The Travis Corner

[Travis]

What about calcium oxalate kidney stones? And oxalates in the urine are much higher in individuals with autism than in normal children (Figure 1)?View attachment 7895

OXALATES CONTROL IS A MAJOR NEW FACTOR IN AUTISM THERAPY

What are those units? Do you think spinach has enough oxalate to approach the amount produced by the body?

 

[Travis]

methyl esters Methyl palmitate 1431603

Metabolism of topically applied fatty acid methyl esters in BALB/C mouse epidermis. - PubMed - NCBI

This article is cool because it talks about an unusual fatty acid: vaccenic acid.

'After methyl palmitoleate treatment, palmitate 16:0, 16:1 and vaccenate (18:1 delta 11) were elevated at the expense of linoleate in acylglucosylceramide.' ―Wertz​

I can see how it would be nice to reduce arachidonic acid on the skin. I wonder if there are more studies on this?

 

[Mito]

What are those units?

mmol/mol creatinine

 

[Travis]

This seems significant. This article has oxalic acid in spinach at 1.18·g/100·g. This is higher than found in urine, but only about ~30% is adsorbed—being bound to calcium. But this seemed high, so I kept looking. Here is a more believable number:

'Oxalic acid content in spinach is 4.2 mg/g, which is consistent with the result reported by Chen et al. (1989).' —Wu​

And it's consistent with Chen, making it even more believable.

This website indicates that males produce 'roughly 1575 mg/day' of creatine, which is ~12·mmol/day. This would make the excreted oxalic acid about ¹⁵⁄₁₀₀₀ of that, assuming a constant ratio and using a number approximating the number in your chart. This yields 180·μmol·oxalate/day, or 16.2·mg/day. This is roughly the amount found in four grams of spinach, or less than ¹⁄₁₀₀ of a pound.

But oxalate produced in the body and is used to create uracil, the nucleic acid.

'This means that the onset of fatty liver in humans is a precursor to the onset of formation of calcium oxalate kidney stones. The apparent confining of this effect to particular species is the result of differences in metabolic reaction rates between species. The above proposals mean that an increase of oxalic acid in human metabolisms is the result either of a failure to completely use the ingested oxalic acid in the formation of uracil and/or orotic acid or that a degenerate condition occurs where the oxalic acid is used normally and the condition results in the release of uracil and/or orotic acid from ruptured cells into the blood stream, where either or both are decomposed as described to give oxalic acid. Uracil is a component of RNA and is produced by all cells. The highest rate of uracil production is associated with the cells with highest rate of division. As shown in Table 3 short-lived and rapidly dividing cells are associated with the digestive system.' ―Stewart Robertson​

So kidney stones can apparently occur without spinach‐eating, and can even be formed from the decomposition of ingested RNA. You would think that a good percentage of ingested oxalic acid in spinach becomes RNA within the body, perhaps to help transfer instructions for enzymes like pyruvate decarboxylase.

Last week I had bought 6 pounds of spinach and ate one pound per day (they stopped selling organic kale in the plastic clamshell.) I haven't noticed any unusual effects, and am now wondering where most oxalates in the urine come from. I'm getting the impression that most of it is endogenous, and the people who get kidney stones don't particularly eat that many vegetables at all.

Wilson III, Charles W. "Analysis of oxalic acid in carambola (Averrhoa carambola L.) and spinach by high-performance liquid chromatography." Journal of Agricultural and Food Chemistry (1982)
Wu, Fengwu. "HPLC determination of oxalic acid using tris (1, 10-phenanthroline) ruthenium (II) chemiluminescence—application to the analysis of spinach." Food chemistry (1999)
Stewart Robertson, Daniel. "The function of oxalic acid in the human metabolism." Clinical chemistry and laboratory medicine (2011)
​

 

[raypeatclips]

@Travis You seem rather cautious of dairy, and highlight some negatives of it, especially compared to the general consensus of this forum. What are your thoughts on calcium, or even the calcium and phosphorus ratio? Do you think other types of dairy such as strained yoghurt are superior compared to something like milk, or do you think they all have the same potential to be detrimental? Thank you

 

[Amazoniac]

Semi-god, how do you clean your produce?
I'm actually more curious about how you disinfect without poisoning the food.
Cooking solves this, but some is consumed raw.

