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neurochemistry is deep and complex, who can help me out? Options
 
TimePantry
#1 Posted : 8/25/2011 7:28:34 PM

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As I've mentioned elsewhere, I just don't seem to have a regular brain with respect to the processing of spice.

The very first time I smoked it, I was at a party and I had taken some SAM-e to help me be comfortable around new people etc.

My best friend tells me I reclined in bliss for half an hour, responding to her inquiries with a huge grin and happy words, but I remember not a thing.

Subsequently, as it stands now I must take an MAOI in order to feel spice at all. Breaking through is a hella complex, hit-or-miss undertaking involving a lot of esphand and a pretty small window of opportunity more capricious than-- well, an elf or something. ;-}

Except not. This morning, I smoked some spice with no preamble or exotic seed intake --- and I can't remember anything!

(no SAM-e for days, either.)

Anybody here who has a theory? With all due respect, I am hoping for neurochemical rather than metaphysical ideas, though all input is welcome.

Thanks!
"What's wrong with that generation? ... Is this what comes of putting on Pink Floyd laser lightshows down at the Planetarium?" --Spider Robinson
 

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۩
#2 Posted : 8/25/2011 7:36:01 PM

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Rick Strassman's studies showed that about 5% of people (if I remember correctly) are not affected by DMT at all.
 
TimePantry
#3 Posted : 8/26/2011 1:38:47 AM

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۩ wrote:
Rick Strassman's studies showed that about 5% of people (if I remember correctly) are not affected by DMT at all.


Indeed they did. I may be, or may have become, one of that small percentage. However, I have had many delicious voyages in between. I often wonder if, had they been given a reversible MAOI prior to the spice, a lot of those 5% might have had a little more fun?

The part that mystifies me is, why can't I remember what happened that first time, and this morning? I believe that I had clearly broken through on both occasions.

I'm thinking that there is some ridiculously complicated thing going on neurochemically that somehow inhibits formation of short-term memory, or short-circuits conscious recollection of experience. Kind of like what often happens with dreams. They can be so vivid and intense and meaningful, and you're fully aware of that in the first moments after waking, but in seconds you can feel the whole thing draining away.

I have noticed that my fellow forum members are a very erudite bunch. Perhaps somebody can explain it.
"What's wrong with that generation? ... Is this what comes of putting on Pink Floyd laser lightshows down at the Planetarium?" --Spider Robinson
 
۩
#4 Posted : 8/26/2011 1:43:35 AM

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Everyone has unique neurochemistry it seems.
I am not a neuroscientist myself so forgive my elementary perspective.
If I were you, I would begin experimenting with synergies since pure N,N-DMT doesn't do it for you.

I would try the House Special:

Eat a good dose of LSD, drink a light to medium dose of ayahuasca at the peak, and when that kicks in, smoke a good dose of N,N- and make sure you hold those hits!

If that doesn't send you where you want to go... Back to the drawing board!
 
TimePantry
#5 Posted : 8/26/2011 5:17:56 AM

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My goodness! I can tell I am in the company of a serious professional! Very happy

If I did all of those things, I would probably run naked through the streets.



errrr ...




Hmmmmmm ... the weather IS pretty warm ...
"What's wrong with that generation? ... Is this what comes of putting on Pink Floyd laser lightshows down at the Planetarium?" --Spider Robinson
 
Jin
#6 Posted : 8/26/2011 6:48:01 AM

yes


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TimePantry wrote:

If I did all of those things, I would probably run naked through the streets.


not really , not unless you take you're pants off , but yes you will be runnin on the streets shouting you just met jesus and played in his arms while he showed you many secrets of the universe

lsd+dmt is a wonderful combo as i've heard , i have not yet mixed these two together , yes i am a little scared and also occupied with work , i am sure to try this combo out by this year end when i am more free and less stressed out

a friend of mine tried this combo a while back and described an amazingly beautiful experience , however he is now sticking to Lsd and not smoking spice anymoreConfused , hmmmm but his description was beyond beautiful , it has encouraged me to go ahead and do this as soon as i can (which is probably in a few months)

illusions !, there are no illusions
there is only that which is the truth
 
۩
#7 Posted : 8/26/2011 8:06:10 AM

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I just sit in trance, no naked street running for me ;]
 
TimePantry
#8 Posted : 8/26/2011 9:34:30 AM

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Seriously, though, acid is much too strong for me; or the wrong kind of strong. It's heavily introspective, and I'm all for introspection -- it makes us better people. I practice introspection often for the purpose of trying to be a better person.

But, for me, spice is more fun than rollercoasters! It's a truly, truly alien landscape. And I always wanted to explore strange new worlds, heh.

