Increasing Cannabis' Effects Through Enzyme Inhibition -Easy, get more from your meds

VladFromOG

Active Member
So much thought lately goes into concentrating marijuana and the various tools used with the various forms of marijuana, but very little is seemingly given to the active compounds methods of action. This is a shame, because there are lots of things you can do to enhance and increase cannabis' effects in the body that are completely independent of the cannabis itself.

The cannabinoids are oxidized in the liver by the enzyme CYP 2C9 after they have circulated through the bloodstream. Inhibiting CYP 2C9 increases the duration and subjective potency of cannabis. There are a number of foods and OTC medications that can inhibit CYP 2C9 strongly:

CYP-29 Inhibitors
The antifungals Flucanazole and Miconazole (found in OTC jock itch preparation and in oral fast melt tabs by script)
Amentoflavone (found in Ginko biloba and St Johns Wort)
Quecertin (Weak inhibitor, flavone, found in your grocers supplement aisle and in low concentrations in most foods)
Piperine (Long/Black/West African Pepper)

What this means is that, for example, if you take half a gram of gingko or st johns wort, and wash it down with a 00 capsule full of ground african pepper, and a single dose of miconazole if you've got it, all about 30-45 minutes before you dose, you will need about 1/3 to 1/2 as much marijuana as you regularly do. Its surprising how well this works. Its especially handy if you dose orally - instead of getting relief for only an hour or two, an oral dose can last all day! By inhibiting this enzyme, you do make your initial experience a bit stronger, but where its really useful is in increasing the duration the cannabinoids are in your system. Its even useful if you smoke/vape your dose - instead of a half hour high, your steadily stoned for three, very handy when going out to the movies etc where you cant sneak away or light up.

Now, there is some risk with medication interaction anytime you inhibited liver enzymes, but the great thing is that, although CYP 2C9 is on of the all important Cytochrome P450 set, the inhibitors I list will not inhibit Cytochrome P450s, just CYP 2C9, which limits a lot of potential harmful interactions.

You can use any combo of the inhibitors I listed, the example I gave is just the easiest to acquire and my favorite combo. The african pepper, besides inhibiting CYP 2C9, also contains large amounts of beta-caryophyllene, which is a potent peripheral CB2 agonist, that has massive anti-inflammatory effects on its own, and really synergizes well with the pain killing effects of marijuana. Just be sure to grind the peppercorns yourself, the preground stuff has lost most of the goodies.

These simple, cheap supplements can really help you maximize your medication and boost its effectiveness as a pain killer. Hit up amazons supplement section, amd give it a try, you'll be amazed at how a $.25 cap of gingko and a $.05 cap of crushed african pepper can turn a single oral dose into an all day experience.
 

Chuckdizzle

Well-Known Member
That's really really interesting. I've never heard of doing anything like that before and I think I'll have to give it a try!
 

VladFromOG

Active Member
...I live in a medical state and have had a script for ten years - I only vape hash oil, for a long long time. Vaping hash oil properly (in an oil bowl not burning it away on a nail) delivers so much more cannabinoids to ones system, that now after all these years, smoking medical grade weed doesnt even get me high, much less dirt weed.

Which is a common problem amongst long term medical patients: eventually, your tolerance goes up, and at a certain point you just cant concentrate the cannabinoids any further because youve already reached 100% purity and you cant smoke any more than the *constantly* you already do, which is why I've presented this information, and presented it here, in the medical section- So the medical patients who are having issues with tolerance or needing to frequently dose can extend the duration that weed lasts in the body.
 

VladFromOG

Active Member
Oh and nizza - just eat it. Eat any of the supplements I recommended, about 30-45 minutes before you dose with weed. A single 00 capsule of herb material is a good amount.
 

UncleReemis

Well-Known Member
Of course the pepper from West Africa would be long and black.. But I'm totally going to try this out. If my liver squeals and shrivels up...
 

gsgkill

New Member
Would this be a possible for the increase strength at lower doses, for the internal use of hash oil for fighting cancer? It's hard to come by in my state in any form. Can you point to research terms, I could use to further investigate this?
 

gsgkill

New Member
http://www.ncbi.nlm.nih.gov/pubmed/17995595
Potent inhibition of human cytochrome P450 3A4, 2D6, and 2C9 isoenzymes by grapefruit juice and its furocoumarins.
Girennavar B, Jayaprakasha GK, Patil BS.
Source

Vegetable and Fruit Improvement Center, Dept. of Horticultural Sciences, Texas A &M Univ., College Station TX 77843-2119, U.S.A.
Abstract

