Well, hello, I just wanted to say thank you for those who may be participating or watching this presentation. I just want to give you a little background about myself. My name is Ken Finn. I am a practicing pain medicine physician in Colorado Springs since 1994. I am board certified in physical medicine and rehabilitation, pain medicine, and pain management. I am the current president of the American Board of Pain Medicine, and I have served on their exam council for over 20 years. I served on Colorado's Governor's Task Force for Amendment 64, which legalized marijuana for recreational use, and served on the Consumer Safety and Social Issues Workgroup, and served four years on our state's Medical Marijuana Scientific Advisory Council. I'm certified in cannabis science from the University of Colorado Health Science Center, and I've been an invited speaker to the United Nations Commission on Narcotic Drugs in Vienna this past March, and I've testified to the Canadian Senate on their marijuana bill, as well as the New York General Assembly, and I speak internationally on the health impacts of marijuana, including being invited speaker to the Mayo Clinic, Jacksonville, Royal College of Surgeons in Ireland, UCLA VA Medical Center, Texas Medical Society, among many, many others. I'm the editor of Cannabis in Medicine, an evidence-based approach, and currently co-vice president of the International Academy on the Science and Impacts of Cannabis, which is now a member of the Vienna NGO Committee on Drugs, working with the United Nations on international drug policy. So we have a lot of ground to cover, and I want to initially talk about this relationship between cannabis, opioids, and then discuss some of the public health concerns. Some of the objectives I want to cover is explaining the effects of increasing access to marijuana that may have on communities, describe the public health impacts across multiple organ systems, and illustrate to your colleagues kind of these public health impacts, particularly to the healthcare system when there's an increased access to marijuana. Some disclosures, I do get honoraria for public speaking and royalties for my medical book, but I can tell you it's not a very good retirement plan. When you're talking about the basic science of cannabinoids, here you have three molecules. One is the real plant-based tetrahydrocannabinol, or THC. The other is the synthetic THC, dronabinol, which has been around for nearly 40 years. And the other one is CBD, or cannabidiol, which is the other cannabinoid isolated from the plant that doesn't have really psychoactive properties, but does have its own bag of problems, which we can discuss later. But you can see they're very molecularly similar. And that's the answer to what the molecules are. So even though they look very much alike, they do have similar yet different actions in the body. For those that may have participated in the pain clinic, sometimes this is how you feel at the end of the day. It is a very challenging patient population, but can be rewarding at the same time when you can alleviate a person's pain and suffering. This is a very important slide to understand what the difference is between cannabis-based medication and medical cannabis. Cannabis-based medications are registered extracts. They have very well-defined and standardized content in terms of THC or ratios of THC to CBD. Examples, like I've already mentioned, dronabinol, which is semi-synthetic, Sativex, which is a natural cannabinoid that comes from the plant that is a one-to-one, nearly a ratio of THC to CBD, but is not available in the United States. And I'm going to bring up Sativex later when we talk about the National Academy's paper from 2017. Epidiolex is FDA-approved natural CBD that has very little to no THC in it, and it's approved for a very narrow spectrum of pediatric seizure. The people from Alabama that got Epidiolex through the FDA and did the research were those who wrote my chapter on seizure, so it's very well done. Medical cannabis, on the other hand, are just plants, plant material, like the flowers, the buds, concentrates that are used for medical purposes, but unfortunately are poorly regulated or tested for contaminants. I've been following this data for many, many years. I don't think they have any updated one. The data is very similar over time, is why do people go to their doctor? They go for hypertension and diabetes and asthma and obesity, et cetera. But as a pain physician, there's only one pain diagnosis in the top 20 reasons people go to the doctor, and that's knee pain. Others not in the top 20 are things like back pain, neck pain, fibromyalgia, cancer pain, seizure, et cetera, because pain is a very large umbrella with different types of pain underneath that. But knee pain, likely osteoarthritis of the knee, is the only diagnosis why people go to their doctor. So coming back to a kind of a scientific molecular basis, why, and I want to highlight and outline this relationship between cannabinoids and opioids. The systems are very synergistic. They both belong to the same kind of receptors, the G-protein-coupled receptors. When they're activated, both of them reduce intracellular levels of cyclic AMP, which in turn helps modulate neurotransmission. Both receptors are found at presynaptic terminals of the nerve endings, and they also co-localize in what are called GABAergic neurons, which are the interneurons in the central nervous system that modulate pain pathways. And they actually share pharmacologic profiles like antinosusception or pain relief. So from a molecular basis, cannabinoids should provide, and do, I think, provide antinosusception. Other things like drug reward, reinforcement, hypotension, and sedation are very similarly modulated by both the cannabinoid and opioid systems. Naloxone, which you know is the antidote for opioid overdose, has been shown to have effects on the cannabinoid system in many animal model studies. So why do people use or turn to cannabis for use? This was a very nice review of reviews published a couple of years ago. And pain, by far, is the number one reason people seek the use of cannabis. And as I mentioned before, pain is a very broad diagnosis. There is somatic pain, visceral pain, neuropathic pain, psychogenic pain. So there's different types of pain. But pain as an umbrella is kind of the primary reason people tend to use or recommend the use of cannabis for. And pain is a problem. I mean, this came out just a few months ago at NIH. Despite the fact more states are legalizing for medical use, and despite the fact that they're touting marijuana as a pain reliever and it's going to help our pain problem, opioid epidemic, the cases of chronic pain continue to get worse over time. So it doesn't seem to be impacting chronic pain. And we are in the middle of an opioid epidemic, an overdose epidemic. It's been on the radar for many, many years. And going back to the National Academy's paper that I mentioned earlier in 2017, the conclusion was there's substantial evidence that cannabis is an effective treatment for chronic pain in adults. However, if anybody's read that particular paper, the devil's in the details, and they didn't look at dispensary cannabis or medical cannabis. They looked at things that aren't available in the United States, like the nabixamols, I mentioned Sativex, and they looked at synthetic cannabinoids. But that's what people are not using. They're not using the synthetics, and they can't use things that are not available. So the National Academy's paper didn't even look at what people are actually using. And I tried to get in contact with the authors, but they never responded. But the data, and again, from a