Comment · Sun, November 2, 2014 · Ceretropic
physiological opiate tolerance & dependence on Tianeptine?
Original post in this thread
crabcakebenny · 9 points
starting taking it 3x daily. This seems like a recipe for absolute disaster since it's a mu-opiod agonist. what's the consensus on this? plenty of people seem to use it chronically w/o problems.
What they were answering
Direct reply to the original post — see the thread post above.
u/MisterYouAreSoDumb · Ceretropic
It is a very mild μ-opioid agonist (Ki Human of 383±183 nM, and EC50 Human of 194±70 nM, and EC50 Mouse of 641±120 nM for G-protein activation). That is not its main mechanism of action, and only really comes into play in higher dosages.
Tianeptine's main actions are modulating the glutamate receptors in the CA3 region of the hippocampus. It's essentially a signal transduction modulator between the various types of glutamate receptors; normalizing the scaling of the amplitude ratio of NMDA receptor to AMPA/kainate receptor-mediated currents. It also increases the presynaptic uptake of serotonin out of the synapse by the SERT. This does not seem to be the primary mechanism, though. And tianeptine is often administered along side SSRIs for treatment-resistant depression. Nevertheless, it is a mediating factor. Tianeptine also increases BDNF in various brain regions. This is where the neurogenic effects come from, and has become a big focus recently with SSRIs, as they also increase BDNF after a few weeks of treatment. Tianeptine has been shown to prevent stress-induced neuroplastic remodeling in the hippocampus. This is most likely due to the glutamate modulation, and due to the increased BDNF. And yes, tianeptine has minor opioid affinities. However, the main nootropic and antidepressant effects are not due to the interaction with the opioid receptors, or we would see more powerful opioids causing the same neurogenetive and antidepressant effects that tianeptine does. Could it be adding some minor antidepressant effects, or increasing the withdrawal for some? Perhaps. But it has 3 times less affinity for the μ-opioid receptors than codeine, which is over the counter in much of the world. It has over 50 times less affinity than kratom. If the effects were due to μ-opioid affinities, we would be seeing much better antidepressant effects in these substances.
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Here are some pKi values for real μ opioid agonists:
7-hydroxymitragynine (Kratom)- 8.01 nM
Morphine- 4.55 nM
Methadone- 3.16 nM
Naltrexone- 0.39 nM
Oxycodone- 23.4 nM
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Stick to the 12.5mg dosage, and you will be fine.