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THC Neuropharmacology

Essentially what THC does, is "trick" the brain into activating cannabinoid neurons, by mimmicking an other neurotransmitter.

In your brain you have "cannabinoid receptors". These are activated by a neurotransmitter called anandamide.... THC is also a cannabinoid chemical, so it will mimmick anandamide by binding neurotransmitters, which then activates the neurons.
 
I've often wondered the same thing myself. Can anybody post links/paste articles from other sources for all to read?
 
^Grrr... was my explanation not good enough!

Here's a link just for you -

http://science.howstuffworks.com/marijuana3.htm

If we look at this picture, we can see what areas of the brain weedage effects...

marijuana-brain.gif


cannabinoid receptors exist in the 3 coloured areas.

According to the site, those areas are responsible for:

Short-term memory
Coordination
Learning
Problem solving
 
Then how are the other effects of marijuana explained? Hunger, possible paranoia, etc? There must be more stimulationg that that
 
notice the lack of cannabinoid receptors in the brain stem region...hence the "safeness" of the drug.

in reply to nenarOPI: In your brain, normal(everyday, sober)feelings of hunger, paranoia etc. are all regulated by anandamide interacting with the endocannabinoid system in the brain. When you smoke weed, you "super-saturate" the receptors, thus causing these effects to be intensified.
 
This was a pretty informative read. I reckon more people should learn about how their drug works before they dive right into it .
 
This seems to simplistic. THere must be other neurotransmitters involved (even if it is simply the result of cannabinoid receptor mediation).

Dr. McBudstoke said:

in reply to nenarOPI: In your brain, normal(everyday, sober)feelings of hunger, paranoia etc. are all regulated by anandamide interacting with the endocannabinoid system in the brain.

There's far more than that going on. Anxiety and panic (i.e., "fight or flight" responses) in part originate in the limbic system (in the amygdala specifically), and in turn involves a norepinephrine release.

I'm asking about THC neuropharmacology because I'm trying to determine if there is a neurochemical reason for concurrent pot/MDMA users to experience anxiety/panic attacks (almost all anxiety reports I've seen from MDMA users show concurrent pot use).

Any authoritative scientific leads on this would be greatly appreciated.
 
I would suggest that it's due to the fact that ecstacy is a stimulant (stimulants are notorious for potentiating anxiety and paranoia, when concurrently used with cannabis). MDMA's effect on dopamine may contribute to people's anxiety when smoking cannabis. It's interesting to note that on the come-up, people using MDMA sometimes experience feeling of anxiety as a result of this dopamine release.
 
The research in this field is all pretty new and not much is known. But what can be said is THC and related compounds are CB1 (cannabinoid1, CB2 also exists but not in the brain) receptor agonists (or at least partial agonists), and have a wide range of effects including probable direct and indirect release of dopamine in many areas of the brain pertaining to anxiety, paranoia, and reward systems (=euphoria)- probable mechanisms and causes being; CB1 acts as an intermediary in the opioid-to-mesolimbic DA pathway and agonism of CB1 at DAergic GABA nerve terminals causes disinhibition of DA release (similar to alcohol). Indeed its actions on the glutamate system seems to hold the key to a large range of weed's effects including sedation, relaxation, loss of motor coordination, etc., also directly affecting the "psychedelic" glutamate systems that are activated upon 5-HT2a receptor agonism, which as you should know is the primary site of LSD and most of the other psychs (excluding things like salvia), and some NMDA antagonism causing dissociation/disconnectedness effects similar to ketamine. Also there is noradrenaline release which gives the stimulant effect, and effects on the acetylcholine system (in the hippocammus) seem to be the probable cause of memory impairment. A lot of other things happen, I didn't even touch on its analgesic properties and long list of other known effects, but these are probably the ones which interest you the most.
note: I am just a layman but this is what I can gather from current literature.
 
CB1 receptors have been thoerised by some to be a kind of volume control for neurons in the cortex (and area left out of the above diagram), infact, if one really wants to see the distribution of CB1 receptors, then they should look at this JPG here.

CB1 receptors are linked broadly inside the neuron. The classical linkage is to the G-protein Gi, which inhibits the enzyme adenylate cyclase... that goes on and goes a bunch of things like inhibiting protein kinase A, which can do various things, such as inhibit presynaptic NMDA receptors. Importantly though CB1 receptor activation inhibits voltage sensitive calcium channels (VSCC). VSCC are the channels which cause neurotransmitters to be release when a neuron fires. By inhibiting the VSCC, CB1 receptors inhibit neurotransmitter release. They have this action of both excitatory glutamate releasing cells, and inhibitory GABA releasing cells, as well as on dopamine and presumabley on most other cell types.

This is one reason why cannabinoids have such a unique action, that one can't classify as either excitatory or inhibitory, because they inhibit both excitatory and inhibitory transmission, and hence don't really alter the balance of excitation to inhibition in the brain.

CB1 receptors also stimulation G-protein coupled Inward-rectifier pottasium channels (GIRK), which does the same thing as above, by allowing increase K+ to flow into the cell, and keep the neuron polarized/hyperpolarized.
 
