How do different opioids compare in strength to morphine. What are the weaker and stronger opioids available. How do synthetic opioids like fentanyl impact the opioid crisis. What factors determine an opioid’s potency and effects.

Understanding Opioid Potency and the Morphine Equivalence Scale

Opioids are a class of powerful pain-relieving drugs that have been used for centuries to manage various types of pain. However, not all opioids are created equal. Their potency can vary significantly, which is crucial for healthcare providers to understand when prescribing these medications. To standardize comparisons, most opioids are measured against morphine, which serves as the benchmark for potency.

The concept of morphine equivalence allows medical professionals to compare different opioids and determine appropriate dosages. This scale is essential for safe prescribing practices and helps prevent accidental overdoses due to miscalculations in opioid strength.

How is opioid potency measured?

Opioid potency is typically expressed as a ratio compared to morphine. For instance, if an opioid is described as being “2 times as potent as morphine,” it means that a smaller dose of that opioid would be needed to achieve the same pain-relieving effect as a standard dose of morphine. This comparison helps healthcare providers make informed decisions about dosing and medication switches.

Opioids Less Potent Than Morphine: Exploring Milder Options

While morphine is often considered the standard for opioid potency, several opioids are less potent and may be suitable for managing milder pain or for patients who are more sensitive to opioid effects.

Codeine: A Mild Opioid with Multiple Uses

Codeine is derived from the opium poppy plant, just like morphine and heroin. However, it is significantly less potent, being about 7 to 14 times weaker than morphine. Codeine is commonly found in:

• Cough syrups
• Mild to moderate pain medications
• Antidiarrheal treatments

Often combined with acetaminophen (Tylenol), codeine’s analgesic effects can be enhanced while keeping the opioid dose relatively low.

Meperidine (Demerol): A Synthetic Option with Limitations

Meperidine, also known by the brand names Demerol and Meperitab, is a synthetic opioid that has been used since the 1940s. It is approximately 7 to 10 times less potent than morphine. While it has been used for post-surgical pain relief, meperidine comes with some significant drawbacks:

• Produces a toxic byproduct in the body
• Can cause tremors and seizures, especially in patients with kidney problems
• Has a relatively short half-life, making it less effective for acute or chronic pain management

Due to these limitations, meperidine use has declined in recent years, with many healthcare providers opting for safer alternatives.

Tramadol: A Popular Synthetic Opioid

Tramadol, marketed under brand names such as Ultram and Ultram ER, is a synthetic opioid that gained popularity in the United States in the 1990s. It is approximately one-tenth as potent as morphine, making it a suitable option for moderate pain relief. Tramadol works by:

• Targeting mu-opioid receptors in the brain
• Blocking pain signals
• Providing analgesia with a lower risk of addiction compared to stronger opioids

However, it’s important to note that while the addiction potential is lower, it still exists, and patients should be monitored for signs of dependence.

Tapentadol: A Newer Option for Moderate to Severe Pain

Tapentadol, sold under the brand name Nucynta, is a relatively new opioid that was first approved in the United States in 2008. It is stronger than tramadol but still 2 to 3 times less potent than morphine. Tapentadol is unique in that it:

• Can be used for both acute and chronic pain
• Is particularly effective for diabetic neuropathy pain
• Comes in immediate-release and extended-release formulations
• Has shown lower rates of abuse compared to similar narcotics

This makes tapentadol an attractive option for patients requiring long-term opioid treatment with a potentially lower risk of addiction.

Opioids Equivalent to Morphine: The Benchmark and Its Peers

Morphine serves as the standard against which other opioids are measured, but there are several opioids that are considered to have equivalent potency. Understanding these equivalencies is crucial for proper pain management and safe opioid prescribing.

Hydrocodone: A Common Opioid with Changing Regulations

Hydrocodone, often found in combination products like Vicodin (hydrocodone/acetaminophen), is considered to have roughly equivalent potency to morphine. However, the regulatory approach to hydrocodone has evolved over time:

• Initially classified as a Schedule III drug, indicating a lower potential for abuse
• Reclassified as a Schedule II drug in 2014, recognizing its higher abuse potential
• Now subject to stricter prescribing and dispensing regulations

This change in classification reflects the growing concern over opioid abuse and the need for more careful control of these potent medications.

Morphine: The Gold Standard

Morphine, discovered over 200 years ago, remains a widely used opioid analgesic. Its characteristics make it the benchmark for opioid comparisons:

• Well-understood pharmacokinetics and pharmacodynamics
• Available in various formulations (oral, injectable, extended-release)
• Predictable pain-relieving effects

Understanding morphine’s effects helps healthcare providers gauge the potential impacts of other opioids and adjust dosages accordingly.

Opioids Stronger Than Morphine: Potent Pain Relief and Increased Risks

Several opioids surpass morphine in potency, offering more powerful pain relief but also carrying increased risks of side effects and addiction. These stronger opioids require careful management and are often reserved for severe pain or patients who have developed tolerance to weaker opioids.

