• MDMA &
    Empathogenic
    Drugs

    Welcome Guest!

MDMA Recovery (Stories & Support - 4)

Status
Not open for further replies.
ADubbs said:
http://www.xojane.com/it-happened-t...rnight-and-im-still-recovering-6-months-later

Notice pharmaceuticals seem to be helping her....No HPPD symptoms mentioned though.
Click to expand...

Sounds familiar to me, but in my case the real improvements with the SSRI also only worked after 1 year, I definetly feel much more myself now, in percent 80%, compared to 0% before the treatment that's a huge difference ;)

I can't imagine how HPPD feels but I can say that this kind of depression is the worst thing I ever experienced, it just feels like ALL your emotions and passions are locked in a box made of concrete and there is no way to get them out…
 
Last edited:
Hellome said:
Is it possible to screw up your dopamine system from MDA?
Click to expand...

There can be some short term effects on dopamine receptors and changes to the dopaminergic system (in one study MDMA users actually showed slightly increased dopamine, probably reflecting sensitization after repeated use) but MDMA/MDA don't actually harm dopamine cells at all if that's your question. There is a lot of communication between serotonin and dopamine though.
 
fnono33 said:
One night I decided to take trazadone and I slept really well and felt better the next day. So I kept taking it and I kept feeling better. What I did notice though was that my vision was slipping into HPPD. So I developed visual disturbances. They were fine at first and then it continued to worsen. It has sort of plataued now. I think. So I knew I had to stop the trazadone becuase this may have been a factor. Who knows.
Click to expand...

I thought I would just offer some comments here, especially seeing as a newer drug is making headway being approved for yet another indication having to do with visual hallucinations due to serotonin receptor dysfunction.

Psychedelics that are known to cause HPPD like LSD work by binding to a particular serotonin receptor called 5-HT2A - MDMA releases a lot of serotonin that binds here but MDMA and also MDA (MDMA's major metabolite) also bind directly to 5-HT2A, essentially mimicking serotonin.

The new drug in question is Pimavanserin, and it is what's known as an "inverse agonist" as opposed to Trazodone which is a "silent antagonist". The difference being that Pimavanserin is essentially just causing the 5-HT2A receptor to disappear while Trazodone sits on top of the receptor and just blocks serotonin from binding to it, which means that in the mean time the 5-HT2A receptors are building up.

Even if you maintain a high degree of blockade of 5-HT2A with a silent antagonist, you can see issues at some point because 5-HT2A receptors are "constitutively active", meaning that sometimes they are signaling even without serotonin binding to them. So these 5-HT2A receptors can still cause trouble when being blocked by a silent antagonist after a lot of them begin to pop up.

Pimavanserin was approved for Parkinson's disease psychosis - the reason why 5-HT2A inverse agonism helps with the visual hallucinations of Parkinson's disease is that after a huge amount serotonin (and other) cell death the amount of serotonin signaling drops quite a lot. But because the 5-HT2A receptors are expressed post-synaptically on cells that aren't degenerating as much, they respond to this drop-off in serotonin signaling by upregulating and sensitizing quite a lot.

Pimavanserin (an inverse agonist) was developed specifically because the real issue is the constitutive activity of the receptors - a silent antagonist wouldn't help there because there isn't much serotonin actually binding to the receptors anyways, and the receptors are signaling away without serotonin binding to them.

Pimavanserin just did good in phase II trials for Alzheimer's disease psychosis and selective inverse agonists of 5-HT2A have historically done very good for insomnia, although they suspiciously never made it to market (it was theorized they were going to take a large portion of the sleep-drug market that was cornered by the Z-drugs like Ambien).

So essentially a silent antagonist like Trazodone could be a poor choice because the 5-HT2A receptors will just keep popping up even though they are supposed to desensitize after long term blockade, but Pimavanserin is something to talk about with your doctor if you're feeling like a guinea pig. I'd like to hear what Dr. Henry Abraham has to say on the matter of Pimavanserin for HPPD.
 
I can email him. He retired on the 15th of December but maybe he can answer the question.
 
Cotcha Yankinov said:
Bleh, doesn't jive with me personally - I get the homeopathic vibes big time.

But as far as LTC and HPPD - depersonalization is really co-morbid with HPPD.
Click to expand...

The symptoms listed as co-morbid with HPPD in the literature seems quite often to be congruent with what we call the LTC:

Hallucinogen persisting perception disorder and the serotonergic system: A comprehensive review including new MDMA-related clinical cases (2014) said:
Besides recurring visual symptoms, a large group of
patients also reported other perceptual symptoms, like
auditory and sensory symptoms. A relatively large subgroup
(45%) reported peculiar sensations in the head such as
pressure, clicks, dryness or ‘a shrinking brain’. Striking also,
is the co-occurrence of derealization and depersonalization
symptoms (39% and 32%), which are characterized by the
external environment and own body coming across as unreal
or not one's own. Most frequent is the comorbidity with
anxiety and panic. Approximately two thirds of the patients
(71%) reported to have experienced anxiety or panic in the
weeks before or following the use of drugs.
Click to expand...
 
