29 votes
Posted 26 April 2016 - 09:59 PM
Ok. I ordered a week ago. Guess I'll just have to wait and hope it gets to me.
Yeah, it took a while for mine to get to me as well. Unfortunately, it's the only place online that I know of that has ibudilast. If anyone else finds another reliable source then please feel free to share. =)
Posted 27 April 2016 - 04:04 AM
Alibaba shows quite a few "medicine grade" and pharmaceutical grade suppliers. (mainland China) I just sent 5 or 6 requests for quotes for various quantities from 1g to 10g. Will report back if any beat the price from the Japanese lab.
Posted 27 April 2016 - 04:03 PM
Am I understanding this correctly, I-Insulin would help someone who has insulin resistance in the brain?
It's somewhat of an open question at this point. I-insulin seems to work better in healthy people but there have been some encouraging results in disease models as well.
https://www.ncbi.nlm...pubmed/25659889
J Gerontol A Biol Sci Med Sci. 2016 Jan;71(1):30-9. doi: 10.1093/gerona/glu314. Epub 2015 Feb 6.
Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging.Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer's disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca(2+)-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP.
Posted 27 April 2016 - 04:09 PM
Alibaba shows quite a few "medicine grade" and pharmaceutical grade suppliers. (mainland China) I just sent 5 or 6 requests for quotes for various quantities from 1g to 10g. Will report back if any beat the price from the Japanese lab.
Thanks, streamlover. Keep us updated.
Just a quick suggestion if you don't mind indulging me. If you haven't tried ibudilast before I would suggest testing it out before going all in on a group buy. It is a bit expensive but not unreasonable for a one time experiment to test effects. If you like it, then I'm all for a group buy from a reliable supplier. I wouldn't want you to spend a huge sum on something that doesn't have great results for you. Just my humble opinion.
Edited by lostfalco, 27 April 2016 - 04:09 PM.
Posted 27 April 2016 - 09:12 PM
Got no responses from the requests for 1g quotes, got several ridiculously high, one back asking if I was going to use it for research and one of $250 for 10g, shipping included. That will likely be the best but I agree that a group buy isn't warranted at this point, especially since the savings isn't that great over the Japanese supplier.I think I paid $40something for 1g bulk from there inc. the $16 or so shipping. Anyway, it's good to have backup in case something happens with the Japanese supplier.
Lostfalco, would certainly appreciate any ongoing updates you'd like to give beyond your initial experience with this dynamic duo. Thx.
Posted 27 April 2016 - 11:12 PM
Anyway, it's good to have backup in case something happens with the Japanese supplier.
Lostfalco, would certainly appreciate any ongoing updates you'd like to give beyond your initial experience with this dynamic duo. Thx.
Agreed!
Will do. =)
Posted 27 April 2016 - 11:24 PM
Lostfalco, in your opinion is it worth trying galantamine alone? Or should I wait for ibudilast?
Thanks.
Yeah, it's pretty much always a good idea to try things alone first before you combine them. I would start low with galantamine and get a feel for it until ibudilast arrives.
Admittedly though, ibudilast is the bigger hitter here imo. It enhances cerebral circulation, inhibits platelet aggregation, causes bronchodilation (enhances breathing/oxygen), lowers brain inflammation, increases neurotrophic factors, etc. Not too shabby.
Most recent blog post: http://www.lostfalco...n-fog-two-step/
Edited by lostfalco, 27 April 2016 - 11:32 PM.
Posted 28 April 2016 - 04:27 PM
http://www.ncbi.nlm....les/PMC2449371/The cannabinoid CB₂ receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain.
The widespread plant volatile beta-caryophyllene (BCP) was recently identified as a natural selective agonist of the peripherally expressed cannabinoid receptor 2 (CB₂). It is found in relatively high concentrations in many spices and food plants. A number of studies have shown that CB₂ is critically involved in the modulation of inflammatory and neuropathic pain responses.
Beta-caryophyllene is a dietary cannabinoid
The psychoactive cannabinoids from Cannabis sativa L. and the arachidonic acid-derived endocannabinoids are nonselective natural ligands for cannabinoid receptor type 1 (CB1) and CB2 receptors. Although the CB1 receptor is responsible for the psychomodulatory effects, activation of the CB2 receptor is a potential therapeutic strategy for the treatment of inflammation, pain, atherosclerosis, and osteoporosis.
