Erla Kushner. I'm gonna be talking to you today about cannabis and medical marijuana. My background is in family medicine and addiction medicine, and I am certified in addiction medicine through the American Osteopathic Association. And I'm really happy for all of you to be involved in this review course. I think it's gonna be really helpful for you when taking the exam. So welcome everybody. I have no disclosures today. The objectives for this session are to understand the short and long-term effects of exposure to any cannabis substance, to understand the short and long-term risk of exposure to cannabis, and understand what medical marijuana is and what research is being done on this. So quick overview. We're gonna talk about the history, go over some statistics, the pharmacology, adverse effects, the use during pregnancy. We'll talk about the DSM-5 criteria. We'll talk about urine drug testing, what treatments are available, and then we're gonna finish off with medical marijuana. So let's look at the cannabis history. Cannabis dates back 12,000 years. It was first cultivated in America for its fiber, and the medical use dates back to 2700 BCE. It was placed into Schedule I of the Controlled Substance Act in 1970. And when you look at some statistics on marijuana, it's the most used illicit drug in the United States. The estimates of reported use of marijuana in the past year for those over 12 years old, 49.6 million or 17.9%. Between the ages of 12 and 17 years, two and a half million or 10.1%. And for those 18 to 25 years, 11.6 million or 34.5%. And over 26 years, 35.5 million or 16.3%. And these were from SAMHSA. Use amongst both sexes and pregnant women is going up. And this may be because the perception of harm is declining. People are starting to think that it's safe to use marijuana so then the rates are starting to go up. More young people today do not consider marijuana use as risky behavior. And approximately three in 10 people who use marijuana will develop cannabis use disorder. And starting prior to age 18, the rate will increase to one in six people. The Monitoring the Future study, which also looks at cannabis, is a study that's been going on for many years that was developed by the University of Michigan and funded by the National Institute on Drug Abuse of the National Institutes of Health. And this looks at school populations for eighth, 10th and 12th graders and looks at their current use, their past year use and what their perceived harm of these drugs are. So cannabis use remains stable for all three grades surveyed according to 2023 data, 8.3% of eighth graders, 17.8% of 10th graders and 29% of 12th graders reporting cannabis use in the past year. Reported vaping cannabis within the past year reflecting a stable trend among all three grades. So 6.5% of eighth graders, 13.1% of 10th graders and 19.6% of 12th graders. The pharmacology of cannabis is interesting. Cannabis sativa is an annual herbaceous flowering plant indigenous to Eastern Asia used as a source of industrial fiber, seed oil, food, recreation, religious and spiritual moods and medicine. So tetrahydrocannabinol, THC comes in three different forms. The herbal, which is most frequently used, the dry leaves and the flowering tops, cannabis oil which is a mixture from the extraction of the active ingredients of the plant and the cannabis resin and hashish which is the cannabis resin the press secretion of the plant. Let's talk a little bit about cannabinoid receptors. So CB1, it's a G protein coupled cannabinoid receptor located primarily in the central and peripheral nervous system with a particularly high abundance in the brain. As part of the endocannabinoid system, it's activated by the endogenous neurotransmitters anadamide and 2-arachidonoylglycerol as well as other natural occurring compounds including the phytocannabinoids found in cannabis. The CB2 receptor is associated with immune cells and endocannabinoids, these are naturally produced by the body and bind to the cannabinoid receptors. THC and endocannabinoids decrease neuronal excitability in the brain by binding to the presynaptic CB1 receptors and inhibiting presynaptic neurotransmitter release. So if we look at cannabidiol CBD versus tetrahydrocannabinol, THC, THC is the main psychoactive compound in marijuana. It was first isolated in 1964, it's psychotropic, it makes people feel high. And CBD, it doesn't cause that high. It was first isolated in 1940 and it's considered a negative allosteric modulator of CB1, meaning it effectively alters the shape of the CB1 receptors. And this change makes it more difficult for CB1 agonists like THC and other endogenous CB1 agonists to stimulate the receptor. The fact that CBD does not bind to or stimulate CB1 is also the reason it doesn't produce the same psychotropic effects associated with THC. And they have the same chemical formula. They both have 21 carbons, 30 hydrogen atoms and two oxygen atoms. The difference is in how they're arranged. So if you look at the THC, it contains a cyclic ring and the CBD contains a hydroxyl group. So, cannabis formulation, so tetrahydrocannabinol THC concentrations. In marijuana, there's 0.5 to 5% and this is THC leaves and stems. In sensimilla, 7 to 14% THC flowering tops from the unfertilized plants. In hashish, the dry cannabis resin, 2 to 8% THC. Hash oil, extracting the THC from hashish or marijuana with an organic solvent, 15 to 50% THC. DABS is extracting THC with butane products and it can be up to 90% THC. And then hemp is the fibroid form. It has less than 4% THC. Delta-8 is a cannabis compound that can produce a high like marijuana. Delta-8 stands for Delta-8 THC, which is chemically a close cousin of Delta-9 THC, the principal psychoactive compound of marijuana. The purchase of Delta-8 products typically has no age restriction. And most Delta-8 is derived from hemp, a variety of the cannabis plant. There's no conclusive evidence that it's safer than marijuana. 