Serotonin and euphoria and other stuff

[neurotic]

I'm no neurologist, all I know is stuff I read online, but serotonin intrigues me. Like, some people say it is associated with the euphoria of drugs, right? Like both coke and MDMA are euphoric and although via different mechanisms (coke being a reuptake inhibitor and MDMA being a releasing agent), increase the concentration of serotonin on the synapse, right? Of course they also increase dopamine and norepinephrine.

And I guess it is thought that this plays a role in the euphoria/feeling good, hence why some antidepressants are serotonin reuptake inhibitors themselves, with long half-lifes so that for a long time, there is more serotonin in the synapses, making the people feel better, right? But I just believe like may be serotonin isn't that simple and that merely higher levels of serotonin haven't much to do with euphoria.

I mean, if I IV a dopamine and norepinephrine reuptake inhibitor, such as methylphenidate, right away, on my brain, there will be an increased concentration of these neurotransmitters which is what causes the high. But, so if low levels of serotonin are depression, and higher concentrations (but not high enough to cause serotonin syndrome) of serotonin are pleasure, this makes me think that if IV a serotonin reuptake inhibitor (which will instantly raise serotonin levels in the synapse) I'll feel at least euphoric, right?

Do opioids have some action on serotonin? Because they do induce euphoria/feeling good.

Any thoughts on that?

 

[sekio]

there is more serotonin in the synapses, making the people feel better, right?

Nope. Dopamine and norepinephrine activity in reward circuits of the brain probably have more roles to play than brain serotonin levels. A norepinephrine transporter blocker is effective at decreasing the effects of MDMA, for instance. [ref].

Serotonin isn't any sort of magical happy chemical, the commonly held myth that it's responsible for feeling good is a load of hooey. It was basically coincidence that some depressed folks have lower levels of brain serotonin and SSRIs are sometimes effective in treating them, but they are far from reliable and just like you pointed out, there's many drugs that don't neccesarily have an effect on serotonin levels that are euphoric in their own right (THC, nicotine, metylphenidate, ketamine). There are also many other antidepressants that don't work by elevating serotonin concentrations.

It is also curious that even though SSRIs are well absorbed and likely are binding to brain tissue and having an effect mere hours after administration, yet it takes several weeks to see visible improvements in some... so there must be some other downstream action taking place.

The number of people who find SSRIs directly euphoric are probably minimal. SSRI abuse is not a big problem.

 

[neurotic]

Sweet, I thought no one was gonna pay attention to this thread.

I second that thought that serotonin isn't responsible for feeling good, may be I didn't make it clear in my first post, glad to see someone else agrees with me, because when I'm talking to most people, they swear by SSRIs and serotonin bullshit. One thing I'd like to see is how an administration of a (selective) serotonin antagonist would affect the high of for example coke, in a similar experiment to that one you mentioned about a NET blocker decreasing the effects of MDMA.

I even feel like IVing myself some SSRI just to see if there's anything noticeable in a dramatic increase in serotonin concentration. Good way to end up with serotonin syndrome, but I'm pretty curious about it. Just for science, you know.

I'm quite interested too about serotonin's relationship with psychedelia. I mean, molecules different to serotonin binding to the 5HT2A cause changes in perception in all senses, visual, tactile and all that stuff (right?). So 5HT2A would be responsible for our perception (at least to some point), and while there's serotonin doing its thing there, we have our regular perception, but when you put some other stuff there, our perception gets altered. Am I making sense? What would increased serotonin levels cause here? Nothing it seems otherwise SSRIs would be psychedelic, right?

EDIT: Also, people always seem to say that those week-long depressions following heavy MDMA abuse are caused by depletion of serotonin. I remember a pic (I guess it was in thedea.org) of a babboon's brain, before and after the administration of a high MDMA dose, with serotonin neurons or the likes (I don't know really) highlighted, and post-MDMA dose picture in fact had way less of those neurons. But, if serotonin isn't related to feeling good, what would cause this?

