Hydromorphone (Dilaudid) Addiction: Signs & Treatment

Hydromorphone addiction is a severe form of opioid use disorder caused by compulsive, and uncontrollable use of hydromorphone. Hydromorphone is a high-potency Schedule II opioid that is sold under the brand name Dilaudid, despite serious physical, psychological, and social consequences.

Five to ten times more potent than morphine at equivalent doses, hydromorphone produces an intense euphoric rush that restructures the brain’s reward circuitry far more rapidly than less potent prescription opioids.

Recognizing the signs early and accessing evidence-based treatment gives individuals the strongest possible chance at sustained recovery.

Key Takeaways

• According to NIDA (2023), approximately 5.7 million people in the United States had opioid use disorder, and hydromorphone’s extreme potency means dependence can develop in as few as four to eight weeks of regular use.
• SAMHSA’s 2024 NSDUH reports that 8.9 million people aged 12 or older misused a prescription opioid in 2023, yet only one in five individuals with opioid use disorder receives medication-based treatment, according to NIDA.
• Hydromorphone is 5 to 10 times more potent than morphine, crosses the blood-brain barrier faster due to greater lipid solubility, and produces a dopaminergic surge in the mesolimbic pathway that makes compulsive redosing physiologically driven rather than voluntary.
• The Clinical Opiate Withdrawal Scale (COWS) is the primary tool clinicians use to assess hydromorphone withdrawal severity and guide medication dosing during medically supervised detox.
• FDA-approved medications including buprenorphine, methadone, and naltrexone, combined with behavioral therapies such as CBT and DBT, are the standard of care for hydromorphone use disorder and dramatically reduce overdose mortality.

What Is Hydromorphone (Dilaudid)?

Hydromorphone is a semi-synthetic opioid analgesic derived from morphine and classified by the DEA as a Schedule II controlled substance, indicating high abuse potential and severe risk of psychological or physical dependence.

Pharmacology and Potency

The pharmcology and potency of Hydromorphone is:

• Receptor binding profile: Hydromorphone acts as a full agonist at mu-opioid receptors (MOR) in the brain, brainstem, and spinal cord, and binds to a lesser degree at delta-opioid receptors. This full-agonist activity produces maximal receptor activation with no ceiling on respiratory depression.
• Speed of onset: Because hydromorphone is more lipid-soluble than morphine, it crosses the blood-brain barrier faster, producing an onset of euphoria within 15 to 30 minutes orally and within seconds to minutes when administered intravenously in hospital or illicit settings.
• Potency relative to morphine: Hydromorphone is 5 to 10 times more potent than morphine by weight, meaning a 2 mg oral dose of Dilaudid produces roughly the same analgesic effect as 10 to 20 mg of morphine. This potency dramatically compresses the margin between therapeutic dosing and overdose.
• Metabolite risk: Hydromorphone undergoes hepatic glucuronidation, producing hydromorphone-3-glucuronide (H3G), a neuroexcitatory metabolite that does not bind opioid receptors but can accumulate in patients with renal impairment and cause myoclonus, cognitive dysfunction, and paradoxical hyperalgesia, a condition called opioid-induced hyperalgesia (OIH).

Medical Uses and Street Context

• Legitimate clinical use: Physicians prescribe hydromorphone for moderate-to-severe acute pain unresponsive to less potent analgesics, including post-surgical pain, cancer-related pain, and palliative care. It is frequently used intravenously in hospitals because of its controllable dosing.
• Diversion and illicit use: Because of its extreme potency and euphoric effect, Dilaudid commands significant black-market value. Street names include D’s, dillies, big D, hospital heroin, M-80s, and juice. Its reputation for a rapid, intense high makes it particularly attractive to individuals already tolerant to other opioids, who are among those at highest addiction risk.

Why Hydromorphone Addiction Develops

Hydromorphone addiction develops through interconnected neurobiological, genetic, and environmental mechanisms, none of which operates in isolation from the others.

