The illicit drug supply has changed dramatically in recent years. Fentanyl, fentanyl analogs, xylazine, and other substances can now appear in drugs without a person knowing they are there, making it increasingly difficult to predict what someone is actually taking. For people who use drugs, and for the people who care about them, having accurate information can mean the difference between life and death.
Harm reduction is not about judging why someone uses drugs or demanding that they stop. It is about keeping people alive. Simple measures such as carrying naloxone, using fentanyl or xylazine test strips, recognizing the signs of an overdose, and making sure someone knows when and where you are using can reduce the risk of a fatal overdose.
This guide brings together practical overdose-prevention information and resources, including free naloxone by mail, fentanyl test strips, overdose warning signs, information about xylazine and fentanyl analogs, and services that can help make drug use safer. You do not have to be ready to quit using drugs to deserve information, support, and the chance to stay alive.
Never Use Alone
Never Use Alone is the U.S. National Overdose Response Line for people who are using drugs alone and may not have anyone nearby to help in an emergency. When you call, a trained volunteer (a peer) will ask for your location and stay on the line with you. If you stop responding after using, the volunteer will contact emergency medical services and send help to your location.
Call 800-484-3731 or 877-696-1996, 24/7 – 365 days a year.
Free Naloxone by Mail
If you need naloxone, you may be able to get it for free through NEXT Distro’s Naloxone for All program. This mail-based naloxone distribution program can send naloxone directly to your door or connect you with a local organization that can provide it, all at no cost.
Fentanyl Test Strips
Fentanyl has made drug use significantly more dangerous because people often have no way of knowing whether fentanyl is present in a drug or how much it contains. For people who use opioids, this uncertainty has increased the risk of overdose compared with the risks associated with prescription opioids or heroin alone. The danger can be even greater for people who use cocaine, methamphetamine, or other non-opioid drugs because they may have little or no opioid tolerance. Even a small amount of fentanyl can cause a fatal overdose, and people may not realize that the drug they are using contains fentanyl at all.
Fentanyl test strips are small strips of paper that can detect the presence of fentanyl in many types of drugs, including cocaine, methamphetamine, and heroin, as well as different drug forms such as pills, powders, and injectables. Because fentanyl cannot be reliably seen, tasted, or smelled, there is no way to know by appearance alone whether a drug contains it. Fentanyl test strips offer a simple way to check for the presence of fentanyl before using a drug and can help reduce the risk of an accidental overdose.
Signs of an Overdose
Signs of an opioid overdose may include:
- Very small, constricted “pinpoint” pupils
- Extreme sleepiness, loss of consciousness, or inability to wake up
- Not responding to voices, touch, or other stimulation
- Slow, shallow, irregular, or stopped breathing
- Choking, snoring, or gurgling sounds
- A limp or unresponsive body
- Cold or clammy skin
- Pale, gray, or bluish skin, especially around the lips, fingertips, or nails
If you suspect an opioid overdose, treat it as an emergency. Administer naloxone if available and call 911. A person who is making choking, snoring, or gurgling sounds may not simply be “sleeping it off.”
Xylazine (Tranq)
Xylazine, commonly known as “tranq,” is a powerful animal sedative that is increasingly being found in the illicit drug supply, particularly in combination with fentanyl. Xylazine is not an opioid, but it can cause profound sedation, slowed breathing, and loss of consciousness, increasing the risk of a fatal overdose. Because it is not an opioid, naloxone does not reverse the effects of xylazine itself. However, naloxone should still be given during a suspected overdose because xylazine is often found alongside fentanyl or other opioids.
The most reliable way to determine whether a drug contains xylazine is to use a xylazine test strip. Because xylazine may not be evenly distributed throughout a drug sample, testing each batch you plan to use can help reduce risk. Xylazine test strips can indicate whether xylazine is present, but they cannot tell you how much is present or how concentrated it may be.
For more information on xylazine, see Xylazine | Overdose Prevention | CDC.
Fentanyl Analogs
Fentanyl analogs are drugs that are chemically similar to fentanyl but have been modified in ways that can change their potency and other effects. Like fentanyl, they act on opioid receptors and can dangerously slow or stop breathing, leading to a fatal overdose.
