<p>If you want to have a drug affect only a certain area of the brain, your options are:</p>
<ol>
<li><p>Deliver the drug locally</p>
</li>
<li><p>Use a very specific drug that only affects a specific receptor found in a specific location</p>
</li>
</ol>
<p>Those are the only physical possibilities. For option (2), there is an important biological constraint: this method is only plausible if there is in fact a specific receptor found in the specific target location. No amount of drug discovery can help you if the receptors in the target area are also found something else; the perfect drug is going to affect them both.</p>
<p><a href="https://en.wikipedia.org/wiki/Dopamine_receptor_D2" rel="nofollow noreferrer">D2 receptors</a> are not found only in the mesolimbic area. From <a href="https://en.wikipedia.org/wiki/Dopamine_antagonist" rel="nofollow noreferrer">Wikipedia</a> you can expect to find them in:</p>
<blockquote>
<p>striatum, substantia nigra, ventral tegmental area, hypothalamus, cortex, septum, amygdala, hippocampus, and olfactory tubercle</p>
</blockquote>
<p>There are splice variants but I'm not aware of one that is exclusive to mesolimbic areas.</p>
<p>That leaves you with local delivery. You can do local delivery simple enough with a tube and a syringe: put the tube in the brain region you want, put your drug in the syringe. However, if you want to use this in a human rather than a laboratory animal, you'll have to consider the possible side effects of drilling a hole in the skull and having a long-term catheter present. Those procedures might be worth doing in emergency and extreme situations, but it's not going to be a feasible solution for most cases. The risks of infections inside the brain and direct damage to surrounding brain tissue if the tube moves around are going to be too great. You'll also have to deal with an immune response that will disrupt and eventually clog your catheter. All that said, if you want to answer the question of whether it's even <em>possible</em> to do what you want (prevent psychosis by specifically targeting D2 receptors in mesolimbic structures), this is probably the way to start in animal models: deliver your antagonist physically to the target brain region.</p>
<p>For cancer treatments, researchers have been working on other options for <a href="https://en.wikipedia.org/wiki/Antibody%E2%80%93drug_conjugate" rel="nofollow noreferrer">targeted drug delivery such as using antibodies</a>. The idea is that while you may have a drug that's toxic to all cells, if you use an antibody that binds to something on a cancer cell, the concentration of your toxin that the cancer cells are exposed to is much higher than the rest of the body. This might be technologically plausible for your use case, but likely not a real solution without extensive research (you'll need to find an antibody that binds specifically in your target areas) and it's unclear whether the risks and problems with introducing an antibody are worthwhile for your purpose. If your goal is to avoid drug-induced psychosis it would be far simpler to avoid exposure to the psychosis-inducing drug in the first place.</p>

CC BY-SA 4.0
2023-11-30T15:50:57.343Z
Thanks for the interesting insights! What I don't understand is why your options are limited to receptors? e.g. SSRIs work by blocking SERT, the transporter protein. Targeting a mechanism other than directly binding to receptors. So if there were a mechanism that causes the release of dopamine couldn't that be targeted as well? 

I'm not aware of such mechanisms and my neurobiology knowledge is very limited, so this is all just being a wild guess. 

Of course avoiding exposure to psychosis-inducing drugs is the easiest option and this is what's done in clinical environments.
Moritz Roessler
CC BY-SA 4.0
2023-11-30T15:53:03.507Z
However, over 80% of people with drug induced psychosis relapse and could benefit from psychotropics better suited for drug induced psychosis rather than the usual 2nd gen antipsychotis (which work very well, but have many side-effects)
Moritz Roessler
CC BY-SA 4.0
2023-11-30T15:57:00.887Z
@MoritzRoessler Since your question stated "main treatment option is to block D2" it seemed you were talking about receptors, so I wrote my answer about receptors. Everything would apply equally to any other drug target involving release, reuptake, synthesis, etc: to target a specific location, you either need your drug to be delivered only to that location or you need your target to be something found only in that location.
Bryan Krause
CC BY-SA 4.0
2023-11-30T14:21:18.027Z
2023-11-30T14:21:18.027Z
Bryan Krause
<p>Thinking about the treatment of (drug induced) psychosis I'm having the following thoughts.</p>
<p>Drug induced psychosis makes up for 25% - 50% of cases of patients experiencing psychosis . Nevertheless treatment options seem to mainly target psychosis independet of drug use and treatment is based on the <strong>d</strong>opamine <strong>h</strong>ypothesis.</p>
<p>So the main treatment option is to block D2 in the mesolimbic area in order to treat the symptom of D2 hyperactivity which can cause the positive symptoms of schizophrenia e.g. auditory hallucinations.</p>
<p>In my mind, I think if substance (ab)use releases dopaine in the mesolimbic area and causes a D2 hyperactivity than the dopamine being released should also cause a hyperactivity of D1,3,4 which might have other side-effects.</p>
<p>I wonder why we solely block the effects of excessively released dopamine on D2 rather than preventing dopamine from being released in that area to begin with? or would that introduce additional problems?</p>
<p>Would there be a mechanism that causes dopamin to be released upon taking recreational drugs like THC, MDMA, Psylocibin, LSD, Cocaine, DMT, etc.. where you could hook into?</p>
<p>I think a refined strategy could increase the efficiency of antipsychotics used to treat drug-induced related diseases.</p>

<psychiatry><drugs><dopamine><psychosis>
Would it be possible to directly block dopamine release in the mesolimbic area?
Moritz Roessler
# Would it be possible to directly block dopamine release in the mesolimbic area?

(Asked by: username_0 on 2023-11-30)

Thinking about the treatment of (drug induced) psychosis I'm having the following thoughts.

Drug induced psychosis makes up for 25% - 50% of cases of patients experiencing psychosis . Nevertheless treatment options seem to mainly target psychosis independet of drug use and treatment is based on the **d**opamine **h**ypothesis.

So the main treatment option is to block D2 in the mesolimbic area in order to treat the symptom of D2 hyperactivity which can cause the positive symptoms of schizophrenia e.g. auditory hallucinations.

In my mind, I think if substance (ab)use releases dopaine in the mesolimbic area and causes a D2 hyperactivity than the dopamine being released should also cause a hyperactivity of D1,3,4 which might have other side-effects.

I wonder why we solely block the effects of excessively released dopamine on D2 rather than preventing dopamine from being released in that area to begin with? or would that introduce additional problems?

Would there be a mechanism that causes dopamin to be released upon taking recreational drugs like THC, MDMA, Psylocibin, LSD, Cocaine, DMT, etc.. where you could hook into?

I think a refined strategy could increase the efficiency of antipsychotics used to treat drug-induced related diseases.

**Tags:** psychiatry, drugs, dopamine, psychosis


---

## 1 answers

### Answer by username_1 on 2023-11-30. Score: 1 | Accepted answer

If you want to have a drug affect only a certain area of the brain, your options are:

1. Deliver the drug locally
2. Use a very specific drug that only affects a specific receptor found in a specific location

Those are the only physical possibilities. For option (2), there is an important biological constraint: this method is only plausible if there is in fact a specific receptor found in the specific target location. No amount of drug discovery can help you if the receptors in the target area are also found something else; the perfect drug is going to affect them both.

[D2 receptors](https://en.wikipedia.org/wiki/Dopamine_receptor_D2) are not found only in the mesolimbic area. From [Wikipedia](https://en.wikipedia.org/wiki/Dopamine_antagonist) you can expect to find them in:

> striatum, substantia nigra, ventral tegmental area, hypothalamus, cortex, septum, amygdala, hippocampus, and olfactory tubercle

There are splice variants but I'm not aware of one that is exclusive to mesolimbic areas.

That leaves you with local delivery. You can do local delivery simple enough with a tube and a syringe: put the tube in the brain region you want, put your drug in the syringe. However, if you want to use this in a human rather than a laboratory animal, you'll have to consider the possible side effects of drilling a hole in the skull and having a long-term catheter present. Those procedures might be worth doing in emergency and extreme situations, but it's not going to be a feasible solution for most cases. The risks of infections inside the brain and direct damage to surrounding brain tissue if the tube moves around are going to be too great. You'll also have to deal with an immune response that will disrupt and eventually clog your catheter. All that said, if you want to answer the question of whether it's even *possible* to do what you want (prevent psychosis by specifically targeting D2 receptors in mesolimbic structures), this is probably the way to start in animal models: deliver your antagonist physically to the target brain region.

For cancer treatments, researchers have been working on other options for [targeted drug delivery such as using antibodies](https://en.wikipedia.org/wiki/Antibody%E2%80%93drug_conjugate). The idea is that while you may have a drug that's toxic to all cells, if you use an antibody that binds to something on a cancer cell, the concentration of your toxin that the cancer cells are exposed to is much higher than the rest of the body. This might be technologically plausible for your use case, but likely not a real solution without extensive research (you'll need to find an antibody that binds specifically in your target areas) and it's unclear whether the risks and problems with introducing an antibody are worthwhile for your purpose. If your goal is to avoid drug-induced psychosis it would be far simpler to avoid exposure to the psychosis-inducing drug in the first place.

> **Comments:**
> **username_0**: Thanks for the interesting insights! What I don't understand is why your options are limited to receptors? e.g. SSRIs work by blocking SERT, the transporter protein. Targeting a mechanism other than directly binding to receptors. So if there were a mechanism that causes the release of dopamine couldn't that be targeted as well?   I'm not aware of such mechanisms and my neurobiology knowledge is very limited, so this is all just being a wild guess.   Of course avoiding exposure to psychosis-inducing drugs is the easiest option and this is what's done in clinical environments.  
> **username_0**: However, over 80% of people with drug induced psychosis relapse and could benefit from psychotropics better suited for drug induced psychosis rather than the usual 2nd gen antipsychotis (which work very well, but have many side-effects)  
> **username_1**: @MoritzRoessler Since your question stated "main treatment option is to block D2" it seemed you were talking about receptors, so I wrote my answer about receptors. Everything would apply equally to any other drug target involving release, reuptake, synthesis, etc: to target a specific location, you either need your drug to be delivered only to that location or you need your target to be something found only in that location.  

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