Cytochrome P-450 isozymes in metabolic activation of delta 9- tetrahydrocannabinol

[apothecary]

Doing some research into P-450, thought some people might appreciate this

I think 11-OH-d9-THC is supposed to be the primary metabolite produced when ingesting cannabis orally (possibly smoking too but I'm not sure on that one), and supposedly an extremely potent cannabinol in that form.

The paper indicates inhibiting P-450 could halt the conversion from d9-THC ->11-OH-d9-THC...so maybe increasing P-450 levels could enhance this metabolisation (get you more stoned when ingesting orally)?

I think vitamin A increases P-450 availability...

Carrots, milk, eggs, spinach...all good vitamin A sources...

http://intl-dmd.aspetjournals.org/cgi/cont...stract/18/6/943

Cytochrome P-450 isozymes in metabolic activation of delta 9- tetrahydrocannabinol by rat liver microsomes

S Narimatsu, K Watanabe, T Matsunaga, I Yamamoto, S Imaoka, Y Funae and H Yoshimura

Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.

delta 9-Tetrahydrocannabinol (THC) was incubated with a reconstituted system consisting of dilauroylphosphatidylcholine, NADPH-cytochrome c reductase, cytochrome b5, and cytochrome P-450 (P-450) isozyme UT-2, UT- 4, or UT-5, which was purified from liver microsomes of adult male rats. It was biotransformed by UT-2 to 11-OH-delta 9-THC and 3'-OH- delta 9-THC, and by UT-4 to 8 beta-OH-delta 9-THC and 11-OH-delta 9- THC. UT-5, however, showed only a little activity for 11-OH-delta 9-THC formation. Activity of the isozyme UT-2 for 11-OH-delta 9-THC formation from delta 9-THC was calculated to be 4.07 nmol/min/nmol P-450 while those of UT-2 for the formations of 16 alpha-OH-testosterone (16 alpha- OH-T), 2 alpha-OH-T, and androstenedione from testosterone were 14.7, 6.6, and 2.2 nmol/min/nmol P-450, respectively. Anti-P-450 UT-2 IgG fraction obtained from rabbit serum dose-dependently suppressed formations of 16 alpha-OH-T, 2 alpha-OH-T, and androstenedione from testosterone with liver microsomes of adult male rats. The antibody, in the amount that inhibited above 90% of 16 alpha-OH-T and 2 alpha-OH-T formations from testosterone, also reduced 80% of the microsomal formations of 11-OH-delta 9-THC and 3'-OH-delta 9-THC from delta 9-THC, as compared with control experiments using preimmune IgG fraction.

(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 18, Issue 6, pp. 943-948, 11/01/1990

Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics

[Evil Genius]

Thanks for posting apothecary! A very interesting text.

[alkatrope]

Thanks, quite intersting

[oxydiser]

Nice one apoth, you are always pushing the boundaries of drug inhibition/synergy

I am unfamiliar with the CYP450s UT-2, UT- 4, or UT-5, however I was under the impression that the main metabolising CYP450 enzymes were 1A2, 2B6, 2C8, 2C19, 2C9, 2D6, 2E1 and 3A4/5

A few papers I have read suggest that that cannabinoids are metabolised by 3A4 and also inhibit this enzyme. Grapefruit juice is a 3A4 inhibitor also, so what we need is for someone to chug ~1L of grapefruit juice and smoke up to see if there if there is any significance in this... bags not it

Also found this paper, keep in mind fellas the next time you mix prescription and recreational :saufen2: dRugS!?!?

Truth be told, CYP450s have only really started to be looked at and there is a lot of work to be done yet

Myocardial Infarction Following the Combined Recreational Use of Viagra® and Cannabis

A. L. MCLEOD, M.D., MRCP, C. J. MCKENNA, M.D., MRCP, D. B. NORTHRIDGE, M.D., MRCP

Department of Cardiology, Western General Hospital, Edinburgh, U.K.

Summary

Sildenafil citrate (Viagra®,Pfizer, Inc., New York, N.Y.) is widely prescribed as a treatment for male erectile dysfunction. It is metabolized predominantly by the cytochrome P450 3A4 hepatic microsomal isoenzyme and effects can, therefore, be potentiated by such inhibitors. The vasodilatory effects of Viagra necessitate caution in its use in patients with cardiovascular disease and it is contraindicated in patients receiving nitrates. Previous literature has drawn attention to Viagra use and myocardial infarction. This paper reports the case of a young man who presented with a myocardial infarction after taking Viagra in combination with cannabis, a known inhibitor of the cytochrome P450 3A4 isoenzyme.

Edited May 9, 2006 by oxydiser