Tokyo. 作家. Neurobiologist, pharmacologist, writer on psychedelics, especially DMT. "Death by Astonishment", OUT NOW: https://t.co/F25GjiDSxu
@lisaxiaolu This study comes almost seven years after Rick Strassman and myself proposed a retooling of target-controlled intravenous infusion for extending the DMT state from a few minutes to potentially much much longer... 
Bromo-DragonFLY is a beautiful example of drug design performed by one of the best in the business — Dave Nichols at Purdue — and shows how a deep understanding of drug-receptor interactions can be used to generate molecules of truly exceptional potency... 
At lower doses, this is a typical report:
In my series of Substack posts on a possible “entourage effect” in Psilocybe mushrooms, I discuss whether or not different relative concentrations of three major alkaloids, psilocybin, baeocystin, and norbaeocystin, might be responsible for such an effect.
All of these “essential precursors” are derived from the amino acid phenylalanine, with differing patterns of oxygen-bearing groups around the phenyl ring. 
The medical literature includes many examples of people consuming large quantities of ground nutmeg and being presented to the emergency room with symptoms ranging from nausea and blurred vision to multi-sensory hallucinations and “bizarre behaviour”...
Muscimol works by activating the inhibitory GABA-A receptor, which is also the site of activity of some of the most popular sedatives used to treat anxiety and insomnia, as well as alcohol (ethanol)... 
The beta-carbolines form the crucial MAO inhibitory component of the ayahuasca brew that allows DMT to be orally active.
For a psychoactive tryptamine to be orally active, it has at least two hurdles to jump:
Psilocybe cubensis: mainly psilocybin and, to a lesser extent, psilocin.
With the proper set and setting, the likelihood of a so-called “bad trip” can be minimised. Further, with the aid of an experienced sitter, trips that take a negative turn can often be shifted in a more positive direction. 
In 2005, a reader of Sasha and Ann Shulgin's TIHKAL wondered why Sasha hadn’t included the DMT derivative with both groups — a kind of structural blend of psilocin and 5-MeO-DMT... (2/15) 
Participants received either 10mg, 25mg, or a control of 1mg synthetic psilocybin, accompanied by psychological support over 6 hours (75-79 in each group). They were then followed up for 12 weeks and their depression rating scores monitored...
The human brain generates inordinately complex patterns of information using sequences of electrochemical signals known as action potentials fired by the vast network of neurons from which it is constructed... 
In line with these subjective effects, ketamine has been shown to increase neural activity at low concentrations, but shift to an overall suppressive effect on the brain as the concentration is increased...
In Fear and Loathing in Las Vegas, Hunter S. Thompson claimed that adrenochrome “makes pure mescaline seem like ginger beer. You’ll go completely crazy if you take too much.” 
What does this mean and how can this study inform what’s happening in the brain when you smoke DMT and are transported to an entirely different reality?
DMT (and other classic psychedelics, such as LSD, psilocin, and mescaline) act primarily via the 5HT2A serotonin receptor — a type of metabotropic receptor. 