The cytochrome P450 enzyme family is the most abundant and responsible for the metabolism of more than 60% of currently marketed drugs and is considered central in many clinically important drug interactions. Seven different grapefruit and pummelo juices as well as 5 furocoumarins isolated from grapefruit juice were evaluated at different concentration on cytochrome P450 3A4 (CYP3A4), cytochrome P450 2C9 (CYP2C9), and cytochrome P450 2D6 (CYP2D6) isoenzyme activity. Grapefruit and pummelo juices were found to be potent inhibitors of cytochrome CYP3A4 and CYP2C9 isoenzymes at 25% concentration, while CYP2D6 is inhibited significantly low at all the tested concentration of juices (P < 0.05). Among the 5 furocoumarins tested, the inhibitory potency was in the order of paradisin A > dihydroxybergamottin > bergamottin > bergaptol > geranylcoumarin at 0.1 microM to 0.1 mM concentrations. The IC(50) value was lowest for paradisin A for CYP3A4 with 0.11 microM followed by DHB for CYP2C9 with 1.58 microM.
PMID: 17995595 [PubMed - indexed for MEDLINE]

Also http://www.ncbi.nlm.nih.gov/pubmed/21704641
IGNIFICANCE:

This study indicated that CBD was extensively metabolized by HLMs. These results suggest that CYP3A4 and CYP2C19 may be major isoforms responsible for 6&#945;-, 6&#946;-, 7-, and/or 4&#8243;-hydroxylations of CBD in HLMs.

http://www.ncbi.nlm.nih.gov/pubmed/17303175

These results indicate that CYP2C9 and CYP3A4 are major enzymes involved in the 11-hydroxylation and the 8-(or the 7-) hydroxylation, respectively, of the cannabinoids by human hepatic microsomes. In addition, CYP3A4 is a major enzyme responsible for the 7alpha- and 7beta-hydroxylation of Delta(8)-THC, and the 9alpha,10alpha-epoxidation of Delta(9)-THC.

So perhaps drinking a can of concentrated grapefruit juice just might slow down and shrink the dosage making each dose count for greater progress in killing Cancer.
 

polar

Well-Known Member
I usually don't post a lot, but I found this thread very interesting! I love this type of "out of the box" thinking, but I feel obligated to give some warnings about trying this (especially if you are sick / have chronic illness).
First thing I want to say: DON'T USE ANTIFUNGALS! Fungi, like bacteria are living things and as they reproduce they develop resistance to drugs. Save antifungals and antibiotics for when you really need them!!!
Second of all, 2C9 is a type of CYP 450 (the full enzyme name is actually CYP 450 2C9). Although I agree with the statement that if the inhibitors selectively inhibit 2C9 (and not the other types from the CYP 450 group) the adverse reactions are minimal, there are some things to keep in mind. For example, Warfarin, a very common drug used to treat coagulopathies (and has a very narrow therapeutic range), also uses CYP450 2C9. This means that if you are inhibiting 2C9 you will need a smaller dose of warfarin than what you would normally need. This is important because too much warfarin will cause you to bleed excessively (could lead to a stroke if you start a hemorrhage in the brain). This is just one example that quickly came to my mind of a possible complication that can arise from trying to mess with your liver enzymes (in this case, specifically CYP450 2C9). If you are chronically ill and take a lot of medications already, it is best (in my opinion) to try to avoid messing with your enzymes because the medicines you take already do a number on your liver and kidneys.
Like I said earlier, I found this post super informative, and in no way do I mean to "bash" the author since they obviously know a thing or two about liver enzymes and human biochemistry, but just be warned that there could be downsides to trying this method. The warfarin example is only ONE that came to my mind as I was reading the post and I'm sure there are others that I'm not thinking about. So please be careful, guys. If you want a stronger / longer high I would suggest either taking smoking breaks or trying edibles since digested THC is more potent than smoked.
Lastly, I know that there are a lot of ignorant doctors, and a lot of doctors that are against cannabis, but hopefully if you have a smart doctor who is pro-cannabis and knows his stuff you could discuss this topic with him/her.
Stay safe and Healthy!
-peace

P.S. Thanks again for this thread! I love reading real science about cannabis!!!
 

VladFromOG

Active Member
Your quite right polar, messing with enzymes is messy stuff, esp when you're on a lot of different scripts. Folks on things like warfarin should never attempt any enzyme pathway modification of any kind, and anyone who is on any medication other than marijuana should check with their doctor about interactions first!

That said, you'd be surprised by how few things are controlled exclusively by the 2C9 enzyme - most things that are broken down by this are also broken down by other CYP 450s (I made a typo in "the inhibitors I list will not inhibit Cytochrome P450s" which should have read "the inhibitors I list will not inhibit only Cytochrome P450s 2C9", but alas I cannot edit the OP, only my subsequent replies) I think this may be a viable option for a large number of patients.

