For this module, covering substances of abuse, we are very grateful for preparation of materials from two addiction medicine specialists, Dr. Wes Clark and Dr. Jim Ferguson. For those who you are not aware, an addiction medicine specialist can come from any specialty and usually is the physician who's had a minimum of a one-year fellowship in addiction medicine and substance abuse management. Here are the five basic classes of psychoactive substances, and we will begin with opiates and opioids. Although these terms are often used interchangeably, opiates and opioids are different. Opiates come directly from opium, and you see here the three chemicals that were included in the original federal panels. More recently, four of the semi-synthetic opioids were added to the federal panel because they're frequently prescribed as medications and also are subject to misuse. The opiates and opioids are all clinically useful as pain relievers, and they bind to opiate receptors. The United States is the predominant user of opioid products throughout the world. Although we represent only 4.5% of the world population, note here that we consume 99% of all hydrocodone, 80% of all oxycodone, almost half of all fentanyl, and 43% of Demerol, which is meparidine. There are literally dozens of opiates and opioids that are currently used, but I want to point out that the compounds on the left are the ones that are included in the federal panel set forth by SAMHSA. The ones on the right are also frequently prescribed medications, but they are not tested for. A practical use of this is that, as an MRO, if someone tells you, for example, that they're taking buprenorphine or meparidine or fentanyl and that that would explain a positive drug test result, the answer is no. Those chemicals are not going to cross-react with the tests for the items on the left. Opiates and opioids enter the body in a variety of different ways. Many of them are injected. Many of the semisynthetic opioids are taken orally as pills. Opium is usually smoked, if you can think of the hookah pipe, and drug users often will snort or insufflate heroin and morphine. And as I mentioned earlier, fentanyl can be administered by a transdermal skin patch. The way that I think of the effects of opioids is that they are central nervous system depressants. So even though they can cause euphoria and a flush and a rush as depressants, they basically are going to cause drowsiness. One of the big concerns about medical use of opioids is causing respiratory depression. They can cause pinpoint pupils. And of course, they can, like all of these drugs, impair judgment, social functioning, attention, memory. And in the case of a depressant, people may have a case of the nods. When I think of someone with an opioid overdose, I imagine someone lying in the street who's just barely conscious. They're barely breathing. Their skin is cold and clammy. Their pupils are pinpoint. They have blue lips. They may have had a convulsion or be in a coma. And certainly, they can die of an overdose. When someone is withdrawing from an opioid overdose, they're going to, of course, have just the opposite. The central nervous system depressant is suddenly going to leave them in a very excited place. Notice that they will have a lot of glands, which will be running, the eyes, the nose, and often the intestines. The pupils will be now dilated. They'll often have fever, be unable to sleep, and have tachycardia. One of the classic things that a physician can look for are physical signs of injection along veins, looking for needle puncture sites and old abscesses. The only issue there is, are they acute, or are they scarred from prior use? It's easy to think of looking for track marks along the veins in the arms and the forearms. But drug users often use their feet, their thighs, their neck, or even less visible parts of the body. Drug users will often masquerade injection sites by injecting into hairy areas, or tattoos, or scars. You notice in this picture that there are linear scars from the injection of hypertonic solution. The only question is, are these old scars, or are these fresh? Because this is a quick overview, we're now going to move to the category of stimulants. Again, there are many categories of stimulants. And you'll notice that only three, cocaine, amphetamine, and methamphetamines, are included in the federal panel. We won't talk about nicotine, caffeine, the theobromine that's found in chocolate, which are also stimulants. You can see bath salts here. They are frequently misused by people who want to avoid being detected. And so they use an innocent sounding substance, which in fact, can be quite harmful. Cocaine can often be in very small quantities that fit in a pocket. Here you see what might be called a nickel bag. Because crack cocaine is not very water soluble, the powder is often put onto a sheet of tinfoil. Water is dripped on top of it. And then it is heated until the water mixes with the cocaine. And then it's vaporized and inhaled or snorted. You can see how quickly cocaine enters the body. If it