Oxycodone: A Potent Oral Opioid

Oxycodone is approximately 1.5 times stronger than morphine, making it a popular choice for managing moderate to severe pain. It is available in various formulations:

• Immediate-release tablets (e.g., OxyIR)
• Extended-release tablets (e.g., OxyContin)
• Combination products with acetaminophen (e.g., Percocet)

The higher potency of oxycodone allows for effective pain relief with smaller doses, but it also increases the risk of addiction and overdose if not used properly.

Hydromorphone: A Powerful Option for Severe Pain

Hydromorphone, sold under the brand name Dilaudid, is significantly more potent than morphine:

• 4 to 8 times stronger than morphine when given orally
• 7 to 8 times more potent when administered intravenously

This high potency makes hydromorphone an effective option for severe pain but also increases the risk of respiratory depression and other opioid-related side effects.

Fentanyl: A Synthetic Opioid with Extreme Potency

Fentanyl represents a significant leap in opioid potency, being 50 to 100 times stronger than morphine. This synthetic opioid has both medical and illicit uses:

• Used medically for severe pain, often in patch form for chronic pain or in hospital settings
• Increasingly found in illicit drug supplies, contributing to the opioid crisis
• Rapid onset of action and high potency increase the risk of overdose

The extreme potency of fentanyl has made it a major contributor to opioid-related deaths, with a significant increase in fentanyl-involved fatalities in recent years.

The Impact of Synthetic Opioids on the Opioid Crisis

The introduction and proliferation of synthetic opioids like fentanyl have dramatically altered the landscape of the opioid epidemic. These powerful drugs have contributed to a surge in overdose deaths and presented new challenges for public health officials and law enforcement.

Why are synthetic opioids so dangerous?

Synthetic opioids pose unique risks due to several factors:

• Extreme potency compared to natural opioids
• Rapid onset of action, leaving little time for intervention in case of overdose
• Often mixed with other drugs without the user’s knowledge
• Difficult to dose accurately, especially in illicit preparations

These characteristics have led to a sharp increase in opioid-related deaths, with synthetic opioids playing a central role in this tragic trend.

The rise of carfentanil: An elephant tranquilizer on the streets

Carfentanil, a synthetic opioid even more potent than fentanyl, has emerged as a particularly dangerous substance in the opioid crisis:

• 10,000 times more powerful than morphine
• Originally developed as a large animal tranquilizer
• Lethal to humans in extremely small doses
• Often mixed with heroin or other drugs, unknown to the user

The presence of carfentanil in street drugs has further complicated efforts to combat the opioid epidemic and save lives.

Factors Influencing Opioid Potency and Effects

The potency and effects of opioids are not solely determined by their chemical structure. Several factors contribute to how these drugs interact with the body and produce their pain-relieving and euphoric effects.

Chemical structure and receptor binding

The unique chemical structure of each opioid determines how it interacts with opioid receptors in the brain:

• Speed of crossing the blood-brain barrier
• Affinity for specific opioid receptor subtypes
• Strength of binding to receptors

These characteristics influence the onset, duration, and intensity of the opioid’s effects.

Individual factors affecting opioid response

Patient-specific factors can significantly impact how an individual responds to opioid medications:

• Genetic variations in opioid receptors and metabolism
• Tolerance developed through previous opioid use
• Presence of other medical conditions
• Interactions with other medications

These factors explain why opioid responses can vary widely between individuals and why personalized pain management approaches are crucial.

The Role of Opioid Equivalence in Pain Management and Addiction Treatment

Understanding opioid equivalence is not just an academic exercise; it has practical implications for both pain management and addiction treatment. Healthcare providers use this knowledge to make informed decisions about opioid prescribing and to manage patients with opioid use disorders.

Opioid rotation in pain management

Opioid rotation involves switching from one opioid to another to improve pain control or reduce side effects. This practice relies on understanding opioid equivalence to ensure appropriate dosing when transitioning between medications. Benefits of opioid rotation include:

• Improved pain relief
• Reduced tolerance development
• Minimized side effects

Careful calculation of equivalent doses is crucial to prevent under- or over-dosing during the rotation process.

Medication-assisted treatment for opioid addiction

In treating opioid use disorders, medications like methadone and buprenorphine are used to manage withdrawal symptoms and cravings. Understanding opioid equivalence helps in:

• Determining appropriate starting doses for medication-assisted treatment
• Adjusting doses based on the patient’s previous opioid use
• Managing the transition from illicit opioid use to controlled medication

This knowledge is essential for providing safe and effective treatment for individuals struggling with opioid addiction.

Future Directions in Opioid Research and Development

As the opioid crisis continues to evolve, researchers and pharmaceutical companies are exploring new approaches to pain management and addiction treatment. These efforts aim to develop safer and more effective alternatives to traditional opioids.

Novel opioid formulations and delivery systems

Innovative approaches to opioid development include:

• Abuse-deterrent formulations that make misuse more difficult
• New delivery systems that provide more controlled release of medication
• Combination therapies that target multiple pain pathways

These advancements aim to provide effective pain relief while reducing the risks of addiction and overdose.

