I’ve been taking 30mg of CBD for the past year and started rapamycin last month increasing now to 6 mg/week. Some research has been published showing that CBD increases the blood level of rapa similar to grapefruit–to the extent of 200% or more. But they don’t talk of how much CBD does this. Does anyone have any input on how much CBD is needed to have this effect? I’m a patient of Dr Green & he thinks 30mg of CBD is not a problem but he didn’t have any direct knowledge of the issue. Any feedback would be appreciated as I’d like to keep taking CBD but don’t want to overdose on rapa. Thanks
Jim
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Hi Jim,
Welcome to the site, and thanks for posting on this. I had not heard of this - but a quick check on Pubmed shows you are absolutely right. I will dig deeper into this to see if I can find more and answer your questions - but you should definitely be careful:
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Thanks! I’ve stopped taking CBD starting last week until I get more info. The best news would be that 30mg of CBD is reliably synergistic w/ rapa & consistently increases its biological effect by some known percentage. I could then continue w CBD & cut my rapa dose. But so many unknowns. Don’t want to overdose or underdose!
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After reading the Dog aging project update recently, I took 13 mg Pfizer Rapamune (0,15 mg/ kg) at the start of a 3 day fast in the morning on an empty stomach with water and experienced no sides. In the past I also took 6 mg with 2 glasses grapefruit juice also without sides. I am 44 years old and exercise daily.
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Looking to hear more. My issue with grapefruit juice is that it comes with a bunch of sugar
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Yes - I agree on the sugar issue. There is also the issue of the large amount of variability (in terms of its effectiveness in increasing the bioavailability) in the grape fruit juice that you buy.
When I have done the grapefruit with rapamycin dosing I eat the actual fruit an hour before I take the rapamycin. That seems like it might be better, and I’m guaranteed to get “fresh grapefruit juice” - and all the fiber from the fruit.
I have also done more research on the drug called “ketoconazole” that is mentioned in the same research study that used the grapefruit juice. This drug also is very good at increasing the bioavailability of the rapamycin - by a pretty consistent 5.6 X it says in the study. In the study they were giving it to cancer patients who were taking 90mg of rapamycin / Sirolimus a day - a huge amount, but with the ketoconazole they only needed to use 16mg / day to achieve the same blood Sirolimus levels.
ketoconazole is a cheap, and easily available generic medication - so if that is something that is of interest to you, talk to your doctor about it. The key issue the mention in the study that they were concerned about with regard to the ketoconazole, was toxicity or overdosing because they were using it every day. This wouldn’t be an issue in the sirolimus / anti-aging protocol I suspect because it would only be used once every week or two.
More information here:
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Hi, my name is Ross Pelton and I am The Natural Pharmacist. I have written a book titled Rapamycin, mTOR, Autophagy & Treating mTOR Syndrome which is in the final stages of editing and will soon be published.
Regarding “optimal” dose of rapamycin. I think this needs to be individualized. Everyone is different…ie. biochemical individuality.
I was taking 6 mg once weekly. My lab tests revealed that I had become anemic…so I have reduced my dose to 6 mg every other week. I just had a blood draw today. I will post the outcome when I get the results.
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Welcome to the forum Dr. Ross. Please post a link to the book once its available. More information is great.
What is your opinion about doing peak and trough sirolimus blood level tracking or testing? Since there is quite a variation in half-lifes (between people) and dependent on diet, etc. - and the risk of mTORC2 inhibition over time.
Life Extension now offers a cheap $95 blood sirolimus test that we could use for this purpose.
I think testing peak and trough sirolimus would provide very important information for the LIfe Extension community. We are truly in the very beginning of this new frontier. I think ultimately, we will find that there is great biochemical individuality in what is the optimal dose and frequency for different individuals. I just made a comment earlier about reducing my dose from 6 mg weekly to 6 mg every other week…based on labs that revealed I had become anemic (low iron & hemoglobin). Lots to learn…Ross
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Did switching to a 2 week interval reverse the anemia? Is your book out yet?
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What optimal iron/ferritin levels and hemoglobin levels do you aim for?
Could you provide a link to the Life Extension, sirolimus blood test? I tried looking it up but no luck:(
For those interested, here is a link to Ross Pelton’s book:
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Here is a post with information about the blood sirolimus test, you need to call them and specify the test number. It may take a bit of work - some the lab test people don’t seem too familiar with it:
See this post for details on how to identify the test (you have to call their lab test customer support, its not yet listed on their website): Life Extension Blood Sirolimus Test
also mentioned here:
Hi Rapamycin enthusiasts,
I’ve encountered a delay in getting my book published. New books need to get a registration number and bar code from the Library of Congress. This process has traditionally taken 8-10 days. Currently, due to COVID and staffing problems, the wait is 1-2 months. Stay tuned…I’ll shout out as soon as Rapamycin, mTOR, Autophagy & Treating mTOR Syndrome is available. Healthy regards, Ross
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Anyone planning on doing a Sirolimus test, play very close attention to the pharmakinetics. There is a very rapid peak of blood concentration (1st 2 hrs), and then rapid drop off. See Figure 1 in attached paper.
https://sci-hub.se/https://doi.org/10.1016/S0009-9236(97)90192-2
Depending on dose, and time of blood draw after dosing, you might not get a meaningful signal.
Perhaps schedule an firm appt, and take your dose a couple hours before.
Yes - given the rapid rise and fall I’m not sure there is much value in trying to get the peak blood sirolimus level. The trough level - via a blood draw just prior to the next dose of rapamycin - seems like the most useful to make sure you are waiting long enough before taking the next rapamycin dose, and thereby minimizing risk of mTORC2 inhibition.
Agree with your logic for maintenance reasons, combined with side effects.
But if you’ve never had a Sirolimus blood test then:
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Do you even know for sure what your’re taking is Sirolimus, especially those of us sourcing overseas? There could be many people who have no idea if they are taking any rapamycin at all.
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Bioavailability is very poor, so unless you’re taking a high dose, you might not even catch the signal at all if you do the blood test before next dose.
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Fair points. The lab analyses I’ve seen of the generic sirolimus / rapamycin medicines out of India seem to suggest they are of reasonable quality, but the sample size is very small - so yes, the idea of the peak blood sirolimus levels as a proxy for validating at a very rough level the dosing / purity of the tablets sort of works (though without information on contaminants its still far from ideal).
Given the low price of generic rapamycin, I don’t think there is too much of an incentive for rogue pharma resellers to sell “fake” rapamycin with low or zero levels of the actual sirolimus (it seems more likely they would target the high-priced name brand drugs that they could sell for a much higher price).
I suspect the bigger risk is the potential for contaminants like nitrosamines like we’ve seen even in generic versions of metformin sold in the USA and other western countries (as Katherine Eban has highlighted in her book)
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This is why I’m prepared to pay more and get Rapamune (Pfizer)
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