Yeah, I have lots of questions haha

 

[JWills20]

The subjective effects of drugs tend to come down to the overall neurochemical balance they produce, as opposed to just the one dominant neurotransmitter. Drugs like cocaine and MDMA are euphoric because they tend to create a good balance of the catecholamines, albeit not always being equally released. For example, MDMA wouldn't be half as recreational without the DA/NE increase. The serotonin spike alone wouldn't be enough to cause such a profound state of euphoria, it just distinguishes the subjective effects from that of your usual DA/NE-based amphetamines. Another complex part of neuropharmacology is the fact that the drug's subjective effects may not always be caused by direct drug-induced cellular release. What I mean is that causing neurotransmitter release and receptor activation can cause downstream effects on systems that it governs. In the instance of MDMA, some of the dopamine release is hypothesised to occur as a result of downstream activation from 5-HT2(A) activation initially caused by the serotonin flood. Spikes of dopamine are probably what creates the feeling of 'rolling' in MDMA users (the sensation of psychologically going up and down).

Also, people always seem to say that those week-long depressions following heavy MDMA abuse are caused by depletion of serotonin. I remember a pic (I guess it was in thedea.org) of a babboon's brain, before and after the administration of a high MDMA dose, with serotonin neurons or the likes (I don't know really) highlighted, and post-MDMA dose picture in fact had way less of those neurons. But, if serotonin isn't related to feeling good, what would cause this?

These images were science taken out of context and manipulated to fit their picture. IIRC, they actually reflected blood flow which is always changing. Whenever you perform a cognitive task, blood flow increases in the region that is performing the task. These principles are how fMRI works, as it measures the amount of oxygenated blood, thus serving as a marker of brain activation during cognitive tasks. A respective area of the brain could have lots of de-oxygenated blood (indicating activation and usage) or lots of oxygenated blood (indicating little usage), depending on what you're doing. So in reality these images were just bullshit.

I'm quite interested too about serotonin's relationship with psychedelia. I mean, molecules different to serotonin binding to the 5HT2A cause changes in perception in all senses, visual, tactile and all that stuff (right?). So 5HT2A would be responsible for our perception (at least to some point), and while there's serotonin doing its thing there, we have our regular perception, but when you put some other stuff there, our perception gets altered. Am I making sense? What would increased serotonin levels cause here? Nothing it seems otherwise SSRIs would be psychedelic, right?

This is kind of different. The reason psychedelic drugs are psychedelic are because they don't cause a natural serotonin binding and release (like MDMA does), but rather slot into the receptor site and change how it actually functions. SSRI's work in the typical sense of just causing increased serotonin via blocking of the reuptake transporter, so they don't alter any way in which the receptors function, thus why they don't produce any psychedelia. This is why MDMA is also much less psychedelic, despite causing a drastic increase in extracellular serotonin.

 

[neurotic]

These images were science taken out of context and manipulated to fit their picture. IIRC, they actually reflected blood flow which is always changing. Whenever you perform a cognitive task, blood flow increases in the region that is performing the task. These principles are how fMRI works, as it measures the amount of oxygenated blood, thus serving as a marker of brain activation during cognitive tasks. A respective area of the brain could have lots of de-oxygenated blood (indicating activation and usage) or lots of oxygenated blood (indicating little usage), depending on what you're doing. So in reality these images were just bullshit.

So do you have any idea of what's behind post-MDMA abuse depression? Could it be just depletion of dopamine and stuff just like any other stim comedown? Why would some people be depressed for so long?

This is kind of different. The reason psychedelic drugs are psychedelic are because they don't cause a natural serotonin binding and release (like MDMA does), but rather slot into the receptor site and change how it actually functions. SSRI's work in the typical sense of just causing increased serotonin via blocking of the reuptake transporter, so they don't alter any way in which the receptors function, thus why they don't produce any psychedelia. This is why MDMA is also much less psychedelic, despite causing a drastic increase in extracellular serotonin.

Yeah, I see. And I believe then that MDA - never tried but apparently is a more psychedelic brother of MDMA - besides releasing serotonin just like MDMA, will also bind to 5HT2A and cause psychedelia just like other serotonergic psychs, right?