11% of 12th grade students across the United States in the past year, according to the Monitoring the Future study used Delta-8 THC. Remember this study is taken in school settings so it doesn't take in account students that were absent that day or students who are not attending school. Synthetic cannabinoids like Spice or K2 have a higher affinity for cannabinoid receptors than THC. Prolonged duration of action which increases accumulation in the body and increased potential for toxicity. These may not be detected in standard urine drug screens. If you're looking for these synthetic cannabinoids, you may wanna talk to the lab about specifically looking for those. And not all of them are scheduled by the DEA. Pharmacokinetics. For inhalation, it produces the most rapid onset and the most intense high. Orally in food products, it's a slower onset and a less intense high. And with the synthetics, it has a high potency and a short duration. Metabolites are more toxic and it's hard to identify in a urine drug screen. For the pharmacodynamics with tolerance, there's tolerance with heavy use after to many of the effects of marijuana. So there can be cognitive impairment, a risk of chronic psychosis including schizophrenia, psychomotor and chronic bronchitis. Cannabis withdrawal or abstinence syndrome can present as the opposite effects of the drug. So trouble sleeping, mood swings, decreased appetite, irritability, headaches, loss of focus, cravings, sweating, chills, increased feelings of depression and stomach problems. For toxicity and adverse effects, consider risk versus benefits when considering therapeutic use. Strongly advise patients with cardiovascular disease, liver disease, disorders of the pancreas and lung disease. For psychomotor effects, in humans, depending on the dosage, it may impair object distance and shape discrimination, reaction time, information processing, perceptual motor coordination, motor performance, signal detection, tracking behavior, and there could be slowed time perception. And behavioral, it varies due to dosage, frequency, and duration. Studies do link marijuana use to depression, anxiety, suicide planning, and psychotic episodes. They're not sure if it's the cause or if it's just linked to these behaviors. And as far as cognitive, with memory, maybe due to changes in the plasticity of the hippocampal system, and there can be a permanent loss of IQ as much as eight points when use starts at a young age. Psychiatric issues, increased risk of at least one other mental health condition. There's been shown to be an increase in schizophrenia, a worsening of the psychiatric symptoms, and a poor prognosis. When we look at organ systems that are affected by cannabis, when we look at the respiratory system, with smoking, there can be damage to the respiratory system, the same mutagens found in cigarettes. Immunologic, they're still researching the benefit due to the non-psychoactive effects on the CB2 receptor. And cardiovascular, it increases heart rate. You can get orthostatic hypotension, and the synthetics may lead to cardiovascular damage and myocardial infarction in previously healthy young people. With the liver, it's a predictor of fibrosis progression in daily users. Inhibition of liver microstomes, altering the metabolism of endogenous and exogenous compounds. And kidneys, synthetics can cause acute kidney failure. Endocrine, it contribute to development of diabetes. Reproduction and pregnancy, it's been shown to show decreased fertility in males and females. In females, decreased pregnancy success. And in males, there may be a decreased sperm motility and counts. There may be decreases in success of in vitro fertilization. There's a rapid transfer of cannabis to the fetus through the placenta and into breast milk due to lipid solubility. Let's talk about marijuana and pregnancy. So marijuana is the most widely used illegal drug during pregnancy in the United States, and it's on the rise. Many pregnant women view it as safe, a natural way to treat nausea, morning sickness, and vomiting. No amount has been proven safe during pregnancy. There's been fetal growth restriction, greater risk of stillbirth, preterm born before 37 weeks gestation, low birth weight, and long-term brain developmental issues affecting memory, learning, and behavior. Marijuana in breast milk, it may cause harm. THC and other chemicals in marijuana can pass into the breast milk, and there's increased risk for problems with brain development later on. Let's look at the definition of cannabis use disorder according to the DSM-5. A problematic pattern of cannabis use leading to clinically significant impairment or distress is manifested by at least two of the following occurring within a 12-month period. So cannabis is often taken in larger amounts or over a longer period than intended. There is a persistent desire or unsuccessful efforts to cut down or control cannabis use. A great deal of time is spent in activities necessary to obtain cannabis, use cannabis, or recover from its effects. Cravings or a strong desire to use or urge to use cannabis. Recurrent cannabis use resulting in a failure to fulfill major role obligations at work, school, or home. Continued cannabis use, despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of cannabis. Important social, occupational, or recreational activities are given up or reduced because of cannabis use. Recurrent cannabis use in situations in which it's physically hazardous. Cannabis use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that's likely to have been caused or exacerbated by cannabis. And then tolerance as defined