Psychedelic Bump XXXIV

^ Had a reply but it got erased, I'll respond later

 

I came up staring at some clouds that were absolutely beautiful, there were various shades of color in the clouds and sun rays pierced through them to give this grandiose skycape, forming images that were interpretative in various ways. The Sun had some rays scatter through the clouds which added to the beautifulness of the sky.

I could have spent most of my trip out there but I decided to go inside and was on the computer for most the trip. The visuals were kinda "drowned out" by the computer screen but every now and then something would make me laugh or in one instance I got nauseous and was reminded how heightened/altered my senses were. I listened to the new Radiohead album, one of my favorite bands, in a hodgepodge of studio, live and acoustic recordings and was really impressed by with what I heard. I explored some coding stuff which basically turned what I may have considered a "Bad Setting" in previous years to a fascinating and unique experience. I still think psychedelics shine when out/exploring nature but I've grown fond of coding, so it was pretty fascinating.

I've never tripped on any beaches in SF

 

Being inside on a computer on acid makes me feel like I'm going mad after a while! Pretty awesome it allows the code juices to flow for you.

Waiting on some DPT in the mail. I think it is my favourite psychedelic.

 

trying Tramadol hydrochloride for the first time
50mg time-released tablets.

Dosed one so far ~8pm. Thinking of dosing two more, 30 minutes apart for total of 150 mg Tramadol HCL.

(would love to here other peoples exp with this drug if possible)

 

probably better luck in the opiate forum. i've actually taken Tramadol in an attempt at recreation, but dose was too low to do much of anything. can't recall specifics.

 

While we're mentioning opiates, I'm currently on a little hydrocodone. Whacked my shin on a plane of glass while moving into my new house and got 14 stitches and some crutches :/

 

oooh damn. heal up well.

 

Ouch bro! Sending the healing vibes your way! I just recently had the pins and rods in my back adjusted to try and fix the compaction/scoliosis problems that popped up. Currently have a temp prescription of 2mg dilaudid. Of course, about 10 of those went up my arm last weekend... Just couldn't help myself! Saving them for recreational use (10 per weekend). I have sweet sweet medical Mary Jane for the pain!

Soooo, how you been do Porky and Popularity?

 

Bummer. Rain rain rain. Looks like our festie gonna be rained/flooded out. Probably end up in a warehouse for just Saturday into Sunday morning. I was planning on heading to the land yesterday afternoon to work on set-up, but everyone just waiting around to see what will happen.

 

I took about a dozen of those one time. Got so sick but not very high. Opiates are not my thing but I am told these are not good ones for a buzz anyway.

 

Bump for MDMA

 

Here's a general question for you guys; which RC psychedelics do you find to be the most "unique" in terms of qualitative effects? Specifically ones targeting the 5-HT2A receptor sub-type. I am in the process of writing up a research proposal related to 5-HT2A receptors and hallucinogens, but I'm not sure if my PI (principal investigator) would be willing to jump through all the regulatory hoops required for mescaline/psilocybin/LSD research. There are, however, a number RC's available (as I'm sure you all know, lol) which present slightly less difficult research avenues. I would be looking at receptor conformation versus binding agonist, and as such I think it could be interesting to have a selection of RC's which are qualitatively different from each other in some ways.

Actually, that makes me think, if DiPT binds the 5-HT2A receptor it could be a very interesting drug to look at..

 

Kind of a broad question so it's difficult to answer in a sense. My initial reaction is to say DMT or assuming that that has some of the same obstacle hoops as the other illicit psychedelics you mentioned, then maybe DPT.

Other than that, I found 2ct2 quite unique but perhaps more from the standpoint of having particular expectations about the 2c(x) class of chems. Also, sans the baggage that comes with it, which we have discussed here numerous times, I thought 25i-nbome was quite unique.

 

Hm, interesting. I hadn't really thought about exploring the 2c-t-x drugs nor any NBOMe substances, but those would both be interesting targets. Especially NBOMe, given that they are potent at such low dosages compared to other 2c-x substances.

DMT/DPT is definitely one of the ones I've considered, given that it is one of the most intense ones. (And that DPT has heavily influenced my thoughts about psychedelics, haha).

