Amphetamines

Amphetamines represent a class of central nervous system stimulants that have both therapeutic benefits and significant risks. While these medications play an important role in treating several medical conditions, understanding the side effects of amphetamines (as well as their potential for misuse) is essential for healthcare providers and patients. This comprehensive guide examines the nature of these powerful substances, their medical applications, potential risks, and treatment options for those struggling with dependence.

What are Amphetamines? 

Amphetamines are a type of stimulant that speeds up the body’s systems. They’re available as both legally prescribed substances (e.g., Adderall, Vyvanse) and illegally manufactured and distributed substances (e.g., methamphetamine and 3,4-methylenedioxymethamphetamine [aka ecstasy and MDMA]) ^[1]. 

Many amphetamines are classified as Schedule II controlled substances by the Drug Enforcement Administration, indicating they have a high potential for abuse but also a recognized medical value. Amphetamines are available in various forms, including tablets, capsules, liquids, and powders. While therapeutic doses are usually swallowed, amphetamine misuse occurs in oral ingestion, smoking, and intravenous injection.

How do Amphetamines Work? 

Amphetamines are powerful central nervous system stimulants that work through a sophisticated mechanism in the brain that starts when amphetamine enters the brain’s nerve cells. Here, amphetamine elevates the levels of important brain chemicals like dopamine, norepinephrine, and serotonin. Then, amphetamine does several things simultaneously: It stops these chemicals from being stored away, prevents them from being broken down, and forces more of them to be released into the spaces between brain cells ^[2]. 

However, amphetamine also triggers a special receptor called TAAR1, which turns the brain’s normal chemical recycling system into a one-way street, pushing out even more of these neurotransmitters. This combination creates a powerful stimulating effect on the central nervous system.

These neurochemical changes result in various physiological effects, including desired effects like alertness and euphoria, as well as adverse effects like seizures, hypertension, hyperthermia, or delirium. Most amphetamines have similar effects, but there’s significant variation between substances in the duration of the psychoactive effects and the intensity ^[1]. 

Therapeutic Use of Amphetamines 

The FDA has approved amphetamines for specific medical conditions, with their primary applications focused on neurological and psychiatric disorders. Some of the more common therapeutic uses include treatment for attention-deficit/hyperactivity disorder (ADHD) and narcolepsy.

Amphetamines such as lisdexamfetamine (Vyvanse) and methylphenidate (Ritalin) serve as a first-line treatment for ADHD, helping to improve attention span and focus and reduce impulsivity. The medications work by normalizing neurotransmitter levels in the prefrontal cortex, the brain region responsible for executive functioning ^[3]. Research indicates that these medications are effective in approximately 70-80% of children and 70% of adults with ADHD ^[4]. 

For people with narcolepsy, amphetamines such as dextroamphetamine (Dexedrine) help regulate sleep-wake cycles and combat excessive daytime sleepiness. These medications promote wakefulness by increasing the activity of norepinephrine and dopamine in the brain ^[3]. 

Are Amphetamines Addictive?

Amphetamines have a high potential for abuse, with use potentially leading to severe physical or psychological dependence. According to insights from the 2023 National Survey on Drug Use and Health (NSDUH), more than 3.5 million people misused amphetamines in the last year ^[5]. 

Amphetamine addiction falls under the classification of a stimulant use disorder. The DSM-5 (the standard classification and diagnostic tool for mental disorders) identifies several key diagnostic criteria for a stimulant use disorder, including ^[6]: 

• Taking larger amounts of the substance or for longer periods than intended
• Persistent desire or unsuccessful efforts to cut down or control use
• Spending significant time obtaining, using, or recovering from the drug
• Experiencing cravings or strong urges to use
• Continued use despite physical or psychological problems caused by the drug
• Development of tolerance requiring increased amounts
• Withdrawal symptoms when stopping use

Unwanted Side Effects of Amphetamines 

The side effects of amphetamines vary significantly depending on whether they’re used therapeutically or misused. 

Unwanted side effects of amphetamines employed for therapeutic use include ^[3]:

• Agitation, anxiety, nervousness
• Bladder pain, bloody or cloudy urine, difficult, frequent, or painful urination
• Delusions of persecution, mistrust, suspiciousness, or combativeness
• Depression
• Euphoria and feelings of grandiosity
• Excessive sweating
• False or unusual sense of well-being, detachment
• Heart palpitations
• Increased alertness and concentration
• Lower back or side pain
• Pupil dilation
• Rapid mood changes
• Tremor
• Withdrawal

Repeated use of amphetamines, whether for therapeutic or recreational use, can lead to dependence. Additional chronic effects of dependence can lead to ^[1]:

