be for something like benzos, benzodiazepines for anxiety.

Brent: I think of course there are benefits for the reduction of anxiety, but they're highly addictive and there are a whole bunch of negative pieces. So a thing can be two things. But if I were to some all of those up and I could wave my magic wand, and the magic wand that I'm waving is whether or not benzodiazepines exist, I would say get rid of them.

Brent: In my scenario, I'd say no. The benefits, even though there are benefits, do not outweigh the harms. These are these are basically bad medications. Let's get rid of these things. Where would you be on the side of that? Because you've got addiction. You've got this recreational use I don't know. You're harming the lungs. And you know, there's a bunch of downsides, but there are cases in which it's beneficial.

Brent: So as it relates to strictly to human health, set the policy. Step aside. What do you do if you wave your magic wand?

Ryan: I don't think you can make your wave your magic wand and make it go away because it's here. And I think part of the issue with the policy thing for me is that having it be illegal didn't stop most people from using it. So the rates of use have gone up, but they haven't gone up so dramatically that we're like, all right, this wasn't a problem before, and now it's a problem actually see it as not terribly different either on the positive or negative side.

Ryan: And I think the the difference there depends on which population you drill down on. So where we actually see the highest increase in use, it's in older adults, not younger adults or kids. And that was everybody's concern. And when you look at the use among older adults it's usually for therapeutic purposes. Most of what we know and understand about cannabis as a drug of abuse is focused on non-medical applications.

Ryan: It's the people who use it to get high, and it was heavily focused on adolescents and young adults. We don't quite understand or we don't have enough data. At this point, I don't think we're probably getting close to where we'll have it. But to understand the rate of misuse among people who begin to use it for therapeutic purposes, and I think that that's a very important piece of all of this.

Ryan: So we've got the legalization, the approval for as a therapeutic, and then we've got the adult use stuff. But I think if you look just as the as the medical application, we're going to see more benefit than harm there simply because we've seen I've seen personally many, many instances of tremendous therapeutic benefit. Now, part of what we're missing from that data is the people that tried it and were harmed, or the people that tried it and it didn't do anything for them.

Ryan: And that's one of the key outcomes of this new research project that we're doing, trying to track people as they newly initiate and follow on. Because what ends up when you do these survey studies of, hey, you're a medical cannabis user, let's ask you about your health. And hey, here's a non user. Well, we have a very selective biased sample of people that tried it, liked it and kept using it.

Ryan: We're rarely capturing in those survey studies people who tried it and it made their symptoms worse. We tried it and it didn't work. And so I think one of the big things for us to understand the value of this policy change is to know the rate at which people try it, it helps them versus they try it and it makes things worse versus they try it.

Ryan: Nothing really happens and they move on to the next therapeutic opportunity.

Brent: And then is there are there benefits just for general wellness or longevity? Almost all the examples we've been talking about today are are reactive. I've got some anxiety, I've got some trouble sleeping, I've got some nausea, but none of them would fall into the category of I should have a CBD drink every day, because that's going to prove the length of my life, or it's going to keep me healthier longer.

Brent: You know, nothing we've talked about would be would fall in the preventative health category. But how do you think about it?

Ryan: So that's an area where there's some interesting really early science looking at that kind of thing. There is a publication that came out, I don't know, maybe 3 or 4 years or so ago that in this preclinical model with this microorganism called C elegans, if you kind of dosed them with CBD, they lived a lot longer than the microorganism that didn't.

Ryan: So from a longevity perspective, people latched onto that like, oh look, this stuff's really good. When you look at again what the endocannabinoid system does, it's a it's a homeostasis maintaining up and down regulating system for a lot of key parts of our physiology and our health. I think where wellness promotion kind of comes in and where we have to do a better understanding before we can answer that question is, does boosting that system long term?

Ryan: Is that okay or not? Because again, I mentioned before, in the context of addiction, if you repeatedly take and exogenous drug, your body adapts to the presence of that drug starts to kind of counteract it. So do you dampen your body's endocannabinoid system by chronically taking a cannabinoid when you don't need it, and does that end up harming your health long term, or does boosting this system generally just make it better and helpful?

Ryan: And we don't really know the answer to that yet. So I think we have to understand that before we can answer that question. And again, you know, and then like a second part of that is Ethan Russo is a good friend and colleague of mine. He has this theory that just like everybody is different in many other ways, people are different in the functioning of their endocannabinoid system and argues that some people have a deficient endocannabinoid system just by nature, by their genetics and chronically taking some of these things, if you have a deficient system, will boost it up to regular processing and therefore might be helpful for long term health.

Ryan: So again, there's some signals for those kinds of things, but we don't quite understand exactly how it works and how to modulate it appropriately.

Brent: Do you consume THC or CBD?

Ryan: I've tried it all. This is not something that I take on a regular basis. You know, as a scientist, I feel like, you know, this new thing comes along. Check it out and see what it's like. You know, my early formative years definitely got after the cannabis a little bit, but you know, that does not. Not my drug choice.

Brent: But you when you go to a, I don't know, Whole Foods. Are you looking at the CBD drinks and considering them for your own health? Or you feel like the science is still too early there? It's not something that you would do regularly.

Ryan: I always check them out, but I do it because I'm interested and curious of what's out there. I don't shop for any of this stuff for me personally at the moment. So and again, I don't have a medical need, so that's not something that I've considered now. I have tried CBD and products post-surgery to try to see if it worked for my pain and how it compared to opioids or ibuprofen.

