Also, I know it's just AI and that AI can be wrong, but ChatGPT is saying that studies on mice have shown that SR-17018 produced dependence and respiratory depression in mice, so if that were actually true for people also then that wouldn't make it such a miracle drug at all. I don't know if I can really trust the anecdotes here that it can just magically get rid of opioid WD while itself acting as an opioid but not having any negative side effects:
Me: Is there any real proof that it can lead to respiratory depression or dependence? Have mice experienced either?
AI: Good question—and this gets at why biased agonism drugs like SR-17018 attracted attention in the first place.
What makes SR-17018 different?
SR-17018 is a
μ-opioid receptor agonist, but it was designed to favor
G-protein signaling over β-arrestin pathways. Early theory suggested that might:
preserve pain relief
reduce side effects like
respiratory depression
Respiratory depression: what’s actually been shown?
In mice:
Studies
did measure breathing effects
Compared to classical opioids like morphine:
SR-17018 caused
significantly less respiratory suppression
At equianalgesic doses, it showed a
wider safety margin
BUT:
It
still produced measurable respiratory depression at higher doses
It was
not completely “respiratory-safe”
So the evidence suggests:
Reduced risk ≠ no risk
Dependence and tolerance
In mice:
There
is real evidence here.
Tolerance:
Much
less tolerance develops compared to morphine in some pain models
Especially in
hot plate (supraspinal) pain tests
However, tolerance
still appears in other contexts (e.g., spinal reflex models)
Dependence:
Mice given chronic SR-17018
do show signs of physical dependence
This is typically tested by precipitating withdrawal with naloxone
Withdrawal signs were:
present
but often
less severe than morphine
Big picture from animal data
Across studies, SR-17018 shows a consistent pattern:
Strong analgesia
Reduced respiratory depression vs morphine
Reduced (but not eliminated) tolerance
Still causes dependence
Still causes respiratory depression at sufficient doses
Important reality check
Even though results look promising in mice:
Many “safer opioids” (including other biased agonists)
failed in humans
The relationship between β-arrestin signaling and breathing suppression is
more complex than originally thought
No human trials =
no confirmed safety profile
Bottom line
There
is real experimental evidence in mice showing:
Respiratory depression: yes, but less than morphine
Dependence: yes, clearly demonstrated (though somewhat reduced)
So SR-17018 isn’t a “non-addictive” or “non-respiratory-depressant” opioid—it’s more accurate to think of it as:
a
potentially improved, but still fundamentally opioid-like compound
If you want, I can compare it to other “next-gen opioids” (like oliceridine) to show how this whole class has held up in real-world use.
Me: Is it even an opioid or does it just get rid of opioid withdrawal which is what I've heard? Does it kill pain by itself?
AI: This is where a lot of confusion online comes from—what you’ve heard has a
kernel of truth, but the interpretation is off.
“How can it be an opioid if it reduces withdrawal?”
Because
that’s exactly what opioids do.
Drugs that activate the μ-opioid receptor—like:
morphine
heroin
methadone
buprenorphine
…can all
suppress withdrawal symptoms from other opioids.
Why?
Withdrawal happens when the receptor is suddenly
not activated.
If you give another drug that
activates the same receptor, withdrawal symptoms go away.
So if SR-17018 reduces withdrawal, that’s actually strong evidence that:
it behaves like an opioid at the receptor level
Does SR-17018 relieve pain on its own?
Yes—
in animal studies, it is a potent analgesic.
Produces strong pain relief in mice (tail-flick, hot plate tests)
In some cases,
comparable to morphine
Effects are
blocked by naloxone, which confirms:
its pain relief is mediated through opioid receptors
So it’s not just a “withdrawal helper”—it’s a
true opioid analgesic.
Why people think it’s “different”
SR-17018 was designed with biased agonism in mind:
It still activates the μ-opioid receptor
But it
biases signaling toward pathways thought to cause:
pain relief
less tolerance
less respiratory depression
That led to claims like:
“non-addictive opioid”
“no respiratory depression”
“withdrawal-free”
But animal data doesn’t support those extreme claims:
It
still produces dependence
It
still can cause respiratory depression
It
still acts like an opioid overall
Why it might
Compared to some traditional opioids, it may:
produce
less euphoria
cause
less rapid tolerance in certain pathways
So users sometimes report:
smoother effects
fewer “ups and downs”
But mechanistically, it’s doing the same core thing:
activating the μ-opioid receptor to stabilize the system
Bottom line
SR-17018
is an opioid because it activates the same receptor as morphine
It
does relieve pain on its own (in animal models)
It can
reduce withdrawal—but that’s a typical opioid effect, not a contradiction
The key misconception is this:
“Reduces withdrawal” doesn’t mean “not addictive”
It usually means
“functions like an opioid substitute”
If you want, I can break down how it compares specifically to buprenorphine—that comparison helps clarify
why some drugs reduce withdrawal with less abuse potential.
Me: no. I've heard people say it does not produce dependence so i think you might not have solid proof that it does or doesn't
AI: It’s fair to question that—because the claims online about SR-17018 are
much stronger than what the data actually shows.
