Opioids can relieve severe pain, produce sedation and, in some people, create powerful reinforcing effects. The same receptor system that makes opioids medically useful can also produce tolerance, physical dependence, withdrawal and opioid use disorder.
Understanding opioid pharmacology helps explain why a person can begin with prescribed pain medication and later find that stopping has become difficult, why fentanyl can cause overdose so rapidly, why withdrawal occurs when opioid exposure suddenly falls, and why different medications used in recovery work in very different ways.
Opioids do not simply “increase dopamine.” Their effects begin when opioid molecules interact with specific receptors distributed throughout the brain, spinal cord, gastrointestinal system and other tissues.
The mu-opioid receptor is particularly important. Activation of this receptor contributes to analgesia, reward, sedation, constipation, physical dependence and — at sufficiently high opioid effect — dangerous respiratory depression.
With repeated opioid exposure, the nervous system adapts. These adaptations help explain tolerance and physical dependence. They also explain why abruptly stopping an opioid can produce withdrawal even in somebody who has taken the medication exactly as prescribed.
Physical dependence, however, is not automatically the same as addiction. Opioid use disorder is a broader medical condition involving a problematic pattern of opioid use that causes significant impairment or distress.
Treatment therefore needs to distinguish between several different situations: short-term therapeutic opioid use, long-term prescribed use, physical dependence, opioid withdrawal, opioid use disorder and acute opioid overdose.
This guide explains the pharmacology behind all of these processes and compares the three principal medication approaches used in opioid use disorder: methadone, buprenorphine and naltrexone.
It also explains the role of long-acting naltrexone and naltrexone implants, why patients must be appropriately opioid-free before antagonist treatment, and why naloxone and naltrexone should never be confused.
Opioid receptors, agonists and antagonists, analgesia, reward, respiratory depression, tolerance, physical dependence, withdrawal, fentanyl, overdose, loss of tolerance, medication treatment and the role of long-acting naltrexone in opioid recovery.
Prepared for medical review by Dr. Fergus Law, BSc, MBChB, FRCPsych
Consultant Psychiatrist specialising in substance misuse and addiction psychiatry
Review status: Pending clinical approval
View Dr Fergus Law’s Clinical & Scientific Profile →What Are Opioids?
Opioids are substances that interact with opioid receptors in the nervous system and other tissues.
The term includes naturally occurring, semi-synthetic and fully synthetic drugs. Some are prescribed medically. Others are produced or distributed illegally.
Morphine & Codeine
These drugs originate from naturally occurring opium alkaloids derived from the opium poppy.
Heroin, Oxycodone & Hydrocodone
These opioids are chemically modified from naturally derived opioid compounds.
Fentanyl & Methadone
These drugs are manufactured synthetically but still interact with opioid receptors.
Opioids are particularly effective at reducing some types of pain because opioid receptors are located in pain-processing pathways in the brain, spinal cord and peripheral nervous system.
But those receptors are not limited to pain pathways.
They are also present in regions involved in breathing, gastrointestinal activity, reward, stress and other physiological functions.
This explains why one opioid drug can simultaneously reduce pain, cause constipation, produce sedation and suppress breathing.
The benefits and risks of opioids arise from the same receptor system. The drug cannot selectively activate only the “pain relief” effect while completely ignoring every other opioid effect.
Opioid Receptors Explained
The body has its own endogenous opioid system.
Natural peptides such as endorphins, enkephalins and dynorphins interact with opioid receptors as part of normal physiology.
External opioids such as morphine, heroin and fentanyl can activate many of the same receptors.
Mu Receptor
The receptor most strongly associated with clinically important opioid analgesia, reinforcement, euphoria, physical dependence, constipation and respiratory depression.
Kappa Receptor
Kappa receptors contribute to pain modulation and can also be associated with dysphoric or unpleasant effects when activated.
Delta Receptor
Delta receptors also participate in pain modulation and other nervous-system functions.