 

[Travis]

@Travis You seem rather cautious of dairy, and highlight some negatives of it, especially compared to the general consensus of this forum. What are your thoughts on calcium, or even the calcium and phosphorus ratio? Do you think other types of dairy such as strained yoghurt are superior compared to something like milk, or do you think they all have the same potential to be detrimental? Thank you

Well dairy is the only food produced exclusively for that purpose, so it certainly shouldn't be toxic to a growing animal. On the toxicity scale, it would have to be zero if you trust nature. However, you could make the argument that it's a bit rich for an animal already grown. But still, it should still be relatively nontoxic since it's one of the few foods purposely created as such.

Fruits are made by plants, and can be thought of as seeds baited with a sugary coating loaded with vitamin C and B vitamins. Plants don't eat their own fruit; the only logical reason they'd take the effort to produce it would be to attract fruit‐eaters for seed dispersal (and keep them healthy with B vitamins, so they come back.) By this logic, it would defeat the purpose for the plant to intentionally make its fruit toxic. The existence of toxic berries is somewhat confusing, but perhaps these are only toxic when unripe (or only to certain species.) I think fruit is the #2 food because it seems purposeful like milk.

Leaves were designed for photosynthesis, and not to feed pandas and giraffes. Despite what little cousins may say, plants neither 'hate being eaten' or 'like being eaten.' Evidence suggests that plants are impartial to being eaten—having no nervous systems.

What can be said about plants can be said doubly about seeds. Eating a seed is eating the potential for an entire tree, and intentional toxins are often found more concentrated in seeds than in leaves.

Animals don't seem to enjoy being eaten, and even take active steps to avoid this: running, clawing, and climbing are evasive techniques sometimes observed. (Koala bears hate being eaten.) Despite what a few ecclesiastics have said in the past, there is no evidence that 'God' had created animals to be food for humans.

The über‐taxonomist Carl Linnæus had viewed humans as frugivores. ​

But milk is a complex biological product which can release the most potent exorphin, a five‐to‐nine amino acid long peptide called β-casomorphin. This peptide works on the μ-opioid receptor, is blocked by naloxone, and actually conforms to the 'morphine rule:' a series of properties an opiate must oblige to; discovered by eliminating all unnecessary components from morphine—and associated compounds—revealing a non‐reducible opiate blueprint:

1) A tertiary nitrogen with a small alkyl substituent
2) A quarternary carbon
3) A phenyl ring or its equivalent attatched to the quarternary carbon
4) A 2 carbon spacer between the quarternary carbon and the tertiary nitrogen​

As you can see, β-casomorphin‐7 fulfills these requirements:

click to embiggen: β-casomorphin within bovine casein sequence.​

The working end is the one having tyrosine . . . followed by a proline. Besides amplifying the opiate properties, and helping to fulfill the 'morphine rule,' the three prolines within this seven‐amino‐acid segment confer the property of enzymatic resistance (to pepsin and trypsin). The reason why proline resists digestion so well is that proline has a unique peptide bond; the ring structure of proline is the peptide bond. Proline‐rich regions are more resistant to pepsin hydrolysis and are much more likely to be absorbed in longer fragments. These peptides have been found in the cerebospinal fluid of people so you can be sure they can enter the brain.

So why does morphine work at all? Is this an accident? or is morphine and codeine interfering with an extant opiate system? Evidence suggests the latter; we do have endogenous peptide optiates called the enkephalins:

The peptide to the left is named leucine-enkephalin. ​

As you can see, this one also has an N‐terminal tyrosine with a phenylalanine separated by two amino acids. This endogenous opiate has no prolines, and thus would then have a shorter half-life in the blood. The β-casomorphins can be thought of as interfering with our endogenous opiate signalling while also being relatively resistant to degradation (compared to the enkephalins.)

