Synthetic opioids and overdose harms
What are synthetic opioids? And what are the risks of synthetic opioid overdoses and other harms?
- Synthetic opioids are prescribed for severe pain conditions.
- These medicines may be prescribed for use during/after surgical procedures, for breakthrough cancer pain, or as otherwise warranted.
These are powerful medicines. When used without appropriate medical supervision (or if recommended dosing levels are exceeded), synthetic opioids can lead to overdose toxicity symptoms and/or overdose fatalities.
Synthetic opioids can be 80 to 100 times stronger than morphine (Source: DEA).
Synthetic opioids: overdose toxicity risks
The potency of opioid derivatives and synthetic opioid products, if use is not appropriately Supervised and monitored, can result in an overdose fatality.
Risks of overdoses from opioids/synthetic opioids may be significantly increased if individuals:
- use synthetic opioids attained from unregulated/illicit supply chains that do not comply with GMP
- use synthetic opioids mixed into various other substances of intoxication (polysubstance use)
- engage in concurrent usage of synthetic opioids with other opioids or medicines
- purchase synthetic opioid products from illicit online pharmacies and/or street-drug dealers (counterfeits)
The importance of GMP compliance and Pharmacovigilance systems
Why the supply chain — and good manufacturing practice (GMP) compliance — matters for ensuring quality and drug use safety.
Products purchased from unregulated suppliers — including unauthorised online chemists (illegal websites):
- lack quality testing and potency testing
- contain inconsistent amounts of active ingredients (undetermined levels of synthetic opioid(s) potency can readily prove fatal)
- are typically contaminated with highly toxic substances such as paint thinners, metal or glass fragments, and deadly bacteria
This is why unregulated ‘street purchased‘ products can lead to unintentional overdoses – and visits to the hospital (or morgue).
Unintentional overdose deaths are at epidemic levels. Without quality assurance product testing and batch tracing capacity, the potency of illicitly distributed products are likely to be inconsistent and — quite often — deadly.
In regulated/cGMP supply chains for synthetic opioids, quality systems, regulatory audits, pharmacovigilance reporting — and frequent product testing — are important safety mechanisms helping to protect patients.
But when it comes to illicit synthetic opioids and other opioid products being sold through unregulated distributors?
There’s very little chance of intercepting a dangerous batch of opioid products (distributed via illicit channels) before they reach consumers. And if there is a particularly deadly batch of illicit synthetic opioid products, and people die — there is zero likelihood that anyone will be held accountable. Or that that illegal supply chain of dangerous drugs could be stopped.
Note: You are currently reading Blog 4 (synthetic opioids and opioid overdose risks) in a 10-part overdose awareness and overdose prevention research series.
Clicking the links below will open the other blogs in a new tab on your browser.
- Click here to read Blog 1 of 10 (non-medical use of prescription medications).
- Click here to read Blog 2 of 10 (factors contributing to the increase in overdose fatalities such as polysubstance use).
- Click here to read Blog 3 of 10 (the impact of Covid-19 on substance use and overdose rates)
- You are currently reading Blog 4 of 10 (synthetic opioids and overdose risks).
- Read blogs 5 to 10 on Overdose Awareness resources and Prevention research being published in late August 2021.
Synthetic Opioids and Overdose Risks
General prescription safety (drug safety) for opioid products including synthetic opioids
It is important that care teams — and family members — stay alert for overdose toxicity symptoms experienced by patients who are being prescribed synthetic opioids and other opioid-based medications (such as prescribed for cancer pain, acute surgical pain, or other conditions).
- Medical teams/other carers must remain alert to the risks of dangerous drug-drug interactions and overdose risks.
- Excess use (or prolonged use) can lead to dependencies or overdose harms, as can mixing synthetic opioid products with other medications or changing the recommended route of administration.
Opioid dependencies and heroin substitutes for prescription medications
Opioid dependencies (and NMU of opioid medicines) can also lead to ‘substitution’ efforts by patients, such as when their legal access to prescription medications ends.
Substitute opioid substances — and alternative opioid substance seeking — may involve not only the use of contaminated street drugs such as heroin but the use of injection-based administration methods.