Great talking to you guys by the way, I hope you don't mind all my questions

 

[Lightning-Nl]

The number of people who find SSRIs directly euphoric are probably minimal. SSRI abuse is not a big problem.

I recently read an erowid trip report (dated 1999) where someone claimed that when Paroxetine was combined with Tranylcypromine (irreversible MAOI), that they experienced very powerful stimulating effects almost identical to that of Amphetamine. Personally, I believe the story to be true... however, doing so was quite idiotic of the person who did it.

I think in combination with an MAOI, SSRI's could be recreational. However, if you play with fire... eventually, you will get burned.

 

[JWills20]

So do you have any idea of what's behind post-MDMA abuse depression? Could it be just depletion of dopamine and stuff just like any other stim comedown? Why would some people be depressed for so long?

This is a complex one. Acutely, post-MDMA abuse depression is probably linked to decreased serotonin neurotransmission, which probably has downstream effects on other systems (or even upstream, but I don't know, serotonin seems to be very high up in terms of processing). This probably lasts until the enyzme that metabolizes L-tryptophan into 5-HTP is back online (thus vesicular 5-HT is restored) and receptors return back to baseline after reducing themselves as a defense mechanism to the MDMA abuse (note the difference between use and abuse).

The problem with interpreting long-term depression is the complex link between the brain-development-behaviour (as exhibited in developmental neuroscience research). As human beings, the way in which develop and change over time is extremely dynamic. What I mean is that you are pre-disposed with a set of genes from your parents, but the way in which these genes express themselves (remember these genes essentially govern the development of cells and so control brain processes such as neurogenesis & synaptogenesis) can be changed by your individual behaviour and environment. This kind of genetic-environmental interaction is most pertinent when you're young and the brain is most neuroplastic. Long-term depression probably reflects an initial neurochemical balance interruption (caused by MDMA abuse), which then changes your behaviour and the environment you live in (not wanting to go outside, loss of motivation for things you enjoy so you don't do them etc), and begins to work against your favour as you battle with it all. This is why cognitive strategies are still useful and why pharmacological interventions aren't always very effective. Long-term depression isn't as simple as low serotonin = depression. Low serotonin, and the downstream effects this causes, may act as a trigger for psychiatric conditions which then begin to manifest themselves even while the brain is trying to recover and then has recovered. I personally feel that long-term comedowns go further than simple brain alterations, because we know the brain is remarkably neuroplastic and able to recover quite quickly. Anything persisting for longer than a few months is no longer likely to be simply brain changes. These are just my thoughts.

Yeah, I see. And I believe then that MDA - never tried but apparently is a more psychedelic brother of MDMA - besides releasing serotonin just like MDMA, will also bind to 5HT2A and cause psychedelia just like other serotonergic psychs, right?

Great talking to you guys by the way, I hope you don't mind all my questions

Not sure about this one. But it probably imposes a higher psychedelic serotonin-binding than MDMA yeah.

 

[thikal]

It is also curious that even though SSRIs are well absorbed and likely are binding to brain tissue and having an effect mere hours after administration, yet it takes several weeks to see visible improvements in some... so there must be some other downstream action taking place.

I read somewhere (I forgot sorry) that Prosac increase neuro-plasiticy, and it can be that effect and not the effect on serotonin that can alleviate depression. Im I wrong? Antidepressive effect of sport, fasting, meditation and some antidepressive are linked to this effect on increase neuronal plasticity in my (poor) understanding. Maybe an increase on autophagy too. I may be all wrong, I don't have link to support my assumptions but maybe you already know that sekio or an other one

 

[neurotic]

This is a complex one. Acutely, post-MDMA abuse depression is probably linked to decreased serotonin neurotransmission, which probably has downstream effects on other systems (or even upstream, but I don't know, serotonin seems to be very high up in terms of processing). This probably lasts until the enyzme that metabolizes L-tryptophan into 5-HTP is back online (thus vesicular 5-HT is restored) and receptors return back to baseline after reducing themselves as a defense mechanism to the MDMA abuse (note the difference between use and abuse).

