Opioid Addiction: Signs, Effects and Withdrawal

This page covers how opioid dependence develops, its signs, what withdrawal involves, why overdose risk rises sharply after any period of abstinence, and what treatment consists of.

Key Takeaways

• 4.8 million people in the United States had opioid use disorder in the past year, and 17.0% of them received medication for it, according to SAMHSA's 2024 National Survey on Drug Use and Health.
• Opioid withdrawal is severe but rarely fatal on its own, which is the opposite of alcohol and benzodiazepine withdrawal.
• Tolerance falls within days of stopping, so a dose that was routine before a break in use can be fatal on return. This is the single largest driver of overdose after detox, release from custody or a hospital stay.
• 68% of United States overdose deaths in 2024 involved opioids, and 88% of those involved fentanyl or other synthetic opioids, according to CDC NCHS.
• In Montana, 123 of the 185 drug overdose deaths in 2023 involved opioids, which is 68%, matching the national share.

What is opioid use disorder?

Opioid use disorder is the DSM-5-TR diagnosis for a pattern of opioid use causing clinically significant impairment or distress, established by meeting at least two of eleven criteria within twelve months. Severity is mild at 2 to 3 criteria, moderate at 4 to 5 and severe at 6 or more.

Opioids reach people by three routes that look socially distinct and are pharmacologically identical. A prescription written after surgery, heroin bought on the street, and a counterfeit pill containing fentanyl all act on the same mu-opioid receptors. The receptor does not distinguish between a legitimate prescription and an illicit supply, and neither does the dependence that follows.

What separates opioids from most other drug classes is the narrowness of the margin between a dose that produces the desired effect and a dose that stops breathing. Opioids suppress the brainstem's respiratory drive. That single mechanism is why opioid overdose kills, why naloxone works, and why a period of abstinence raises mortality risk.

Opioids are a drug class defined by action at the mu-opioid receptor, not by legal status. The class includes prescription analgesics such as oxycodone, hydrocodone and morphine, illicitly manufactured fentanyl and its analogues, heroin, and medications used in treatment such as methadone and buprenorphine.

Two adaptations develop with sustained use and are frequently confused. Tolerance means a given dose produces progressively less analgesia and less euphoria, so intake climbs. Physical dependence means the body has adjusted to the drug's presence and produces a withdrawal syndrome in its absence. Both are physiological and both occur in patients taking opioids exactly as prescribed. Neither on its own constitutes opioid use disorder.

The DSM-5-TR draws this distinction explicitly. Tolerance and withdrawal are not counted as criteria when a person is taking opioids under appropriate medical supervision. The diagnosis requires the behavioral features: loss of control over use, craving, continued use despite harm, and the reorganization of life around obtaining the drug.

• 4.8M people aged 12+ with past-year opioid use disorder (SAMHSA NSDUH, 2024)
• 17.0% of them received medication for opioid use disorder (SAMHSA NSDUH, 2024)
• 68% of US overdose deaths in 2024 involved opioids (CDC NCHS Data Brief 549)

The treatment gap is the striking figure in that set. SAMHSA found 4.8 million people with past-year opioid use disorder in 2024, of whom 818,000, or 17.0%, received medication for it. More than four in five people with the diagnosis received no medication at all.

What are the signs of opioid addiction?

The signs of opioid addiction are pinpoint pupils, sedation alternating with alertness, constipation, itching, withdrawal symptoms between doses, escalating dose requirements, and behavioral changes such as early prescription refill requests and withdrawal from ordinary activity.

Physical signs are relatively specific to this drug class. 5 physical indicators clinicians look for:

• Constricted pupils that stay small regardless of ambient light, described on the page on pinpoint pupils
• Sedation that comes and goes in cycles, including the head-dropping state covered on the page on nodding out
• Persistent constipation, since opioids slow gut motility and this effect does not develop tolerance
• Generalized itching and skin picking, caused by opioid-induced histamine release
• Runny nose, yawning, sweating and gooseflesh appearing hours after the last dose

The last of those is diagnostically important. Symptoms that resemble influenza and then resolve completely within minutes of taking an opioid are not influenza. They are withdrawal, and withdrawal relieved by dosing is the clearest indicator of physical dependence.

