On behalf of the American Osteopathic Academy of Addiction Medicine, let me welcome you to this presentation entitled Other Substance-Related Disorders. My name is Dr. Gregory Landy, and I will be with you throughout this presentation. In that regard, let me announce at this point that I have no ethical or financial conflicts in regards to this presentation. Now in our time together, the objectives for this presentation is that I hope you will learn about other substance-related disorders with a focus on their epidemiology, their diagnosis, and their management. This is the presentation outline to give you an idea from a bird's-eye view. We will start with caffeine-related disorders, and DSM-5TR identifies caffeine intoxication, caffeine withdrawal, caffeine-induced mental disorders, and unspecified caffeine-related disorders in that group. We'll then move on to the hallucinogen-related disorders, and DSM-5TR recognizes a phencyclidine use disorder, other hallucinogen use disorder, phencyclidine intoxication, other hallucinogen intoxication, the hallucinogen persisting perception disorder, which is very interesting, phencyclidine-induced mental disorders, hallucinogen-induced mental disorders, the unspecified phencyclidine-related disorder, and unspecified hallucinogen-related disorder. We'll then move on to our last major topic, which is the inhalant-related disorders. And in that group, we have inhalant use disorder, inhalant intoxication, inhalant-induced mental disorders, and unspecified inhalant-related disorders, and that being other combinations. And one we will be focusing on during this presentation are the anabolic steroids. We'll then have a brief overview of examples of misused over-the-counter medications, followed by a brief overview of examples of emerging substances of misuse. And in the latter portion of this, we have an interesting surprise, and I hope you'll stick around and find that portion of this presentation particularly interesting. So let's begin with this table, diagnoses associated with a substance class. And the purpose of this particular slide is really to highlight the broad differential that is associated with a number of these particular substances. So if we begin with caffeine, we see that anxiety disorders and obviously sleep disorders are among the differential diagnoses to consider. Among the hallucinogens, we have to consider psychotic disorders, bipolar and related disorders. We have to consider depressive disorders, anxiety disorders. Now with encyclodine, it too has a similar pattern. Psychotic disorders are in the differential, along with bipolar and related disorders, depressive disorders, and anxiety disorders. Now the inhalants have a slightly less broad differential, but it does still include psychotic disorders, depressive disorders, and anxiety disorders. So again, this table is just giving us an overview of the differential diagnoses. Caffeine-related disorders. We're going to spend our time looking at caffeine intoxication and caffeine withdrawal. Now I know it's tedious, but it's very important that we have a solid understanding of the DSM-5 TR diagnoses of these particular substances. And so join me in going through this line by line. And we're going to start with caffeine intoxication. The A criteria requires the recent consumption of caffeine, meaning typically a high dose, well in excess of 250 milligrams. The B criteria requires five or more of the following signs or symptoms developing during or shortly after caffeine use. And let's go through these 12 signs or symptoms. Beginning with restlessness, nervousness, excitement, insomnia, flushed face, diuresis, gastrointestinal disturbance, muscle twitching, a rambling flow of thoughts and speech, tachycardia or cardiac arrhythmias, periods of inexhaustibility, and psychomotor agitation. Now remember, for the diagnosis, there must be five or more of these 12 signs or symptoms. Now the C criterion requires that the signs or the symptoms that we just went through cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. And the D criterion, the signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication with another substance. Now let's look at some caffeine epidemiology. And we're breaking this down through these two illustrations among two different age groups. Let's start with total caffeine intake among those 15 to 19 years of age. And we see, perhaps interestingly enough, that soft drinks represent nearly one-third of the total caffeine consumption among this age group, 32.9%, followed by, again it's interesting, tea at 27.9%, coffee coming in third at 24.9%, and energy drinks at 10%. And we'll spend some more time talking about energy drinks in just a moment. Now let's turn our attention to the total caffeine intake among those 35 to 49 years of age. And here we see a different picture. Among this age group, coffee, 65% of individuals in this age group are getting their caffeine from coffee, followed by soft drinks at 16%, tied with tea also at 16%. So the average caffeine intake among those 15 to 19 years of age is around 61 milligrams. Among those 35 to 49, it's 188 milligrams. Now let's look at this table, which gives us some idea about how much caffeine is in some of the more common beverages that all of us consume at one time or another. So if you go to a coffee