These opiates could perhaps create emotional bonding between lactating animals and their greedy, spaced‐out, and addicted children; they could also make milk seem 'cool,' and nipples even cooler than they already are; giraffes, piglets, cows, sheep, acalpacas, cats, and cows not excluded. Not all caseins have been sequenced, and there is no way to tell what opiates are lurking inside the amino acid sequence of . . . panda milk, for instance.

These opiates have been experimentally shown to decrease intestinal transit time—and blocked by naloxone. ​

Is there a way to ingest dairy while circumventing these opiate-like effects? Can we improve on nature? Can we turn the perfect food for a calf into the perfect food for a human? Perhaps there is a way; one can buy enzyme tablets online which contain enzymes experimentally proven to cleave proline peptide bonds. Since these have been shown to nullify wheat gluten, a protein having far more prolines, you would expect them to eliminate the opiate effects in dairy—should this be desired—since the proline-rich region is small (see above sequence).

But other than the potentially problematic exorphins, cheese seems to be a good food. The amino acid ratio of cheese is decent and its fatty acid profile is on the same tier as chocolate, beef, and coconuts. If a person's immune cells do not react with the proline-rich fragments, then the prostaglandin potential of dairy should be quite low. But like chocolate, people sometimes do react to the proline-rich peptides found in dairy.

 

[Travis]

Gluten exorphin B5 is similar. This peptide is thought to work on the δ-opioid receptor, not the μ-opioid receptor like β-casomorphin. This has been shown to be absorbed after eating pizza in all test subjects despite not having a proline bond. It has also been shown to release prolactin, ostensibly by reducing dopamine in the brain.

'Gluten exorphin B5 (GE-B5) is a food-derived opioid peptide identified in digests of wheat gluten. We have recently shown that GE-B5 stimulates prolactin (PRL) secretion in rats; this effect is abolished by preadministration of the opioid receptor antagonist naloxone' ―Pennington

​

'...we can hypothesize that GE-B5-stimulated PRL secretion is exerted at this level via the inhibition of dopamine release from TIDA neurons' ―Fanciulli​

It makes you wonder then how much of morphine's effects come from the reduced dopamine, a neurotransmitter that I think is half-responsible for nerve impulses (acetylcholine responsible for the other half).

Beta-casomorphins have also been shown to increase prolactin in the rat. This does makes sense when you realize that prolactin powerfully increases intracellular calcium by releasing inositol phosphates from cell membrane phospholipids; this could be a way to stimulate bone growth in young animals by making use of the calcium found in milk.

'Morphin, beta-casomorphin and its analogue Tyr-Pro-Gly..Pro-Phe-Pro-Ilo were tested by intraperitoneal route for their ability to alter prolactin levels (Table. 1). Morphin at a dose 10 mg/kg w., beta-casomorphin (at a dose 15 mg/kg w.) and analogue I (at a dose 15 mg/kg w.) increased plasma levels of prolactin 15 min after injection.' ―Nedvidkova​

So this prolactin release seems to be a near‐universal property of opiates, although some like DPDPE appear to be without prolactin‐releasing effects (Leadem, 1987).

Nedvidkova, J. "Effect of beta-casomorphin and its analogue on serum prolactin in the rat." Experimental and Clinical Endocrinology & Diabetes (1985)
Fanciulli, Giuseppe. "Gluten exorphin B5 stimulates prolactin secretion through opioid receptors located outside the blood-brain barrier." Life sciences (2005)
Pennington, Christopher L. "Detection of gluten exorphin B4 and B5 in human blood by liquid chromatography-mass spectrometry/mass spectrometry." The Open Spectroscopy Journal (2007)
Leadem, Christopher A. "Effects of specific activation of mu-, delta-and kappa-opioid receptors on the secretion of luteinizing hormone and prolactin in the ovariectomized rat." Neuroendocrinology (1987)​

 

[Travis]

...how do you clean your produce?
I'm actually more curious about how you disinfect without poisoning the food.
Cooking solves this, but some is consumed raw.