The illicit products used AND the method of administration both increase the risks of overdose toxicity; and can prove far more deadly than, for example, a controlled-dose skin patch.
Diversions of synthetic opioid(s) medications are also a dangerous occurrence.
Opioid products must always be securely stored, and monitored, to avert diversion attempts (potential thefts).
Learn more about how to prevent deaths from opioid medication overdoses. Read more about opioid overdose prevention and the use of Naloxone during an overdose (resources from the Penington Institute).
Read about the LIFEGUARD app designed by Jeff Hardy (Founder of Lifeguard Digital Health and Informatics). This app was designed by Hardy, inspired to take direct action to find a way to prevent opioid overdose deaths — after losing a loved one (Evan).
Example of synthetic opioids: transdermal patch/skin patch (shown below).
Synthetic opioid(s) drug safety measures
Drug safety measures in the patient care settings including hospitals, pharmacies, and research centres)
- Only specially trained physicians and surgeons should prescribe opioid-based pain-management medications.
- The effects of prescribed medications such as synthetic opioid(s) should be closely monitored.
- Family members, carers, and healthcare professionals should learn how to respond to a suspected overdose (Do’s and Don’ts).
- Patients should be warned of the potential habit-forming nature of these opioid medications, and educated on the dangers of non-medical use and overdose risks and the risks of pharmaceutical diversion (including medicine theft).
In every setting, these medicines should be:
- monitored for dosing accuracy / with remaining quantity accounted for after every administration
- used only as directed
- stored safely and securely away from children and pets (and thefts)
Drug safety measures and quality controls in pharmaceutical manufacturing settings
GMP, GaMP, inventory management, batch tracing/packaging serialisation, and other GMP compliance measures can help manufacturers:
- prevent diversion of product shipments
- preventing diverted products from entering criminal supply chains and leading to toxicity harms
- reduce risks of counterfeit products/substandard products and uneven potency levels
These protective measures should remain a priority for manufacturing companies and clinical trial sponsors. Additionally, all personnel require training in product security measures and GMP/GxP. That includes your distribution teams (e.g. your warehouse teams and transportation teams/pilots and delivery drivers).
- Opioid medication inventories – including raw materials/active pharmaceutical ingredients (APIs) should be closely tracked and audited throughout the manufacturing lifecycle, through delivery to patients.
- Quality risk management (QRM) principles should be used to implement robust supply chain protections/product security measures to reduce theft and other forms of product diversions.
- Compliance with GMP, GRK and Good Distribution Practice (GDP) should be maintained through pharmaceutical quality systems, regulatory audits, CAPA investigations, and reviews.
All personnel and contractors with access to APIs and/or finished products should be adequately trained in cGMP compliance, including data integrity, Good Recordkeeping Practice (GRK), GWK (where appropriate), GDP, and other supply chain security “diversion prevention” training.
Why are synthetic opioids like synthetic opioids dangerous?
When synthetic opioid(s) dosing exceeds the recommended amounts — or when illicit products are taken, with varying potency levels — synthetic opioid(s) can cause significant harm and potentially lead to death.
“[Synthetic opioids are] a respiratory depressant – [that] interferes with the user’s ability to breathe. Because it is so concentrated, people can misjudge the dose for themselves to a dangerous degree.” Source: UNSW/NDARC – National Alcohol and Drug Research Centre.
Ensure everyone understands what to do in the event of a suspected overdose of an opioid product.
Street names for synthetic opioids: Apace, China Girl, China Town, China White, Dance Fever, Goodfellas, Great Bear, He-Man, Poison and Tango & Cash. (Source: DEA)
What do synthetic opioids look like?
Synthetic opioids come in various forms.
What synthetic opioids look like (colours, textures) — and how they are being used (administration routes) — can vary greatly. It depends on where they are obtained, and how they’re being used.
Examples: Legally prescribed medicines (or diverted pharmaceuticals) include a transdermal patch/skin patch (a clear skin patch containing a synthetic opioid for treating cancer pains). Illicit synthetic opioid supplies include but are not limited to powder-based formulas, mixed with other chemicals and/or liquids, and administered via injection methods, through nasal inhalation, or by smoking inhalation.
What colour is a synthetic opioid product?
