Hello guys,

SWIM had an idea of doing the reverse tolerance thing with rue, and the only time SWIM could do it would probably be in the morning.

SWIM is sadly addicted to caffeine and nicotine and will get withdrawals after not using it for a certain time (headache, snappy mood etc).. getting of topic...

Anyways..

SWIM makes his own energy drink, that contains about 400mg of caffeine, 1,5 grams taurine, b complex vitamins, and stevia, citric acid and flavor drops (usually herbal) for flavor, along that he vapes nicotine.

To that mix SWIM is considering adding 1 gram of rue to get that mood boost and build a reverse tolerance so SWIMs ayahuasca analogue experiences could have less body load in the future.

Would that be safe?

My guess is yes, since caffeine-containing plants are occasionally used as ayahuasca admixture, but probably not dosed that high...

Drinking the rue at night is also not an option, because SWIM is also a medical cannabis patient, and anything that could boost the effects of his medication is not favorable, because it feels rather uncomfortable if it gets outside of his "sweet spot" range.

Oh man, i totally feel ya on the Cannabis lol, i smoked Cannabis all day everyday for 10 years, and together with the Harmalas at least it got to be too much, psychologically-speaking, heck i had more of an issue from the Cannabis than i did from my daily/near daily 4 year Aya excursion lol, surprisingly. I ultimately had to quit Cannabis due to it's intensity and trippiness, but shortly after Delta 8 and then HHC came along, which i've been using since, which Delta 8 while mild seems to be the most favorable psychologically as in no real anxiety or paranoia or trippiness in the sense of Delta 9, while HHC can be a bit more similar to Delta 9 but milder and with no anxiety/paranoia. I did find that when i abstained from Harmalas for a bit and then tried Cannabis again that i seemed to respond more favorably to it again, which was nice, so yeah i'd say the Harmalas definitely potentiate it to some degree.

As for the Caffeine, Caffeine is metabolized by CYP1A2 which Harmine/Harmalas potently inhibit, even 1 gram of Rue can provide definite CYP1A2 inhibition. As an example, i take a medication for sleep called Tizanidine, it's metabolized by CYP1A2 as well, and i use Harmalas to potentiate it so i don't have to take as much, normally without the Harmalas i need 8 to 10mgs of Tizanidine for the needed sedative effect, whereas with Harmalas i only need 2 to 4mgs to achieve the same effect, so the CYP1A2 inhibition is pretty potent, and can potentiate the dosage primarily, but can also lengthen the duration if things are consumed at the right time.

The CYP inhibition of the Harmalas seems to move around depending on the dosage, so with the reverse tolerance for example, the duration of the Harmalas starts to stretch out and with it the CYP inhibition timeframe, although if the Harmalas and the CYP substrate are consumed at the same time there seems to be more consistent inhibition/potentiation, but ime CYP inhibition is also present around hours 4, 5, 6, 8, up to 10 hours after the Harmalas, depending on dosage/where the reverse tolerance is, and you can gauge this by taking a CYP substrate at different times and you will find the timeframe moving up as the dosage of Harmalas increases because say you take the CYP substrate at hour 4, at a certain dosage of Harmalas it would potentiate the CYP substrate at hour 4, but as the Harmala dosage gets stronger the CYP inhibition moves up to around hour 5, and then to 6, 8, 10, and so then hour 4 seems to lose it's CYP inhibition/CYP potentiation, which then moves to around hour 5 and so on because then it's potentiated again, and so it might even go up to hour 12 of the Harmalas if a particularly heavy dosage is taken which is where one inevitably ends up if taking the same dosage, even a small dose like 1 gram of Rue on a daily basis for a good long while.

Which, with the reverse tolerance, how strongly it builds up depends on the dosage of the Harmalas, and so lower dosages will build up the reverse tolerance more weakly/slowly, higher dosages will build it up stronger/faster. And so if you want a more steady/consistent/slower reverse tolerance build up, 1 gram of Rue works nicely, it's what i've been dosing the last few months although i've been taking 1 gram 12 hours apart, so technically 2 grams a day, which may play a role, but i figure the CYP2D6 inhibition of Harmalas (which Harmalas are metabolized by CYP2D6 but also inhibit CYP2D6 as well) wouldn't be there due to the low dose at hour 12 and so far it's been fine 12 hours apart so i don't think there's any CYP potentiation of the Harmalas themselves going on there in my case. So perhaps 1 gram would do nicely.

So back to the Caffeine though, ime a few sips of Caffeinated soda for example can be as strong as a cup of Coffee, when consumed alongside the active CYP1A2 inhibition of the Harmalas. So 400mgs of Caffeine, imo, too much, you will want to reduce your Caffeine dosage at least by half, possibly down to a quarter of the usual dosage, to equal the same effect as what you'd normally consume without the CYP inhibition.

However, if you consume the Caffeine before the Harmalas (outside of the active CYP inhibition) there won't be any potentiation of the Caffeine because CYP1A2 isn't yet inhibited and so it gets absorbed as usual, although i'm not sure how long before the Harmalas one should consume the Caffeine, could be 30 minutes, could be an hour or two, but the safe bet would be to like i said reduce the dosage by half, possibly a quarter of what you usually consume, and then try out the Rue like an hour or two later, if you can, if you can't though, then i'd say just take the Rue and reduce your dosage and you will be fine, although the Caffeine may last longer due to the potentiation and lengthening of duration, which the duration can be a bit finicky and depends on catching the CYP inhibition at it's max i guess, so like with my Tizanidine, every now and then i take it at the "right time" and it's normal 4 hour duration turns more into an 8 hour duration, but most usually i seem to still get potentiation of dosage but no lengthening of duration.

With all that said though, yes it's safe, i've been doing it for years personally, just make sure of your Caffeine dosage so that you don't overdo it, i imagine 800mgs or more of Caffeine is probably not gonna feel too good lol.

Definitely agreeing here with Stamen's suggestion to scale back the caffeine dose. Something I've noticed as well is that residual caffeine from preceding high intake can seemingly get released from what I can only infer are physiological binding sites (on the platelets perhaps, or maybe by getting displaced from CYP1A2?) and this can cause tachycardia. These post-harmala cardiovascular effects have now abated since having reduced my intake of caffeinated beverages.