MCAT Behavioral Sciences Review - Kaplan Test Prep 2021–2022

4.4 Consciousness-Altering Drugs
Cognition, Consciousness, and Language

LEARNING OBJECTIVES

After Chapter 4.4, you will be able to:

· List the drugs (or drug classes) known to increase GABA activity in the brain

· Recall the drugs (or drug classes) known to upregulate dopamine, norepinephrine, or serotonin activity

· Identify the three main structures in the mesolimbic reward pathway and the primary neurotransmitter of the pathway:

Consciousness-altering drugs, also known as psychoactive drugs, are generally described in four different groups: depressants, stimulants, opiates, and hallucinogens. Biologically speaking, marijuana has depressant, stimulant, and hallucinogenic effects, and will be considered separately.

DEPRESSANTS

Depressants reduce nervous system activity, resulting in a sense of relaxation and reduced anxiety. Of the depressants, alcohol is certainly the most common. Another is sedatives, or "downers", which calm and induce sleep.

Alcohol

Alcohol has several different effects on the brain. It increases activity of the GABA receptor, a chloride channel that causes hyperpolarization of the membrane, as shown in Figure 4.11. This hyperpolarization causes generalized brain inhibition at the physiological level, resulting in diminished arousal at moderate doses. The changes in brain activity also cause changes in outward behavior. For example, excessive consumption of alcohol may be associated with a notable a lack of self-control known as disinhibition, which occurs because the centers of the brain that prevent inappropriate behavior are also depressed. Alcohol also increases dopamine levels, causing a sense of mild euphoria. At higher doses, brain activity becomes more disrupted. Logical reasoning and motor skills are affected, and fatigue may result. One of the main effects on logical reasoning is the inability to recognize consequences of actions, creating a short-sighted view of the world called alcohol myopia. Alcohol use is implicated in many automobile accidents, homicides (for both perpetrator and victim), and hospital admissions. Intoxication with alcohol is often measured using blood alcohol level.

Figure 4.11. GABA ReceptorGABA is the primary inhibitory neurotransmitter in the brain; its receptor is a chloride channel that causes hyperpolarization of the membrane.

Alcohol is one of the most widely abused drugs. Alcoholism rates tend to be higher for those of lower socioeconomic status (SES), but low-SES alcoholics tend to enter recovery sooner and at higher rates. Alcoholism tends to run in families, and children of alcoholics are also likely to suffer from major depressive disorder. Long-term consequences of alcoholism include cirrhosis and liver failure, pancreatic damage, gastric or duodenal ulcers, gastrointestinal cancer, and brain disorders including Wernicke—Korsakoff syndrome, caused by a deficiency of thiamine (vitamin B₁) and characterized by severe memory impairment with changes in mental status and loss of motor skills.

Sedatives

Sedatives tend to depress central nervous system activity, resulting in feelings of calm, relaxation, and drowsiness. Two types of sedatives are barbiturates and benzodiazepines. Barbiturates were historically used as anxiety-reducing (anxiolytic) and sleep medications, but have mostly been replaced by benzodiazepines, which are less prone to overdose. Barbiturates include amobarbital and phenobarbital; benzodiazepines include alprazolam, lorazepam, diazepam, and clonazepam. These drugs also increase GABA activity, causing a sense of relaxation. However, both of these drug types can be highly addictive. If taken with alcohol, overdoses of barbiturates or benzodiazepines may result in coma or death.

STIMULANTS

Stimulants cause an increase in arousal in the nervous system. Each drug increases the frequency of action potentials, but does so by different mechanisms.

Amphetamines

Amphetamines cause increased arousal by increasing release of dopamine, norepinephrine, and serotonin at the synapse and decreasing their reuptake. This increases arousal and causes a reduction in appetite and decreased need for sleep. Physiological effects include an increase in heart rate and blood pressure. Psychological effects include euphoria, hypervigilance (being “on edge”), anxiety, delusions of grandeur, and paranoia. Prolonged use of high doses of amphetamines can result in stroke or brain damage. Users often suffer from withdrawal after discontinuation, leading to depression, fatigue, and irritability.

Cocaine

Cocaine originates from the coca plant, grown in the high-altitude regions of South America. Cocaine can be purified from these leaves or created synthetically. Similar to amphetamines, cocaine also acts on dopamine, norepinephrine, and serotonin synapses, but cocaine decreases reuptake of the neurotransmitters instead. Hence, the effects of cocaine intoxication and withdrawal are therefore similar to amphetamines, as listed above. Cocaine also has anesthetic and vasoconstrictive properties, and is therefore sometimes used in surgeries in highly vascularized areas, such as the nose and throat. These vasoconstrictive properties can also lead to heart attacks and strokes when used recreationally. Crack is a form of cocaine that can be smoked. With quick and potent effects, this drug is highly addictive.

