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Who here would do a thumbprint?

^^ Are the receptors just on and off switches? Or work more like a transistor?
That's a surprisingly complicated question. Most of these receptors are G-protein coupled receptors, so when an agonist binds, what it does is stabalize the G-protein into a formation where it's G-protein has high affinity for it, this means that when an agonist binds, G-proteins bind to the receptor more frequently. It's the binding of the G-protein which then causes the subsequent effect in the cell.

So different agonists can produce different states in the G-protein, so that it can higher or lower affinities for the G-protein. Agonists that cause higher affinity G-protein - receptor states, are more active.
 
As I perceive the graph above it looks like the LSD plasma level in the brain reaches a certain point and then bang, the brain cell switches on. I'd imagine it to be alot more complicated than that, as in the brain cell is almost always active, tho the frequency or power of the cell is whats affected. Rather than a simple on or off state.

So in saying that, wouldn't a LSD ingestion from 100 to 200ug have a stronger effect on certain 5htp cells, even tho at <100ug dose those 5htp receptors for those same cells are activated?

Sorry if I sound confusing, hard question to ask.... :)
 
fastandbulbous said:

for example, from GSK's Terry Kenakin's article in An.Rev. of Pharm. & Tox., Vol. 42, April 2002, Drug Efficacy at GPCRs:

"receptor behaviors discussed are activation of G proteins; ability to be phosphorylated, desensitized, and internalized; formation of dimers and oligomers; and the interaction with auxiliary membrane and cytosolic proteins."

...
 
Still Waiting

So, I have to wait until someone offers me a thumbprint? If I'm worthy? OK. I can see where this is going. Well, come and find me. You decide if I'm worthy.
 
nanobrain said:
for example, from GSK's Terry Kenakin's article in An.Rev. of Pharm. & Tox., Vol. 42, April 2002, Drug Efficacy at GPCRs:

"receptor behaviors discussed are activation of G proteins; ability to be phosphorylated, desensitized, and internalized; formation of dimers and oligomers; and the interaction with auxiliary membrane and cytosolic proteins."

...

It's just that for any additional behaviour of LSD at extremely high concentrations, you'd think that there'd be lots of articles about it's interaction with isolated cell preparations etc (especially of the anti-drug lobby could use any of it to decry it as being even more dangerous), how LSD dimer formation occurrec and interacted with a new receptor, or caused genes to be expressed in a different manner to that found at lower doses. LSD does cause different genes to be expressed in different ways, but as far as I'm aware there's no sudden (or even gradual) big change in that behaviour as you go from large doses to extreme doses. That's where my belief that thumbprints have nothing to offer over saturation doses except for a much prolonged trip and some elitist '8 miles high' club membership type of thing.
 
As I perceive the graph above it looks like the LSD plasma level in the brain reaches a certain point and then bang, the brain cell switches on. I'd imagine it to be alot more complicated than that, as in the brain cell is almost always active, tho the frequency or power of the cell is whats affected. Rather than a simple on or off state.

So in saying that, wouldn't a LSD ingestion from 100 to 200ug have a stronger effect on certain 5htp cells, even tho at <100ug dose those 5htp receptors for those same cells are activated?

You're getting a bit confused. Comparing brain concentrations of drugs to the drugs affinity for a receptor is a way of looking at things. When the concentration of a drug reaches it's affinity constant for that receptor, you'll get 50% occupancy, much bellow that concentration, you don't get much effect. Clinical drugs are usually dosed to get ~50% occupancy [1, 2, 3]. (Actually with benzos you usually need less than 50% binding (5-25%) because there effect is so large, and with reuptake inhibitors you need more than 50% (>75%) because transporters are usually never near saturation).

Meanwhile, G-protein coupled receptors don't turn cells on or off, thier effects are usually more complicated (effecting the miximum rate at which cells fire, the effectiveness of synaptic input, basal resting potential etc), furthermore, the effects arent on 5-HTP cells, or 5-HT cells, exclusively at least, the effect is probably on cortical or thalamic nerons.
 
fastandbulbous said:
As I mentioned previously, considering that you're not going to be activating any extra receptor types/subtypes in the jump in dosage from 1.5mg to say 30mg I can't see that they could be so different except in terms of time to peak, duration of trip etc. Although it may be a very good way of excluding DEA agents from infiltrating the higher echelons of the LSD manufacure & distribution, it also seems to seriously increase the possibilities of long term psychological damage due to the duration of a trip from a 30mg dose.

IMO it's simply not worth the risk - but then I'd be very wary of taking 1500ug in one go; the largest dose I've had is probably about 500ug (4 dots of stronger than average dose in the early 80's) and that left it's mark on me!


I am in agreement with all of your statements you seem to be very educated and i respect your opinion, and your knowlede.

I have personally dosed + of 500ug and yes, it is a totally different trip. I WOULD however risk takng a thumbprint, because if i was even in the position to be offered one the chance would certainly NEVER come again.

I am not going to be able to break more than i have already been broken, IMHO.
 
I can understand the ‘right of passage’ thing, but I too think this ‘thumbprint’ legend is stupid. The saturation dose of LSD is just under a milligram. Having a thumbprint may allow one to have bragging rights, but as far as I am concerned it is really just a big waste of LSD. Besides, I have had so much LSD in my day that I’ve lost all interest in it (unless I mix it with MDMA) so if a thumbprint were offered to me, I’d take it…but not to eat…to put in a vial to add to the collection. LSD powder is neater than frozen blotters in my opinion. 
 
People who usually do “thumb prints” or any kind of prints are usually laying sheets or eating LSD like candy and have a huge tolerance and their body is very familiar with the chemical. If a person had not done any LSD for mouths or years and did a print I think they would possibly have a very difficult time. I have done a print on a match head not the whole match head just part of it. You can only get so high before you are Dead, One of all, the void or how ever you try to describe it, if you can physically see crystal LSD and you eat it you are going to that place, it is just a matter of how long you are going to be there. When I did a print it was a time when I was eating a lot of LSD at least once a week so it was not a total shock to my system, well yes it was, but it didn’t put me in a bad frame of mind thank God. I think the whole huge dose “thumb print” or “print” initiation started with people getting turned on to laying sheets which is a big responsibility. If someone could go though a print they were probably not a cop, they were born into a spiritual brotherhood, and very important they would not freak out if the laid too many sheets. Laying sheets exposes people to massive amounts of LSD there is no way around it you need a very large tolerance. That is the only reason I could see for doing 30-40mgs of crystal. 3-5mgs is going to take you to that same place ( if your tolerance is not though the roof) just not for 5-7days. No, I would pass on a 30-40mg print. You never know what will happen after something like that a persons mind is like hot metal when you are in a place like that it is too hard to say what it will be forged into by the time you come back. Hope you have a good babysitter. LOL!
 
Wow, never for me.

That's just a rediculous amount of LSD for my mind. My body may not die, but I'm sure I would be a complete nut job, or kill my self in the process.
 
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