Nootkatone - a sequiterpene natural stimulant?

[paracelsius]

So lately I’ve been reading about this compound Nootkatone? It is a sesquiterpene ketone found in grapefruits, Valencia oranges and the bark of Alaskan yellow cedar tree. It is used as a natural insects repellent and also as flavouring agent in drinks/foods/cosmetics to give distinctive grapefruit flavor or aroma.

A very interesting thing about this compound is the way it works with the Alaskan cedar tree to ward off insects. Once in contact with the compound, insects become hyper stimulated and aroused to the point of vibrating senselessly like they having sex, running around like crazy until they drop from the tree. Basically intoxicating them, making them tweaking hard. Quite amazing how Nature works sometime (getting a pest intoxicated, tweaking, restless and unable to eat..LoL. What a way to solve the problem!?! Can’t be smarter than that!! Why am I saying tweaking?

Well it turns out this compound is a potent octopaminergic, ie adrenergic (ref: doi:10.1021/bk-2018-1289.ch012). In insects Octopamine is the equivalent of what Norepinephrine is to vertebrates). Octopamine is actually Norepinephrine molecule without the meta-hydroxy on the phenyl ring. No surprise then that it gets insects “tweaking” hard. Whether it is a direct agonist or releaser and also dopaminergic/serotonergic nobody knows only that it potently activates Octopamine receptors in insects.

Now how about in humans? well in humans it is a potent antidepressant according to this Chinese patent/clinical trial, with 95%+ remission after six weeks in severely depressed patients. Granted sample size is only 40 patients but still 95% remission is huge. The Chinese claim it acts as antidepressant by inducing some liver enzymes that eventually activate some brain receptors. I doubt it. IMO in humans it is probably also a stimulant like in insects, a monoaminergic amphetamine-like stimulant but with a chemical structure totally unlike any adrenergic/dopaminergic stimulant described in the literature afaik. Which won’t be surprising it has antidepressant activity if it is monaminergic.

No other studies in humans have been done afaik but this Japanese paper shows that in mice it is actually anorexic, reduce belly fat and increase motor performance/endurance further confirm it is probably just plain stimulant. Here is an abstract:​

Long-term intake of diets containing 0.1% to 0.3% (wt/wt) nootkatone significantly reduced high-fat and high-sucrose diet-induced body weight gain, abdominal fat accumulation, and the development of hyperglycemia, hyperinsulinemia, and hyperleptinemia in C57BL/6J mice. Furthermore, endurance capacity, evaluated as swimming time to exhaustion in BALB/c mice, was 21% longer in mice fed 0.2% nootkatone than in control mice. These findings indicate that long-term intake of nootkatone is beneficial toward preventing obesity and improving physical performance and that these effects are due, at least in part, to enhanced energy metabolism through AMPK activation in skeletal muscle and liver.....

Now would it make a recreational stimulant? Who knows. At the very least it would probably be a functional stimulant and anorexic (for weight loss) and more important a potential sport doping agent. It is unlike any banned substance (in sports and otherwise) and can’t be detected with current tests. And it is perfectly legal! 20% increase in endurance is pretty huge in competitive sports, really huge if one is inclined to cheat!. But then again I don’t condone cheating!

This will be my next project on novel stimulants I am researching (will post a trip report once I get my hand on that compound). Good’day Blighters STAY SAFE.​

 

[simstim]

Interesting find. Keep us posted