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Estradiol + Gabapentin ... lots of strange mental effects, possible hppd, weirdness .

lenses

lenses

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I am taking Estradiol (sublingual 2mg) with 300-600mgs gabapentin ... Just kicked suboxone , w/ds and functionality came back about 5 days ago.

I've been taking the gabapentin for about 14 days and the estradiol about 5 and my memory has been absolutely horrible!Driving skills and general concentration have been affected strongly as well. I noticed it getting worse as I started taking the estradiol , and my moderate hppd got very strong, I know in part to the SERT effects of estradiol.Pretty bad photosensivity as well. It feels like I took about 50mgs of MDMA ,thats an almost perfect example. This has been going on for 3 days... as I started lowering my dose of gabapentin, the weird serotogenic effects got stronger.

I don't mind it, just my memory is hit.I have a strong adversion to cigarettes as well, and I can feel my cardiovascular system getting stressed as well as the increased blood pressure. Perhaps an acetlycholine issue as well. I am also 14 days clean of buprenorphine after a 6 year addiction...Is this just hormonal, or is this something to do with the gabapentin...

This article makes a lot of sense, but I couldn't decipher it all.

I stumbled across this Article : http://www.sciencedirect.com/science/article/pii/S0006899304010868

Estradiol-induced changes in the activity of hippocampal neurons in network culture are suppressed by co-incubation with gabapentin

"Abstract:The ovarian steroid hormone estradiol, in addition to its function in the maintenance and regulation of reproductive capacity, can alter neuronal excitability. Estradiol is proconvulsant, increases neuronal excitability and decreases the threshold for seizure activity. Over onethird to one-half of women with epilepsy experience catamenial seizures, which are seizures influenced by cyclical hormone changes. These hormone-sensitive seizures respond to the anti-epileptic drug gabapentin, which is a structural analogue of the inhibitory amino acid neurotransmitter GABA. We studied the effects of $17-\beta$-estradiol alone and estradiol co-incubated with gabapentin on neuronal activity in network cultures of rat hippocampal neurons using a fluorescent calcium binding dye fluo-3 AM, FM 1-43 labeling of synaptic vesicles and electrophysiological recordings. Significant changes in the neuronal network activity were observed in the estradioltreated neuronal cultures; the reactivity of the neurons to KCl depolarization induced intracellular calcium changes, and FM 1-43 destaining was increased as was the frequency of spontaneous miniature excitatory postsynaptic currents (mEPSC). All these excitatory effects of estradiol were nullified by co-incubating the neurons with a combination of estradiol and gabapentin. This suggests that gabapentin can indeed affect the estradiol-induced changes in neuronal network hyperexcitability by influencing the neuronal calcium levels, exocytosis and synaptic activity. Our findings could provide an understanding of the cellular basis of hormone-sensitive seizure control by gabapentin."

So I take it that gabapentin modifies estradiol effects in the hippocampus , perhaps leading to inhibition of serotogenic mediated activity in the hippocampus?Gabapentin seems to have held back the receptors and now they are super sensitive. WEIRD O_o

Basically it seems I am having some sort of hypersensivity and large amounts of SERT and NE release,with memory,possible actylcholine levels, affected... I just want to make sure I am not doing an damage w/ any excitotoxicity...


Reccomendation on what to do? It's affecting my work skills and is making me tired and achey as hell. My sleep is definitely affected.It feels like I slept but I know i'm not that rested. The only thing that really helps me sleep is clonidine , and that works for exactly long as it should : 4 hours, then pop, and i'm up...

-lenses
 
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Lenses - I will get back to you ASAP on this - I need to look into it a bit. Hang in there lady.
 
have you talked to the doctor about it?

I would suggest to go without it for a day or two to see if it is what's causing your symptoms.

TAoW is a really smart veteran though, whatever he says is probably going to be your best bet. I am just going off of common sense, if I begin taking a drug and I notice I don't feel very good due to the effects, I usually discontinue taking it to see if it is the source of the problem or not.
 
Update : I believe the gabapentin was chiefly responsible for the symptoms... I had taken 300 mg gabapentin in the morning, and now about about +12:00, the "weirdness" from the extra serotonin is diminishing. From what I can figure out, gabapentin was inhibiting the plasticity of the neuron, and spontaneous miniature excitatory postsynaptic currents (mEPSC) were getting affected, which are minature currents towards the end of the snyapse from what I understand.

I had been taking the gabapentin to alleviate withdrawl symptoms of buprenorphine a few weeks before... So it's been in my system for a bit.

I believe the inhibited neuronal plasticity was chiefely to blame, as estradiol is know to change around the structure of serotonin receptor density in the brain, and the part of the serotonin affecting the receptor was not allowed in , i.e. LSD agonism/antagonism ... Wouldn't inhibiting part of a 5HT receptor cause strange effects , like what the gabapentin was doing to the mEPSC?

This could be a big part of the picture, as cannabis, another neuronal plasticity inhibitor was causing MDMA like pattern matrixing effects when I used it...could also be syngerism , but i'm not sure. I think there is some sort of correlation.