Clean the leaves? No way; they come in a plastic clamshell container pre‐washed—and organic!

I suppose some things are better off washed, but I live next to the best grocery store ever. Whenever I leave my state, I am disappointed since most other stores are smaller and the organic produce costs ~1.5 – 2× as much. I just got organic apples in a 3# bag for $2; most places don't even have conventional apples that cheap.

The pineapples are also $2. These ones I bought are Dole, but they appear to be good and weren't frozen during shipping (accurately confirmed by squeeze test). I'll let you know how these Doles compare to the Del Montes. I know that that the Dole Hawaiian pineapples tend to be green and overly‐acidic, as most are, but the best pineapple I ever had was a Dole—from Panama! You can look at the label and tell which country they are from, and I think I have noticed a trend by country (state):

Panama > Guatamala > Costa Rica > Hawaii ​

I didn't avoid using the 'greater‐than, or equal‐to' symbol (≥) because I was lazy, but because no two pineapples are the same (lol).

I wonder if the pineapple enzyme bromelain can help cleave these proline bonds in cheese? How can we mix pineapples and cheese together in an interesting way? to test for the opiate effect? I honestly cannot see them going together; you might just have to cut them up into cubes and eat them piece‐by‐piece with chopstix (the only thing that doesn't seem completely absurd).

 

[Koveras]

These opiates have been experimentally shown to decrease intestinal transit time—and blocked by naloxone. ​

Is there a way to ingest dairy while circumventing these opiate-like effects? Can we improve on nature? Can we turn the perfect food for a calf into the perfect food for a human?

Did you know that coffee contains opioid antagonists?

Beyond Caffeine: Coffee Contains Opioid Antagonists
Whittle Robin. Journal of Caffeine Research. March 2015, 5(1): 1-2. https://doi.org/10.1089/jcr.2014.0024​

 

[Lee Simeon]

Clean the leaves? No way; they come in a plastic clamshell container pre‐washed—and organic!

I suppose some things are better off washed, but I live next to the best grocery store ever. Whenever I leave my state, I am disappointed since most other stores are smaller and the organic produce costs ~1.5 – 2× as much. I just got organic apples in a 3# bag for $2; most places don't even have conventional apples that cheap.

The pineapples are also $2. These ones are Dole, but they appear to be good and weren't frozen during shipping (accurately confirmed by squeeze test). I'll let you know how these Doles compare to the Del Montes. I know that that the Dole Hawaiian pineapples tend to be green and overly‐acidic, as most are, but the best pineapple I ever had was a Dole—from Panama! You can look at the label and tell which country they are from, and I think I have noticed a trend by country (or state):

Panama > Guatamala > Costa Rica > Hawaii ​

I didn't avoid using the 'greater‐than, or equal‐to' symbol (≥) because I was lazy, but because no two pineapples are the same (lol).

I wonder if the pineapple enzyme bromelain can help cleave these proline bonds in cheese? How can we mix pineapples and cheese together in an interesting way? to test for the opiate effect? I honestly cannot see them going together; you might just have to cut them up into cubes and eat them piece‐by‐piece with chopstix (the only thing that doesn't seem completely absurd).

Clean the leaves? No way; they come in a plastic clamshell container pre‐washed—and organic!

I suppose some things are better off washed, but I live next to the best grocery store ever. Whenever I leave my state, I am disappointed since most other stores are smaller and the organic produce costs ~1.5 – 2× as much. I just got organic apples in a 3# bag for $2; most places don't even have conventional apples that cheap.

