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Chauvin Trial Analysis: Opioid Tolerance Issues

Chauvin Trial Analysis: Opioid Tolerance Issues

Science suggests opioid-addicts with tolerance are more, not less, likely to suffer overdose.

Welcome to our ongoing coverage of the Minnesota murder trial of Derek Chauvin, over the in-custody death of George Floyd.  I am Attorney Andrew Branca for Law of Self Defense, providing guest commentary and analysis of this trial for Legal Insurrection.

Anyone interested in a free podcast version of our daily legal commentary and analysis of the Chauvin trial can access the Law of Self Defense News/Q&A Podcast, available on most every podcast platform, including PandoraiHeartSpotifyApple PodcastGoogle Podcastsimple RSS feed, and more.

I wanted to share with all of you some additional information that has been shared with me on the issue of opioid tolerance. I caution again that I remain thoroughly non-expert on the subject, but I do now have some actual research papers that I can share with you, and perhaps we can all develop a better-founded understanding of tolerance in the context of this case.

Opioid tolerance is of relevance in this case because it ties into the issue of cause of death of George Floyd. Specifically, was it Chauvin’s knee that killed Floyd, or was it Floyd’s three-fold fatal dose of fentanyl, in combination with methamphetamine, that killed him.  (Also relevant, of course, is Floyd’s existing severe hypertensive and cardiovascular disease, as well as the physiological context of Floyd choosing to forcibly resist efforts by multiple officers to make his lawful arrest, but those factors are outside the scope of this content.)

During opening arguments Prosecutor Blackwell suggested to the jury that although Floyd’s levels of fentanyl might have been a fatal dose to a typical person, they would not have been a fatal dose to Floyd.  Why?  Because Floyd was not a typical person, he was an opioid addict, and opioid addicts develop tolerance to their drugs.  Thus, according to this line of argument, Floyd would have been substantially less vulnerable to death by fentanyl overdose than would the non-addict.

This line of argument struck me as inconsistent with my own understanding—admittedly a layman’s understanding—of how tolerance works in this context.

In. yesterday’s wrap-up post I wrote:

I don’t believe tolerance works to make an addict more resilient against death by overdose, but merely makes it harder to get the desired high.  The mechanism of death by overdose and the mechanism of the high are fundamentally different. The brain develops tolerance to the drug and so requires a greater concentration of drug to get the same high. But that has nothing to do with how the drug kills. In the case of fentanyl, death is usually the result of the drug achieving a level sufficient to stop respiration—and I don’t believe the body develops any tolerance to that biological mechanism.

In other words, if an addict first needs 2 units of drug to get high, he’ll eventually need 4, then 8, then 10, etc.  But if a fatal dose is 20 units, then whenever the addict hits 20, he dies, and it matters not a whit how much tolerance he’s developed in the context of getting high. Indeed, one of the great dangers to addicts is that they grow ever closer to fatal overdose as their increasing tolerance to achieve a high demands doses that approach ever closer to fatal levels.

Again, however, that’s a layman’s understanding of these issues. I look forward to hearing expert testimony during the trial.

Now, it appears now that there is a fundamental error in that statement–in fact tolerance develops with respect to both the “high” and with respect to respiratory depression.  The fundamental point remains, however, because the rate at which tolerance develops for each is different. Specifically, it appears that tolerance to the “high” grows much more rapidly than does tolerance to respiratory depression.

This morning I found that a helpful comment (thanks Dan, over at the Law of Self Defense blog!) that kindly provided links to two scientific papers on this subject, and I’d like to share those with all of you.  I caution again, I’m just a small-town lawyer, not a doctor, and two papers do not make a claim authoritative, but they do constitute more scientific support than I’d cited previously, so I thought them worth sharing.  (Both papers are freely accessible without cost, and I’ve linked them below.)

I also caution that the scientific papers are written in the same style and tone as scientific papers are typically written, which can make them rather cumbersome and somewhat opaque to the non-expert reader, but that’s the way these things go.

Both papers make the argument, supported by their findings, that while tolerance may develop both in terms of the “high” (or, in a therapeutic setting, the pain relief or analgesic effect sought) and in terms of fatal overdose (in the case of opioids, usually fatal respiratory depression, referred to as opioid-induced respiratory depression, or OIRD), that these tolerances do not develop at the same rate.

