The Food and Drug Administration has not approved tianeptine for use in the United States; however, it is readily purchased in elixir formulations online or at gas stations informally referred to as “gas station heroin” - from reference 1
That brings me to the latest gas station intoxicant – tianeptine.
It was originally intended to be an antidepressant based on a very general tricyclic structure. I made the graphic below for a rapid
structural comparison with standard tricyclic antidepressants (nortriptyline)
and selective serotonin reuptake inhibitors (escitalopram). It is obviously not
structurally like either class of compounds and has a unique moiety – the 5,5
dioxo structure on the central cycloheptane ring.
|
NET |
SERT |
DAT |
5-HT2A |
5-HT1A |
MOR |
tianeptine |
- |
>10,000 |
>10,000 |
>10,000 |
>10,000 |
383 nM |
nortriptyline |
1.8 nM |
15 nM |
1,140 nM |
294 nM |
5 nM |
|
escitalopram |
6,514 nM |
1.1 nM |
>10,000 |
>10,000 |
>10,000 |
|
A recent CDC report (1) describes a spike in tianeptine ingestions and complications due to contamination from synthetic cannabinoid receptor agonists (SCRAs) between June and November 2023. Fourteen of the 17 exposure calls involved patients drinking an elixir called Neptune’s Fix – a mixture of tianeptine and kavain or Piper methysticum root. Six of the patients ingested other compounds including benzodiazepines, Kratom, trazodone, tramadol, and gabapentin. Nine had previously used tianeptine. Thirteen of the 17 patients were admitted to intensive care units (ICU) and 7 required intubation and ventilatory support. There were cardiovascular complications including conduction abnormalities, hypotension, tachycardia, and a cardiac arrest. All the patients had altered mental status.
Six samples of the Neptune’s Fix preparation from 2 of the patients were analyzed by gas chromatography-(GS-MS) and compared with a standard database of compounds of interest. All of the bottles were labelled tianeptine and kavain. Two of the samples contained THC and CBD. Two of the samples contained the SCRAs ADB-4en-PINACA and MDMB-4en-PINACA.
The overall message of the report is that tianeptine preparations
available as unregulated preparations can potentially be addictive and may
contain adulterants that can produce severe adverse effects requiring resuscitation
or ICU admission. This has been noted in
previous literature about SCRAs including severe psychiatric effects. There have been 144
synthetic cannabinoids identified since 2014. In some circles these compounds are referred
to as JWH compounds after the organic chemist who first synthesized and
researched them.
The way that tianeptine is described in the literature seems
to parallel the interests of the authors.
The FDA references are uniformly negative because they are focused on
severe side effects including death and addiction. Authors who are interested
in the opioidergic system in depression will describe how it is a legal antidepressant
in several countries and minimize both potential addiction and severe side
effects. Either way it maps well onto the current American pro-drug culture.
The sheer number of new intoxicants and widespread access to these intoxicants
is staggering. Hundreds of new compounds in the past ten years. Addictive compounds readily available at gas
stations? Those compounds laced with
additional problematic intoxicants? The so-called War on Drugs is obviously non-existent at this time.
One of the questions I always get from people in response to
posts about contaminated, adulterated, and counterfeit intoxicants is why? Why would drug dealers or semi-legitimate
businesses want to kill off or injure their customers? What is their motivation? The most obvious one
is that they don’t care. There always
seems to be a significant number of people out there interested in a new or
higher high so demand is never a problem.
The second is marketing. In a previous
post I described a case where fentanyl was being pressed into tablets that
looked like Xanax bars and the purchasers were not only aware of that but preferred
to purchase those tablets even after directly observing them being made. A third
possibility is ignorance. People looking to find intoxicants and sell them on
the street are not medicinal chemists – even though they may talk like it. Some
of these compounds vary in potency by a factor of a hundred or a thousand. The fourth is a lack of accountability. Even the most cynical conceptualization of
the pharmaceutical industry recognizes the fact that the products are approved,
manufactured, and monitored according to standards. Manufacturers are subject
to regulatory bodies, criminal and civil liability, and accountability at the business
level from a board of directors and at the shareholder level. It is fairly easy
to find that the industry has paid tens of billions of dollars in civil and
criminal penalties over the past 30 years. None of these incentives applies at
the level of small companies marketing unapproved but unregulated drugs or
street sales of illicit drugs. For that matter it probably also does not apply
at the level of legal cannabis dispensaries. Even though legally prescribed and
regulated medications have risks – unregulated and street drug risk is much
higher. As demonstrated in this post
that risk starts with what is really in the bottle complicated by even higher
risk adulterants.
I always think of the former President of Mexico Vincente
Fox in these situations. When asked
about the American drug problem and the involvement of Mexico he characterized
the problem as “America’s insatiable appetite for drugs.” When I think about people going into a gas
station and buying Neptune’s Fix or Kratom or Delta-10 THC and not really
knowing what they are getting in the bottle – he can’t be wrong.
George Dawson, MD, DFAPA
Supplementary:
On not caring that I mentioned in the above post. I think there is a case to be made that the
same attitude can fuel legitimate retail sales of drugs that reinforce their
own used including alcohol, cannabis, and tobacco. Increasing liquor stores will increase
alcohol consumption by increasing access.
That increased access comes with smaller distances to liquor stores, home delivery, placing
liquor stores in proximity to other retail stores and supermarkets, and the
commoditization of alcohol – you will always be able to find a cheaper drink.
Since a significant portion of any population are problematic drinkers all this
increased access directly impacts them. The people that create all this access,
typically argue that the intoxicants are legal, they run a legitimate business,
and not creating all this access puts them at a disadvantage compared to other
sellers. That argument leaves out the significant
morbidity and mortality associated with alcohol and ironically that argument is
typically used when advocates are trying to legalize another intoxicant as
in: “Our new intoxicant is not as
dangerous or lethal as alcohol.”