• Paranoid psychosis, hallucinations, delusions
• Erectile dysfunction
• Enhanced sexual desire
• Necrotizing vasculitis
• Valvular heart disease (associated with some variations)

Effects associated with toxicity or overdose include ^[1]:

• Tachycardia (fast heartbeat), arrhythmias (irregular heartbeats)
• Chest pain
• Hypertension (high blood pressure)
• Dizziness
• Nausea, vomiting, and diarrhea
• Stroke
• Seizures, muscle rigidity
• Hyperthermia

Long-term Impact of Amphetamines 

While amphetamines certainly have their therapeutic uses, prolonged use, short-term, high-dose use, or misuse can lead to several adverse effects. Plus, those who’ve developed physical dependence can also experience severe withdrawal symptoms and show signs of psychosis, anti-social behavior, and increased aggression ^[7]. 

Chronic central nervous system stimulation from amphetamines such as Adderall can also cause long-term effects including: abnormal heart rhythms, seizures, psychosis, damage to nerve cells, and stroke ^[8]. Beyond these physiological effects, long-term amphetamine dependency often leads to significant psychosocial deterioration. Many people experience persistent depression, cognitive impairments affecting memory and decision-making, and deteriorating relationships due to irritability, mood swings, and social withdrawal. Professional and educational performance typically suffers, which can lead to job loss, financial instability, or academic decline.

Long-term users also frequently develop co-occurring mental health disorders, including severe anxiety, treatment-resistant depression, and sometimes persistent psychotic symptoms. The combination of neurochemical changes and mounting life problems significantly increases suicide risk, which remains elevated even during early recovery. Effective treatment must address not only physical dependency but also the psychological, social, and practical consequences that accumulate over time.

Amphetamines vs. Methamphetamine 

Many people confuse amphetamines with methamphetamine not just because of their similar-sounding names but also because of their clearly related chemical structures and shared classification as stimulants. Conflating the two types of substances can lead to serious misconceptions about their respective risks, legal status, and medical applications, which can differ significantly.

While most people are familiar with illegally manufactured and distributed forms of meth, there are FDA-approved versions of both amphetamines and methamphetamines. Generally speaking, methamphetamine is more potent than other amphetamines, producing more intense effects with smaller doses and causing more severe long-term consequences. The speed and intensity of effects also distinguish these substances significantly. 

Treatment for Amphetamine Addiction 

Treatment for amphetamine addiction requires a comprehensive, individualized approach that addresses both the physical and psychological aspects of dependence. Successful recovery typically involves a combination of medical supervision, behavioral therapy, and ongoing support.

Treatment often begins with medical detoxification. Amphetamine withdrawal can produce intense symptoms including depression, anxiety, fatigue, and intense drug cravings. Medical supervision during this period is vital for managing these symptoms and preventing complications. Following detox, many people enter inpatient (aka residential) treatment. They provide 24-hour care, structured therapy, and a drug-free environment that supports early recovery. Inpatient treatment typically lasts 30-90 days, depending on specific needs and progress.

Partial hospitalization programs (PHPs) and intensive outpatient programs (IOPs) serve as effective step-down options or alternatives to residential care. They offer intensive therapy while allowing people in recovery to maintain some daily responsibilities. As the higher intensity version of the two options, PHPs typically involve four or more hours of treatment most days of the week, while IOPs require three to four hours of treatment several days per week. With both options, patients live at home or in a sober living environment.

Regardless of the level of care, behavioral therapies can play an important role in recovery. Cognitive behavioral therapy (CBT) and contingency management are important parts of addiction treatment, as are psychoeducation and group and family therapy.  Support groups and ongoing aftercare can also significantly improve long-term outcomes. These approaches help people identify triggers and develop coping strategies to maintain their recovery.

Healing from Drug Addiction and Amphetamine Misuse 

While amphetamines have valuable therapeutic applications for conditions like ADHD and narcolepsy, they present a complex picture of potential benefits weighed against significant risks. Their ability to rapidly alter brain chemistry underlies both their efficacy and their high potential for misuse and addiction. The distinction between prescribed, therapeutic use and illicit abuse is critical, as misuse can lead to severe consequences, including cardiovascular issues, neurological damage, and significant psychological dependence.

Understanding the powerful effects of amphetamines, and the potential for both benefit and harm, is necessary for healthcare providers and for those who use them. By recognizing the delicate balance between therapeutic use and potential abuse, we can mitigate the risks associated with these potent substances and promote healthier outcomes.

If you or someone you know is dealing with substance misuse, help and hope are available. Call or text the Suicide & Crisis Lifeline at 988. The free and confidential call offers access to empathetic staff and myriad resources.