Potentiation? Elongation? Modification? Through Enzyme Inhibition

[f33lg00d]

The enzymes CYP2C9, CYP2C19, and CYP3A4 play significant role in the metabolism of THC, CBD, and CBN (also metabolized by CYP1A2, and CYP2D6). Easily available inhibitors include Ginkgo Biloba (CYP2C9, CYP3A4), Antihistamines (CYP2C9, CYP3A5), Ketoconazole (CYP2C19, CYP3A4), Grapefruit juice (CYP3A4, CYP1A2), Milk Thistle (CYP3A4), and Cumin (CYP1A2). So I hypothesised that taking inhibitors would result in an elongated high and overall modified high significantly different from a normal high. As anyone attempted this?

 

[Achten]

Interesting. I will test during the coming week !

 

[Okami]

I regularly take antihistamines for hay fever and I haven't noticed any difference in high when on them but I haven't been paying specific attention, if there is a difference then not a significant one. The amount you'd need to take to inhibit them to the necessary amount would be impractical methinks. Although my opinion is based more on common sense than scientific deduction.

 

[Jibult]

As anyone attempted this?

Personally? No, I haven't tried it but I do know a pair of siblings that swear by drinking grapefruit juice with their sessions. They don't seem to get more stoned than non-grapefruit-drinking smokers, but they definitely claim that they do.

 

[Chainer]

lol grapefruit juice. this shit barely works with opiates or benzos. I don't buy it for a second.

 

[Snake_Eyes]

I used to take diphenhydramine (50mg) about an hour before smoking every night but it wasn't done to add to the high just to sleep. I guess it makes it more couchlockish but other than that I never noticed much of a change.

 

[how the gods chill]

Similar to Snake_Eyes, i used to take 50mgs to 75mgs of hydroxyzine at night along with a smoke session to get to sleep. The highs definitely felt more sluggish, but ive always assumed thats just the nature of the antihistamine in itself.

 

[sekio]

I don't think that most people would have access to enzyme inhibitors strong enough to block cannabis from beign metabolised effectively. Most of them are not "meant" for enzyme inhibition anyway... e.g. ketoconazole is a broad spectrum anti fungal drug.

Cyp2C9 is the one you want to inhibit I would reckon. Not 2d6 or 3a4.
http://www.ncbi.nlm.nih.gov/pubmed/17303175

11-OH-delta 9-THC is actually about 20% more potent than delta 9-THC and perhaps more intense as well. It is mostly produced during oral consumption. The 11-OH metabolite is one of the reasons why oral consumption of THC can be so much more sedating and/or anxious compared to smoking and inhibiting cyp2d6 may actually decrease the potency, especially after oral consumption. I don't know what is responsible for the 11-nor-9-carboxy metabolite however.

http://www.zoklet.net/bbs/archive/index.php/t-160380.html

 

[5HToInfinity]

Ginkgo Biloba does NOT affect 3A4, according to this paper.

http://www.ncbi.nlm.nih.gov/pubmed/14624188

However, from this case it seems that Ginkgo may actually INDUCE CYP3A4, INCREASING metabolism of 3A4 substrates. This means that Ginkgo would ACCELERATE THC metabolism, decreasing duration.

http://www.hivmedicationguide.com/details.asp?ID=8472&name=Efavirenz / Ginkgo Biloba

However, this paper indicates mild to moderate inhibition of 3A4

http://www.ncbi.nlm.nih.gov/pubmed/15992226

What the fuck? Can anybody explain these three contradictory results?

 

[PriestTheyCalledHim]

If you really want to get super high just vaporize your herb or make it into an edible and eat it. The high from vaping or eating it is different than smoking it IME. Also you will be getting 100% THC with both ROAs, and you'll stay high longer than if you just smoke herb.

 

[sekio]

5HTToInfinity, Read those papers more closely.

The first one is the relevant one. It says ginkgo had no effect on liver functioning in normal healthy volunteers, when administered as a supplement.

The second is not a medical paper. It's an anecdotal case report. Note how it's never explicity noted that ginkgo interferes with CYP3A4 - only that it is suspected in interfering with proper blood levels of efavirenz, and CYP3A4 is one of the ways it could interact.

The third is a paper from a result of a high-throughput enzyme screening assay, aka "in vitro" scanning, where ginkgo extract was applied directly to a culture of the enzyme in a petri dish. It isn't exactly represesntative of how a drug will behave because not all drugs are well absorbed or distributed.
'
These results mean, to me, that ginkgo probably is a mild inhibitor at CYP3A4 at best, because it is of low activity and is probably not extensively absorbed. It likely interferes with other enzymatic pathways as well.