The pineapples are also $2. These ones are Dole, but they appear to be good and weren't frozen during shipping (accurately confirmed by squeeze test). I'll let you know how these Doles compare to the Del Montes. I know that that the Dole Hawaiian pineapples tend to be green and overly‐acidic, as most are, but the best pineapple I ever had was a Dole—from Panama! You can look at the label and tell which country they are from, and I think I have noticed a trend by country (or state):

Panama > Guatamala > Costa Rica > Hawaii ​

I didn't avoid using the 'greater‐than, or equal‐to' symbol (≥) because I was lazy, but because no two pineapples are the same (lol).

I wonder if the pineapple enzyme bromelain can help cleave these proline bonds in cheese? How can we mix pineapples and cheese together in an interesting way? to test for the opiate effect? I honestly cannot see them going together; you might just have to cut them up into cubes and eat them piece‐by‐piece with chopstix (the only thing that doesn't seem completely absurd).

I think taco and Hawaii-pizza are the best options

 

[Travis]

Did you know that coffee contains opioid antagonists?

Beyond Caffeine: Coffee Contains Opioid Antagonists
Whittle Robin. Journal of Caffeine Research. March 2015, 5(1): 1-2. https://doi.org/10.1089/jcr.2014.0024​

No I hadn't.

This could be a mind‐blowing revelation, depending of course on how strong these anti‐opiates are and what concentrations they are found in.

I have two coffee brands from Costa Rica right now, just ground course yesterday for the French press. I think I can still feel the echos from the cheese I had over a week ago (are β-casomorphins still in my cerebospinal fluid?) I think I'm going to make another quart of coffee and read that article.

 

[Amazoniac]

The type of pineapple that you enjoy has a clear pulp? Those tend to be the mildest in my experience.
You find the popular sticks alternating cubes of cheese, pineapple, and cherry, a bizarre combination?
__
Isn't it crazy that reptiles can digest an entire prey for a long time without being poisoned? All that being cold-blooded animals. I wonder how they go through the night. If I remember it right, the stomach acidity is what prevents the decay. Still impressive.
__
How would you clean your produce?
Not an exciting question but less exciting than that is a 3m roundworm.

 

[raypeatclips]

Did you know that coffee contains opioid antagonists?

Beyond Caffeine: Coffee Contains Opioid Antagonists
Whittle Robin. Journal of Caffeine Research. March 2015, 5(1): 1-2. https://doi.org/10.1089/jcr.2014.0024​

@Travis @Koveras Do you know if this trait is shared with decaf coffee too? I couldn't see the article but it mentions coffee, rather than solely caffeine, in the title, which made me wonder.

 

[Wagner83]

The opiate effects of wheat and dairy goes very well with a lot of the issues I have experienced. If dairy is so good for bone growth then perhaps having smaller amounts of goat cheese would be good for long term health.
Do you have any idea why some people react much more to dairy than others? Have thyroid function and overall metabolism anything to do with it?

 

[Koveras]

@Travis @Koveras Do you know if this trait is shared with decaf coffee too? I couldn't see the article but it mentions coffee, rather than solely caffeine, in the title, which made me wonder.

It is, it’s in one of the references

 

[Tarmander]

Well dairy is the only food produced exclusively for that purpose, so it certainly shouldn't be toxic to a growing animal. On the toxicity scale, it would have to be zero if you trust nature. However, you could make the argument that it's a bit rich for an animal already grown. But still, it should still be relatively nontoxic since it's one of the few foods purposely created as such.

Fruits are made by plants, and can be thought of as seeds baited with a sugary coating loaded with vitamin C and B vitamins. Plants don't eat their own fruit; the only logical reason they'd take the effort to produce it would be to attract fruit‐eaters for seed dispersal (and keep them healthy with B vitamins, so they come back.) By this logic, it would defeat the purpose for the plant to intentionally make its fruit toxic. The existence of toxic berries is somewhat confusing, but perhaps these are only toxic when unripe (or only to certain species.) I think fruit is the #2 food because it seems purposeful like milk.