Neurobiological Causes

The neurobiological causes of Dilaudid addiction are:

• Mesolimbic dopamine surge: Hydromorphone activates mu-opioid receptors in the ventral tegmental area (VTA), which disinhibits dopaminergic neurons and produces a massive dopamine release in the nucleus accumbens, the brain’s primary reward center. This surge is estimated to be four to five times greater than natural rewards such as food or sex, creating a reinforcement signal so powerful that the brain begins encoding the drug as a survival-level priority.
• Receptor downregulation and tolerance: With repeated hydromorphone exposure, the brain reduces GABA-A-mediated inhibitory signaling and downregulates mu-opioid receptor density through a process called receptor internalization. This forces the person to use higher doses to achieve the same effect, a defining feature of tolerance that escalates addiction risk.
• Opioid-induced hyperalgesia (OIH): Paradoxically, chronic hydromorphone use sensitizes central pain pathways via H3G accumulation and neuroplastic changes in descending pain modulation. The result is a state where the drug both drives continued use and progressively worsens the pain condition it was originally treating, a neurobiological trap that distinguishes opioid addiction from voluntary substance misuse.

Genetic and Hereditary Factors

The genetic factors of Dilaudid addiction are:

• OPRM1 gene variants: The OPRM1 A118G single nucleotide polymorphism (SNP) is the most studied genetic risk factor for opioid addiction. Individuals carrying the G allele experience altered mu-opioid receptor function, affecting both pain sensitivity and the magnitude of opioid-induced euphoria, which directly influences addiction vulnerability. Nora Volkow, MD, then-director of NIDA, and colleagues identified that this and related dopamine system gene variants substantially predict who develops compulsive opioid use following medical exposure.
• Family history heritability: Opioid use disorder carries a heritability of approximately 40 to 60%, meaning genetic factors account for roughly half of addiction risk. A family history of opioid addiction is one of the strongest individual predictors of hydromorphone dependence following medical prescription.

Developmental and Environmental Causes

The developmental and environmental causes of Dilaudid addiction are:

• Adverse childhood experiences (ACEs): Individuals with a history of childhood trauma, neglect, or abuse have altered hypothalamic-pituitary-adrenal (HPA) axis reactivity, making opioids’ anxiolytic and pain-numbing effects more powerfully reinforcing. Research consistently shows that ACE scores above 4 substantially increase lifetime opioid misuse risk.
• Chronic pain as an entry pathway: A significant proportion of hydromorphone addictions begin with legitimate pain management. When acute pain treatment extends into prolonged prescribing without adequate monitoring or dose management, physical dependence develops before either the patient or prescriber recognizes the transition into disordered use.

Comorbid and Secondary Causes

The secondary causes of Dilaudid addiction are:

• Depression and anxiety disorders: Both are primary drivers of opioid misuse through the self-medication hypothesis. Hydromorphone’s anxiolytic, dissociative, and mood-elevating properties reduce acute psychological distress, reinforcing use in individuals whose underlying mood disorders remain undiagnosed or undertreated.
• Prior stimulant or sedative use disorders: Cross-sensitization of the mesolimbic dopamine system by prior cocaine or methamphetamine use lowers the neurobiological threshold for opioid addiction by pre-priming reward pathway hyper-reactivity.

Hydromorphone Withdrawal Timeline

Hydromorphone withdrawal follows a predictable sequence tied to the drug’s half-life of approximately 2 to 3 hours, making it one of the faster-onset short-acting opioid withdrawal syndromes in clinical practice.

Hours 4 to 12: Onset Phase

• Early physical signals: Yawning, lacrimation (tearing), rhinorrhea (runny nose), diaphoresis (excessive sweating), restlessness, and low-grade anxiety typically emerge within 4 to 8 hours of the last dose. These reflect acute sympathetic nervous system rebound as the brain’s opioid-suppressed systems reassert baseline activity without the drug’s regulatory effect.
• COWS score guidance: Clinicians administer the Clinical Opiate Withdrawal Scale (COWS) at this stage. A score of 13 to 24 indicates moderate withdrawal, which guides initiation of comfort medications and, where appropriate, early buprenorphine induction.

Hours 12 to 36: Peak Phase

• Severe physical symptoms: Intense muscle cramping, bone pain, piloerection (goosebumps), nausea, vomiting, diarrhea, hypertension, tachycardia, and insomnia reach maximum intensity. The kappa-opioid receptor (KOR) system, dysregulated by chronic hydromorphone use, contributes significantly to dysphoria, anxiety, and anhedonia during peak withdrawal, creating a psychological suffering component beyond the physical symptoms alone.
• Cognitive and emotional intensity: Severe cravings, heightened irritability, dissociation, and intense drug-seeking behavior emerge at this stage. Without clinical support, the psychological distress of peak hydromorphone withdrawal is the primary driver of immediate relapse.

