Opioids Is it an oddity that Milk Thistle RADICALLY potentiates Oxycodone?

[Poodles!]

A little more on topic... useful info on Silymarin and enzyme inhibition in general

This is a good thread. I've posted some useful stuff in this thread about enzyme inhibition and opioids (near the bottom).
• Opiate/Opioid Potentiators [INDERALL?]

Also recommended:
•Project - Codeine-6-Glucuronide (C6G)
• Messing with drug metabolism beyond the CYPs
• Sweet UGT enzyme chart (inhibitors/inducers)
• Awesome CYP-450 Chart!
• potentiation of drugs from milk thistle?
• Potentiate benzos with milk thistle?
• Milk Thistle Liver Detox = Lowered Opiate Tolerance?

Various useful stuff I've picked out:

Indeed, in recent experiments using milk thistle and human liver cells, the researchers found that
relatively small concentrations of milk thistle did significantly slow down the activity of the liver enzyme
CYP3A4 by 50% to 100%.

source: http://www.hcvadvocate.org/news/News...s/mthistle.pdf

The flavonolignans silybin A and silybin B from milk thistle (Silybum marianum) inhibit CYP2C9-mediated warfarin metabolism at clinically achievable concentrations

source: http://jpet.aspetjournals.org/content/332/3/1081.full

Interactions between Natural Health Products and Antiretroviral Drugs: Pharmacokinetic and Pharmacodynamic Effects

There is a lot of good stuff in this review (pub.2006), the whole text is available so I recommend having a skim through at least, and also checking out relevant references... but here's some particularly thread-relevant bits:
…"Silybins, the active components of milk thistle, were found to inhibit CYP3A4 in vitro [25] and, thus, could increase ARV drug concentrations."…
…"Silymarin, a component of milk thistle, inhibits P-gp activity and enhances doxorubicin toxicity in vitro [36]. Other NHPs that inhibit P-gp in vitro include garlic, green tea, turmeric, ginseng, rosemary, flavonoids from many plants [37], African potato, and S. frutescens [28]. However, data are lacking on the clinical significance of these effects on P-gp."…
…"Two uncontrolled clinical studies [41, 42] revealed trends toward reduction in concentrations of indinavir after coadministration of milk thistle. A 3-period, randomized, controlled trial revealed a similar trend; however, there was an even greater reduction in area under the curve (AUC; 21.5%), trough concentrations (Cmin; 53.1%), and peak concentrations (Cmax; 9.4%) in subjects in the control group, which persisted after a washout period [43]. Compared with the control group, the milk thistle group demonstrated a significant but small increase in Cmin and trends toward increases in AUC and Cmax (table 1). Other clinical studies involving milk thistle and CYP3A4 [44] or P-gp [45] probe drugs revealed no pharmacokinetic interactions, indicating that clinically important interactions between milk thistle and PIs or NNRTIs are unlikely."…
http://cid.oxfordjournals.org/content/43/8/1052.full

Clinical Evidence of Herbal Drugs As Perpetrators of Pharmacokinetic Drug Interactions.

..."The clinical evidence was found to be most robust and informative for Gingko biloba (GB; 21 studies) and milk thistle/silymarin (MT; 13), and appears still limited for ginseng (9), goldenseal/berberine (GS; 8), garlic (8), and Echinacea (7). Collectively, the available evidence indicates that, at commonly recommended doses, none of these herbs act as potent or moderate inhibitors or inducers of cytochrome P450 (CYP) enzymes or P-glycoprotein (ABCB1). Weak effects in terms of either induction or inhibition were found for GB (presystemic/hepatic CYP3A4 induction/inhibition, CYP2C19 induction at high doses), milk thistle/silymarin ([weak]CYP2C9 inhibition), GS/berberine (CYP3A4 and CYP2D6 inhibition), Echinacea (presystemic/hepatic CYP3A4 inhibition/induction, CYP1A2 and CYP2C9 inhibition at high doses). Information was found not always complete for the major drug metabolizing CYP enzymes in the less well-studied herbs and is largely limited to P-glycoprotein (ABCB1) when effects on drug transporters have been investigated."
http://www.ncbi.nlm.nih.gov/pubmed/22855269

A review of the bioavailability and clinical efficacy of milk thistle phytosome: a silybin-phosphatidylcholine complex (Siliphos).