Leaves were designed for photosynthesis, and not to feed pandas and giraffes. Despite what little cousins may say, plants neither 'hate being eaten' or 'like being eaten.' Evidence suggests that plants are impartial to being eaten—having no nervous systems.

What can be said about plants can be said doubly about seeds. Eating a seed is eating the potential for an entire tree, and intentional toxins are often found more concentrated in seeds than in leaves.

Animals don't seem to enjoy being eaten, and even take active steps to avoid this: running, clawing, and climbing are evasive techniques sometimes observed. (Koala bears hate being eaten.) Despite what a few ecclesiastics have said in the past, there is no evidence that 'God' had created animals to be food for humans.

The über‐taxonomist Carl Linnæus had viewed humans as frugivores. ​

But milk is a complex biological product which can release the most potent exorphin, a five‐to‐nine amino acid long peptide called β-casomorphin. This peptide works on the μ-opioid receptor, is blocked by naloxone, and actually conforms to the 'morphine rule:' a series of properties an opiate must oblige to; discovered by eliminating all unnecessary components from morphine—and associated compounds—revealing a non‐reducible opiate blueprint:

1) A tertiary nitrogen with a small alkyl substituent
2) A quarternary carbon
3) A phenyl ring or its equivalent attatched to the quarternary carbon
4) A 2 carbon spacer between the quarternary carbon and the tertiary nitrogen​

As you can see, β-casomorphin‐7 fulfills these requirements:

View attachment 7897 click to embiggen: β-casomorphin within bovine casein sequence.​

The working end is the one having tyrosine . . . followed by a proline. Besides amplifying the opiate properties, and helping to fulfill the 'morphine rule,' the three prolines within this seven‐amino‐acid segment confer the property of enzymatic resistance (to pepsin and trypsin). The reason why proline resists digestion so well is that proline has a unique peptide bond; the ring structure of proline is the peptide bond. Proline‐rich regions are more resistant to pepsin hydrolysis and are much more likely to be absorbed in longer fragments. These peptides have been found in the cerebospinal fluid of people so you can be sure they can enter the brain.

So why does morphine work at all? Is this an accident? or is morphine and codeine interfering with an extant opiate system? Evidence suggests the latter; we do have endogenous peptide optiates called the enkephalins:

The peptide to the left is named leucine-enkephalin. ​

As you can see, this one also has an N‐terminal tyrosine with a phenylalanine separated by two amino acids. This endogenous opiate has no prolines, and thus would then have a shorter half-life in the blood. The β-casomorphins can be thought of as interfering with our endogenous opiate signalling while also being relatively resistant to degradation (compared to the enkephalins.)

These opiates could perhaps create emotional bonding between lactating animals and their greedy, spaced‐out, and addicted children; they could also make milk seem 'cool,' and nipples even cooler than they already are; giraffes, piglets, cows, sheep, acalpacas, cats, and cows not excluded. Not all caseins have been sequenced, and there is no way to tell what opiates are lurking inside the amino acid sequence of . . . panda milk, for instance.

These opiates have been experimentally shown to decrease intestinal transit time—and blocked by naloxone. ​

Is there a way to ingest dairy while circumventing these opiate-like effects? Can we improve on nature? Can we turn the perfect food for a calf into the perfect food for a human? Perhaps there is a way; one can buy enzyme tablets online which contain enzymes experimentally proven to cleave proline peptide bonds. Since these have been shown to nullify wheat gluten, a protein having far more prolines, you would expect them to eliminate the opiate effects in dairy—should this be desired—since the proline-rich region is small (see above sequence).

But other than the potentially problematic exorphins, cheese seems to be a good food. The amino acid ratio of cheese is decent and its fatty acid profile is on the same tier as chocolate, beef, and coconuts. If a person's immune cells do not react with the proline-rich fragments, then the prostaglandin potential of dairy should be quite low. But like chocolate, people sometimes do react to the proline-rich peptides found in dairy.