Non-opioid pain management strategies

Researchers are also exploring alternative pain management approaches that don’t rely on opioids:

• Targeted nerve blocking techniques
• Advanced non-opioid medications
• Neuromodulation therapies
• Integrative pain management approaches combining pharmacological and non-pharmacological treatments

These strategies may offer new options for patients with chronic pain, reducing the need for long-term opioid use.

As our understanding of pain mechanisms and opioid pharmacology continues to grow, the field of pain management is likely to see significant advancements. These developments hold promise for more effective and safer pain relief options, potentially reducing the impact of the opioid crisis on public health.

Opioid Conversion | Other Opioids Compared to Morphine

Author: Amy Keller, RN, BSN

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Last Updated: 3/02/20

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26 sources

Two hundred years after its discovery, morphine remains one of the most popular opioid painkillers in use — but it’s far from the strongest. Synthetic opioids hundreds to thousands of times stronger than morphine are now turning up on America’s streets and contributing to a wave of overdoses and deaths.

Opioid abuse is not a new phenomenon, but it has become a worsening epidemic. Opioid-related overdose deaths have doubled since 2000, making drug overdose the leading cause of death for Americans under the age of 50.

Among the factors fueling this deadly epidemic is the exploding popularity of potent synthetic opioids such as fentanyl, which is 50 to 100 times stronger than morphine, and its chemical cousin carfentanil, an elephant tranquilizer that is 10,000 times more powerful than morphine.

Every day, 91 Americans die from an opioid overdose and more than 1,000 people are treated in emergency departments for not using prescription opioids as directed.

Source: Centers for Disease Control and Prevention

Most opioids work in roughly the same way. They attach to receptors in the brain that send signals to block pain, slow breathing and create a sense of euphoria. But what makes one drug more powerful or euphoric than another is its unique chemical structure — and how quickly and tightly it binds to those pain receptors.

As one of the faster prescription opioids, fentanyl zooms through the blood-brain barrier to the brain’s opioid receptors with remarkable efficiency and hugs those receptors more tightly than many other drugs. These characteristics make fentanyl particularly deadly among opioids.

Of the 60,000 drug overdose deaths recorded in 2016 in the United States, 20,000 involved fentanyl. The death rate increased more than fivefold since 2013, when fentanyl was implicated in 3,105 fatalities.

In medical literature, the analgesic strength, or potency, of most painkillers is measured as a comparison to morphine. For example, oxycodone is roughly 50 percent stronger than morphine. Therefore, researchers might say the drug is 1.5 times as strong as morphine. A single dose of Tylenol or aspirin is about 360 times weaker than a dose of morphine.

Opioids Weaker than Morphine

While morphine is the pharmacologic standard bearer in the lineup of prescription opioids, there are several milder prescription painkillers on the market. These range from codeine, a common ingredient in many cough syrups, to tapentadol, a relatively new drug that is being marketed to patients requiring long-term opioid treatment, such as those suffering from diabetic leg pain.

Codeine

Like morphine and heroin, codeine comes directly from the opium poppy plant. The drug is an ingredient in many cough syrups and is also prescribed to treat mild to moderate pain and diarrhea. Codeine, which is seven to 14 times less potent than morphine, comes in a variety of dosages. The opioid is often combined with Tylenol to increase both drugs’ analgesic effects.

Meperidine (Demerol, Meperitab)

A synthetic opioid similar to morphine, Demerol has been used to treat pain since the early 1940s. It is sometimes used for post-surgical pain relief. While it is about seven to 10 times less potent than morphine, caution must be exercised because Demerol produces a toxic byproduct in the body that can cause tremors and seizures, particularly in patients with kidney problems. For this reason, meperidine should only be used by patients with normal renal function. Because of its relatively short half-life, meperidine doesn’t work well for acute or chronic pain.

Tramadol (Ultram, Ultram ER)

This synthetic opioid was a popular prescription painkiller for decades before it made its debut in the United States in the 1990s. Tramadol, which is about one-tenth as potent as morphine, works similarly to morphine, targeting the brain’s mu-opioid receptors to block pain signals. While it is considered to be less addictive than other opioids, the potential for addiction still exists.

Tapentadol (Nucynta)

Stronger than tramadol but two to three times less potent than morphine, tapentadol can be used to treat moderate to severe pain that is acute or chronic. A relatively new drug that was first approved for use in the United States in 2008, tapentadol is frequently prescribed for controlling pain related to diabetic neuropathy. It comes in both immediate-release and extended-release formulations. Studies have shown lower rates of abuse with tapentadol than with similar narcotics.

Opioids Equivalent to Morphine

Morphine and its chemically similar cousin hydrocodone might be equal in strength — but they haven’t always been treated as such. For years, Vicodin and other drugs containing a mixture of hydrocodone and acetaminophen had less stringent prescribing regulations than other opioids.

Originally a Schedule III drug, Vicodin was once deemed to have a moderate to low potential for dependence and a lower abuse potential than other narcotics. Unfortunately, those laxer standards helped propel the combination opioid to become the most prescribed drug in the United States, contributing to widespread abuse of the substance.

