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Metabolism of Tetrahydrofuran

polymath

polymath

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I happen to have a shit-ton of THF in the lab I work in... I've seen some synth talk in other sites about the oxidation of THF to gamma-butyrolactone, but I'm not going to discuss it here.

It looks like the THF to GBL conversion doesn't necessarily have to be done synthetically, as the same reaction actually occurs in the liver after an exposure to THF. See http://www.epa.gov/iris/toxreviews/1023tr.pdf , Page 3-11, Figure 3-1. GHB is the main metabolite of THF. So in theory, one could take a few-grams dose of tetrahydrofuran and experience a GHB high...

Tetrahydrofuran has a low acute toxicity, oral LD50 is about 3000 mg/kg in rats. There's also a case report of a suicide attempt where someone drank a massive amounts of THF, was comatose for some time, and a huge concentration of the metabolite GHB was detected in her blood. (can someone else find that article, I lost it and can't find it anymore)

Does someone know more about this and the possible risks of ingesting THF? I'm not going to go and recklessly try a dose of an industrial solvent without considering the risks first.
 
THF is a pretty strong solvent, I wouldn't be surpised if it induced liver damage. I really don't think it's suitable for use as a GHB prodrug. Most human exposures (inhalation uually) don't result in typical GHB-like symptoms...

Conversion to GHB is going to be not nearly as efficient as e.g. butanediol or GBL, because THF is notably more volatile and is excreted in the breath.
 
There was some enlargement of the liver in animals who were exposed to high concentrations for a long time. Also some plumbers who used THF-containing glues in their work without protective equipment got toxic symptoms and had elevated liver enzymes (similar to what is observed in heavy alcoholics).

THF is a local irritant so at least it would have to be diluted with lots of water before ingestion... Also the half life of the THF->GHB conversion is probably some hours, so it would have a slow onset and long duration.

I think I'm not going to actually try ingesting the stuff...
 
I think I'm not going to actually try ingesting the stuff...
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I think that's advisable. Seems like too much hassle to have GHB build up relatively slowly.

Now, if there were some diethyl ether around, that's another situation.
 
The only advisory I can make is that you shouldn't have any open fires around, and you shouldn't hang out with anyone who doesn't mind you smelling like a solvent spill on an oil derrick for the next 24 hours, 'cause your breath is gonna reek. Other than that it's an interesting experience.
 
I store my THF, and EtOEt under argon. I sparge the liquid with a fish-tank air pump and bubbler-diffuser airstone, squeeze the bottles to expel as much air as possible, while filling the bottles with argon gas, in order to retard peroxidation, which can happen pretty quickly with THF in contact with air. THF peroxides, hydroperoxides, or the peroxides and/or hydroperoxides of diethyl ether are seriously fucking unstable explosives, and can go off with little more agitation than opening the cap of a bottle of peroxidized EtOEt or THF. I've heard reports of lab accidents where its happened, in one case, in a fridge, I forget weather it was ether or THF, off the top of my head, but it blew the fridge through the roof of the lab.

As far as ether intoxication goes...there I can give a bit of background at least. I've inhaled quite a bit of diethyl ether in my time, and found it quite a pleasant dissociative. And I have tried it orally, mixed with a mixture of vodka and codeine linctus. Very much a different beast to when its inhaled. Quite potent, only a spoonful or two were needed to produce strong dissociative effects.
 
Still about the original question... Here is an article about the neuropharmacological profile of THF in mice. Some quotes from the full-text version:

Increasing abuse of GHB and its analogs GBL and 1,4-BD, which led to stricter regulations and decreased availability for users, has created a potential market for additional analogs. While there are reports of the use of gamma-valerolactone and gamma-valeric acid, the five carbon homologs of GBL and GHB, respectively, some reports of THF use have also emerged from Internet websites and other sources, including law enforcement.
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Therefore, in the present study we first compared THF with the well known and preferred GHB precursor, GBL. We used equimolar amounts of THF (MW=72 Da) and GBL (MW=86) in all comparisons for the most appropriate quantitative analysis. In experiments involving measurements of animals' neuro-motor control and coordination, THF was shown to be approximately one-third and one-tenth as potent as GBL in the righting reflex and rotarod tests, respectively. Failure to exhibit a righting reflex is often used by investigators as an index of hypnosis, or sleep, especially when a central nervous system depressant is evaluated.
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Also, a GABA-B antagonist was able to block the effects of both GBL and THF. THF was found to have slower onset and longer duration than GBL, as expected.

Here's a case report about an intentional poisoning case with THF: http://www.ncbi.nlm.nih.gov/pubmed/11386640 (can someone access the full text?) I'm not sure about the dose of THF that person had ingested, but a huge GHB concentration of 2,977 mg/L was detected in the urine in toxicological analysis. Note that the urine levels observed after a typical recreational GHB dose are less than one tenth of that (see here).
 
I don't like the idea of THF being only 1/3 as potent as GBL/GHB. That makes it a poor prodrug in my book. I'm sure it has activity that's outside GHB/GABAb as a nonspecific solvent intoxicant. (But not a 'fun' one like diethyl ether, I'm thinking more like cyclopentane)

I feel in the interest of harm reduction I should point out that the process of converting THF to GBL involves much more toxic and involved chemistry than the ring opening of GBL to GHB. It is by no means kitehcn chemistry.
Of the numerous THF oxidation citations listed on [redacted]'s page, the majority of the papers deal with oxidation procedures surpassing the typical level of chemistry expertise of clandestine laboratory chemists. The reaction conditions are either too sophisticated or the oxidizing agent is too obscure for the average underground chemist to pursue the proposed reaction route despite superior yields.
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sekio said:
I feel in the interest of harm reduction I should point out that the process of converting THF to GBL involves much more toxic and involved chemistry than the ring opening of GBL to GHB. It is by no means kitehcn chemistry.
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I looked up some synthetic routes and I think I could probably oxidise THF to GBL if I just made up a bullshit reason for my boss to order the required chemicals... Then again, I'd be in a lot of trouble if I got caught.

Maybe there's some easier way to hydrolyse it to butanediol...
 
I don't think you can go that way, ether hydrolysis is pretty hard.

This is getting pretty close to synth discussion though.
 
Here's the full text in case no one else has sent it to you yet:

[deleted]

Let me know if that won't work.
 
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^ Got it, thanks! :)

Too bad there was no mention in the article about the amount of THF that person had ingested. It must have been at least tens of grams, considering the extremely high GHB concentration found in the body fluids. Apparently the patient recovered without getting liver damage or other long-term complications...
 
You should be able to find another route through something less toxic if you dig your heels in the library a little... But no synth discussion here.
 
Limpet_Chicken said:
And I have tried it orally, mixed with a mixture of vodka and codeine linctus. Very much a different beast to when its inhaled. Quite potent, only a spoonful or two were needed to produce strong dissociative effects.
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How was the vodka ether cocktail? I'm intrigued. What kind of amounts did you try?
 
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