- Synthetic opioids/opioid powders (ground up) can range in colour from off-white to light brown, but colour variations are common.
- When mixed into other powders, the addition of synthetic opioids tends to bring an off-brown colour (or sometimes yellowish-tint) to the mixture – but this can vary widely.
Overdose risks related to unknown potency of illicit/untested products
The trouble with synthetic opioids is that it’s not always [visually] evident that a highly-potent opioid product has been added to a product purchased illegally for non-medical use; nor what other chemicals/toxins it’s been mixed with; nor the potency; nor the contamination levels.
With ‘street-purchased’ products, in particular, including counterfeit opioids sold through illicit online pharmacy chains, it’s very difficult to gauge the actual overdose fatality risks, yet alone the deadly bacteria that may have found their way into the substance being sold.
Prescription and illicit drugs can both be harmful.
But the fact remains that unregulated products are notoriously more dangerous, and have higher overdose risks because they are unpredictable in terms of dosing and other ingredients.
These are unregulated products, where diverted active pharmaceutical ingredients (APIs) are mixed in dirty labs with ‘who knows what’.
- In the United States alone, overdose statistics reveal nearly 1 million people a year are attending the Emergency Room for an overdose toxicity event.
- And in that region, over 90,000 died of an overdose in a single year.
- Over 7 in 10 of those deaths were linked with opioid use, including synthetic opioid(s) (a synthetic opioid up to 100 x more powerful than morphine).
- Overdoses involved illicit opioid products as well as prescribed pharmaceuticals used in higher-than-recommended doses and/or mixed with other substances.
This is the 4th of 10 blogs in a series of articles bringing awareness to overdose risks, non-medical use of prescription medications, and overdose prevention research such as being conducted by the Penington Institute.
For additional information, read this entire series of blogs being published from 22 August 2021 through 31 August 2021 in support of polydrug-use overdose awareness and overdose prevention day.
Please get involved in the International Drug Overdose Awareness Day and ongoing research efforts.
This year, drug overdose awareness day is on August 31, 2021 (31 August 2021).
It is a project led by the Penington Institute, a key driver of overdose awareness programs, prevention efforts, and drug-use safety campaigns.
Non-medical use (NMU) of Synthetic opioid(s) (product diversion)
Synthetic opioid products and/or opioid derivatives are commonly diverted into the hands of ‘recreational users’ and/or illicit, unregulated supply chains (criminal supply chains). After diversion, the purity and safety of these products are severely compromised.
- These drugs are often mixed with a variety of toxic chemicals and/or contaminated substances.
- When used, these substances can lead to respiratory dysfunction, other organ damage, and/or death.
- These substances are also subject to being consumed/administered using non-recommended methods and/or in excess quantities/frequencies leading to overdose toxicity.
Non-recommended routes of administration often bring additional harms (such as harms from sharing needles, unless administered in a safe injecting facility)
Overdose symptoms and harms from opioids/synthetic opioids can range from symptoms of dizziness and confusion to coma-like states (unresponsiveness), to permanent brain damage and/or to a drug-induced death (fatal overdose).
Dangers of synthetic opioids include dosing errors, polysubstance use, unpredictable toxicity levels, and opioid dependency.
Opioid medications such as synthetic opioid(s) are potentially habit-forming medications.
As part of overdose prevention efforts, medications recognised as habit-forming (and subject to diversion attempts or non-medicinal use) should be:
- only prescribed by physicians with expertise and formal training in pain-management
- closely monitored by treatment teams
- used only as prescribed
- used only by the patient and only for the authorised medicinal purpose
- kept secure (including safely away from children and potential diversions)
Learn more about the dangers of NMU use of prescription medications.
In addition to Synthetic opioid(s), other opioid products that can be habit-forming include:
- codeine oxycodone (oxys)
Stay alert: Active ingredients (APIs) and packaged opioid medications (including synthetic opioids, are frequently subjected to non-medical use.
Non-medical use of opioids can involve a variety of factors.
