Disulfiram for anxiety, new research

[Skorpio]

Fair point! Interestingly it seems that THP could contribute to the endogenous synthesis of morphine in humans.

Does endogenous morphine occur at levels that have pharmacological relevance? Also pharmacological relevance could mean something like being a toll like receptor agonist.

This might be a factor in Disulfiram's effects and implies that other ALDH inhibitors would do the same thing - eg diallyl trisulfide from garlic, diethyl disulfide from durian (ref1, ref2).

I have some doubts in the efficacy of these molecules (when consumed in a dietary context), as I have never heard of consumption of large quantities of garlic (or durian) causing a disulfiram like reaction (as coprine does). Have these effects been shown in vivo? It is possible that they may work to inhibit ALDH in vitro, but their reactive disulfide bonds are expended in nonspecific reactions before they reach ALDH (or that these compounds never reach their Ki when consumed as food).

 

[bigjackaal96]

Love how science Is proving how a humanoid rat would be far more manic at a pub than a humanoid canine or human male would. This can used for people with Rat fursonna's.

 

[Allylbenzene]

Does endogenous morphine occur at levels that have pharmacological relevance?

Perhaps, I suppose this depends on where it's synthesised. It's possible that usual testing methods might not give a realistic representation of it's true levels.

I have some doubts in the efficacy of these molecules (when consumed in a dietary context), as I have never heard of consumption of large quantities of garlic (or durian) causing a disulfiram like reaction (as coprine does). Have these effects been shown in vivo? It is possible that they may work to inhibit ALDH in vitro, but their reactive disulfide bonds are expended in nonspecific reactions before they reach ALDH (or that these compounds never reach their Ki when consumed as food).

I don't think that anyone will have set out to consume high doses of a garlic supplement combined with alcohol to find out.
As for durian, the "active" dose doesn't seem that much. There are several scattered reports of health issues/fatalities linked to a the combination of alcohol & durian.
As for the literature:

The unpleasant, or at times lethal, effect of drinking alcohol with durian is reminiscent of the clinical manifestations seen in patients that binge on alcohol while under antidipsotropic medication with disulfiram (tetraethylthioram disulphide), a sulphur-containing drug.
- https://doi.org/10.1016/j.foodchem.2011.09.039

 

[Skorpio]

Perhaps, I suppose this depends on where it's synthesised. It's possible that usual testing methods might not give a realistic representation of its true levels.

Could be. Not a lot of functional evidence for that (like a lack of compensatory activity in dual POMC and proenkephalin knockout mice).

I don't think that anyone will have set out to consume high doses of a garlic supplement combined with alcohol to find out.
As for durian, the "active" dose doesn't seem that much. There are several scattered reports of health issues/fatalities linked to a the combination of alcohol & durian.
As for the literature:

that’s pretty interesting. I wish they had a negative and positive control with the cabbage and durian feeding experiment (like sucrose and disulfram respectively) to tell baseline and maximal acetaldehyde levels.

For some anecdotal evidence, I ate over 20 cloves of garlic in a dish for dinner tonight and had two cocktails over the course of the meal. I do not feel hungover (though I did cook the garlic which could very well have driven off the allyl disulfide).

 

[4DQSAR]

For some anecdotal evidence, I ate over 20 cloves of garlic in a dish for dinner tonight and had two cocktails over the course of the meal. I do not feel hungover (though I did cook the garlic which could very well have driven off the allyl disulfide).

Oh dear - is there an 'inervention' at hand where family and friends make you accept that your garlic addiction is destroying THEIR lives?

 

[Allylbenzene]

For some anecdotal evidence, I ate over 20 cloves of garlic in a dish for dinner tonight and had two cocktails over the course of the meal. I do not feel hungover (though I did cook the garlic which could very well have driven off the allyl disulfide).

Both aliinase and allicin are unstable at high temperatures so it's unlikely your garlic contained any allicin.

When fresh garlic is chopped or crushed, the enzyme alliinase converts alliin into allicin, which is responsible for the aroma of fresh garlic.
Diallyl trisulfide is one of several compounds produced by hydrolysis of allicin.

A large dose of standardised allicin extract might be more convenient than raw garlic, but as this is a harm reduction forum I can't recommend that anyone try combining alcohol with large doses of standardised allicin extract.

 

[Skorpio]

Both aliinase and allicin are unstable at high temperatures so it's unlikely your garlic contained any allicin.


A large dose of standardised allicin extract might be more convenient than raw garlic, but as this is a harm reduction forum I can't recommend that anyone try combining alcohol with large doses of standardised allicin extract.

Oh I wasn’t trying to test anything beyond a modified recipe for sinangag (Filipino garlic fried rice). I broiled it, rather than cooking it in a wok due to lack of stove btu’s to really properly cook it without crowding the pan.

I’m not really interested in replicating the disulfiram effect myself.