In 2014, the federal government tightened its controls on hydrocodone/acetaminophen, elevating the combination drug to Schedule II status. This category is for substances considered to have a high potential for harm and abuse.

Vicodin’s popularity hasn’t waned much though. In 2016, American pharmacies and long-term care facilities dispensed 90 million prescriptions for Vicodin, making it the fourth most prescribed medicine in the nation, according to a report by the IQVIA Institute for Human Data Science.

Hydrocodone (Vicodin, Lorcet, Norco)

Equal in strength to morphine, hydrocodone is one of the most popular opioid medications on the market. As such, it’s also the most commonly abused substance in the nation, with 24 million Americans reporting they use hydrocodone for nonmedical purposes. Some of the most popular formulations of the drug, including Norco, Vicodin and Lorcet, contain hydrocodone in combination with acetaminophen.

Morphine (MS Contin, Avinza, Kadian, Oramorph)

Two centuries after it was first discovered, morphine remains one of the most widely used painkillers in the world, with more than 230 tons of morphine prescribed legally each year. Morphine is approximately three times as strong as codeine and “remains the standard against which all new medications for postoperative pain relief are compared,” according to Dr. Jonathan Moss, a professor of anesthesia and critical care at the University of Chicago.

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Opioids Stronger than Morphine

The opioid death toll in this country is growing rapidly, and increased use of the drugs is not solely to blame. It’s also because people are taking increasingly strong opioids recreationally. Among them is the potent painkiller fentanyl. Stronger still is carfentanil, an elephant tranquilizer so powerful that sometimes Narcan cannot even counter its effects.

Oxycodone (OxyContin, Percocet, Percodan, Roxicodone)

Milligram for milligram, oxycodone is about 50 percent stronger than morphine. At one time, oxycodone was rarely used in settings outside of hospice or cancer treatment. That changed, however, in 1995, when Purdue Pharma released a new extended-release formulation of the drug called OxyContin.

While the drug manufacturer touted OxyContin as nonaddictive and safe, the opposite was true. Amid Purdue’s aggressive marketing campaign, OxyContin prescriptions soared. The drug made its way onto the streets and into the hands of abusers who snorted and injected it, methods that increase the potency of the time-release medication.

Methadone (Methadose, Dolophine)

Three times stronger than morphine, methadone is often prescribed to help people recover from addiction to heroin and other opioid pain medications. It lessens the painful symptoms of opioid withdrawal, and it is effective at reducing cravings. It also lacks the euphoric effects of other opioids. Methadone can be taken in the form of a pill, a liquid or a wafer. It is sometimes used for pain management in cancer patients and others with chronic pain.

Hydromorphone (Dilaudid)

Though it has a comparatively shorter duration of effect than morphine, Dilaudid is five to 10 times stronger. Hydromorphone is a popular second-line treatment for pain after morphine, but it has a high potential for abuse and dependence. An extended-release version of hydromorphone called Palladone was pulled from the market in 2005 amid safety concerns when several patients died after mixing the medication with alcohol.

Heroin

Depending on who is using it and how it’s consumed, heroin is approximately two to five times stronger than morphine. Heroin is a naturally occurring substance that comes from the seed pod of certain types of poppy plants. When it’s snorted, smoked or injected, heroin users experience a euphoric rush lasting several hours. The rush is followed by a state of stupor or sleep that may also last multiple hours. Though heroin’s heyday was in the 1960s and 1970s, there’s been a resurgence in heroin use in recent years — particularly among young people — as prescription painkillers have become increasingly expensive and harder to obtain.

Oxymorphone (Opana)

This controversial opioid is 10 times stronger than morphine when taken intravenously and about three times more potent than morphine in pill form. In 2017, Opana manufacturer Endo Pharmaceuticals agreed to pull the extended-release formulation of drug, Opana ER, from the market at the request of the Food and Drug Administration because of its high abuse potential. Individuals found ways to crush and inject the medication despite its hard coating, and intravenous use of the medication was associated with in a 2015 outbreak of HIV in Indiana and a 2011 outbreak of hepatitis C in New York.

Buprenorphine (Subutex)

Buprenorphine is an opioid doctors prescribe to help treat opioid addition. It can be 25 to 100 times stronger than morphine depending on the formulation and other factors. It suppresses withdrawal symptoms and cravings, but unlike methadone, which is dispensed through clinics, buprenorphine can be prescribed and dispensed at a physician’s office.

Fentanyl (Sublimaze, Duragesic, Subsys)

This synthetic opioid that killed pop icon Prince is 100 times stronger than morphine. It moves quickly from the blood stream into the brain and binds tightly to pain receptors, making a fentanyl overdose extremely difficult to counteract. Rescue attempts may require multiple administrations of the reversal agent Narcan. A side effect known as “wooden chest syndrome,” which causes rigidity of the chest wall, can make doing CPR compressions on an overdose victim impossible.

Approximately 2 to 3 milligrams of fentanyl — which is roughly the same size as two to three grains of table salt — can cause respiratory depression, respiratory arrest and even death.