Scenarios for opioid misuse include:
- diversions of prescription medicines or active ingredients for non-medical use include:
- theft and/or substitution of the real material for a counterfeit product or drug
- ‘borrowing’ or use of prescriptions, such as synthetic opioid skin patches, by friends, relatives, and/or carers (which may include individuals with hidden dependencies on opioids or heroin)
- illegal distribution through illicit online pharmacies and street-drug gangs
- dangerous routes of administration (dirty needles, heated products/toxic smoke inhalation)
Risks of using synthetic opioids include harmful overdose toxicity levels in the bloodstream, which require urgent emergency medical care.
Snapshot: Synthetic opioids, overdose risks, and drug-induced deaths
Synthetic opioids use can result in an unintended drug-induced death (overdose fatality) such as:
- when synthetic opioids are mixed with other toxic substances (chemicals, alcohol, etc) and/or
- when intentional or accidental dosing of synthetic opioid products or derivatives exceeds the recommended dosing potency or frequency of intake and/or
- when used for non-medical purposes (e.g. when used recreationally as a ‘party drug’ or taken in an attempt to alleviate social anxiety) and/or
- when used by persons other than the person prescribed the medication
Potential harms: Overdose toxicity, oxygen deprivation, brain damage related to the impact of synthetic opioids on the respiratory system, breathing difficulties, organ failure, non-responsive states, and death.
Other risks of using synthetic opioid medications or illicit products:
- allergic reactions
- drug-drug interactions if taking synthetic opioids with certain other medications or mixing these products with illicit drugs
- substance use dependencies
- motor vehicle accidents, risk-taking behaviours, etc.
- overdose fatalities (drug-induced deaths)
Many deaths related to synthetic opioids (opioid overdose fatalities) are not intentional.
Drug-induced deaths from synthetic opioids are often related to:
- non-medical use of prescription opioids, or
- use of substitute drugs when prescription medicines become unavailable (no longer prescribed)
- taking more of the prescribed medication than recommended by the treatment team (intentional or unintentional dosing errors)
Quality of life and the risks of substance-use dependencies
People with acute pain and chronic pain are often desperate for relief. There’s no denying that quality of life (QOL) – particularly HRQoL (health-related quality of life) is impacted by conditions causing pain, from a back or neck injury to fibromyalgia to cancer.
Synthetic opioid products [are similar to] morphine — but can be 80 to 100 times more potent.
Sources: DEA, CDC, Higashikawa Y, Suzuki S, Schiller E & Goyal A, UNSW/NDARC, others.
The theme of International Overdose Awareness Day is “Time to Remember. Time to Act.”
This is the 4th of 10 articles/blogs discussing drug overdose statistics and polydrug use harms.
You are currently reading Blog 4 of 10 (risks of overdoses from use of synthetic opioids)
Dependency risks and prescribed synthetic opioids
How do dependencies on pain medications develop?
Given pain is disabling and can lead to serious consequences (including severe depression and/or suicidal ideation), pain-relieving pharmaceutical products are a life-saving option for numerous patients.
Whether prescribed for post-surgical pain, breakthrough cancer pain, and/or for back pain/neck pain or knee pain – pain-relieving medications such as synthetic opioid(s) have helped many individuals progress through their healing processes. But some pain-relieving medications, if overused and/or overprescribed, may lead to dependencies.
Sometimes a prescribed pain-relieving medication is also being used to treat a mental health condition (in other words, off-label use/self-medication purposes). Some patients also find the euphoric effects of opioid medications help reduce emotional/psychological pains, or trauma reactions, as well as physical pains.
Overall, there are many reasons – some social, some psychological, some bio-physiological – that lead to dependencies on certain types of medications such as synthetic opioids.
In addition to relieving physical pains, opioid products — including synthetic opioids — can be overused and habit-forming. They can also lead to deadly overdose toxicity when used in excess of dosing recommendations or when used with alcohol and other drugs.
Certain types of pain medications result in a ‘feel good’ release of excess amounts of the neurotransmitter dopamine.
- This excess dopamine can lead to a ‘euphoric state’ that the brain finds quite alluring.
- Dopamine is one of the brain chemicals that can also reduce anxiety and alleviate some forms of depression (for certain patients).
