Benzos Temazepam: euphoria decreases with dosage?

[Memantine]

I have been using Temazepam on and off for a few months now. I noticed that 20mg clearly gives me a euphoric mood. However when I upped my dose to 60mg the intoxication increased but the euphoria didn't. I actually got a depressive episode on 60mg one time.

I think this is odd because Alprazolam did exactly the opposite. A low dose Alprazolam makes me dull and a high dose gives me euphoria.


Are there more people that notice such differences between benzodiazepines?

 

[keeping]

benzo euphoria is such a disputed topic that you're highly unlikely to get a solid answer, i myself have only experienced 'euphoria' from benzos when being administered IV midazolam in the middle of a panic attack. i think the 'euphoria' was purely the relief from trauma, not actual euphoria/

 

[Memantine]

Well there is theoretical ground for the euphoria of benzo's. The α1 subunit containing GABA-A receptor is expressed on GABA-interneurons in the ventral tegmental area(VTA) projecting on dopaminergic neurons projecting on neurons in the nucleus accumbens(reward centre). By specifically inhibiting these interneurons the dopaminergic neurons(VTA) lose their GABA mediated inhibition and start to excite and release larger ammounts of dopamine onto the nucleus accumbens.

The mechanism of action is similar to the action of opioids. The μ opioid receptor is also expressed on GABA interneurons in the VTA. Their activation also leads to hyperpolarization of the neuron.




However the α3 subunit containing GABA-A receptor is expressed on the dopaminergic neurons in the VTA. Therefore activating this receptor counteracts the activation of the α1 receptor. That's why I get the idea that there is a sweet spot of maximal α1 saturation vs α3 occupancy. Going above that level stimulates both receptors equally.




By the way yes relieve from anxiety and negative thoughts can also give some sense of euphoria I guess.