What Happens Inside the Cell?
Classical opioid receptors are G-protein-coupled receptors.
When an opioid agonist activates these receptors, intracellular signaling changes. Neuronal excitability and neurotransmitter release can be reduced in specific circuits.
In pain pathways, that can reduce transmission and perception of painful signals.
In brainstem respiratory networks, however, excessive opioid receptor activation can suppress the neural drive to breathe.
Understanding Opioids and How They Affect the Brain
This medical animation gives a visual explanation of opioid receptors, pain signaling, dependence, withdrawal and overdose.
Educational medical animation. The video is supplementary and does not replace individualized medical advice.
Opioid Agonists, Partial Agonists and Antagonists
One of the most useful ways to understand opioid treatment is to look at what different drugs do after they bind to the mu-opioid receptor.
Activates the Receptor
Full opioid agonists can produce increasing opioid effects as exposure increases.
ExamplesMorphine, heroin, fentanyl, oxycodone and methadone.
Activates the Receptor Partially
Buprenorphine binds strongly to the mu receptor but produces only partial receptor activation.
ExampleBuprenorphine.
Binds Without Activating
An antagonist occupies opioid receptors but does not produce opioid agonist effects.
ExamplesNaltrexone and naloxone.
Why This Matters in Treatment
Methadone treats opioid use disorder while continuing controlled opioid-receptor agonism.
Buprenorphine also activates the receptor but only partially and has a ceiling effect on some opioid effects, including respiratory depression.
Naltrexone takes a fundamentally different approach.
It is an antagonist. It does not activate the mu receptor and does not substitute an opioid agonist effect.
Read SAMHSA’s MOUD Pharmacology Overview →How Opioids Produce Pain Relief, Reward, Sedation and Constipation
Opioid receptor activation affects different circuits and tissues throughout the body.
Analgesia
Opioid activity in the brain and spinal cord can reduce the transmission and perception of pain.
Reinforcing Effects
Opioids can alter reward pathways and increase the motivational significance of drug-related effects and cues.
Respiratory Depression
Excessive opioid effect can suppress brainstem networks that normally maintain breathing.
Constipation
Peripheral and central opioid effects can slow gastrointestinal motility.
Sedation
Opioids can reduce alertness and impair coordination, particularly at higher exposures or when combined with other sedatives.
Miosis
Constricted or “pinpoint” pupils are a characteristic opioid effect and can be present during overdose.
What About Dopamine?
Dopamine is involved in motivation, learning, reinforcement and salience.
Opioids can indirectly alter dopamine signaling in reward pathways, which contributes to reinforcement and learning around drug use.
It is more accurate to describe dopamine as part of a learning and motivational system than simply calling it a “pleasure chemical.”
Repeated opioid exposure can teach the brain that opioid use is highly significant. Environmental cues, stress, withdrawal and memories can then influence future drug-seeking behavior.
How Opioid Tolerance Develops
Tolerance means that repeated exposure to a drug produces less effect than it previously did, so a greater dose or more frequent exposure may be required to reproduce the same effect.
Opioid tolerance develops because the nervous system adapts to repeated receptor stimulation.
These adaptations can involve changes in receptor signaling, receptor sensitivity and intracellular pathways.
Tolerance Does Not Develop Equally to Every Effect
A person may become tolerant to some opioid effects more rapidly than others.
For example, constipation can remain a significant problem even after other subjective opioid effects have changed.
A person who has developed tolerance can still overdose, especially if dose, potency, route of administration or drug supply changes, or if opioids are combined with other respiratory depressants.
Tolerance is also reversible.
After a period of abstinence, tolerance can fall. Returning to a previously tolerated dose can therefore become much more dangerous.
Physical Opioid Dependence Explained
Physical dependence occurs when the body has adapted to the continued presence of an opioid.
If opioid exposure is then stopped or substantially reduced, the adapted nervous system is suddenly operating without the drug it has adjusted to.
