Fioricet sounds pretty odd, 3 drugs in one pill.. as an ADHDH/ADD person the caffeine worries me a bit, would interact with my own meds probably. Is it a lot of caffeine there that you take daily? I can look into complementing ketamine treatment for you, give me some time
.
EDIT: (I'll just quote relevant parts from articles which may contain tons of info I think is useless here, if you google parts of the text you will find the articles.) I don't know if you're taking benzos, but this is from doc that administers ketamine infusion treatment for depression:
"In addition, Abreu has found that addiction to benzodiazepines is a big problem. Ketamine doesn’t work at all in these patients, says Abreu. This is an effect that he says has been noticed by all the doctors who run clinics, although at the moment they can only guess at why this is the case. “So these patients have to be weaned off this drug before we can treat them,” he adds."
"In addition, he mandates that patients take part in ongoing cognitive behavioural therapy (CBT) ... “Patients have to have CBT to continue to be patients at our clinic,” he says. “But it’s also about diet, exercise and lifestyle. It’s not a magic trick, it requires effort on their behalf and my behalf.”
and from another one "In May 2016, researchers from NIMH and the University of Maryland — Zarate among them — published a study conducted in mice showing that a chemical byproduct, or metabolite, created as the body breaks down ketamine might hold the secret to its rapid antidepressant actions. This metabolite, hydroxynorketamine, reversed depression-like symptoms in mice without triggering any of the anesthetic, dissociative or addictive side effects associated with ketamine, Zarate said." -
https://med.stanford.edu/news/all-n...-hallucinogen-as-potential-ocd-treatment.html
So I'm thinking, something that slows down the metabolism of hydroxynorketamine? CYP2B6 and CYP2A6 are responsible for the hydroxylation of norketamine, so make sure you aren't inhibiting them through other drugs. Off the top of my head, I think propranolol and buprion either inhibit or are substrates (or both) of CYP2B6. Orphenadrine (muscle relaxant) is a potent one too
About the benzos: "Plasma concentrations of ketamine are increased by diazepam and other CYP3A4 inhibitors due to inhibition of conversion to norketamine" Maybe this is the reason why infusions are preferred, if it's indeed about metabolites of ketamine more than ketamine itself? On the other hand, phenobarbital
https://www.ncbi.nlm.nih.gov/pubmed/11996099 induces both CYP2B6 and CYP3A4 (3A4 is partially responsible for ketamine -> norketamine). Carbamazepine is a similar drug, but with a twist: "CBZ stimulates the transcriptional upregulation of genes involved in its own metabolism, with autoinduction of CYP3A4 and CYP2B6" so you most likely don't want to be taking it during ketamine infusion rather take it before to upregulate the enzyme production and make sure it's out of your system when you take the infusion? Not a lot of documented ways to complement this therapy, so I'm just theorizing, probably should consult a pro doctor. Maybe print them the articles related to pharmacokinetics?
https://www.pharmgkb.org/pathway/PA165817070 "Carbamazepine Pathway, Pharmacokinetics" Pretty off-label, but that's just medical treatment we haven't explopred properly yet. In the future, people will most likely be prescribed drugs according to their genetics, and the expression of CYP450 related genes is a big reason why some drugs work very well on some people while they could be dangerous to some, like DXM.
There's also talk about the anti-depressive action not being related to NMDA-antagonism, as hydroxynorketamine is a pretty weak NMDA-antagist compared to ketamine itself, but it is a far more potent anti-depressant.
"However, hydroxynorketamine does still show biological activity, having been found to act as a potent and selective negative allosteric modulator of the α7-nicotinic acetylcholine receptor (IC50 < 1 µM).[4] Moreover, (2S,6S)-hydroxynorketamine was tested and was found to increase the function of the mammalian target of rapamycin (mTOR), a marker of the antidepressant activity of ketamine, far more potently than ketamine itself (0.05 nM for (2S,6S)-hydroxynorketamine, 10 nM for (S)-norketamine, and 1,000 nM for (S)-ketamine (esketamine), respectively), an action that was observed to correlate closely with their ability to inhibit the α7-nicotinic acetylcholine receptor."
α7-nicotinic acetylcholine receptor, gotta dig deepr for that one. Hopefully this helps you.
