Drugs and Substances: Learn It 3—Stimulants

Stimulants

stimulants

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 this category include cocaine, amphetamines (including methamphetamine), cathinones (i.e., bath salts), MDMA (ecstasy), nicotine, and caffeine.

An illustration of a presynaptic cell and a postsynaptic cell shows these cells’ interactions with cocaine and dopamine molecules. The presynaptic cell contains two cylinder-shaped channels, one on each side near where it faces the postsynaptic cell. The postsynaptic cell contains several receptors, side-by-side across the area that faces the presynaptic cell. In the space between the two cells, there are both cocaine and dopamine molecules. One of the cocaine molecules attaches to one of the presynaptic cell’s channels. This cocaine molecule is labeled “bound cocaine.” An X-shape is shown over the top of the bound cocaine and the channel to indicate that the cocaine does not enter the presynaptic cell. A dopamine molecule is shown inside of the presynaptic cell’s other channel. Arrows connect this dopamine molecule to several others inside of the presynaptic cell. More arrows connect to more dopamine molecules, tracing their paths from the channel into the presynaptic cell, and out into the space between the presynaptic cell and the postsynaptic cell. Arrows extend from two of the dopamine molecules in this in-between space to the postsynaptic cell’s receptors. Only the dopamine molecules are shown binding to the postsynaptic cell’s receptors.
Figure 1. As one of their mechanisms of action, cocaine and amphetamines block the reuptake of dopamine from the synapse into the presynaptic cell.

Cocaine

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, extending the feeling of pleasure from the release of dopamine.

Amphetamines

Amphetamines have a mechanism of action quite similar to cocaine in that they block the reuptake of dopamine in addition to stimulating its release.

Understanding “Meth”

Methamphetamine is a synthetic stimulant. In its smokable crystal form (“crystal meth”), it reaches the brain quickly and can produce an intense but short-lived euphoria—especially when smoked or injected—which can lead to repeated dosing over hours or days (“runs”). Common harms include cardiovascular strain, overheating, sleep loss, agitation/paranoia, skin-picking, and severe dental problems (“meth mouth”).

Methamphetamine is a type of amphetamine that can be manufactured from readily available precursor chemicals. Despite regulatory changes designed to restrict access to pseudoephedrine (found in over-the-counter cold remedies), methamphetamine production has shifted primarily to sophisticated cartel-run laboratories. This has resulted in a more potent, pure, and inexpensive product flooding U.S. markets.

Methamphetamine use poses numerous serious long-term health risks:

  • Dental problems: Often called “meth mouth,” characterized by severe tooth decay and gum disease
  • Dermatological issues: Skin abrasions and sores caused by excessive scratching
  • Cognitive impairment: Memory loss and difficulty with executive function
  • Sleep disturbances: Chronic insomnia and disrupted sleep patterns
  • Psychiatric symptoms: Paranoia, hallucinations, and violent behavior. Methamphetamine-involved psychiatric hospitalizations increased by 68% between 2015 and 2019, reflecting the drug’s significant impact on mental health.
  • Cardiovascular complications: Increased risk of heart attack and stroke

The Polysubstance Crisis: Methamphetamine and Fentanyl

A concerning development dubbed the “fourth wave” of the overdose epidemic involves the increasing contamination of methamphetamine with fentanyl. Nearly 93% of fentanyl-positive urine samples contain additional substances, with stimulants like methamphetamine frequently detected. In 2023, 60% of specimens from patients who had used fentanyl also tested positive for methamphetamine, representing an 875% increase since 2015.[1]

This combination creates unique dangers. People who use methamphetamine without prior opioid tolerance face unexpected fentanyl exposure, dramatically increasing overdose risk.[2]

While amphetamines are often abused, there are also instances where amphetamines are a treatment option for various medical conditions or disorders. Amphetamines, such as Adderall, are 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.

MDMA

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 can be altered after repeated use as a result of an overall depletion of 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 re-establish the person’s physical and psychological pre-use baseline. (Jayanthi & Ramamoorthy, 2005; Rothman, Blough, & Baumann, 2007).