molecular basis, it should work. And papers several years ago, nine years ago, showing that medical cannabis laws show a lower state-level opioid overdose mortality. This is a Bok-Huber study from 2014. Bradford study a few years later show that medical cannabis laws show reduction in opioid prescribing in a very select patient population. And that's part of the flaw of this study. They didn't use whole patient population, they use a very select patient population. And by 2018, the opioid epidemic was on our radar already, and pharmaceutical companies were creating long-acting formulations, abuse deterrent, tamper-resistant formulations. So yes, the number of prescriptions were going down. This is not necessarily related to passing medical cannabis laws, but in terms of partly a response to the opioid epidemic from the pharmaceutical companies. The pendulum began to swing around 2018, and a Lancet article shows that there's no evidence that cannabis showed a reduction in pain severity or an opioid sparing effect, because one of the platforms to legalize is going to help our opioid crisis. We're going to get people from a substance like an opioid that will cause an overdose and get them onto something that may be considered more safe, because people don't stop breathing typically when they use cannabis. Chelsea Shover and Keith Humphreys from Stanford in 2019 actually used the same methodology of Bokuber and showed that states passing medical cannabis laws actually showed nearly 23% increase in overdose deaths. So despite public sentiment and public opinion that passing medical cannabis laws are going to help our opioid crisis and improve our overdose crisis, it doesn't seem to be the case. More data continues to come out. Babylonis out of Kentucky reviewed the same literature and concluded that it doesn't help with chronic pain. There's no cannabinoid-mediated opioid sparing impacts. Segura out of Columbia in 2019 shows that medical marijuana law enactment does not show a reduction in individual prescription opioid use. It kind of goes against the grain of the hypothesis that people are going to substitute marijuana for prescription opioids. Kim came out with the same conclusion last year, that the impact of having a medical marijuana card ownership on pain. As just a disclosure, I was a former registered medical marijuana patient in the state of Colorado. Full disclosure, I don't use. However, based on my interactions with my patient, I was curious to see how easy it was to obtain a medical marijuana card. And without lying or making anything up, I was approved for my medical marijuana in 60 seconds. There was no physical exam. There was no medical record review. I wasn't even asked my level of pain because I need my knees replaced because I've been a very active youth and I've had multiple knee surgeries. And on a day-to-day basis, my personal pain runs between zero and two at a 10 scale. But I was approved for severe pain in one minute. And it was so easy to get and obtain my medical marijuana card. And I renewed it a year later with no fanfare. It was very easy to get that renewal without any questions asked, really. If you obtain a medical marijuana card, you actually may have a higher incidence and severity of cannabis use disorder and no impact on your pain. Here in Colorado, if you look at the number of marijuana recommendations, more than half of them were provided by 10 medical providers in 2022. Three of those providers or three of all the providers made one-fourth of all of the recommendations. And one person made between seven and 8,000 marijuana recommendations in one year. And if you do the math, that's physically impossible to do a comprehensive history and physical examination on person. I mean, you are really basically, it's the pill mill of marijuana. You are just seeing a patient every 20 minutes. It's cash, $2.50 for every 15 minutes, so $1,000 an hour. Do the math. This person's making a ton of money off these bogus marijuana recommendations. In Washington, D.C., you don't even need a physician's supervision to be a medical patient, which I don't really understand why even call them a patient if you're not supervised or managed by a medical provider. This happened around June, July of 2022, I believe. And you can see the number of medical marijuana patients in Washington, D.C. significantly increased after that requirement or lack of requirement to have a physician involved in your care. Here, it was a nice paper showing that medical marijuana users actually use medically 20% of the time and recreationally nearly 80% of the time. So are people simply medicinalizing their recreational use? This appears to be the case. And I've had similar discussions with some of my patients that tell me it really doesn't help with their pain. And really, it's cheaper to go through the medical marijuana program than the recreational here in Colorado because of the tax structure. It's more expensive to get the recreational marijuana. So here's a nice paper that came out of San Diego looking at the therapeutic window of pain relief. And again, I know I may sound nihilistic, but from a basic science and molecular perspective, cannabinoids do modulate pain neurotransmission. You need a lot of marijuana in your system to have any significant impact of your pain. The therapeutic window based on this one study, it was a small study, shows pain relief is going to occur when you have between 16 and 30 nanograms per ml in your system. That's a lot of marijuana. And although I don't believe in per se limits for driving impairment, Colorado has a 5 ngs per ml to be considered impaired driving. So you need three to six times of what will be considered impaired driving in Colorado to have a therapeutic impact on your pain levels. But similar to opioid hyperalgesia, higher doses of THC actually lead to less effect and actually an increase in pain. And that was followed up by a paper just a couple of months ago in the American Journal of Addictions that daily cannabis use may make chronic pain worse by reducing tolerance. Here's similar to hyperalgesia that we see in opioids. A couple of months ago, there was no effect found between placebo and active treatment of cannabinoids alone or in combination on neuropathic pain or spasticity in patients with multiple sclerosis or spinal cord injury. This kind of was a pretty big statement because for many, many years, the nabixamol, the Sativex that's not available in the U.S. was utilized in Canada and Europe for MS-related spasticity, which can be painful. But just a couple of months ago, this was found not to be the case. So I want to, again, circle back to this relationship between cannabinoids and opioids because it's very tight and very integral to each other, partially because of the basic science and how they are stable mates, for lack of a better term, and how they work very similarly. This is a very important point. I'm going to circle back to this one later. The number one risk factor for an adolescent to misuse their opioids is having ever used marijuana, lifetime use. This was based on the Youth Risk Behavior Survey from 2020. So remember this point because I will come back to it. A second point that I'm going to come back to later, after three years of first trying marijuana compared to opioids, marijuana has a higher percentage of addiction in adolescents. And I was very surprised to see this as a pain physician. I would have laid, I would have bet money that opioids were higher addiction rate than marijuana in the adolescent population. This was JAMA Pediatrics from a few years ago. Wateker actually came up with a very interesting matrix in adult opioid misuse, and the predominant predictor was