Days 2 to 7: Resolution Phase

• Gradual improvement: Physical symptoms begin subsiding by day 3 to 5, with most acute physical withdrawal resolving by day 7. Sleep disturbance, appetite suppression, and mood dysregulation may persist beyond the acute window.
• Post-acute withdrawal syndrome (PAWS): Anxiety, insomnia, dysphoria, and opioid cravings can persist for weeks to months after acute withdrawal resolves. PAWS is not widely recognized by individuals leaving unsupported detox, and it is the leading reason why detox without continuing residential treatment or medication-assisted treatment fails to produce sustained recovery.

Signs and Symptoms of Hydromorphone Addiction

Hydromorphone addiction produces recognizable behavioral, physical, and psychological signs that escalate in severity as the disorder progresses from mild to severe under DSM-5-TR criteria for opioid use disorder.

Behavioral Signs

The behavioral signs of Hydromorphone addiction are as follows:

• Doctor shopping and prescription fraud: Visiting multiple prescribers or emergency departments to obtain additional Dilaudid prescriptions, or falsifying injury severity to access the drug through legitimate medical channels.
• Social and occupational deterioration: Withdrawal from family relationships, declining job performance, abandonment of hobbies and commitments previously valued, and increasing isolation that centers daily life around obtaining and using hydromorphone.
• Compulsive use despite consequences: Continuing to use Dilaudid despite awareness of physical harm, legal risk, family damage, or financial consequences. This loss of control over use, despite its costs, is the defining behavioral criterion that separates addiction from physical dependence.

Physical Signs

The physical signs of Hydromorphone addiction are as follows:

• Pinpoint pupils (miosis): Constriction of the pupils to 2 mm or smaller in any lighting condition, a direct pharmacodynamic effect of full mu-opioid receptor agonism in the Edinger-Westphal nucleus.
• Respiratory depression: Slowed, shallow breathing is the most dangerous acute physical sign. Hydromorphone-induced respiratory depression carries a narrower margin than longer-acting opioids because of its potency. Nodding off mid-sentence, profound drowsiness, and inability to stay alert are visible signs of respiratory compromise.
• Injection site damage: In individuals who transition to intravenous use, track marks, bruising, collapsed veins, and soft tissue infections develop at injection sites, reflecting the progressive escalation from oral to parenteral administration that often occurs as oral tolerance increases.
• Physical dependence markers: Appearing acutely unwell, sweating, and visibly agitated between doses signals the emergence of physical dependence, where absence of the drug produces a withdrawal syndrome rather than simply the absence of intoxication.

Long-Term Effects of Hydromorphone

The long-term effects of Hydromorphone addiction are as follows:

• Opioid-induced hyperalgesia (OIH): Paradoxical worsening of pain sensitivity with chronic hydromorphone use driven by H3G accumulation and central sensitization. Individuals experience generalized pain that is worse than their original pain condition, perpetuating continued use in a neurologically driven cycle.
• Endocrine disruption: Chronic opioid exposure suppresses the hypothalamic-pituitary-gonadal (HPG) axis, producing testosterone deficiency in men (opioid-induced androgen deficiency, OPIAD) and menstrual irregularity in women. These hormonal effects compound mood disorders and contribute to PAWS.
• Cognitive impairment: Long-term hydromorphone misuse damages prefrontal cortex function, impairing executive decision-making, impulse control, and working memory. These deficits persist well into recovery and are directly addressed by behavioral therapies used in dual diagnosis treatment.
• Overdose mortality risk: The fentanyl-contaminated illicit drug supply has substantially elevated the overdose risk for individuals who transition from diverted Dilaudid to street opioids. Fentanyl-laced counterfeit pills that mimic Dilaudid appearance are now a documented and deadly feature of the illicit opioid market.

Hydromorphone Addiction vs. Physical Dependence: How to Tell the Difference

Hydromorphone addiction and physical dependence are distinct clinical states that are routinely confused by both patients and family members, but the distinction determines treatment approach.

Physical dependence is a predictable physiological adaptation. A cancer patient taking prescribed Dilaudid daily for six months will develop dependence, their body adapts to the drug’s presence, and abrupt cessation produces a withdrawal syndrome without that person ever engaging in compulsive drug-seeking behavior. Their use remains purposeful, controlled, and directed by clinical need.

