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Ketamine + Grapefruit Juice?

B

blase deviant

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May 9, 2004
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Anyone ever tried this?

I found my K to be packing a much harder punch, and remembered that I'd taken grapefruit juice yesterday.

Could the two be related?
 
^ No, I said it might inhibit the metabolism of ketamine to nor-ketamine (nor ketamine being an essentially inactive compound). That's only if the enzyme responsible for ketamine's metabolism is cyp 3A4 (if it's a different enzyme, it wouldn't have any effect).
 
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=11353758&dopt=Abstract

Ketamine is metabolized by cytochrome P450 (CYP) leading to production of pharmacologically active products and contributing to drug excretion. We identified the CYP enzymes involved in the N-demethylation of ketamine enantiomers using pooled human liver microsomes and microsomes from human B-lymphoblastoid cells that expressed CYP enzymes. The kinetic data in human liver microsomes for the (R)- and (S)-ketamine N-demethylase activities could be analyzed as two-enzyme systems. The K(m) values were 31 and 496 microM for (R)-ketamine, and 24 and 444 microM for (S)-ketamine. Among the 12 cDNA-expressed CYP enzymes examined, CYP2B6, CYP2C9, and CYP3A4 showed high activities for the N-demethylation of both enantiomers at the substrate concentration of 1 mM. CYP2B6 had the lowest K(m) value for the N-demethylation of (R)- and (S)-ketamine (74 and 44 microM, respectively). Also, the intrinsic clearance (CL(int): V(max)/K(m)) of CYP2B6 for the N-demethylation of both enantiomers were 7 to 13 times higher than those of CYP2C9 and CYP3A4. Orphenadrine (CYP2B6 inhibitor, 500 microM) and sulfaphenazole (CYP2C9 inhibitor, 100 microM) inhibited the N-demethylase activities for both enantiomers (5 microM) in human liver microsomes by 60 to 70%, whereas cyclosporin A (CYP3A4 inhibitor, 100 microM) failed to inhibit these activities. In addition, the anti-CYP2B6 antibody inhibited these activities in human liver microsomes by 80%, whereas anti-CYP2C antibody and anti-CYP3A4 antibody failed to inhibit these activities. These results suggest that the high affinity/low capacity enzyme in human liver microsomes is mediated by CYP2B6, and the low affinity/high capacity enzyme is mediated by CYP2C9 and CYP3A4. CYP2B6 mainly mediates the N-demethylation of (R)- and (S)-ketamine in human liver microsomes at therapeutic concentrations (5 microM).
 
Whether 3A4 inhibition is important or not, I'm pretty sure you won't be getting any noteworthy inhibition two days after drinking some juice.
 
S-ketamine concentrations are greatly increased by grapefruit juice.

Eur J Clin Pharmacol. 2012 Jun;686:979-86.

PURPOSE:
We examined the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral S-ketamine.
METHODS:
A randomized crossover open-label study design with two phases at an interval of 4 weeks was conducted in 12 healthy volunteers. Grapefruit juice or water was ingested 200 ml t.i.d. for 5 days. An oral dose of 0.2 mg/kg of S-ketamine was ingested on day 5 with 150 ml grapefruit juice or water. Plasma concentrations of ketamine and norketamine were determined for 24 h, and pharmacodynamic variables were recorded for 12 h. Noncompartmental methods were used to calculate pharmacokinetic parameters.

RESULTS:
Grapefruit juice increased the geometric mean value of the area under the plasma ketamine concentration-time curve(AUC0-∞) by 3.0-fold (range 2.4- to 3.6-fold; P<0.001), the peak plasma concentration (Cmax) by 2.1-fold (range 1.8- to 2.6-fold; P<0.001), and the elimination half-life by 24% (P<0.05) as compared to the water phase. The ratio of main metabolite norketamine to ketamine (AUCm/AUCp) was decreased by 57% (P<0.001) during the grapefruit phase.Self-rated relaxation was decreased (P<0.05) and the performance in the digit symbol substitution test was increased (P<0.05) after grapefruit juice, but other behavioral or analgesic effects were not affected.

CONCLUSIONS:
Grapefruit juice significantly increased the plasma concentrations of oral ketamine in healthy volunteers.Dose reductions of ketamine should be considered when using oral ketamine concomitantly with grapefruit juice.
PMID: 22286159 [PubMed - indexed for MEDLINE]
Click to expand...

http://www.ncbi.nlm.nih.gov/pubmed/22286159

Gonna buy some grapefruit, today... ;)
 
most people dont take ketamine orally as its metabolised to nor ketamine and what this study shows is that when taking it orally less is metabolised and you get a better oral ketamine effect when taking grapefruit juice at the same time.

how this relates to IM use or snorting i dont know
 
There definatly is some increase in effects when taking grapefruit juice with ketamine but that definatly wouldn't go for grapefruit juice one or two days ago; effect is really only there the same day.. doesn't make a húge difference, but definatly some..
 
If you believe it works better with grapefruit juice then for a percentage of people it will - just by the placebo effect.
 
Just wanted to add that: just because GFJ is a known inhibitor of certain enzymes doesn't mean it won't affect the others. I've experienced a noted effect on MDMA and mushroom trips with GFJ, and those are processed by CYP2D6, yet GFJ is not a listed inhibitor of that enzyme.

Just like there are polymorphisms in people's CYP450 genetics, I think there may also be a polymorphism in how the inhibitors are applied across the enzyme categories.

In short, you have to try it to know. GFJ can inhibit an enzyme anywhere from 6-24 hours depending on the person. For other people it does nothing.
 
Most important part is this :
"The ratio of main metabolite norketamine to ketamine (AUCm/AUCp) was decreased by 57% (P<0.001) during the grapefruit phase."
Grapefruit juce may decrease by 50% the domage made to your blader.
 
Dr Mamba said:
Most important part is this :
"The ratio of main metabolite norketamine to ketamine (AUCm/AUCp) was decreased by 57% (P<0.001) during the grapefruit phase."
Grapefruit juce may decrease by 50% the domage made to your blader.
Click to expand...

If this is the case surely through insufflation more ketamine will remain unconverted to norketamine in the body resulting in a greater concentrations in the bloodstream (considering most people swallow the drip, which by first pass metabolism gets converted to norketamine?). Whether this results in a stronger high is debatable, but i'm going to go buy some high potency grapefruit juice to test it out. Anyone know what chemicals it is in grapefruit juice which prevents the metabolism of ketamine specifically and whether its available in powder/pill form? (potential business idea)
 
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