The problem with interpreting long-term depression is the complex link between the brain-development-behaviour (as exhibited in developmental neuroscience research). As human beings, the way in which develop and change over time is extremely dynamic. What I mean is that you are pre-disposed with a set of genes from your parents, but the way in which these genes express themselves (remember these genes essentially govern the development of cells and so control brain processes such as neurogenesis & synaptogenesis) can be changed by your individual behaviour and environment. This kind of genetic-environmental interaction is most pertinent when you're young and the brain is most neuroplastic. Long-term depression probably reflects an initial neurochemical balance interruption (caused by MDMA abuse), which then changes your behaviour and the environment you live in (not wanting to go outside, loss of motivation for things you enjoy so you don't do them etc), and begins to work against your favour as you battle with it all. This is why cognitive strategies are still useful and why pharmacological interventions aren't always very effective. Long-term depression isn't as simple as low serotonin = depression. Low serotonin, and the downstream effects this causes, may act as a trigger for psychiatric conditions which then begin to manifest themselves even while the brain is trying to recover and then has recovered. I personally feel that long-term comedowns go further than simple brain alterations, because we know the brain is remarkably neuroplastic and able to recover quite quickly. Anything persisting for longer than a few months is no longer likely to be simply brain changes. These are just my thoughts.

So, post MDMA abuse, the enzyme that converts L-tryptopahn into 5-HTP and later in serotonin is like 'off', and that's why there's lower serotonergic activity? The tryptophan you're eating isn't being converted in serotonin? Cool.

And yeah, I agree with about the fact that we are born with certain genetic traits but it is a combination of them and our experiences and learning that make us. That being said, a kid (kids have greater neuroplasticity right?) growing up with parents with depressive behaviours due to their depressive beliefs, will quickly learn these behaviours and thought patterns, and bam, become and depressive adult themselves. That's what makes me think that SSRIs are unnefective, unless it is just a lack of serotonin which like you said will have downstream/upstream effects on other systems, but on chronic long term depression, I believe it's all about learned behaviours and thought patterns.

I recently read an erowid trip report (dated 1999) where someone claimed that when Paroxetine was combined with Tranylcypromine (irreversible MAOI), that they experienced very powerful stimulating effects almost identical to that of Amphetamine. Personally, I believe the story to be true... however, doing so was quite idiotic of the person who did it.

I think in combination with an MAOI, SSRI's could be recreational. However, if you play with fire... eventually, you will get burned.

I'm very skeptic of several reports of Erowid, regarding those less recreational drugs at least, I've seen 'trip reports' about Xanax completely what the fuck, complete placebo. I used to have my Fluoxetine in gel caps with powder inside and I'd promptly slam that shit, and make a report. I bet there'd be no euphoria or noticeable effects, may be only serotonin syndrome.

So, if I get it right, serotonin is related to perception, at least the 5HT2A receptor (when we're sober our perception is due to serotonin in our synapses, but when there's LSD binding there, we have a whole perceptual craziness going on), but is still responsible for regulation of other systems (like, I remember you said that 5HT(2A?) activation caused a release in dopamine, something like that, might be wrong), hence the multitude of serotonin receptors and its possible effects on mild depression, but is not directly related to pleasure or anything, did I get it right?

 

[JWills20]

So, post MDMA abuse, the enzyme that converts L-tryptopahn into 5-HTP and later in serotonin is like 'off', and that's why there's lower serotonergic activity? The tryptophan you're eating isn't being converted in serotonin? Cool.

While I haven't read much MDMA literature in a while, the following is based upon my prior research. Everytime you take MDMA it causes, at least partially, an inhibition of the enzyme that metabolizes L-tryptophan into 5-HTP. Similarly, everytime you take MDMA it causes, at least partially, serotonin depletion (kinda obvious really, if it didn't you wouldn't get the specific subjective effects!). Put these two together and you've got lower than usual vesicular serotonin (where it's stored within the cell), and an inability to naturally synthesize serotonin from L-tryptophan in your diet. This probably causes the acute & delayed hangover (the 'Tuesday blues' as it were). Depending on the dose, many MDMA users actually feel better the day after MDMA. This is because the serotonin flood has increased receptor densities of key mood-altering receptor sites (notably the 5-HT2 site). Thus, users can get the afterglow. Now depending on the dose, over the next few days the brain will either return back to baseline (explaining the afterglow with no noticable comedown, usually associated with lower doses) or regress into a worse condition than baseline (explaining a comedown, probably a defense mechanism to higher doses and the serotonergic stress higher doses would impose). Hope that all makes sense, if it doesn't I can clarify. These are also some of my own theories and probably don't have any direct empirical support, so add a pinch of salt.

And yeah, I agree with about the fact that we are born with certain genetic traits but it is a combination of them and our experiences and learning that make us. That being said, a kid (kids have greater neuroplasticity right?) growing up with parents with depressive behaviours due to their depressive beliefs, will quickly learn these behaviours and thought patterns, and bam, become and depressive adult themselves. That's what makes me think that SSRIs are unnefective, unless it is just a lack of serotonin which like you said will have downstream/upstream effects on other systems, but on chronic long term depression, I believe it's all about learned behaviours and thought patterns.

Gene development is some complex shit, seriously. I just glaized over it really, so as to not waste time being stodged down with the complexity of it all (I wrote an essay on it for my MSc). But the way genes cause who we are is not innate, nor acquired (like traditional developmental cognitive psychology seems to obsessed with testing). Neuroplasticity and genetic-environment interactions have shown that pretty convincingly. SSRI's can work by increasing the brain neurotransmission, but yeah cognitive elements should not be forgotten. It's also part of my own theories as to why SSRI's aren't so effective. The best studies need to appreciate both neuroscience and psychology IMO. That is what 'Cognitive Neuroscience' is meant to do, but it really fucking fails in places. Everyone has their little niche of paradigmatic focus (say neuropsychology, neuroscience, cognitive psychology) that they want to use, instead of trying to combine the disciplines.

 

[endotropic]

You might find this review interesting, very recent:

The role of serotonin in drug use and addiction.

Abstract
The use of psychoactive drugs is a wide spread behaviour in human societies. The systematic use of a drug requires the establishment of different drug use-associated behaviours which need to be learned and controlled. However, controlled drug use may develop into compulsive drug use and addiction, a major psychiatric disorder with severe consequences for the individual and society. Here we review the role of the serotonergic (5-HT) system in the establishment of drug use-associated behaviours on the one hand and the transition and maintenance of addiction on the other hand for the drugs: cocaine, amphetamine, methamphetamine, MDMA (ecstasy), morphine/heroin, cannabis, alcohol, and nicotine. Results show a crucial, but distinct involvement of the 5-HT system in both processes with considerable overlap between psychostimulant and opioidergic drugs and alcohol. A new functional model suggests specific adaptations in the 5-HT system, which coincide with the establishment of controlled drug use-associated behaviours. These serotonergic adaptations render the nervous system susceptible to the transition to compulsive drug use behaviours and often overlap with genetic risk factors for addiction. Altogether we suggest a new trajectory by which serotonergic neuroadaptations induced by first drug exposure pave the way for the establishment of addiction.

 

[neurotic]

looks like serotonin controls a whole lot of stuff in our brain then, the different 5HT receptors are so different from each other in terms of function

 

[WSH]

looks like serotonin controls a whole lot of stuff in our brain then, the different 5HT receptors are so different from each other in terms of function

Yes, and sometimes they even have completely OPPOSITE effects, like 5-ht1a vs 5-ht2a/c.

 

[crOOk]

^what sekio first said.

On the other hand, I am bipolar and EVERY serotonergic drug I've tried causes considerable euphoria in me. SSRI's, Tramadol, all the recreational serotonergic drugs, shit even lithium does a great job in killing my depression. Primarily dopaminergic and noradrenergic do usually cause some euphoria as well, but the type of classical hypomanic response I'm talking about has usually been triggered by serotonergic agents.

Still... Attributing such complex processes to single receptors is very problematic and doesn't do reality justice at all. It's always a multitude of neurons interacting with each other and with themselves through a number of different receptors and most people knowledgable on this will not like to hear this kind of over simplification which unfortunately spans through the whole range of the recreational drug scene and the media.
We simply do not know all the answers to the question of how exactly activity of certain groups of neurons and their receptors relate to mood.

 

[St3ve]

Do opioids have some action on serotonin? Because they do induce euphoria/feeling good.

Opioids it seems have the most direct mechanism in terms of creating good feelings. Berridge and his colleagues have found so called hedonic hot spots in a few areas in the brain. When they injected very tiny amounts of opioids in small local areas of the brain they found a few places that subsequently increased the pleasure rating of rats to the taste of sweet. They propose that the assignment of "feeling good" to a sensation/stimulus is done by these hotspots. Opioids can modulate the amount of feeling good to something. Eg. gently stroking your arm under normal conditions feels nice, under the influence of certain drugs this can be changed to feeling orgasmically good. Opioids in these hot spots act like gain buttons, where more opioid receptor activation is equal to turning the dial up a few notches.
See Pecina et al, 2006 for a review on this subject. Link: http://www.smith-lab.org/wp-content...idge-Hedonic-hotspots-Neuroscientist-2006.pdf

As for the role of serotonin in perception, I don't think there's a simple answer for that... I am going to try and give you an idea of how I understand it works though! I'll start with the early work done by Kandel on the seaslug as it makes for a nice simple model. He studied seaslugs because they have a relatively simple neural network and their neurons are nice and big, making them easier to work with.

The seaslug has a gill withdrawal reflex, this means that normally if the sea slug gets poked it will withdraw it's gill to protect it from harm. This involves a sensory neuron to detect touch and a motor neuron to signal to the muscles to contract. However if you "scare" the slug with another first and then poke it elsewhere, the reflex is more intense. This is because the sensitivity of the motor neuron to input from the sensory neuron can be changed through neuromodalutory input from serotonin.
There's more info on basic learning mechanisms here: http://michaeldmann.net/mann18.html
Other neuromodulators like dopamine and noradrenaline do the same thing on a circuit level, it's just that these will affect different intracellular pathways and depending on their location in the brain can have drastically different functions.

The visual system is a bit more complex, it's basically a long chain of different processing centres in the brain that each process an extra layer of complexity. The basic idea is that photoreceptors in the retina respond to light hitting them. These already help separate input, some receptors will only respond to green light, some only with red light, etc. A group of photoreceptors then project to ganglion cells (via a few interneurons) which in turn project to the lateral geniculate nucleus which projects to the primary visual cortex. These areas split the input from both eyes and do some processing on the input. From the primary visual cortex the visual input is sent into two different directions called the ventral and dorsal stream. The ventral stream specialises in processing details on colour, shape, object recognition, and also projects to structures involved in emotion and memory etc. The dorsal stream is concerned with detecting motion, calculating and predicting trajectories and updating and connects the motor cortex so that you can respond to motion with motion of your own.

The primary visual cortex is relatively upstream in terms of visual processing and is rich in 5HT2A receptors. If you go and activate these in unnatural ways with LSD, they will respond very differently to input coming from the lateral geniculate nucleus. In turn they will send abnormal signals to all the structures downstream and thereby change the conscious percept. For example, the fusiform gyrus, is thought to be specialized in recognizing faces. Hyperactivity of this area due to modulation of input by LSD might explain why some people will see faces whilst tripping! Other areas are specialized in recognizing squares, triangles, circles, certain movements, people, animals, gradients, and so on and so on. I think there was even a study that found a so called Jennifer Anniston neuron. It only responded to pictures Jennifer Anniston's face (even on different photos), but not to other faces!

The same general pattern holds true for the auditory system, the olfactory system and the other sensory system. It starts with receptors detecting a stimulus and sending it from one area to the other, each area processing the input and sending it to other areas for further analysis. In between these areas you have multiple neuromodulatory systems that alter the firing rate of other neurons and allow for adaptability.

I hope that makes some sense... xD

 

[neurotic]

That did make sense and i really liked reading it. Thanks for the contribution man.

Edit: i understand now how the whole perceptual changes from serotonergic psychs happen, but what about weed? We all know that at high enough doses it becomes mildly psychedelic and i myself have already experienced light OEVs and all that shit with lots of weed. Lots of people report that after a trip, the weed high becomes more psychedelic. Could weed have some kind of connection with serotonin or shit? What would be the mechanism producing weed's psychedelia? In the end weed is a psychedelic, its just we're used to doin only small doses of it imo. May be i should start a new thread to discuss about this, ill do it later when im on my computer, on my phone right now.

 

[Lightning-Nl]

^^
In addition to the post above. This is believed to be the causing mechanism behind psychotic illness in the current literature. Somewhere in the process of interpretating stimulus - incorrect receptor activation happens (whether this is a lack of stimulus or an over abundance of stimulus or a mix if both is not certain at this time) this causes the brain to misinterprete information.

This misinterpretation of stimulus causes the brain to believe things are happening (or not happening) that really aren't (or are) - causing inappropriate emotional responses as well as extreme thought disorder.

It's currently believed that schizophrenics have a lack of ganglionic and glutamatergic stimulation. To componsate for this lack neuralplasticity - Monoaminergic neurons have to up regulate monoaminergic activity to keep the person alive as well as down regulate and up regulate GABAnergic transmission in other areas.

Specifically - GABAnergic activity spikes in the cerebellum and hippocampus, but completely disintegrates in the frontal lobe.

 

[St3ve]

I have no idea how weed can cause the mild visual effects it does... I've only gone in depth in investigating how it affects memory.

Natural cannabinoids in the brain generally act as a sort of safety valve. Normally signalling occurs in an upstream to downstream fashion, ie. from sensation to perception. From neuron 1->2->3->4 and so on, cannabinoid messaging takes place in a retrograde fashion as in neuron 4->neuron 3 ->2. In doing so the downstream neuron can prevent itself from getting stimulated again by the upstream neuron in order to prevent over-activation. In some cases it can also increase it's own stimulation by encouraging the neuron before it to fire again. Cannabinoid receptors are spread pretty much across the whole brain and are found in a variety of neuron types. So activating a cannabinoid in one are in the brain might increase serotonin action there, or decrease it. It might also increase/decrease GABA release, dopamine, NA, or neuropeptide release. They do a lot of different things depending on where they are located.

Here's a paragraph from an essay from my BSc times I wrote on cannabinoids and memory. The interesting thing here is that normal cannabinoid signalling acts to induce memory (LTP)! It's by overflooding the hippocampus with THC that the sensitive nature of this mechanism is disrupted and causes memory impairment:

In a crucial study by Carlson et al (2002) it was found that cannabinoids can facilitate the induction of LTP in hippocampal neurons. In the CA1 of the hippocampus pyramidal cells release endocannabinoids to induce depolarization-induced suppression of inhibition (DSI). This prevents firing of inhibitory cells for a short moment of time, so that a normally ineffective train of excitatory post-synaptic currents (EPSCs) during this time window is able to induce LTP in the pyramidal cell, but not neighbouring cells. This suggests that endocannabinoids may act to facilitate LTP induction in individual cells, by effectively increasing the signal-to-noise ratio of surrounding EPSCs. It also explains how systemic administration of cannabinoid receptor agonists would antagonize LTP induction, as it affects all CB receptor containing cells. This would lead to a global facilitation of LTP rather than at specific sites, effectively reducing the signal-to-noise ratio (Riedel and Davies, 2005). Furthermore, it could explain how a low dose administration of Δ9THC resulted in increased spike potentiation (Nowicky and Teyler, 1987). Activation of few CB receptors is less likely to interfere with the high specificity of this single cell facilitation of LTP than systemic activation of all CB receptor containing cells.

Refs:

Carlson et al. 2002. Endocannabinoids facilitate the induction of LTP in the hippocampus. Nature Neuroscience 5, 723 - 724
Nowicky AV and Teyler TJ.1987.The modulation of long-term potentiation by delta-9-tetrahydrocannabinol in the rat hippocampus, in vitro. BRB, 19:663-672.
Riedel G and Davies SN. (2005). Cannabinoid function in learning, memory and plasticity. HEP, 168:445-477.