How do different opioids compare in strength. What factors influence opioid potency. Which opioids are considered the strongest and weakest. How can healthcare providers use opioid equivalence charts safely. What risks are associated with high-potency opioids.

The Basics of Opioid Potency and Equivalence

Comparing the strength of different opioids is a complex but crucial task in pain management. Opioid potency refers to the amount of a drug needed to produce a given effect. Understanding relative potencies allows healthcare providers to safely switch between opioids or combine them.

Morphine is typically used as the standard for comparison, with other opioids described in terms of their potency relative to morphine. However, creating a simple linear scale of opioid strengths is challenging due to various factors that influence potency.

Key Factors Affecting Opioid Potency

• Route of administration (oral, intravenous, transdermal, etc.)
• Individual patient factors (age, genetics, tolerance)
• Specific opioid receptor affinities
• Duration of action
• Dose ceiling effects

Do all opioids work the same way in the body? No, different opioids can have varying effects on different opioid receptor subtypes, leading to differences in analgesia, side effects, and potency that aren’t captured by simple numerical comparisons.

Interpreting Opioid Equivalence Charts

Opioid equivalence charts provide approximate conversions between different opioids based on their relative potencies. These charts are valuable tools, but they must be used cautiously and in conjunction with clinical judgment.

The World Health Organization (WHO) provides a widely-referenced opioid equivalence chart in its Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents. This chart lists the approximate potency of various opioids relative to morphine.

Sample Opioid Relative Potencies (Oral Route)

• Morphine: 1 (reference standard)
• Codeine: 0.13
• Tramadol: 0.1-0.2
• Oxycodone: 1.5-2
• Hydromorphone: 5
• Fentanyl: 100-150 (transdermal)

How should healthcare providers use these equivalence ratios? They should multiply the dose of a given opioid by its relative potency to determine the equivalent morphine dose. Conversely, dividing a morphine dose by the relative potency yields the equivalent dose of another opioid.

The Strongest Opioids: Potent but Potentially Dangerous

While high-potency opioids can provide powerful pain relief, they also carry significant risks. Understanding which opioids are considered the strongest is crucial for both healthcare providers and patients.

Top High-Potency Opioids

1. Carfentanil
2. Sufentanil
3. Remifentanil
4. Fentanyl
5. Hydromorphone

Why are these opioids considered so potent? These drugs have very high binding affinities for opioid receptors, particularly the mu-opioid receptor, which is primarily responsible for analgesia. This means they can produce strong effects at very low doses compared to morphine.

Carfentanil, for example, is estimated to be 10,000 times more potent than morphine. Its legitimate use is limited to veterinary medicine for very large animals. Fentanyl, while less potent than carfentanil, is still 50-100 times stronger than morphine and has become notorious for its role in the opioid epidemic.

Weaker Opioids: Lower Potency but Still Effective

On the other end of the spectrum, weaker opioids can still provide significant pain relief with potentially lower risks of severe side effects or overdose. These drugs are often used as first-line treatments for moderate pain or in opioid-naive patients.

Common Lower-Potency Opioids

• Codeine
• Tramadol
• Hydrocodone
• Tapentadol

Are weaker opioids always safer? While lower-potency opioids may have a reduced risk of severe respiratory depression, they can still cause dependence and other side effects. Additionally, some patients may metabolize these drugs differently, potentially increasing their effects.

Codeine, for example, is a prodrug that must be converted to morphine in the body to be effective. Some individuals are poor metabolizers and may not receive adequate pain relief, while others are ultra-rapid metabolizers and may experience stronger than expected effects.

Special Considerations: Methadone and Buprenorphine

Methadone and buprenorphine occupy unique positions in the opioid potency spectrum due to their complex pharmacology and varied uses in pain management and addiction treatment.

Methadone: A Potency Paradox

Methadone’s potency relative to morphine is highly variable and dose-dependent. While a single 5 mg dose of methadone may be equivalent to only 7.5 mg of morphine, regular administration can result in a much higher relative potency due to methadone’s long half-life and broad-spectrum receptor affinity.

Why is methadone conversion so challenging? Methadone’s accumulation in the body and its variable effects on different opioid receptors can lead to unexpected potency increases over time. This makes conversions to regularly administered methadone particularly complex, often requiring specialist guidance.

Buprenorphine: Partial Agonist with Unique Properties

Buprenorphine is a partial mu-opioid receptor agonist with high binding affinity but lower intrinsic activity compared to full agonists. This results in a ceiling effect on respiratory depression, potentially improving its safety profile.

How does buprenorphine’s partial agonism affect its potency? While buprenorphine can be very potent at low doses, its effects plateau at higher doses. This makes direct potency comparisons with full agonists like morphine challenging and dependent on the specific dose range being considered.

Practical Applications of Opioid Potency Knowledge

Understanding opioid potencies and using equivalence charts appropriately is crucial for safe and effective pain management. Healthcare providers must consider multiple factors when making opioid conversions or adjusting treatment regimens.

