79 replies to this topic

[normalizing]

i did gene test and it shows i have reduced expression and low density on DRD2 receptor which from what i know is related to drug addiction and such. im trying to connect to anyone else having the same problem and how they feel and deal with it, do you have history of drug addictions?

also, anyone has a clue what to take or do with such a problem? from what i read, antipsychotics are completely out of the question as the expression of this receptor is so low, inhibiting it will cause severe side effects. so i cant use those, but what can i use to enhance expression then?

[Dextroamphetamine]

Inositol upregulates D2DR: http://www.ncbi.nlm....pubmed/11267629

 

 

Abstract

A large body of evidence suggests that the neuropathology of obsessive-compulsive disorder (OCD) lies in the complex neurotransmitter network of the cortico-striatal-thalamo-cortical (CSTC) circuit, where dopamine (DA), serotonin (5HT), glutamate (Glu), and gamma-amino butyric acid (GABA) dysfunction have been implicated in the disorder. Chronic inositol has been found to be effective in specific disorders that respond to selective serotonin reuptake inhibitors (SSRIs), including OCD, panic, and depression. This selective mechanism of action is obscure. Since nigro-striatal DA tracts are subject to 5HT(2) heteroreceptor regulation, one possible mechanism of inositol in OCD may involve its effects on inositol-dependent receptors, especially the 5HT(2) receptor, and a resulting effect on DA pathways in the striatum. In order to investigate this possible interaction, we exposed guinea pigs to oral inositol (1.2 g/kg) for 12 weeks. Subsequently, effects on locomotor behavior (LB) and stereotype behavior (SB), together with possible changes to striatal 5HT(2) and D(2) receptor function, were determined. In addition, the effects of chronic inositol on dexamphetamine (DEX)-induced motor behavior were evaluated. Acute DEX (3 mg/kg, ip) induced a significant increase in both SB and LB, while chronic inositol alone did not modify LA or SB. The behavioral response to DEX was also not modified by chronic inositol pretreatment. However, chronic inositol induced a significant increase in striatal D(2) receptor density (B(max)) with a slight, albeit insignificant, increase in 5HT(2) receptor density. This suggests that D(2) receptor upregulation may play an important role in the behavioral effects of inositol although the role of the 5HT(2) receptor in this response is questionable.

 

Also forskolin(http://www.ncbi.nlm..../pubmed/9376541):

 

 

Abstract

Intracerebroventricular (i.c.v.) forskolin infusion for 5 days resulted in a concentration-dependent increase in rat striatal dopamine (DA) D2 receptors measured with [3H]raclopride. In animals given 50 nmol/h forskolin, the highest concentration used, raclopride-mediated suppression of spontaneous locomotor activity was attenuated, and (+/-)-7-hydroxy-dipropyl-aminotetralin HBr (7-OH-DPAT)-mediated inhibition of striatal DA synthesis, as estimated by the accumulation of DOPA following inhibition of cerebral decarboxylase, was enhanced. These data suggest that the DA D2 receptor increase comprises receptors localized both post- and presynaptically. The density of striatal DA D1 receptors was also changed with the forskolin treatment, in a concentration-dependent fashion, but in the opposite direction to DA D2 receptors. These findings suggest that striatal DA receptor sensitivity can be changed by manipulation at the second messenger level (e.g. independent of direct neurotransmitter-receptor interactions) in vivo.

 

[Guinga]

http://www.hindawi.c...pd/2014/684973/

 

Parkinson’s Disease: Low-Dose Haloperidol Increases Dopamine Receptor Sensitivity and Clinical Response

Craig J. Hudson,1 Philip Seeman,2 and Mary V. Seeman2

1Department of Psychiatry, Alexandra Marine and General Hospital, 120 Napier Street, Goderich, ON, Canada N7A 1W5
2Clera Inc., 260 Heath Street West, Unit 605, Toronto, ON, Canada M5P 3L6