by either the following. The first is a need for markedly increased amount of cannabis to achieve intoxication or desired effect or markedly diminished effect with continued use of the same amount of cannabis. And withdrawal is manifested by either of the following. The first, the characteristic withdrawal syndrome for cannabis or cannabis is taken to relieve or avoid withdrawal symptoms. So remember at least two of those occurring within a 12 month period. And when we look at cannabis intoxication, the diagnostic criteria are the following. A recent use of cannabis, clinically significant problematic behavioral or psychological changes that develop during or shortly after cannabis use. Two or more of the following signs or symptoms developing within two hours of cannabis use. Conjunctival injection, increased appetite, dry mouth or tachycardia. And the signs or symptoms are not attributed to another medical condition and are not better explained by another mental disorder, including intoxication with another substance. And then cannabis withdrawal diagnostic criteria. So cessation of cannabis use that's been heavy or prolonged. And then we need three or more of the following signs and symptoms develop within approximately one week after the cessation of use. So irritability, anger or aggression, nervousness or anxiety, sleep difficulty, decreased appetite or weight loss, restlessness, depressed mood, and at least one of the following physical symptoms causing significant discomfort. Abdominal pain, shakiness or tremors, sweating, fever, chills or headaches. The signs or symptoms in criteria B cause clinically significant distress or impairment in social, occupational or other important areas of functioning. And the signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance. One thing we're seeing more and more of, and I'm seeing more in my practice is cannabinoid hyperemesis syndrome. This is caused by long-term cannabis use. And I have patients who have been worked up by their GI doctor, they've undergone endoscopy, all sorts of testing to try and figure out what's going on. And when they really looked into it, it turns out to be cannabinoid hyperemesis syndrome. There's three phases to this syndrome. First is the prodromal, nausea and vomiting following long-term cannabis use. This often leads to a person using more cannabis to reduce the nausea. And this is really common. The second phase is hyperemetic, triggered by increased cannabis use, nausea, abdominal pains and vomiting increases. And then the recovery. Once a person stops using cannabis, symptoms may take several weeks to decrease and disappear until they begin using again when the cycle starts over. Rare syndrome caused that occurs in long-term heavy users of TH rich cannabis. And what we found is this can be relieved by taking hot showers. And patients will tell you that, oh, I don't feel any better until I get into a hot shower after they've been using and vomiting and been worked up. But it's not uncommon to see these patients return to use because they're not quite convinced that that's what caused it and that that's not what's going to help them feel better. The most common emergency caused by marijuana injection is a panic attack. It definitely triggers anxiety, panic attacks. We'll see patients in the emergency room because they're having a panic attack. And when you really discuss their history, they've been recently using cannabis. This is followed by dizziness, dry mouth, nausea, disorientation, euphoria, confusion, sedation, increased heart rate and breathing problems. What about cannabis overdose? We're seeing more and more of this due to edibles. And some of the common signs and symptoms that you'll see are troublesome hallucinations, pronounced confusion, lethargy, depression, anxiety, fear, panic, acute psychosis, including hallucinations, delusions, paranoia, and depersonalization, rapid heart rate, postural hypotension, so a pathological drop in their blood pressure, respiratory depression, and nausea and vomiting. Talk a little bit about urine drug testing. And when we look at urine drug testing and we look at the THC, remember that it's quickly absorbed and stored in fat tissue. So the inactive metabolite 11-nor-9-carboxy-delta-9 tetrahydrocannabinol is measured. The federal cutoff is 50 nanograms per milliliter. With intermittent cannabis use, it could be out of the system in two to four days, but with chronic use, it could be up to 30 days, and sometimes we've seen it a little bit more, a little longer than that. Hemp seed oil and dronabinol may show positive. Cannabinol, CBD, and products without THC are not likely to be detected. Remember, most of the products that they advertise as CBD have some THC. So if you look at the ingredients, if patients say, oh, I only use CBD, and you really look at the ingredients, there is a percentage of THC that may show up. But for pure CBD, it's not likely to be positive. And passive exposure to marijuana smoke is really unlikely to show positive. And again, we have especially some young adults who will say, well, I was in the car with somebody who was using, or it's, you know, I walk in the house and it's there, and that's why it's positive. Very unlikely. What's the treatment for cannabis use disorder? Well, right now there aren't any medications that are FDA approved to treat cannabis use disorder currently. There is research going on for pharmacologic interventions. They're actively being studied. Psychosocial treatments are very helpful. Motivational enhancement therapy based on motivational interviewing. You know, where are they at now? What are they willing to do? Coming up with some goals, having them reach their goals. Cognitive behavioral therapy. Identify contingencies of using behavior, develop