Withdrawal symptoms can result.
Physical dependence can occur during legitimate medical treatment. Developing dependence does not by itself mean that somebody has opioid use disorder.
This distinction is particularly important for patients taking opioids for chronic pain.
A patient can be physically dependent while taking every dose exactly as prescribed.
If treatment needs to be reduced, the medication may need to be tapered gradually rather than abruptly stopped.
Dependence Can Reinforce Continued Use
Once withdrawal becomes established, taking another opioid dose can rapidly relieve some withdrawal symptoms.
This creates a form of negative reinforcement: the person uses the drug partly to escape an unpleasant state.
That process can become clinically important even when the original reason for opioid use was pain treatment.
Why Opioid Withdrawal Happens
Withdrawal occurs when opioid receptor stimulation falls substantially in somebody whose nervous system has adapted to ongoing opioid exposure.
Withdrawal Timing Depends on the Opioid
Short-acting and long-acting opioids do not produce identical withdrawal timelines.
Methadone and buprenorphine can remain in the body considerably longer than many short-acting opioids, so the timing of withdrawal and transition to other treatment can differ.
Naltrexone has strong affinity for opioid receptors but does not activate them. If given while a patient is still physically dependent on opioids, it can rapidly displace opioid agonists and produce an abrupt withdrawal syndrome.
This is why antagonist treatment must be medically timed and should not be self-initiated during active opioid dependence.
Read SAMHSA Guidance on Naltrexone Preparation →Physical Dependence vs Opioid Use Disorder
Tolerance, physical dependence and opioid use disorder are related concepts, but they are not interchangeable.
Reduced Response
The same opioid exposure produces less effect after repeated use.
Physiological Adaptation
Withdrawal may occur when opioid exposure is suddenly reduced or stopped.
Problematic Pattern of Use
Opioid use causes clinically significant impairment or distress across behavior and daily life.
What Can Opioid Use Disorder Look Like?
OUD can involve difficulty controlling opioid use, persistent unsuccessful attempts to cut down, craving, spending substantial time obtaining or using opioids, continued use despite harm, hazardous use or major interference with work, family or other responsibilities.
Diagnosis should be made by an appropriately qualified healthcare professional.
Describing every physically dependent patient as “addicted” is medically inaccurate and can create unnecessary stigma. At the same time, physical dependence should not be used to dismiss clear signs of opioid use disorder.
Why Fentanyl Is Especially Dangerous
Fentanyl is a highly potent synthetic opioid.
Pharmaceutical fentanyl has legitimate medical uses, including severe pain and anesthesia.
The major public-health danger comes from illegally manufactured fentanyl, which is frequently found in the unregulated drug supply.
CDC describes pharmaceutical fentanyl as approximately 50 to 100 times more potent than morphine.
High potency means a comparatively small amount can produce a large opioid effect. If the amount in an illicit product is unpredictable, the difference between an expected effect and severe respiratory depression can become dangerously small.
Why Illicit Fentanyl Is Difficult to Dose Safely
Unregulated powders and counterfeit tablets do not provide the quality controls available with pharmaceutical products.
A person may not know whether fentanyl is present or how much fentanyl is contained in the drug they are taking.
Fentanyl can also be mixed into drugs sold as heroin, counterfeit prescription tablets and other substances.
Read CDC Fentanyl Information →How Opioid Overdose Suppresses Breathing
Fatal opioid overdose usually becomes dangerous because opioids suppress the brain’s control of breathing.
Normally, rising carbon dioxide levels stimulate the respiratory system to keep breathing.
Excessive opioid receptor activation can blunt that drive.
Breathing may become slow, shallow and irregular before eventually stopping.
Extensive opioid-receptor activation.
Breathing becomes slower or shallower.
The brain and organs receive inadequate oxygen.
Without reversal and respiratory support, overdose can become fatal.
Signs of Possible Opioid Overdose
- The person cannot be awakened.
- Breathing is very slow, shallow, irregular or stopped.