Received 23 July 2014; Accepted 9 November 2014; Published 20 November 2014

Academic Editor: Jose Rabey

Copyright © 2014 Craig J. Hudson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. It is known that ultra-low doses of haloperidol can cause dopamine supersensitivity of dopamine D2 receptors and related behaviour in animals. Objective. The objective was to determine whether a daily ultra-low dose of 40 micrograms of haloperidol could enhance the clinical action of levodopa in Parkinson’s disease patients. Method. While continuing their daily treatment with levodopa, 16 patients with Parkinson’s disease were followed weekly for six weeks. They received an add-on daily dose of 40 micrograms of haloperidol for the first two weeks only. The SPES/SCOPA scale (short scale for assessment of motor impairments and disabilities in Parkinson’s disease) was administered before treatment and weekly throughout the trial. Results. The results showed a mean decrease in SPES/SCOPA scores after one week of the add-on treatment. Conclusion. SCOPA scores decreased after the addition of low-dose haloperidol to the standard daily levodopa dose. This finding is consistent with an increase in sensitivity of dopamine D2 receptors induced by haloperidol. Such treatment for Parkinson’s disease may possibly permit the levodopa dose to be reduced and, thus, delay the onset of levodopa side effects.

 

[gamesguru]

red ginseng

• KRGE inhibited anxiety-like behavior and the over secretion of plasma CORT during EW. Furthermore, the behavioral effect was blocked by a selective DA D2 receptor (D2R) antagonist (eticlopride) but not by a selective DA D1 receptor (D1R) antagonist (SCH23390).

ginkgo

• A significant decrease in the level of DA and its metabolites and an increase in the number of dopaminergic D2 receptors in striatum were observed after 6-OHDA injection, both of which were significantly recovered following EGb treatment.

bacopa

• ... in the rat experimental model of neonatal hypoglycaemia, Bacopa extract improved alterations in D1, D2 receptor expression, cAMP signalling and cell death resulting from oxidative stress.

tea

• EGCG also inhibited hyperlocomotion and rearing activity induced by apomorphine, a D1/D2-like agonist.
• EGCG has strong pharmacological activity against the development of morphine dependence, which can be partly explained by its inhibitory effects on the morphine-induced increase in the cAMP levels in the locus coeruleus and the signaling of the dopamine D2 receptor.

[Autumn Knight]

I have the same problem. 

What's funny is I actually did take antipsychotics to treat it- NOT A GOOD IDEA 

 

The only thing I've ever seen to help this problem TAGsync neurofeedback, but even then, there's no evidence that the receptors are reformed with that. If you ever find an answer, let me know. I'm also forever looking. 

[normalizing]

autumn knight, antipsychotics are very very bad idea for people like us to take them. thats why this guy recommending haloperidol is just uneducated about DRD2 problems. you definitely do not take antipsychotics! forskolin doesnt work either i took it for a month or so and gamesguru's suggestions are always a huge fail as those have been used for many years with mostly negative long term effect.

[Autumn Knight]

Has anything you've done helped, normalizing? 

 

I've tried so many, many things.  

[normalizing]

what are your problems, symptoms? this is just minor genetical problem compared for various other factors i dont think anyone having this as solely one problem really relates to everyone else having it

[Autumn Knight]

I also took several kinds of antidepressants. Also a horrible, horrible idea. 

[Autumn Knight]

what are your problems, symptoms? this is just minor genetical problem compared for various other factors i dont think anyone having this as solely one problem really relates to everyone else having it

 

Oh I thought you said it was from drugs? 

 

I took MDMA megadoses for an extended period of time, over a year. 

 

I have major cognitive deficits, speech problems, huge amounts of trouble remembering things long term + short term, problems figuring things out, etc

[normalizing]

man, you serious, you took MDMA for years? i took it for few months with some severe problems. bro, i wish to help but, this shit is beyond us. it took me through hell for months before i kind of managed, not sure if ever the same years later but honestly stabilize yourself no abuses of any type and you might get better by next years considering you did it 1 year damn it will take me 2-3 years to recover specifically. but nobody is the same different types and all, google if you dont believe my poor exhausted soul, i suggest you really bite it and fight with that shit for the next few months head on no drugs either antidepressants or antipsychotics those are NOT HELPING, pure suffering is! sorry to say it to you, you cant expect life to work this way man, extasy and fantasy and easy recover to normalcy. :(

