Clinical/Prescription Context

• Atorvastatin calcium (brand name Lipitor), a medication for high cholesterol, and levothyroxine sodium (brand name Synthroid), a thyroid medication, are among the most frequently prescribed drugs in the U.S. based on the number of prescriptions filled.
• When measured by spending, semaglutide (brand names Ozempic, Rybelsus, Wegovy) was the top drug in the U.S. in 2023. 

In the Context of the Drug Crisis

• Fentanyl is described as the primary driver of the current worst drug crisis in U.S. history due to its potency, low cost, and high involvement in overdose deaths. 

The term “America’s favorite drug” is an informal label applied to several different substances depending on the context (legality, usage rates, etc.). The most common interpretations are:

Caffeine: The Most Widely Used Psychoactive Drug 

Caffeine is widely considered “America’s favorite drug” because an estimated 90% of North American adults consume some form of it daily, making it the most widely used psychoactive drug in the world. 

• It is a legal and virtually unregulated substance found in coffee, tea, soft drinks, energy drinks, and some medications.
• While not associated with life-threatening physical withdrawal symptoms like some illicit drugs, caffeine can cause dependence, and withdrawal can result in headaches, fatigue, and irritability. 

Alcohol: The Most Commonly Abused Addictive Substance 

When discussing substance use disorders (addiction), alcohol is the most regularly used addictive substance in America. 

• As of 2023, nearly 29 million people aged 12 or older reported struggling with an alcohol use disorder (AUD).
• Its legality and social acceptance contribute to its high rate of use and abuse, which causes tens of thousands of deaths annually from overdose, liver disease, and drunk driving. 

Marijuana: The Most Used Illicit Drug 

Marijuana (cannabis) is the most used illicit drug in the United States, with over 64 million people using it in 2024. 

• A recent study even suggested it has surpassed alcohol as the substance of choice for daily use among Americans.
• Usage has been increasing with growing state-level legalization for medical and recreational purposes. 

The Best-Selling Prescription Drug

If the term refers to legal pharmaceuticals by sales, recent top-selling drugs in the U.S. by spending include semaglutide (Ozempic, Rybelsus, Wegovy) and adalimumab (Humira). By prescription volume, common medications for conditions like high cholesterol (atorvastatin) or high blood pressure (lisinopril, amlodipine) often top the lists. 

In summary, the answer depends on the definition of “favorite drug”:

• Caffeine is the most widely consumed overall.
• Alcohol is the most widely abused legal substance.
• Marijuana is the most widely used illicit substance.