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Pharmacology Paleopsychopharmacology & Mankind's Evolution in Symbiosis with Psychoactives in Our Environment

This thread contains discussion about a Pharmacology-related topic

Pharmanaut

Bluelighter
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Mods, I read your "Quality over Quantity" rule & if this is too long I will happily chop it up into chunks. But it was written in one sitting & I feel it flows...
But I will, of course, bow to your direction.


Prohibition has stripped away the social rules, techniques & custom of drug use. We evolved in symbiosis with khat, opium, mushrooms, cannabis & a myriad of other substances. We have to rediscover the techniques of beneficial, social/ ritual use of all of them as smuggling makes purification (size reduction) more commonplace.
There's 22 alkaloids in opium, heroin fucks you up. Coca has been used safely for millennia, coke fucks you up.
Ganja was once a pleasant, mild buzz. Skunk fucks you up! Khat is a great social stimulant, helps endurance, concentration... Meth fucks you up!
It's time we rediscovered the natural drugs & how to use, not abuse, and reclaim the survival advantage that they so obviously gave mankind originally.
Paleopsychopharmacologists have a puzzle. It's stumped them for decades. It's called the human drug reward paradox.
Why does poisoning your system feel good? It should make you feel ill
Well, once you realise that these chemicals have a survival advantage, just like eating, drinking, sex, breastfeeding... If it's good for the tribe's survivability, it feels good.
The human drug reward paradox disappears as soon as you realise that a hunter that runs down it's prey will have an advantage with the pain relief from opium. That nomads looking at a camels arse all day can use khat to reduce food intake, increase endurance & take pleasure & interest in conversation... An advantage over other nomadic hominids. Coca for altitude sickness. Psychedelics for those thoughts that link widely disparate subjects give us a huge cognitive boost!
Just observing what happens to the poppy seeds when making poppy tea tipped us off about farming . Much more likely than grains, don'tcha think?
There were some N. African nomads that their government thought were primitive & backwards so they were forced into social housing.
All of them, every single one, not only became morbidly obese but, en masse, they developed AD/HD!This puzzled doctors and sociologists alike!
No one had the foggiest why these two comorbofities should appear on these ex-nomads.
I thought that if my idea about the human drug reward paradox evaporating in the face of positive advantages in survival, cognition, social & technological progress caused by our symbiotic relationship with psychoactive plants & fungi over many millions of years had a solid foundation then those fat, ad/hd riddled ex nomads should have had an amphetamine mimic in their diets when they were nomads.
I googled their home range plus "local drug of choice".
When khat popped up it was solid confirmation of what I'd been thinking about for decades!
Khat is a stimulant. The active ingredient is cathinone. Beloved of the research chemical industry, cathinone is a very respectable direct replacement for amphetamine. Yo make it stronger & longer lasting you can make methcathinone. To make an excellent mdma analogue you can make methylenedioxymethcathinone!
In fact, it's the other way around, we evolved in Africa, khat has been in our diet for millions of years.
It's little wonder that these nomads, deprived by law & by being forced to live in the city of their khat, they started overeating, not exercising due to lethargy & developed AD/HD to a man!
So when amphetamine is prescribed for weight loss, and to regain concentration, calmness & comprehension in the seemingly universal affliction of AD/HD what we are in fact doing is replacing a psychoactive chemical that we evolved into Homo sapiens in the continuous presence of since Homo habilis, Homo erectus and before!
The withholding of cathinone and it's mimic, amphetamine by outlawing them is a legally enforced dietary deficiency causing untold suffering & problems in people so deprived.
It's obvious that the worldwide seeking out of stimulants, the poor and ineffective caffeine, ephedrine and gaurana plus the continued popularity of cocaine is merely humans seeking a replacement for the cathinones that our brain & CNS needs for normal, healthy function.
To evolve in the presence of such a stimulant since before we were even human means that without it we are not functioning as we should. The withholding of cathinones & amphetamines is akin to the purposeful hobbling of our intellect, concentration, comprehension, hunger suppression (no wonder morbid obesity is a worldwide problem.)
Also why it's difficult to get kids to read, motivated, interested and to actually take in information.
The more you look into it, the more you find.
The Cytochrome P450 array of enzymes that scientists thought were there to break down toxins were startled to discover that not only did these enzymes change some of the alkaloids found in the opium poppy into forms that LASTED LONGER in the body than the bog standard alkaloids but that these longer lasting opiates got across the blood / brain barrier more efficiently.
Also, that genotypes that evolved in the opium poppies natural range, Turkey and the stans, were much more efficient in their Cytochrome P450 array of enzymes handling of the alkaloids in the opium poppy pointing to it being part of our diet in that area long enough for the people there to have co-evolved in symbiosis with Papaver somniferum. They crack the alkaloids into forms that stay in the body longer much more efficiently than populations elsewhere.
So the human drug reward paradox simply doesn't exist once you take account of the benefits of psychoactive chemicals in our NB actual diet. We're a walking collection of receptor sites, ready and tuned to take advantage of these chemicals, to hang on to them for as long as possible and extract every & any scrap of benefit we can from them.
We should be called "The Drug Using Ape". Not tool use, not speech, not technology... Other species do these things to a greater or lesser degree.
It's our symbiosis with psychoactives in our natural diet and environment that sets us apart.
And the so called war on drugs is really a war on the effects of prohibition. Concentrating the active ingredients for easier smuggling, adulterants, prohibitive cost, the loss of ritual and social regulation due to artificial stigma and necessary covert use are all products of prohibition, not the chemicals themselves.
I feel that this goes way beyond the "Stoned Ape" hypothesis of the sixties. This is only a truncated version, there's more and more as you look into this.
I'd love some input. What do you think?
Pull it apart, I'll see if I can counter. This way of looking at drugs and humanity's use of them is a radical rethinking of what has been our approach to psychoactives.
I believe they firm an important part of our diet & nominal functioning.
I'd love to find out what you think about this short taste of what I've been pondering for a couple of decades.

