While opium-based opioids have extremely high addictive potential, that of synthetic opioids such as nitazenes and newly emerging non-opioid sedatives, is exponentially worse due to their potency.
The medical community has been overwhelmed by the onslaught of contaminated drug supplies, containing synthetic opioids like fentanyl, and the nitazenes, and the novel synthetic non-opioid analogs like xylazine, known on the street as “tranq.”
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Alternative to Meds has helped thousands of clients to reduce or eliminate their dependence & need for drugs for close to 20 years now, with great success. Please take a look at an independently reviewed performance summary spanning many years of client care. Clearly, anyone who is taking drugs, whether to manage mental health, reduce pain, or for recreational reasons, may be at risk of neurotoxic effects. Adding to the problem is the extremely wide range of toxic contamination saturating opioid drug supply that may put many people, especially those with an addictive neurochemistry profile, at elevated risk.
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Alternative to Meds Center has researched the factors that contribute to a person’s propensity toward certain classes of drugs. These factors are important in successfully undoing the bio-physiological chains of addiction, whether to natural opioids, synthetic opioids, benzodiazepines, or other classes of drugs.
Bypassing these contributing factors often leads to failure, much like trying to fix a car that won’t start by painting it, or perhaps changing the tires. You can find out much more about biochemical drivers of addiction and dependence by reviewing the above links on our website. Here, we will focus on the synthetic opioids & analogs to gain better understanding of their high risk in users for damage and fatality.
While the effects of organic and lab-created drugs may present in similar ways, their mechanisms of action may differ in important ways. These differences make overdose treatment to avoid fatality very different from each other. And, navigating the path to true recovery also demands individualized protocols to address each client’s physiological & psychological uniqueness.
Overdose Mechanics and the CNS — Natural vs Synthetic Opioids
The DEA reports that as of 2022, synthetic opioid deaths have exponentially outpaced heroin and other overdose deaths. The numbers of synthetic opioid deaths are staggering, rising from 2600 yearly for 2011 and 2012, to over 68,000 in 2021 alone. From 2013 to 2021, the reported death toll is 258,000.22
It has been found that opioids and synthetic opioids (including non-opioid analogs) bind to certain opioid receptors in the brain/body/CNS. However, the entire process is not entirely understood, and in the case of synthetic opioids the mechanism of action is even less understood.
It is generally considered that a cascade of other effects involving other receptors and transmitters and chemicals occurs following exposure to opioids or opioid analogs, and this affects a multitude of functions. A shutdown of vital functions occurs, such as pain perception, breathing, heart rate, transport of vital nutrients, and hundreds or thousands of other reactions. Unconsciousness, slowed or stopped breathing, choking or gurgling sounds, difficulty speaking, standing, or walking, pinpoint pupils, and bluish/grayish color of skin & lips, are signs of overdose. If this shutdown is not reversed, this portends death of the body.7,20
Exposure to some synthetics such as the nitazenes respond more slowly to overdose reversal agents such as Narcan or Naloxone, and would require 4 or more doses to prevent death. Xylazine exposure does not respond to Narcan or Naloxone and cannot prevent overdose death. Research is ongoing, but many of these analogs come from unknown and untraceable sources, and have rapidly increased in number and variation over the years.6,7
Worldwide Statistics on Illegal Drug Contamination
Interestingly, the UN reported on a threat of emergence of synthetic opioid analogs in 2018 — before they were even detected in North America.17
And, since 2018, the presence of synthetic adulterants to drug supplies has seen a sudden spike in overdose fatalities, damage to health, and profound negative social impacts in urban areas in North America, Europe, and around the world.1,3,4,8,9,16
In Canada, nitazenes were first detected in street drug supplies in 2019, and Health Canada reports an exponential rise of overdoses involving these drug additives since that time, continuing into the present.5
The UK Gov has issued a request for newly classifying a number of these drugs as controlled substances, over concerns of increasing presence, overdoses, and other known harms to drug users.14
In the US, the DEA reports that the majority of drug overdose deaths are now synthetic-opioid-or analog related, whether in combination with other street drugs such as meth or heroin, fake Xanax pills, or as the singular cause of death.21
Relative Potency of Fentanyl, Nitazenes, Xylazine (“tranq”)
To frame an understanding of potency, many opioid drugs have been analyzed for relative strength compared to morphine. Morphine is 3-5X weaker than heroin. Both opiates (such as heroin) and synthetic opioids (such as fentanyl) target the same opioid receptors in the human body/brain/CNS. Synthetics including fentanyl were found to be more potent and faster acting than either morphine or heroin. The effectiveness of Narcan or Naloxone in overdose reversal diminishes in direct ratio to the potency & volume of the drug that was ingested. EMTs as well as laypersons need to be aware that much higher and repeated doses of reversal agents may be needed in such cases.4,6,11
The relative potency of some opioids and synthetic opioids vs morphine:
Codeine – 1/10th
Heroin – 3-5X
Hydromorphone – 4-5X
Methadone – 5-10X
Fentanyl – 100-150X
Carfentanyl – 10,000X
Nitazenes have been around since the 50s, but never approved for therapeutic human use.2 Potency of nitazenes, has been compared in lab studies using rat brain tissues against morphine and heroin. In vitro results showed synthetic opioids, morphine, and heroin all have equal ability to bind to these receptors. However, nitazenes, which are opioid analogs, have structures unrelated to other opiates and are known to induce potentially far more intoxicant and other effects on the CNS.11
If overdose agents respond at all, it is a much slower process, requiring higher dosage to prevent death.
