@perpetualdawn
Welp, I found one.
It’s called amentoflavone. According to Wikipedia, “Amentoflavone has a variety of in vitro activities including antimalarial activity, anticancer activity (which may, at least in part, be mediated by its inhibition of fatty acid synthase), and antagonist activity at the κ-opioid receptor (Ke = 490 nmol L−1) as well as activity at the allosteric benzodiazepine site of the GABAA receptor as a negative allosteric modulator.”
Amentoflavone is a natural component of multiple herbs including St. John’s wort and ginkgo biloba. According to the
study that Wikipedia links to as a citation, “We have shown that amentoflavone (4) and hyperoside (6), flavonoids present in H. perforatum, have κ antagonist activity in vitro. In addition, preliminary SAR investigations have identified that the stereochemistry of the C2 and C3 positions is important for antagonist activity and selectivity. Further exploration of these findings is underway and will be reported in due course.”
Flavones and their derivatives are popular and relatively well-studied at this point. It’s not uncommon to actually find them being sold pure (or close enough) in supplement form. In fact,
here’s an amentoflavone supplement being sold at Walmart.
I also found an old
Reddit post by a user who claimed to enjoy taking 200 mg of amentoflavone while working out. They claim to get an “anti-dysphoric” effect and are of the opinion that the kappa-opioid receptor antagonist is involved, but it should be noted that, as that post goes into, it is not entirely clean and selective in this mechanism of action. I haven’t looked into it enough to know why they were taking it while working out, but I feel it should be noted that many flavones and their derivatives can actually have steroidal effects, via mechanisms such as being agonists or antagonists at androgen, estrogen, and progesterone receptors, or even aromatase inhibition (a mechanism sought by users of synthetic steroids, which prevents metabolism of testosterone into estradiol, the primary estrogen). Personally, I do not recommend using flavones willy-nilly, at least not on a chronic basis, but taking one a few times for an experiment like this probably wouldn’t do any non-negligible damage.
The question that remains is still how active of a kappa-opioid receptor antagonist it actually is? If I was to run an experiment on amentoflavone, salvia, and DPT, I would do it in the following steps:
1. Take a full dose of amentoflavone and then try smoking salvia. If salvia still works exactly the same way, repeat this step with increasing dosages of amentoflavone until a tolerable limit is reached. If salvia still feels the same, the experiment is over. If the salvia trip is actually noticeably inhibited, progress to step 2.
2. Take the same dosage of amentoflavone that was successful in step 1 and then try using a psychedelic that is not suspected to have kappa-opioid receptor agonist activity, or more specifically is relatively likely not to. Document the changes in effect, if any, very carefully. The fact that amentoflavone is also a negative allosteric modulator of GABA(A) receptors means that it might potentiate psychedelics in the opposite way of how things like benzodiazepines suppress them. It is also possible that some unappreciated part of the downstream effects of 5-HT2A receptor agonist involves dynorphin release and that the effects of even a selective psychedelic would be altered by a kappa-opioid receptor antagonist. Of course, it’s also important to know if any potential off-target effects, like steroidal effects or whatever, will alter the trip. If the trip seems relatively unchanged or like the differences are easily accounted for, progress to step 3.
3. Take the same dosage of amentoflavone and try using DPT. If the DPT trip is relatively unaffected or affected in the same way as the psychedelic from step 2, I would consider that evidence that there is no kappa-opioid receptor agonist component to the DPT trip. If the DPT trip is more significantly inhibited than the psychedelic from step 2 and in a way more similar to salvia, I would consider that evidence that there might actually be a kappa-opioid receptor agonist component to the DPT trip - although, it would still be unclear if the effect is direct, like salvia, or resulting from DPT causing more dynorphin release downstream than other psychedelics, or something like that. And again this would all just be evidence either way, not proof, but still, evidence.
I do not recommend trying this if the combination of amentoflavone and the psychedelic from step 2 makes you physically uncomfortable. GABA(A) receptor negative allosteric modulation should lower the seizure threshold for the same reason that positive allosteric modulation raises it, and DPT has rarely been associated with seizures before. Don’t push yourself if the amentoflavone seems to potentiate the psychedelics in an uncomfortable way.
So that would be the best plan I think I can come up with so far. I’d consider trying it myself if I still had some DPT, but again I sadly do not. But I’ll leave it here at least for you and others to consider.
Do you mind posting it in TR, too?