shop and it's brewed coffee, 12 ounces, typical size, you're getting roughly 235 milligrams of caffeine. If you're brewing coffee at home, for example, eight fluid ounces, 92 milligrams of caffeine. Espresso, one fluid ounce, 63 milligrams of caffeine. Now if we move to black tea, eight fluid ounces has considerably less caffeine at 47 milligrams. But now let's look at energy drinks. And of course this can vary. Eight and a half fluid ounce, 80 milligrams of caffeine. An energy shot, on the other hand, typically two fluid ounces, can have 200 milligrams of caffeine. Again, maybe more. And let's not forget over-the-counter drugs, which are sometimes taken by individuals to promote their alertness. Those may consist of 200 milligrams of caffeine. And as you well know, there are some headache medications that are compounded with caffeine. And in those cases, it's typically 65 milligrams of caffeine. Now let's turn our attention to some pharmacology as it relates to caffeine. Caffeine is broadly construed as a methylxanthine. It's absorbed in 45 minutes, and it peaks within two hours of consumption. The half-life is fairly short. In adults, it's approximately two and a half to four and a half hours. It's metabolized by the cytochrome P450 system, but predominantly by the CYP1A2. Now caffeine is metabolized and excreted in humans primarily as parazanthine, which by itself also has pharmacologic activity and may contribute to the development of tolerance. Interestingly, smoking increases caffeine metabolism by around 50%. On the other hand, pregnancy reduces metabolism, and even more so in the third trimester. Now caffeine may improve pain relief when added to common analgesics, or at least that's thinking of those who are compounding those particular analgesics. Now let's talk a bit about caffeine and its relationship with your health. Caffeine affects primarily the heart, respiration, the kidneys, and the nervous system. Its actions result from the antagonism of adenosine receptors. The antagonism of the adenosine receptors indirectly releases norepinephrine, dopamine, acetylcholine, serotonin, glutamate, and gamma-aminobutyric acid. Now the consumption of up to six standard cups of filtered, and I emphasize the word filtered, caffeinated coffee per day is not associated with an increased risk of adverse cardiovascular outcomes. There's an inverse relationship, however, between coffee consumption and coronary artery disease. And I quote, coffee consumption may prevent cholesterol gallstone formation by inhibiting the absorption of gallbladder fluid, increasing cholecystokinin secretion, and stimulating gallbladder contraction, end of quote. Now continuing that, the consumption of two to five standard cups of coffee per day has been associated with reduced mortality in cohort studies across the world. Now if you look at this slide and the title, you'll see a number in superscript. That number is the reference from which this information was obtained. And I invite you, at your leisure, to look at those references for even more information about these particular topics. Now continuing with caffeine physiology, the net effects of caffeine consumption can be summarized on the heart as it's stimulated with increased blood flow. As we well know, on the kidney, it results in diuresis, which again results from the increased blood flow. In the lungs, it causes smooth muscle relaxation and bronchial dilation. And in terms of the behavior, mood, memory, alertness, and physical and cognitive performance can all be affected. Now let's turn our attention to energy drinks, as I mentioned a few moments ago. Men between the ages of 18 and 34 years of age consume the most energy drinks. But keep in mind that one-third of those 12 and 17-year-olds also drink energy drinks regularly. There are more problems, health-related and behavioral problems, when energy drinks are combined with alcohol. 25% of college students consume alcohol with their energy drinks. And this definitely increases the rate of intoxication. Now the number of emergency department visits doubled between 2007 and 2011, and you can see the numbers there. And 42% of all energy drink-related emergency department visits involve combining the energy drink with alcohol, marijuana, or over-the-counter medications. Now Figure 1 provides this in graphical form. The data is the latest there is from the DAWN report, and we'll discuss why that is a little bit later. But again, this is the latest data looking at energy-related drinks and their admissions to emergency departments. Now in quotes, the daily intake of energy drinks should only not exceed the safety limits for caffeine established by European and American regulatory authorities, but should be even lower. Indeed, these drinks also contain other neurostimulants, the effects of which are not fully understood. We recommend no more than one can at a time and two cans per day to remain within an acceptable safety limit. And again, superscript number four will bring you to that particular quotation and much more information. Now in the table, we see some of the common energy drinks and their other ingredients that can contribute to the effects we just talked about, such as targary. Let's look at some fast facts when it comes to caffeine intoxication. It's estimated that 7% of caffeine