Since THC and the other cannabinoids ingested in marijuana usage are quite "sticky" molecules and bind to many surfaces in the brain, it would be hard to pinpoint the exact mechanism of paranoia and other effects such as anxiety, as THC indirectly effects endless other neural systems such as 5HT, DA, NE, NMDA, MCR, BDNF, opioids, ACh etc. As the above two posters have pointed out, the "pharmacology" of THC has just begun to be unraveled. Research is discovering non-CB receptor mediated cannabinoid effects. Vanilloid type receptors, related to the capsaicin(think hot pepper) molecule, are also interestingly involved in cannabinoid pharmacology (PubMed: 15140635). What all this means is that we don't really know how cannabinoids work in vivo, although we scientists can manufacture some cool dose-response or concentration-variance charts of cannabinoid ligands such as SR141716a (which in the literature is labelled anything from a partial agonist (PMID: 15075622), to a inverse agonist, and an antagonist (PMID: 14709326), WIN 55,212-2 (agonist), and inverse agonist AM251.

If I was to guess factors influencing paranoia produced by pot/MDMA, the indirect release and retrograde signaling of dopamine in various corticotemporolimbic regions probably plays a role, possibly causing a temporary temporolimbic dysfunction, as hypothesized is to occur in schizophrenics, who often display paranoia (Weinberger D., 2003). Psychologically, the distortion of reality, STM loss, along with the temporal distintegration and over-thinking associated with cannabis intoxication could all be contributing factors. Again, with chaotic quantum biological systems such as our CNS, it is possible one's person's paranoia is another's euphoria, as we all function differently on diverse levels of top-down and bottom-up organization of the nervous system. As they say, different strokes for different strokes, especially since each of our brains is constantly rewiring themselves in response to the environment.

Let's not even start on second and third messenger systems, the actual effectors of the genetic and short term changes caused by cannabinoids. The more I learn about neurobiology the more I feel sure one man cannot figure out how we think, instead it will have to be done by an array of supercomputers incorporating unbelievably complex chemical, electrical and genetic knowledge.
 
One final note, Invalid Username stated:
"I'm asking about THC neuropharmacology because I'm trying to determine if there is a neurochemical reason for concurrent pot/MDMA users to experience anxiety/panic attacks (almost all anxiety reports I've seen from MDMA users show concurrent pot use)."
Your observation concerning a correlation between concurrent pot use and anxiety with MDMA could quite well be a main effect of the synergistic effects of pot and MDMA.

However the correlation is confounded by the fact the anxiety/paranoia you are observing could be a product of the actual combo or a indication of the tendency of a certain group of individuals to use pot.

To provide ancedotal evidence to refute the anxiogenerating effects of pot + MDMA, I know many people who have done more than their share of both MDMA and pot, and lack any anxiety attacks or paranoia.
 
are you trying to figure out a cause for the paranoia whilst on mdma and pot, or simply pot by itself as an ecstacy user?

in conjunction with mdma, its not hard to see why anxiety can occur. in simplest terms i would just say that your body is stressed on mdma. when you smoke it leads to confusion and further stress on your mental state. the dopamine release from mdma combined with the adrenaline release from stress could easily cause some to panic.

I also noticed that when i was pilling a lot that i would have a shitload of anxiety if i just smoked pot alone. I've heard others have had this too. I really don't know why that occurs. that would be the more interesting question to me.

if indeed it is dopamine related, perhaps the solution to your question could be found in the collective insights on peoples experiences with pot + coke/speed/opiates
 
Anxiety isn't dopamine related. It is to do with noradrenaline, which MDMA releases both centrally and peripherally, cannabis casues a peripheral release of noradrenaline and adrenaline... all of these things contribute to anxiety, in anxiety prone people.
 
What is your reasoning to support your assumption that anxiety isn't dopamine related? In fact, dopamine is released in response to ANY salient stimulus, either rewarding or negative. This DA release is found in various parts of the brain, especially the Prefrontal cortex and the striatum. As anxiety is a construct made up by psychologists, it is incorrect to associate one neurotransmitter (noradrenalin) with so-called anxiety. Anxiety is the result of a complex interaction of various NT, 2nd messenger, effector, transcription factors, and who knows what else, glial cells, etc...Noradrenaline might be a player in the cascade of neural events producing the construct defined as anxiety, but it is surely not sufficient, and probably not even necessary in all cases.
 
MDMA users smoke a lot of weed on the come down. Continuous use, comedowns, and scattered sleepless nights can all together brew many problems like anxiety.
 
^^
Continuous use, comedowns, and scattered sleepness nights are all effects of heavy MDMA and pot usage-and the link to anxiety has already been made. However, I believe the above posters' and the entire thread's intent is to probe the complex pharmacology of THC, along with delving into neuroscience behind the additive anxiety noticed by some MDMA/pot users. "Comedowns" and "scattered sleepless nights" are useful constructs in terms of defining certain behaviors/experiences, however they are not useful in explaining the actual mechanisms of anxiety, which involve indefinite complex quantum electrochemical neural systems.
 
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