Comment · Wed, February 11, 2026 · Natrium Health & Nootropics Depot
The story behind the FDA raid of Nootropics Depot
What they were answering
RarageInTheGarage · 3 points
A lot of other tricyclic antidepressants also have opioid affinity, as it turns out. Some friends of mine with neuropathic pain were prescribed certain TCA's for just that reason.
u/MisterYouAreSoDumb · Natrium Health & Nootropics Depot
Well the opioid affinities for some of the TCAs are delta and kappa opioid receptors, not mu opioid. Even then, they are low affinities.
https://pubmed.ncbi.nlm.nih.gov/19828880/
At the cloned mu-opioid receptor, TCAs showed low affinity and no significant agonist activity. These results show that TCAs differentially regulate opioid receptors with a preferential agonist activity on either delta or kappa subtypes and suggest that this property may contribute to their therapeutic and/or side effects.
Tianeptine is a full agonist at the mu opioid receptor, which is what is causing all the problems with abuse. Even so, it does not cause respiratory depression in the same way other mu opioid agonists, which makes it safer than other opioid agonists like oxycodone. Tianeptine's AMPA receptor modulation likely counteracts some of that effect. I do think extremely high doses do tip the scales, though. Some people were taking insanely high doses, and even IVing it, which likely can push it past the bell curve of the AMPA modulation and let the respiratory depression take over. It's really hard to say, because almost every single case report out there found other drugs in their system at the time. The only one that seems to have only seen tianeptine in their system was a 2018 case report.
https://pubmed.ncbi.nlm.nih.gov/29566235/
However, there is not a lot of information there, and the blood concentration they found was nowhere near what it would take to cause death. So I am still suspicious that it was caused by tianeptine. Once people started putting it in shots in gas stations with synthetic 7-hydroxymytraginine, phenibut, and other undisclosed substances, and then news agencies gave it name gas station heroin, it became more demonized. But let's look at the numbers. From the year 2000 to 2017, there were 218 total reported tianeptine exposure calls in the US. That's around two hundred total cases in 17 years! Respiratory depression was reported in only 5% of those cases, and not a single death among the 114 tianeptine-only exposures. This is all from the CDC/NPDS. Now let's look at acetaminophen.
There are between 56,000 and 80,000 hospitalizations EVERY YEAR from acetaminophen, with 150 to 500 deaths per year. That means in the same time period where there were 218 reported total tianeptine adverse event reports, there were between 952,000-1,360,000 hospitalizations and 2,550-8,500 deaths from acetaminophen overdose. That's just from over the counter Tylenol. Now I am not saying tianeptine abuse isn't something to be concerned about, but things need to be put into proper context. There is no way for me to know this, but with the experience I have had with depression and suicide, and the people that I have spoken to over decades, I would bet more people have died from suicide after losing their access to tianeptine than have died from all tianeptine related deaths. There are 45,000-50,000 suicides in the US every single year. That's one suicide every 11 minutes of the day, every day of the year. Look at the clock, and just mentally put ticks off on every 11 minutes of the hour. That's one American taking their own life. From the year 2000 to the year 2017, more than 650,000 people took their own life in the US. 218 total CDC reports for tianeptine complications, 114 were tianeptine-only, 0 tianeptine-only deaths... but over 650,000 deaths from suicide.