With repeated use of many central nervous system depressants, such as alcohol, a person becomes physically dependent upon the substance and will exhibit signs of both tolerance and withdrawal. Psychological dependence on these drugs is also possible. Therefore, the abuse potential of central nervous system depressants is relatively high.
Drug withdrawal is usually an aversive experience, and it can be a life-threatening process in individuals who have a long history of very high doses of alcohol and/or barbiturates. This is of such concern that people who are trying to overcome addiction to these substances should only do so under medical supervision.
Stimulants are drugs that tend to increase overall levels of neural activity. Many of these drugs act as agonists of the dopamine neurotransmitter system. Dopamine activity is often associated with reward and craving; therefore, drugs that affect dopamine neurotransmission often have abuse liability. Drugs in
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this category include cocaine, amphetamines (including methamphetamine), cathinones (i.e., bath salts), MDMA (ecstasy), nicotine, and caffeine.
Cocaine can be taken in multiple ways. While many users snort cocaine, intravenous injection and inhalation (smoking) are also common. The freebase version of cocaine, known as crack, is a potent, smokable version of the drug. Like many other stimulants, cocaine agonizes the dopamine neurotransmitter system by blocking the reuptake of dopamine in the neuronal synapse.
Methamphetamine in its smokable form, often called “crystal meth” due to its resemblance to rock crystal formations, is highly addictive. The smokable form reaches the brain very quickly to produce an intense euphoria that dissipates almost as fast as it arrives, prompting users to continuing taking the drug. Users often consume the drug every few hours across days-long binges called “runs,” in which the user forgoes food and sleep. In the wake of the opiate epidemic, many drug cartels in Mexico are shifting from producing heroin to producing highly potent but inexpensive forms of methamphetamine. The low cost coupled with lower risk of overdose than with opiate drugs is making crystal meth a popular choice among drug users today (NIDA, 2019). Using crystal meth poses a number of serious long-term health issues, including dental problems (often called “meth mouth”), skin abrasions caused by excessive scratching, memory loss, sleep problems, violent behavior, paranoia, and hallucinations. Methamphetamine addiction produces an intense craving that is difficult to treat.
Amphetamines have a mechanism of action quite similar to cocaine in that they block the reuptake of dopamine in addition to stimulating its release (Figure 4.16). While amphetamines are often abused, they are also commonly prescribed to children diagnosed with attention deficit hyperactivity disorder (ADHD). It may seem counterintuitive that stimulant medications are prescribed to treat a disorder that involves hyperactivity, but the therapeutic effect comes from increases in neurotransmitter activity within certain areas of the brain associated with impulse control. These brain areas include the prefrontal cortex and basal ganglia.
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Figure 4.16 As one of their mechanisms of action, cocaine and amphetamines block the reuptake of dopamine from the synapse into the presynaptic cell.
In recent years, methamphetamine (meth) use has become increasingly widespread. Methamphetamine is a type of amphetamine that can be made from ingredients that are readily available (e.g., medications containing pseudoephedrine, a compound found in many over-the-counter cold and flu remedies). Despite recent changes in laws designed to make obtaining pseudoephedrine more difficult, methamphetamine continues to be an easily accessible and relatively inexpensive drug option (Shukla, Crump, & Chrisco, 2012).
Stimulant users seek a euphoric high, feelings of intense elation and pleasure, especially in those users who take the drug via intravenous injection or smoking. MDMA (3.4-methelynedioxy-methamphetamine, commonly known as “ecstasy” or “Molly”) is a mild stimulant with perception-altering effects. It is typically consumed in pill form. Users experience increased energy, feelings of pleasure, and emotional warmth. Repeated use of these stimulants can have significant adverse consequences. Users can experience physical symptoms that include nausea, elevated blood pressure, and increased heart rate. In addition, these drugs can cause feelings of anxiety, hallucinations, and paranoia (Fiorentini et al., 2011). Normal brain functioning is altered after repeated use of these drugs. For example, repeated use can lead to overall depletion among the monoamine neurotransmitters (dopamine, norepinephrine, and serotonin). Depletion of certain neurotransmitters can lead to mood dysphoria, cognitive problems, and other factors. This can lead to people compulsively using stimulants such as cocaine and amphetamines, in part to try to reestablish the person’s physical and psychological pre-use baseline. (Jayanthi & Ramamoorthy, 2005; Rothman, Blough, & Baumann, 2007).
Caffeine is another stimulant drug. While it is probably the most commonly used drug in the world, the potency of this particular drug pales in comparison to the other stimulant drugs described in this section. Generally, people use caffeine to maintain increased levels of alertness and arousal. Caffeine is found in many common medicines (such as weight loss drugs), beverages, foods, and even cosmetics (Herman & Herman, 2013). While caffeine may have some indirect effects on dopamine neurotransmission, its primary mechanism of action involves antagonizing adenosine activity (Porkka-Heiskanen, 2011). Adenosine is
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