The landscape of illicit drug use has undergone a dangerous transformation, with synthetic opioids now representing the deadliest category of substances in the overdose crisis. While fentanyl has dominated headlines, a new wave of even more potent synthetic compounds—including nitazenes and their analogs—are emerging on streets across North America, some being 10 to 40 times stronger than fentanyl itself. Understanding these emerging threats is critical for individuals, families, and communities navigating the complexities of substance use disorders and public health safety.
What Are Synthetic Opioids?
Synthetic opioids are laboratory-manufactured drugs that mimic the effects of natural opioids like morphine but are created entirely from chemical compounds rather than plant extracts. Unlike semi-synthetic opioids such as heroin and oxycodone, which are made by chemically processing natural opioids, synthetic opioids like fentanyl are manufactured entirely in laboratories with no natural ingredients.
These substances interact with the same opioid receptors in the brain as prescription pain medications and heroin, producing pain relief, euphoria, and sedation. However, their extreme potency makes them exponentially more dangerous.
How Potent Are Synthetic Opioids Compared to Heroin?
Fentanyl is up to 50 times stronger than heroin and 100 times stronger than morphine. But fentanyl is no longer the most dangerous player in this crisis. Certain nitazenes could be hundreds to thousands of times more potent than morphine, making even microscopic amounts potentially lethal.
Potency Comparison Table:
| Substance | Potency Relative to Morphine |
|---|---|
| Morphine | 1x (baseline) |
| Heroin | 2-3x |
| Fentanyl | 50-100x |
| Carfentanil | 10,000x |
| Isotonitazene (ISO) | 250-900x |
| Etonitazene | 1,000-4,300x |
The New Wave: Nitazenes and Beyond
What Are Nitazenes?
Nitazenes are a class of synthetic opioids that contains more than 20 unique compounds, including isotonitazene (ISO), protonitazene, metonitazene, and etonitazene—substances that were never approved for medical use by the FDA.
Originally developed in the 1950s and 1960s as potential analgesics, these compounds were abandoned due to their severe adverse effects. These drugs had failed to become licit medical analgesics because of severe side effects such as respiratory depression and physical dependence.
Why Are Nitazenes Appearing Now?
As law enforcement has cracked down on fentanyl, illegal labs have used historical pharmacology research to formulate analogs of nitazenes as street drugs. Drug traffickers constantly seek new compounds to circumvent legal restrictions and maximize profits.
Nitazenes are frequently mixed with or counterfeited as other drugs (such as heroin, fentanyl, benzodiazepines, or other synthetic drugs) to increase potency and cut costs. This means many consumers are unaware they’re consuming nitazenes, leaving them particularly vulnerable to overdose.
Geographic Spread
Isotonitazene was first identified around 2019 in the Midwest, then moved into the Southern states and more recently along the Eastern seaboard. In Canada, nitazenes were first identified in the drug supply in 2019 in Quebec, and by February 2021 in Toronto, with detection steadily increasing.
Other Emerging Non-Fentanyl Synthetic Opioids
Beyond nitazenes, several other synthetic opioid families are circulating in illicit drug markets:
U-Compounds (U-47700 and U-49900)
U-47700 has been implicated in recent overdose deaths and law enforcement sources show increasing confiscation. These benzamide opioids were developed decades ago but never marketed commercially.
Brorphine
A relatively newer addition to the illicit market, brorphine represents another non-fentanyl synthetic opioid with high abuse potential.
MT-45 and Derivatives
MT-45 was developed in the 1970s and has similar potency to morphine but can produce hearing loss and dissociative-like effects. After its scheduling, fluorinated derivatives began appearing on streets.
Key Characteristics of Emerging Synthetic Opioids:
- Extremely high potency (often exceeding fentanyl)
- Never approved for human medical use
- Limited clinical research on human effects
- Difficult to detect with standard drug tests
- Often sold as or mixed with other substances
- Sourced from clandestine laboratories, primarily in China
Why Are Synthetic Opioids More Dangerous Than Traditional Drugs?
Speed of Onset
While heroin overdose can take 20-30 minutes before leading to a fatality, fentanyl can precipitate a profoundly dangerous and life-threatening respiratory arrest within 2-5 minutes. With even more potent compounds like nitazenes, this window becomes even narrower.
Unpredictable Drug Supply
Synthetic opioids are typically sold on the street as counterfeit medications or mixed with heroin and other drugs. Users often believe they’re purchasing prescription opioids or heroin but receive much more powerful synthetic compounds.
Detection Challenges
Specialized lab testing is required to identify nitazenes in toxicology samples, and fentanyl test strips can’t detect nitazene analogs. This means standard harm reduction tools have limited effectiveness.
Higher Naloxone Requirements
Naloxone (Narcan) is reportedly effective in reversing nitazene overdoses, but larger and multiple doses might be required. Doses of 10 to 20 mg of naloxone may be required to reverse the effects of potent synthetic opioids.
Common Questions About Synthetic Opioids
Can Naloxone Reverse a Synthetic Opioid Overdose?
