Substance Abuse, Intoxication & Withdrawal: Uppers, Downers & Hallucinogens

Substance dependence is an adaption to a pattern of substance use. It is primarily characterized by withdrawal (symptoms that occur when use of the drug is discontinued), tolerance (needing more to obtain the same effect), and spending a significant portion of their time engaged in drug related activities. Substance abuse is an overindulgence in an addictive substance as a result of a lack of control. It can be thought of as a more extreme version of substance dependence in which individuals have significant negative life effects (work/relationships/school), poor health, or legal problems as a result of their substance use. In the general public this pattern of substance abuse would more generally be referred to as an addiction.

For simplicity sake we will break the drugs down into 3 different categories. The 3 categories are Uppers, Downers and Hallucinogens. There are slight differences between drugs within individual categories, but for the most part you can get questions right by just knowing the general characteristics of the entire group. For example, you won’t see both cocaine and NDMA listed as answers on the same question.


Also don’t confuse intoxication and withdrawal. Most questions are on drug intoxication, but they may specifically ask you about withdrawal which usually has symptoms that are just the opposite of intoxication. Make sure you read the question carefully. For example, the question stem may sound similar to stimulant withdrawal and depressant intoxication, but the last sentence of the question specifically asks about withdrawal.

Keep in mind the most important things for Step 1 questions are the changes to the vitals and pupils. You will almost always be given this information in these types of questions and if you just have that info you can usually narrow it down to at least 2 options.

And make sure you don’t get mydriasis vs. miosis confused. Mydriasis is the bigger word and has the bigger pupils. Miosis is the smaller word and has the smaller pupils.

Obviously, the best way to confirm a diagnosis of drug use is a urine drug screen and mental health services are important in the treatment of addiction. However, that is too easy so you won’t see that as an answer on the exam.

Uppers (Stimulants)

Most of the questions related to this category will be about cocaine, which is usually smoked in the form of crack cocaine or snorted. However, other street drugs such as Methamphetamines (Meth) & MDMA (Ecstasy & Molly) are also in this group. Prescription drugs used for ADHD, narcolepsy and weight loss are also stimulants, but are less likely to show up in this type of Step 1 question. This group of drugs functions through a number of different mechanisms, but primarily increases dopamine and/or norepinephrine in the synaptic cleft by inhibiting the reuptake of these neurotransmitters.

Patients under the influence of these drugs will have an acceleration of the nervous system. Symptoms of stimulant use can include “increased vitals” (tachycardia, hypertension, temp and/or respirations), pupillary dilation, irritability, anxiety, hyperactivity, diaphoresis & elevated mood. Nasal septum ulceration/perforation and nasal mucosal atrophy is a result of vasoconstriction in individuals who snort cocaine. Accelerated tooth decay and tooth loss is seen more commonly in users of meth and is sometimes referred to as “Meth Mouth.” Higher doses of these drugs result in overdose which can lead to MI/Angina, seizure, hyperthermia, stroke, arrhythmias, psychosis, rhabdomyolysis or sudden death. Treatment for an acute intoxication often includes a combination of benzodiazepines, antihypertensive and/or antipsychotics. Withdrawal from Uppers usually presents with a “crash” following drug cessation. It is generally not life threatening, but presents with fatigue, depression, irritability, and psychomotor retardation.

Downers (Depressants)

Alcohol, opioids/opiates (heroin, morphine, hydrocone, oxycodone etc.), Sedative-hyponotics (benzos & barbs) fall into the category of downers. These drugs decrease neurotransmitters in the nervous system and as you would expect largely has a presentations that is the opposite of uppers. This class of drugs works through a number of different mechanisms, but mostly is due to activation of inhibitory GABA and inhibition of excitatory glutamate.


The use of downers can result in “depressed vitals,” pupillary constriction, ↓ pain perception (hence why opioids are pain medications), ↓ gastrointestinal motility (abdominal pain & constipation), agitation, decreased anxiety (hence why benzos are used as anxiolytics), and somnolence/sedation. At higher doses an overdose can lead to loss of consciousness and respiratory depression (shallow or slow breaths). Alcohol intoxication can more commonly present with disinhibition, slurred speech, falls, incoordination, blackouts, nausea & vomiting. A hangover classically presents with nausea, headache, fatigue, dizziness, gastrointestinal problems, changes in mood & dehydration. There are a couple laboratory tests that should also make you consider alcoholism. The two most important one are an elevation in gamma-glutamyl transpeptidase (GGT) and elevated liver enzymes (with an AST:ALT ratio ≥ 2:1). Heroin users may have identifiable needle marks or track marks.