And of course youre absolutely correct about saving the antifungals for when we need it. I was being facetious, forgive me. African pepper, st johns wort, and gingko work quite well by themselves

gsgkill, do not attempt what you have described. If you say you are attempting to treat cancer, I must assume that you are on more than just marijuana. Grapefruit juice will interact with basically any other medication you would be on for treatment of cancer. That is why, despite the fact that it is a potent inhibitor of 2C9, I didnt list it. I repeat; grapefruit juice is too dangerous and has too many interactions as it shuts down a whole range of enzymes.
 

Hilary

Member
I'm trying to help my son through a psychotic episode. He was involuntarily injected (at Rockingham Memorial Hospital) with 'Invega Sustenna', a long-acting anti-psychotic that I believe is a CYP34A inhibitor. He is having a terrible reaction to it. He is absolutely depondent and can barely tolerate the constant misery. I've been encouraging him to take CBD oil, which has been used successfully to treat symptoms of Schizophrenia. But I just found out that Cannabinoids are also CPY34A inhibitors. I'm not sure what part this enzyme plays in psychosis, if any. I'm not sure if I am helping him or hurting him at this point.
 

ttystikk

Well-Known Member
Fascinating! I find it interesting how many other pathways these inhibitors affect. I'm just guessing here because I don't have the necessary biomedical background, but this explains to me why cannabis has so many medicinal benefits.
 
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qwizoking

Well-Known Member
well im bout to head out for a min.

depending on your answer i would actually suggest the opposite.
if he was as you say injected with invega sustenna were talking about an extremely long lasting drug. depending dosage he will feel it..not be in system but feel it for several weeks.

as you said cbd can in cases be used to treat what may ail your son. however if hes having a reaction worse than the episode or ongoing problem its being used to treat. then you may desire to couneract some of these effects. in the future you could certainly go back and try cbd.

i have actually done exactly what im describing. but with oral risperidone (basically same drug)

good luck


oh and dont worry about enzyme inhibition with this. take caution with other meds though
 

Hilary

Member
I'll try to keep my discussion in one thread...
He's having multiple problems - the biggest one is extreme anxiety. I gave him a snow shovel as a gift (for whenever we get snow again) and said jokingly, that all he'll be able to shovel is dirt right now. He thought I was suggesting that he dig his own grave. I was horrified, and hugged him and reassured him that was the furthest thing from my mind.

He can't seem to sit still, he has to keep moving. He can't concentrate on anything, feels worthless. He wants to try to do something about getting a job, but he really can't function well enough to work right now. He got expelled from school, and the lease on his apartment was terminated because his roomates were terrified of him. He was getting really angry and difficult with them (with everyone). But now, he's like a scared kitten. He's acting more loving and appreciative than he has in 10 years. I don't know if that's the medication or the CBD oil, or his mental health problem.

He's not on any other medication, and is in good physical shape.
 

Hilary

Member
I'm curious what you actually did to counteract the side effects of the risperidone, when you took that. My son had the same reaction (except not as bad) 6 years ago when he was given Risperdal after another psychotic episode.

I suspect the THC in the week he's smoking is causing these episodes. The episodes keep happening after a period of drinking, smoking, stress, lack of sleep, and not eating right. There's been some fairly recent genetic research on specific genetic variations (in a minority of individuals) that implicate susceptibility to psychosis from THC.

https://www.researchgate.net/publication/274401580_Interaction_Between_Functional_Genetic_Variation_of_DRD2_and_Cannabis_Use_on_Risk_of_Psychosis

I think sleeping, exercise, and drinking a lot of fluids should help. We're going to the gym tomorrow morning. I hope it helps a little.
 

bird mcbride

Well-Known Member
I'm curious what you actually did to counteract the side effects of the risperidone, when you took that. My son had the same reaction (except not as bad) 6 years ago when he was given Risperdal after another psychotic episode.

I suspect the THC in the week he's smoking is causing these episodes. The episodes keep happening after a period of drinking, smoking, stress, lack of sleep, and not eating right. There's been some fairly recent genetic research on specific genetic variations (in a minority of individuals) that implicate susceptibility to psychosis from THC.

https://www.researchgate.net/publication/274401580_Interaction_Between_Functional_Genetic_Variation_of_DRD2_and_Cannabis_Use_on_Risk_of_Psychosis

I think sleeping, exercise, and drinking a lot of fluids should help. We're going to the gym tomorrow morning. I hope it helps a little.
It sounds more like a disease or an underlying infection causing toxic(septic) build up in the blood(chemical imbalance). It's not the weed. It's the going without sleep and not eating reducing the bodies ability to fight off this unknown infliction. I would take the victim regularly to a public swimming pool that still uses basic chlorine to keep the pool sanitized. This will reduce the level of toxicity to a point were you may be able to reason with the victim. Proper hygiene and using an anti-septic toothpaste along with a powerful mouthwash will also help.

If you know anything about swimming pools you can get sanitized in a bath tub.

Cleanliness is IMO next to Godliness, about six feet closer:)
 
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