Ecstasy (3,4-methylenedioxy-N-methylamphetamine, MDMA)

Ecstasy, commonly called “E,” acts as a hallucinogen combined with an amphetamine. As a designer amphetamine, its mechanism and effects are similar to other amphetamines. Physiologically, ecstasy causes increased heart rate, increased blood pressure, blurry vision, sweating, nausea, and hyperthermia. Psychologically, ecstasy causes feelings of euphoria, increased alertness, and an overwhelming sense of well-being and connectedness. Ecstasy is an example of a club or rave drug, and is often packaged in colorful pills, as shown in Figure 4.12.

Figure 4.12. Pills of Ecstasy (MDMA)

OPIATES AND OPIOIDS

Opiates and opioids are types of narcotics, also known as painkillers. Derived from the poppy plant, opium has been used and abused for centuries. Today, we have numerous drugs, used both recreationally and therapeutically, derived from opium. Naturally occurring forms, called opiates, include morphine and codeine. Semisynthetic derivatives, called opioids, include oxycodone, hydrocodone, and heroin. These compounds bind to opioid receptors in the peripheral and central nervous system. They act as endorphin agonists and cause a decreased reaction to pain and a sense of euphoria. Overdose, however, can cause death by respiratory suppression, in which the brain stops sending signals to breathe.

Heroin, or diacetylmorphine, was originally created as a substitute for morphine. Once injected, the body rapidly metabolizes heroin to morphine. Usually smoked or injected, heroin was once the most widely abused opioid; however, this designation has shifted to prescription opioids like oxycodone and hydrocodone. Treatment for opioid addiction may include use of methadone, a long-acting opioid with lower risk of overdose.

HALLUCINOGENS

Hallucinogens are drugs which typically cause introspection, distortions of reality and fantasy, and enhancement of sensory experiences. Physiologic effects include increased heart rate and blood pressure, dilation of pupils, sweating, and increased body temperature. Examples of hallucinogens include lysergic acid diethylamide (LSD), shown in Figure 4.13, peyote, mescaline, ketamine, and psilocybin-containing mushrooms. The exact mechanism of most hallucinogens is unknown, but is thought to be a complex interaction between various neurotransmitters, especially serotonin.

Figure 4.13. Sheet of LSD Blotter PaperLSD is often sold on colorful paper, reflecting the fact that, like ecstasy, LSD is considered a club drug.

MARIJUANA

Marijuana, shown in Figure 4.14, primarily refers to the leaves and flowers of two plant species: Cannabis sativa and Cannabis indica. It has been the subject of many news reports in the last few years as many states move toward the legalization of marijuana for medical or recreational use. While talks about the legal status of marijuana in the United States are fairly recent, marijuana has been used for centuries, with the earliest known accounts originating from approximately 3 B.C.E.

Figure 4.14. Cannabis

The active chemical in marijuana is known as tetrahydrocannabinol (THC). THC exerts its effects by acting at cannabinoid receptors, glycine receptors, and opioid receptors. How these receptors interact to create the “high” achieved from marijuana use is unknown. It is known, however, that THC inhibits GABA activity and indirectly increases dopamine activity (causing pleasure). Physiological effects are mixed, including eye redness, dry mouth, fatigue, impairment of short-term memory, increased heart rate, increased appetite, and lowered blood pressure. Psychologically, effects seem to fall into the categories of stimulant, depressant, and hallucinogen.

DRUG ADDICTION

Drug addiction is highly related to the mesolimbic reward pathway, one of four dopaminergic pathways in the brain, as shown in Figure 4.15. This pathway includes the nucleus accumbens (NAc), the ventral tegmental area (VTA), and the connection between them called the medial forebrain bundle (MFB). This pathway is normally involved in motivation and emotional response, and its activation accounts for the positive reinforcement of substance use. This addiction pathway is activated by all substances that produce psychological dependence. Gambling and falling in love also activate this pathway.

Figure 4.15. Dopaminergic Pathways in the BrainThe reward pathway is composed of the nucleus accumbens, ventral tegmental area (VTA), and the medial forebrain bundle between them (not labeled).

MCAT Concept Check 4.4:

Before you move on, assess your understanding of the material with these questions.

1. Which three drugs (or drug classes) are known to increase GABA activity in the brain?

o

o

o

2. Which three drugs (or drug classes) are known to increase dopamine, norepinephrine, and serotonin activity in the brain?

o

o

o

3. What are the three main structures in the mesolimbic reward pathway? What is this pathway’s primary neurotransmitter?

o Structure:

o Structure:

o Structure:

o Neurotransmitter: