View Full Version : Upregulating Dopamine Receptors Via Microdosing


Info Seeker
03-15-17, 05:16 PM
Recently, I read a post on reddit cautioning recreational stimulant users not to take ultra low doses of dopaminergic drugs, as there is evidence that this acts to irreversibly sensitize dopamine receptors.

As the post outlines, this can have various permanent detrimental effects for neurotypicals, such as motor tics, irrational behavior, and decreased sleep quality. This seems to be because of a replacement of low-sensitivity dopamine receptors with high sensitivity receptors. It appears that this also destroys stimulant tolerance, and MDMA users have used similar techniques for a while to extend the longevity of their supplies.

While this is clearly not worth the risk in recreationally using neurotypicals, it seems as if ADHD brains, clearly documented to have an insufficient dopamine response, could benefit from this immensely. It could even eradicate the need for stimulants entirely. It also appears as if certain NMDA antagonists, which are known to reduce stimulant tolerance, such as memantine and amantadine, have had varying degrees of success on their own in ADHD treatment.

Now, I have not tried this, and I highly caution anyone who wants to attempt this to consult with a uniquely knowledgeable psychiatrist or neurologist.

That being said, does anybody know of any research on dopamine sensitization specifically in ADHD treatment? Does anyone have any anecdotes of knowingly or unknowingly doing this?

sarahsweets
03-16-17, 12:34 PM
Can you elaborate more? Im tryng to understand better-but I have some brain farts going on.

Cyllya
03-18-17, 12:31 AM
C15H25N3O posted about micro-dosing a few months ago, saying low doses of Vyvanse worked well for him. (http://www.addforums.com/forums/showthread.php?t=178415)

Did the reddit post specify what doses count as "micro"? I've taken Adderall XR 5mg (so approximately 2.5mg at a time) daily for a few months. It was temporarily effective pharmacotherapy, but I had to raise the dose a few months later due to increased tolerance. It definitely didn't remove the need for stimulants.

Might be worth keeping in mind that caffeine is a dopaminergic drug, and "moderate" intake is 400mg per day, but an ounce of dark chocolate has 5-10mg. So if micro-dosing ANY dopaminergic drug had a high likelihood of causing ill effects to neurotypical people, society would be a lot more screwed up than it is. (But caffeine, apparently (https://en.wikipedia.org/wiki/Caffeine), doesn't bind directly to dopamine receptors, which would probably be the reason it's different.) Also, traditional South American cultures use coca similar to how we use coffee and tea, and it seems to work out okay for them. (Coca is the plant cocaine comes from, and I think it actually does bind to dopamine receptors. At least it's a dopamine reuptake inhibitor.)

That aside, while I'm no neuroscientist, I'm having trouble imagining that higher sensitivity to dopamine would help us much. My understanding (from this research (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085579/) and similar) is that ADHD people tend to have a low tonic level of dopamine but then a compensating high phasic release of dopamine, and that the sudden dopamine surge from the phasic release is the actual cause of the symptoms. (That aforementioned paper only lists hyperactivity/impulsivity symptoms being caused this way; not sure if it also applies to inattentive symptoms.) The reason the dopamine-boosting drugs help is that it raises the tonic dopamine level, which normalizes the phasic dopamine release. If the overly high phasic dopamine whiplash still happened but we had more sensitive dopamine receptors, wouldn't that make symptoms worse?

It also appears as if certain NMDA antagonists, which are known to reduce stimulant tolerance, such as memantine and amantadine, have had varying degrees of success on their own in ADHD treatment.

I have heard of amantadine helping with ADHD, although I thought the reason was that it was itself a dopamine-raising drug. It's also useful for Parkinson's, apparently. Not familiar with memantine.

adhdpi
06-20-17, 03:20 AM
Read this:

I am really not quite sure, but I think I found a way to trigger upregulation within brain cells in order to decrease the negative impact of ADD... The upregulation process involves proteins and increases brain receptors in number. However, I have no proof and no real knowledge of what really happens in brain.

In the brain and body there are homeostasis(equilibrium / stable balance)... Just like temperature homeostasis. Your body seems to maintain a fixed body temperature. If your body temperature is too low then your body will adjust. It has many ways to do this. We call this negative feedback. This is where A (low body temperature) -> causes B (heat up body temperature).

I read from scientific resources that sensitisation and desensitisation (and up-regulation and down-regulation) of brain receptors are ways to maintain homeostasis(equilibrium) of receptor signalling. So neurons only sensitise or desensitise to maintain this homeostasis. So "disturbing" this homeostasis might be a good idea, as it can trigger this process.

When I got treatment with ritalin/ concerta then especially with concerta I felt anxiety, excessive tiredness etc. I thought it could be true that the autonomic nervous system was responsible for this. The autonomic nervous system might also be responsible for tachycardia and the losing weight.

The autonomic nervous system has 2 subdivisions. They are the sympathetic nervous system and the parasympathetic nervous system. The sympathetic nervous system and the parasympathetic nervous system oppose each other in many ways. They are like a balance. While sympathetic nervous system increases heart rate the parasympathetic nervous system is more like a break: decreases heart rate.

Then I found a very low dosage that only produced parasympathetic nervous system effects. This dosage is within therapeutic range.

I found out that concerta disturbed some homeostasis and ultimately as a feedback meganism, this also affected autonomic nervous system (parasympathetic nervous system). But if I "disturb" this homeostasis then sensitisation is what can occur, which is what is triggerd as a result.

Essentially I was thinking about this:

Methylphenidate -> "disturbed" homeostasis -> hypothalamus -> autonomic nervous system -> parasympathetic nervous system

Methylphenidate -> "disturbed" homeostasis -> sensitisation / upregulation (to restore homeostasis/ equillibrium in brain)

Then, I realised these symptomes were likely to be effects of either parasympathetic nervous system domination, med usage or the "disturbing" homeostasis which triggers sensitisation/ upregulation:

Anxiety (scared of having a heart attack for example)
Blood flows to skin, feeling hotter on skin.
Very mild postular hypotension
Decrease of fitness
Self-care behaviour
"Rest and digest" behaviour
More salivation (resulting in spitting on street alot)
Constant feeling of pessimism (thinking with negative feeling, usually about past time happenings)

All very subtle symptomes.

Parasympathetic nervous system seems to control the "flee/ stay safe/ stay in your cosy home" behaviour. This is the reason I felt anxiety. Also pessimism might be adding to this self-protective behaviour. (don't go out, it's unsafe)

Sensitisation takes place within seconds or minutes but upregulation takes place within hours or days. But upregulation is more permanent then sensitisation.

I have done this treatment for a long time (for more then 2 years). I found it to be effective. But there are downsides. It's takes a lot of time and it is unproven. About the upsides: it seems to be way more effective then meds (concerta) alone. It may be useful when it comes to battleing ADD symptomes on long term basis.

Feel free to PM me if you want to comment me with any outstanding knowledge you have about neuroanatomy, proof, disproof, questions etc. Thank you.

disclaimer: I am not a doctor. Please do not take my experience, information or anything as a substitute for a doctor advice. Please visit your doctor if you have any problems concerning your health. Some of the presented information is based on experiences and it is unproven. Please don't see it as proven, scientific literature.