Behavioral signs follow the pharmacology. Because tolerance climbs, a prescribed supply runs out early, which produces requests for early refills, appointments with multiple prescribers, and eventually a shift to the illicit supply when the prescription route closes. That shift is where the risk profile changes completely, because prescribed tablets have a known dose and the illicit supply does not.

Route of administration escalates in a recognizable order for many people, from swallowing to snorting to injecting, and injection leaves the marks described on the page on track marks. Each step increases the speed at which the drug reaches the brain, and speed of onset drives both reinforcement and overdose risk.

How long does opioid withdrawal last and what does it feel like?

Opioid withdrawal from short-acting opioids begins 8 to 24 hours after the last dose, peaks at 36 to 72 hours and resolves over 5 to 10 days. Withdrawal from long-acting opioids such as methadone begins later, at 24 to 48 hours, and lasts 10 to 20 days.

The experience is best understood as the mirror image of what opioids do. Opioids relieve pain, so withdrawal produces diffuse aching in muscles and bones. Opioids constipate, so withdrawal produces cramping and diarrhea. Opioids sedate, so withdrawal produces insomnia and agitation. Opioids constrict pupils, so withdrawal dilates them. Every symptom is a rebound.

Clinicians score severity with the Clinical Opiate Withdrawal Scale, the COWS, published by Wesson and Ling in the Journal of Psychoactive Drugs in 2003. The instrument rates eleven items including resting pulse, sweating, restlessness, pupil size, bone or joint aches, gastrointestinal upset, tremor, yawning, anxiety and gooseflesh. The score guides both comfort medication and the timing of buprenorphine initiation.

Opioid withdrawal is rarely fatal in an otherwise healthy adult, which is the crucial contrast with alcohol and benzodiazepines. It is, however, severe enough that people reliably return to use to end it, and vomiting and diarrhea can produce dangerous dehydration and electrolyte disturbance in someone medically frail. Each stage brings its own symptoms along the opioid withdrawal timeline.

Protracted withdrawal follows the acute phase for a substantial minority, with disturbed sleep, low mood, low energy and intermittent craving persisting for weeks to months. The danger in that period is not the discomfort. It is that tolerance has already collapsed.

Why does overdose risk increase after a period of abstinence?

Overdose risk rises after abstinence because opioid tolerance falls far faster than the desire to use does. A person returning to their previous dose after days or weeks without opioids is taking a dose their body can no longer tolerate, and respiratory depression follows.

The mechanism is receptor-level. Sustained opioid exposure downregulates mu-opioid receptor responsiveness, which is what tolerance is. Remove the opioid and that downregulation reverses over days. The person's memory of an effective dose is unchanged. Their physiology is not, and the mismatch between the two is what kills.

This makes several transition points unusually dangerous. Completing detoxification, leaving custody, being discharged from hospital and returning from any enforced break in use all place a person at peak risk precisely when they are counted as having done the right thing. Withdrawal management delivered without a plan for what follows it therefore raises mortality risk in the weeks afterwards rather than lowering it.

The contaminated supply compounds the problem. CDC NCHS recorded 80,391 overdose deaths in the United States in 2024, of which 68% involved opioids and 88% of those involved fentanyl or other synthetic opioids. A person cannot judge the potency of what they are taking by looking at it, which is the subject of the page on fentanyl and why it is so dangerous.

Naloxone reverses opioid overdose by displacing opioids from the mu receptor, and it is the reason many overdoses do not become deaths. Montana distributed over 78,000 naloxone kits in 2023, according to the Montana Department of Public Health and Human Services. How to recognize an overdose and use naloxone is covered on the page on Narcan and naloxone.