is snorted intranasally, 30 seconds to two minutes and a person is having a full dose. If it's injected, it can be even quicker, within 15 seconds. And even smoking, as a route of entry, it only takes 10 seconds. So people get high on cocaine very quickly. It also doesn't last very long. And so they need to take repeated doses throughout a few hours. The synthetic cathinones represent a wide variety of chemicals. You can see that the routes of administration are many. They can be snorted or smoked or swallowed. They have very strong psychoactive effects. And they produce many symptoms, including panic attacks and sometimes violent behavior. Essential nervous system stimulants, these chemicals will have the opposite effect of the opiates and opioids. So here you'll have tachycardia, pupillary dilatation, elevated blood pressure, often hyperthermia. People who take stimulants chronically can take them for weight loss. And chronic users also often have severe impairment of memory and attention. A stimulant overdose can be truly life-threatening. As an emergency room doctor, I used to see people coming in who were extremely agitated. They were hyperthermic. They were having active hallucinations. And often, they had convulsions. And some died. Stopping using a stimulant can cause central nervous system depression and also a lot of confusion. Sometimes it produces insomnia. Sometimes it produces insomnia. And sometimes people can't sleep. Heavy doses of stimulants can sometimes be life-threatening. Imagine, for example, the All-American Basketball Center. Leonard Bias from the University of Maryland, who was first-round draft pick, went out to celebrate with his friends and died that night from a heart attack. The nation was shocked. But what happened was that he had been using cocaine. These are often treated as medical emergencies. They require intensive care units and sedative and hypnotic medication. A third category of psychoactive substances are the psychedelics, or so-called hallucinogens. There are many different psychedelic compounds. As you see, only the first three are tested for in the federal panel, marijuana, fencyclidine, and MDMA, or ecstasy, and its related compounds. So the federal panel does not test for the mimics of marijuana, so-called cannabinomimetics, nor does it test for LSD, ketamine, the psilocybin found in mushrooms, and mescaline found in the cactus plant. Many marijuana growers plant a plant or two in a field of corn, because to the human eye, it looks about the same color of green. However, surveillance aircraft can spot it very easily. Marijuana has very distinctive leaves. Marijuana grows best in bright and hot sun. The sunlight hits the top of the marijuana plant, the flower, and it produces an oily, sticky substance, which contains most of the tetrahydrocannabinol. The cut marijuana leaves can be rolled into cigarettes, some of which are very funny looking. Because of outdoor surveillance, a lot of marijuana growing has now been moved indoor to greenhouses, or in this case, into a designer living room. So there you see a tank of carbon dioxide, which is making the plants grow more quickly. There are intense sunlights in the ceiling, and you see fans to circulate the air. Marijuana cigarettes are usually smoked. The effects begin in a few minutes and only last sometimes 30 or 60 minutes, which is why joints are often passed around multiple times during one sitting. Marijuana is not very bioavailable, so when it's taken orally, sometimes it's baked in brownies. The effect takes longer, particularly on an empty stomach, and it also lasts longer. And because the titration of dose is more difficult, people often do have overdoses. That's what we saw in the state of Colorado when people started eating THC gummy bears. So the effects of marijuana begin within a few minutes. A person comes up and may get what is called high. They will plateau in 15 to 30 minutes, which is why they often have another hit. And then they begin to come down after 45 to 60 minutes. But the effects linger, and the psychomotor effects linger for a number of hours as well. Marijuana is described as a pleasant and relaxing drug. One of its effects is to affect the central nervous system and increase sensory awareness. So people smoking marijuana may want to do it before they go to a rock concert or listen to music. They may do it before they're eating or have a case of the munchies. And if you remember the very colorful psychedelic posters in the 60s, there's also increased visual awareness. For people who are not used to smoking, of course, it can cause upper respiratory irritation, and it can trigger asthma. There's no question that the effects of THC are to slow down the psychomotor system, and there are clearly adverse effects in eye-hand coordination. Interestingly, it does not produce physiologic dependence, but it does produce psychological dependence. 