The most important intervention for severe overdose of a downer is ventilatory support for respiratory depression. For opioid overdose you often use an opioid antagonist such as Naloxone (Narcan), but you also have to be careful with the dose you give as you can easily cause withdrawal by giving too much. Flumazenil is a benzo receptor antagonist that is sometimes used to treat benzo overdose. Gastric lavage (AKA getting your stomach pumped) and activated charcoal are rarely used in overdoses.


Opioid use disorder is usually going to be treated with a combination of psychosocial interventions and pharmacologic interventions. This usually involves a medication such as Methadone (long acting opioid agonist), Buprenorphine (AKA Suboxone, a partial opioid agonist) or Clonidine (an alpha-2 adrenergic agonist).


You can use a hangover to you advantage when Disulfiram is used to treat alcoholism and prevent relapse. This drug Inhibits Acetaldehyde Dehydrogenase and makes patients very sick if they drink any alcohol as Acetaldehyde builds up much faster. You are essentially giving them a really bad hangover on purpose to dissuade them from drinking. However, this it is not always effective as there is relatively low compliance for this drug. Patients considering drinking can think ahead and easily not take their medication to avoid the consequences. This is why Disulfiram is not commonly used, but since it has basic science correlations it still shows up in test questions. There are other pharmacologic agents that are sometimes used to prevent relapses such as Naltrexone. More commonly counseling and mental health interventions like a 12 step program are going to be the treatment of choice for alcoholism and opioid addiction.


Most of the withdrawal questions you get will be about the downers. Withdrawal presents with symptoms that are the opposite of intoxication. So you will have elevated vitals, dilated pupils, rhinorrhea, diarrhea, excessive perspiration, restlessness, insomnia, anxiety, irritability & nausea/vomiting. An odd presentation that should stick out as a buzzword to you is yawning. Opioid withdrawal is extremely uncomfortable, but is not usually life threatening. Benzodiazepine withdrawal and alcohol withdrawal present very similarly and can be life threatening. Prescription benzodiazepines, especially short acting benzodiazepines, should be tapered to prevent withdrawal.


Alcohol withdrawal has all of the withdrawal symptoms we have discussed, but can also have tremor, seizures, confusion, hallucinations (mostly visual), delirium, coma and death. The severe form of alcohol withdrawal is referred to as Delirium Tremens or DTs. The first line treatment for DTs is benzodiazepines. You also have to monitor electrolytes (like magnesium) and vitamins (like thiamine & folate). Antipsychotics and/or temporary restraints may be necessary for severe agitation.


PCP (Phencyclidine), LSD (Lysergic acid diethylamide) and psychedelic mushrooms are in a category of drugs called Hallucinogens. As you might guess by the name the main feature of this class is hallucinations and other psychotic features. This can be in the form of visual or tactile hallucinations and may be tough to differentiate from cocaine induced psychosis and other psychiatric illnesses that are unrelated to substance abuse.


Use of these drugs is not always accompanied by hallucinations, but you are unlikely to see a question on the exam that is missing this classic presentation. However, it may be useful to know that this diverse group of substances can also cause disorganized thoughts, paranoia, euphoria, anxiety, labile mood, belligerence, synesthesia (letters or numbers are perceived as color), incoordination and hyperthermia. The effect on vitals and pupils varies with dose and the specific agent being used. PCP is associated with violence & aggression more than any other drug. PCP intoxication also classically presents with Vertical or Horizontal Rotary Nystagmus (rhythmic eye motions). Benzodiazepines and antipsychotics may be used for treatment, but you can often just monitor the patient for dangerous behavior. These substances usually don’t present with withdrawal symptoms



Marijuana can cause conjunctival injection (red eyes), increased appetite (“the munchies”),

euphoria, perceptual changes, mild tachycardia, anxiety, and dry mouth. Marijuana may also be associated with schizophrenia and transient psychosis which is why some may put it in the hallucinogen category. Users of marijuana usually do no present with overdose or withdrawal symptoms. No pharmacologic treatment is needed.




Pictures Used:

  • Derivative of “Occhi222” by Ladysiria17 available at via Public Domain
  • Derivative of “Anizokoria” by Radomil available at via Creative Commons 3.0 Attribution-Share Alike
  • “Crystal Meth” by Radspunk available at via Creative Commons 4.0 Attribution-Share Alike
  • “Man sniffing” available at
  • “Alcohol desgracia” by RayNata available at via Creative Commons Attribution – Share Alike
  • Derivative of “Amanita muscaria crop” by Onderwijsgek available at via Creative Commons 3.0 Attribution-Share Alike
  • Derivative of “kaleidoscope explosion colors” available at via Public Domain

Free USMLE Step1 Videos