relapse prevention skills and alternative behaviors. And contingency management's been shown to be very successful in treating substance use disorders. As long as the contingency is offered, you know, soon after the positive result that you're waiting to see, and frequent, and you may have to up the contingency as you go along. Let's talk a little bit about medical marijuana. Medical marijuana refers to using the whole unprocessed marijuana plant or its basic extracts to treat symptoms of illness and other conditions. The U.S. Food and Drug Administration has not recognized or approved the marijuana plant as medicine at this time. Cannabinoids. So scientific study of cannabinoids has led to two FDA approved medications that contain cannabinoid chemicals in a pill form and much research is needed to lead to more. And there's a lot going on right now. Here's a list of the states that have legalized marijuana for medical use. And it continues to grow. Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, District of Columbia, Florida, Hawaii, Illinois, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Montana, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Dakota, Utah, Vermont, Virginia, Washington, and West Virginia. And looking at over the past few years, this list is continuing to grow and will probably continue moving forward. The states that legalize recreational marijuana is less, but we see some of them have both. Some have a little bit of mix, but I only put on here the ones that have fully legalized recreational marijuana. So Alaska, Arizona, California, Colorado, Connecticut, Delaware, D.C., Illinois, Maine, Maryland, Massachusetts, Michigan, Minnesota, Missouri, Montana, New Jersey, New Mexico, New York, Nevada, Ohio, Oregon, Rhode Island, Vermont, Virginia, and Washington. As far as FDA approval, as of now, researchers have not conducted enough large-scale clinical trials that show that the benefits of the marijuana plant outweigh its risk in patients it's meant to treat. Talk about medical marijuana and opioid use. There's still additional research needed on the effects of medical marijuana laws on opioid overdose deaths, and the research has varied outcomes. So many patients will tell you that they're going to be using medical, they're using marijuana to help them to get off of opioids or help with some of the withdrawal symptoms as they occur, but there still needs to be some more research to see if it's helpful. There has been some that's shown some varied outcomes as to whether or not it will help with stopping opioid use or if it just alleviates some of the withdrawal symptoms in between use. So how cannabinoids might be useful as medicine? Well, THC increases appetite, it reduces nausea, it may decrease pain, it may decrease inflammation, it may help muscle control problems. And then CBD, it doesn't make people high and it may reduce pain, reduce inflammation, controlling epileptic seizures and possible treating mental illness and addictions. So there is a medication, Epidiolex, it's FDA approval, it's FDA approved, it's a CBD-based liquid medication. It's treatment of two forms of severe childhood epilepsy. So Dravot syndrome, formerly known as severe myoclonic epilepsy of infancy, SMEI, it's a genetic epilepsy characterized by temperature-sensitive febrile seizures, treatment-resistant epilepsy that begins in the first year of life and differences in childhood development. So this is approved to treat that. And Lennox-Gastaut syndrome is a severe form of epilepsy, these seizures begin in early childhood, usually before the age of four. Children, adolescents, and adults with Lennox-Gastaut syndrome have multiple types of seizures that vary among individuals. Dronabinol and Nabilone are FDA approved drugs, they both contain THC, they treat nausea caused by chemotherapy and increase appetite and extreme weight loss caused by AIDS. Sativex is not FDA approved, it's approved in Canada, United Kingdom, and some other European countries. It's a mouth spray, it contains CBD and THC, and it treats muscle control problems caused by multiple sclerosis. So many researchers are continuing to explore the possible use of THC and CBD and other cannabinoids for medical treatment. Medical marijuana during and after pregnancy. So some women report using it for severe nausea during pregnancy. There's no research that shows that this is safe. Animal studies do show that moderate amounts of THC given to pregnant and nursing women could have long-lasting effects, including abnormal patterns of social interactions and learning issues. So the key points of medical marijuana, the term medical marijuana refers to treating symptoms of illness and other conditions with the whole unprocessed marijuana plant or its basic extracts. The FDA has not recognized or approved the marijuana plant as medicine at this time. However, scientific study of the chemicals in marijuana called cannabinoids has led to two FDA approved medications in pill form, dronabinol and nabalone, used to treat nausea and boost appetite. Cannabinoids are chemicals related to the delta-9 tetrahydrocannabinol, THC, marijuana's main mind-altering ingredient. And currently the two main cannabinoids from the marijuana plant that are of interest for medical treatment are THC and cannabidiol. The body also produces its own cannabinoids or chemicals called endocannabinoids. And scientists are conducting preclinical and clinical trials with marijuana and its extracts to treat symptoms of illnesses and other conditions. Thank you for your attention. And I'll be available at the question and answer sessions to answer any questions that you may have or feel free to email me.

cannabis

medical marijuana

cannabinoids

THC and CBD

cannabis use disorder

pharmacology

medical research