A new study has investigated the purity and quantity of fentanyl consumed each day by individuals in Los Angeles. By comparing these figures to standard doses of morphine and hospital dosing, the study highlights unprecedented dangers in the supply and use of street fentanyl, including exceptional levels of tolerance, indicating critical implications for treatment protocols.
What the study found
The study’s core finding was that people who use illicit fentanyl regularly are administering daily doses that are hundreds of times more than a standard prescribed dose of typical opioids, equivalent to, on average, 8887 morphine milligrams.
The study (Godvin et al, 2026), published in Drug and Alcohol Dependence, assessed the purity of over 500 fentanyl samples and the consumption methods and amounts of 47 people who regularly use fentanyl. [1]
Findings of this study include: [1][2]
- Among the fentanyl samples analyzed in this Los Angeles-based study, the average fentanyl concentration was 12.5%. The average daily dose of fentanyl was 1.07g, which contains 120mg of pure fentanyl
- The average morphine milligram equivalent (MME) was 8888. This exposure was several orders of magnitude higher than opioid doses typically administered in clinical settings.
What does “morphine milligram equivalent” (MME) mean?
Morphine milligram equivalent (MME) is a standardized measuring tool that compares different types of opioids. It uses the potency of morphine as the baseline and compares other opioid potencies against this. [3]
The MME was designed to safely compare a standard dose of morphine with a comparable opioid, such as hydrocodone or oxycodone, to enable safe and effective treatment transitions. If morphine is 1 on the MME, hydrocodone is 1, oxycodone is 1.5, and fentanyl is over 100. This huge difference means that even minuscule changes in the weight of fentanyl can significantly impact the MME comparison. [3]
For context, in a hospital setting, fentanyl is usually administered in microgram (mcg) doses, such as 100 mcg, which is 0.1 mg. Morphine might be administered at around 2.5 to 5 mg intravenously. As such, this highlights the intricate precision required to safely administer fentanyl, in comparison to other prescription drugs. [1][2]
Illicitly produced fentanyl is very commonly found in the drug supply, which varies significantly in its content, purity, and consistency. [1]
How researchers made the estimate
The researchers ran one million bootstrap simulations, which encompassed a range of fentanyl purities based on self-reported data, recognizing the fluctuations in fentanyl purity and content, along with other variables. The large-scale simulation then accounts for these variable figures to determine an MME figure. [1][2]
Limitations of the study and estimate method include: [1]
- Relying on self-reported data, which is not always accurate.
- Using proxy data for drug purity figures, which might over- or underestimate the purity and could miss data, such as from batches with much higher purities.
- Self-reported data was gathered from only 47 participants, which isn’t a large sample and may not be generalizable outside of the LA area.
However, despite these limitations, the findings of this study still highlight the extreme amounts of fentanyl being used and the high tolerance levels developed in these individuals. This is crucial information for researchers and professionals involved in the development and implementation of OUD treatments.
Why fentanyl tolerance gets so high
If someone develops fentanyl tolerance, this means that the effect of the drug has a lower impact the more they use it. For example, someone who has never taken opioids may experience a fatal overdose from a 2 mg dose of fentanyl. For someone who has developed a tolerance over many months or years of use, this dose might be ineffectual. [2][4]
A very small amount of fentanyl can cause fatal respiratory depression in someone without opioid tolerance, although there is no universal lethal dose because individual risk varies substantially.
Fentanyl has a potent effect on the brain’s opioid receptors. When it binds to the receptors so intensely, the receptors adapt quickly by downregulating to protect the body. People who are dependent on fentanyl are likely to use increasing doses as their tolerance develops, in an attempt to experience the same level of effects.
Researchers in this study found that the participants in their study were using around 120 mg per day, 60 times more than a fatal dose for an opioid-naïve individual. As fentanyl is incredibly potent, slight increases in dosage can rapidly increase the level of dependence and tolerance over a short period, while significantly increasing the risk of overdose. [1]
What this means for addiction treatment
Addiction treatment is developed through research and evidence-based approaches. For instance, opioid use disorder (OUD) treatment has been carefully researched, and there are three evidence-based, approved medications: methadone, buprenorphine, and naltrexone. These medications have been rigorously trialed and studied and proven to be effective against opioids such as heroin and prescription analgesics. [4]
However, this study highlights issues with current treatment approaches that will need to be addressed to effectively manage the full spectrum of opioid dependence that encompasses these levels of fentanyl use. The high levels of opioid tolerance observed in this population create challenges for treatment. However, medications for OUD like methadone and buprenorphine are still recommended for people with fentanyl dependence. [4]
Because of this, people with severe fentanyl dependence report that they struggle to commence and maintain buprenorphine, as it can trigger severe and rapid precipitated withdrawal. Additionally, buprenorphine doses are often ineffective at reducing cravings in people with this level of tolerance due to its “ceiling effect”. [4][5]
As such, OUD treatment approaches will require updating and refining to determine the most effective plan to support recovery within those with such high tolerance levels and prevent or manage severe withdrawal and relapse risks. This might mean utilizing significantly higher doses of medications such as methadone or changing the way buprenorphine treatment is initiated. [5][6]
Implications for public health
This has significant implications for people who use opioids, including:
- Recognizing the need for easily accessible naloxone and the potential for multiple doses to be required in fentanyl overdoses.
- Recognizing the huge differences between fentanyl and other opioids, and how they can implement harm reduction strategies to keep themselves safe, such as using a small dose of a new batch to test the purity and potency.
Similarly, this can impact future research, such as:
- Providing a baseline for further research looking at fentanyl purity that goes beyond proxy data gathering.
- Investigating improvements to treatment protocols for methadone and buprenorphine that can support people with high tolerance levels through withdrawal.
- Expanding research from just fentanyl-related tolerance and harm to incorporate other common contaminants and substances that are found in the illicit drug supply, including new synthetic opioids.
Conclusion
This study demonstrates the vast increase in opioid tolerance found among people who use fentanyl, highlighting the critical limitations of current treatment protocols. Illustrating its extreme potency and the unprecedented levels of tolerance that can develop is crucial to understanding and managing the current dangers faced by many individuals.
This is hugely significant for the future of OUD treatment, revealing an urgent need to improve the management of severe fentanyl withdrawal and the stabilization of initial and maintenance OUD medications.
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