The Five Worst Drugs in America

Man holding woman's hands acting as support while battling addiction

It’s no secret that we have a drug problem in the United States; tens of thousands are dying, but ranking the worst drugs in America is more complicated than it may seem. We must consider several factors to truly understand what it means for a substance of abuse to be the “worst.” Opioids are varied and dangerous drugs that have recently garnered the most significant headlines. Fentanyl, for example, probably the worst offender, is 50 times more potent than heroin and can kill someone in unbelievably small quantities. But what about nicotine, which keeps people hooked to smoking and causes upwards of 500,000 deaths yearly? What about food, particularly sugar, behind the obesity epidemic and a staggering rise in chronic disease, cardiovascular problems, and even higher risk of death due to infectious diseases like COVID-19? To honestly answer this question, we must look at the dangers of drugs holistically, understand the psychological issues that may underlie the use and abuse of these substances, and look at the prevalence and even legality of these drugs. In other words, developing this list is more art than science, and no answer can fully satisfy the question of “What is the worst drug in America?”

The National Institute on Drug Abuse (NIDA) offers telling information on drug-involved overdose deaths:

  • Overall drug-involved overdose deaths have increased almost every year from 1999 to 2021. However, the trendline steepened dramatically when fentanyl was introduced into the illicit drug market around 2013. To that end, 2021 represented the first time drug overdose deaths crossed the 100,000 mark.
  • Over 80,000 of these deaths in 2021 are a result of opioids.
  • Prescription opioid deaths have been relatively stable over the past decade after a significant increase from 1999 to 2011.
  • Heroin-related deaths have decreased dramatically from their peak in 2015, while heroin plus synthetic opioids other than methadone have shown a significantly slower drop than heroin-only deaths.

The data above shows that there must be a relatively newer opioid culprit driving these deaths.


Fentanyl is a relative newcomer to the illicit drug scene as a potent opioid. It is a synthetically produced opioid approved by the FDA with a clinical interest in mind. Fentanyl has been used to treat severe pain resulting from surgical procedures or complex and chronic pain conditions. As we know from previous opioid abuse concerns – specifically the history with Oxycodone – even in the healthcare setting, there is room for abuse, typically from a small number of bad actors that wish to benefit financially from people’s pain and, ultimately, addiction. However, in the case of fentanyl, the healthcare system is not the primary distribution platform for the drug. Fentanyl is relatively easy and cheap to produce, and over the past decade or two, it has been manufactured and distributed illegally to bolster the addictiveness of other illicit drugs.

When looking at any charts involving drug overdose deaths, the numbers are significantly higher when a synthetic opioid other than methadone is included. The fact is that fentanyl is the additive causing the meteoric rise in overdose deaths. While accounting for only a fraction of the deaths associated with smoking, fentanyl must be considered the most dangerous drug currently available and abused in the United States.

Unfortunately, fentanyl is no longer difficult to find. It does not require an unethical doctor or a street-corner drug dealer to get access to it. Fentanyl is marketed online from sources in Mexico and, more commonly, in Asia, particularly China. Rand Corporation researchers found several firms in China willing to ship a kilogram of fentanyl to the US for as low as $2000. The equivalent potency of heroin would cost 50 times more.1

That and other research into fentanyl have shown a) how difficult it is to control, b) how easy it is to find, and c) how cheap it is to purchase. Knowing this, it makes sense that fentanyl would be used to cut other drugs of abuse to reduce cost and increase potency and addictiveness.

Because of its potency, fentanyl must be attacked in two ways. The first is prevention. Prevention is critically important because it’s difficult for a community to recover from an influx of fentanyl. Unfortunately, fentanyl is so powerful that it is tough for communities to control. That being said, appropriate treatment options with evidence-based care are also critical to reducing the likelihood that a patient returns to their drug of choice after completing a course of treatment.


Approximately 480,000 people die in the US annually due to smoking, representing about one in every five deaths in our country. It is the leading cause of preventable death and increases the risk of death from all causes. People who smoke have a 2-4 times increased risk of coronary heart disease and increased risk of stroke by the same amount. The risk of lung cancer is 25 times higher than in non-smokers.

Does the fact that nicotine is legal make it any less concerning? The short answer is no. Unfortunately, while efforts have been made to curtail the use of this drug in cigarettes, and smoking rates have decreased over the past few decades (from about 40% of the adult population in the 1960s to about 20% now), it remains a significant cause of morbidity and mortality. The addictive properties of nicotine tell us why quitting is so hard. Across the general population, the chance of becoming dependent on nicotine after using tobacco at least once is about 32%. This compares to heroin at 23%, cocaine at 17%, and alcohol at 15%. In other words, nicotine is highly addictive.2

Smoking is particularly problematic in those with substance use disorders and mental illness, and tobacco use is far higher in these populations than in the general public. These same people are less likely to quit.3 Not only is nicotine addictive, but smoking has psychoactive effects. Early on, smoking can reduce symptoms of depression and anxiety. However, once dependence sets in; there is evidence to show the opposite. Nicotine has been shown to enhance the effect of other drugs and can even lead users toward marijuana or cocaine use. Nicotine has also been shown to possibly cause increased binge drinking of alcohol and reduce the effects of critical psychiatric medications like antidepressants and antipsychotics.

Smoking creates a bidirectional cause-and-effect relationship that can worsen mental illness and substance use disorders while making treatments less efficacious.