- There may be snoring, choking or gurgling sounds in an unresponsive person.
- Lips, fingertips or skin may become blue, gray or unusually pale.
- Pupils may be very small or “pinpoint.”
In the United States, call 911 and give naloxone if available. Follow the emergency operator’s instructions and do not leave the person alone.
Why Benzodiazepines and Alcohol Increase Risk
Opioids should be treated with particular caution when combined with other substances that depress the central nervous system.
Alcohol, benzodiazepines and some other sedatives can add to sedation and respiratory depression.
CDC: How to Respond to Opioid Overdose →Loss of Opioid Tolerance and Overdose Risk
Opioid tolerance is not permanent.
When opioid use stops, tolerance can decrease.
A dose that somebody previously tolerated may therefore become much more dangerous after a period of abstinence.
This is one reason overdose prevention must remain part of recovery planning.
It is also one reason detoxification by itself should not be treated as a complete treatment for opioid use disorder.
Removing opioids from the body does not remove the psychological, environmental and biological factors associated with opioid use disorder. Continuing treatment and relapse-prevention support remain important.
How Opioid Use Disorder Can Develop
There is no single pathway from first opioid exposure to opioid use disorder.
Some people receive opioids medically and never develop OUD.
Others may develop escalating use through a combination of repeated exposure, reinforcement, pain, mental-health problems, stress, genetics, environment, withdrawal and availability.
The brain experiences opioid effects such as analgesia, sedation or reinforcement.
Repeated exposure can lead to tolerance and physical dependence.
Stress, withdrawal and environmental cues can become linked with drug-seeking behavior.
In OUD, opioid use continues despite significant harm or the person’s intention to reduce or stop.
Withdrawal Can Become Part of the Cycle
Opioid use may initially be driven by pain relief, intoxication or another desired effect.
After dependence develops, avoiding withdrawal can become an additional reason to continue using.
A person may be dealing simultaneously with craving, physical withdrawal, reduced tolerance, learned environmental triggers, social problems and an underlying pain or mental-health condition.
Medications for Opioid Use Disorder
In the United States, the FDA recognizes three medications for treatment of opioid use disorder: methadone, buprenorphine and naltrexone.
They all interact with the opioid system, but their pharmacology is fundamentally different.
Methadone
Methadone is a long-acting full opioid agonist.
When appropriately dosed in OUD treatment, it can prevent withdrawal, reduce craving and stabilize opioid exposure without the repeated rapid intoxication-withdrawal cycle associated with shorter-acting opioids.
Buprenorphine
Buprenorphine is a high-affinity partial mu-opioid receptor agonist.
Its strong receptor affinity allows it to occupy mu receptors and reduce withdrawal and craving.
Because it is a partial agonist, its maximum opioid effect is more limited than that of a full agonist.
Naltrexone
Naltrexone is different from both methadone and buprenorphine.
It does not activate opioid receptors.
It is used after appropriate opioid withdrawal and blocks the effects of opioid agonists while adequate receptor blockade is present.
Methadone and buprenorphine have particularly strong evidence for reducing mortality in opioid use disorder. Naltrexone is also an FDA-approved treatment, but mortality evidence should not be presented as identical across all three medications.
Naltrexone, Long-Acting Formulations and Naltrexone Implants
Naltrexone takes a different pharmacological approach from methadone and buprenorphine because it blocks opioid receptors rather than activating them.
Naltrexone has strong affinity for mu-opioid receptors.
When receptors are occupied by naltrexone, an opioid agonist such as heroin, oxycodone or fentanyl may produce substantially less opioid effect while an adequate blockade is present.
Naltrexone does not activate the mu receptor and does not produce the same opioid agonist effects as methadone or buprenorphine.
Receptor occupancy can block or substantially reduce the expected effects of subsequently used opioids.
Starting naltrexone while significant physiological opioid dependence remains can precipitate severe withdrawal.