Source: Drug Enforcement Administration

Prescription fentanyl comes in many forms, including lozenges, lollipops and transdermal patches that are applied to the skin. The drug is also created illicitly and sold on the street. Fentanyl is commonly mixed with heroin, cocaine and other chemicals in counterfeit pills.

Carfentanil

Though molecularly similar to fentanyl, this synthetic opioid is 100 times stronger than its chemical cousin and 10,000 times more potent than morphine.

Carfentanil was never intended for use in humans. It is so lethal, in fact, that it’s been classified as a chemical weapon in international arms control treaties. The only legitimate use of the drug is as a tranquilizer for elephants and other large animals. Nevertheless, the lethal substance has made its way from labs in China onto American streets.

“Carfentanil is 1000 times more powerful than morphine, and we’ve seen a lot of carfentanil on the streets. ”

— Steve Collins, Director of the Central Florida High Intensity Drug Trafficking Area

Carfentanil is just one of the substances — along with fentanyl, heroin and a synthetic opioid called U-47700 — that’s been turning up in a deadly new street drug called “Gray Death.” A minuscule grain of the combination drug, which resembles a chunk of concrete, can kill someone instantly. Gray death was associated with 50 overdoses in Georgia over a three-month span in the first half of 2017, and the DEA confirmed that U-47700 caused 46 deaths nationwide in 2015 and 2016.

While powerful opioids may carry a high risk of accidental overdose and death, weaker opioids are not necessarily safer than stronger ones. All opioids are addictive and carry significant risks and potential side effects. If you are prescribed an opioid pain reliever, take it only as directed. If you are unsure how to take your medication, contact your doctor or pharmacist.

Medical Disclaimer: DrugRehab. com aims to improve the quality of life for people struggling with a substance use or mental health disorder with fact-based content about the nature of behavioral health conditions, treatment options and their related outcomes. We publish material that is researched, cited, edited and reviewed by licensed medical professionals. The information we provide is not intended to be a substitute for professional medical advice, diagnosis or treatment. It should not be used in place of the advice of your physician or other qualified healthcare provider.

Author

Amy Keller, RN, BSN,
Content Writer,
DrugRehab.com

As a former journalist and a registered nurse, Amy draws on her clinical experience, compassion and storytelling skills to provide insight into the disease of addiction and treatment options. Amy has completed the American Psychiatric Nurses Association’s course on Effective Treatments for Opioid Use Disorder and continuing education on Screening, Brief Intervention and Referral to Treatment (SBIRT). Amy is an advocate for patient- and family-centered care. She previously participated in Moffitt Cancer Center’s patient and family advisory program and was a speaker at the Institute of Patient-and Family-Centered Care’s 2015 national conference.

[email protected]

@DrugRehabAmy

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Relative Doses of Opioids – West Midlands Palliative Care

Converting between morphine and diamorphine

Approximate equivalent doses of oral morphine and subcutaneous morphine and subcutaneous diamorphine:

3mg oral morphine = 1.5mg SC morphine = 1mg SC diamorphine

These conversion ratios apply to PRN. and regular dosing.

Example 1
60mg morphine slow release tablet BD PO
=total daily dose oral morphine 120mg PO
=60mg SC morphine/24 hrs
=40mg SC diamorphine/24 hrs

Example 2
30mg Oramorph PO PRN
=15mg SC morphine PRN
=10mg SC diamorphine PRN

Converting between morphine and transdermal patches

See Section: Transdermal opioids

Diamorphine

1mg SC diamorphine = 3mg oral morphine = 1. 5mg SC morphine

Diamorphine was traditionally used as the first line injectable strong opioid as it is more water soluble than morphine. Morphine sulfate injection is now used in many centres as the first line injectable strong opioid.

Diamorphine preparations:

Injection: 5mg, 10mg, 30mg, 100mg, 500mg in packs of 5 ampoules

Oxycodone

10mg oral oxycodone = 5mg SC oxycodone

10mg oral oxycodone = 15mg–20mg oral morphine = 7.5mg–10mg SC morphine

• Oxycodone has good oral bioavailability

• Oxycodone is usually the second line alternative if morphine is not tolerated

• The example above illustrates the dose conversion when oxycodone is regarded as being 1.5 – 2 times more potent than oral morphine

Care should be taken to ensure clarity when prescribing immediate release capsules or modified release tablets, particularly in view of differing generic brands now on the market.

Oxycodone preparations:

Immediate release (OxyNorm®) capsules, for PRN use:
5mg (orange/beige), 10mg (white/beige), 20mg (pink/beige) (packs of 56)

Oral solution (OxyNorm®) : 1mg/ml (250ml)

Concentrated oral solution (OxyNorm®): 10mg/ml (120ml)

Modified release tablets (OxyContin®) for 12-hourly administration:
5mg–light blue, 10mg–white, 15mg–grey, 20mg–pink, 30mg – brown, 40mg–yellow, 60mg–red, 80mg–green, 120mg–purple (packs of 56)

Injection: 10mg/ml: 1ml, 2ml ampoules. 50mg/ml: 1ml ampoules

Targinact®: The opioid antagonist naloxone is added to counteract opioid induced constipation by blocking the action of oxycodone at opioid receptors locally in the gut. Seek advice from specialist palliative care before prescribing (see chapter: Constipation).