1: Counts CJ, Spadaro
AV, Cerbini TA, et al. Notes from the Field: Cluster of Severe Illness from
Neptune’s Fix Tianeptine Linked to Synthetic Cannabinoids — New Jersey,
June–November 2023. MMWR Morb Mortal Wkly Rep 2024;73:89–90. DOI: http://dx.doi.org/10.15585/mmwr.mm7304a5.
2: El Zahran T,
Schier J, Glidden E, et al. Characteristics of Tianeptine Exposures Reported to
the National Poison Data System — United States, 2000–2017. MMWR Morb Mortal
Wkly Rep 2018;67:815–818. DOI: http://dx.doi.org/10.15585/mmwr.mm6730a2
3: Samuels BA,
Nautiyal KM, Kruegel AC, Levinstein MR, Magalong VM, Gassaway MM, Grinnell SG,
Han J, Ansonoff MA, Pintar JE, Javitch JA, Sames D, Hen R. The Behavioral
Effects of the Antidepressant Tianeptine Require the Mu-Opioid Receptor.
Neuropsychopharmacology. 2017 Sep;42(10):2052-2063. doi: 10.1038/npp.2017.60.
Epub 2017 Mar 17. PMID: 28303899; PMCID: PMC5561344.
4: Nobile B, Ramoz N,
Jaussent I, Gorwood P, OliƩ E, Castroman JL, Guillaume S, Courtet P.
Polymorphism A118G of opioid receptor mu 1 (OPRM1) is associated with emergence
of suicidal ideation at antidepressant onset in a large naturalistic cohort of
depressed outpatients. Sci Rep. 2019 Feb 22;9(1):2569. doi:
10.1038/s41598-019-39622-3. PMID: 30796320; PMCID: PMC6385304.
5: Wikipedia contributors. Nortriptyline. Wikipedia, The
Free Encyclopedia. December 20, 2023, 17:01 UTC. Available at: https://en.wikipedia.org/w/index.php?title=Nortriptyline&oldid=1190922632
Accessed February 4, 2024. Wikipedia table was used for nortriptyline because
the PDSP database was no longer working.
6: Jelen LA, Stone
JM, Young AH, Mehta MA. The opioid system in depression. Neurosci Biobehav Rev.
2022 Sep;140:104800. doi: 10.1016/j.neubiorev.2022.104800. Epub 2022 Jul 30.
PMID: 35914624; PMCID: PMC10166717.
7: FDA. Tianeptine Products Linked to Serious Harm,
Overdoses, Death. https://www.fda.gov/consumers/consumer-updates/tianeptine-products-linked-serious-harm-overdoses-death
8: FDA. Tianeptine in Dietary Supplements. https://www.fda.gov/food/dietary-supplement-ingredient-directory/tianeptine-dietary-supplements
9: FDA. FDA warns consumers not to purchase or use
Neptune’s Fix or any tianeptine product due to serious risks. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-consumers-not-purchase-or-use-neptunes-fix-or-any-tianeptine-product-due-serious-risks
Very informative post about this problem. Neptune's Fix is illegal in several states and you can find a list on some web pages. I wonder how states enforce the law?
ReplyDeleteGood question Jim. I would be interested in seeing the state by state illegal drugs list. Just considering the 2 drugs on my gas station window:
DeleteKratom - is illegal in WI, IN, AR. AL, VT, and RI. It is legal by the Kratom Consumer Protection ACT (KCPA) in NV, UT, AZ, and GA. It is unregulated in the remaining states.
Delta-10 THC - is illegal in AK, AZ, AR, CO, DE, ID, IA, MS MT, RI, UT. It is legal and unregulated in remaining states.
My speculation is that the current increasing list of unregulated intoxicants greatly exceeds any state by state regulations.
George, excellent piece and too scary for words! Thanks, Bob Geist
ReplyDeleteThanks Bob!
DeleteWe the people of the US have the resources to buy a lot and in some cases most anything. Sadly, we seem to also be interested in the "low hanging easy fruit", which in my opinion isn't always the best for us and in some cases can be rotten... In general I believe this is reflective of our society being in pain. Sadly, these things are a quick short term fix, which sadly turn into other problems and even more pain... Don't know how to fix this but good to be aware of it and stay away from places of this nature. On another note. I wonder your opinions on the recent increase in the use of psychedelics? (https://www.npr.org/sections/health-shots/2024/02/06/1229298615/psilocybin-magic-mushrooms-drug-bust ) What is going on here? I guess it depends. In some cases I have heard it promotes positive brain health while others its a recreational fascination?
ReplyDeleteWe are in the midst of a long term drug epidemic with no end in sight. Alcohol was promoted for decades as a glamorous drink rather then a cause of cancer, cirrhosis, and pancreatitis. It was promoted as a "heart healthy" beverage based on faulty research. It is currently promoted as a designer beverage by wealthy Americans with their own brands. We have witnessed at least a decade of promoting cannabis as something "medical" even though now it appears that there are minimal to no medical applications. Psychedelics are the next wave even though the clinical trials are problematic (subjects can correctly guess whether they get placebo or not) and side effects appear to be minimized. I wrote about this in the following post:
Deletehttps://real-psychiatry.blogspot.com/2016/06/are-hallucinogens-new-miracle-drugs.html
The only conclusion that come to is that Americans are easily duped into thinking that drugs will improve them in some way and that they don't have to worry about side effects. I doubt that happens in any significant way. I have had to treat people for persistent side effects after psychedelic/hallucinogen use and it is generally a difficult to treat persistent problem.