[Autumn Knight]

man, you serious, you took MDMA for years? i took it for few months with some severe problems. bro, i wish to help but, this shit is beyond us. it took me through hell for months before i kind of managed, not sure if ever the same years later but honestly stabilize yourself no abuses of any type and you might get better by next years considering you did it 1 year damn it will take me 2-3 years to recover specifically. but nobody is the same different types and all, google if you dont believe my poor exhausted soul, i suggest you really bite it and fight with that shit for the next few months head on no drugs either antidepressants or antipsychotics those are NOT HELPING, pure suffering is! sorry to say it to you, you cant expect life to work this way man, extasy and fantasy and easy recover to normalcy. :(

Yeah dude. Like around 1 1/2 years. It was majorly stupid. 

That was 8 years ago (that I quit cold turkey) and I'm still pretty screwed up. Not as much, but I'm losing hope I'll ever be the same again. Some people on here try to boost my spirits and help as much as they can and that's pretty awesome, but I just don't know anymore. I haven't done any drugs at all but alcohol for years (and I don't drink that much). 

Yeah, it was years ago I tried anti-ds and about a year ago I tried antipsychotics, still had a really negative effect; makes me feel like my brain hasn't changed much. 

What are you recovering from specifically? 

[normalizing]

look man, you slowed down your problem's recovery further by inhibiting them with crap like antipsychotics and antidepressants. you can recover because do a genetical test on 23andme, its all this, a drive, this all comes as obstacles. you are predisposed to all in life and toxins only can influence your recovery better in various ways. so i have to think of what will work for you short term to manage this pain, its impossible to avoid it, you have to suffer to get the truth so to say. its how your body copes to anything that disturbs its atmosphere. you will get better tho, fact truth, i guarantee if you are still young. you will get better you will see and not even notice, because your body owns you, you cannot have exact perception of its timing. were you born this way? thats different problem. there is no solution. but what goes around in time, comes around, like it is, complete cell reaction with the instructions of its genes.

[Autumn Knight]

look man, you slowed down your problem's recovery further by inhibiting them with crap like antipsychotics and antidepressants. you can recover because do a genetical test on 23andme, its all this, a drive, this all comes as obstacles. you are predisposed to all in life and toxins only can influence your recovery better in various ways. so i have to think of what will work for you short term to manage this pain, its impossible to avoid it, you have to suffer to get the truth so to say. its how your body copes to anything that disturbs its atmosphere. you will get better tho, fact truth, i guarantee if you are still young. you will get better you will see and not even notice, because your body owns you, you cannot have exact perception of its timing. were you born this way? thats different problem. there is no solution. but what goes around in time, comes around, like it is, complete cell reaction with the instructions of its genes.

 

Same to you. 

[Guinga]

autumn knight, antipsychotics are very very bad idea for people like us to take them. thats why this guy recommending haloperidol is just uneducated about DRD2 problems. you definitely do not take antipsychotics! forskolin doesnt work either i took it for a month or so and gamesguru's suggestions are always a huge fail as those have been used for many years with mostly negative long term effect.

 

If you read the article i posted, you'll notice that the dosage used was about 1/50 of the lowest therapeuthic dose, (2mg), at this levels the antipsychotic won't block any dopamine receptors, but will rather sensitize then, by an unknown mechanism. the study was conducted on parkinson's patients. as you might imagine, blocking their dopamine receptors would be disastrous, so i'm sure that you'll be okay if try this.

 

"A possible method of enhancing the action of dopaminergic therapy is to increase the sensitivity of dopamine D2 receptors that are the main targets for dopamine agonists [2]. For example, very low doses of dopamine antagonists can increase the number of D2 receptors that are in the high-affinity state for dopamine, known as D2High receptors [3]. Such an increase in brain striatal D2High receptors is consistently associated with increased motor activity in animals [4, 5], indicating increased behavioural sensitivity.

For example, Alttoa et al. [4] found that spontaneous exploratory behavior was related to the proportion of D2 receptors in the high-affinity state in laboratory animals. On the basis of their initial spontaneous exploratory behavior, one-month postnatal rats were divided into high- and low-curiosity groups. The low-curiosity group showed a level of high-affinity D2 receptors that averaged 22.5% of the total D2 population of receptors, while the high-curiosity animals revealed a D2High receptor level of 43.8%. These results suggest a relationship between the D2High state and the increased motor and exploratory behavior in rats.