Here, we report that the widespread plant volatile (E)-β-caryophyllene [(E)-BCP] selectively binds to the CB2 receptor (K i = 155 ± 4 nM) and that it is a functional CB2 agonist. Intriguingly, (E)-BCP is a common constituent of the essential oils of numerous spice and food plants and a major component in Cannabis.
Edited by sativa, 28 April 2016 - 04:29 PM.
Posted 29 April 2016 - 06:05 AM
Your blog should be required reading for all General Practitioners. I think you could become the Khan of the Nootropic world.
I really enjoy it as well!
I like the fact that you can throw some comedy in there, Spinal tap :P
I am sure I will be reading it for years to come!
Posted 30 April 2016 - 06:03 PM
Your blog should be required reading for all General Practitioners. I think you could become the Khan of the Nootropic world.
I really enjoy it as well!
I like the fact that you can throw some comedy in there, Spinal tap :P
I am sure I will be reading it for years to come!
haha Thanks, Bluecheer. I'm glad you're liking it so far. Gotta get some Spinal Tap in there whenever I can.
Posted 30 April 2016 - 06:12 PM
Your blog should be required reading for all General Practitioners. I think you could become the Khan of the Nootropic world.
Thanks Junk Master! I definitely have a lot more to learn from most General Practitioners then they do from me but I appreciate your kind words.
I love Khan's videos. I've toyed around with making some similar ones on nootropics and their mechanisms. Def something I'll be thinking about down the road.
Thanks for the info, sativa. Have you tried it?
Posted 30 April 2016 - 08:44 PM
Yes, it's present in cloves and hops (and cannabis of course) all of which I have tried.Thanks for the info, sativa. Have you tried it?An easily accessible CB2 agonist...
http://www.ncbi.nlm....pubmed/24210682
Edited by sativa, 30 April 2016 - 08:45 PM.
Posted 03 May 2016 - 03:04 AM
Falco, I couldn't locate where you posted about your results with Montelukast... I was wondering if you could share again your experience with it? Aswell as method of administration.
I am thinking of experimenting with it to lower my cholesterol/asthma as per a recently read study ( as an alternative to statins ) I'm at work - and cant copy the link over... but if you care let me know and ill post this link later.
I'm interested if/how effective you found it.
Also do you see any complications with it and ibudilast (and/or galantamine) .. I have no reason to suspect a problem, I am just curious if two separate Asthma preventing medications could cause unseen side effects.
cheers,
If you've already posted your results with this medication or not using it because of ibudilast im sorry I must have missed it.
Edited by Bluecheer, 03 May 2016 - 03:15 AM.
Posted 03 May 2016 - 05:37 PM
hey lost how in the world did you purchase ibudilast from that site? Which option did u choose and what type of card you used?? I got an error using my creditcard :(
Nevermind i used payolla with my card. order complete
Did you do anything special to get it to go through? My order went fine until the payment processor (PayDollar?) took my cc info then returned a message rejecting my payment due to an unspecified one of several reasons (wow, I'm trying to fix brain fog and they want me to play Sherlock Holmes ;-). No, really, there is nothing wrong with my card, I use it online all the time. Though this is the first time I've ordered something from overseas.
Has anyone else had this problem?
Lostfalco, is there a next best if I am ultimately unable to get ibudilast? Am I interpreting your blog right? I'm taking the list of "Microglia Inhibitors" on which ibudilast appears to be a list of alternatives addressing that mechanism, and that of those alternatives, ibudilast is the preferred selection. On reviewing the research, I can see why, but for those of us who are having trouble getting it, maybe a substack of the others might come close, or at least be better than nothing.
On a related point I note that you characterize microglia overactivation as a consequence of mast cell activation. If so, then maybe the mast cell activation inhibitors you list would fit in here. Sort of going one step further upstream in the causal cascade. I'm happy to report that my trial of palmitoylethanolamide has revealed utterly no unwanted effects. Still too early to draw any firm conclusions on benefit (only been two days), but the studies look promising and if anyone's interested I'll follow up in a couple weeks with my anecdotal impressions. The other item you list in this category, btw, luteolin, is promoted in at least one study as being synergistic with palmitoylethanolamine, http://www.ncbi.nlm....pubmed/23844686, and is listed as a PDE4 inhibitor at https://en.wikipedia...ase-4_inhibitor.
In any case, thank you for sharing your research, and for doing it with such flair.
Edited by Kinesis, 03 May 2016 - 06:01 PM.
Posted 03 May 2016 - 09:57 PM
Ibudilast arrived! Will try it out tomorrow without galantamine, and if there aren't unpleasant side effects, will try them together a day or two later.