What counts as “proof” of dependence?
In research (especially with opioids), scientists don’t rely on opinions—they use standard tests:
Chronic dosing (give the drug repeatedly)
Then trigger withdrawal with naloxone
Look for physical withdrawal signs (jumping, tremors, weight loss, etc.)
If those appear → that’s
physical dependence
What happened with SR-17018 in mice?
Studies that did exactly this found:
Mice given SR-17018 chronically
did show withdrawal signs when naloxone was given
The withdrawal was:
real and measurable
often
less severe than with morphine, but still present
That’s the key point:
It did
not eliminate dependence—it
reduced its severity in some comparisons.
So why do people say “no dependence”?
A few reasons:
1. Misinterpretation of “less” as “none”
Because SR-17018 showed:
less tolerance in some tests
milder withdrawal signs
People simplified that into:
“no dependence”
which isn’t what the data actually says
2. Early hype around biased agonism
There was a big theory that these drugs could:
keep pain relief
remove side effects like dependence
That idea has
not fully held up, even beyond SR-17018.
3. Anecdotal reports ≠ controlled evidence
Human claims online:
aren’t controlled
vary wildly (dose, purity, tolerance, expectations)
So they can’t override controlled animal data.
What we can say with confidence
Based on actual experiments:
SR-17018 activates the μ-opioid receptor
It produces analgesia (pain relief)
It produces
physical dependence in mice
Dependence may be
less severe than morphine in some conditions
There is
no solid evidence it eliminates dependence
Important nuance
“Less dependence” can still be meaningful scientifically—but it’s very different from:
“non-addictive” or “no withdrawal”
And without human trials, we don’t know:
how strong dependence would be in people
how it compares clinically to drugs like buprenorphine or methadone
Bottom line
There
is controlled experimental evidence, and it shows:
SR-17018
can cause dependence (in mice), just not necessarily to the same extent as traditional opioids.
So the claim “it doesn’t produce dependence” isn’t supported by the available data—it’s an
overstatement of more modest findings.
If you want, I can point to the exact study designs and what withdrawal behaviors they measured—that makes it clearer how strong (or weak) the effect really is.
only if you can explain it as simply and briefly as possible. Also, if something shows dependence in mice does that mean that it will in humans? And what withdrawal effects did it produce in mice?
Got it—here’s the
simple, no-fluff version:
Did studies actually show dependence?
Yes (in mice).
How they tested it:
Give SR-17018 repeatedly
Then give naloxone (which blocks opioids)
See if withdrawal happens
Withdrawal did happen, which =
physical dependence
What withdrawal signs did mice show?
Typical opioid-type signs, including:
Jumping
Tremors / shaking
Paw tremors
Teeth chattering
Weight loss / stress signs
These were
real but generally milder than with morphine
Does “dependence in mice” mean it will happen in humans?
No—but it’s a strong warning sign.
Not guaranteed
But very likely if:
same receptor is involved (it is)
same drug class (opioid)
In practice:
Almost every drug that causes opioid dependence in animals
also does in humans
Bottom line
SR-17018
did produce dependence in mice
Withdrawal signs were
clear but somewhat less severe than morphine
Animal results don’t guarantee human effects—but here, they
strongly suggest it would still be dependence-forming
If you want it even tighter:
It behaves like a **“somewhat milder opioid,” not a dependence-free one.
Me: Ok, but could we eventually find out that it really doesn't produce dependence or respiratory depression in humans if there are already people saying it hasn't for them?
AI: Short answer:
it’s very unlikely—but not impossible—that it turns out to have no dependence or respiratory depression in humans. The current evidence points the other way.
Why anecdotes aren’t strong evidence
People saying “I didn’t get withdrawal” or “it didn’t affect my breathing” can happen because:
Short use → dependence hasn’t had time to develop
Low or inconsistent dosing
High opioid tolerance already
Unreliable product purity/identity
Subjective perception (withdrawal and breathing effects aren’t always obvious)
So individual reports ≠ proof of absence
What the science suggests
SR-17018 activates the
same μ-opioid receptor as morphine
In animals, it:
causes dependence (withdrawal appears with naloxone)
can depress respiration at higher doses
That puts it firmly in the “opioid-like risk” category.
Could humans be different?
Technically yes—but here’s the realistic view:
We’ve studied many “safer opioids” based on biased agonism
None have turned out to be:
non-addictive AND non–respiratory-depressant
Even drugs designed to be safer (like buprenorphine) still:
cause dependence
can suppress breathing (just with a ceiling effect)
What would have to be true for it to be “risk-free”?
For SR-17018 to truly have
no dependence or respiratory depression, it would need to:
Activate opioid receptors
without triggering adaptation (dependence)
Provide analgesia
without affecting brainstem breathing centers
So far, no drug has cleanly achieved both in humans.
Bottom line
Anecdotes can’t rule out risks
Animal data + pharmacology strongly suggest:
it would still cause dependence and respiratory depression in humans
The most realistic best-case scenario:
“less than traditional opioids,” not “none at all”
