Monday, December 16, 2013

pCA NEUROTOXICITY: DIABLO XXX FORMULA 3?


With the recent news that a variety of legal high products featuring 4-chloroamphetamine (pCA) as an active ingredient have appeared on the gray market I thought I'd post an excerpt from my Harper's article published earlier this year that describes the experimental use of pCA as an antidepressant:
One of the most frightening things about the human brain is how poorly it gauges its own functioning. Things quickly become complicated when you attempt to measure the performance of an instrument with the instrument performing the measurement. In 1969 a Dutch psychiatrist named Herman M. van Praag conducted a series of experiments on depressed patients with 4-chloroamphetamine, a new drug that possessed a significant therapeutic effect and was tolerated excellently; not a single patient complained of side effects. Though Praag discontinued his work in the mid- ’70s, 4-chloroamphetamine is still used widely today, not as an antidepressant but as a neurotoxin for selective depletion and destruction of serotonergic neurons in experimental animals. The point being that humans cannot necessarily feel neurological changes. Many disorders of the brain are accompanied by a commensurate inability to perceive the disorder. The later stages of Alzheimer’s, for example, are characterized by memory loss so severe that the deficits are forgotten.
A more intuitive example of this phenomenon is encountered in the peripheral nervous system where superficial first and second degree burns are extremely painful but deep third and forth degree burns can be relatively painless due to complete destruction of sensory receptors in the skin, just because there is no sensation doesn't mean there hasn't been damage done. I wanted to post all this in response to a number of claims that pCA's lack of acute adverse effects could be interpreted as an indicator that it lacks toxicity.

Chemically pCA is highly optimized for depleting serotonin stores and virtually all structural modifications such as N-methylation, N-hydroxylation, β-hydroxylation, ketoximidation*, or 3,4-dichlorination decrease its toxicity. It also possesses a much higher toxicity than pIA or pFA, with only pBA exhibiting comparable potency. The mechanism of pCA's toxicity is still unclear and after reviewing the literature the only thing that can be said with certainty is that it's SERT dependent and blocked by SERT inhibitors. 

I've been reading a lot of the discussion posted on Reddit, Bluelight, and other forums and it seems the harm reduction community succeeded in preventing the sale of pCA containing products as they have recently been removed from the vendor's website. If the tablets were actually pressed then I wouldn't rule out the possibility that the vendor simply responded to the outcry by removing the offending items and reintroducing them under a different name so I would treat any of their offerings with extreme caution. If anyone did purchase the pCA containing tablets please email me as I would very much like to confirm that this material was actually being sold.

*Presumably the nounal form of ketoxime 

4 comments:

Borega said...

They Guys over at http://legal-high-inhaltsstoffe.de/ have also agreed to test all accused products but need a source for purchase. If any products that are accused of containing pCa turn up in sales again plz also give them a notice.
(Due to legal reasons they can not accept sent in products but must purchase the product themselves)

Coyote said...

Looking for info on neurotoxicity of salvinorin A. I've google scholared it but haven't found anything. Most psychedelics are not neurotoxic but salvinorin A acts like a dissociative, I guess?--from my limited understanding of neurochemistry.. and I know there's some evidence of neurotoxicity in a few dissociatives...

SDR said...

Borega,surprisingly pCA (CAS 64-12-0) is not yet regulated under the German BtmG yet but it, depending on the purpose it is bought, used, manufactured, possessed our owned will be considered a prescription drug. So if this German group stil just wants to take a look at it and teach about its toxicity without considering animal or human use, it won't be a problem for them to order it. I would advise them to stop by the university, college of pharmacy in frankfurt to talk to the "fachschaft" student's board.http://www.fspharma.de

Steve Gill said...

And yet the 4-fluoroA and 4-fuuoroMA seem to be pretty harmless.....strange stereochemical receptor mysteries///// What about the 4-trifluoromethyl?