having used marijuana before the age of 18. So again, this tight relationship between cannabis use and opioid use or misuse. And I'm going to circle back to these in a little bit. I don't know what happened here. Resume, there we go. This was a nice paper out of, let me go back. This was a nice paper, Olson's paper from 2018. Cannabis use increases the risk of developing opioid use disorder or misuse of opioids. This was a very large study that was published in 2018. The only concern I have about this particular study was they were looking at products that had a very, very low potency compared to the products of today. This was in the early 2000s to 2004. They did two waves and followed them three years later. And I think the retention rate was 34,000 people, so it was again, a very large study looking at much less potent products. That was the only concern I had about this study. So even back then, using cannabis increases your risk of opioid use disorder or opioid misuse. And if you look at the fatality analysis data and the National Roadside Survey data, drivers testing positive for marijuana were much more likely to test positive for prescription opioids more than other substances. It was the number one substance. The National Survey Drug Use and Health a couple years ago published nearly 76,000 people over the age of 50. Again, past year marijuana use significantly associated with an increased odds of opioid dependence and past year non-medical opioid use. This relationship is very, very tight. And it seems to be the marijuana use precedes the opioid use. I'm going to talk about that in a little bit. So here are some of the pain organizations from around the planet. The International Association for the Study of Pain is the largest international pain organization in the world. And they had a nice paper, actually they had a series of I think 11 papers that kind of outlined, scouring the literature, dozens of researchers and scientists and experts in the field. And they actually concluded that the lack of high quality clinical evidence, they don't endorse the general use of cannabis or cannabinoids for relief of pain. That was shortly followed by ANZA, the Australian New Zealand College of Anesthetists and their pain medicine faculty. They felt that the data was very low quality and is unsupportive of using cannabinoid products for chronic non-cancer pain. Other organizations like the Australian Pain Society, the New Zealand Pain Society, the British Pain Society, European Pain Federation, all have these kind of very similar recommendations. The thing I liked about the European Pain Federation was it was the first organization to address potency, and it was the first organization to address kind of a black box warning of not recommending cannabis-based medications to patients that are taking opioids or benzos. So because they're all centrally acting and there was maybe a higher risk of overdose. I don't know how or why they came up with a 12.5% THC number, and I think I may have time to cover the psychosis in some of the European data on potency products. National Institute of Healthcare Excellence in the UK, they don't even recommend using CBD unless part of a clinical trial. So here in Colorado, we voted for medical marijuana in 2000, and we implemented it in 2001. And again, the platform to legalize is going to help our overdose crisis because the overdose crisis and opioid crisis was kind of starting to hit mainstream media and get more attention from providers and pharmaceutical companies. But the mantra was, it's going to help our problem. And over 80% of the marijuana recommendations in Colorado are for pain. So here is the state of Colorado in a map. I live in El Paso County, which is kind of almost center right in the map, about an hour south of Denver. This is 2002, so a couple of years after we implemented our medical marijuana program. And this is what happened to our overdose problem, 2005, 8, 11, and 14. It hasn't helped our overdose problem, has not helped our opioid problem. It just seems to have gotten worse. But again, public doesn't understand this. They don't see this data, and it's just gotten worse. We talked earlier about opioid prescriptions going down. And the CDC is following this, and yes, they are going down. And I think it's multifactorial. I mean, some doctors are fearful of prescribing or they're reluctant to prescribe. There's long-acting formulations, tamper-resistant formulations. Even some pain physicians in my community don't prescribe opioids. But our deaths continue to rise. This is the 2021 data. 22 data, it's actually gotten worse. I think there were 111,000 overdoses in the year prior. It went up during the pandemic. And here in Colorado is kind of a graphic from the Colorado Department of Public Health Environment, who I have a pretty good relationship with. And you can see in 2001, we implemented medical marijuana. And it's kind of laid dormant until 2009, because there simply wasn't really any infrastructure. There were no dispensaries. Doctors were afraid to recommend. Patients didn't know where to go. They didn't know where to get product. So it was kind of dormant for a while. But in 2009, we had for what I would term de facto legalization, where the dispensaries opened across the state to the point that even currently they outnumber the number of Starbucks and McDonald's combined. And then we had legal, we voted to legalize for recreational in 2012, implemented in 2014. And you can see that our drug, multiple drugs, you know, meth, other psychostimulants, cocaine started to rise after that. Heroin, interestingly, is somewhat on the decline. I think it's been replaced by things like fentanyl and tranq and some of these other analogs that are coming out that much more addictive than heroin, as cheap and readily available as it is. So that was the 2019 data, the 2020 data. You can see that fentanyl kind of, I thought, took off kind of on its own. And it looks like the COVID curve. But other drugs also continue to rise, like methamphetamine and cocaine and fentanyl and opioids. And the 21 data, actually the CDPHE had to compress the graphic because we had so many more people dying from drug overdoses in the state. And here's the preliminary 2022 data. And, you know, maybe we have hit a nadir, I guess, or if you want to call it a low point, you know, nadir, but maybe we're hitting a turning point where we're maybe seeing a plateau or hopefully a decrease in our drug overdoses in the state of Colorado. But one to one, a year to year data point does not equal trend. You can see in the blue graphic on the top, it's kind of up and down, up and down, up and down, but the overall trend is up. And interestingly, marijuana mentions became more prevalent around 2018-19 and have continued to rise. Is this a companion drug? Is it a synthetic THC? I've been trying to work with our state public health department and coroners because they don't tend to differentiate between synthetic cannabinoids and the THC from the plant. So it's a big question I have, and I'm trying to have the state coroners and the CDPHE further clarify this because it seems to be on the rise. And I don't know, maybe there's some people that are dying from synthetic THC like K2 and spice, or is this simply a companion drug that is being found incidentally in overdose deaths that seems to be on the rise? They tend to play well together. Just last month, Monitoring the Future came out with marijuana use and hallucinogen use and binge drinking are historic highs among adults, 35 to 50. But here in Colorado, we have legal psychedelics and we've had legal marijuana, and these are all quote medicine. But the historic use is certainly going