Okay, here's an interesting one. Ever since I rolled on literally .1g MDA, my hair/nail growth speed/health has gone up shockingly. What's up with that?
Edit: that was 4 months ago, by the way.
 
Last edited:
fnono33 said:
I can email him. He retired on the 15th of December but maybe he can answer the question.
Click to expand...

Pity that he retired, but in regards to the email I guess you could send him the following (although I wish I knew how much to write, hopefully this isn't TL;DR, feel free to just ask him about the Pimavanserin as I have no idea how open to communication he is and if he is still passionate about his brainchild HPPD)

"Hello doctor, I was hoping to hear from you about Pimavanserin and if it may have use in treating HPPD.

Do you think that changes to parvalbumin positive GABA interneurons like decreased expression of PV (caused by glutamate release via 5-HT2A activation in the case of MDMA) can cause HPPD and other issues (rather than excitotoxic destruction of said interneurons), and then the changes in PV/GAD67 expression could reverse to some degree with chronic 5-HT2A blockade?

Even if 5-HT2A blockade leads to a temporary decrease in the activity of PV GABA interneurons and a surge in symptoms, I wonder if the possible changes associated with 5-HT2A over-activation are bi-directional, and hence I'm curious if Pimavanserin holds any promise for treating HPPD.

The various case reports of HPPD seem difficult to piece together. There are reports of initial exacerbation of HPPD when starting treatment with AAPs and SSRIs, but then there is a gradual decrease in symptoms.

I'm wondering in particular if Pimavanserin may hold any promise as opposed to a silent/neutral antagonist like Trazodone that may allow the receptors to build up (even though regulation of 5-HT2A is atypical in regards to chronic blockade causing desensitization) and then the constitutive activity of 5-HT2A may wreak havoc, as appears to be the case with Parkinson's disease psychosis due to 5-HT2A supersensitivity.

MDMA users show upregulation of 5-HT2A in visual cortex among other regions, so I wonder if there isn't already an element of some excess constitutive activity (if only at particular synapses) that wouldn't be stopped by a neutral antagonist. Unfortunately it seems that the orthosteric site binding antagonists like Risperidone are going to have the issue of dopaminergic blockade, and seeing as COMT inhibitors are helpful to some HPPD patients that could be expected to worsen symptoms/cause side effects in the meantime while waiting for desensitization of 5-HT2A with chronic blockade.

I'm told it is the case with ketamine that parvalbumin positive neurons are still there but no longer expressing parvalbumin. Recent studies have shown there is a decrease in GAD67 and PV immunoreactivity after MDMA administration in animals.

If the PV neurons have undergone such changes like decreased expression of GAD67/PV after excess 5-HT2A activation and this is relevant a cause of symptoms, how may we go about reversing these changes? There seems to be evidence that HDAC inhibitors and clozapine may help with PV interneuron issues in schizophrenia.

Many thanks for any thoughts."


Something like that... Too long? I'm thinking about posting this possible email over in Neuroscience in Pharmacology and seeing if I can get any critique. In addition I might try to email some university staff, some have been open to communication in the past.
 
Last edited:
ScaredFirstTimer said:
The symptoms listed as co-morbid with HPPD in the literature seems quite often to be congruent with what we call the LTC:
Click to expand...

Indeed, I guess the question is what is causing what. It seems to me that a syndrome as significant as HPPD doesn't need to confine itself to visual systems in all cases, especially when occurring with MDMA as opposed to LSD.
 
Hellome said:
Okay, here's an interesting one. Ever since I rolled on literally .1g MDA, my hair/nail growth speed/health has gone up shockingly. What's up with that?
Edit: that was 4 months ago, by the way.
Click to expand...

Hmmmmm maybe stress related signaling can have such effects? Try not to over-analyze though ;)
 
Hellome said:
Okay, here's an interesting one. Ever since I rolled on literally .1g MDA, my hair/nail growth speed/health has gone up shockingly. What's up with that?
Edit: that was 4 months ago, by the way.
Click to expand...

For me, its the opposite. Maybe the MDMA tipped the hormones in a good direction. Have you been taking zinc? Or a multi-vitamin with a lot of zinc?
 
fnono33 said:
For me, its the opposite. Maybe the MDMA tipped the hormones in a good direction. Have you been taking zinc? Or a multi-vitamin with a lot of zinc?
Click to expand...
No I haven't, yeah I feel it may be a hormonal change due to the MDA/LTC, I've had other strange symptoms of abnormal hormone levels
 
my sleep has gone downhill.....Haven't felt right since the relapse a few weeks ago and getting worse.....Plus I'm sick as a dog which doesn't help
 
Status
Not open for further replies.
Top