Ryan: I can't say that I've done that enough times to know the answer, yet it wasn't shockingly effective or ineffective either way. I just kind of tried it to see what would happen, you know? So so I again, not an advocate, I'm trying to kind of bring science to bear on this and to try to bring the work to help other people make those decisions when they do have a need.

Brent: Well, and maybe I mean, I always find that to be a helpful question to understand this distinction between and you answered the question well, but between wellness and then use for some very specific medical condition. You know, if you ask that question to a cardiologist or somebody studying the hard about statins, they typically take the stat, you know, they're convinced they're around the research all day long, and there's very little downside.

Brent: And it has this preventative benefit. And so they're doing it. And in your case you're saying hey I'm convinced of I mean I don't want to put words in your mouth. You'll be able to find to this, but you're convinced of the research as it relates to nausea or seizures or increasing appetite and even the, you know, I would assume you would say something similar about anxiety and depression, but you're not really suffering from any of those things.

Brent: So you don't take it and you're not totally convinced of just the general wellness that basically they take the CBD pill every day. And so, you know, you're optimistic about that and you'd love to see that succeed. But all right, it's not there for you yet. So it's not really a regular part of your life personally.

Ryan: Correct. Yeah. And again, I think if I were to suffer from some certain maladies, I would probably consider it based on the research and the data that I've seen. And I think that when you look at where there's good evidence, it's in seizure control, it's an appetite stimulation, it's in reduction of nausea and vomiting. It's in anxiety. But again, steering more towards CBD products.

Ryan: On the anxiety side of things, I think THC we've seen really well in our research can be a very effective hypnotic. But like other hypnotics, you shouldn't take it every night. And that's again one of those things that people kind of don't really recognize. You talk to sleep medicine specialists, even the benzos and the other hypnotic medications. No one prescribes those to be taken every night for indefinitely.

Ryan: But that the problem is, is that's what a lot of people how a lot of people use THC as they say, well, you know, I been using smoking cannabis for 20 years, and it's the only thing that helps me go to sleep. I kind of argue back to some of them that, have you gone a month without smoking?

Ryan: Have you taken a tolerance break? And a lot of people are surprised that when they do that, maybe after the withdrawal wears off, because what ends up happening you will roughly stop. You don't sleep well. We talked about that withdrawal thing earlier. By the time your brain readopted to not consuming THC every night, you could be sleeping just as good, if not better, without it.

Ryan: And then you get into some some behavioral sleep medicine treatments and even better after that. So but we've also had people where, you know, it turns out that it's been masking underlying mental health disorders or sleep disorders for years.

Brent: Yeah. Those cycles are so pernicious. I know the same thing happens with alcohol. I need a little red wine before I go to sleep, and whenever I don't have the red wine, I sleep really poorly. Well, it gets worse before it gets better. You have to not drink the red wine for a week or whatever it is, to really see what impact it's having on your sleep.

Brent: You can't just drink it every night and then one night say, I'm not going to drink it, and then complain that you know you and then assume that you that you need the wine to fall asleep. You got it. You got to let your brain, your body adjust. Same is true for for THC. So maybe lastly, what are you most excited about from a research perspective?

Brent: What is baking and in the oven that we're looking at that you're looking at that you're just really excited to see the results of, or you're really optimistic about what's coming.

Ryan: I think a couple different things on my end right now. One is, again, this longitudinal study that we're running right now, I think is going to be really fascinating. Any listeners out there who are thinking about trying cannabis and want to be part of this study, cannabis and health, if you go there, you can click on our study and register.

Ryan: But we're going to be following people for a year, any health condition, any cannabis product. And I think that this study is going to help us identify rare health conditions that don't have good alternative treatments for which cannabis could be particularly helpful. And these are things like endometriosis, things like Crohn's disease, Tourette's, where you at autism, where the existing treatments are just leave a gross unmet clinical need PTSD again, and that we can use that data from this long observational study to identify not only patient cohorts that show really good benefit, but what kinds of products and at what doses and what frequency that they're taking.

Ryan: So we can reverse engineer this natural history data into targeted clinical trials. We can say, all right, given everything that people say cannabis is good for, these are the 3 or 4 things that really stand out. And this is where we need to invest resources in clinical research to figure things out and help these folks. That to me is I think the what I'm most excited about moving forward is, is to get out and get away from the cannabis is good for everything.

Ryan: Let's find out what it's really good at and drill down and get really targeted. Therapeutics developed. Harnessing the endocannabinoid system to help folks. And along the way, we'll probably find a couple things where it's pretty good for this, but we're not really any different from something else. And we'll probably identify certain subgroups of people that should not try cannabis.

Ryan: And just like any other medication, there's going to be a subgroup of people that don't respond well to it that have more harm than good. And we need to know and identify those folks and educate them to keep them from going through that. Just as much as we want to identify the people that we think it might be helpful for.

Brent: Wonderful. Well, Doctor Ryan, thank you so much for the time. And thank you so much for your work.

Ryan: I appreciate you having me on your podcast, man. Thank you.

Brent: The Life Lab by Death Clock is recorded in Boulder, Colorado, sometimes San Francisco, California, produced by Patrick Godinho, music by Patrick Lee, and hosted by yours truly, Brent Franson, founder and CEO of Death Clock.