Does neuroplasticity mediate responses like that , and have you heard of anything weird like that happening with other SERT agonists + gabapentin ?

The first night of taking estradiol with 900mgs of gabapentin lead to the strongest experience,with LSD like shifting and breathing qualities , matrixing , and 3-D glasses color splitting... I was really, really quite blown away by it.

Captain Heroin: No I haven't talked to a Dr. about it... I doubt they would know, as gabapentin is not contraindicated with estradiol on any health websites I have seen... It freaking should be.

-lenses
 
Wow! That is a lot to learn, thanks for sharing lenses!

I am amazed by the intensity of that sort of reaction! I believe you can leave an anonymous memo to the FDA about drug interactions, as patients have a right to privacy and the FDA still wants to know what the potential problems could be with a certain medication.

I had certainly heard of nothing like this before.
 
This is fascinating paper, esp. full text ...
Modulation by estradiol of serotonin receptors in brain

Abstract

Estrogens were found to exert a biphasic effect on the density of serotonin receptors in the female rat brain: an acute reduction in serotonin receptor density throughout the brain is followed 48 to 72 hr later by a selective increase in those brain regions known to contain estrogen receptors--hypothalamus, preoptic area, and amygdala. The acute reduction in serotonin receptor density can be mimicked by estradiol in vitro. We conclude that estradiol may have a fast, direct effect on brain membranes to modify serotonin receptor availability, while exerting a slow effect on the same receptors through an interaction with intracellular estrogen receptors in those brain regions that contain them. The observation that female sex hormones are involved in the regulation of serotonin receptors may have important implications in the understanding of female sexual behavior in the female rat and in the understanding of hormone-linked emotional disturbances in women.

http://www.jneurosci.org/content/2/2/199.full.pdf-Full Text

Those ^ brain regions were the ones affected, and the symptoms seem to correlate : hypothalamus- (memory and confusion) , preoptic - crazy vision problems and HPPD and MDMA - LSD like vision effects, and the amygdala - which explains the hypertensive effects ... As the gabapentin is leaving my system... all these effects are reducing. It seemed like about 75 percent of so of the signal was getting into my brain ... and then the tail end of the signal would be not be allowed in , causing mixed agonism / antagonism... Fascinating method of action !

Might be important to note that sub-lingual estradiol has roughly 4x potency , and different pharmacokinetics ( much much quicker peak of levels, +2 hrs estradiol levels are starting to go down, and estrone levels are becoming dominant ) . So a 2mg dose will feel like 8mgs.

I think I may notify the FDA , at least for case study purposes. I just wanted to make sure what my hypothesis was somewhat rational . :P

-lenses
 
All I can say is that gabapentin on its own at 900mg or even 600mg will make me see visuals, sort of "trip" (but not mentally), visuals distinctly different than LSD or typical psychedelics, but it always happens when i take 600+ mg's of gabapentin. Really weird visuals like looking at walls the patterns will move all around etc. Have no idea about the estradiol though.

What is the purpose of taking the estradiol if i may ask? Also after a while you might want to ask the mods to move this to the ADD forum you might get more answers/information over there.
 
theartofwar: I am trangendered and have just started a hormone replacement... Dosage is 1mg sublingually.

This is getting very silly though, and friends of mine (male) have agreed there is something big going on as well. Still feels like 50mgs of MDMA, and this has been going on for almost a week now , even without the gabapentin.

I'm going to do a writeup soon of all the research i've put together... but there are some big correlations between neuronal remodeling , nootropics and neuroprotectants, . It's shedding a lot of light on how neuroplasticity is mediated.

Seems the screwey agonism/antagonism mechanism with the gabapentin + estradiol mESPC shedded some light on neuronal remodeling mechanisms, and it carries over into MANY more categories of drugs . I'll elaborate with the writeup later, but it's pretty exciting. Could be an acetylcholine/astrocyte mechanism at play as well.

In a pretty big nutshell - Calcium Ion Channel Mixed Agonism + Antagonism is at play here ... I've never heard of this MOA ! Does anyone know any drugs with similar properties?Gabapentin, Pregabalin,Tianeptine and THC analogues would be interesting to investigate in correlation ...

Could someone with access find the full text of this article, and PM it to me? "Estradiol-induced changes in the activity of hippocampal neurons in network culture are suppressed by co-incubation with gabapentin" ? It would be greatly
appreciated.

Can a mod please move this to ADD? Thank you :)

-lenses
 
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I have known [transsexual] people who have combined the two with no noticable new effect or potentiation... So, I'm not really sure. Gabapentin on its own can behave erratically and cause a lot of the symptoms you have mentioned, and has variable pharmacokinetics depending on whether or not you consume it with food and what dose you consume it at. For instance, the lower the dosage of gabapentin the more of the drug is absorbed, so at lower oral doses your plasma concentrations of the drug may not be hugely different from higher doses.
 
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