Hydromorphone addiction, formally diagnosed under DSM-5-TR as opioid use disorder (OUD), requires at least two of eleven specified diagnostic criteria within a 12-month period, including tolerance, withdrawal, use in larger amounts or for longer than intended, persistent desire to cut down without success, and continued use despite clinically significant harm. The key distinction is loss of control: the person continues using hydromorphone despite clear and recognized negative consequences that a person with only physical dependence would not face.

Treatment for Hydromorphone Addiction

Evidence-based treatment for hydromorphone use disorder integrates medically supervised detox, pharmacotherapy, behavioral therapies, and structured residential programming within a continuum of care designed to address the full biological and psychological scope of opioid addiction.

First-Line Pharmacological Treatments

The first-line pharmacological treatments for hydromorphone use disorder includes:

• Buprenorphine (Suboxone): A partial mu-opioid receptor agonist with a ceiling effect on respiratory depression, buprenorphine-naloxone is SAMHSA- and ASAM-approved first-line treatment for opioid use disorder. It suppresses withdrawal, reduces cravings, and dramatically reduces overdose mortality risk. Buprenorphine induction requires waiting for a COWS score indicating moderate withdrawal to prevent precipitated withdrawal.
• Methadone: A long-acting full mu-opioid receptor agonist dispensed through licensed opioid treatment programs (OTPs). Methadone maintenance is particularly effective for individuals with severe physiological dependence or prior buprenorphine treatment failure. Its extended half-life of 24 to 36 hours eliminates the cyclical peaks and troughs of short-acting opioid use.
• Naltrexone (Vivitrol): A full opioid receptor antagonist that blocks all opioid effects, available as a once-monthly intramuscular injection. Naltrexone carries no abuse potential and is appropriate for individuals who have completed detox and are highly motivated for abstinence-based recovery.
• Lofexidine (Lucemyra): An FDA-approved alpha-2 adrenergic agonist that reduces noradrenergic rebound symptoms during acute withdrawal, including muscle cramps, sweating, tachycardia, and anxiety, without opioid receptor activity. It is the first non-opioid medication FDA-approved specifically for opioid withdrawal management.

First-Line Behavioral Therapies

The first-line pharmacological treatments for hydromorphone use disorder includes:

• Cognitive Behavioral Therapy (CBT): CBT addresses the thought patterns and situational triggers that drive compulsive opioid use. By identifying cognitive distortions that rationalize hydromorphone use and building alternative coping strategies, CBT reduces both craving intensity and relapse likelihood in the post-detox period.
• Dialectical Behavior Therapy (DBT): DBT targets the emotional dysregulation that both predates and results from opioid addiction. The four skill modules, distress tolerance, emotion regulation, mindfulness, and interpersonal effectiveness, directly address the emotional pain states that hydromorphone was often originally misused to suppress.
• Contingency Management (CM): A behavioral therapy using positive reinforcement for drug-free urine tests and treatment adherence. CM has the strongest empirical evidence base of any behavioral intervention for stimulant and opioid use disorders, and significantly improves treatment retention.
• EMDR (Eye Movement Desensitization and Reprocessing): For individuals whose hydromorphone use is rooted in trauma, EMDR targets maladaptive traumatic memory processing. It is particularly relevant given the high co-occurrence of PTSD and opioid use disorder in clinical populations.

Second-Line and Adjunct Treatments

The second-line treatments for hydromorphone use disorder includes:

• Motivational Interviewing (MI): A client-centered approach that resolves ambivalence about recovery. MI is most effectively deployed during early engagement when individuals are not yet committed to full treatment participation, and has strong evidence for improving treatment entry and retention.
• 12-Step Facilitation (Narcotics Anonymous): Structured peer support through NA complements formal clinical treatment and provides long-term community support that extends well beyond the clinical episode of care.

Emerging and Investigational Treatments

• Extended-release naltrexone (Vivitrol) for high-risk populations: For justice-involved individuals or those without stable housing who cannot reliably self-administer daily oral medications, once-monthly injectable naltrexone has demonstrated significant superiority over oral naltrexone in maintaining treatment engagement.
• Low-dose naltrexone (LDN): Under investigation as an adjunct to buprenorphine to address the glial immune mechanisms that contribute to opioid-induced hyperalgesia and PAWS, though not yet FDA-approved for this indication.
• Ketamine-assisted therapy: Early-phase research at Yale and other academic centers is exploring subanesthetic ketamine infusions to reduce opioid cravings and address treatment-resistant comorbid depression in patients with severe OUD. Currently off-label; Phase 2 trials ongoing.