up. Marijuana use and vaping were at the highest levels ever. And seeing marijuana hallucinogens and vaping nicotine and marijuana are higher than ever among young adults. So it's kind of social norming 101. This happened with big tobacco, it's safe, doctors prefer camels, dentists prefer viceroys or what have you, and everybody thought it was cool. And I think we're seeing the same playbook unfold before our eyes despite trying to show the comparisons and illustrate these relationships that now these people are using more marijuana hallucinogens over time. This is kind of Texas data, they've kind of gone up as well. They don't even have marijuana other than medical. Canadian overdose data is going up as well. They legalized in 2018 and they've seen an increase in the overdoses in Canada. So I helped publish a paper a couple years ago showing that fentanyl death rates are higher in marijuana legal states. And again, I was a little surprised. Initially, I thought fentanyl kind of spun off into its own beast because it is somewhat of a scourge. But opioid deaths are increased more where marijuana was legalized. Here's the graphic from that paper. And you can see that there's a pretty significant gap between the states at the time that had legalized and the ones that did not legalize in terms of the fentanyl death rates. This was followed up by a very similar conclusion by a different paper, different authors, that legal medical marijuana, particularly when you get it through a dispensary, shows a higher opioid mortality. So independently, other authors came to the same conclusion. We just published a paper earlier this month showing that marijuana legalization opioid mortality trends before and during the first year of COVID. And there's plenty of data showing that cannabis use went up during the pandemic. And our paper shows that the jurisdictions that implemented recreational marijuana prior to 2019 had significantly greater increases in both overall opioid and fentanyl death rates than those jurisdictions with medical only legalization. So even those that are not using medically and using more recreationally, those states are showing higher opioid and fentanyl death rates. So again, this really goes against the grain of what public sentiment may be and what the states that are going down this road are telling the voters. Just last year, that cannabis isn't any better than placebo in the treatment of pain, June of this year, there was no impact on prescribing opioids, prescribing non-opioids, or any interventions for pain with medical cannabis laws. So again, the data is mounting and piling up that it's just not helping our drug crisis. This paper a few months ago looked at some of those trials in cannabinoids for pain management, and actually most of them showed no benefit. And so the current body of evidence just simply does not support the use of cannabis or cannabinoids for pain or PTSD. And they did use a very particular military population. But again, and we won't have time really to discuss PTSD and the use of cannabinoids in that patient population. Perioperative cannabis use, I published a paper a few years ago that patients using cannabinoids, either medically or recreationally, need to be thoroughly evaluated prior to surgery. This was followed up earlier this year by ASRA, the American Regional Anesthesia and Pain Society, shows that cannabinoids in the perioperative period may have significant negative implications. So ASRA is recommending screening patients that are undergoing surgery because of drug-drug interactions, pain management, both pre- and post-operatively, sleep impacts, et cetera. So this national organization really says, if somebody is undergoing surgery and they're using cannabis, that you have to screen them. I actually have had colleagues in my community cancel patient surgeries and say, you need to be off your marijuana at least two weeks prior to undergoing surgery because it's fat soluble. And, you know, sometimes during those pursuit can be released and cause, you know, cardiovascular events, et cetera. July of this year, increased risk of morbidity and mortality after major elective inpatient non-cardiac surgery. That was JAMA surgery. Earlier this year, looking, focusing on young adults and adolescents, this population, which is vulnerable, they don't show reductions in prolonged use of opioids post-op when they have access to medical marijuana. So more data coming up, JAMA psychiatry from a couple of months ago, you know, most docs wouldn't consider prescribing crude cannabis or even FDA-unapproved cannabinoids for insomnia, pain, or other addiction. And the data just isn't there to support their use. So before I switch gears, and in summary is talking about cannabis and opioids. Currently, there's no evidence to support the use of dispensary cannabis for chronic non-cancer pain. And there's no evidence of substituting opioids with dispensary marijuana. There's no package insert. There's no safety precautions when patients go to or consumers go to a dispensary. And cannabis users are more likely to develop opioid use disorder, misuse their opioids, have higher negative psychiatric effects like depression and anxiety. And states with medical marijuana programs typically have higher opioid overdose deaths than non-medical states. So any real benefit, again, from a molecular and basic science perspective, there is evidence that there is some antinosusceptive effects, but that evidence is far outstripped by the current evidence of harm and lack of help. So I want to shift gears and talk about pregnancy and in utero exposure data. And again, if you're talking about marijuana as medicine, this data alone would pull it off the shelves, in my opinion. So this is a graphic of a police investigation in Colorado that had nothing to do with marijuana. However, it led police to a storage unit. And in the storage unit was this Polaroid. And I think it speaks volumes when you have the nutrient bottle at the side and somebody holding a locked and loaded marijuana pipe to an infant's face. If you look at the state of Texas and you have a child neglect or abuse fatality, what substance by the perpetrator is most often seen, either current use or active use, and clearly marijuana leads the pack. And interestingly, the number two substance is nothing. There's no substance when there's an accidental death by abuse or neglect in the state of Texas. And a lot of states don't track this data. I use this slide as an illustration that is important for states to look at this type of data, because I think Arizona, Texas, and Florida are the only states that I am aware of that are tracking this information. Not even California, Oregon, Washington, or Colorado that have led the charge in the marijuana space. But this is somewhat frightening data to really digest. So I'm going to give you a few data points as to why I am very concerned about marijuana use in pregnancy. In Colorado, more than 70% of the dispensaries recommend women use marijuana during the first trimester. And that was a survey of over 400. And so the person behind the counter is called the bud tender. And the only requirements to be a bud tender in the state of Colorado is age of 21, experience with marijuana, and a pulse. There is no medical requirement. There's no training on health impacts. But here you have 70% of 400 dispensaries tell women to use during trimester, which for me, is practicing medicine without a license to a certain extent. And we know that it stays in breast milk for up to six weeks after cessation, even though they may be breastfeeding, the baby is still getting exposed. The SAMHSA data earlier this year showed that use during pregnancy is on the