Amphetamines are a class of potent central nervous system (CNS) stimulants that have a well-documented effect on body weight. These compounds work by increasing the activity of certain neurotransmitters in the brain, leading to a cascade of physical and psychological effects. Historically, amphetamines were widely known and used as “diet pills” because they reliably produce a reduction in appetite and subsequent weight loss. Although they are effective for shedding pounds, the significant health risks and high potential for dependence have severely limited their use in modern medicine for weight management.
The Physiological Mechanism of Weight Reduction
Amphetamines exert their weight-reducing effect through a dual mechanism: appetite suppression and increased energy expenditure. The drug rapidly increases the release of catecholamines, primarily norepinephrine and dopamine, in the brain. This surge affects the hypothalamus, the region regulating hunger and satiety signals, leading to a powerful feeling of fullness and significantly reduced desire to eat. This anorexigenic effect, which causes a decrease in daily energy consumption, is the most significant factor in the resulting weight loss.
The second major mechanism is the drug’s influence on the sympathetic nervous system, which causes an increase in metabolism and energy expenditure. Amphetamines are sympathomimetic, meaning they mimic the effects of the body’s natural fight-or-flight response. This stimulation increases heart rate, blood pressure, and body temperature, creating a thermogenic effect.
By stimulating the cardiovascular system, the body burns more calories even at rest. The stimulant properties also provide an energy boost, which can lead to increased physical activity. However, this is generally considered a secondary contributor compared to the profound appetite suppression.
Current Medical Status and Prescribed Use
Amphetamines were first recognized for their potential to cause weight loss in 1937, leading to widespread use as an obesity treatment in the mid-20th century. However, the high rate of addiction and severe adverse health events eventually led to significant governmental restrictions and their removal from the market for general weight loss.
In the current medical landscape, amphetamine-based medications are no longer considered a first-line treatment for obesity. Pure amphetamine is not approved by the Food and Drug Administration (FDA) for treating obesity. However, certain amphetamine-derived compounds, such as phentermine, remain approved for short-term use in weight management.
Phentermine is an anorectic agent structurally similar to amphetamine but with a lower potential for CNS stimulation and abuse. It is reserved for individuals with severe obesity (BMI of 30 or greater) or a BMI of 27 or greater with co-morbidities, and only when other weight loss methods have failed.
Medications primarily used for Attention-Deficit/Hyperactivity Disorder (ADHD), like Adderall and Vyvanse, are classified as Schedule II controlled substances due to their high potential for abuse. These stimulants are sometimes used off-label for weight management, but this practice is highly restricted due to the significant risks. Lisdexamfetamine is also approved to treat moderate to severe binge eating disorder, which can lead to weight loss as a secondary effect. For all medically prescribed uses, the duration is usually limited, and the patient must be under strict medical supervision to monitor for adverse effects.
Associated Health Risks and Dependence
The powerful stimulant effect that causes weight loss also carries a significant risk of severe side effects, particularly for the cardiovascular system. Amphetamines cause tachycardia (rapid heart rate) and hypertension (high blood pressure). Chronic use or abuse increases the risk of serious cardiac events, including heart attack, stroke, and arrhythmias.
The drug’s profound impact on the central nervous system can also induce serious psychiatric and neurological issues. Users may experience anxiety, paranoia, and extreme mood swings. In larger doses or with chronic misuse, amphetamines can precipitate psychosis, including hallucinations and delusions.
A major concern with the use of amphetamines for weight loss is the rapid development of tolerance and dependence. Tolerance occurs when the initial weight loss effect diminishes, requiring higher doses to achieve the same result. The risk of physical and psychological addiction is high, and the drug’s Schedule II classification reflects this abuse potential.
Cessation of amphetamine use after dependence has formed often results in severe withdrawal symptoms, such as debilitating fatigue, intense depression, and anxiety. The extreme appetite suppression can also lead to poor nutritional intake and deficiencies. The weight loss achieved is frequently temporary, and when the drug is stopped, the body often regains the lost weight and sometimes more.