Monday, July 28, 2014

PwKHAL Part 3: Mescaline. Part I

Psychedelics we Have Known And Loved
Reflections on Shulgins Death Part IV

The Basic Structure of the Magic Half Dozen: The Phenethylamine. 
“Use them with care, and use them with respect as to the transformations they can achieve, and you have an extraordinary research tool. Go banging about with a psychedelic drug for a Saturday night turn-on, and you can get into a really bad place, psychologically. Know what you're using, decide just why you're using it, and you can have a rich experience. They're not addictive, and they're certainly not escapist, either, but they're exceptionally valuable tools for understanding the human mind, and how it works.” S. Shulgin

Shulgin's "Magical Half Dozen" were created - literally invented - by Sasha in his backyard laboratory in California. All 6, except the molecule mescaline, which occurs naturally in several species of Cacti, were hand crafted by the Einstein or Armstrong of Psychonautics. This chapter will cover the basic structuce behind all of these psychedelic molecule's. All of Shulgin's Magic 6 are molecules called phenethylamines. I will explain what a phenethylamnie is and provide some basic facts which in later chapters will be useful for understanding why phenethylamines are psychoactive and psychedelic.This reflection will begin to cover the fascinating compound that is Mescaline, but there will be follow up chapters that go deeper into the subjective effects of mescaline and Shulgin's deep facination with this powerful molecule.

To begin, here is the 6 phenethylamines that Shugin found were the most important or noteworthy for our species. These are the 6 he chose from the 150+ he created and the 200+ he examined experientially. These 6 are the compounds we will examine in detail in this series. By doing so, we will learn what these molecules are, how they work their "magic" in the brain, and why they are important at all. The Magic 6 psychedelics all acheive psychoactivity because they exploit the brains naturally occuring neuro-synaptic receptors. The Magic 6 virtually all work by targeting specific serotonin sites. Serotonin is one of the most interesting and one of the most indispensible neurotransmitter's in our brains - it is here that these molecules do their mysterious work, an enigmatic lock we are slowly building the keys to unlock. 

1. Mescaline         (3,4,5 - trimethoxyphenethylamine)
2. DOM               (2,5-dimethoxy-4-methlyamphetamine)
3. 2C-B               (2,5-dimethoxy-4-bromophenethylamine)
4. 2C-E               (2,5-dimethoxy-4-ethylphenethylamine)
5. 2C-T-2           (2,5-dimethoxy-4-ethylthiophenethylamine)
6. 2C-T-7           (2,5-dimethoxy-4-propylthiophenethylamine)


Peyote Mescaline Cacti. 
Lophophora williamsii
To understand what Mescaline is, on a molecular and structural level, you need to know a few basic things. Compreheding the structure of a compound is important as one can then compare it to the serotonin molecule, which is where most psychedelic activity takes place - serotonin 2a to be exact. Furthermore, it is then easier to deal with the harder problem of why, or rather how, mescaline targets certain serotonin receptor sites and not others.


Mescaline (3,4,5-trimethoxyphenethylamine) is a Phenethylamine, as the end-half of the chemical name suggests. The 2D molecule to the right, is the basic construction that all phenethylamines share. The hexagon to the left of this molecule is called a Benzene Ring. A benzene ring is 6 Carbon atoms double bonded to one another and each bonded to 2 Hydrogen atoms. The lines inside the hexagon represent carbon atoms. double bonded to other carbon atoms. Carbon has four electrons in it's outer shell and thus wants four chemical bonds to complete this outer shell, this makes the molecule stable and happy. Carbon is the base atom for all organic chemistry and for all of organic life - including your brain's neurotransmitters.

The up-down-up line attached to the benzene ring, in the middle of the molecule to the right, represents a 2 Carbon chain. This is called an ethyl molecule and it represents the ethyl in phen'ethyl'amine. Each is bonded to Hydrogen and each is bonded to one-another. Except the last atom which is bonded to Nitrogen as the picture to the right illistrates. 4 bonds completes the outer electron shell for each carbon atom and thereby making it 'happy'. Hydrogen is not usually named or labelled on 2D molecule diagrams, such as in the one on the right. If it's blank or unlabelled it's a hydrogen atom. Carbon is often represented with just a join or bond on the diagram, rather than the letter C - unless there is another letter saying otherwise such as N or O, then it's carbon bonded to hydrogen. This simplifies the pictures as labelling all the carbon and hydrogen atoms quickly makes the diagram's tedious to draw or read. Also it makes it messy, especially with large molecules with dozens of hydrogen atoms. The simplified version represents exactly the same molecule, only in a neat and conscise fashion.