rise. And that really kind of turned the corner in 2015. And I think that was kind of correlating with more states and more states legalizing for marijuana use, maybe more access, more perception of less harm, that it's more safe. And so you can see that near daily use, that blue line over time going back to 2002 is on the rise. Total percentage is low. But the fact of the matter is that more women are using daily or near daily throughout their pregnancy, the red line. They broke it down by trimester, and there's kind of ups and downs. But the general trend for near daily use and throughout total pregnancy is on the rise. The second data point I want to bring up is that what happens to those babies? Is marijuana exposure low or high or medium? Who knows? A lot of states aren't tracking this data either. I think Colorado is on the cusp of starting to look at this information despite as long as we've had program, both medical and rec. But the state of Connecticut published some information a year ago looking at the number of exposures in babies. And they looked about 4,700 over 28 months. There's about 6.6 babies a day. And the vast majority, the highest exposure was in marijuana, nearly 80%. Lower percentages for other substances, including opioids and alcohol, which was less than 3%. So in the state of Connecticut, most exposed babies are exposed to marijuana. So what happens to those babies as they grow? And the ABCD study, if anybody's not familiar with it, I recommend you look at this information. And all my slides are cited, and they will be available for your review. So if you look at nearly 12,000 exposed babies in the ABCD study, they looked at them at middle childhood, around average age of 10. And the ones that were exposed for cannabis only, both before and after the mother knew of their pregnancy, they had greater offspring psychopathology. And those were like problems with attention, thought, and even psychotic-like experiences. So I did a literature search on PubMed when I saw this paper. And I said, well, women use all sorts of stuff during pregnancy. Is there any evidence of psychotic-like experiences to heroin exposures, meth, cocaine, tobacco, alcohol? And I wasn't able to find anything about psychotic-like experiences in those offspring. So it seems to be very unique to marijuana exposures. So prenatal cannabis exposure shows greater risk of psychopathology during middle childhood. So that's data point number three. That was followed up last year by the NIH and NIDA is that what happens to those kids as they enter early adolescence? And those behavior problems persist. And that was an N of nearly 12,000. So these cannabis exposures and the problems associated with it in the offspring continue to remain through middle childhood into early adolescence. And on the animal data that persists intergenerationally as well. So I think we're kind of in uncharted waters in terms of what happens to those kids that they hit adulthood or late adulthood, or even elderly, that what kind of problems are they going to have? So June of this year, this was a very interesting study and kind of related to the ABCD study. And the question was, what is the highest risk for early cannabis use initiation? And the number one risk factor was exposure during pregnancy. And that remained despite all the other things. And here's the graphic from that paper, looking at all sorts of things, all sorts of substances, but the early initiators of cannabis use, the most, highest correlation was with cannabis exposure prenatally. So very interesting information. And we know that harm can persist and interesting. They always point the finger at the mom or bad mom for using substances. Paternal THC use has also shown to have an impact on neurodevelopment in the offspring behavior, attention reward. Here's some links to some of those. We know that first trimester exposure indirectly predicts a young adult memory. So we know that there's going to be problems with these kiddos that may be exposed during pregnancy. This one showed lifelong cognitive deficits. This came out two months ago. Prenatal exposure to animal study, prenatal exposure to cannabis and rats led to lasting substantial effects on cognitive and memory functions. And the endocannabinoid system is a very important system in the human body, particularly during neurodevelopment in utero. But the fact that there's lifelong deficits is very, very concerning. And I didn't realize why they use rodents in studies. And I think I found the answer after talking to some researchers that they have a very short lifespan, like three years. So they can study in utero to childhood, to adolescent, to adult in a very short period of time and do all the testing and research. But here in this animal study a couple of months ago shows lifelong cognitive deficits. You know, small for gestational age, stillbirth, hypertensive disorders. You know, there's plenty of information in the literature showing the harms of early use during pregnancy, low birth weight, decreased head circumference. And we know just in the alcohol world, for instance, what those physical markers may reference in terms of what happens down the road. You know, small head, low birth weight, problems with neurologic and psychological issues in childhood. So this seems to be the case as well in cannabis. Increased risk of preterm birth, increased risk of autism. This was a very interesting study from a couple of years ago. And Stuart Reese from Australia actually published a paper a few years ago showing and demonstrating that medical marijuana states had an over 20% higher incidence of autism spectrum disorders than non-marijuana states. And there's plenty of information about the autism link due to DNA methylation for autism genes. So this we know can help, you know, the THC alters placental and fetal DNA methylation at genes that are involved in neurobehavioral development, and that may impact offspring outcomes. So despite the fact that we've known that there may be this link, the more recent data is showing from a scientific perspective how and why there may be this link. Paternal cannabis use a couple months ago, adverse reproductive health and offspring outcomes. I mean, the data is more clear, and this is the graphic from this JAMA article about maternal and paternal marijuana use during pregnancy in the placenta, the fetus, and the offspring. You know, there's harm, and I think the data is becoming much more clear. And we talked about use during pregnancy with the SAMHSA data, and this was a follow-up study just a few months ago about increasing risk of use during pregnancy and the health disorders. Pregnancy hospitalizations in Colorado increased when there's a higher density of dispensaries. So there's a more two-fold increase in pregnancy-involved hospitalizations between 11 and 18, which is just post-de facto legalization and just prior and after implementation of recreational marijuana. So the recreational market may influence cannabis use among pregnant individuals in the state of Colorado. Canadian Medical Association also shows the same type of data. And here's kind of a graphic from a different paper showing the animal and human impacts of in utero exposures. I want to talk about pediatric exposures, you know, so now the kids are born and what's going on here in Colorado. The number of kids, zero to five, and their accidental marijuana poisonings are going up, despite the fact we are required to have childproof and tamper-resistant packaging, et cetera. They obviously get into the products and end up with a poisoning. This interesting paper came from the Academy of Pediatrics, January of this year. Over time, there's been a 1,375% increase in pediatric poisonings, marijuana poisonings. 