Longer-acting delivery is designed to reduce the adherence problem associated with remembering a daily tablet.
How Long Must a Patient Be Opioid-Free?
SAMHSA TIP 63 describes typical preparation periods of approximately 7–10 days after short-acting opioids and 10–14 days after long-acting opioids before naltrexone initiation.
These are general clinical guidelines rather than a do-it-yourself detox timetable.
The correct preparation depends on the opioid, dose, duration of use, metabolism, medical history, withdrawal state and clinical assessment.
A clinician may also use toxicology testing or a naloxone challenge in appropriate circumstances.
Because naltrexone can displace opioid agonists from receptors without replacing their agonist effect, starting it too early can cause abrupt, severe precipitated withdrawal.
What About Long-Acting Naltrexone Implants?
Sustained-release naltrexone implants have been researched and used in some countries and clinical settings.
The purpose is to maintain antagonist exposure for a longer period and reduce dependence on daily adherence.
However, implant formulations can differ substantially in dose, release profile, manufacturing, duration and regulatory status.
Research on one implant should therefore not automatically be applied to every implant product.
In the United States, the FDA-approved long-acting naltrexone product for opioid use disorder is extended-release intramuscular naltrexone. Naltrexone implants are not FDA-approved in the United States.
Does Naltrexone Guarantee Protection From Overdose?
No medication should be described as guaranteeing that an opioid overdose cannot occur.
Naltrexone can block opioid effects while adequate antagonist concentrations are maintained, but the blockade is competitive and can potentially be overcome by very large opioid exposure.
There is also overdose vulnerability when blockade decreases or treatment stops because opioid tolerance may have fallen.
Long-acting naltrexone can provide a sustained pharmacological barrier to opioid effects and may reduce craving pressure for some patients, creating a longer period in which recovery work, counselling and rebuilding routines can take place. It should not be described as an absolute overdose guarantee.
Want to Understand Whether Antagonist Treatment Could Fit Your Recovery?
DeBinge provides individual assessment and education around preparation, long-acting naltrexone and ongoing recovery support.
Suitability depends on opioid history, current medication, medical condition and the ability to complete an appropriate opioid-free preparation period.
Naloxone vs Naltrexone: Do Not Confuse Them
Naloxone and naltrexone both block opioid receptors, but their clinical roles are very different.
Emergency Overdose Reversal
Naloxone acts rapidly and is used when somebody may be experiencing an opioid overdose.
It can displace opioids from receptors and reverse life-threatening respiratory depression when administered in time.
Ongoing Antagonist Treatment
Naltrexone is used as an ongoing treatment for opioid use disorder after appropriate opioid withdrawal.
It is not the standard emergency rescue medication for somebody who is currently overdosing.
If opioid overdose is suspected, use an approved overdose-reversal medication such as naloxone when available and contact emergency services.
From Opioid Pharmacology to a Recovery Plan
Pharmacology explains why opioid dependence can become powerful, but medication alone does not describe the whole recovery process.
A comprehensive plan should consider the person’s opioid exposure, withdrawal risk, overdose risk, pain, mental health, living environment, social support and long-term treatment preference.
Identify the Current Opioid Exposure
Determine what opioid is being used, how often, the approximate dose, route, duration and whether fentanyl, methadone or buprenorphine is involved.
Assess Physical Dependence
Establish whether stopping or reducing opioids produces withdrawal and whether medical withdrawal management is needed.
Assess for Opioid Use Disorder
Look beyond tolerance alone and assess control over use, craving, harmful consequences and interference with daily life.
Discuss Medication Options
Methadone, buprenorphine and naltrexone use different pharmacological strategies and should be considered through shared decision-making.
Build Overdose Protection Into the Plan
Naloxone access, fentanyl awareness, avoiding dangerous sedative combinations and understanding loss of tolerance can save lives.
Continue Recovery Beyond Detox
Counselling, follow-up, treatment of coexisting conditions, rebuilding routine and addressing triggers can help turn initial stabilization into sustained recovery.