Opioid tolerance and overdose risks
Tolerance – when it comes to substance use or prescription opioid use – means that attaining the initial state of pain relief and/or euphoria, requires higher dosing levels of the product in the bloodstream. And higher levels of opioids in the bloodstream can reach fatal levels of toxicity.
That is, at least, temporarily, until the body builds up its tolerance levels to the prescribed or illicit opioid product or synthetic opioid(s).
It is often an increased quantity of the substance (e.g. opioids/synthetic opioids), along with an increase in dosing frequency, that leaves patients with overdose toxicity (or an overdose fatality).
Opioid use can lead the body to develop tolerance to these medicines over time. But substance tolerance doesn’t necessarily reduce the risks of overdose.
What does it mean to have developed tolerance to medicines and other substances?
Tolerance, in terms of pharmaceutical products and illicit drugs, means “the ability of an organism to endure unfavourable environmental conditions”. Source: OECD
It’s a form of down-regulation that minimises the body’s responses to toxicity.
Tolerance is defined as the diminished response to alcohol or other drugs over the course of repeated or prolonged exposure. This mechanism allows physiological processes to achieve stability in a constantly changing environment. Source: Alcohol Research & Health
As tolerance builds, the body tends to self-regulate (or down-regulate, meaning reduces or minimises) the effects of those medications over time. This reaction is, essentially, a ‘status quo seeking’ safety-mechanism. It reduces the impact of toxins in the bloodstream, and ‘balances out excess levels of dopamine’ and other brain chemicals.
But another part of the brain – the reward centre – can leave individuals with seemingly compulsive (or extremely strong) drives to take more of the product — or to take it more frequently.
This drive for ‘more’ and ‘more frequent’ dosing of drugs like synthetic opioids is actually the brain’s inherent tendency to:
- take ‘enhancing’ substances that lead to a perceived social or physical advantage and/or to an advantageous mental state
- reach a similar effect as experienced during early dosing (before tolerance developed)
- maintain a certain ‘psychological state’ (feeling) that can minimise, or disguise, underlying thought patterns linked to depressive states or anxiety
- feel more comfortable with social engagement and/or
- feel less stressed, momentarily, by employment stressors or relationship breakups
The brain will sometimes feel ‘driven to seek out’ higher dopamine levels via products such as opioids.
Being a novice user of a particular substance may lead to more damaging outcomes in response to dosing errors (compared to a person with tolerance to that particular substance).
Medication tolerance doesn’t, however, fully minimise the risk of an overdose. In fact, increased tolerance and increased dosing as a result are contributors to overdose fatalities.
Neurobiological effects, self-medicating behaviours, drug dependencies, and overdose risks
Seeking out enhanced levels of dopamine (or other brain chemicals) isn’t limited to people with an affinity to medications. In fact, an ‘addictive personality is a scientifically challenged concept.
The fact is that ALL human brains are neurologically wired to seek out substances and activities that “enhance their physical or emotional states”.
Just ask anyone who is caffeine-dependent — how they feel when missing their morning coffee routine!
But certain substances that enhance our physical or emotional states — can lead to overdose toxicity harms.
- These are the risks we need everyone in our community to recognise.
- We need more community members, and businesses, to take ACTIONS to help remedy overdose risks (helping others understand why overdoses occur, how to recognise one, and what to do to help) — and to support International Overdose Awareness Day.
In summary, overdose risks and/or drug-induced deaths are increased when there is:
- Overuse of a particular substance
- Polysubstance use (drug mixing)
- Long-term use and dependencies / increased dosing levels
- Self-administration above recommended doses over time
- Mixing potent medicines with alcohol, raising blood toxicity levels
- Criminal diversions into contaminated street drug supply chains
- An allergic reaction to certain medications or unrecognised/unreported drug-drug interactions
A note about synthetic opioid(s)-related dangers and overdose risks (street drugs)
Excerpt: “Synthetic opioid(s): This category of drugs has recently appeared in the black market, where synthetic opioid(s) and its analogs are often laced into other drugs or misleadingly sold as heroin. Since synthetic opioid(s) is more potent than heroin, this creates a higher risk of overdose, which could explain an increase in deaths. [Synthetic opioid(s)] is believed to have taken off in the black market around 2013 — three years after the OxyContin reformulation [which aimed to reduce illegal drug use/drug injections].”