The DHA issued their 2024 report assessing current national drug threats in the US and states that nitazenes coming from China are now more frequently found mixed with fentanyl and other street drugs. Combining nitazenes with other opioids intensifies the effects of both, resulting in more frequent overdose deaths. The drug suppliers at their source have begun to introduce new nitazenes, as novel versions are not yet illegal and can fly under DEA’s radar and avoid importing restrictions.21
Relative potency of some nitazenes vs heroin:8
Metonitazene – 50X
Prolonitazene – 100X
Isontonitazene – 250X
Elonitazene – 500X
Xylazine:
Xylazine is an animal tranquilizer (street name “tranq”), that has dominated street drug supplies in very recent times, and its effects are incompletely understood. Earlier, in 2009, researchers found a high percentage of “speedballs” (a mixture of cocaine and heroin) and a collection of used injection needles in ranching communities, contained xylazine. Skin ulcers and poor health were characteristics of users in the researched area.10,18
The exact relative potency of xylazine (tranq) in relation to opiates has not been fully determined. However, what is known is that this drug is used predominantly in humans as an additive to opiates and other classes of drugs that are sold or acquired in non-clinical settings. Xylazine has been discovered in drug supplies in all 50 US states. In some regions of the US, xylazine was found present in up to 80% of all surveyed opiate samples. Xylazine overdose deaths increased by 35 times from 2018-2021. Xylazine was found to prolong and enhance the effects of the drugs it is added to, and more research is needed to discover more about its mechanisms of action.12,13,21
Unfortunately, Xylazine does not respond at all to usual overdose reversals like Narcan or Naloxone.
In addition to its addictive characteristics, Xylazine causes skin necrosis, chronic skin ulcers, and deep tissue wounds, which suffer from slow healing due to the shutdown of circulation both at and away from the injection site.15
The Role of Research in Finding Effective Withdrawal Strategies
For far too long, adequate care in addressing addiction and withdrawal from synthetic opioids and other drugs has been hampered by lack of information and research on things that really matter for recovery. Some believe that strategies like drug substitution, safer drug supply strategies and harm reduction are helpful. In the short term, perhaps for some this is true. Yet others question whether these actions really can provide long-term sustained recovery. Some question whether such strategies have been driven by something other than a pure and heartfelt intention to help.
It is expensive to carry out research, and sponsorship for it is difficult to get, especially if the findings may show certain aspects of drug manufacturing, promotion, and even certain modes of treatment in a less than favorable light.
It could be worth your or your loved one’s life to spend time finding information that provides solutions that do not inflict further harm, and provide a non-toxic pathway back from the physical AND mental suffering of addiction. You may find the articles which are listed below helpful, along with the references they link to, to broaden your personal knowledge base.
One of the greatest advantages of inpatient care is that it removes a person from one’s usual landscape that may be a minefield of potential triggers. In a safe and secure environment one can take advantage of increasing one’s understanding of the mechanics of addiction and true recovery, and apply these skills with support from our caring and attentive staff.
Please call on us for more information and guidance if you or a loved on is struggling with the aftermaths of addiction to synthetic opioids. We are here to help you find the best path to regaining self-empowerment and true recovery.
Originally Published March 15, 2024 by Diane Ridaeus
This content has been reviewed and approved by a licensed physician.
Dr. Samuel Lee
Dr. Samuel Lee is a board-certified psychiatrist, specializing in a spiritually-based mental health discipline and integrative approaches. He graduated with an MD at Loma Linda University School of Medicine and did a residency in psychiatry at Cedars-Sinai Medical Center and University of Washington School of Medicine in Seattle. He has also been an inpatient adult psychiatrist at Kaweah Delta Mental Health Hospital and the primary attending geriatric psychiatrist at the Auerbach Inpatient Psychiatric Jewish Home Hospital. In addition, he served as the general adult outpatient psychiatrist at Kaiser Permanente. He is board-certified in psychiatry and neurology and has a B.A. Magna Cum Laude in Religion from Pacific Union College. His specialty is in natural healing techniques that promote the body’s innate ability to heal itself.
Diane is an avid supporter and researcher of natural mental health strategies. Diane received her medical writing and science communication certification through Stanford University and has published over 3 million words on the topics of holistic health, addiction, recovery, and alternative medicine. She has proudly worked with the Alternative to Meds Center since its inception and is grateful for the opportunity to help the founding members develop this world-class center that has helped so many thousands regain natural mental health.
Medical Disclaimer: Nothing on this Website is intended to be taken as medical advice. The information provided on the website is intended to encourage, not replace, direct patient-health professional relationships. Always consult with your doctor before altering your medications. Adding nutritional supplements may alter the effect of medication. Any medication changes should be done only after proper evaluation and under medical supervision.
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Alternative to Meds Center has researched the factors that contribute to a person’s 
One of the greatest advantages of inpatient care is that it removes a person from one’s usual landscape that may be a minefield of potential triggers. In a safe and secure environment one can take advantage of increasing one’s understanding of the mechanics of addiction and true recovery, and apply these skills with support from our caring and attentive staff.