users may actually meet the diagnostic criteria for intoxication. Heavy use, which is defined as 400 milligrams a day or greater, can confound mood disorders, particularly anxiety and somatic differentials. Very high doses in the 5 to 10 gram range can actually be legal. Again, the differential diagnosis for caffeine intoxication, fairly broad, includes bipolar disorder, naturally sleep disorders, other depressive disorders, anxiety disorders, and other substance-related disorders. Treatment begins with awareness, clinical history, and education. Other cases of toxicity may need more aggressive medical management. Now let's turn our attention to caffeine withdrawal. And again, bear with me as we go through this diagnosis line by line so that it's firmly implanted in our minds. Criterion A, there's a prolonged daily use of caffeine. Criterion B, abrupt cessation or reduction in caffeine use followed within 24 hours by three or more of the following signs or symptoms. Headache, marked fatigue or drowsiness, dysphoric mood, depressed mood, or irritability, difficulty concentrating, and flu-like symptoms, nausea, vomiting, muscle pain, and stiffness. Now again, let's remember, within 24 hours, three or more of those signs or symptoms were the diagnosis of caffeine withdrawal. C, the signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of function. In Criterion D, the signs or symptoms are not associated with the physiologic effects of another medical condition, in this case, say, a migraine or viral leprosy. And they're not better explained by another mental disorder, including intoxication or withdrawal from another substance. Some fast facts about caffeine withdrawal. The average American consumption across all age ranges, 280 milligrams per day, but keep in mind that withdrawal may occur with much less use. The primary consequence of caffeine withdrawal is headache. I'm going to repeat it. The primary consequence of caffeine withdrawal is headache, and it can vary in its type and its intensity. Withdrawal symptoms generally began 12 to 24 hours after last caffeine consumption, and those symptoms may peak one to two days and may persist up to nine days. Some more facts regarding caffeine withdrawal. Consumption of caffeine, obviously, quickly reverses the symptoms. In attempts to permanently stop caffeine use, more than 70% of individuals may experience at least one caffeine withdrawal symptom, with 47% experiencing that headache. 24% may experience headache plus one or more other symptoms, as well as functional impairment due to that withdrawal. Now among individuals who abstain from caffeine for at least 24 hours, but are not trying to permanently stop caffeine use, 11% may experience headache plus one or more other symptoms, as well as functional impairment. Now, as I mentioned earlier, we now have a figure looking at findings from drug-related emergency department visits from 2022, and this is the latest data. Now this data is calculated on a regular basis, and the top 10 substances involved in drug-related ED visits are then tabulated, and caffeine did not make this list, therefore the data we looked at earlier was the last situation where that occurred. But as you can see, emergency department visits, latest data from 2022, not surprisingly would show that alcohol-related visits are the most common, followed by opioids, and you can see that's further broken down in terms of the type, heroin, a prescription or other opioid, and fentanyl, which of course is a major social concern nowadays. And then finally, as we kind of rest down this figure, we see cannabis and methamphetamines, but no caffeine. Now, this particular table, Key Substance Use and Mental Health Indicators in the United States, this is from a 2022 national survey on drug use and health, and I've highlighted the areas that we'll be covering in this presentation, and you can see how it varies among the different age groups, and we'll talk about this in more detail as we get to each one of these particular topics. But you can see among the hallucinogens, the age range where it's most commonly misused, 18 to 25. And among those hallucinogens, the most common is LSD, again, in that same age group of 18 to 25. Now, inhalants on the other hand, are most common among those, and isn't this interesting, ages 12 to 17. And again, we're gonna have to look at this in more detail in just a few minutes. So, in DSM-5-TR, the hallucinogen-related disorders, once again, include the fincyclidine use disorder, other hallucinogen use disorder, fincyclidine intoxication, other hallucinogen intoxication, hallucinogen-persisting perception disorder, fincyclidine-induced mental disorders, hallucinogen-induced mental disorders, unspecified fincyclidine-related disorder, and finally, unspecified hallucinogen-related disorder. A little bit about fincyclidine. It's also known, of course, as PCP, or angel dust, and it comes in many forms, including as a powder, a crystal, a tablet, capsule, and a liquid. Keep in mind, it's often smoked with marijuana. Fincyclidine has been around for a while. It first emerged in the 1960s, and its popularity has fluctuated over time since those 1960s. Now, again, let's go through the fincyclidine intoxication diagnosis, as reported by DSM-5-TR, line by line, starting with criterion A, which requires