..."The standardized extract known as silymarin contains three flavonoids of the flavonol subclass. Silybin predominates, followed by silydianin and silychristin. Although silybin is the most potent of the flavonoids in milk thistle, similar to other flavonoids it is not well-absorbed. Silybinphosphatidylcholine complexed as a phytosome provides significant liver protection and enhanced bioavailability over conventional silymarin."...
http://www.altmedrev.com/publications/10/3/193.pdf [Full text .PDF]

Bioavailability and Activity of Phytosome Complexes from Botanical Polyphenols: The Silymarin, Curcumin, Green Tea, and Grape Seed Extracts

..."Silybin is a proven liver protectant; in animal experiments it blocked the oxidative toxicities of acetaminophen, alcohol, carbon tetrachloride, and the mushroom toxins phalloidin and alpha-amanitin"...
..."Although in animal experiments and some human studies, milk thistle constituents have conserved liver glutathione, inhibited liver fibrogenesis, and supported liver regeneration,4,8 clinical trials have been inconsistent. In trials of viral hepatitis,18 alcoholic liver damage,19 or other liver diseases, silymarin and silybin improved enzyme damage indicators and (at times) improved antioxidant status,4,18,19 but did not consistently improve symptoms."...
…"The utilization of non-phytosome silybin intravenously in mushroom-toxic patients (at 20-50 mg/kg/day) or of high-dose silymarin at 600 mg/day in diabetic patients has resulted in meaningful symptom improvement,19 presumably because the preparations were given either intravenously or at a high oral dose. Overall, the efficacy patterns are consistent with poor intestinal absorption of these important flavonolignans, making the phytosome form a more appropriate oral delivery vehicle for this class of polyphenols."...

NSFW:

NSFW as it's a pretty large image/graph
http://www.altmedrev.com/publications/14/3/226.pdf [Full text .PDF]

Occurrence of aflatoxins in milk thistle herbal supplements.

..."A total of 83 MT samples from the US market were analysed. AFs were detected in 19% of the samples with levels ranging from 0.04 to 2.0 µg kg(-1). Additionally, an aflatoxigenic A. flavus strain from ATTC and an A. parasiticus strain isolated from MT herb powder were found to produce high amounts of aflatoxins (11,200 and 49,100 µg kg(-1), respectively) when cultured in MT seed powder. This is the first study reporting on aflatoxin contamination of MT botanical supplements and identifying methodology for AF analysis of these commodities."
http://www.ncbi.nlm.nih.gov/pubmed/22439650

Another good review article on Silymarin, although much of it isn't particularly relevant to the thread... It's just interesting :

SILYBIN AND SILYMARIN – NEW EFFECTS AND APPLICATIONS
http://mefanet.upol.cz/BP/2005/1/29.pdf [Full Text .PDF]

 

[mrflowers00]

i tried milk thistle 500mg than 1000 and it did nothing for me

 

[endlessnameless]

i tried milk thistle 500mg than 1000 and it did nothing for me

It'll tend not to, unless you take it with a narcotic; milk thistle isn't a psychoactive substance.

 

[mrflowers00]

nah i meant with oxycodone and as well with xanax and nothing

 

[Aporia]

Hey all. I don't mean to hijack a thread but I didn't want to start a whole new one when the topic has been covered already, in away. So here's my question. I'm on 4-6 lortabs a day for chronic pain. I told my doc that I was concerned about my liver and constantly tells me I have nothing to worry about. I asked him about milk thistle today at my appointment and he told me he wouldn't say he was for nor against it. I've been taking them for about three months. The information I have gotten on BL is contradictory saying that if taken with apap it could increase the toxicity..but then I come across the post above and it seems that I ought to be taking it daily along with my meds. Could anyone give advice on whether it is helpful to take while taking medication with apap and maybe what doses I ought to be looking into taking? Thank you so much everyone!

 

[Fire&Water]

Normally oxy will always grind up his 80's with a hose clamp and snort them because he finds the effects much stronger than any other method. However, after repeated use, tolerance has lead to in many cases absolutely no high from doing as much as 50 - 60mg. He's looked at potentiators, but there's always a counter argument for every argument for things such as grapefruit juice and others like it. This milk thistle seems very promising so oxy thinks he'll try it tomorrow. Since it peaked his interest, he discovered this article http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2010.03653.x/abstract, which interestingly tested exactly what we're all interested in, whether or not inhibiting the enzymes CYP 2D6 (milk thistle) and 3A4 would increase the potency of oxycodone. Skipping to the conclusion, he found the results to state that inhibiting just CYP 2D6 made minor changes, but the metabolization of oxycodone mostly just shifted to the other enzyme CYP 3A4. But, if the test subjects inhibited both CYP 2D6 and 3A4 there were significant increases in potency. Significant increases sounds good to oxy So he promptly went and found a product called biaxin purchasable without a prescription with the active ingredient clarithromycin, which is known to be a strong inhibitor of CYP 3A4.

So, today oxy will hunt down some milk thistle and biaxin and see what improvements this will have. Although he doesnt have much to go on because he has only once or twice ground up some ox to place under his tongue and has never ingested it, besides drips. He doesn't have a very good reference then, but the plan is to pop some milk thistle (750mg) with biaxin (750mg) and half an hour later, buck a 60 of ox and then drop another 40 or so.

Its hard for oxy to eat it because it feels like such a waste, but nowadays so is putting it up his nose so he'll give it a try for the sake of science. Oxy will return to the forum with results later.

Thank you Oxychem for sharing this fantastic information!

Does "oxy" always talk about himself as the 3rd person ?

 

[HYDRO_CHRONIC]

I take milk thistle all the time just the other day I ate 56mg of oxy and had 1000mg of mt before it and never notice any affect on the high