Basically, I would be looking at receptor conformations versus effects given. I'm trying to build up a good therapeutic connection to my research ideas however, and as such I would want to have some substantial differences between substances that might be reflected in their different receptor conformations.

As many of you probably know, lots of hallucinogens bind the 5-HT2A receptor, but clearly effects differ when you take different psychedelics. Now some of it of course is related to metabolites and the distribution of said substances in the body, however there must also be some difference in how the receptor reacts to different agonists. So ideally, I would be able to draw some possible correlations between mental action and cellular response. And more specifically than simply "this binds the 5-HT2A receptor and is a full/partial agonist".

So as of now I still want to avoid drugs like salvia which have different mechanisms of action. Another interesting angle is that lots of anti-psychotics bind the 5-HT2A receptor, but clearly they don't make you feel like psychedelics do, lol. The old theories dictate that these drugs, such as clozapine, haloperidol etc. acted through binding D2 Dopamine receptors as an antagonist. But the correlation between the drugs that work and their effects at the D2 receptor is falling apart, and the 5-HT2A receptor is a new possible mechanism of action. It would be cool if they had differing intra-cellular effects.

Anyway, TL;DR - Anything that helps give a correlation between special/unique action and protein mechanisms helps. That, or anything that gives my project a stronger therapeutic angle, other than "psychedelics are cool, man!".

 

there have been a handful of (or at least 1-2) studies about receptor affinities of different psychedelics for the various 5HT receptors. one paper had a table listing each psychedelic they tested (many such as 2cx, DPT, etc) along with the receptor that it binds tightest too.

what exactly do you mean about receptor conformation, CS? or i guess my question is, how are you going to measure or look at receptor conformation? the only way that comes immediately to mind is x-ray crystallography of the purified receptor protein (hard and time consuming for several reasons) along with the bound psychedelic chemical(s).
alternatively, you could use computational modeling to make predictions about the same thing.

 

I have seen papers from Dr. Nichols discussing the 5-HT2C receptor as a possible target for psychedelic action, but I believe that the theory has more or less been discredited now, or at least that 5-HT2A would be the major player in terms of the effects. But I am going to take a closer look at specific ligands which would bind 5-HT2A if I can get the project on the road.

Essentially it is a BRET florescence measurement. Whack a Renilla Luciferase onto the C-Tail of a GPCR and then place another flourescent-dye binding motif in the various intra-cellular loops of the GPCR. Then, when the receptor takes on certain conformations you get a signal read-out, and by having a modified receptor for various ICL's you can sort of see some of the conformational information. It's somewhat of a new technique, but the idea is that it is a way to work on drug-discovery which is cell-line independent. As the downstream signal is largely dependent on the G-proteins available within the cell you may get different results from HeLa v. HEK293 cells etc. This way, you catch some signalling information before it is passed on downstream and distorted by the cell's own machinery.

But I guess it isn't quite "conformation", rather patterns of read-out and hopefully by testing various substances there could be some insight

So the whole idea would be to look for some sort of reaction pattern which could predict certain kinds of effects, thus why I would want to test a panel of very "different" psychedelics. This technique has been done on a few receptors, but not the 5-HT2A yet. If you're interested in reading some papers I could send you some.. but I'm sure you have more than enough science on your plate atm

 

Haha, well that one was for pork, as he probably knows what I am talking about (more or less), but to be a bit more simple;

GPCR's (G-Protein Coupled Receptors) are very common in the body. For example your cannabinoid, serotonin, opioid, adrenergic receptors etc. are for the most part GPCR's.

These receptors cross the membrane of the cell seven times. So you have these rigid "helices", which cross the membrane, and then some more flexible linkers/loops which are found inside and outside the cell, connecting these helices together.

Renilla Luciferase is an enzyme which, when given a certain substrate, produces fluorescent emissions. Then, all-through these loops on the inside of the cell, you genetically insert a "tag" which will bind another fluorescent dye. BRET (Bio-luminescent Resonant Energy Transfer), relies on two of these fluorescent emissions coming in close enough contact to cause an energy transfer. When you put those tags all around the receptor's interior loops, with the R. Luc enzyme at the "tail" end of the receptor, you can test them with different drugs side by side and see which loop is closest to the tail. Then you use a fluorescent microscope to read-out the signals and you try to assess which of these "conformations" will give different effects.