The 15 Most Dangerous Drugs and How They Impact the Brain

Most Dangerous Drugs


Did you know that more people in the U.S. die of drug overdoses each year than from car accidents, drowning, or falls combined? Which drugs are the most dangerous? They may not be the ones you expect. A report from the Centers for Disease Control and Prevention (CDC) lists the 15 most harmful substances based on overdose deaths, negative health effects, and risk of addiction. This blog sheds additional light on how these substances harm the brain.


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The 15 Most Dangerous Drugs and How They Impact the Brain

#15 Ketamine

Developed over 50 years ago, ketamine, also called “Special K,” is an anesthetic that dulls pain. It has hallucinogenic effects, makes people feel detached or dissociated from their body, and is known as a recreational party drug. In the 21st century, research shows that ketamine is a possible treatment for depression that improves mood faster than traditional antidepressant medications. Traditional antidepressants are thought to work by enhancing the availability of neurotransmitters such as serotonin in the brain, whereas ketamine is believed to alter how brain cells communicate with each other. Despite the promise, caution is needed. A 2020 study in the American Journal of Psychiatry found that ketamine activates the opioid system.

#14 MDMA

MDMA, commonly known as ecstasy or Molly, is a mood-altering chemical associated with feelings of euphoria. MDMA triggers the release of feel-good brain chemicals, most importantly serotonin. Following the brief surge, however, serotonin levels may become depleted. MDMA users report experiencing depression, memory problems, anxiety, paranoia, confusion, and trouble with attention. Research shows that long-term use of the drug is associated with brain changes in areas involved in impulse control and attention, working memory, and visual information processing. In recent years, a growing number of people are showing interest in MDMA and other psychedelics as possible treatments for psychiatric conditions.

#13 Synthetic Cannabinoids (K2 or Spice)

Synthetic cannabinoids—such as “K2” or “ Spice”—that are produced in labs have a more potent effect on the brain than marijuana. Synthetic cannabinoids stimulate receptors in the brain concentrated in the limbic system (hypothalamus, basal ganglia, and hippocampus). Excess stimulation can impair executive function (decision making), cognitive flexibility, and memory, and distort time. Research shows that using these drugs can also induce psychosis, as well as anxiety, panic, and paranoia

#12 Nicotine

Smoking is the leading preventable cause of death, according to the CDC. Smoking or ingesting nicotine constricts blood flow to the brain, which reduces oxygen to the brain and lowers brain function. Do you know who smokes almost 40% of all cigarettes? According to the CDC, it’s

people with psychiatric issues or addictions. Research shows an estimated 80% of those with schizophrenia are tobacco users. Vaping nicotine is just as harmful. The rate of young people vaping is rising so rapidly that in 2018, the U.S. Surgeon General called e-cigarette vaping among youth an epidemic.

#11 Diazepam (Valium)

Diazepam, or Valium, is a benzodiazepine, a medication that is often prescribed for anxiety. Overdose deaths involving these drugs reached 12,290 in 2020, according to the National Institute on Drug Abuse. A study in the American Journal of Public Health found that the number of prescriptions for benzodiazepines has increased by 67%. Benzos can be helpful in the short-term, but they are associated with long-term problems. Brain SPECT imaging studies show that these drugs reduce brain activity. Using these drugs long-term raises the likelihood of developing dementia by more than 50%, according to a 2019 review. And once you start taking these medications, they can be very hard to stop.

#10 Alprazolam (Xanax)

As with other benzodiazepines, alprazolam (Xanax) suppresses brain activity and SPECT scans show it can give the brain a toxic appearance. Long-term use has also been found to raise the risk of developing dementia.

#9 Methamphetamines

Methamphetamines decrease brain function and causes an array of problems, including memory loss, mood changes, depression, anxiety, paranoia, delusional thinking, and permanent psychological damage. Memory impairment can be so dramatic that teens may have symptoms typically seen in people who have Alzheimer’s disease. How do methamphetamines harm the brain? Research shows that long-term use causes brain cell death, damages the blood-brain barrier, alters the release of dopamine and serotonin, and rewires the brain’s reward system.

#8 Cocaine

Cocaine causes structural brain changes that impact cognitive performance, according to a 2021 study on rhesus monkeys. Harmful brain changes include decreases in gray matter density, which is correlated to decreased cognitive function. Previous research has shown that monkeys using cocaine experienced problems with memory, learning, planning, cognitive flexibility, and decision-making.

