> the data from the studies included in the aforementioned literature reviews (i.e. General Accounting Office (1993); World Health Organization (2004)) rely on small sample sizes and self-reported data regarding individ- uals’ drug use, and do not typically consider attrition nor spillover effects on those not directly treated. Additionally, many studies use data from Canada, Sweden, or New Zealand to serve as a comparison group for drug rates in the US. Such methods are problematic for addressing causality, given that other developed countries have differing policies on the operations of SEPs and greater access to substance abuse treatment.1 I overcome these existing limitations by cre- ating a novel dataset that combines information on SEP opening dates with restricted administrative county-level data on HIV diagnoses. These data proxy for drug use without relying on self-reporting behavior, and are representative of counties across the US.
It’s using newly-opened SEPs for a discontinuity analysis, which does provide evidence of causation (and furthermore notes that previous studies were correlational).
Your parent comment said they expected counties facing a crisis to open SEPs. That would be a newly opened SEP caused by drug deaths. So how does using newly-opened SEPs for discontinuity analysis make any sense at all?
It was linked elsewhere in the thread, but here it is: https://apackham.github.io/mywebsite/opioidpaper_webcopy.pdf
Emphasis on seemed. I started with "I'm probably missing something" because I haven't studied anything relevant .
> And finally, even if the causation is correct, all it indicates is that needle exchange programs need to also provide drug testing capabilities so the presence of fentanyl can easily be identified.
This assumes that there are no individuals that are knowingly injecting fentanyl or that a drug user would not take drugs in their possession if they knew it contained fentanyl. Yes, there are individuals that unknowingly take a fentanyl containing substance but I am doubtful that those deepest in opioid addiction avoid it.
https://www.sciencedirect.com/science/article/abs/pii/S09553...
The Economist predisposes it’s readers to believe that this indicates needle exchange programs are bad, as opposed to leaving open the possibility that due to changing circumstances needle exchange programs which have proven to be extremely successful, also need to adapt, much like every other individual, program, company or non-profit at any time.
That being said, a needle exchange program could always require the testing of fentanyl and if fentanyl is found decline service.
So the people who apparently want fentanyl and are encouraged by the needle exchange programs would not have them as an incentive anyways.
I don't understand why doctors are still so quick to prescribe opioids.
In the heavier cases, a flap of gum tissue and covering jaw bone are cut away to expose a submerged tooth that is oriented the wrong way. The tooth is then demolished in place so that the chunks can be lifted out. The patient would be sedated during this procedure, and the wound and recovery period is significantly different.
Went from fine one day with the caveat that one day I'd need oral surgery to have them removed, to burning with a fever while finding an oral surgeon ASAP.
Needed invasive oral surgery. Had to be put under twice-once before operation, and once when bringing me out after, as I had a paradoxical reaction and was thrashing about. Me screaming I didn't know the surgeon and anesthesiologist and thrashing about isn't super good after oral surgery.
Hurt like the dickens afterwards and had to eat soup for a good while.
They gave me ibuprofen and tylenol with codeine afterwards. I only used the ibuprofen and was fine. It only blunted the pain but was definitely manageable after the first day or so.
I've had doctors try and prescribe narcotics for some weird things. I've always denied them as I had a friend who became addicted to heroin after being prescribed oxys for serious 3rd degree burns.
Every time I have to deny narcotics multiple times before they relent and offer something non-narcotic.
Anyways just one person's experience.
I got no opioid painkillers during or after. It horrifically painful for about a week, but I could drink fluids and the wound healed well, so just acetaminophen and ibuprofen. The attitude of doctors and dentists to short term pain here seems to be mostly that if it's not so severe the person is driven to self-harming behaviours as a consequence, then just deal with it. I can see the wisdom in that, so to speak, but oh it was miserable for a few weeks.
Especially not if you haven't first tried if Ibuprofen or Tylenol/Paracetamol or one of a dozen other mostly harmless painkillers do the trick.
So from my perspective, as a very acute surgical drug, it would seem to be a great innovation, but it's probably not something you want to use to relax after a tough day at the office.
Users often have preferences for which is most pleasurable, but nobody would say fentanyl doesn’t get you high.
https://en.wikipedia.org/wiki/Endorphins
> "Endorphins are released from the pituitary gland, typically in response to pain, and can act in both the central nervous system (CNS) and the peripheral nervous system (PNS). In the PNS, β-endorphin is the primary endorphin released from the pituitary gland. Endorphins inhibit transmission of pain signals by binding μ-receptors of peripheral nerves, which block their release of neurotransmitter substance P. The mechanism in the CNS is similar but works by blocking a different neurotransmitter: gamma-aminobutyric acid (GABA). In turn, inhibition of GABA increases the production and release of dopamine, a neurotransmitter associated with reward learning."
All that matters is that the drug molecule binds to the receptor proteins in the brain and peripheral nerves. Studies show that the active dose is directly related to the binding strength of that specific molecule (fentanyl binds more strongly than heroin, so less is needed to get the same effect, oxycontin is about as strong a binder as heroin, about twice as potent as morphine).
Overdose deaths are generally due to (1) unusually high concentrations of active substances or (2) Users who've lost tolerance for some reason taking too much.
Legalization would likely eliminate most accidental overdose deaths as products would be clearly labeled as to contents.
Opioids aren’t pure mu-agonists, they also have sigma agonists effects which produce non-opioid effects and also have off effects (histamine release). Combine that with the onset and duration of action, users can definitely tell if they got fentanyl versus say morphine. But not really between heroin and morphine.
As neuropharmacology and biology remain fields of active investigation, there are several other putative opioid receptors which aren't characterized very well at all but probably have some relevance. Diverse multiple-receptor heteromers are beginning to demonstrate pharmacological relevance (e.g. different binding profiles at mu-delta heteromers) and also at other protein-protein interaction sites (e.g. some drugs inhibit arrestin recruitment and activity dependent receptor internalization).
Also the pharmacokinetics/dynamics matter, things like the central/peripheral availability (e.g. how much constipation) and speed of availability to CNS. Metabolites may be psychoactive or may affect metabolism of the primary drug.
Off-target activity is present in everything and may be meaningful especially in some analogues (e.g. pethidine has significant dopamine transporter inhibiton) or in plant-derived morphine/heroin which comprise a complex mixture of compounds with diverse activities).
All of these things color the subjective experience of a drug. There is not much study made of subjective qualia because the models to describe this sort of thing are not very nuanced or descriptive, but more because it is not very relevant to clinical clinical practice. However, people who use tons of these drugs all the time do report subjective differences along dimensions such as "speediness", sedation, euphoria, "rushiness", malaise, therapeutic index, timecourse, etc. For example a user might report "Compared to heroin, oxycodone feels more energetic, while fentanyl has a nice initial rush but is much more sedating and wears off quicker", stuff like that.
TL;DR in vitro mu-opioid activity is not sufficient to explain objective or subjective variance between opioid drugs, and like much other biology there is much work to be done for all the nuance to be well understood.
And the correlation can very easily be backwards. In fact, its more likely backwards.
Counties which are facing an increasing barrage of opioids and all the issues related to it, especially spread of disease and an increase in deaths due to unsafe use are almost certainly more likely to create safe needle exchanges.
For the economist to write this article as if causation is established, and further to moralize is insane.
Especially since the Economist famously doesn’t provide bylines so this becomes the official view of the magazine as opposed to a specific editor’s.
And finally, even if the causation is correct, all it indicates is that needle exchange programs need to also provide drug testing capabilities so the presence of fentanyl can easily be identified.