5 Facts About Tianeptine You’ve Never Heard Of
Tianeptine sodium is a novel antidepressant used in Europe. It’s a pretty interesting drug, pharmacologically speaking. Since tianeptine is unregulated in the US and elsewhere, it’s increasingly being used for mood enhancement by individuals who experiment with nootropics.
Here are five facts about tianeptine that you may not be aware of. Some of these claims are controversial; I’m sure there are some nootropics enthusiasts out there who would completely disagree with me. Bearing that in mind:
1) Tianeptine is a tricyclic without typical tricyclic side effects
In terms of chemical structure, tianeptine is a tricyclic antidepressant (TCA). But it doesn’t behave like one at all.
The reason SSRIs were developed as antidepressants in the first place is because of TCA’s harsh side effect profile. Tricyclics are anticholinergic - they elicit constipation, dry mouth, orthostatic hypotension, amnesia - and other nasty effects of blocking the parasympathetic nervous system.
TCA’s are also cardiotoxic (bad for the heart); they can cause QT prolongation. Not so with tianeptine! For one reason or another, tianeptine is technically a tricyclic but mysteriously lacks these side effects.
2) There’s a lot of bogus information about tianeptine floating around
Tianeptine was originally thought to “work” (relieve depression) by enhancing serotonin uptake. Tianeptine was dubbed a selective serotonin reuptake enhancer. This is precisely the opposite effect that SSRIs have - they inhibit serotonin reuptake, which globally elevates serotonin levels. So the antidepressant effect of tianeptine was cited as a reason to reject the “neurotransmitter imbalance” theory of depression (also called the monoamine hypothesis).
The truth is, tiaeptine either isn’t a selective serotonin reuptake enhancer, or if it is, this effect is negligible and doesn’t contribute to its clinical efficacy. It was just a red herring all along!
3) Tianeptine binds to the same receptor as heroin in the brain
Tianeptine is a full agonist at mu-opioid receptors. Likewise, heroin’s euphoriant properties is also attributed to mu-opioid binding.
Activation of mu-opioid receptors suppresses GABA inputs to dopaminergic neurons. Recall that GABA is an inhibitory neurotransmitter. So if you inhibit an inhibitory signal you end up activating dopaminergic neurons. This results in dopamine release in the ventral tegmental area (VTA), eliciting euphoria. It’s likely that the antidepressant effects of tianeptine are related to its opiate effects. There are obviously much safer and more sustainable ways to boost dopamine than heroin. This post about dopamine supplements is a good place to start your research.
4) The claim that “Tianeptine works by reversing stress-induced impairments in neuroplasticity” is neurobollocks
Neuroplasticity is a dirty word in neuroscience:
The latest refrain in popular science is that ‘your brain is plastic’, that experience has the potential to ‘rewire’ your brain, and that many previous mysteries in cognitive science can be explained by ‘neuroplasticity’. What they don’t tell you is that these phrases are virtually meaningless.
Moreover, if tianeptine does rescue impaired neuroplasticity - this observation does not constitute a mechanism of action. It’s an epiphenomenon that doesn’t give us any more information about the drug works. If lesioning the brain with radiation or drugs made circuits more plastic - would we assume that’s a good thing?
5) Tianeptine is (arguably) not really a nootropic
Here’s the definition of a nootropic from Examine:
Many supplements that are touted to increase cognition, focus, alertness, or well being are grouped under this vague blanket statement.
There’s pretty convincing evidence that the antidepressant efficacy of tianeptine are comparable to SSRIs and typical tricyclic antidepressants (TCAs). But there’s no solid empirical evidence that tianeptine enhances mood in euthymic individuals. Moreover, it’s unclear that the umbrella term “nootropic” should include mood enhancers. Strictly speaking, aren’t nootropics cognitive enhancers? I can think of a few relatively benign drugs that can elicit euphoria but aren’t regarded as nootropic.