#7 Oxycodone

A prescription painkiller, oxycodone can be highly addictive. About 25% of people with chronic pain who are prescribed oxycodone misuse it and approximately 5-10% develop an addiction. A 2020 animal study found that dependence on oxycodone leads to permanent changes in the brain. In particular, lasting changes were seen in the central nucleus of the amygdala and impacted the transmission of the neurotransmitter GABA.

#6 Morphine

An opioid prescribed for pain relief, morphine has profound effects on the brain. A brain imaging study in the journal Pain analyzed brain changes in people taking morphine for low-back pain. The researchers did brain scans before and after 30 days of treatment with the opioid medication. The results showed significant increases or decreases in gray matter volume. Other research shows morphine decreases neuroplasticity, alters synaptic communication, and impacts the neurotransmitter dopamine. Long-term use of morphine is associated with anxiety, depression, and memory problems.

#5 Methadone

A drug that is commonly used as part of an opioid withdrawal program, methadone can have damaging effects on the brain when used long-term. Studies show it can impact nerve cells and cause changes in brain regions associated with learning and memory, as well as the reward system.

#4 Hydrocodone

A prescription opioid, hydrocodone is typically used for the treatment of chronic pain. Like other opioid medications, it produces negative impacts on the brain.

#3 Heroin

All drugs impair brain function, but from a neuroscientist’s perspective, heroin is one of the worst substances for your brain. On SPECT scans, brains on heroin look like Swiss cheese, with holes throughout indicating low brain activity. Research shows that long-term heroin use causes structural changes, including reduced gray matter volume in the frontal lobes, cingulate, and occipital lobes. Opiates like heroin can cause temporary or permanent changes in the brain and alter brain chemistry, which may lead to mood swings, severe depression, anxiety, irritability, aggressiveness, sleep disturbances, and confusion, among other problems.

#2 Fentanyl

Considered to be 100 times more potent than morphine, fentanyl is a prescription opioid that can produce feelings of euphoria. Like other opioids, it rewires the brain’s reward system. Fentanyl’s potency makes it even more addictive. Growing evidence suggests that fentanyl use can lead to deterioration of white matter in the brain, changes in emotional regulation, and problems with decision-making, among other issues.

#1 Alcohol

Every year, excessive alcohol use kills over 140,000 Americans. A previous study in The Lancet also named alcohol the most dangerous substance based on its harm to users and to others. Alcohol negatively impacts physical health, and the American Cancer Society calls it one of the most important preventable risk factors for cancer. Drinking also contributes to mental health problems, leads to addiction, and is the third leading preventable cause of death. In terms of alcohol’s impacts on the brain, it shrinks brain volume, lowers blood flow, causes atrophy of the hippocampus (a major memory center), reduces new brain cell growth, and increases the risk of dementia.


The most important lesson from the brain imaging work at Amen Clinics, which includes over 200,000 brain scans, is that the brain can change. Even if you’ve been bad to your brain, you can make it better. The before-and-after SPECT scans of people with addictions show some of the most dramatic improvements. There is hope for healing.

Alcohol abuse, drug addiction, and other mental health issues can’t wait. At Amen Clinics, we’re here for you. We offer in-clinic brain scanning and appointments, as well as mental telehealth, clinical evaluations, and therapy for adults, teens, children, and couples. Find out more by speaking to a specialist today at 888-288-9834 or visit our contact page here.


  1. Very interesting

    Comment by Michael Lewis — August 31, 2022 @ 5:09 AM

  2. Thank you very much Dr. Amen. This what I was looking for.

    Comment by Maria Daidone — August 31, 2022 @ 8:05 AM

  3. Thanks for the advice

    Comment by jatchat — August 31, 2022 @ 10:18 AM

  4. Thank You so much! This article has broadened my perspective of how drugs & substances could potentially harm our precious brain if abused or used incorrectly.
    Such a marvelous organ it Is,,, but so delicate and should be treated with loving care and respect! I appreciate your help & information!! Bless you all

    Comment by Susan Flaming — January 18, 2023 @ 9:02 PM

  5. Every time I've had surgery they want to give you Fentanyl and I refuse it has messed me up badly. They offer NO other options 🙁

    Comment by Carol Komassa — October 4, 2023 @ 1:37 PM

  6. Interesting article! thanks for posting this.

    Comment by Doug Morris — October 4, 2023 @ 2:02 PM

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