70% of those cases that were followed with a known outcome had central nervous system depression. So little children do not metabolize cannabinoids like an adult does, and they can be much more harmful. Nearly 23% of those patients were admitted to the hospital. And here's the graphic from that paper showing the significant increase over time of pediatric cannabis ingestions. Academic Pediatrics showed a very similar data. This is a huge study looking at 52 children's hospitals in the Pediatric Health Information System database over a 14-year period, and it came up with a similar percentage, a 13-fold increase or 1,300% increase of exposures in 2018 compared to 2004. In that particular data set, 15% of those kiddos required ICU care, 4% required mechanical ventilation. So these kids are getting intubated when they have cannabis poisonings. And here in Canada, this was very interesting because you can look at some of the more populated provinces of Ontario, Alberta, and BC, and Quebec. And you can see that the pediatric poisonings over time, you know, they implemented legal in 2018. You can see what happened after 2018. But why did Quebec have a flatter curve? And in this paper, they kind of discussed the fact that Quebec has a potency cap of 30%, which in my opinion, personally, I think it's too high. But the other provinces do not have a cap on potency. And they did try to address it in the paper that maybe that would be an explanation as to why Quebec has a flatter curve in terms of the number of kiddos with marijuana poisonings. And there's the Texas graphic again. Here's a picture from Odessa, Texas. You know, they have, you know, legal, they don't have recreational marijuana. They don't have medical marijuana for THC, Delta-9, that sort of stuff. But they have a lot of hemp products where you can manufacture THC analogs. And you can see in here, they actually say THC in it, even though that's on the left hand side. And there's a drive up window. And my friend that took this picture said there's a line out the door at six o'clock in the morning, you know, buying these analogs like Delta-8-THC and THC-O, the acetylated THC, et cetera. So now we're gonna move to the adolescent population here. Monitoring the future study shows adolescents that are smoking and vaping nicotine were more likely to report past 30-day cannabis use. So cannabis use with vaping has continued to accelerate in this population. May of this year shows nicotine pattern use were strongly associated with a higher likelihood of cannabis use and binge drinking with cannabis use being much higher. In Colorado, they're not really doing age checks very well. There was a 90% decrease in compliance checks for age by the Marijuana Enforcement Division. In 2021, they only did 80 underage compliance checks with twice as many employees where the Liquor Enforcement Division did 25 times more of that with half as many employees. I don't know what makes it so challenging to do compliance checks when you have those employees. Sam Wong, who's a pediatric emergency room specialist at Denver, published a paper that there was an increase in teens coming to the emergency department after legalization. Again, we had de facto legalization in 2009. Even though we voted to legalize in 12 and implement it in 2014, the dispensaries and the access was widely available starting in 2009. And the number of kids going to the emergency department continue to go up with nearly 70% of them with psychiatric events. And you're talking about depression, psychosis, suicidality, panic attack, that sort of stuff. So I'm gonna circle back to one point I mentioned earlier when now we're talking about the adolescent population. And the link, again, I'm circling back to this link between opioids and cannabinoids in this adolescent population. Here we have, after three years of first trying marijuana compared to opioids, marijuana has a higher percentage of addiction. And here's the graphic. And this, for me, is more helpful. It's a kind of, this comes from the paper. If you look at the first and third line, with the early onset users of cannabis and opioids, they have a very similar addiction rate after one year, about 11%. Three years later, they had, those early onset users had nearly twice the addiction rate than the opioid early onset users. And again, and that remains somewhat stable, around 11%. That didn't go up in terms of addiction. But the early onset users showed a nearly double addiction rate three years later. So this early onset use, the early developing brain, and remember, what is the highest risk factor for early onset user? It was having been exposed in utero. So I find this very fascinating relationship and dots that are being connected. If you look at the later onset users of the 18, you know, the late teen, early adult users of cannabis and opioids, they did have a lower addiction rate after one year compared to the early onset users, about six, 7%. And three years later, the opioid late onset users had a very stable addiction rate, about 7%. But the cannabis users did have an increase in their addiction rate three years later, and higher than the opioid onset users. So I was very fascinated by this paper as a pain physician. I would have laid dollars to donuts that the opioids were gonna be much more addictive than marijuana in any population, but that doesn't appear to be the case. Just a couple of months ago, again, early onset cannabis use, we talked about that. There's the graphic. Depression is a very known relationship between cannabis use, particularly in the daily or near daily users and individuals with depression. These are adults and of nearly 16,000. Adults with depression have double the odds using cannabis compared to the people without depression. A couple of months ago, cannabis use disorder, common among patients who use cannabis. I mean, that's kind of a no-brainer, but moderate to severe cannabis use disorder was more prevalent in those patients that were reporting any non-medical use. So kind of the recreational users. Again, another more recent paper showing consuming marijuana was linked to the development of depression in a lot of individuals. So there's kind of this causal relationship, not necessarily a correlated relationship because I always get this argument, correlation doesn't mean causation, but I think the data is mounting that there is somewhat a causal relationship between marijuana and depressive disorder. Just last month, people that use drugs, what happens to them is in BMC psychiatry, opioids followed by cannabis and stimulants were the most prevalent drugs of use in people who use drugs who died by suicide. So all these drugs tend to play well in the sandbox and cannabis is always at the dance. I mean, it's always reported to be so benign and so herbal and natural and safe, but it seems to be at the dance very often. There's a strong association between young adult depression and cannabis use following legalization recreationally in the US. So maybe increased access, coping mechanisms, et cetera, may be at play here. Here's a patient of mine who became suicidal after consuming CBD oil. And people are like, well, that's interesting. But if you actually go to the Epidiolex website, which is FDA approved CBD or cannabidiol, and you look at warnings and precautions, you're gonna see liver damage, sedation and suicidal ideation behavior. This patient of mine fit the bill of consuming CBD and becoming acutely suicidal. So we know this relationship between depression and suicidality. GMA Pediatrics a couple of years ago, cannabis use disorder was a risk marker for self-harm, all cause mortality and death by