How much milk would you need to extract enough β-casomorphin to work as an opiate for street purposes...and how hard would it be to chemically extract? Asking for a friend...

 

[Travis]

He starts out with a bold statement, in dashing style:

'Dear Editor,

In support of your efforts with Lauture and Broderick to address researchers’ all-too-frequent conflation of caffeine with coffee, I wish to highlight research concerning the opioid receptor antagonist compounds that are found in coffee [...] In the past decade, researchers at the Vanderbilt Institute for Coffee Studies (VICS) have identified these compounds—including 4-Caffeoyl-1,5-quinide—which are created in the roasting process and ‘‘show in-vivo inhibition of morphine-induced anti-nociceptive behavior in mice with the same order of magnitude as that reported for naloxone.’’ This research seems to be little known, and I was unable to find any reference to it in the pre-eminent journal and reference book for pain researchers and clinicians.' ―Robin Whittle: Independent researcher, Australia
​

He cites eleven references in the footnotes, three of which are given below (including one with a hilarious title:)

1. Lauture J. Coffee is to a square as caffeine is to a rectangle. J Caffeine Res 2014
2. Boublik JH. Coffee contains potent opiate receptor binding activity. Nature 1983
3. de Paulis T. 4-Caffeoyl-1,5-quinide in roasted coffee inhibits [³H]naloxone binding and reverses anti-nociceptive effects of morphine in mice. Psychopharmacology 2004​

But the analogy from Ref. 1 breaks down since coffee isn't really 'square;' coffee is revolutionary.

'One of the ironies about coffee is it makes people think. It sort of creates egalitarian places — coffeehouses where people can come together — and so the French Revolution and the American Revolution were planned in coffeehouses," Pendergrast says.'―NPR​

I think these naloxone‐like properties of caffeoylquinide could have been stimulating revolutionary activity directly at the δ-opioid receptor by inhibiting gluten exorphin B5, an opiate which had been imposed upon the working classes ever since it's cultivation in the fertile crescent thousands of years ago. But to know for certain, we have to see what it can to rats:

The anti‐morphine effect of coffee had first reported in nature in 1983, but it took until 2004 for the precise characterization of the molecular species. In 1983 it had been shown to displace morphine and naxolone from the opiate receptors, and also reduce nerve transmission in guinea pig illeum muscle: the two classic assays for opiate effect.

'a cup of coffee contains the equivalent of one‐third of an ampoule of naxolone.' ―Boublik​

Since it didn't migrate with morphine or naxolone during thin layer chromatography, it was determined not to be of similar structure. Also, any resemblance too the aforementioned opiate‐peptides was discounted based on its resistance to papain degradation—an enzyme exuded from the green papaya fruit which had even been shown to nullify the immunogenic effects of gluten. Papain can do what trypsin and pepsin cannot do, and that is break proline peptide bonds.

In the search for the mythical morphine inhibitor in coffee first reported by Boublik twenty years before, Brazillian–American phytopsychopharmacologist Tomas de Paulis had decided to investigate the ability of the quinolactones to do just this after noting μ-receptor affinity in his previous study on adenosine receptors. He had bought synthetic standards and had determined the amounts found in roasted coffee. He was not disappointed, as two coffee compounds showed high-affinity binding:

​

Though the dicoumaroyl lactone was a stronger inhibitor at 3.9·μM, its low abundance seriously precludes any further consideration. The molecule caffeoylquinide is the only one to consider—which according to Boublik's Table 2, has an affinity similar to naxolone.