Hmmmm, does anyone know if there's an explanation as to why we don't remember our dreams? That may yield a clue.
"What's wrong with that generation? ... Is this what comes of putting on Pink Floyd laser lightshows down at the Planetarium?" --Spider Robinson
 
arcanum
#9 Posted : 8/26/2011 9:43:26 PM

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Five years ago I was taking the antidepressant Tianeptine ( Stablon) a serotonin reuptake enhancer ( not inhibitor like Prozac et al.) A common side effect of this drug are vivid complex and strange dreams, every single night. Five years later I can remember every detail of at least half of those dreams. Not suggesting you take it of course, just interesting that it caused total recall of dreams.
 
TimePantry
#10 Posted : 8/28/2011 11:01:33 AM

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arcanum wrote:
Five years ago I was taking the antidepressant Tianeptine ( Stablon) a serotonin reuptake enhancer ( not inhibitor like Prozac et al.) A common side effect of this drug are vivid complex and strange dreams, every single night. Five years later I can remember every detail of at least half of those dreams. Not suggesting you take it of course, just interesting that it caused total recall of dreams.

Hmmmm, that's very interesting, especially since I have read that both serotonin reuptake inhibitors AND reuptake enhancers can be effective in treating depression. (In different people, that is.)
So possibly there is some connection between MAOI and recall of dream/trip state. That is most definitely a very helpful clue. Thank you!
<sigh> However, it means that my window of opportunity is not just small, but also intermittently made of one-way glass.
Argh.
"What's wrong with that generation? ... Is this what comes of putting on Pink Floyd laser lightshows down at the Planetarium?" --Spider Robinson
 
TimePantry
#11 Posted : 9/3/2011 3:14:50 AM

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I'm just posting to bitch. Sorry. I appear to be DMT-proof again. Dammit!

Probably what I need to do is lay it down for a week or two. Yikes.

[Kitty Is A Very Bad Mystic] "Damn! Blast!" [/KIAVBM]
"What's wrong with that generation? ... Is this what comes of putting on Pink Floyd laser lightshows down at the Planetarium?" --Spider Robinson
 
ouro
#12 Posted : 9/3/2011 3:42:31 AM

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blacking out and not remembering a thing doesnt sound like "immune to spice" to me at all. If I dose high I can't remember anything. Maybe you are smoking too much or are very sensitive. Eating it along with maoi always gave me a much better experience.
 
mindexplorer01
#13 Posted : 9/5/2011 3:33:30 AM
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Perhaps there exists a much more subtle, progressive tolerance that could develop? As with any other, the more a chemical/ligand binds its receptor, the more likely/more-so that these receptors will be downregulated [typically by the cell engulfing the receptor... pinching inwards]. If this were true, it would explain why an MAOI is needed for SWIY now. Binding occurs by randomly colliding which means that the concentration alters the duration needed to reach a certain threshold value.

Now, if this were not true, then perhaps something quite similar to excitotoxicity induced by excessive, extracellular glutamate which both inhibits the glutamate/cysteine antiporter [used to synthesize antioxidant glutathione] and allows for extrasynaptic binding both of which lead to neuronal cell death in the case of glutamate. Perhaps, excessive stimulation could destroy the cells..... or at least cause permanent conformational change of the receptor preventing binding.

There's a lot of possibilities... but just keep that syrian smile Very happy
 
TimePantry
#14 Posted : 9/7/2011 9:45:32 AM

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mindexplorer01: Okay, I think I follow all of that. In the first instance, is the downregulation reversible? And in the second instance ... err, can I grow new ones?
"What's wrong with that generation? ... Is this what comes of putting on Pink Floyd laser lightshows down at the Planetarium?" --Spider Robinson
 
AlbertKLloyd
#15 Posted : 9/7/2011 6:14:03 PM

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is there a notable difference or sensitivity that you have regarding GABA ligands or in relation to benzos?

are you extra sensitive to stimulants that resemble or affect dopamine?

I believe that you may have some receptor proteins with a different shape than most people or a difference in terms of the metabolism of glutamate or dopamine.
 
TimePantry
#16 Posted : 9/9/2011 10:44:08 AM

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AlbertKLloyd: Well, first I had to go look up "GABA ligands." This from Wikipedia:

"The protein also contains a number of different allosteric binding sites which modulate the activity of the receptor indirectly. These allosteric sites are the targets of various other drugs, including the benzodiazepines, nonbenzodiazepines, barbiturates, ethanol,[4] neuroactive steroids, inhaled anaesthetics, and picrotoxin, among others."

Not sure I've ever had a benzo. I've had Valium a few times in medical settings; honestly I didn't feel any different. Never had a barbiturate. Is amyl nitrate an inhaled anaesthetic? Tried that back in the 80's and I hated it! Smells absolutely poisonous, like car exhaust and bleach do. Don't like whippets either.