The potency of fentanyl analogs varies widely. Some are less potent than fentanyl, while others are significantly more powerful. Carfentanil, for example, is estimated to be about 100 times more potent than fentanyl and 10,000 times more potent than morphine. Fentanyl analogs can also be difficult to distinguish from one another, and some standard drug tests may not identify exactly which analog is present. This makes an already unpredictable drug supply even more dangerous.
Carfentanil
Carfentanil is one of the most potent fentanyl analogs found in the illicit drug supply. It is estimated to be approximately 100 times more potent than fentanyl and 10,000 times more potent than morphine. Originally developed for use as a tranquilizer for very large animals, carfentanil has no approved use in humans. Even extremely small amounts can be deadly.
In the United States, carfentanil has been detected in the illicit fentanyl supply and linked to clusters of fatal overdoses. After becoming less commonly detected for several years, it has more recently reemerged in the drug supply, raising concerns about an increased risk of overdose and death.
Acetylfentanyl
Acetylfentanyl is a fentanyl analog estimated to be about one-third as potent as fentanyl and approximately 16 times more potent than morphine. Despite being less potent than fentanyl, it can still cause severe respiratory depression and fatal overdose. It has been identified in numerous overdose deaths and may be found alone or mixed with other drugs.
Acetylfentanyl can also be difficult to detect using routine drug screening methods. Standard immunoassay tests may not reliably identify or distinguish fentanyl analogs such as acetylfentanyl, meaning specialized laboratory testing may be needed to determine exactly which substance is present. This adds another layer of uncertainty to an already unpredictable illicit drug supply.
Fluorofentanyl
Fluorinated fentanyl analogs have become increasingly common in the illicit drug supply. One example, para-fluorofentanyl, is believed to have a potency similar to or somewhat lower than fentanyl. Like other fentanyl analogs, however, it can cause severe respiratory depression and fatal overdose.
These substances also present challenges for drug testing. Fluorinated fentanyl analogs can be difficult to distinguish from fentanyl and from one another using routine testing methods, and identifying the specific substance may require specialized laboratory analysis. Their presence adds to the unpredictability of the illicit fentanyl supply.
Medication for Opioid Use Disorder (MOUD)
Three medications are approved by the FDA to treat opioid use disorder (OUD): buprenorphine, methadone, and naltrexone. These medications can reduce opioid use and support long-term recovery, and medications such as buprenorphine and methadone substantially reduce the risk of overdose and death. Treatment can be tailored to the individual, and medication may be combined with counseling and other recovery supports based on a person’s needs and preferences.
Buprenorphine
Buprenorphine is a medication used to treat opioid use disorder (OUD) by reducing opioid cravings and withdrawal symptoms. Unlike methadone for OUD, which generally must be dispensed through federally certified opioid treatment programs, buprenorphine can be prescribed in office-based and other healthcare settings, making treatment more accessible. It can be used as part of a broader treatment plan that may also include counseling, behavioral health services, peer support, and other recovery resources based on each person’s individual needs.
Methadone
Methadone is a long-acting opioid medication used to treat opioid use disorder (OUD). When taken as prescribed, it reduces withdrawal symptoms and cravings and can lessen or block the effects of other opioids. By providing a stable, controlled dose, methadone can help people reduce or stop illicit opioid use and remain engaged in treatment. Methadone treatment for OUD is provided through federally certified opioid treatment programs, with take-home doses available to eligible patients under applicable rules.
Naltrexone
Naltrexone is a non-opioid medication used to treat opioid use disorder (OUD). It works by blocking opioid receptors in the brain, preventing opioids such as heroin and prescription pain medications from producing their usual euphoric effects. Unlike methadone and buprenorphine, naltrexone does not cause physical dependence or withdrawal when discontinued. Because opioids must be cleared from the body before naltrexone treatment begins, patients generally need to complete a period of opioid abstinence first. Naltrexone is available as a daily oral medication or a long-acting monthly injection.
Overdose Prevention and Harm Reduction Resources
1. DanceSafe DanceSafe is a drug checking, earplug slinging, party servicing nonprofit that was founded on social justice principles. Programs include drug education, sexual health and consent deep-dives, political advocacy, and event outreach, where volunteers distribute information and resources at the fabled DanceSafe Booths.
2. Education — NEXT Distro The NEXT Distro Resource Library is an extensive collection of practical harm reduction resources for people who use drugs, their loved ones, and those who support them. The library covers safer drug use and injection, overdose prevention, wound care, specific drugs and emerging substances, HIV and hepatitis C, treatment, sexual health, stigma, and more. It also highlights timely resources on substances appearing in the changing drug supply, including carfentanil, nitazenes, and medetomidine.