Image showing lactone formation during roasting.
​

Although de Paulis appears to be a good phytopsychopharmacologist, nothing good can be said about morals. He actually appears, on all accounts, to be a cold-hearted bastard. Instead of choosing the classic and cute-sounding 'tail pinch test' to assay the anti-nociceptice activity of caffeoylquinide, de Paulis chose the much more cruel 'hot plate method:'

'Hot plate nociception

Eight-month-old male and female mice (C57BL/6J, Bar Harbor, Maine, USA) were placed on a hot plate maintained at 52°C (Model 35D; IITC Corp., Woodland Hills, Calif., USA). Animals were confined to the hot surface area...' ―de Paulis​

For Americans, this temperature translates to 125.6°F. At this temperature, rats predictably avoid the hot plate. The administration of morphine delays the time (latency) it takes for the rats either jump, yelp, or ask de Paulis to be removed. However, the administration of caffeoylquinide reversed the effects of morhine:

'However, when coffee extract was given after morphine, complete reversal of the antinociceptive effect of morphine was seen from 18.50 s with morphine alone to 5.36 s with morphine plus coffee extract.' ―de Paulis​

​

'By using these nociceptive responses to the hot plate at 52°C and a low dose of morphine, we found that instant coffee extract reversed the anti-nociceptive effect of morphine. It could be argued that by including paw lifting, paw shaking or animal retreating in the measured behaviors,' ―de Paulis​

This Jeffery Dahmer‐like rat torture is even more troubling since de Paulis had been fully aware of the 'tail flick method.'

'The dose of morphine used by Strubelt was relatively high (10 mg/kg IP) and the analgesic activity was measured by the tail flick method after administration of instant coffee (Strubelt et al. 1986).' ―de Paulis​

Despite the shameful rat torture—something Mr. Black probably wouldn't even do—this study did provide proof of the anti‐opiate effects of coffee; moreover, they had identified the molecules most responsible for this effect. Since opiates delay intestinal transit time, you would expect the converse from naxolone and coffee. This effect is indeed noted, by many, and caffeoylquinide has been shown to cross the blood–brain barrier.

'In particular, 4-CQL showed remarkably high anti-morphine activity with significant inhibition at 0.10 mg/kg IP. [...] In particular, the caffeic acid derivative 4-CQL, which is found in all roasted coffees, showed in vivo inhibition of morphine-induced anti-nociceptive behavior in mice with the same order of magnitude as that reported for naloxone. This suggests that the previously reported anti-opioid activity of instant coffee is caused primarily by the presence of 4-CQL and that the combined affinities of 4-CQL and other cinnamoyl-1,5-quinides in roasted coffee have the potential to occupy mu opioid receptors.' ―de Paulis​

In a way similar to how nicotine antagonizes the lobotomizing effects of histamine in the brain, coffee antagonizes the mind‐numbing effects of food opiates released from the ∂‐enzymatic hydrolysis of proteins found in grains and dairy. This could could be the real reason for the well‐known effects of coffee, not simply the caffeine as is commonly thought.

 

[Travis]

How much milk would you need to extract enough β-casomorphin to work as an opiate for street purposes...and how hard would it be to chemically extract? Asking for a friend...

You need enzymes to break the casein into the small peptides you need. Then, you need to design a sort‐of immunoaffinity chromatography column or dialysis with recombinant human μ-receptors, or anything which will allow you to separate the β-casomorphins around seven peptides long—the ones starting with the N‐terminal ⁷⁵Tyrosine. These are the ones we need. We can sell these completely legally (out of trenchcoats, shhh...) even in front of policeman. The powerful dairy industry will have our backs, as they have a strong interest in maintaining the public perception of safety.

 

[Tarmander]

You need enzymes to break the casein into the small peptides you need. Then, you need to design a sort‐of immunoaffinity chromatography column or dialysis with recombinant human μ-receptors, or anything which will allow you to separate the β-casomorphins around seven peptides long—the ones starting with the N‐terminal ⁷⁵Tyrosine. These are the ones we need. We can sell these completely legally (out of trenchcoats, shhh...) even in front of policeman. The powerful dairy industry will have our backs, as they have a strong interest in maintaining the public perception of safety.

Niiccee. How much milk will be used in this process?