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Synthetic Opioids Deaths on the Rise

Last Updated on July 8, 2024 by Carol Gillette

Alternative to Meds Editorial Team
Medically Reviewed by Dr Samuel Lee MD

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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Addictive Biochemistry & Synthetic Opioids/Analogs

synthetic opioid addictionAlternative 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 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.

Alternative Mental Health Philosophy | Alternatives To Medications (

Treatment for Emotional & Physical Symptoms | Alternative To Meds Ctr

ATMC Mental Health and Future of Treatment Podcast (

The Link Between Mental and Physical Wellness | Fueling Both (

Inpatient Care & Recovery at ATMC

opioid recovery sedona drug rehabOne 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.

ATMC is based on key principles of regaining health, including neurotoxin removal, neurotransmitter rehabilitation, peer support & education, counseling and a wealth of other adjunctive therapies for stress, trauma, and healing.

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.


1. CDC Report Notes from the Field: Nitazenes-related Deaths 2019-2021 published online Sept 16 2022 [cited 2024 Mar 15]

2. Pergolizzi J Jr, Raffa R, LeQuang JAK, Breve F, Varrassi G. Old Drugs and New Challenges: A Narrative Review of Nitazenes. Cureus. 2023 Jun 21;15(6):e40736. doi: 10.7759/cureus.40736. PMID: 37485167; PMCID: PMC10361140. [cited 2024 Mar 15]

3. Vandeputte MM, Tsai MM, Chen L, Glatfelter GC, Walther D, Stove CP, Shi L, Baumann MH. Comparative neuropharmacology of structurally distinct non-fentanyl opioids that are appearing on recreational drug markets worldwide. Drug Alcohol Depend. 2023 Aug 1;249:109939. doi: 10.1016/j.drugalcdep.2023.109939. Epub 2023 May 23. PMID: 37276825; PMCID: PMC10330921. [cited 2024 Mar 15]

4. Baumann MH, Tocco G, Papsun DM, Mohr AL, Fogarty MF, Krotulski AJ. U-47700 and Its Analogs: Non-Fentanyl Synthetic Opioids Impacting the Recreational Drug Market. Brain Sci. 2020 Nov 23;10(11):895. doi: 10.3390/brainsci10110895. PMID: 33238449; PMCID: PMC7700279. [cited 2024 Mar 15]

4a. Jordan MR, Morrisonponce D. Naloxone. [Updated 2023 Apr 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from:  [cited 2024 Mar 15]

5. Health Canada At-a-glance: The emergence of nitazenes/brorphine in Canada since 2019 published online 22/06/23  [cited 2024 Mar 15]

6. Shafi A, Berry AJ, Sumnall H, Wood DM, Tracy DK. Synthetic opioids: a review and clinical update. Ther Adv Psychopharmacol. 2022 Dec 10;12:20451253221139616. doi: 10.1177/20451253221139616. PMID: 36532866; PMCID: PMC9747888. [cited 2024 Mar 15]

7. Edinoff AN, Martinez Garza D, Vining SP, Vasterling ME, Jackson ED, Murnane KS, Kaye AM, Fair RN, Torres YJL, Badr AE, Cornett EM, Kaye AD. New Synthetic Opioids: Clinical Considerations and Dangers. Pain Ther. 2023 Apr;12(2):399-421. doi: 10.1007/s40122-023-00481-6. Epub 2023 Feb 24. PMID: 36826742; PMCID: PMC9950705. [cited 2024 Mar 15]

8. Holland A, Copeland C, et al Nitazenes-heralding a second wave for the UK drug-related death crisis? [published in The Lancet Volume 9, Issue 2, E71-E72 Feb. 2024 [cited 2024 Mar 15]

9. Advisory Council on the Misuse of Drugs. ACMD advice on 2-benzyl benzimidazole and piperidine benzimidazolone opioids. 2023. [cited 2024 Mar 15]

10. Ayub S, Parnia S, Poddar K, Bachu AK, Sullivan A, Khan AM, Ahmed S, Jain L. Xylazine in the Opioid Epidemic: A Systematic Review of Case Reports and Clinical Implications. Cureus. 2023 Mar 29;15(3):e36864. doi: 10.7759/cureus.36864. PMID: 37009344; PMCID: PMC10063250. [cited 2024 Mar 15]

11. WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents. Geneva: World Health Organization; 2018. Table A6.2, Approximate potency of opioids relative to morphine; PO and immediate-release formulations unless stated otherwise. Available from: [cited 2024 Mar 15]

12. CDC report What You Should Know about Xylazine published online Feb 22 2024 [cited 2024 Mar 15]

13. CDC Vital Statistics #030 Drug Overdose Deaths Involving Xylazine United States 2018-2021 published online June 2023 [cited 2024 Mar 15]

14. UK Gov Advisory Council Report A Review of the evidence on the use and harms of Xylazine, Medetomidine, and Detomidine published online 2023 [cited 2024 Mar 15]

15. Malayala SV, Papudesi BN, Bobb R, Wimbush A. Xylazine-Induced Skin Ulcers in a Person Who Injects Drugs in Philadelphia, Pennsylvania, USA. Cureus. 2022 Aug 19;14(8):e28160. doi: 10.7759/cureus.28160. PMID: 36148197; PMCID: PMC9482722. [cited 2024 Mar 15]

16. The Lancet Nitazenes represent a growing threat to public health in Europe published Feb 23, 2024 [cited 2024 Mar 15]

17. The United Nations Office on Drugs and Crime UNODC launches toolkit on synthetic drugs to support member states in addressing challenges published March 2019 [cited 2024 Mar 15]

18. Rodríguez N, Vargas Vidot J, Panelli J, Colón H, Ritchie B, Yamamura Y. GC-MS confirmation of xylazine (Rompun), a veterinary sedative, in exchanged needles. Drug Alcohol Depend. 2008 Aug 1;96(3):290-3. doi: 10.1016/j.drugalcdep.2008.03.005. Epub 2008 May 9. PMID: 18472231; PMCID: PMC2527692. [cited 2024 Mar 15]

19. Schiller EY, Goyal A, Mechanic OJ. Opioid Overdose. [Updated 2023 Jul 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: [cited 2024 Mar 15]

20. Gov of Canada Opioid Overdose published online Sept 2023 [cited 2024 Mar 15]

21. DEA authors, National Drug Threat Assessment 2024 published online May 2024 [cited 2024 June 27]

22. DEA Drug Fact Sheet: Fentanyl published online October 2022 [cited 2024 June 27]

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.

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