Key Considerations for Opioid Conversions

• Start with conservative dose estimates and titrate carefully
• Account for incomplete cross-tolerance between opioids
• Consider the patient’s age, renal function, and other medications
• Be aware of differences in side effect profiles between opioids
• Monitor patients closely during and after conversions

How can providers ensure safe opioid rotations? It’s generally recommended to reduce the calculated equianalgesic dose by 25-50% when switching to a new opioid to account for incomplete cross-tolerance and individual variability. Gradual titration and close monitoring are essential to achieve optimal pain control while minimizing risks.

Risks and Challenges of High-Potency Opioids

While high-potency opioids can provide powerful pain relief, they also present significant risks and challenges in both medical and non-medical contexts.

Medical Risks of Potent Opioids

• Increased risk of respiratory depression and overdose
• Narrow therapeutic window
• Rapid onset of tolerance
• Potential for severe withdrawal symptoms

Why are high-potency opioids particularly dangerous? Their potency means that even small dosing errors can have severe consequences. The rapid onset of action of some potent opioids like fentanyl can quickly lead to respiratory depression before naloxone can be administered effectively.

Public Health Concerns

The high potency of synthetic opioids like fentanyl has contributed significantly to the ongoing opioid epidemic. Illicitly manufactured fentanyl and its analogs have been increasingly found in the drug supply, often mixed with or substituted for other drugs without users’ knowledge.

How has fentanyl impacted overdose rates? According to the CDC, synthetic opioids (primarily fentanyl) were involved in 66% of all overdose deaths in 2021, highlighting the devastating impact of these high-potency drugs.

Future Directions in Opioid Research and Pain Management

As our understanding of opioid pharmacology and pain mechanisms continues to evolve, researchers are exploring new approaches to pain management that may provide effective analgesia with reduced risks.

Emerging Strategies in Pain Management

• Biased agonists targeting specific opioid receptor signaling pathways
• Dual-action compounds combining opioid and non-opioid mechanisms
• Abuse-deterrent formulations
• Personalized medicine approaches based on genetic factors
• Advanced drug delivery systems for more precise dosing

Can we develop safer yet effective opioid analgesics? Researchers are working to design novel opioids that maintain analgesic efficacy while reducing side effects like respiratory depression and dependence. For example, some biased agonists aim to activate pain-relieving pathways without triggering pathways associated with adverse effects.

Understanding opioid potency and using this knowledge judiciously is crucial for balancing effective pain management with patient safety. As research progresses, we may see new tools and approaches that further refine our ability to tailor opioid therapy to individual patient needs while minimizing risks.

Table A6.2, Approximate potency of opioids relative to morphine; PO and immediate-release formulations unless stated otherwisea – WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents. Geneva: World Health Organization; 2018.

WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents.

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Table A6.2Approximate potency of opioids relative to morphine; PO and immediate-release formulations unless stated otherwise

^a

Source: Adapted with permission from Twycross et al. 2017:371 (Table 4) (3).

a

Multiply dose of opioid in the first column by relative potency in the second column to determine the equivalent dose of morphine sulfate/hydrochloride; conversely, divide morphine dose by the relative potency to determine the equivalent dose of another opioid.

b

Dependent in part on severity of pain and on dose; often longer-lasting in very elderly and those with renal impairment.

c

The numbers in parenthesis are the manufacturers’ preferred relative potencies.

d

A single 5 mg dose of methadone is equivalent to morphine 7.5 mg, but a variable long plasma half-life and broad-spectrum receptor affinity result in a much higher-than-expected relative potency when administered regularly – sometimes much higher than the range given above. Therefore, guidance from a specialist is recommended for conversions to regularly administered methadone.

From: ANNEX 6, Pharmacological Profiles and Opioid Conversion Tables

© World Health Organization 2018.

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Discover the List of Opioids From Strongest to Weakest to Avoid Overdose Updated 2023

September 11, 2017
by Mark Adams

A Guide to Addictive Opiates: List of Opioids Strongest to Weakest

Post updated 3-10-2023

Creating a list of opioids from strongest to weakest is not as straightforward as simply listing them by potency or by an analgesic effect. A report released by the CDC (1) listed various narcotic pain medications by strength as they compared to morphine. Yet the list doesn’t determine whether the medication also has a similar mechanism of action. Some of the strongest types of pain medication in a hospital may have a similar potency to morphine, but they may also be formulated with a dose ceiling, while morphine does not, rendering them less potent overall.  

The actual potency of some narcotic pain medications and prescription opioids, or pain relievers by strength, may also vary, depending on the route of administration.  Essentially, the list of opioids strongest to weakest is determined by factoring in that a smaller dose of certain painkiller medications may be required to achieve the same pain-relief response to treat severe pain as can be reached with morphine.

With those determinations in mind, the list of common opioids from strongest to weakest is also broken down into three classifications: stronger than morphine, morphine-equivalent and weaker than morphine.

Stronger than Morphine

Opioid use disorders (OUD) are on the rise. Let’s take a look at some of the drugs that are stronger than morphine.