Methamphetamine, or crystal meth, is a highly addictive drug that targets the central nervous system. It is chemically like the stimulant amphetamine used to treat ADHD, and Meth increases dopamine in the brain and stimulates the reward system. However, because meth creates a quick high, the steep drop is speedy, resulting in users often binging and crashing throughout the day. You may have heard of phenomena like meth mouth and noticed that users typically do not practice good self-care. This is because they often binge on methamphetamine day and night every few hours for days on end to maintain the high, with their usage becoming their sole focus at the cost of self-care.

Second, only to the rise in fentanyl overdose deaths, methamphetamine has shown a dramatic increase in abuse and, ultimately, overdose over the past one to two decades. It is estimated that over 16,000 deaths were caused by methamphetamine in 2019, and that number has risen since. Often, methamphetamine is laced with fentanyl, increasing the number of deaths associated with the drug.

The long-term effects of methamphetamine addiction are severe and can include anxiety, depression, severe dental issues, extreme weight loss, paranoia, and hallucinations. These effects can also lead to changes in behavior that ultimately worsen physical and mental health. Some of the changes to the brain caused by meth cannot be reversed and can even lead to Parkinson’s disease, stroke, heart attack, and organ failure.

There are no reliable, FDA-approved treatments for methamphetamine use disorder, and traditional therapy, including cognitive behavioral therapy, while effective, has a lower success rate compared to treating addiction to other drugs. Repetitive transcranial magnetic stimulation, or rTMS, has shown promise in treating those with a methamphetamine use disorder; there is hope that emerging technologies can offer even greater benefits.

The facility and therapist directing treatment must be well-versed in addiction and mental illness treatment protocols to assist patients in achieving long-term recovery and sobriety. Due to the nature of methamphetamine, more so than most other drugs, patients require a holistic approach to their care and cannot simply be treated for either addiction or mental illness alone.


Although it is not something we immediately relate to addiction, there is little question about whether sugar is an addictive substance that leads to dependence and, ultimately, a substance use disorder. Food addiction has not been shown significant attention despite the considerable rise in excess weight, obesity, and related diseases; however, while some may dismiss this as a traditional “substance use” disorder, ultimately, sugar stimulates the brain pathways and reward system in the same way as other addictive drugs. Sugar releases dopamine, and as such, it may have addictive consequences. How we discuss overeating and sugar consumption is very similar to addictive substances, with cravings, withdrawal, and binging all playing a part. Many people exhibit traits of dependence on sugar, both physically and mentally, that people with substance use disorders do, albeit often less dramatically. Some of the commonalities between drugs of abuse and sugar include:4

  • Binging – drugs are often self-administered in limited periods, known as binges. This can also be true for food and sugar, where the absence of food later creates a compensatory action to receive the euphoric effect. Animal studies have shown that binging sugar often significantly increases daily intake versus eating it regularly throughout the day.
  • Just as with many traditional drugs of abuse, withdrawal can also occur when sugar is removed. Indeed, very interestingly, the opioid antagonist naloxone can cause physical signs of withdrawal in animal subjects, including anxiety, tremors, teeth chattering, and head shakes. These effects were similar to food and sugar deprivation.
  • Craving is also a sign of dependence and addiction in users. After a time of abstinence, sugar cravings also increase, and ultimately, users often consume more when once again exposed to it. Increased length of abstinence heightens the motivation to return to the substance of abuse, whether a drug or sugar.

Interestingly, studies have shown cross-sensitization between sugar and other drugs. Sugar intake and drug abuse can make the subject more sensitive to the other substance. Amphetamines and cocaine, for example, showed definitive cross-sensitization with sugar.

Sugar abstinence also seems to lead to increased use of other drugs and substances of abuse. Often referred to as the gateway effect, animal subjects subjected to intermittent sugar deprivation increased their alcohol intake. Other studies have shown that animals with a “sweet tooth” will self-administer cocaine more readily. This all ties into sugar’s effect on the brain and reward system.

4Avena NM, Rada P, Hoebel BG. Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev. 2008;32(1):20-39. doi: 10.1016/j.neubiorev.2007.04.019. Epub 2007 May 18. PMID: 17617461; PMCID: PMC2235907.

The Rest – Not to Be Overlooked

The above list does not negate the significantly negative impact of other substances often abused. Cocaine, heroin, prescription opioids, and benzodiazepines represent a significant part of the drug problem in the United States. Tens of thousands still lose their lives due to their use and abuse. We cannot overlook this while recognizing that many illicit substances are mixed with Fentanyl, becoming a conduit for the most addictive drug to be introduced to someone abusing other substances. Without these carrier drugs, fentanyl would not be as prevalent today.

As is the belief of The Sylvia Brafman Mental Health Center and Through the Archway, addiction cannot be treated unidimensionally. Yes, there is a need to treat the underlying addiction, but we cannot forget the mental illness component that is a significant part of many patients with active addiction. Whether caused by mental illness or the cause of cognitive concerns, the whole person must be treated in a comprehensive and compassionate program. With the proven spiritual benefits of Through the Archway’s program, we have collectively given thousands of patients the tools to stay clean for long-term recovery.


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  • ²Smith PH, Mazure CM, McKee SA. Smoking and mental illness in the U.S. population. Tob Control. 2014 Nov;23(e2):e147-53. doi: 10.1136/tobaccocontrol-2013-051466. Epub 2014 Apr 12. PMID: 24727731; PMCID: PMC4201650.
  • ³Morar T, Robertson L. Smoking cessation among people with mental illness: A South African perspective. S Afr Fam Pract (2004). 2022 Aug 30;64(1):e1-e9. doi: 10.4102/safp.v64i1.5489. PMID: 36073100; PMCID: PMC9453116.

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