20 years ago, the potency of marijuana might have been 4% or 5% THC. But with the hybridization and the growing techniques, the potency has increased dramatically, sometimes to 15% or 20%. So people can get an overdose from just a few puffs of marijuana, particularly an inexperienced user. This can lead to agitation, to a racing heart, to extreme anxiety and panic attacks. Increased number of emergency room visits are from people who are having these attacks and believe that they're going to die and they seek medical care. Ecstasy and its many analogs are basically synthetic methamphetamines. They have both stimulant properties as well as mild hallucinogenic properties. So they combine the effects of two classes of drugs. They're usually used in recreational and social settings such as raves, which I mentioned earlier. And so they're often called designer drugs or club drugs. So MDMA and its analogs have stimulant properties similar to that of an amphetamine or a methamphetamine, but also the hallucinogenic qualities that might resemble mescaline. They can be very risky and include dehydration, inappropriate ADH, and produce visual and sometimes verbal memory impairment. MDMA is often called an empathogen because it's taken in a social setting. It not only increases one's mood, but brings about a willingness to communicate, to connect, feeling of comfort and belonging and closeness to other people, feelings of love and empathy. Like marijuana, it increases sensory awareness and appreciation of music and color and taste, but it can cause visual distortion. It's one of the few drugs that can cause open-eyed nystagmus, and it can also affect temperature regulation. Here you see additional adverse effects of ecstasy. It often leads to a post-trip crash with a hangover that can last from days to weeks and is often accompanied by depression. Fencyclidine or PCP is one of the most dangerous of the psychedelic drugs. People who are smoking marijuana, some cigarettes will sometimes have the powder sprinkled into the cigarette before it is rolled, and they sometimes experience a bad trip, not due to the marijuana, but due to the PCP. PCP acts as a dissociative anesthetic, so a person can literally have their mind leave their body, and you can see that there are many different routes of administration. Because it is a dissociative anesthetic, PCP can sometimes cause change of body awareness, sort of a dreamlike state and depersonalization, and people seem like they're almost zombies. As an emergency physician, I once saw a fellow who had walked through a plate glass window and was brought to the emergency room in a stretcher just covered with glass and cuts. He was so agitated and so combative that it took four policemen to hold him down just as we debrided his wounds, and he had such muscle rigidity that we gave him intramuscular valium just to settle him down. It was a very scary experience. The synthetic cannabinoids or cannabinomimetics consist of a large group of different drugs. Many of them have innocent sounding names like K2, the second highest mountain in the world after Mount Everest, or Spice. The initials JWH represent a pharmacologist who worked for a pharmaceutical company and was synthesizing many agents looking for one with therapeutic effects. The effects of these drugs are often much more potent, though, than the natural cannabinoids, and as a result they can produce much more severe effects. Not only can they trigger acute psychosis, but sometimes the psychosis can be persisting. So in summary, the psychedelics or hallucinogens represent a wide variety of compounds that affect the central nervous system, alter perceptions, sensory awareness, and feelings. Interestingly, although all of these drugs can produce hallucinations and induce psychosis, hallucinogens rarely produce frank hallucinations. The fourth category of psychoactive drugs are the sedatives. The sedatives are a wide variety of central nervous system depressants. The most commonly used, of course, is alcohol, which is used by about half of the population. The benzodiazepines, which are short-acting drugs, and Ambien, which is a benzodiazepine-like sleeping medication. They also include the longer-acting barbiturates and barbiturate-like drugs. Chloral hydrate was the liquid drug that was sometimes used in the Old West. Someone would be at the bar, leave their horse outside, they would go into the restroom, and someone would slip them a Mickey fin, and they would be drinking their sarsaparilla, and then they would end up on the floor and their horse would be gone. Soma is a muscle-relaxing drug. It's often used by physical fitness and trainers, and it can also lead to addiction. Like all of the psychoactive drugs, men tend to use them more than women. But interestingly, women absorb alcohol more quickly than men do, and they metabolize it more slowly. That's the reason why women should not get into drinking contests with men. At some college campuses, we see these drinking contests where a man and a woman stand chin-to-chin, each one taking one more shot, one more shot, to see who can drink the most. But a half an hour or an hour later, the woman may be unconscious, lying on the floor. Alcohol use peaks the same age as the other