Fentanyl (Duragesic)

 Fentanyl is common among drug abusers and is one of the strongest opioids on the market and is the strongest pain medication in hospital settings. This drug can lead to abuse and addiction. The opioid painkiller medication has a rapid onset and short duration of action. It’s occasionally used as a part of the anesthesia process to help prevent pain following surgery but it is also used to treat severe pain. Depending on the method of administration, it’s estimated that fentanyl can be up to 100 times more potent than morphine and is classified as one of the strongest opioids.

Oxymorphone (Opana ER, Numorphan)

Oxymorphone is a semi-synthetic opioid painkiller medication commonly used to treat severe to chronic pain and to maintain anesthesia. The powerful opioid medication is highly addictive and requires an opioid addiction treatment program to overcome, leading the FDA to ask the manufacturer to remove it from the US market in 2017.

Hydromorphone (Dilaudid, Exalgo, Contin)

Hydromorphone is synthesized from morphine and is commonly used in hospital settings to treat moderate to severe pain. The medication is more soluble in water than morphine, which allows the drug to be delivered in a smaller amount of water.

Heroin (diamorphine)

Heroin is created by combining the morphine alkaloid with acetic anhydride to create a more potent opioid analgesic drug. While heroin was once used in medical settings, it was made a Schedule I Substance under the Controlled Substances Act in 1924 and is now an illicit drug used primarily for recreational purposes. It’s estimated that heroin is approximately 2 to 4 times more potent than morphine. Heroin addiction is a contributing factor to the drug epidemic that the U.S. is facing and is leading to mass overdose deaths. 

Levorphanol (Levo-Dromoran)

Levorphanol is a synthetic opioid painkiller medication created from the compound racemorphan and used to treat moderate to severe pain. Levorphanol is produced using one of the two enantiomers of the compound racemorphan. Levorphanol is several times more potent than morphine and is strongly addicting.

Methadone (Dolophine, Methadone)

Methadone is an opioid painkiller medication used to treat moderate to severe pain. It’s also prescribed to treat opioid dependence in methadone maintenance programs.  It is considered more potent than morphine due to its effectiveness against neuropathic pain. There is also a lower risk of the user developing dose tolerance with methadone (2) as compared to other types of opioids.

Oxycodone (OxyContin, Roxicodone)

Oxycodone has a greater analgesic effect than morphine (6). The semi-synthetic opioid is synthesized from thebaine, an alkaloid found in the opium poppy and is approximately 1.5 times stronger than morphine.

Morphine-Equivalent

Tapentadol (Nucynta, Palexia SR): Technically, tapentadol could be classified as stronger than morphine, as clinical trials (3) indicate the medication provides superior analgesic effects than equivalent doses of oxycodone, but with significantly lower gastrointestinal side effects. However, as tapentadol has a dose ceiling, so it’s listed as a morphine-equivalent ahead in order of strength to morphine.

Morphine (Astramorph, Avinza, Kadian)

Morphine is created from the morphine alkaloid found within the opium poppy and is commonly used to treat moderate to severe pain. Approximately 70% of morphine produced is used as a base to create other opioid medications (5), including oxymorphone, hydromorphone, and heroin.

Hydrocodone (Zohydro ER)

Hydrocodone is a semi-synthetic opiate analgesic created from the codeine alkaloid found within the opium poppy.  Hydrocodone is commonly used to treat moderate to severe pain and is predominantly used within the United States, with 99% of the world’s volume of hydrocodone consumed in that country. Hydrocodone is also commonly available in a variety of formulations, including combinations with paracetamol (Vicodin), ibuprofen (Vicoprofen), or aspirin (Lortab).

Weaker Than Morphine

Pethidine (Meperidine, Demerol)

Pethidine is a synthetic opioid painkiller medication and is usually prescribed to treat moderate to severe pain. While it provides almost equivalent levels of pain relief to morphine in treating post-surgical pain, the method of administration may differ and the dosage used may need to be slightly higher than the comparative dose of morphine to achieve similar results (4).

Codeine

Codeine is created from the codeine alkaloid found within the opium poppy that is commonly used to treat mild to moderate pain. Codeine’s efficacy comes from the drug being broken down in the liver into morphine. Codeine is the most commonly taken opiate medication in the world (5).

Tramadol (Ultram)

Tramadol is an opiate painkiller medication used to treat moderate pain. The medication is synthesized as a racemic mixture using both components of R- and S-stereoisomers.

Laudanum (Opium Tincture)

Of the list of opioids strongest to weakest, the least potent opiate is still available from some pharmacies in the US and UK. The formulation is used primarily to control diarrhea or to ease withdrawal symptoms in babies born to opiate-addicted mothers. In the 1800s morphine was known as laudanum and was readily available from grocers and markets, but was soon restricted once its addictive qualities were known. Today, laudanum is sold as a ‘tincture of opium,’ which contains approximately 10% (100mg) powdered opium, or the equivalent of 1% (10mg) morphine per milliliter. The tincture is considered a single formulation, as it contains all of the alkaloids found within the opium poppy.

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