3. Grassroots Harm Reduction Grassroots Harm Reduction Network is a national nonprofit that supports peer-based harm reduction organizations across the United States. Its online store provides low-cost drug-checking reagents and test strips, with 100% of proceeds distributed back to local harm reduction groups. Organizations that provide free harm reduction supplies can also join its Buyers’ Club for reduced bulk pricing, making the site a particularly useful resource for grassroots programs working directly with people who use drugs.
4. Harm Reduction Fundamentals CATIE’s Harm Reduction Fundamentals offers free, self-directed courses on substance use and harm reduction. Topics include the principles of harm reduction, reducing substance-related harms, supporting people who use drugs, stigma and discrimination, and Canada’s drug toxicity crisis. The courses are designed to provide practical, evidence-informed knowledge for individuals, frontline workers, and service providers.
5. Harm Reduction – Recovery Research Institute The Recovery Research Institute’s Harm Reduction resource provides a research-based introduction to harm reduction and explains how these strategies can reduce overdose, infectious disease, and other risks associated with drug and alcohol use. It covers practical approaches including naloxone and overdose education, syringe access programs, safer consumption spaces, connections to treatment, and safer-use education, while also addressing common misconceptions about harm reduction.
6. National Harm Reduction Coalition National Harm Reduction Coalition is a national organization dedicated to improving the health and dignity of people who use drugs. The site offers harm reduction education, training, advocacy, and practical resources, including information on naloxone, safer drug use, overdose prevention, and syringe access.
7. NEXT Distro NEXT Distro is an online and mail-based harm reduction organization that helps people access lifesaving supplies and information. The site provides naloxone, syringe-access resources, drug-testing information, educational materials, and other harm reduction services designed to prevent overdose and reduce health risks for people who use drugs.
8. North American Syringe Exchange Network | NASEN: NASEN Directory Founded in 1992, NASEN was created to support syringe services programs (SSPs) and to grow a strong, connected network of organizations and individuals working to ensure that people who use drugs receive the highest quality care, tools, and support available. NASEN is the first and largest low-cost distributor of harm reduction supplies in the United States.
9. Opioid Overdose Prevention and Reversal | SAMHSA SAMHSA’s Overdose Prevention hub brings together reliable, evidence-based resources for preventing and responding to drug overdoses. Visitors can find practical guidance on naloxone, recognizing and responding to an overdose, reducing overdose risk, and connecting people with treatment and recovery services. The site also includes toolkits and resources for families, communities, and professionals who want to help prevent overdose deaths.
10. Overdose Prevention | HHS.gov The U.S. Department of Health and Human Services Overdose Prevention hub brings together trusted federal resources for preventing overdose and finding help. Visitors can access treatment locators and crisis services while learning about overdose prevention, evidence-based substance use treatment, recovery support, safer prescribing, and federal efforts addressing the changing drug supply. It’s a useful starting point for finding reliable, nationwide overdose information and services.
11. The People’s Harm Reduction Alliance People’s Harm Reduction Alliance (PHRA) is a community-based organization that provides practical, judgment-free services for people who use drugs. PHRA offers free safer-use supplies, naloxone, drug checking, syringe services, wound-care supplies, safer-sex supplies, and connections to health and social services. Its approach centers the dignity and autonomy of people who use drugs, with a simple goal: give people the tools and support they need to stay safer and stay alive.
12. Remedy Alliance / For The People Remedy Alliance/For The People is working to put lifesaving naloxone directly into the hands of people most likely to witness an overdose. The organization supplies low-cost and free naloxone to harm reduction programs across the U.S., prioritizing community-based groups and people who use drugs. Its website also offers practical overdose-prevention resources and information on expanding naloxone access, making it a valuable resource for anyone interested in preventing overdose deaths.
13. The SOAR Initiative The SOAR Initiative is a harm reduction organization offering practical tools to help prevent overdose and make drug use safer. One of its most useful nationwide resources is a state-by-state directory showing where people can obtain free drug test strips across the U.S. The site also provides free naloxone, educational information on substances such as xylazine and medetomidine, instructions for using test strips, and overdose-prevention resources. SOAR also operates a Bad Batch Alert system in Ohio that warns people when overdose spikes or dangerous drugs are detected in their area.