 (not including the amine, which can also be altered)
This leaves 5 'free' carbon positions on the benzene ring (the carbon attached to the up-down-up line or ethyl group is used), and 2 carbon atoms on the up-down-up line where atoms or molecules can be added are also free giving 7 total. As it turns out this is exactly what Shulgin did with these 7 'free' carbon positions. Some positions are better than others to attach new molecules or atoms to, something Shulgin learned from trial and error. Knowing where to put what atom(s) means you have a greater chance at making a novel drug which you can then evaluate for any psychoactivity - the hope or aim is to create a profoundly new psychedelic, such as Mescaline or 2C-B.

Basically Shulgin would remove the hydrogen atom stuck to the carbon atoms and replace it with another atom, or a group of atoms; a molecule. By doing this one can add atoms or molecules which are of more intrigue, such as Bromine, Ethyl, Carbon or Oxygen etc. Shulgin was so proficient at this process, after decades of doing the laborious but rewarding procedure, that he developed a methodology of 'knowing' where to put what atom to acheive a more promising end compound. Sasha more or less "knew" where to add what atom(s), to get plausibly psychoactive molecules. Furthermore he could make good predictions about what the approximate psychactive effectes of the new creation may be. Most combinations are not active, or are not very interesting to the Psychonaut, but practice as Shulgin demonstrated more than anyone else, makes one significantly more proficient if not quite perfect.

Finally the N, to the far left of the molecule (on the right of the page), is a Nitrogen atom bonded to hydrogen atoms and one carbon atom. This part is called the amine and represents the amine in phenethyl'amine'. The amine is connected to the benzene ring via the ethyl or 2 carbon chain. The 2 carbon chain incidentally is why Shulgin named 2C-B with a 2 at the front - the 2 represented the 2 carbon atoms.

This is the simplified, but accurate for our purposes, molecular structure of all the magic 6 phenethylamines. Shulgin created over 150 novel psychedleic molecules by following this process of attaching interesting atoms or combinations of atoms to the 'free' carbon atoms on the phenethylamine. This is all we need to know about the basic strucutre of the organic molecule called the phenethylamine.

San Pedro (Echinopsis Panachoi)
This molecule is the building block of many of the brains neurotransmitters, notably Dopamine and Adrenaline, called the Catecholamines. It also bears a striking resemblance to the neurotransmitter Serotonin. Serotonin is where Mescaline produces it's unique and often profound effects. The phenethylamine is also the base molecule of many illegal drugs, not just psychedelics but central nervous system stimulants, such as Methamphetamine and empathic/entactogens drugs, such as MDMA. Just because these drugs are phenethylamines does not mean they are psychedlic, a psychedelic has special charateristics that must be met to be called a psychedleic.

 All of Shulgins magic half dozen psychedelics are phenethylamines and are true psychedlics - meaning they activate specific serotonin receptors in the human brain. Below is a diagramatic comparison of mescaline, phenethylamine and the neurotransmitter serotonin. Notice the basic structure of all is largely the same. Mescaline has three identical molecule's attached to the right hand side (benzene ring positions 3,4,5) in the diagram below, this is the only difference between it and a basic phenethylamine. We will discuss the structure of Mescaline further, but in the next chapter on Mescaline we will examine it's qualitative, experiential side - what happens when you take the drug and is it really better than over 150 other psychedelic phenethylamines? We will also examine why Sasha Shulgin was so fascinated and captivated by this molecule. His first dose of Mescaline began his career in psychopharmacology after all.

In the following chapters we will discuss my experiences with Mescaline. I will try and contrast these with Shulgin's reports. I agree with Shulgin regarding the addition of Mecaline to the Magic 6 list. There are literally thousands of psychedelic drugs, deciding which one's are the most important for humanity is difficult - and thats putting it mildly. It is subjective by it's very nature, but there must be a reason why the Godfather of jourying into the mind AKA Psychonautics, found mescaline more than compelling.


Notice the similarities in the molecules. For example mescaline and serotonin share similiarities and this is a reasonable indication of what kind of psychaoctive effects mescaline might produce. So if it is similiar to serotonin it is plausibly a psychedelic, but not always. Mescaline is a phenethylamine with three methoxy molecules bonded to 3 carbon positions on the left of the phenethylamine. These positions are called 3,4 and 5. Think of the benzene ring (the hexagon) as a clock. The positions where the carbon atoms are located are called 1,2,3,4,5 and 6. Position 1 is carbon attached to the up-down-up line (the ethyl molecule), and working anti-clockwise you count through positions 2,3,4,5 and 6, which is below the up-down line. Dont worry I will walk us all through the basic chemcial structure of Mescaline and Serotonin in coming chapters for anyone who is confused. Just observe their similarities and differences. ;) This is one key to PwKHAL.



Thanks Brady.

PwKHAL. Reflections on Shulgins Death. Part 1

PwKHAL. Reflections on Shulgins Death. Part 2

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