Opioid Pharmacology Knowledge Quiz
This educational quiz contains 20 questions, but only one question appears at a time.
Use the Back and Next buttons to move through the quiz. Your score appears at the end.
This quiz is educational. It does not diagnose opioid dependence, opioid use disorder or treatment suitability.
Opioid Pharmacology and Dependence FAQ
1. What exactly is an opioid?
An opioid is a substance that interacts with opioid receptors. Examples include morphine, heroin, oxycodone, fentanyl, methadone and buprenorphine.
2. Which opioid receptor is most important in opioid dependence?
The mu-opioid receptor is particularly important in analgesia, reward, respiratory depression, tolerance and physical dependence.
3. What is an opioid agonist?
An agonist binds to and activates an opioid receptor. Morphine, fentanyl and methadone are examples of full mu-opioid receptor agonists.
4. What is a partial opioid agonist?
A partial agonist activates a receptor but produces a lower maximum effect than a full agonist. Buprenorphine is the principal example used in opioid use disorder treatment.
5. What is an opioid antagonist?
An antagonist occupies opioid receptors without activating them. Naltrexone and naloxone are opioid antagonists.
6. What is opioid tolerance?
Tolerance is a reduced response after repeated exposure, meaning greater exposure may be required to produce an effect similar to one previously achieved at a lower dose.
7. What is physical opioid dependence?
Physical dependence means the body has adapted to ongoing opioid exposure and withdrawal can occur when opioid exposure falls substantially.
8. Is physical dependence the same as opioid addiction?
No. Physical dependence can occur during appropriately prescribed opioid treatment. Opioid use disorder is a broader pattern of problematic opioid use causing clinically significant impairment or distress.
9. Why does opioid withdrawal happen?
Withdrawal reflects nervous-system adaptations to repeated opioid exposure. When opioid receptor stimulation falls abruptly, those adaptations produce symptoms such as anxiety, sweating, aches, gastrointestinal symptoms and craving.
10. Why can fentanyl cause overdose so quickly?
Fentanyl is highly potent. A comparatively small amount can produce a strong opioid effect, including severe respiratory depression. Illicit fentanyl products also have unpredictable concentration.
11. What actually kills somebody during an opioid overdose?
The principal immediate danger is respiratory depression. Breathing can become too slow or stop, depriving the brain and other organs of oxygen.
12. Why is overdose risk higher after abstinence?
Opioid tolerance decreases during abstinence. Returning to a dose previously tolerated can therefore produce a much stronger and potentially fatal opioid effect.
13. How does methadone treat opioid use disorder?
Methadone is a long-acting full opioid agonist. Appropriate maintenance dosing can suppress withdrawal and craving and stabilize opioid exposure.
14. How does buprenorphine work?
Buprenorphine is a high-affinity partial mu-opioid receptor agonist. It can reduce withdrawal and craving while producing a more limited maximum opioid effect than full agonists.
15. How does naltrexone work?
Naltrexone is an opioid receptor antagonist. It binds to opioid receptors without activating them and can block opioid agonist effects while adequate antagonist exposure is present.
16. Can naltrexone be started immediately after heroin or fentanyl?
No. A physiologically opioid-dependent patient must first complete an appropriate opioid-free preparation period. Starting naltrexone too early can precipitate severe withdrawal.
17. How long must somebody be opioid-free before naltrexone?
SAMHSA guidance commonly describes approximately 7–10 days after short-acting opioids and 10–14 days after long-acting opioids, but individual assessment is required.
18. Are naltrexone implants FDA-approved in the United States?
No. The FDA-approved long-acting naltrexone formulation for opioid use disorder in the United States is extended-release intramuscular naltrexone. Implant products have different regulatory status.
19. Does a naltrexone implant guarantee that overdose is impossible?
No. Naltrexone can block opioid effects while adequate blockade is present, but overdose can still occur, particularly if somebody attempts to overcome blockade or returns to opioid use as the blockade wanes after tolerance has decreased.