Instead, tolerance of the “high” grows much faster than does tolerance for overdose. The result is that the “window” of safe dosing by opioid addicts, in which the desired high is achieved without fatal overdose, grows smaller and smaller over time, meaning the danger of overdose grows increasingly likely over time.

The first paper, published in the scientific journal Anesthesiology, is titled “Differential Opioid Tolerance and Opioid-induced Hyperalgesia: A Clinical Reality”, and it reads in relevant part:

In the early postoperative setting, differential tolerance development to analgesia and respiratory depression is most relevant. Patients receiving chronic opioids for pain control, especially at high doses, should be assumed to have developed less tolerance to opioid-induced respiratory depression than to analgesia. This means that equianalgesic doses of opioids administered perioperatively will induce more respiratory depression in opioid-tolerant than in opioid-naive patients (note that the dose required to reach this equianalgesic effect will likely be much greater in the opioid-tolerant patient). In other words, contrary to what intuitively would seem to be the case, the opioid-tolerant patient is at an increased risk for respiratory depression when his or her postoperative pain is treated adequately with opioids.

The second paper, published in the scientific journal Clinical Pharmacology and Therapeutics, is titled “Tolerance to Opioid‐Induced Respiratory Depression in Chronic High‐Dose Opioid Users: A Model‐Based Comparison With Opioid‐Naïve Individuals,” and it reads in relevant part:

Prolonged use of opioids, such as morphine, oxycodone, or fentanyl, is associated with addiction, physical dependence, and tolerance.Tolerance occurs due to adaptive changes at the neuronal level and results in the need for dose escalation to maintain the desired intensity of response.Importantly, the consumption of high‐dose or potent opioids is potentially life‐threatening, as it may cause opioid‐induced respiratory depression (OIRD) and ultimately death from silencing of neurons in brainstem respiratory networks.When tolerance to analgesic and euphoric opioid effects coincides with tolerance to opioid respiratory effects, tolerance may reduce the respiratory effects of opioids. However, several animal studies indicate that tolerance to the analgesic and respiratory effects are dissociated with lower and slower development of tolerance to OIRD than of other opioid effects.

Assuming that tolerance to the “high” of opiates develops substantially more rapidly than does tolerance to OIRD, and that the window of safe dosing thus grows ever smaller and the risk to the addict of fatal overdose ever greater, this would run counter to the state’s apparent argument that Floyd’s admitted opioid addiction actually made him less likely to experience a fatal opioid overdose than would be the case for a non-addict.

OK, folks, that’s all I have for now.

Join us later this morning for our LIVE coverage of the court proceedings in Minnesota v. Chauvin, and for our end-of-day wrap-up commentary and analysis, both right here at Legal Insurrection.

Until next time, stay safe!


Attorney Andrew F. Branca

Law of Self Defense LLC

Attorney Andrew F. Branca’s legal practice has specialized exclusively in use-of-force law for thirty years.  Andrew provides use-of-force legal consultancy services to attorneys across the country, as well as near-daily use-of-force law insight, expertise, and education to lawyers and non-lawyers alike in the form of blog posts, video, and podcasts, through the Law of Self Defense Membership service.  If this kind of content is of interest to you, try out our two-week Membership trial for a mere 99 cents, with a 200% no-question- asked money-back guarantee, here:  Law of Self Defense Membership Trial.

[Featured image is a screen capture from video of George Floyd’s arrest on May 25, 2020.]




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An anesthesiologist (thanks, spellcheck) weighed in on the wrap-up thread. Would be worth revisiting because that post seemed to indicate some more nuance to the issue. Finding the right dose in opioid tolerant individuals is a matter of finding the narrow window between no-effect and death. Both of which happen at higher doses than for the addict, but the level of tolerance makes it a dangerous fishing expedition. I might be reading that wrong and I hope that the OP returns to weigh in more.s

    rabid wombat in reply to f2000. | April 2, 2021 at 10:39 am

    From bigskydoc on the previous posting:

    “Just wanted to touch on the question of fentanyl, and overdose threshold. By way of foundation, I’m an anesthesiologist, who administers fentanyl to multiple patients every day. In my career, I have treated many individuals with opiate addiction from mild to quite severe.

    In addicts, the threshold for both the desired effects (pain control, getting high), and undesired effects, like apnea (stopping breathing) go up significantly. Where those new thresholds lie, can be somewhat unpredictable, however.