the recent use of fincyclidine, or a pharmacologically similar substance. Criterion B, there are clinically significant problematic behavioral changes, that is, belligerence, assaultiveness, impulsiveness, unpredictability, psychomotor agitation, impaired judgment, that develop during or shortly after fincyclidine use. Criterion C requires that within one hour, two or more of the following signs or symptoms. Now, DSM-5 wants to make note of the fact that when the drug is smoked, snorted, or used intravenously, the onset may be particularly rapid. But with that in mind, again, criterion C, within one hour, two or more of the following signs or symptoms, including vertical or horizontal nystagmus, hypertension or tachycardia, numbness or diminished responsiveness to pain, ataxia, dysarthria, muscle rigidity, seizures or coma, and hyperacusis. Criterion D, the signs or symptoms are not attributable to other medical conditions and are not better explained by another mental disorder, including intoxication with another substance. Now, let's turn our attention to the fincyclidine use disorder diagnosis, again, from DSM-5-TR. So bear with me and let's go through this. Criterion A, a pattern of fincyclidine or a pharmacologically similar substance used leading to clinically significant impairment or distress as manifested by at least two of the following occurring within a 12-month period. So let's start. One, fincyclidine is often taken in larger amounts or over a longer period than was intended. Two, there's a persistent desire or unsuccessful efforts to cut down or control fincyclidine use. Three, a great deal of time is spent in activities necessary to obtain fincyclidine, use fincyclidine, or recover from its effects. Four, craving or a strong desire or urge to use fincyclidine. Six, excuse me, five, recurrent fincyclidine use resulting in a failure to fulfill major role obligations at work, school, or home. That is, repeated absences from work or poor work performance related to fincyclidine use. Fincyclidine-related absences, suspensions, or expulsions from school, neglected children, or household. Six, continued fincyclidine use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by its effects, such as arguments with a spouse about the consequences of intoxication or even physical fights. Seven, important social, occupational, or recreational activities are given up or reduced because of fincyclidine use. Eight, recurrent fincyclidine use in situations which it is physically hazardous, such as driving an automobile or operating a machine when impaired by fincyclidine. Nine, fincyclidine use is continued despite having knowledge or having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the fincyclidine. And finally, number 10, tolerance. As defined by either of the following, A, a need for markedly increased amounts of the fincyclidine to achieve intoxication or desired effect, or B, a markedly diminished effect with continued use of the same amount of the fincyclidine. Now, DSM-5-TR wants to make note of the fact that withdrawal symptoms and signs are not established for fincyclidine, and so this criterion does not apply. So again, remember, for fincyclidine use disorder, you need at least two of the signs and symptoms occurring within how long? A 12-month period. Now, some fast facts here about fincyclidine use disorder. It causes hallucinations. It can produce hostile behavior. Users may feel detached or distant, and they may experience distorted sights and sounds. Severe symptoms of PCP use can include irregular breathing, seizures, and even coma. Again, PCP is most commonly used among males aged 25 to 34, and 48% of ED visits included the presence of other drugs combined with the PCP, such as marijuana, cocaine, heroin, and no doubt fentanyl. Now, let's look at some of the pharmacology of fincyclidine. So PCP is a dissociative anesthetic. It blocks the uptake of dopamine and norepinephrine. It is a non-competitive antagonist to the NMDA receptor, N-methyl-D-aspartate receptor, non-competitive antagonist. It binds to the acetylcholine receptors and the gamma-aminobutyric acid receptors. The sigma receptor is stimulated, which leads to lethargy. As a result of the biochemical actions, PCP is both a CNS stimulant and a depressant. Now, analgesic, anesthetic, caudity effects, depression, and psychosis, hypertension, tachycardia, bronchodilation, irritability, agitation, and sedation. Interesting mix, and it's metabolized in the liver. Some more. Most commonly inhaled, leading to symptoms in five minutes or less, and it's the same if they inject the fencyclidine. The halfway of fencyclidine is fairly long, it's 21 hours. The symptoms are dose-dependent, and they can last up to 48 hours. Because PCP is fat-soluble, and because of that, lipid storage, it can be released over days or months after its initial use. The I signs include nystagmus, that can be horizontal, vertical, and rotary, and occur in 60 to 90% of the cases, along with meiosis. Toxicity from fencyclidine is, and can be, a rather serious matter, and it can include rhabdomyolysis, hypoglycemia, seizures, hypertensive crisis, and coma. Now let's take just a moment to look at some of the management ideas when it comes to fencyclidine. When it comes to toxicity, you obviously want to do a thorough history and