unintentional overdose and homicide among use with mood disorders. So violence is kind of in the mix. Cannabis use associated with non-fatal self-harm and all cause mortality. American Academy of Pediatrics, I actually talked or had conversation with the author on this one. They looked at adolescence and suicide related behaviors and adolescent prescription opioid misuse had an increased risk of suicide related behaviors. But remember, I was gonna circle back to the point is what is the number one risk factor for an adolescent to misuse their opioids? It was having ever used marijuana, lifetime use of marijuana. So is there, we know there's a direct pathway between cannabis use and suicidality, but now is there an indirect pathway by progressing to opioid misuse and then to suicidality based on this paper? It's a good question. But now marijuana is the most prevalent substance found in completed teen suicide in Colorado. And this was from a couple of years ago, 2020 data, nearly one third of completed teens, teen suicide in Colorado had marijuana followed by number two, alcohol, which is about half of the marijuana presence. And then that's just gotten worse. This was the 21 data that nearly 43% of completed teen suicides in Colorado, marijuana was present followed by number two, alcohol. It never used to be that way. Alcohol was typically number one. Marijuana was somewhere in the pack, nowhere leading the pack. And you can see on the left-hand side of the screen, there's clearly some behavioral issues with thoughts of suicide, treated for mental health issues, current depressed mood, recent crisis, all the risk factors, but marijuana seems to be there most often. And it's probably a bidirectional relationship. I mean, they're not dying from their marijuana use. It just happens to be in their system, but are they using because they're depressed or are they depressed because they're using? It probably goes both ways. Here's the toxicology of all Colorado residents in suicide where most of the time there's no substance present, but very close after that, marijuana is present followed by the other usual suspects like alcohol, opioids, and other illicit substances. This was a very interesting, this came from the CDC and the YRBS from 2021 that was published a few months ago, where youth suicide risk, cannabis use and guns intersect. I find this very interesting because this is a very vulnerable population. I'm sure many of the mental health providers take care of adolescents like this. So if you look at the suicide risk, either you're packing heat or not packing heat. For me, it's like, I don't know how many kids are actually carrying guns, but apparently there are. But if you have some that are carrying guns, they have a higher risk of considering or attempting suicide. And this is the gun toting population. If you look at the substances involved, either carrying guns or not carrying guns, marijuana is the most common substance in those kids that are carrying guns or not carrying guns. And then, you know, reference that to attempting or considering suicide. So there's this intersection between youth suicide risk, cannabis use and guns. Earlier this year, there's a higher rate of suicidal behaviors among youth that use marijuana in the past year. Archives of suicide research just a few months ago, cannabis use, higher increased risk of transitioning from suicidal ideation to suicide attempt, whereas there was no association found with alcohol. So medical marijuana laws, recreational marijuana laws showed an increased suicide-related mortality in female youth. They tend to be a little more risk category. And the youth 14 to 16, a higher rates of suicide in states with recreational laws compared to states with medical and states without medical. In Colorado, you know, the CDPHE in Colorado, the Public Health Department Environment, they actually do a lot of good data tracking, although I think there's a couple of other things they need to start tracking. They had outcomes in these adolescents. Patients age 13 to 17 had a higher discharge rate from hospitals due to marijuana of any age group from both emergency departments and the hospital. And they were basing it on coding with cannabis poisoning, abuse, dependence, and intoxication. This was a very good study because not every adolescent is gonna develop a cannabis use disorder. And actually non-disordered cannabis use was four times as prevalent as past year cannabis use disorder. So it's a larger population, but those patients that had non-disordered use still had two to four times greater odds of all adverse psychosocial events, including depression, suicidal ideation, concentration issues, lower GPA, arrest, fighting, and aggression. So this violence thing that we don't have enough time to talk about is certainly part of the picture, particularly in a younger developing brain. Our Colorado Department of Public Health and Environment, frequent use by Colorado youth associated with psychotic disorders. So we're starting to bridge this gap into psychoses. Daily or near daily marijuana use by adolescents is strongly associated with developing a psychotic disorder such as schizophrenia. I mean, we know schizophrenia is on that spectrum of psychoses, and it's probably the end all be all of psychoses, persistent psychosis. And we know there's a huge health impact on that. But in Colorado, we're showing that those kids with daily or near daily use can develop psychotic disorders, which includes schizophrenia. Worse with higher doses, and probably potency has a role in that as well, I would believe. Interpersonal abuse. This is an interesting study from about six months ago, looking at college students. Those who only use cannabis had higher odds of psychotic experiences, as well as those who only experienced interpersonal abuse. But those that are using cannabis and have interpersonal abuse had the highest odds, which exceeded the sum of the individual impacts. So if you have somebody that's an abusive relationship that's using marijuana, they may have some psychotic issues. May of this year, we know cannabis is a very well-established risk factor for psychosis. This is interesting because people reporting their reason for first using cannabis was to kind of feel better, but kind of, I guess, from a medical perspective, they were more likely to progress to heavy use and then develop a psychotic disorder than those that were kind of using because of friends or more recreational. This is kind of a direct quote from the paper. So does the history of cannabis use influence onset and course of schizophrenia? And the burden of schizophrenia is greater in those who have used cannabis during adolescence. So again, this adolescent vulnerable population is a very, very critical population to educate and try to avert their cannabis use. And this was a very fascinating study that came out of Denmark earlier this year. And I can't pronounce the guy's name, but he's one of our physician advisors at Isaac. But he looked, it was a very large, long study, 6 million Danes over 50 years going through the health records and young men with cannabis use disorder have a higher risk of developing schizophrenia. And they, the authors estimated that nearly up to 30% of schizophrenia cases may have been prevented by averting cannabis use disorder. That is a huge number, a very huge study, very important study. And, you know, this correlation causation debate on cannabis and schizophrenia is ongoing. And actually we have this particular author did author another paper that if you actually use the Bradford Hill criteria, there is, that you can show there's probably a causal relationship using that criteria, which we don't have time