Treatment at New Spirit Recovery

New Spirit Recovery treats hydromorphone addiction within an integrated, medically supervised framework that addresses opioid use disorder alongside co-occurring mental health conditions from day one of admission.

Medical Detox

• 24-hour clinical oversight: New Spirit Recovery’s medical detox program provides continuous nursing coverage and physician oversight throughout the hydromorphone withdrawal process. The Medical Director and Nurse Practitioner implement COWS-guided medication protocols, including comfort medications and medication-assisted treatment, throughout the 7 to 10-day average detox period, with extensions to 10 to 21 days based on medical necessity.
• Medication-assisted treatment integration: Buprenorphine induction, naltrexone evaluation, and comprehensive psychiatric medication management are available from day one. Every client receives a psychiatric evaluation within 24 hours of admission, ensuring that co-occurring depression, PTSD, or anxiety disorders are identified and treated alongside the opioid use disorder rather than sequentially.

Residential Treatment

• Structured clinical programming: New Spirit Recovery’s residential treatment program operates seven days per week with six hours of structured daily programming. Individual therapy, group therapy, and evidence-based modalities including CBT, DBT, EMDR, and Acceptance and Commitment Therapy (ACT) are integrated throughout the client’s stay at the San Fernando Valley facilities in Encino and Tarzana.
• Rewired curriculum: The proprietary Rewired curriculum, developed exclusively by co-founder Erica Spiegelman, delivers 10 progressive modules addressing emotional regulation, stress management, self-awareness, trigger identification, and healthy boundary development. Each module integrates with daily individual therapy to create continuity between structured curriculum learning and personalized clinical application.

Dual Diagnosis Treatment

• Integrated mental health care: New Spirit Recovery’s dual diagnosis program treats co-occurring anxiety, depression, PTSD, bipolar disorder, and other conditions simultaneously with opioid use disorder. The Nurse Practitioner evaluates psychiatric medication needs within 24 to 72 hours of admission, with weekly minimum physician consultations throughout the program. Treating both conditions within the same clinical framework is the evidence-based standard of care for opioid use disorder with psychiatric comorbidity.

Medication-Assisted Treatment

• MAT continuity: New Spirit Recovery’s medication-assisted treatment program utilizes FDA-approved medications including buprenorphine (Suboxone) and naltrexone (Vivitrol) alongside behavioral therapies for opioid use disorder. All medication decisions are made collaboratively between the Medical Director, Nurse Practitioner, therapists, and client to ensure treatment is clinically appropriate and individually tailored. Same-day assessments are available for individuals ready to begin treatment.

“Clients coming off hydromorphone often underestimate what the post-acute phase looks like. The acute withdrawal clears within a week, but the anhedonia, the sleep disruption, the dysphoria that follows, that’s where we see relapse attempts. Our clinical focus at New Spirit doesn’t stop at detox. We begin rebuilding the dopaminergic baseline from the first week of residential programming.”

– Dr. Patrick Lockwood, Clinical Consultant at New Spirit Recovery

Frequently Asked Questions

What are the most addictive painkillers?

Among prescription opioids, hydromorphone (Dilaudid), oxymorphone (Opana), and illicitly manufactured fentanyl carry the highest addiction risk due to their extreme mu-opioid receptor potency and rapid onset of euphoria. Hydromorphone’s 5 to 10-fold potency advantage over morphine, combined with its relatively short half-life, produces a cycle of intense euphoria followed by rapid descent, a pharmacological pattern that drives compulsive redosing at a rate that accelerates dependence faster than longer-acting, lower-potency opioids.

What are the long-term effects of hydromorphone?

Long-term hydromorphone use produces opioid-induced hyperalgesia (OIH), a paradoxical increase in pain sensitivity; hormonal disruption including testosterone deficiency in men (opioid-induced androgen deficiency); prefrontal cortex damage impairing decision-making and impulse control; persistent sleep disruption; and immune system dysregulation. Cognitive impairment from chronic opioid use can persist for months to years into recovery, though significant neuroplastic improvement occurs with sustained abstinence supported by evidence-based treatment.

Why do people become addicted to opioids?