In another study [5], rats were administered haloperidol i.p. at a dose equivalent to 0.4% of the human dose for its approved indications (psychosis). After several successive days, the high-affinity D2 receptors increased by more than 50%, resulting in a level approximately twice that of untreated animals. The animals exhibited heightened locomotion, active exploration, and increased grooming behavior. These results were still demonstrable for several days after dosing was stopped."

Edited by Guinga, 16 August 2016 - 02:54 PM.

[Autumn Knight]

Interesting Guinga. 

I took the lowest dose of amitriptyline available and it was still really really awful, but it's not an antipsychotic and the lowest dose probably isn't 2 mg. I don't remember. 

Just saying because it made me react the same way taking antipsychotics does

[Guinga]

hey Autumn knight, if you felt brain fog, sedation, drowsines, etc. on Amtryptiline, it was probably due to the blocking of histamine and muscarinic receptors.  because it actually enhances dopaminergic neurotransmission. also the majority of antipsychotics  have high affinity for the same receptors. 

Edited by Guinga, 16 August 2016 - 03:43 PM.

[Autumn Knight]

hey Autumn knight, if you felt brain fog, sedation, drowsines, etc. on Amtryptiline, it was probably due to the blocking of histamine and muscarinic receptors.  because it actually enhances dopaminergic neurotransmission. also the majority of antipsychotics  have high affinity for the same receptors. 

 

Dude no.

It was horrible, horrible. It felt like I was going to die. I can't even explain it. It was like my mind was exploding and I couldn't breathe. If I had to take more I'd kill myself. 

[Guinga]

I know what you mean, i also felt Like this when i Was on zoloft. What are your symptoms exactly?

Edited by Guinga, 16 August 2016 - 04:42 PM.

[normalizing]

what about this; Memantine acts as an agonist at the dopamine D₂ receptor with equal or slightly higher affinity than to the NMDA receptors; any significant possible amelioration of DRD2 reduced expression or actually no, its worse?

Edited by normalizing, 16 August 2016 - 05:02 PM.

[Autumn Knight]

I know what you mean, i also felt Like this when i Was on zoloft. What are your symptoms exactly?

 

Of taking antidepressants? 

Feeling of swollen brain, shallow and labored breathing, rapid irregular heartbeat, very strange feelings in my body like my limbs aren't coordinated, trouble swallowing, insane thoughts (racing, disturbing images/thoughts that don't make sense), weakness, chest pain. 

 

Even from the lowest dose

[gamesguru]

just hit it with a weak agonist, <12hrs daily.

red ginseng extractum is a known D2R agonist, and a weak one.

[normalizing]

why specifically "weak" agonist?

[gamesguru]

the strong is overpowering, in fact having a possble unwanted effect of further substantially downregulating activity

[normalizing]

such a homopathic way of you viewing some herb as a simple "weak" agonist. it has myriad of unwanted side effects why dont you homopaths ever cite those together with the supposedly "good reactions"

[gamesguru]

if sweating and anxiety and restlessness are the main undesirable side effects of ginseng, I more than gladly tolerate the

[sativa]

such a homopathic way of you viewing some herb as a simple "weak" agonist. it has myriad of unwanted side effects why dont you homopaths ever cite those together with the supposedly "good reactions"

Come now normalising, don't be so prejudiced! Apply some critical thinking to what people are suggesting too! Trollness aside, you could improve your manor (which might improve once you resolve your D2 issues I reckon)

Have you been able to differentiate what type of dopamine receptor you need to focus on? There exists D2(SHORT) and D2(LONG)

D2 receptors have autoreceptors which function to decrease dopamine synthesis / neuron activity...two distinct pathways, but the autoreceptors are ONLY the pre-synaptic ones (D2s), whereas D2 L = D-2-"Long" has it's post-synaptic effects and a stronger downstream effect more indicative of a dopaminergic pathway and having more interaction with the D1-like receptors...

Forskolin only unregulates D2L I think.

There's also bromantane, sulbutiamine, 9 mebc for dopamine upregulation.