to get into. But there's the graphic in the psychosis and schizophrenia. This came out just last month, a few weeks ago, substance-induced psychosis show increased risk of developing schizophrenia spectrum disorder. We know it's a spectrum, there's different levels and grades of schizophrenia, but cannabis had the highest transition risk to schizophrenia or schizophrenia spectrum than those without psychosis. So younger age, male sex, a higher risk of transition to schizophrenia spectrum disorders. I just want to kind of wrap it up with a few other medical impacts. We just don't have enough time to cover all bases. We know there's an impact in memory. The brain is a target organ in marijuana world where we know like the alcohol is liver, smoking is the lung, in marijuana, it's the brain. The brain is a target organ. This was a nice study from last year showing a long-term study of people from adolescence to age 45 or middle age. There was a 94% retention, which is great after a 45-year study and showed a decrease in IQ points of about five and a half compared to the childhood IQ. So there's evidence of IQ decline. If those of us who may be old enough to remember, one of the reasons they pulled lead out of lead-based paint was because it dropped your IQ about four points. But nobody tends to talk about this particular data point showing there may be a loss in IQ with marijuana. And the area that modulates memory, the hippocampus has smaller volumes compared to the occasional and non-users. So the long-term heavy users, frequent daily, near daily users have smaller areas of the brain that modulate memory. We know medical cannabis and recreational cannabis laws show a significant role in the development of cannabis use disorder. So we need to screen them. The heart is the number two target organ. Robert Page, who was another one of my authors who talked about drug-drug interactions was the lead author on the American Heart Association paper showing the risk of a myocardial infarction, arrhythmia, sudden death, stroke. It's there. We know that the cannabis users have a higher risk of heart rhythm disorders compared to non-users. They have more SVT per day, more PACs per hour and more non-sustained VTAC during the day. So it does impact the heart. There's some more science on the cardiovascular system, epithelial cells. Earlier, this is very interesting. This is looking at young adults. People who use marijuana daily were one third more likely to develop coronary artery disease compared to those that never use the drug. So there is an impact on the cardiovascular system. Peripheral vascular disease, they showed things similar to thromboangitis obliterans, which is in the peripheral arterial disease family. This was presented at the Society for Cardiovascular Angiography Interventions at their recent annual scientific conference. Acute cardiovascular events, recreational drugs, a higher rate of in-hospital major adverse events. And cannabis was very high up there, 9% of those recreational drugs. Just last month in Addiction Journal, Canadian adults with cannabis use disorder have a higher risk of experiencing adverse cardiovascular disease events than those without cannabis disorder. And then the use in the elderly, I mean, it's an underrepresented population in the medical literature, but there was a 1,800% increase in older people in California representing the emergency department with marijuana poisonings. And I mean, I have my own theory. I mean, if they're allowing more use or making more recommendations and social norming to the point where it's safe, it's herbal, maybe a safer alternative. There's a lot of drug interactions people don't talk about. For example, CBD, which is considered, particularly in the elderly population, as a safe alternative than ibuprofen, has 586 drug interactions. And you can go to drugs.com and see that. But there's the graphic for the number of older people presenting the emergency department in California. Marijuana users have higher levels of toxic heavy metals in their system, blood, urine, you know, we're talking about lead in blood and urine, cadmium in blood and urine. We've had recalls in Colorado with arsenic, cadmium. We've had anticoagulant rodenticides, all these other things. So have a conversation with your patients. I published this paper for a couple of reasons a few months ago. You know, it needs to be treated like any other centrally acting substance, regardless if it's used medically or recreationally. And this is really to approximate a standard of care. I mean, I have these open conversations with my patients. And the other reason is to really protect the providers. I mean, the lawsuits are here. They're not coming, they're already here against medical providers that are making marijuana recommendations and there is an adverse event. So for example, the patient that has had three MIs, they've been stinted several times, they have hypertension, hyperlipidemia, strong family history of stroke and heart attack. That might be the patient you say, you know what? I know you wanna use marijuana, but this really might be not in your best interest. So this is kind of the reason that prompted me to publish this paper. So in summary, cannabis isn't a medication, it's a plant. We've had a lot of, we have a lot of plant-based medications like aspirin and digitalis, they come from plants. But I support drug development of cannabis-based medications, CBMs, not medical cannabis, because it doesn't meet the definition of medicine because there's hundreds of components that have a physiologic activity. I think we need to support a potency cap and eliminate home grows, track public health impacts like healthcare utilization, birth defects, et cetera, publish environmental impacts. We need to have mandatory drug testing for all violent crimes, because cannabis psychosis is a real thing. It's well-described in the medical literature. And I have a lot of the very notable violent mass shootings and stabbings in the country that have made the news. And I have the toxicology report in many of them. And there's only one substance in the system and it's THC. You know, and psychosis is a very difficult, complicated term. And I'm not saying anybody that uses marijuana is gonna have become a homicidal maniac, but there are risk factors. And there may be some signs of somebody that may go down a road of violence. And we don't have enough time to get into this, but I do have a lot of those toxicology reports. So you need to do this mandatory drug testing and publish it. Monitor kids' use, discourage use during pregnancy and lactation. I mean, they follow the American Academy of Pediatrics and American College of Obstetrics and Gynecology. I remind people we were in the middle of a vaping epidemic before COVID hit, where there was either vitamin E acetate or THC that's causing the Eboli epidemic. Drug tests, all suicides, including adolescents. A lot of states, like the state of Texas does not test, do drug testing in any suicide. And I think it's very important, particularly with the Colorado data showing that it's the most prevalent. And monitor driving-related marijuana fatalities, because they're going up, like in our state here. So it prompted me to edit a book of 70 authors, four countries, a year and a half of my life, I'll never get back, and found a nonprofit. And this is what I tend to do in my before work, so I can kind of center myself before taking care of my patients and try to do the best I can. So with that, I'm gonna wrap it up and take it from there.

cannabis

opioids

public health concerns

marijuana

cannabis-based medications

medical cannabis

neurotransmission

pain relief

chronic pain

opioid crisis