    Addicts regularly require, and tolerate, doses that absolutely would be lethal to all opiate naive individuals, I’ve had heavily addicted individuals who required 5 to 10 times the dose that a opiate naive patient could tolerate.

    The tricky part is figuring out where their thresholds currently lie. As little as a few weeks of being sober can bring the thresholds low enough that a previously well-tolerated dose becomes fatal.

    I suppose it is also reasonable to point out that the mechanism of death from fentanyl overdose is that it stops people from breathing. If someone is there to take over breathing for the recipient, otherwise lethal doses are well tolerated.”

Correct me if I am wrong, but it seemed like the girlfriend told use about a third time Floyd had overdosed.

With #3 being the fatal overdose, Nelson stated during opening that Floyd was hospitalized after the 2019 traffic stop overdose (#2). Then yesterday, the girlfriend testified that she came home and found Floyd curled up on the ground foaming at the mouth and had to drive him to the hospital (#1). Seems like there is a pattern here. Am I missing something?

    Observer in reply to paralegal. | April 2, 2021 at 11:26 am

    Floyd’s girlfriend, “Mama,” testified that Floyd had taken some pills in March of 2020 (just a couple months before his death) and had a very bad reaction — doubled over in pain, foaming at the mouth, etc., and was in such bad shape that she had had to rush him to the hospital. “Mama” also testified that she had tried the same pills that Floyd had taken. The pills did not have the same effect on her body as her usual opiods (which helped her sleep); the pills made her feel jittery and made her feel like she was going to die. We know the pills Floyd swallowed at the time of his arrest contained more than just fentanyl; they also contained methamphetamine and other substances. We don’t know how many of those pills Floyd ingested in March, but it probably wasn’t anywhere near the number he swallowed at the time of his arrest in May, to keep the cops from finding them. Yet even the presumably much smaller dose in March was enough to make Floyd so sick that he needed to go to the hospital.

    Floyd’s drug dealer has refused to testify, and the state has refused to grant him immunity (which they could easily do, and no doubt would be happy to do, if they believed his testimony would help their case) — which suggests that the state believes that the drug dealer’s testimony would help the defense. Makes one curious about what the drug dealer would say. Would he say that he hadn’t sold Floyd any drugs since before Floyd’s hospitalization in March, until the day of Floyd’s arrest and death in May? Would the dealer admit that some of his other customers had also complained that the fentanyl/meth pills had nearly killed them, like they had also nearly killed Floyd in March (and made “Mama” feel like she was going to die)? Or maybe the dealer even had other customers who had actually died from taking the pills? We’ll probably never know what the drug dealer would have said, but we can be sure it wouldn’t help the state’s case.

      henrybowman in reply to Observer. | April 2, 2021 at 10:03 pm

      “Floyd’s drug dealer has refused to testify, and the state has refused to grant him immunity (which they could easily do, and no doubt would be happy to do, if they believed his testimony would help their case) — which suggests that the state believes that the drug dealer’s testimony would help the defense.”

      Another possibility is that both the state and the dealer now recognize that the dealer is at serious risk of being charged with murder 2 in this incident, and the state isn’t willing to give him immunity for that.

I hope Chauvin’s lawyer has hired good medical experts who can explain this drug tolerance issue to the jury, although judging by their answers during voir dire, some of the jurors seem to be predisposed to vote guilty regardless of what the evidence shows, so it may not matter how good Chauvin’s experts are or how persuasive their testimony is. But hopefully at least some of this exculpatory information will filter through to the general public, even if the jury ignores it.

Street smarts inform addicts that overdoses are the result of higher and higher dosage to get the desired high. Addiction by definition, is the addict chasing but no longer attaining, “the sweet spot” they knew when the first started. Social drinkers know this. When you offer another drink, and they decline. Saying they are “feeling it”. That’s a social drinker. An alcoholic, takes another(s) because ‘more’ is always the answer.
As has been pointed out, tolerance. increases, overtime,the probability of overdose. Any street junkie has seen it happen dozens of times, but his addiction tells him he is different and “knows” how to handle it. Knowing in the back of his mind, his overdose is overdue.

I almost mentioned the narrowed therapeutic window in my post in the other thread. I decided against it because it isn’t as cut and dried as we would like. For newish, and casual users, the window is narrowed, For hard core addicts, the window seems wide open.