Another user suggested:

tianeptine and phenyl piracetam together with inositol / CDP-Choline should result in a 7-fold increase in dopamine D2 receptor concentration abroad.

YMMV.

Try this thread for more info on increasing D2:
http://www.longecity...on-and-related/

@Autumn Knight
MDMA will downregulate VMAT which is the principle thing that loads neurotransmitters and prepares them for firing. (It takes neurotransmitters from the cytosol and loads them into vesicles ready to be fired into the synapse)

Less VMAT = highly undesirable.

Mesembrine from kanna has been shown to upregulate VMAT, though the action is unknown.

Edited by sativa, 19 August 2016 - 08:19 PM.

[Autumn Knight]

 

such a homopathic way of you viewing some herb as a simple "weak" agonist. it has myriad of unwanted side effects why dont you homopaths ever cite those together with the supposedly "good reactions"

Come now normalising, don't be so prejudiced! Apply some critical thinking to what people are suggesting too! Trollness aside, you could improve your manor (which might improve once you resolve your D2 issues I reckon)

Have you been able to differentiate what type of dopamine receptor you need to focus on? There exists D2(SHORT) and D2(LONG)

D2 receptors have autoreceptors which function to decrease dopamine synthesis / neuron activity...two distinct pathways, but the autoreceptors are ONLY the pre-synaptic ones (D2s), whereas D2 L = D-2-"Long" has it's post-synaptic effects and a stronger downstream effect more indicative of a dopaminergic pathway and having more interaction with the D1-like receptors...

Forskolin only unregulates D2L I think.

There's also bromantane, sulbutiamine, 9 mebc for dopamine upregulation.

Another user suggested:

tianeptine and phenyl piracetam together with inositol / CDP-Choline should result in a 7-fold increase in dopamine D2 receptor concentration abroad.

YMMV.

Try this thread for more info on increasing D2:
http://www.longecity...on-and-related/

@Autumn Knight
MDMA will downregulate VMAT which is the principle thing that loads neurotransmitters and prepares them for firing. (It takes neurotransmitters from the cytosol and loads them into vesicles ready to be fired into the synapse)

Less VMAT = highly undesirable.

Mesembrine from kanna has been shown to upregulate VMAT, though the action is unknown.

 

Do you know anything else that could help? I'll look into Mesembrine. 

Also, does upregulation mean heal? 

People always say that but it doesn't mean much to me right now.. 

[Mind_Paralysis]

 

Also, does upregulation mean heal? 

People always say that but it doesn't mean much to me right now.. 

 

 

What sort of disorder do you have..? At your baseline. Which drives you to do such amounts of MDMA? Seriously - everyone I've ever heard of who does that, have SERIOUS OTHER ISSUES, which they try to self-medicate.

 

So what ails you, friend? Your ORIGINAL problem, that is.

 

The only thing I can suggest with all of your acquired problems are neurogenics: Dihexa, NSI-189, and some other compounds which my burnt-out mind can't recall at this time.

 

They are all untested and the long-term effects are unknown - several of them, are perceived to be not harmful, but there is little data. Sadly, it's the only thing my own burnt-out brain can think of which would actually help - you've bathed your brain in actual neurotoxins, physically destroying parts of it.

 

The only way to get a true recovery is to make your brain actually regrow damaged parts. It can be done, but it's not for the faint of heart.

 

 

Regarding UPREGULATION:

 

It means to restore receptors, or to increase density of receptors. In a way it can be a healing, if you have damaged your receptors. It can also mean that your receptors are not so much damaged, as in a dormant state, shut down by your body to prevent further damage. (temporarily downregulated. this is often the case with people gaining tolerance to amphetamine - a feedback mechanism notices that amphetamine is altering the balance in your brain, and hence orders your brain to turn off x amount of dopamine-receptors, to decrease the effects of dopamine. often this decrease is greater than necessary - the brain is over-zealous in correcting things)

[normalizing]

uh d2 short and long? sativa not sure of those any scientific literature? also, dont make fun of my d2, asshole. it was diagnosed by psychiatrists in a way to invent new ways to push their stupid drugs. i wont be sure until i do my own testing with 23andme to know.

Edited by normalizing, 19 August 2016 - 11:15 PM.