Keep safe,

Pharmanaut 😃💜☮️🕊️
 
First off, interesting ideas. I don't entirely agree that poppy seed tea/opium is really that much better than heroin in terms of addiction. It's a strong opioid, and causes some brutal withdrawals (also the seeds vary in potency enough that you have to do tester batches like with heroin to be safe).

I guess I also am unsure about the khat bit as well. Khat production is concentrated to a few regions in Africa and the Arabian penninsula (Yemen, Somalia, and Ethiopia). Because cathinone dimerizes, khat needs to be fresh to work, and it is extremely water intensive outside of its natural habitat. Before the 1990s it was restricted to very specific regions in those countries where there was enough rain to cultivate it, and it wasn't broadly traded enough to be a major force among human evolution.

I have a hard time believing that the major factor in adhd development for these folks was loss of khat use. ADHD is pretty common in people who have not historically used stimulants. The big change with these populations is the broader change to a life where sitting at a desk is more valued, so people with ADHD have fewer outlets. ADHD likely has adaptive effects when living as a hunter gatherer or farmer in a group, that becomes detrimental when living in a modern city.

Also, cytochrome p450 enzymes are expressed in every kingdom of life (bacteria, archaea, and eukaryotes) because it can perform some extremely useful chemical transformations in both metabolism and biosynthesis. It's really hard to correlate levels with envinronmental exposure, as they are regulated via the aryl hydrocarbon nuclear receptor, so respond to a range of compounds (often things like polycyclic aromatic hydrocarbons, dioxins, some flavinoids).

I think our reward system has evolved without major selection pressures from recreational/enjoyable/proper drugs. Drugs can override many of the other hedonic drives, which does not increase ones evolutionary fitness. They certainly have had important uses, both as medicines, and tools to feel pleasure, but if there was such strong coevolution you would see much more homogenaity with the global drug diet. Other species use drugs and alcohol too, I think our relationship with drugs is due to our intelligence not that using drugs are something that specifically make us human.
 
I don't think that we've evolved in symbiosis with any psychoactive substance or recreational drug.

First of all purposeful use of what we call recreational drugs has not been going on long enough for us to have evolved with respect to the drugs at all.

The simple fact that psychoactive drugs affect all mammals and many vertebrates the same way they affect us means it's not symbiosis, it's curiosity and for the ones that survived, Good luck.

I think that you would have a hard time showing that the use of psychoactive substances gives a persistent survival advantage over not using it. Especially when dependence, withdrawal, and negative physical sympathomimetic cardiac, cardiovascular effects could easily result in death.

In fact, the majority of psychoactive substances regularly used by humans end up causing fights with either verbal or actual physical violence.

Stimulants cause altercations, khat, meth, cocaine, etc. Dissociatives are not sustainable for a successful survival advantage. Neither are deliriants.

Psychedelics are actually a really good way to relax and experience things. They have a very low potential for abuse very high therapeutic index except for some of these completely batch. It insane research chemicals.

I don't know of any substance that has caused more mayhem murder death war pestilence you name it, then alcohol in the history of mankind.

While there are some people that can be successful, meaning their life doesn't go to shit while doing cocaine or methamphetamine or other stimulants or alcohol or psychedelics or marijuana or opiates over the long term. That number is vanishingly small when people actually admit how fucked up their life got at times even if they were one of the few that could keep it under control.

I guess I can sum it up like this:

It doesn't matter how many times you tell the baby or show the baby that that stove is hot. You can light things on fire. You can hold his hand near it so he can feel the heat. But until he burns his hand, he's still going to want to touch it.

That's humans and drugs. It's not a symbiotic evolution. Humans are curious, lazy, hedonistic, pleasure seeking, pain averse, oxytocin, dopamine, serotonin, and adrenaline addicts.

We're also really good at making up fantasies and if our life isn't the fantasy we want to live, we will find substances that will help us escape the life we have.
 
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