I've been taking a pretty interesting combo lately. Phenibut and kratom. For me, the synergy, is intense to say the least. The body high of kratom seems to be intensified threefold compared to when taken without phenibut. Basically, here is my question. If 2 drugs have a synergy, does it put a stronger strain on the brain that would make withdrawls develop quicker and intensify it. If I were to take kratom in the morning, and phenibut in the evening, implying there is no phenibut, would the withdrawl be the same if you were to take them together and experience the strong synergy? Assume I was to take each of these substances 3 days in a row, in one trial, one is taken in the morning, and one at night, while in another trial, I take them both together and experience the synergy, would the withdrawls be worse if I was to experience the synergy? Does the body high correlate with the stress put on the receptors? Thanks for reading and answering.
-
N&PD Moderators: Skorpio | thegreenhand
If 2 substances have a strong synergy, will withdrawl be worse than each alone
- Thread starter YuppTrees
- Start date
sekio
Bluelight Crew
- Joined
- Sep 14, 2009
- Messages
- 21,994
Receptors don't neccesarily get "stressed" or 'damaged", your body just temporarily turns them off if they remain in an active state for too long, through a process called receptor internalization.
Generally speaking, withdrawing from drugs that have synergistic effects is always more unpleasant than withdrawing from one drug alone. However if you take one in the morning and another in the evening you will still eventually build tolerance to both drugs, just the overall high will be less intense.
Generally speaking, withdrawing from drugs that have synergistic effects is always more unpleasant than withdrawing from one drug alone. However if you take one in the morning and another in the evening you will still eventually build tolerance to both drugs, just the overall high will be less intense.
Generally speaking, at least IME, when quitting multiples at once, the withdrawal of each is protracted and it's much harder to stop because you constantly justify to yourself that youll use the other to ease withdrawal from the one, and then vice versa. Best to just quit them at the same time and just rest and hydrate, perhaps some methyl-B12, N-Acetyl-Cysteine supplements. Valerian is fine for Gabaergic withdrawal IME. But with the kratom thing, as with all opiates, the quickest and most effective way out is also the most arduous - straight through the hellfire. But once you're out on the other side, you'll look back and thank yourself from being free from the prison you've created for yourself. The key then is to remember the battle's not done yet, you've gotta push yourself to start managing healthy and beneficial ways to set you on the path to being able to manage. All the best mate.
aced126
Bluelighter
- Joined
- May 18, 2015
- Messages
- 1,047
Just expanding on receptor internalisation:
Receptor internalisation is a highly regulated process that depends on several proteins.
GPCR internalisation is mediated by a GPCR kinase which phosphorylates the GPCR. Beta-arrestin is then recruited onto the GPCR, and then recruits AP2 adaptors, which cooperatively bind more AP2, and induce membrane bending. This membrane curvature is stabilised by BAR domain proteins. AP2 then recruits clathrin triskelions which start to form a coated pit. Finally, dynamin (a GTP hydrolysing protein), along with the help of a few other proteins it recruits, mediates pinching off of the clathrin-coated vesicle. Once pinched off, an hsp70 chaperone, through cycles of ATP hydrolysis, removes the clathrin coat, and a PIP phosphatase degrades membrane bound PI(4,5)P2 (a phosphoinositide that AP2 uses to bind the membrane), mediating AP2 dissociation. Thus, clathrin and AP2 are recycled for another round of endocytosis. The endocytic vesicle containing the GPCR can then either be directed to lysosomes for degradation by the proteosome, or it can be returned to the same plasma membrane domain it was endocytosed from after a while. The exact fate will probably be dependent on the type of lipid raft the receptor was in to begin with, which will express certain Rab proteins (a monomeric GTPase) that direct to certain intracellular compartments like the lysosome or recycling endosome.
Receptor tyrosine kinase internalisation happens through a similar process. However, here a mono or multiubiquitylated (not polyubiquitylated) which are recognised by ubiquitin binding proteins, which then help to direct the RTKs to clathrin-coated pits.