As for stimulants, I was quite fond of speed, real speed, back in the day. And in fact, I was kinda known for the "lethal underdose," i.e., doing way less than everybody else. Sadly, the constituents thereof are substantially different these days, and substantially more harmful in my opinion. So I don't mess with it now. But, is that the kind of thing you're talking about?

It has been suggested that perhaps I have rapid seratonergic reuptake, and that is consistent with issues others in my family have.

Anyway, then I looked up "glutamate." It's funny how you can encounter a word for years, and never have more than a vague contextual understanding of it...

I think that angle suggests interesting possibilities. If I understand the Wiki article correctly, glutamate is responsible for the umami, or savory, flavor in many foods, and is found plentifully in meat, poultry, dairy, and --- kombu! Now that's really intriguing, because when I was a kid, my mother went on a "fruits of the sea" type kick (it was the 70's) and along with things like boiled barnacles -- swear to God! Barnacles! -- we got a lot of seaweed. And I loved kombu. Also, I have always seemed to need a certain amount of dairy or chicken in my diet to feel right.

I'm fascinated. If you wouldn't mind, can you elaborate on the connection between atypical receptor proteins or glutamate/dopamine metabolism, and my problems with spice?

And thanks for your post.
"What's wrong with that generation? ... Is this what comes of putting on Pink Floyd laser lightshows down at the Planetarium?" --Spider Robinson
 
AlbertKLloyd
#17 Posted : 9/10/2011 2:58:06 AM

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I have to think about this, it seems like you could metabolize catecholamines at a different rate than other people, making you extra sensitive to things like speed.

The thing is that catecholamines are metabolized by MAO and COMT, but say that you hypothetically speaking have a COMT variation or mutation, well COMT would also break down speed, so if you had a COMT issue you might have more MAO activity to compensate and subsequently make you less sensitive to DMT.

however this is just conjecture, i will think some more about this
i would however wonder what your sensitivity to mescaline might be, high or low?
mescaline is a substrate of both COMT and MAO to some degree
 
TimePantry
#18 Posted : 9/10/2011 6:53:33 AM

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I've never had mescaline. It's not something one runs across much in this grim urban setting hereabouts.

I don't know if it's at all relevant, but I react really badly to pot, it's no fun at all for me. And I don't think MDMA affects me the same as others either, it makes me feel anxious and neurotic. (that's not my nature, otherwise.)

Thank you for your input thus far. I'll check back here in a few days, and see if your ruminations have yielded further insight.

And thank you to the others who have commented. This is really a great place to hang out. There is no one around me who is interested in spice at all, so if not for here I'd be left to my own devices, heh heh.
"What's wrong with that generation? ... Is this what comes of putting on Pink Floyd laser lightshows down at the Planetarium?" --Spider Robinson
 
TimePantry
#19 Posted : 9/10/2011 1:19:17 PM

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I can't believe I forgot to mention this other thing: when I smoke spice, whether or not it works, it also makes me feel really wired. You know, awake, alert, clearheaded. Oddly enough, it makes my vision sharper too.
"What's wrong with that generation? ... Is this what comes of putting on Pink Floyd laser lightshows down at the Planetarium?" --Spider Robinson
 
TimePantry
#20 Posted : 9/10/2011 1:43:05 PM

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I had never heard of COMT, so I looked it up too, just now. This is an excerpt from the Wiki page on COMT; this paragraph is in reference to the Val158Met polymorphism:

"The COMT Val158Met polymorphism also has a pleiotropic effect on emotional processing.[16][17] Furthermore, the polymorphism has been shown to affect ratings of subjective well-being. When 621 women were measured with experience sample monitoring, which is similar to mood assessment as response to beeping watch, the met/met form confers double the subjective mental sensation of well-being from a wide variety of daily events. The ability to experience reward increased with the number of ‘Met’ alleles. Also, the effect of different genotype was greater for events that were felt as more pleasant. The effect size of genotypic moderation was quite large: Subjects with the val/val genotype generated almost similar amounts of subjective well-being from a ‘very pleasant event’ as met/met subjects did from a ‘bit pleasant event’. Genetic variation with functional impact on cortical dopamine tone has a strong influence on reward experience in the flow of daily life. Persons with the met/met phenotype describe events as very pleasant or pleasant with twice the numeric amplitude of those absent the met/met genetic polymorphism."

This is very, very cool. I had no idea these things could be teased out of human behavior and mapped onto specific genes and variants. I had always thought of them as part of what we call "temperament." The met/met phenotype sounds utterly like me - at first, as a kid, I thought I must be kind of a freak to get so much joy from small things; ultimately I decided it was a very great blessing for which I am grateful.

Anyway, it would certainly seem to lend credence to your conjecture. Fascinating.
"What's wrong with that generation? ... Is this what comes of putting on Pink Floyd laser lightshows down at the Planetarium?" --Spider Robinson
 
 
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