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[bmk-pmk]

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[goodvibesandchemnotes]

I DID A THING

This is a color-coded chart about ketamine derivatives, or "arylcyclohexylamines". It doesn't entirely tell you what they DO (that's a lot of information) but it does explain how the names correlate to the shapes. This isn't perfectly organized, but aims to cover the major recreational and pharmaceutical drugs in the category.

This is a very wide category but these are mostly dissociative drugs that serve as (human and animal) anesthetics and recreational drugs, either mostly harmless "club drugs" or derivatives of the horrific PCP. What blows me away more than anything is how chemically similar these are. Without getting too technical, the red "O" takes away most of PCP's manic and psychotic properties; replacing P (piperidine, blue) with E (ethylamine) makes PCE more potent; and, now we have two steps of association between the stuff they use to anesthetize your cat and the stuff they use to induce violent schizophrenia and godlike strength. Those are two points on the spectrum, but these drugs are used for everything from treating strokes to PTSD/depression to even tinnitus!

Now, it's human nature: 1)when given something that turns your brain off, you're gonna want more of it, and 2)when told no, humans can be very crafty. And *very unethically* do in 5 years where researchers need 50. In particular, MXE was a nightclub favorite, being a serotonin-inducing relative of ketamine. Disgruntled by their lack of chemically induced warm trance-y vibes, the club scene soon included close derivatives like MXPr and MXiPr. And disgruntled by their lack of whatever the hell inspires PCP users to use PCP, the designer drugs scene soon included all sorts of derivatives.

This segues into another important detail, the number and 2-3 letter code before most of the acronyms. To all the non-chemists, this is whatever we add to the first P (phenyl), the orange hexagonal ring. Generally speaking, adding something thats more negative (HO, MeO, Cl, F) at the #2 position will make the drug act ONLY as an anesthetic, the #3 position tends to make the drug release more serotonin and subjective "warmth", and the #4 position tends to retain the manic and psychotic properties of PCP and derivatives. Adding a "Me" (methyl, -CH3) doesn't tend to make a big difference, meaning 3'-Me-PCP will act almost identical to PCP but 3'-MeO-PCP will have a drastically improved (but still insufficient) safety profile.

There's one odd child in the family, 3-HO-PCP. This one uniquely acts as a mild opioid (as well as "warm", manic, and overall dissociative anesthetic), in no small part from its resemblance to tramadol. Tramadol is a mild opioid often used to treat moderate-to-severe pain, with the similar serotonin "warmth" but absolutely no mania and only weak dissociative effects. Since PCP and 3-MeO-PCP are extremely potent anesthetics on their own, the opioid activity is sedative more than analgesic, and reduces the dangerous manic tendencies associated with many PCP derivatives. It is not known if 3-HO-PCE has opioid activity, or just behaves like it's 3-MeO cousin.

If I try and explain how drugs work in terms of receptors we'll be here all day, so I'll keep it in terms of "design" and "effect". The vast majority of these drugs are dissociative anesthetics, which SAFELY turn a chunk of the brain off and force the user into a trance-like state called a "hole". This is helpful in the case of protecting against damage from strokes and dementia (can't damage whats not currently accessible!), and provides a "reset" in the case of depression and PTSD that cues your brain to provide higher levels of activity when it wears off (as well as providing an out-of-body experience with powerful psychological implications, often compared to a near-death experience). The manic and psychotic (dopamine) properties can be suppressed by adding the red "O", a 2-keto group, which makes the drug significantly safer and more appealing for recreational and therapeutic use. Conversely, changing the phenyl P to a benzothiophenyl BT takes away all anesthetic properties and makes the drug purely a stimulant. Changing it to a thiophenyl T doesn't change end result much on its own, but tiletamine OTCE has seen increased effectiveness in veterinary medicine, and gacyclidine 2-Me-TCP is clearing clinical trials for a neuroprotective agent.

The big take-away here is that tiny changes to a chemical lead to massive changes in safety and effect. This can be used to fine-tune drugs to ideal therapeutic use, but its worth mention that we don't know about the vast majority of fine-tuned combinations yet to come. It's also worth mention that the designer drug market works 10 times faster than the world's professional research labs ever could. This means much quicker human results and descriptions, but an infinitely higher risk of death by overdose and poisoning from drugs no antidote has been developed for. A fantastic example of this danger is in the Spice/K2/synthetic cannabinoid craze of the early 2010s, where we found out making a cannabinoid stronger doesn't make it more effective, it makes it more dangerous. And for every Alexander Shulgin (the man who discovered hundreds of psychedelics and their effects on the mind and soul) there are thousands of unlucky 20s taking a pill they bought at a club.