Yes, naloxone can reverse synthetic opioid overdoses, including those involving nitazenes. However, because of their extreme potency, multiple doses and higher amounts of naloxone are typically required compared to traditional opioid overdoses. First responders should be prepared to administer repeated doses and provide continuous monitoring.
How Can Someone Tell if Drugs Contain Synthetic Opioids?
Unfortunately, it’s nearly impossible to identify synthetic opioids by appearance alone. You can’t see, smell, or taste fentanyl, which allows drug dealers to produce stronger highs for lower costs. While fentanyl test strips exist, they cannot detect many newer compounds like nitazenes. The safest assumption is that any illicit drug may contain synthetic opioids.
Are Synthetic Opioids More Addictive Than Other Opioids?
While all opioids carry addiction risk, data doesn’t definitively show that synthetic opioids are more or less addictive than natural opioids. However, their extreme potency means users develop tolerance faster and face significantly higher overdose risks. Nitazenes are highly addictive and continued use can lead to dependency, with withdrawal having high potential to be severe and painful.
What Makes Someone More Vulnerable to Synthetic Opioid Overdose?
Several factors increase overdose risk, including:
- No tolerance to opioids (first-time or occasional users)
- Using alone without someone nearby to help
- Combining opioids with other depressants (alcohol, benzodiazepines)
- History of overdose
- Recently reduced tolerance (after treatment or incarceration)
- Unintentional exposure through contaminated drugs
Signs and Symptoms of Synthetic Opioid Overdose
Recognizing overdose symptoms can save lives. Look for:
Physical Signs:
- Extremely small (pinpoint) pupils
- Slow, shallow, or stopped breathing
- Blue or purple lips and fingernails
- Limp body
- Cold, clammy skin
- Inability to wake up or speak
- Choking or gurgling sounds
Critical Response Steps:
- Call 911 immediately
- Administer naloxone (Narcan) if available
- Provide rescue breathing if trained
- Place person on their side (recovery position)
- Stay with the person until help arrives
- Be prepared to give multiple doses of naloxone
The Public Health Impact
The CDC reported that 100,306 total drug overdose deaths occurred in the 12 months to April 2021 in the United States, with synthetic opioids being the main cause (75,673 deaths, or 75.4%).
In 2022, there were 107,941 recorded overdose deaths in the US, with fentanyl responsible for nearly 80% of all fatal drug overdoses. As newer, more potent synthetic opioids enter the market, these numbers threaten to climb even higher.
Hidden Casualties
Many medical providers aren’t even aware that nitazenes exist, leading to potential underreporting of deaths. Without specific testing protocols, deaths attributed to heroin or fentanyl may actually involve these newer compounds.
Prevention and Harm Reduction Strategies
While abstinence is the safest approach, harm reduction strategies can save lives:
For Individuals Using Substances:
- Never use alone—have someone nearby who can help
- Start with a small test dose when using a new supply
- Carry naloxone and ensure others know how to use it
- Use fentanyl test strips (though they won’t detect all compounds)
- Avoid mixing opioids with alcohol or other depressants
- Know the signs of overdose
For Communities:
- Increase naloxone distribution and training
- Support drug checking services where available
- Educate first responders about emerging threats
- Advocate for expanded treatment access
- Reduce stigma around substance use disorders
- Support Good Samaritan laws protecting those who call for help
Treatment and Recovery Options
The emergence of ultra-potent synthetic opioids makes professional treatment more critical than ever. Opioid use disorder is a chronic medical condition that responds to evidence-based treatment.
Medication-Assisted Treatment (MAT)
FDA-approved medications like methadone, buprenorphine (Suboxone), and naltrexone can:
- Reduce cravings and withdrawal symptoms
- Block the euphoric effects of opioids
- Improve treatment retention
- Decrease overdose risk
Behavioral Therapies
Counseling and therapy help address the psychological aspects of addiction:
- Cognitive-behavioral therapy (CBT)
- Contingency management
- Motivational interviewing
- Group and individual counseling
- Family therapy
Comprehensive Support Services
Recovery extends beyond clinical treatment:
- Peer support groups
- Case management
- Housing assistance
- Employment support
- Medical and mental health care
- Recovery coaching
Finding Hope and Support at True North Recovery Services
If you or someone you love is struggling with opioid use disorder or any substance use challenge, compassionate help is available. True North Recovery Services offers comprehensive addiction treatment and mental health support in the Denver Metro Area. Our holistic approach recognizes that recovery is deeply personal and multifaceted, not one-size-fits-all.
We provide evidence-based outpatient treatment for opioid and alcohol use disorders, including intensive outpatient programs (IOP) and recovery support services. Our mission is to facilitate your journey away from substance abuse toward self-discovery and a more fulfilling existence. With years of clinical experience, compassionate care teams, and comprehensive medical care, we’re committed to helping you find your path to lasting recovery.
Don’t face this alone. Call True North Recovery Services at (720) 669-6793 or visit our Denver location to begin your journey toward healing and hope.