Caffeine

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 a neurotransmitter that promotes sleep. Caffeine is an adenosine antagonist, so caffeine inhibits the adenosine receptors, thus decreasing sleepiness and promoting wakefulness.

While caffeine is generally considered a relatively safe drug, high blood levels of caffeine can result in insomnia, agitation, muscle twitching, nausea, irregular heartbeat, and even death (Reissig, Strain, & Griffiths, 2009; Wolt, Ganetsky, & Babu, 2012).

In 2012, Kromann and Nielson[3] reported on a case study of a 40-year-old woman who suffered significant ill effects from her use of caffeine. The woman used caffeine in the past to boost her mood and to provide energy, but over the course of several years, she increased her caffeine consumption to the point that she was consuming three liters of soda each day. Although she had been taking a prescription antidepressant, her symptoms of depression continued to worsen and she began to suffer physically, displaying significant warning signs of cardiovascular disease and diabetes. Upon admission to an outpatient clinic for treatment of mood disorders, she met all of the diagnostic criteria for substance dependence and was advised to dramatically limit her caffeine intake. Once she was able to limit her use to less than 12 ounces of soda a day, both her mental and physical health gradually improved. Despite the prevalence of caffeine use and the large number of people who confess to suffering from caffeine addiction, this was the first published description of “cola dependence” appearing in scientific literature.

Nicotine

Nicotine is highly addictive and primarily consumed through tobacco products. It exerts its effects by interacting with acetylcholine receptors in the nervous system. Acetylcholine functions as a neurotransmitter in motor neurons and plays a crucial role in arousal and reward mechanisms in the central nervous system. This interaction with the reward system contributes to nicotine’s highly addictive properties. When tobacco is smoked, nicotine rapidly enters the bloodstream through the lungs, reaching the brain within seconds. This quick delivery contributes to its reinforcing effects and addiction potential.

The use of tobacco products is associated with serious health consequences, including increased risks of heart disease, stroke, chronic obstructive pulmonary disease (COPD), and at least 12 types of cancer. Quitting smoking reduces these risks and can add as much as a decade to life expectancy.

Vaping

Vaping uses battery-powered devices (e-cigarettes, vape pens) to heat liquid containing nicotine and flavorings into an aerosol that users inhale. Initially marketed as a safer alternative to traditional cigarettes, vaping has proven to cause serious health problems.

In 2019, an outbreak of severe lung injuries linked to vaping emerged, leading to a condition known as E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI). Research identified vitamin E acetate—a thickening agent added to some THC-containing vaping products—as the primary cause of EVALI. While safe to ingest or apply to skin, this substance causes severe lung damage when heated and inhaled.[4]

Beyond EVALI, vaping poses additional health concerns. Nicotine can harm brain development, which continues through approximately age 25. E-cigarette aerosols may contain heavy metals from device heating coils (including lead, chromium, and nickel) and other potentially harmful substances. Some research suggests vaping can cause lung damage after only a few days of use.

To learn more about some of the most commonly abused prescription and street drugs, check out the Commonly Abused Drugs Chart and the Commonly Abused Prescription Drugs Chart from the National Institute on Drug Abuse.
  1. Millennium Health. (2025, February 11). Fentanyl use declines in 2024 but people who use fentanyl are increasingly using heroin, methamphetamine [Press release]. Business Wire. https://www.businesswire.com/news/home/20250211045455/en/Fentanyl-Use-Declines-in-2024-but-People-Who-Use-Fentanyl-are-Increasingly-Using-Heroin-Methamphetamine ↵
  2. Innovo Detox. (2025, April 17). Meth statistics in the United States. https://www.innovodetox.com/addiction/drugs/statistics-meth/ ↵
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598894/ ↵
  4. Centers for Disease Control and Prevention. (2021, August 3). Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. https://archive.cdc.gov/www_cdc_gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html ↵