20. What is the difference between naloxone and naltrexone?
Naloxone is primarily an emergency opioid-overdose reversal medication. Naltrexone is an ongoing antagonist treatment used after opioid withdrawal for opioid use disorder.
Opioid Dependence Requires More Than Simply Stopping the Drug
The nervous system adapts to repeated opioid exposure. Treatment therefore needs to consider withdrawal, tolerance, overdose risk, craving and the person’s longer-term recovery goals.
DeBinge can explain long-acting naltrexone, opioid-free preparation requirements, counselling and the wider recovery process.
Scientific References and Further Reading
This article draws on NIDA, CDC, FDA, SAMHSA/NCBI clinical guidance and peer-reviewed pharmacology literature.
NIDA — Opioids
National Institute on Drug Abuse overview covering opioid effects, overdose, dependence, tolerance, withdrawal and opioid use disorder.
Read NIDA Opioid Information →NIDA — Drugs, Brains, and Behavior
Scientific overview of addiction, neuroadaptation, reinforcement and recovery.
Read the NIDA Science of Addiction →Opioid Receptor Physiology — NCBI Bookshelf
Overview of mu, kappa and delta opioid receptors and their physiological effects.
Read on NCBI →CDC — Prescription Opioids
Public-health information on prescription opioid risks, addiction and overdose.
Read CDC Guidance →CDC — Fentanyl
Information on pharmaceutical and illegally manufactured fentanyl, potency and overdose risk.
Read CDC Fentanyl Information →CDC — Reverse Opioid Overdose
Guidance covering overdose recognition and naloxone response.
Read CDC Naloxone Guidance →SAMHSA TIP 63 — Overview of Medications for OUD
Compares methadone, buprenorphine and naltrexone pharmacology.
Read the SAMHSA Overview →SAMHSA TIP 63 — Methadone
Detailed clinical guidance on methadone pharmacology and treatment of opioid use disorder.
Read the Methadone Chapter →SAMHSA TIP 63 — Buprenorphine
Guidance explaining buprenorphine’s high receptor affinity, partial agonism and ceiling effect.
Read the Buprenorphine Chapter →SAMHSA TIP 63 — Naltrexone
Federal guidance covering naltrexone pharmacology, opioid-free preparation, precipitated withdrawal and patient selection.
Read the Naltrexone Chapter →FDA — Medications for Opioid Use Disorder
Current FDA information on approved methadone, buprenorphine and naltrexone formulations.
Read FDA MOUD Information →NIH — Methadone and Buprenorphine Mortality Evidence
NIH-funded research showing reduced mortality after nonfatal opioid overdose among people receiving methadone or buprenorphine.
Read the NIH Research Summary →2025 Cochrane Review — Sustained-Release Naltrexone
Systematic review examining long-acting injectable and implantable sustained-release naltrexone for opioid dependence.
Read the Cochrane Review →Sustained-release naltrexone implants are not all interchangeable. Dose, release profile, duration, manufacturing and regulatory status can differ between products.
Evidence from one implant formulation should not automatically be assumed to apply to another.
NIDA video explaining how naloxone, buprenorphine, methadone and naltrexone work.
Watch NIDA Video → SAMHSA TIP 63Comprehensive clinical guidance on medications for opioid use disorder.
Read TIP 63 → CDC Overdose PreventionOpioid-overdose prevention, naloxone and treatment resources.
Explore CDC → Dr Fergus LawClinical and scientific profile and addiction expertise.
View Profile →Prepared for medical review by Dr. Fergus Law, BSc, MBChB, FRCPsych
Consultant Psychiatrist specialising in substance misuse and addiction psychiatry
Review status: Pending clinical approval
Medical evidence and clinical guidance can change. This article is educational and does not replace individualized diagnosis, detoxification, prescribing advice or emergency medical care.