Did you do anything special to get it to go through? My order went fine until the payment processor (PayDollar?) took my cc info then returned a message rejecting my payment due to an unspecified one of several reasons
That sucks! Did you try the regular cc option or just PayDollar (or whatever the name was)? I clicked the plain credit card option and had no problems. I know you mentioned that your cc was working fine, but have you confirmed that it's still working since placing that attempted order? It's possible purchasing from a Singaporean pharmacy based in Japan was different enough from your usual shopping patterns that it triggered your bank's fraud detection software and that your account has a temporary hold on it until you confirm that the purchase was deliberate. If that's not what happened and if it's the pharmacy that's rejecting your card, have you tried the same card again? Does your bank have a temporary cc generator like Bank of America's ShopSafe? If so, you could try again with different card numbers. It's also probably just good practice to use temporary numbers for online purchases unless you know and trust the security of both the site and their cc provider. Anyway, good luck and I hope you get it to work!
Posted 04 May 2016 - 12:11 AM
Ibudilast arrived! Will try it out tomorrow without galantamine, and if there aren't unpleasant side effects, will try them together a day or two later.
Did you do anything special to get it to go through? My order went fine until the payment processor (PayDollar?) took my cc info then returned a message rejecting my payment due to an unspecified one of several reasons
That sucks! Did you try the regular cc option or just PayDollar (or whatever the name was)? I clicked the plain credit card option and had no problems. I know you mentioned that your cc was working fine, but have you confirmed that it's still working since placing that attempted order? It's possible purchasing from a Singaporean pharmacy based in Japan was different enough from your usual shopping patterns that it triggered your bank's fraud detection software and that your account has a temporary hold on it until you confirm that the purchase was deliberate. If that's not what happened and if it's the pharmacy that's rejecting your card, have you tried the same card again? Does your bank have a temporary cc generator like Bank of America's ShopSafe? If so, you could try again with different card numbers. It's also probably just good practice to use temporary numbers for online purchases unless you know and trust the security of both the site and their cc provider. Anyway, good luck and I hope you get it to work!
Thanks so much for your reply, MindExplorer! I clicked the credit card option which directed me to PayDollar, at which point point I encountered The Wall. But it looks like it may go through after all. My bank called me a little while ago and asked to confirm the charge. Possibly the double-check was triggered by the overseas transaction. But then when I cleared it, the bank said its systems were down. So no clear answer to the mystery, except that the fault was evidently with the bank. In any case, I hope this didn't cause readers any undue alarm, as the problem apparently had nothing to do with either the merchant or the payment processor.
It's good to hear you received your ibudilast. I'm looking forward to hearing how it works with you, as well as the galantamine. Hopefully I will soon be trying the same myself!
Meanwhile, if anyone is trying the palmitoylethanolamide I'd be interested to hear their reactions as well. So far so good here...
Posted 04 May 2016 - 04:55 AM
No problem Kinesis! I'm glad it sounds like it will have gone through, and I'll definitely update you on the ibudilast and galantamine.
After two hours of public transportation, I'm finally the proud owner of a vial of Novolin R! :D Once I got to a Walmart it really was as easy as asking for a vial of Novolin R, just as lostfalco said.
Lostfalco, at what dose of intranasal insulin did you start feeling effects? Should I expect something acute from 10 IU? 20 IU? Or were the mood and memory effects from cumulative dosing? I plan to start with 10 IU b.i.d. and titrate up as long as I don't experience adverse side effects, but if the main effects you reported are acutely experienced, it'll be easy to find a minimum effective dose and stick with it for a while.
Edited by MindExplorer, 04 May 2016 - 05:01 AM.
Posted 04 May 2016 - 11:29 AM
Functional activation of monoamine transporters by luteolin and apigenin isolated from the fruit of Perilla frutescens (L.) Britt.
Abstract
Monoamine transporters playing major roles in regulating normal and abnormal synaptic activity are associated with various neuropsychological disorders. In spite of the discovery of a series of structurally different monoamine transporter antagonists for the therapy approach, no practical pharmaceutical can act as a transporter activator.
Here, we isolated luteolin and apigenin from the fruit of Perilla frutescens (L.) Britt by using an activity-guided extraction technique, and proved that the two compounds possess actions of enhancing monoamine uptake either upon monoamine-transporter transgenic Chinese hamster ovary (CHO) cells or upon wild dopaminergic cell lines, with higher specificity for dopamine (DA) uptake than for norepinephrine (NE)- and serotonin (5HT)-uptake, as well as with more potency and greater efficacy for luteolin than for apigenin.
