FS5 eliminated OCD / oral dosage inquiry

I experimented with two different extracts of kanna from https://bioextracts.co.uk/. They are "Classic Sceletium Extract" and "FS5". I first tried 25 mg of the classic extract buccally. There were some positives from it but I also got a mild headache for the entire day and didn't really like the effects overall.

After a few days, I tried 25 mg of FS5 buccally. From this, I got a mild mood boost, a slight but noticeable and meaningful increase in energy (I have chronic fatigue, maybe undiagnosed CFS), it was a bit easier to focus on the external world (I'm usually stuck in my head most of the time, and still was while using it but to a lesser extent), and the external world looked slightly better than usual (observing more beauty in the same environment). The biggest effect for me was the elimination of my OCD by around 99% on the same day I used it. However, I seemed to get a mild headache from this extract too.

I took another 25 mg dose the next day. The effects from the previous day persisted, so I don't know if the second dose really gave me any additional benefits. I still had a mild headache, so I decided to take a break from this after my second dose.

The day after, my OCD hadn't returned. It was also still easier to focus on the external world, but that effect seemed to have faded a bit. Fast forward to today, 8 days after my last dose of FS5, and my OCD hasn't returned. I also still have some more energy than before, and it's still slightly but noticeably easier to focus on the external world. I've also been taking ginger extract and passionflower the whole time, so I can't exclude the possibility of a positive interaction between ginger, passionflower and FS5. I started taking ginger and passionflower several months prior to experimenting with kanna. Passionflower reduced OCD significantly by itself, with no acute benefits but effects increasing over time, but the effect plateaued after a few weeks.

As for why FS5 had such a positive effect, I suspect it could have something to do with PDE4D inhibition. PDE4D inhibition enhances dlPFC function, and from the linked reddit article:

  • "Enhancing the dlPFC over the whole prefrontal cortex is normally more desirable because you get a more selective outcome and also you don't enhance areas such as the OFC, which can be problematic if overactive (potentially leading to conditions such as OCD) [11][12]. Enhancing the dlPFC can actually bring brain regions back into a harmonic system, for example enhancing the dlPFC through different methods has been shown to reduce OCD phenology through overriding OFC (orbitofrontal cortex) activity."

Mesembrenone, an alkaloid found in kanna, is a relatively potent PDE4 inhibitor:

  • "The extract was a potent blocker in 5-HT transporter binding assays (IC(50) 4.3 μg/ml) and had powerful inhibitory effects on phosphodiesterase 4 (PDE4) (IC(50) 8.5 μg/ml), but not other phosphodiesterases. There were no cytotoxic effects. Mesembrine was the most active alkaloid against the 5-HT transporter (K(i) 1.4 nM), while mesembrenone was active against the 5-HT transporter and PDE4 (IC(50)'s<1 μM)." https://pubmed.ncbi.nlm.nih.gov/21798331/

FS5 has more mesembrenone and less mesembrine than the classic extract. But these are not the only differences between the extracts, so it's possible that something other than mesembrenone (maybe an alkaloid from the "15% other alkaloids") was also having a beneficial effect on me. And of course, it could also be a specific combination of different active compounds.

By the way, I also took and oral dose of 100 mg of blue lotus extract (80% nuciferine) on the second day of using FS5. I've used the same dose of blue lotus extract once before and it didn't affect OCD much. I still wanted to mention it just in case.

Now to the question: If I want to get the same strength of effects from oral administration as from buccal administration, how much do I need to multiply the dose with?