Pharmacology of DMT

[GlutamateTheory]

I've looked how DMT binds to different receptors and I find it very interesting.

5-HT1A	0.075
5-HT2A	0.237
5-HT2C	0.424
D1	6
D2	3
D3	6.3
α1A	1.3
α2A	2.1
TAAR1	2.2
H1	0.22
SERT	6
DAT	22
NET	6.5

(I'm self learned mostly so please correct me)

This is from wikipedia and there's a source for it. Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens
DMT also binds to sigma receptors and it is an agonist. It's not in the list but it's in the text.
Up from down: serotonin receptors, dopamine receptors, alpha or adrenergic receptors, TAAR receptor (full name?), histamine receptor 1, serotonin transporter, dopamine transporter and noradrenaline transporter.
Wikipedia link for pharmacodynamics: Wikipedia

So I'm going to ramble here and tell my thoughts. Nothing scientific. I'm just so interested.
What I find interesting is the Histamine 1 binding that is on par with serotonin binding. So it should make you sleep but there's so much stimulation at the same time so it's cancelled maybe.
Don't know exactly how TAAR1 binding affects the experience.
Sigma receptor binding maybe affects the psychedelic part of DMT. That's just my thought. If you look at dissociatives, almost all bind to sigma receptors. In the DXM fact it's theorized that part of the DXM's psychedelia is made by sigma binding. So
that's where I got this thought. The function of sigma receptors is unknown. At least what I read.
5-HT1a agonism is associated with serotonin, dopamine release. 2a and 2c is associated with the psychedelic effects.
I'm going to stop now. I might be spreading lots of misinformation lol.

What do you think?

 

[mr peabody]

Great post. Maybe have a look here:

PHARMACOLOGY | +80 articles

Psychedelic Pharmacology by James Kent Most psychedelic molecules are structurally similar to neurotransmitters that modulate signal flow in the brain. If we take a close look at the structure of common neurotransmitters, the transmitters most closely related to the classic psychedelics...

www.bluelight.org

 

[GlutamateTheory]

Great post. Maybe have a look here:

PHARMACOLOGY | +80 articles

Psychedelic Pharmacology by James Kent Most psychedelic molecules are structurally similar to neurotransmitters that modulate signal flow in the brain. If we take a close look at the structure of common neurotransmitters, the transmitters most closely related to the classic psychedelics...

www.bluelight.org

I thought people would be more interested but I guess pharmacology is way too nerdy. DMT is extremely interesting and I want to find more
EDIT: oh thanks!

 

[Chris Timothy]

What I understand from reading up on binding affinity is that the trouble is that it says nothing about ligand efficacy, i.e. how much of an agonist it is or whether it agonizes at all upon binding. You need to know more about what the particular substance does at the particular receptor before you can start connecting dots.

 

[mr peabody]

Despite being relatively unknown, DMT was made illegal along with mescaline, psilocybin, and LSD in 1966, (the same 4 compounds mentioned in the introduction of ‘The Psychedelic Experience’ which came out in 1964) and categorized as a Schedule 1 drug in 1971. Due to its general rarity, DMT could have easily vanished from human history had it not been for the fact that one of the members of Leary’s ‘League of Spiritual Discovery’, a young man called Nick Sand, had developed a taste for the compound while acting as a ‘sitter’ for initiates at Millbrook. When LSD became illegal (and its supply more problematic) Leary encouraged Nick Sand to become an underground chemist, something he did with remarkable efficiency when he ‘invented’ Orange Sunshine LSD (the first underground LSD) of which he would go on to produce some 3.6 million hits of for a loose smuggling organization called The Brotherhood of Love, before his subsequent arrest in 1974. Nick Sand would also be the first ‘underground’ chemist to synthesize DMT, and – equally importantly – became the first person to realize that its freebase could be smoked, a discovery which undoubtedly led to an increase in its popularity amongst the psychedelic community of the late 60’s and early 70’s.

Despite being famous for creating Orange Sunshine LSD, Nick Sand has universally declared DMT to be his favorite compound. When his LSD lab was busted in Canada in 1996, the police also found 4 kilograms (!) of pure DMT, and in his subsequent writings about DMT (published in The Entheogen Review), Nick has proven to be one of the most thoughtful and enlightening advocates of the spiritual potential of smokable tryptamines. He was released from prison in 2000, and now lives quietly in the Bay Area, a hero to many of those who know him, and many of those who don’t. (Nick passed away in 2017.)

"The world of DMT is incredibly vast. What DMT opens in us is so profound that it is impossible to truly express. I have been making, using, and initiating people into DMT use for around 40 years. I was the first one who discovered that free-base could be smoked. It has never ceased to amaze me, nor have I ever felt that one could fairly arrive at any hard or fast conclusions about what happens during a DMT trip." - Nick Sand, “Entering the Sacred World of DMT", The Entheogen Review, Volume X, Number 1

DMT Modern Usage

Information and resources on DMT (dimethyltryptamine), 5-MeO-DMT (5-methoxy-dimethyltryptamine), and Visionary Culture.

www.dmtsite.com