Opioid addiction develops through a combination of neurobiological, genetic, and environmental factors. Hydromorphone activates the mesolimbic dopamine pathway, producing a reward signal four to five times stronger than natural rewards. Genetic variants in the OPRM1 gene influence how intensely this reward is experienced. Adverse childhood experiences, trauma, and untreated depression substantially increase vulnerability. Most people do not choose addiction; the neurobiological mechanisms that drive compulsive use operate largely below voluntary conscious control.

What are the symptoms of hydromorphone withdrawal?

Hydromorphone withdrawal begins within 4 to 8 hours of the last dose and includes yawning, sweating, runny nose, muscle cramps, bone pain, nausea, vomiting, diarrhea, hypertension, tachycardia, insomnia, and intense cravings. Peak intensity occurs between 12 and 36 hours. Because of hydromorphone’s short half-life, withdrawal onset is faster than longer-acting opioids. Medical supervision using COWS-guided protocols significantly reduces the severity and safety risks of the withdrawal process.

How long does hydromorphone addiction treatment take?

Acute medical detox typically lasts 7 to 10 days. Residential treatment following detox generally runs 30 to 90 days, with 90-day programs showing substantially better long-term outcomes than shorter stays. Medication-assisted treatment with buprenorphine or methadone is often continued indefinitely, as SAMHSA and ASAM guidelines confirm there is no medically required time limit on MAT when clinically appropriate. Recovery is best understood as an ongoing process rather than a fixed endpoint.

Can hydromorphone withdrawal be fatal?

Hydromorphone withdrawal is rarely fatal on its own, unlike alcohol or benzodiazepine withdrawal. However, it is extremely severe, and the risk of relapse during unsupervised withdrawal is high. If an individual with depleted opioid tolerance relapses after any period of abstinence and uses their pre-treatment dose, the risk of fatal respiratory depression is dramatically elevated. Medical detox under physician supervision eliminates this risk and addresses the cardiovascular and dehydration complications of severe withdrawal.

Is Dilaudid the same as heroin?

Dilaudid (hydromorphone) and heroin (diacetylmorphine) are different opioids but act through the same mu-opioid receptor system. Both produce euphoria, pain relief, and respiratory depression via the mesolimbic pathway. Hydromorphone is a legally manufactured semi-synthetic opioid prescribed under medical supervision. Heroin is a Schedule I substance with no accepted medical use in the United States. Their clinical effects, addiction mechanisms, and withdrawal profiles are nearly identical, which is why street users often describe Dilaudid as “hospital heroin.”

What happens if you stop hydromorphone suddenly?

Abruptly stopping hydromorphone after regular use triggers acute opioid withdrawal within 4 to 8 hours due to the drug’s short half-life. Symptoms include severe muscle cramps, sweating, vomiting, diarrhea, hypertension, and psychological distress. While rarely fatal in otherwise healthy individuals, abrupt discontinuation without medical supervision carries significant relapse risk during the peak withdrawal window of 12 to 36 hours and is not the recommended approach. Medically supervised detox with COWS-guided pharmacotherapy is the standard of care.

References

1. National Institute on Drug Abuse. (2023). Opioids: Drug facts. U.S. Department of Health and Human Services. https://nida.nih.gov/research-topics/opioids
2. Substance Abuse and Mental Health Services Administration. (2024). 2024 National Survey on Drug Use and Health: Key substance use and mental health indicators in the United States. SAMHSA.
3. American Psychiatric Association. (2022). Diagnostic and statistical manual of mental disorders (5th ed., text rev.). American Psychiatric Publishing.
4. Drug Enforcement Administration. (2023). Hydromorphone: Drug scheduling and controlled substances fact sheet. DEA Diversion Control Division.
5. Volkow, N. D., Koob, G. F., & McLellan, A. T. (2016). Neurobiologic advances from the brain disease model of addiction. New England Journal of Medicine, 374(4), 363–371.
6. Weaver, M. F. (2015). Prescription sedative misuse and abuse. Yale Journal of Biology and Medicine, 88(3), 247–256.
7. Lee, M., Silverman, S. M., Hansen, H., Patel, V. B., & Manchikanti, L. (2011). A comprehensive review of opioid-induced hyperalgesia. Pain Physician, 14(2), 145–161.
8. Hayhurst, C. J., & Durieux, M. E. (2016). Differential opioid tolerance and opioid-induced hyperalgesia: A clinical reality. Anesthesiology, 124(2), 483–488.