Further, in the transgenic cells, the principal NE/DA uptake activation by luteolin was significantly prevented by respective transporter inhibitor, and the transmitter-uptake-enhancing action was independent of its ligands, which is in support of the compounds as monoamine transporter activators.
Furthermore, luteolin evoked a marked disinhibition of cocaine-targeted effect in CHO cells overexpressing dopamine transporter.
Thus, luteolin and apigenin function as monoamine transporter activators, which would improve several hypermonoaminergic neuropsychological disorders, especially cocaine dependence, through up-regulating monoamine transporter activity.
Protective effects of luteolin on cognitive impairments induced by psychological stress in mice.
Abstract
In the present study, the protective effects of luteolin were investigated against psychological stress-induced cognitive impairment. To emulate the psychological stress, mice received restraint stress for six hours daily, between 9:00 and 15:00 hours, for 21 consecutive days. The results of step-through test, open-field test and Morris Water Maze test demonstrated that psychological stress treatment could result in cognitive impairments in mice. This cognition dysfunction was improved by treatment with low- and medium-dose luteolin.
In addition, psychological stress induced an increased serum corticosterone concentration with a decreased serum norepinephrine and dopamine concentration.
These alterations were attenuated by treatment with luteolin.
Discovery and synthesis of novel luteolin derivatives as DAT agonists.
Abstract
Luteolin, 5,7-dihydroxy-2-(3,4-dihydroxyphenyl)-4H-chromen-4-one, has been proposed and proved to be a novel dopamine transporter (DAT) activator. In order to develop this potential of luteolin, a series of novel luteolin derivatives were designed, synthesized, and evaluated for their DAT agonistic activities, utilizing constructed Chinese hamster ovary (CHO) cell lines stably expressing rat DAT. Biological screening results demonstrated that luteolin derivatives 1d, 1e, and 4c carry great DAT agonistic potency (EC(50)=0.046, 0.869, and 1.375μM, respectively) compared with luteolin 8 (EC(50)=1.45±0.29μM). Luteolin derivative 1d, notably, exhibited a 32-fold-higher DAT agonistic potency than luteolin.
Edited by sativa, 04 May 2016 - 11:32 AM.
Posted 04 May 2016 - 12:39 PM
Yes, it's present in cloves and hops (and cannabis of course) all of which I have tried.
Clove essential oil produces noticeable psychoactive effects which can be attributed to Eugenol and the afore mentioned Caryophyllene. The hops extract produced much more significant sedation!
I haven't tried isolated caryophyllene but the existing sources are more than adequate for my purposes. Earlier I tried a "customized cannabis combination" (minus any significant THC content) using hemp buds (notably for CBD content) and essential oils to provide terpenes (Mycrene, limonene, terpineol, caryophyllene etc).
I suppose this could be seen as a non stoning version of a regular cannabis experience (re THC) but with a fully customisable experience by simply altering terpene ratios and types. Some are AChE inhibitors, HT1A agonists, HT3 antagonists, GABA interactions etc
Very interesting. Thanks!
Posted 04 May 2016 - 12:43 PM
Falco, I couldn't locate where you posted about your results with Montelukast... I was wondering if you could share again your experience with it? Aswell as method of administration.
I am thinking of experimenting with it to lower my cholesterol/asthma as per a recently read study ( as an alternative to statins ) I'm at work - and cant copy the link over... but if you care let me know and ill post this link later.
I'm interested if/how effective you found it.
Also do you see any complications with it and ibudilast (and/or galantamine) .. I have no reason to suspect a problem, I am just curious if two separate Asthma preventing medications could cause unseen side effects.
cheers,If you've already posted your results with this medication or not using it because of ibudilast im sorry I must have missed it.
I have tried Montelukast a handful of times but decided to pursue other experiments first. I'll let you know when I come back to it.
I was curious about interactions with galantamine and ibudilast as well. I didn't see anything serious theoretically so I tried a 5mg dose of Montelukast and didn't have any problems with the "two step" doses of galantamine and ibudilast. Of course, that's just a one off sort of thing so take it for what it's worth.
Posted 04 May 2016 - 01:03 PM
Lostfalco, is there a next best if I am ultimately unable to get ibudilast? Am I interpreting your blog right? I'm taking the list of "Microglia Inhibitors" on which ibudilast appears to be a list of alternatives addressing that mechanism, and that of those alternatives, ibudilast is the preferred selection. On reviewing the research, I can see why, but for those of us who are having trouble getting it, maybe a substack of the others might come close, or at least be better than nothing.