physical and diagnostic assessment that would include such things as creatinine kinase, which will be elevated in roughly 70% of cases. You'll want to do an ECG, looking for the potential of arrhythmias. Clearly, of course, you want to do a urine drug screen, because again, fencyclidine is often used in combination with other drugs, and a liver function test, which will be elevated in at least 50% of cases. Most patients survive PCP intoxication with supportive care. More severe cases require more aggressive medical and psychiatric management that may include the use of benzodiazepines. And again, at the top of the slide, if you want to learn more about the management of fencyclidine, you can read the reference identified by the superscript number eight. Now let's take a moment and look at the DSM-5 diagnosis of other hallucinogen intoxication. The diagnostic criteria. Criterion A, the recent use of hallucinogen other than fencyclidine. Criterion B, clinically significant problematic behavioral or psychological changes, such as marked anxiety or depression, ideas of reference, fear of losing one's mind, paranoid ideation, impaired judgment, that develop during or shortly after hallucinogen use. Criterion C, perceptual changes occurring in a state of full weight lupus and alertness, that is a subjective intensification of perceptions, depersonalization, derealization, illusions, hallucinations, and synesthesias, that develop during or shortly after its use. This diagnosis requires in criterion D, two or more of the following signs developing during or shortly after its use. Those signs and symptoms include pupillary dilation, tachycardia, sweating, palpitations, blurring of vision, tremors, and incoordination. To make the diagnosis again, you need two or more of these signs or symptoms. And criterion E, once again, the signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication with another substance. In 2018, 1.5% of individuals aged 12 to 17 in the United States reported use of hallucinogens in the past year. Among individuals 18 to 25, the rate was 6.9%. And among those 26 years or older, the rate dropped to 1.3%. Rates are consistently higher for boys and men than for girls and women in every age group. Other hallucinogen use disorder, DSM-5-TR diagnostic criteria. Hallucinogens are a large group of compounds that produce similar effects, affecting perception, mood, and cognition. The examples that would be included in this category include the phenylalkamines, such as mescline, and MDMA, otherwise known as ecstasy or mulling. The endolamines, including psilocybin and dimethyltryptamine, otherwise known as DMT. The ergolines, such as LSD, lysergic acid, diethylamine, and morning glory seeds. And let's not forget the plant compounds, such as the potent salvia divinorum and gemcinelli. In the US general population, about 0.1% of individuals aged 12 or older endorsed the symptoms of past 12-month hallucinogen use disorders in 2018. The rate was 0.2% among those aged 12 to 17, 0.4% among those aged 18 to 25, and less than 0.1% among those aged 26 and older. Now let's drill down to one of these that would be included in this diagnostic category, and that's MDMA, which affects mood and perception. It is both stimulating and it produces hallucinations. Those who use MDMA may experience an increase in their energy level, pleasure, and emotional warmth, and distorted sensory and time perception. It's usually taken by mouth as a pill, while so-called purer forms of MDMA are taken as a capsule and are referred to by the moniker molly. Molly stands short for molecular, keeping in mind that molly is often adulterated with other substances, and it may contain such things as synthetic cathinones. MDMA increases dopamine, norepinephrine, and serotonin. The effective half-life is fairly short, three to six hours, which accounts for why some users stack it, taking repeated doses within that time window. The adverse effects of MDMA include irritability, depression, anxiety, sleep problems, temperature dysregulation, which can be very serious and can lead to organ failure or even death. There really is no specific treatment for MDMA, aside from supportive-slash-symptomatic care. Now let's talk about this interesting diagnosis, the hallucinogen-persisting perception disorder. And as described in DSM-5-TR Criterion A, following cessation of the use of a hallucinogen, the re-experiencing, the re-experiencing of one or more of the perceptual symptoms that were experienced while the individual was intoxicated with the hallucinogen. That can include geometric hallucinations, false perception of movement in the peripheral fields, flashes of color, intensified colors, trails of images of moving objects, positive after images, and halos around objects, necropsia, and mycropsia. Criterion B, the symptoms in Criterion A cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. And Criterion C, the symptoms are not attributed to another medical condition, such as anatomical lesions and infections of the brain, visual epilepsies, and are not better explained by another mental disorder, obviously such things as delirium, major neurocognitive disorder, schizophrenia, or even hypnopompic hallucinations. Some facts, a hallucinogen-percepting perceptual disorder is most common following LSD. It does not