I trained in an area where addicts had excellent access to cheap, high potency heroin, as well as pharmaceutical grade, pure, injectable fentanyl. Their systems were capable of tolerating obscene levels of opiates, with seemingly minimal risk of overdose. I recall patients who I would give 2,500 mcg of fentanyl to, for a 15 min procedure. They woukd often wake up asking for more. In my current, opiate naive patients, it is rare to need more than 100 mcg for all but the most painful procedures.

The tricky part is in new addicts, and the addicts that are not using multiple times every day. My hypothesis is that these are the absolute riskiest patients, with the narrowest therapeutic windows. Mr Floyd would fall into this category.

I believe that the threshold for overdose rises at a much slower rate,, and drops at a much faster rate than the therapeutic threshold. Thus, the window is particularly narrowed for new and irregular users.

If I were advising the defense, I would definitely recommend treading lightly on the fentanyl issue. Positioning and restraint worsen the respiratory depression from a fentanyl overdose. Best to just plant seeds of doubt along the way, than give the state an opening to poison the seeds. Of course. IANAL

    fogflyer in reply to bigskydoc. | April 2, 2021 at 1:27 pm

    “If I were advising the defense, I would definitely recommend treading lightly on the fentanyl issue. Positioning and restraint worsen the respiratory depression from a fentanyl overdose.”

    I am sure that is true, but the officers had no knowledge of what drugs Floyd was on, just an assumption that he was high on something. If anything, they probably suspected a stimulant or PCP based on his actions.

    BTW- I really enjoy your medical insight on this forum. Thanks for sharing😁

    JustSayN2O in reply to bigskydoc. | April 2, 2021 at 1:48 pm

    Glad to see I’m not the only one here.

Seems more than enough for reasonable doubt as to the cause of death.

Over the progression of alcohol addiction, tolerance follows a bell curve. In the beginning, tolerance for alcohol is low and increases to a high; i.e. “Drink you under the table.” But as alcohol damages the liver’s capacity to process the chemical, tolerance decreases, and it takes less and less alcohol to get drunk. Does opioid addiction follow the same progression? How many opioid addicts are cross addicted to alcohol?

    NarcDoc in reply to spetrarca. | April 3, 2021 at 1:45 pm

    Although there are many similarities between opioid and alcohol addiction, the course of the diseases can be different. Opioids are not as toxic to the liver as alcohol. Unfortunately, many addicts inject opioids with dirty needles. This can infect them with viruses like hepatitis, which can damage the liver. The end result may be the same: liver dysfunction or liver failure.

    Many opioid addicts are also addicted to other substances, including alcohol.

Methamphetamine can cause mesenteric ischemia, thus explaining Floyd’s severe abdominal pain. This condition can be fatal.

LukeHandCool | April 2, 2021 at 2:10 pm

With the same layman’s caveats as you, I believe this to be spot on.

I draw this conclusion from the experiences of two addicted family members. Both innocently became addicted to opioids. One because he was young and did not know they were addictive (at the time years ago, their addictive danger had not been in the news yet) and they made him feel good for the first time he could remember (anxiety and depression). His tolerance to the “high” grew and he took more and more. But it reached the point where his mother came home one day to find him unconscious on the floor, blue and near death. (He survived.) Now, after over 15 horrible years of addiction, he is clean.

Your brain will crave more and more as you strain to reach a high comparable to those you achieved in your beginning experiences with these drugs, but in search of achieving that satisfying high you will need increasing amounts to the point where your body can’t cope with the toxicity level.

Regarding the testimony that Floyd got addicted because of opioids prescribed for back pain, this belies his numerous previous arrests for cocaine. His addiction spanned many years. Defense suggested Floyd’s pupil dilation could be related to meth, and pills made Ross jittery, not calm. Excited delirium suggests stimulant or combination stimulant/narcotic. Maybe look at how “speedball” can cause death Just because you did not die one time from overdose doesn’t mean you will survive the next or next.

BigSkyDoc cites his personal experience treating opioid users. I have seen the same as an anesthesiologist, and I agree with the analysis. But I don’t agree with his advice to tread lightly on the fentanyl issue.
People who take opioids chronically are playing with fire. The risk of overdose increases over time. This is absolutely relevant to the case. This man was living on the brink of death, for multiple reasons. After seeing the videotapes, and reading about the case extensively, I still don’t know the cause of death.