On a related point I note that you characterize microglia overactivation as a consequence of mast cell activation. If so, then maybe the mast cell activation inhibitors you list would fit in here. Sort of going one step further upstream in the causal cascade. I'm happy to report that my trial of palmitoylethanolamide has revealed utterly no unwanted effects. Still too early to draw any firm conclusions on benefit (only been two days), but the studies look promising and if anyone's interested I'll follow up in a couple weeks with my anecdotal impressions. The other item you list in this category, btw, luteolin, is promoted in at least one study as being synergistic with palmitoylethanolamine, http://www.ncbi.nlm....pubmed/23844686, and is listed as a PDE4 inhibitor at https://en.wikipedia...ase-4_inhibitor.
In any case, thank you for sharing your research, and for doing it with such flair.
Yep Kinesis, you're interpreting the list on the blog correctly. Ibudilast is the winner but the others are worth a shot for those who don't want to order a prescription drug from overseas (totally understandable! ha). As you said, a substack aimed at microglia inhibition is the way to go if ibudilast isn't used.
As far as microglia and mast cells go, I would say they are 'interactive'. It's not necessarily the case that microglia activation is a consequence of mast cell activation. In some cases, it could be the other way around. Once one of them is activated though, they are likely to activate the other. It makes sense to me to 'dial down the volume' on both if one is dealing with brain fog.
Awesome you're trying PEA! I'm really interested to hear how it goes for you and thanks for the study combining it with luteolin. Makes a lot of sense. I'll link a great video by Dr. Theoharides below where he talks about the importance of mast cells.
Glad you enjoyed the blog post! I like to keep myself entertained. ha
Edited by lostfalco, 04 May 2016 - 01:23 PM.
Posted 04 May 2016 - 01:06 PM
Ibudilast arrived! Will try it out tomorrow without galantamine, and if there aren't unpleasant side effects, will try them together a day or two later.
Nice! Keep us updated. My ability to focus is pretty crazy on this stuff. Hope it works well for you too.
Posted 04 May 2016 - 07:47 PM
Hmm getting (intranasal) insulin seems really difficult in Europe...why on earth it's sold on prescription...it's like no way..doh..I need to visit some nice doctor :P
At least hopefully I will be also able to get Ibudilast from Japan. Was thinking if it's worth investing but decided to try.
Posted 04 May 2016 - 08:54 PM
Hmm getting (intranasal) insulin seems really difficult in Europe...why on earth it's sold on prescription...it's like no way..doh..I need to visit some nice doctor :P
At least hopefully I will be also able to get Ibudilast from Japan. Was thinking if it's worth investing but decided to try.
Im agreeing with you there, getting insulin on prescription in my country is almost impossible here. So my only chance to get hand on insulin is to buy it outside Europe. Any here from the States who want to partner up, and send it from the states for a profit 
?
Posted 04 May 2016 - 10:14 PM
In subthreshold/very small doses ketamine is wonderful in a cognitive enhancement sense, it can bring about interesting & insightful changes in perception. I used small doses as an aid for meditation type activity a few times. It's also good as a withdrawl aid and to reset drug tolerances. (memantine and iboga are much better).very interesting, have you had the chance to try ketamine? Not sure about its noot potential though, but a wonderful drug
Amphetamine and similar "releasing agents" are able to reverse the transport direction of monoamine transporters through the activation of an intracellular receptor, trace amine-associated receptor 1 (TAAR1), which is located within the axon terminal of associated monoamine neuron.[1] TAAR1 signals through protein kinase A and protein kinase C to phosphorylate monoamine transporters. Dependent upon the phosphorylating protein kinase, the phosphorylated transporters will either reverse transport direction, causing neurotransmitter efflux and reuptake inhibition, or withdrawal into the cytoplasm, causing only reuptake inhibition.[1] Amphetamine is also known to release the vesicular stores of monoamines in monoamine neurons through VMAT2, although the precise mechanism has not been established.
Edited by sativa, 04 May 2016 - 10:22 PM.
Posted 05 May 2016 - 04:59 AM
LF, Finally got my Ibudilast after 2 weeks, and the company did send an email with tracking info about a week after I ordered.
Are you still taking Galantamine 7mg BID (14 mg daily) or did you change your dose on that?
Also, are you taking the ibudilast+galantamine with any sort of Choline?
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