Can Naloxone help a person who’s ingested or injected a deadly amount of opioids?
“Naloxone, often known by the brand name Narcan, is available as a nasal spray, a pre-loaded injectable shot or in a vial that can be administered with a syringe. When a person overdoses on an opioid, their breathing and pulse slow, leading to brain damage or death. A dose of naloxone stops those effects for 60 to 90 minutes by binding to the brain’s opioid receptors and essentially switching them off. Naloxone doesn’t “cure” an overdose because opioids remain in the bloodstream for at least four to six hours, but it creates a window during which a person can receive emergency care.” Source: Texas Tribune
This is the 4th of 10 articles/blogs discussing drug overdose harms, including NMU of prescription medications and polysubstance use. Click here to read blog one of 10 in the overdose awareness and polysubstance use blog series.
The series aims to focus attention on:
- the increasing number of overdose toxicity cases attending Emergency Rooms
- the rise in overdose toxicity fatalities caused by polydrug use (polysubstance use)
- the impact of the Covid-19 pandemic on substance use behaviours and overdose rates
Overdose Awareness and Prevention Resources and Research
Please support the Penington Institute.
Please FOLLOW US on LinkedIn and/or return to these is blog pages for the additional blogs on drug overdose awareness and prevention, being published daily from 22 August through 31 August 2021 (inclusive).
Thank you for bringing awareness to this important topic.
RESOURCES and FURTHER READING (Journal articles)
Recommended Research Articles, Peer-reviewed Journals and Government Resources
- Changing drug use in Australia – Australia Bureau of Statistics (ABS)
- Illicit drug use and public health harms (Science Direct)
- Synthetic opioids – Fact Sheet (Source: Drug Enforcement Agency at dea.gov)
Excerpt: The source and diversion of pharmaceutical drugs for non-medical use: A systematic review and meta-analysis
The prevalence of pharmaceutical NMU now rivals the use of illicit drugs in many developed countries around the world.
General population surveys conducted in the United States (US), Canada and Australia have found that the NMU of pharmaceutical opioids is second only to the illicit use of cannabis (Australian Institute of Health and Welfare (AIHW), 2017; Center for Behavioral Health Statistics and Quality, 2015; Health Canada, 2012; Office of National Drug Control Policy, 2011)
“The source and diversion of pharmaceutical drugs for non-medical use: A systematic review and meta-analysis”
- Authors: Shann Hulme (NDARC),⁎ David Bright (UNSW), Suzanne Nielsen (UNSW)
- Affiliations: NDARC – National Drug and Alcohol Research Centre, 22-32 King St, Randwick, NSW, 2031, Australia;
UNSW – School of Social Sciences, UNSW Australia, High Street, Kensington, NSW, 2052, Australia
Opioid Overdose (Continuing Education Resources)
Publication date/updated on: July 18, 2021.
“Studies on 1-(2-phenethyl)-4-(N-propionylanilino)piperidine (synthetic opioid(s)) and its related compounds. VI. Structure-analgesic activity relationship for synthetic opioid(s), methyl-substituted synthetic opioid(s)s and other analogues”
Journal: Forensic Toxicology volume 26, pages1–5 (2008)
“The Molecular Basis of Tolerance”
Recent news stories on the Opioid Epidemic and legal proceedings
Lawsuits by numerous State Attorneys and legal firms against the manufacturers included the following.
McKesson, Cardinal Health and AmerisourceBergen executives were accused of “turning a blind eye to suspiciously large opioid deliveries”. (Source: Bloomberg – Jef Feeley, 20 July 2021)
- J&J is accused of reaping billions from illegal marketing of its former opioid-based products.
- All four companies face legal battles across the U.S. over their role in the public-health crisis, but they are not alone:
- Numerous other manufacturers and/or suppliers, including Teva Pharmaceutical Industries Ltd, Endo International Plc. and even Walmart Pharmacies, are involved in lawsuits where State representatives and/or patient representatives are seeking $2.4 billion in damages.
- McKesson, Cardinal Health and AmerisourceBergen were in a massive trial in West Virginia “over claims they flooded the state with millions of pills to generate billions in profits”.