Hydromorphone

1.3mg oral hydromorphone = 0. 6mg SC hydromorphone = 10mg oral morphine = 5mg SC morphine

An alternative if morphine is not tolerated because of adverse effects under specialist guidance. Immediate and modified release capsules may be opened and sprinkled onto food.

Hydromorphone preparations (Palladone®):

Immediate release capsules:
1.3mg (orange/clear), 2.6mg (red/ clear) for PRN use (packs of 56)

Modified release capsules:
2mg (yellow/clear), 4mg (pale blue/ clear), 8mg (pink/clear), 16mg (brown/clear), 24mg (dark blue/ clear) for 12-hourly administration

Alfentanil

Seek specialist palliative care advice.

1mg SC alfentanil = 10mg SC diamorphine = 30mg oral morphine = 15mg SC morphine

Suitable parenteral opioid for use in advanced renal disease under specialist guidance. Alfentanil has a short duration of action which limits its use for breakthrough analgesia.

Note very different dose conversions than fentanyl (see below for more info).  

N.B. Alfentanil and fentanyl are different drugs.

Alfentanil preparations:

Injection (Rapifen®) 500 microgram per ml, 2ml, 10ml ampoules

Intensive Care Injection 5mg per ml, 1ml ampoules to be diluted before use

Methadone

Always seek specialist advice.

Fentanyl (injectable)

Seek specialist palliative care advice.

150 micrograms SC fentanyl = 10 mg SC diamorphine =morphine 30 mg oral = 15 mg SC morphine

Suitable parenteral opioid for use in advanced renal disease under specialist guidance.

Also available as a transdermal patch see section: Transdermal fentanyl and as immediate release preparations (buccal, intranasal, sublingual and submucosal formulations) for incident pain see section: Transmucosal Fentanyl preparations.

Note very different dose conversions than alfentanil (see above for more information).

N.B. Alfentanil and fentanyl are different drugs.

Be aware that when prescribing a syringe driver/pump for fentanyl that the dose is micrograms per 24 hours whilst when administering a transdermal patch the dose is micrograms per hour.

Fentanyl injectable preparations:
Injection (generic) 50 microgram per ml, 2ml and 10 ml ampoules fentanyl (Sublimaze®) 50 microgram per ml, 10 ml ampoules

Tapentadol

A novel analgesic combining mu opioid properties and noradrenaline reuptake inhibition. This can be helpful for pain that is mixed and has an element of nerve/neuropathic pain associated with it. At the time of writing there is limited experience of this in palliative care. 

Seek specialist palliative care advice.

50mg Tapentadol = 15-20mg oral morphine

Tapentadol preparations:

Immediate release (Palexia®):
Tablets, f/c, tapentadol (as hydrochloride) 50mg (white), 75mg (yellow)
Oral solution, tapentadol (as hydrochloride) 20mg/ml
Modified release (Palexia®SR):
Tablets, f/c, 50mg, 100mg, 150mg, 200mg, 250mg

Obtained detailed 3D images of the most important opioid receptors

Obtained 3D images of the most important opioid receptors that regulate pain and are responsible for euphoria, depression, drug addiction.

For the first time, the three-dimensional atomic structure of two human opioid receptors, specific molecules on the contacting surface of the membrane of the perceiving nerve cell, has been completely determined. Two articles at once describing this discovery, which can be considered as a significant breakthrough in understanding the functioning of the brain and nervous system, as well as, potentially, in the analgesic industry, are published today by Nature ( “Crystal structure of the mu-opioid receptor in conjunction with a morphine agonist” , and “Structure of the human kappa-opioid receptor in complex with JDTic” ).

Opioid receptors are perhaps the most widely known neuromembrane molecules, which are of interest due to the key role they play in the formation of both pain and pleasurable sensations,

as well as drug addiction, depression, psychosis, hallucinations and states of altered consciousness .

Placebo instead of morphine

The placebo effect actually reduces the activity of nerve cells in the human brain. This was able to install…

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A large group of substances, which includes both commonly available analgesics sold in pharmacies, as well as hard illegal drugs and psychedelics, is called “opioids” because their analgesic, sedative, euphoric or hallucinatory effect is based on selective binding to these receptors and enhancing or suppressing their response to electrical and chemical brain signals.

Depending on which endogenous (that is, produced by the body itself) neurotransmitter proteins they bind, there are four main groups of opioid receptors – μ- (mu), κ- (kappa), δ- (delta) and nociceptive receptors . The first Greek letter repeats the first letter of the name of the substance (not necessarily endogenous) for which receptor affinity was first discovered, such as morphine in the case of the mu receptor or ketocyclazocine in the case of the kappa receptor.

Detailed three-dimensional structure up to the spatial arrangement of individual atoms has so far been determined for two of them – “mu” and “kappa”.

It is a sin for these receptors to complain about the lack of interest in their ambiguous biochemical activity on the part of specialists and the general public.

