LSD "trigger hypothesis"

[theWorldWithin]

I don't think any of the above data conclusively invalidates the trigger hypothesis but it still stands on very shaky ground. I find it interesting that it is ineffective after T+4 hours which correlates to aproximately the peak plasma concentrations and peak subjective effects for most trippers. Perhaps the molocule causes a direct effect until the peak is reach and the "tirgger" mechanism comes into play after plasma levels begin to drop below the maximum concentration. (Think alcohol hangover starting after blood plasma reaching 50 percent of max, very different mechanism at play but just a crude example). This would hold consistent with many trippers reporting after effects such as strange color tint and suble breathing the following day/s after a trip. Perhaps the mechanism is a bit of direct agonism at 5ht sites and a "trigger" effect. Also keep in mind that LSD has affinity for more targets than just 5ht2a which makes the trigger hypothesis significantly more credible.

Personally I do not know what to think, just throwing some ideas out there.

reference for peak plasma levels: http://www.erowid.org/chemicals/lsd/lsd_myth1.shtml

 

[Zimurgh]

I still think that trigger hypothesis might be true because psychedelic experience is not a uniform experience for me. If its effects was only due to certain receptor stimulation, we would see that it's effects would increase and then diminish uniformly with time.

But in my experience, psychedelic experience has three distinct parts; coming on, visualizations and then personal introspection.

Similiarly according to Timoty Leary it has three Bardo's

First Bardo: The Period of Ego-Loss or Non-Game Ecstasy (Chikhai Bardo)
Second Bardo: The Period of Hallucinations (Chonyid Bardo)
Third Bardo: The Period of Re-Entry (Sidpa Bardo)

Although, as humans we might be categorizing it artificially for me it still feels like that.

Many Thanks, :D

 

[fastandbulbous]

This is not true.

I thought that all rodents didn't develop Parkinsons like symptoms in response to MPTP, and that of the animals tested only primates did. I know that it's MAO-B that does the metabolizing to MPP+ as primates pretreated with selegeline are protected from the neurotoxic effects

 

[fastandbulbous]

^ No they use radiolabelled LSD so they know precisely where it all is at any given time after administration by using big clanky machines that are sensitive to the isotope used for radiolabelling

 

[qwe]

I think that the short half-life value (20 min) is incorrect, but I'm not sure - that's mostly what I'm hoping to clarify. Aghajanian found a half life of 175 minutes, and Ketchum found a half life of 160 minutes. Both claim that the 20 minute half life was based on rodent studies, so as far as I know that's correct.

i think that's just what he was getting at

aghajanian found a half-life of around 3 hours

you have a consistent level of tripping for 8-12 hours

 

[Nexus9]

What about the fact that you can "max out" an LSD dose? Wouldn't this support the trigger hypothesis?

 

[fastandbulbous]

You max out because you get receptor 'saturation' (the occupancy gets to over 90 percent) At that point adding lots more make little difference as it's an exponential relationship