appear to be a relationship between the amount or the frequency of its use. Use of other drugs, such as marijuana, may actually precipitate this disorder. Its prevalence is not very well known. One theory about its etiology suggests that there's damage to the sensory-related cortical serotonergic inhibitory inner neurons with gamma-immunobutyric acid outputs. We have a merger. It's often preceded by an aura. Management may include such things as a presynaptic alpha-adrenergic agonist, such as clonidine, benzodiazepines, low-dose antipsychotics, and antiepileptic drugs. And again, at the top of the page, as we said before, there's a superscript where you can learn more about this. Now let's turn to the inhalant-related disorders. DSM-5TR recognizes inhalant use disorder, inhalant intoxication, inhalant-induced mental disorders, and finally, unspecified inhalant-related disorder. Now let's go through the diagnosis of inhalant intoxication, criterion A, recent intended or unintended short-term, high-dose exposure to inhalant substances, including volatile hydrocarbons, such as toluene or gasoline. Criterion B, clinically significant, problematic behavioral or psychological changes, that is, belligerence, assaultiveness, apathy, impaired judgment, that develop during or shortly after exposure to the inhalants. Criterion C, two or more of the following signs or symptoms develop during or shortly after inhalant use or exposure. Those signs or symptoms include dizziness, nystagmus, incoordination, slurred speech, unsteady gait, lethargy, psychomotor retardation, tremor, generalized muscle weakness, blurred vision or diplopia, stupor or coma, and euphoria. And again, for inhalant intoxication, there must be two or more of those signs or symptoms. And then Criterion D, the signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication with another substance. Now, moving on to the more serious form of this, we have inhalant use disorder. And here, Criterion A requires a problematic pattern of the use of a hydrocarbon-based inhalant substance, a problematic pattern of the use of a hydrocarbon-based substance, leading to clinically significant impairment or distress as manifested by at least two of the following occurring within a 12-month period. One, the inhalant substance is often taken in larger amounts or over a longer period than was intended. B, there is persistent desire or unsuccessful efforts to cut down or control use of the inhalant substance. A great deal of time is spent in activities necessary to obtain the inhalant substance, use it, or recover from its effects. Four, craving or strong desire or urge to use the inhalant substance. Five, recurrent use of the inhalant substance resulting in a failure to fulfill major role obligations at work, school, or at home. Six, continued use of the inhalant substance despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of its use. Seven, important social, occupational, or recreational activities are given up or reduced because of the use of the inhaled substance. Eight, recurrent use of the inhalant substance in situations in which it is physically hazardous. Nine, use of the inhalant substance is continued despite knowledge of having a persistent or recurrent physical or psychological problem that's likely to have been caused or at least exacerbated by the substance. And finally, number 10, tolerance. As defined by either of the following, a need for markedly increased amounts of the inhalant substance to achieve intoxication or the desired effects. Or B, a markedly diminished effect with continued use of the same amount of the inhaled substance. And again, as a recap, at least two of the following must occur within a 12 mark period. Now let's look at some of the epidemiology here. Approximately 2.3% of those 12 to 17 years of age have used inhalants in the past 12 months. Those 18 years and older past 12 month prevalence of inhalant use is about 0.21%. With 0.04% having a pattern of use that meets criteria for an inhalant use disorder. Among youth, the prevalence of 12 month inhalant use is highest among non-Hispanic whites. And the 12 month prevalence rates of inhalant use disorder among adults are highest among non-Hispanic whites and lowest among non-Hispanic blacks. Now this is a very interesting slide. And it provides us with information about what sort of inhalants are most frequently turned to. And perhaps it's surprising, but the number one most used inhalant is a felt tip marker or magic marker. That's followed by glue, shoe polish, or toluene. Then spray paints. Gasoliner liner fluid is fourth on the list. Then we have computer cleaner or air duster. Correction fluid, degreaser, or other cleaning fluid. But again, interestingly enough, felt tip pen markers or magic markers are number one. Now some of the fast facts and features of inhalant use disorder. It's estimated that roughly 10% will develop tolerance. The impairment is measured in terms of conduct disorders and school problems. Inhalant use, depending on what they're using, can be very serious and can result in organ damage, hearing loss, brain damage, and even death. Street terminology, sniffing, snorting, bagging, or huffing. Now the pharmacology will obviously vary with the selected inhalant, but the sedative effects are most likely due to positive modulations