Thus, mu receptors are responsible for the feeling of pleasure and the attenuation of pain signals, readily binding to neurotransmitters such as endorphins. They are the main targets of popular artificially synthesized opioids – morphine, heroin, as well as strong mu-opioid analgesics, such as Vicodin, Dr. House’s favorite drug.

Kappa receptors have gained fame relatively recently due to the wide distribution of smoking mixtures based on predictive sage (Salvia divinorum) – a plant hallucinogen of American Indians, the active substance of which – neoclerodan diterpenoid salvinorin A – selectively and effectively binds to them .

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In contrast to the sedative function of mu receptors, kappa receptors associated with salvinorin A sharply increase their sensitivity to endogenous neurotransmitters dynorphins,

are responsible for an effect somewhat different from that of the mu receptors, causing emotional imbalance, depression, panic attacks, and very vivid hallucinations – usually of an unkind nature.

Meanwhile, as experiments on animals have shown, activation of kappa receptors also relieves pain, but with one significant difference: unlike morphine, heroin and mu-opioid analgesics, agonists (substances that increase the receptor response) of kappa receptors are not addictive. Therefore, if their formula can be modified to minimize the unpredictable psychotic effect,

doctors will have at their disposal a powerful new generation of painkillers without the “narcotic aura” that mu-opioid agonists do not want to part with.

“Now that we know the structure of the kappa receptor and the exact shape of its molecule, pharmacists can significantly speed up their work,” says Brian Roth, a biochemist at the University of North Carolina who helped decipher the receptor, and one of the authors of the Nature paper.

Magic mushrooms in a CT scanner

Brain scans obtained during psychedelic trips allow for the first time to accurately localize the action. ..

January 24 13:55

However, pharmacists are interested not only in agonists, but also in antagonists that block the activity of kappa receptors, which can be used to treat depression, anxiety, emotional depression and other uncomfortable conditions that are well known to smokers of predictor sage, acting as a kappa activator .

The powerful psychedelic effect of kappa activation should also not be ignored when studying the mechanisms of perception, consciousness and the construction of a picture of the world by the brain.

“Kappa receptors seem to play a very important role in our perception of reality,”

Roth emphasized in one of the publication’s press releases. After several decades of prohibitions on the scientific study of psychedelics, work in this area has finally intensified, and we already wrote about one of such studies .

The work on deciphering the kappa receptor was carried out in several stages.

First, a non-trivial task was solved to isolate and preserve an unstable receptor molecule isolated from a culture of nerve cells of caterpillars of a genetically modified moth ( Spodoptera frugiperda ) carrying the gene responsible for the expression of the human type kappa receptor protein. This was done by reliably stabilizing the desired protein with the help of an antagonist molecule, the experimental drug JDTic (one of the derivatives of 4-phenylpiperidine), which selectively blocks the kappa receptor.

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Next, using the X-ray diffraction effect on a three-dimensional crystal lattice, the atomic structure and 3D shape of the crystallized complex of the kappa receptor molecule and the stabilizing trap, the antagonist molecule, were determined. Finally, having detached the JDTic molecule from the resulting 3D model and made the necessary correction,

The researchers obtained an accurate 3D model of the kappa receptor with a resolution of 2.9 angstroms.

Following the same scheme, only with the participation of genetically modified mice and a different type of trap antagonist, a three-dimensional model of the mu receptor was obtained, which will help to understand exactly how various opioid ligands dock with its molecule, which do not allow drug control officers to sleep peacefully. Which, in turn, will also help clear the side effects of opioid drugs that act on mu receptors.

Prion memory

Prion proteins play a key role in the formation of long-term memory, neurophysiologists have found out…

January 30 13:28

The intricate work to decipher two of the most important opioid receptors was carried out by several American laboratories and institutes under the leadership of the National Institutes of Health (NIH) general fund as part of a long-term publicly funded initiative for structural protein research, as well as a federal scientific program to study receptors associated with G-protein (G protein-coupled receptor network). Of the approximately 800 such receptors, the 3D atomic structure of only 11 has been deciphered to date. Disruption of these receptors leads to many different diseases, and the receptors themselves are the target of almost half of the nomenclature of all currently produced drugs.

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Drugs are distinguished by origin (plant, semi-synthetic and synthetic), chemical structure, clinical effect and mode of action on the body.

Opiates

This group includes narcotic substances of plant and artificial origin derived from the opium poppy. They have a pronounced sedative and – in large doses – hypnotic effect. When using opiates, a person experiences euphoria, peace, and dependence on opiates develops very quickly (after 1-3 doses).

The effects of opiates on the body during long-term use are devastating: damage to the liver by products used in the manufacture of drugs; tooth decay; impotence; decrease in the level of intelligence; diseases of the veins and blood vessels; weakening of the immune system, etc. There is also a high chance of a drug overdose with a fatal outcome.