How is opioid use disorder treated?

Opioid use disorder is treated with medically supervised withdrawal management followed by ongoing care that combines behavioral therapy with recovery support. Three medications hold FDA approval for opioid use disorder: buprenorphine, methadone and extended-release naltrexone.

Withdrawal management addresses the acute phase. It is delivered with comfort medication for the autonomic symptoms, fluid and electrolyte replacement, and monitoring, typically scored against the COWS. The American Society of Addiction Medicine designates medically monitored inpatient withdrawal management as Level 3.7, meaning 24-hour nursing care with daily physician availability.

Medication for opioid use disorder is the element most consistently associated with reduced mortality in the research literature. Buprenorphine is a partial mu-opioid agonist with a ceiling on respiratory depression. Methadone is a full agonist dispensed through federally regulated opioid treatment programs. Extended-release naltrexone is an opioid antagonist requiring full detoxification before initiation. Which medication suits a given person depends on their opioid history, medical comorbidity and access.

Two investigational approaches target overdose rather than the disorder. The FDA approved nalmefene nasal spray in May 2023 for suspected opioid overdose, and it acts longer than naloxone. The American College of Medical Toxicology holds that it should not replace naloxone as the first-line reversal agent. Fentanyl-specific monoclonal antibodies such as CSX-1004, described by Bremer and colleagues, and an anti-fentanyl vaccine entering phase 1 and 2 human trials both aim to bind the drug before it reaches the receptor. Neither is approved for any use.

Behavioral treatment runs alongside medication rather than instead of it. Cognitive behavioral therapy addresses the situations and thinking that precede use, motivational interviewing addresses ambivalence, and family therapy addresses the relationships that surround the disorder. Residential treatment provides the structure and separation from supply that early recovery frequently requires.

Montana's opioid burden is proportionally similar to the national picture and smaller in absolute terms. The Montana Department of Public Health and Human Services recorded 185 drug overdose deaths in the state in 2023, of which 123, or 68%, involved opioids. Montana also dispenses opioid prescriptions at a slightly higher rate than the country as a whole, 40.4 per 100 people against 37.5 in 2023. The full state picture is set out on the page on addiction in Montana.

Frequently asked questions

Sources

1. American Psychiatric Association (2022). Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR). Opioid use disorder criteria, and the exclusion of tolerance and withdrawal under appropriate medical supervision.
2. Substance Abuse and Mental Health Services Administration (2025). Key Substance Use and Mental Health Indicators in the United States: Results from the 2024 National Survey on Drug Use and Health. Opioid use disorder prevalence and medication receipt.
3. Centers for Disease Control and Prevention, National Center for Health Statistics. Drug Overdose Deaths in the United States, 2023-2024, NCHS Data Brief 549. Total overdose deaths, opioid share and synthetic opioid share.
4. Wesson, Donald R. and Ling, Walter (2003). The Clinical Opiate Withdrawal Scale (COWS), Journal of Psychoactive Drugs. Eleven-item withdrawal severity instrument.
5. Montana Department of Public Health and Human Services (2025). Opioid Use in Montana. State overdose deaths, opioid share, naloxone distribution and prescribing rates.
6. American Society of Addiction Medicine. The ASAM Criteria. Definitions of levels of care, including Level 3.7 medically monitored intensive inpatient services.
7. Nallani, S. C. et al. (2025). FDA Approval Summary: Nalmefene Nasal Spray for the Emergency Treatment of Known or Suspected Opioid Overdose, Clinical Pharmacology and Therapeutics, 117(3), 620-626. Approval basis and pharmacology of the 2023 nalmefene approval.
8. Bremer, P. T. et al. (2023). Investigation of monoclonal antibody CSX-1004 for fentanyl overdose, Nature Communications, 14, 7700. Preclinical and early-phase data on fentanyl-specific monoclonal antibodies.