of GABA-A receptors while blocking the NMDA receptor, which may account for the PCP-like effect that some of these inhalants produce. The management, pharmacologic treatments for inhalant use disorders have rarely been evaluated. This is an opportunity to do screening, education, and where appropriate, psychosocial interventions. Now under other substance misuse, let's take a moment to look at anabolic steroids. Now steroidal androgens, of course, include the natural androgens, such as the male sex hormone, testosterone, or synthetic compounds, which simulate the endogenous hormone. It's estimated that three to four million Americans use anabolic steroids for muscle development or for aesthetic purposes. And as you might imagine, it's more common among athletes and males. In fact, anabolic misuse in males is estimated at 6.4%, 1.6% in females. The exogenous androgens suppress testicular function and can result in hypogonadism. Female users of anabolic steroids may suffer hirsutism, acne, temporal male pattern baldness, and a deeper voice. You might suspect anabolic steroid misuse when there's a rapid increase in an individual's muscle mass among those in sports, where there's aggression, depression, or irritability, in the presence of a low luteinizing hormone, high hematocrit, and low sex hormone-binding globulin, heart disease, and male gynecomastia. The treatment for anabolic steroid misuse would be psychotherapy and symptomatic relief, such as with pain medications. In more serious cases, it may need referral to an individual who specializes in that particular area. Now let's look at other substance misuse, and here we want to take a moment to look at over-the-counter medications. And in the United States, there are four broad categories where this misuse is found, among anti-tussives and cough medicines, which mainly means dextromorphan, antihistamines, diphenhydramine, decongestants, pseudoephedrine, and antidiarrheals, which equates with loperamide. Epidemiologic data would suggest that 3.1 million people, age 12 to 25, reported that they'd used an over-the-counter cough or cold medicine to get high. But this data is probably misrepresented because it does not include internet orders of those substances. Now one in particular, let's take a look at, is dextromorphan, otherwise known as DXM, or mansychosis, and roboing. It's the most common over-the-counter medication abused among adolescents, and resulted in 6,000 ED visits per year, among those less than 20. Now dextrophan is the psychoactive component. It blocks in MDA receptors and can produce hallucinations, euphoria, dissociation, agitation, and coma. It binds serotonin receptors, so keep in mind it may cause the serotonin syndrome. It blocks the reuptake of peripheral adrenergic neurotransmitters, and can cause hypertension, tachycardia, arthritis, and diaphoresis. In 2022, the estimated numbers of misused cough and cold medicine in the past year were 162,000 adolescents, 12 to 17 years of age, 296,000 young adults, 18 to 25, and 1.8 million adults aged 26 or older. Now let's look at club drugs and the novel psychoactive substances. And we can group these by their primary psychoactive effects. So those that are primarily stimulants would include the cathinones, the piperazines, the phenylethylamines, and that includes the amphetamines, methamphetamines, methadrone, MDMA, the 2C series, D series, and you see the rest. The primary depressants category would include GHB, GBL, ketamine, nitrous oxide, for examples. The primary hallucinogens we can see include the tryptamines, psilocybin, LSD, and finally, the synthetic cannabinoid receptor agonists include CB1 and CB2 receptor agonists. And that includes a number of these that are being chemically manufactured. Now, these other substances of misuse include such things as gamma-hydroxybutyrate, GHB, otherwise known as G or Georgia oligoid, grievous bodily harm, or liquid G. You can see the numbers. We have kratom, which has resulted in some increased popularity among those 12 or older. In 2022, 0.7% reported using kratom in the past year. We have synthetic marijuana, otherwise known as fake weed, K2, and spice. It's highest among those age 18 to 25. And then we have the synthetic stimulants, synthetic cathinones, otherwise known as basalts or flaka. And you can see that it's very low numbers. Now, in terms of these novel merging substances of misuse, I would suggest that keeping up to date with timely journal articles, such as those published in the AOAAM's Journal of Addictive Diseases, will help you identify and keep up to date with this changing landscape. Now, as I said, at the very beginning of this presentation, we're going to do something a little bit different, hopefully a little interesting. And we're going to go through some clinical scenarios and practical application quizzes to put the knowledge that we just learned to some use. And let's begin with the clinical vignette. A 24-year-old male presents the ED accompanied by local police. The patient is highly agitated, displaying aggressive behavior towards the ED staff and verbalizing nonsensical phrases. He has an unsteady gait, tachycardia, slurred speech, and vertical nystagmus. The patient's history is significant for previous substance misuse, although the specifics are unknown at that time. Blood