• Heroin is the most popular drug in this group. The narcotic effect of heroin is pronounced, and the dependence is disastrous for a person – in people who are physically dependent on heroin, it becomes necessary to take more and more of it in order to get the desired effect. In the end, the dose comes when the addict no longer gets the desired effect, but uses heroin only to delay withdrawal symptoms, which occurs 2-3 hours after stopping the use of the drug.
• poppy straw – dried and crushed parts of poppy stems and pods (seeds do not contain any psychoactive substances). Serves for the subsequent production of various substances.
• raw opium – specially processed poppy juice of the consistency of plasticine, formed into cakes. It serves as a raw material for the manufacture of acetylated opium, a solution that has a characteristic acetic odor and dark brown color. This is the so-called “black solution” or “black” (sometimes also called “khanka”, “chemistry”, “anhydride” – from acetic anhydride added during the “cooking” process). The resulting substance is smoked and administered intravenously (often with the addition of drugs). Acetylated opium is one of the most common drugs in Kyiv.
• Methadone is a powerful synthetic drug. Despite the characteristics of high psychological and physical dependence, methadone is widely used for the treatment of patients dependent on opium drugs – methadone therapy has shown its effectiveness in many countries.
• Crocodile is also a synthetic opiate. In its preparation, highly toxic substances with an admixture of heavy metals are used. Dependence on the drug develops after 2 intravenous injections. The main substance is desomorphine (isolated from codeine-containing drugs).

Cannabis derivatives

Cannabis is a very popular drug legalized in some countries. There is an opinion that cannabis does not give rise to any dependence, but this is not so – dependence on cannabis exists, but the consequences of its use are less detrimental than, for example, after using heroin. Hemp grows in a warm climate, and the more south the region, the more powerful the narcotic effect of the product. Often hemp is grown at home, but this is prohibited by the law of the Russian Federation. The main danger of cannabis is that after it they often switch to opiate drugs.

• marijuana – cannabis leaves, dried or raw.
• hashish – resin, pollen and crushed tops of the plant in a mixture. They are either a viscous paste (“soft”) or compressed rigid plates (“hard”).

Psychostimulants

This group of narcotic substances includes stimulants, stimulants of synthetic and herbal origin. The action of these drugs is pronounced and forms dependence on the psychological and physiological level. Also, with constant use, in addition to all other complications, suicide attempts are possible.

• amphetamines (ephedrine, pervitin, MDMA, or ecstasy) – solutions (pervitin), crystals (ephedrine), or tablets (ecstasy). The constant use of amphetamines leads to devastating consequences for the body, often due to the poor quality of raw materials.
• cocaine and crack are plant products. They are obtained from coca leaves. Cocaine is considered an expensive drug and is therefore often replaced by the cheaper methamphetamine (“hair dryer”). Crack is a vaporized mixture of cocaine and soda.

Dissociatives

Drugs of this group distort the perception of the surrounding reality, cause a feeling of alienation from it and from oneself. These effects cannot be called hallucinations in the full sense, although dissociatives are often referred to as hallucinogens. Dissociative substances, in addition to the synthetic ones described below, are also found in red fly agaric.

• phencyclidine (PCP) is a crystalline powder that is smoked in a specific way. The decline in the effect of use is characterized by severe depression. Phencyclidine is excreted from the body very poorly;
• Dextromethorphan (DXM) is an antitussive and has no narcotic effects at therapeutic doses. But when used in large quantities, the product leads to dependence.
• Ketamine is a white crystalline powder with a slight odor. It became widespread when psychedelics became popular, but there was no LSD in the illegal markets.

Hallucinogens

Hallucinogens have the ability to change, “expand” consciousness. There is an opinion among drug addicts that the use of hallucinogens is harmless and does not cause addiction. Although none of them mention the literal disintegration of the personality and severe consequences like schizophrenia.

There is a case when a young man was arrested in the USA for licking a bufo-bufo toad, the skin of which contains a poison that is deadly for animals and birds, and causes hallucinations in humans.

• LSD is a synthetic drug derived from lysergic acid found in ergot. It is a powder or liquid.
• DOB and its analogues are sold as “stamps” and are more potent and toxic than LSD;
• psilocybe – toadstool mushrooms containing psilocybin, a powerful hallucinogenic substance.
• hallucinogenic plants – salvia (“sage of the soothsayers”), leaves of some species of acacia, peyote cactus and others.

Inhalants

This includes volatile substances found in non-drug products: glue, gasoline, hair sprays, solvents, insect repellents, dyes. To obtain the effect, a very large amount of a substance is needed with all the ensuing consequences, for example, acute intoxication. These substances are especially popular among teenagers who have neither the money nor the opportunity to buy drugs, while Moment glue and everyday products are quite affordable.

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Vashkin Dmitry Vladimirovich

Head physician

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21 years
General narcological experience

15 years
Work experience in the Marshak Clinic

Movchan Dmitry Anatolyevich

Deputy Chief Physician for Medical Affairs

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18 years
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9 years
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Aksenova Marina Gennadievna

Supervisor, Candidate of Biological Sciences, Member of the European Society of Geneticists HUGO

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41 years
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21 years
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Guevara Leonardo Leonardovich

Psychiatrist, narcologist, psychotherapist.