psychedelic drugs in the 18- to 25-year range. Interestingly, about half of alcoholics meet criteria for other psychiatric disorders, and they may actually be self-medicating. Just like we talked about with stimulants, alcohol withdrawal can be very life-threatening, and no longer are people encouraged to come down cold turkey, but medication is given. The effects of alcohol correlate very closely to both the blood and the breath alcohol concentrations. So you can see that on the left, if a person had one or two drinks, they may feel more relaxed, more self-confident, feeling more sociable. Their inhibitions may be reduced, and they may be the life of the party. But these people are already impaired, and that's why the DOT rules are very clear that at 0.02, one may not be working in a safety-sensitive job, and at 0.04, they are violating the federal alcohol rules. On the right, you see the effects of people who have had four or more drinks. So now we see their speech is slurred, their balance may be impaired, their reflexes are diminished, and they may become very emotionally unstable. At 0.18, which is the equivalent of nine drinks, a person is really going to be in trouble, and this is where you could talk about alcohol poisoning. So this person is not going to be able to function without assistance. They'll probably be very sleepy. They certainly won't remember what happened. They may lose bladder and bowel control, and as they lose consciousness, they can slip into a coma and even die. One concern about heavy alcohol drinking is not just the effects on the individual, but the impact on other people. Here you see that alcohol intoxication is very strongly associated with motor vehicle accidents and traffic fatalities, as well as home fires and deaths, falls, drowning, particularly in boating, and child abuse, suicides, and 10% of industrial accidents are estimated to be related directly to alcohol intoxication. When a chronically heavy drinker suddenly stops taking alcohol, it has very, very powerful physiologic effects. These people become extremely anxious. They get a case of the shakes. They may sweat and be agitated, and if they are moving toward classic delirium tremens or the DTs, they may actually feel like bugs or ants are crawling on their skin, like they're hearing voices talking to them, and they're actually seeing things that don't exist. I had a chance to witness somebody going through DTs when I was a psychiatric intern in college, and it was a very, very frightening experience, so I can understand how this alcohol withdrawal can be fatal. Another class of sedatives are the wide range of benzodiazepine drugs, and, of course, these are widely prescribed in clinical medical practice for anxiety, for muscle tension, to help people sleep, and other causes. If you read the PDR insert, you'll see that they definitely are warned not to operate hazardous machinery, not to drive a vehicle until they know what the effects are going to be. You may wonder why they were not included in the federal drug testing panel, and the reason because there's so many different compounds that there are not good laboratory standards for measuring them. The final class of sedatives are the barbiturates. These are longer-acting drugs that used to be used for epilepsy as long-acting sleeping medications and as sedatives, but they have been replaced generally by the safer benzodiazepines, so even though they're not in widely use, they're still often in medicine cabinets, and you can see that young people who are looking for drug experiences will often experiment with them. I mentioned earlier Soma, which is a muscle relaxant that has also been used by trainers and people in physical fitness and has been addictive and gotten them into trouble. The withdrawal symptoms of all of these sedative drugs are very similar. Since they're a central nervous system depressant like the opiates, when one is withdrawing from them, they're likely to be much more up and much more agitated, so people will be anxious. They may be irritable. They may not be able to sleep. They may have the shakes and even have seizures. The final class of psychoactive substances are those that are inhaled. Here you see a long list of the inhalants, all of which are compounds that are volatile enough that they have distinctive odors, they can reach the central nervous system, and have very distinctive effects. All the inhalants are central nervous system depressants, similar to general anesthetic agents. They can be hepatotoxic, they can be cardiotoxic, and they can be toxic to the reticular endothelial system. So there are no inhalants included in the federal panel, but we included them for completeness. This has been a very quick run-through of these five classes of psychoactive drugs. For more information, you probably will want to talk with an addiction medicine specialist, and as an MRO, you'll have an opportunity occasionally to talk with an SAP, and many SAPs are also addiction medicine specialists.

psychoactive substances

opiates

opioids

stimulants

sedatives

inhalants