pressure, 150 over 90. His heart rate, 120. Temperature, 99.8. Based on this clinical presentation, what is the most likely substance involved? Is it caffeine, cannabis, GHB, or PCP? Well, the answer, of course, is PCP. Which of the following best describes the mechanism of action of fincyclidine? A, sigma receptor antagonist. B, noncompetitive antagonist to the NMDA receptor. C, it inhibits the cyclooxygenase enzymes. Or D, it's a selective agonist for the mu-opioid receptor. Which of these best describes the mechanism of action of PCP? The answer, noncompetitive antagonist to the NMDA receptor. Now, here we have a simple true-false question. Inhalant misuse is most common among those 12 to 17 years of age. Is that true or false? True. Now, which of the following is most commonly misused as an inhalant by adolescents? Is it correction fluid? Belt-tip pens? Nitrous oxide? Or gasoline? Which is most commonly misused? They're inhalant of choice. If you said belt-tip pens, then you are correct. Another clinical vignette. A 16-year-old male adolescent is observed by a school counselor for having abrupt mood swings, ranging from euphoria to irritability within a short period during school hours. Additionally, he has been noted to have episodes of slurred speech, dizziness, and difficulty concentrating. When confronted, he admits to using a substance in the school bathroom to cope with stress. On further questioning, he reveals that he has been inhaling computer cleaner sprays. Now, given this information, which of the following is the most indicative sign of acute intoxication with his substance he has been misusing? Hyperactive reflexes? Urinary retention? Nystagmus? Or hyperthermia? The correct answer, nystagmus. Another clinical vignette for your consideration. A 24-year-old graduate student presents to the campus health clinic complaining of a persistent headache, fatigue, and difficulty concentrating. She mentions these symptoms have been worsening over the past two days, significantly impacting her ability to study for upcoming exams. Because of problems with falling asleep, she decided to cut back on caffeine. After realizing she was consuming five cups of coffee daily, in addition to occasional energy drinks to cope with the demanding schedule. For the past two days, she has not consumed any caffeine. Vital signs upon arrival include a blood pressure of 120 over 80, a heart rate of 78. Her general physical neurologic exam is normal. Which is the most likely cause of the student's symptoms? A major depressive disorder? Caffeine withdrawal? Viral meningitis? Or hypothyroidism? Well, naturally, this is a good description for caffeine withdrawal. Now, although the student's history supports the diagnosis of caffeine withdrawal, you should also consider some other diagnoses. Now, take a moment and provide some other examples. What are the differentials of caffeine withdrawal? It's pretty broad. Migraines, tension headache, dehydration, anemia, sleep disorder, mood disorders, viral illness, or for some other substance misuse. Now, a 22-year-old student visits the campus health clinic reporting ongoing visual disturbances, including seeing halos around lights, flashes of color, and occasional geometric hallucinations. These symptoms have been present for about two months, becoming increasingly distressing and impacting the student's academic performance and quality of life. The student reveals a history of occasional recreational drug use, including cannabis and hallucinogens, with the latter last used approximately two months prior to the onset of symptoms. The student denies any current use of substances, including alcohol, tobacco, or recreational drugs, since noticing the onset of those symptoms. Now, the student's diagnosis is not a diagnosis of a severe mental health condition. There's no significant past medical history, an expanded urine drug screen is negative, and the student's blood pressure is 118 over 76, and he has a heart rate of 72. What's the most likely diagnosis? Is it migraine with aura, schizophrenia, hallucinogen-persisting perception disorder, or a retinal detachment? Well, of course, this is a good description of a hallucinogen-persisting perception disorder. Now, with that said, what is the most likely drug related to this diagnosis? Is it marijuana, cocaine, amphetamine, or LSD? The answer, LSD. As I mentioned throughout this presentation, there are references to various drugs or references that are assigned to these slides, and I invite you to look at these and you can learn more about the particular topics. So in summary, during this presentation, we reviewed the diagnosis, epidemiology, and management of caffeine-related disorders, hallucinogen-related disorders, inhalant-related disorders, examples of misused over-the-counter medications, and examples of emerging substances of misuse. And of course, we had some fun with the practical application quiz. So with that, thank you for listening to this presentation. Best wishes on your upcoming exam from the American Osteopathic Academy of Addiction Medicine.

Substance-Related Disorders

Caffeine-Related Disorders

Hallucinogen-Related Disorders

Inhalant-Related Disorders

Anabolic Steroid Misuse

Over-the-Counter Medications

Emerging Substances

Epidemiology

Clinical Presentations

Substance Misuse