I managed to get the following from a cached page on Bodybuilding forum, the thread was originally deleted, not sure why. Can someone with adequate scientific knowledge comment on the veracity of these claims below:
Craze is based solely on trimethylglycine's ability to
1.) Donate methyl groups to neurotransmitter synthesis. (along with obvious other processes, coq10 synthesis for instance). This well known fact about trimethylglycine is what makes it so intriguing.
2.) Lessen platelet aggression, which leads to the introductory point.
Coincidentally enough, Dendrobium, one of the ingredients in craze, has immense APA potential. (also, dendrobium is a convulsant, analgesic, an antagonist of BA, taurine, and GABA and used for sexual enhancement (See the link below for apa and other effects) http://pubs.acs.org/...021/np50111a014
PEA is also well known for this, and you can feel it and how much better it is at it than other stimulants. Guarana is another decent APA, as is aspirin obviously (thus its use in ECA, but ephedrine itself is good enough APA).
So what's the problem? It seems like Craze is chalked full of every constituent, isomer, extract whatever of PEA they could find due to its natural ability to APA and how well it does it.
(Take note that pea and betaine work incredibly synergisticly together, and the ability for TMG to donate a CH3 is due to SAM-E production and the donated methyl group goes to the synthesis of neurotransmitters. As for the pea, or beta-pea specifically, it simply releases norep and dopamine.)
Now citramine in its studies was NOT known as simply an MAO-B inhibitor, but referred to a MAO-B BLOCKER… INHIBIT and BLOCK are NOT equal in scientific language and BLOCK is generally used as the more "effective" word.
So lets sum up what we have
1. Betaine: very good at enhancing neurotransmitter synthesis (donating methyl groups to the synthesis process to form neurotransmitters, homocysteine remethylation, etc). Also, adjuvant for DNA polymerase and DNA sequencing, (MOA unknown). but it performs fairly well in weakening GC nucleosides bonding so that they can splice in RNA sequences and then not affect the reaction negatively. So this leads to Amino sequences, obviously. Now this is a part people have left out about TMG and I think we need to look in to it and understand it.
2. PEA constituents and homologs: release norep and dopamine (two of the most beneficially/easiest synthesized after homocystein remethylation). all the different PEA constituents in here work in similar pharmocokinetics but bioavailability, half lifes, efficacy, all differ. also it helps from a price point.
3. Extracts of Dendrobium. This will be subject to debate but just recently (within months) they have AGAIN changed the standard of what is believed to make up dendrobium. I could (and did for awhile) spend a lot of time looking up every "supposed" chemical in what we will now call DR (dendrobium) but it's useless as nothing will be known on the chemicals that we would be interested in as they are unique to DR. What IS known is that the stem portion of DR (what craze uses), 60-80% of the chemical extracts available from the stem are incredibly good in vitro at APA, so good, they actually performed quite well and OUT PERFORMED some standard units of the top performing drugs available on the market for APA.
4. NMT: RX821002 out performed it as an alpha-2 receptor antagonist but there is a reason RX isn't allowed on the market and interestingly enough NMT had a higher IC50 but somehow RX still had a better affinity. Keep that in mind as honestly that's a little off. NMT performed better than hordenine and caffeine; often used natural MAO-b inhibitors. SO we have a PRETTY GOOD natural MAO-B inhibitor that is holding its own against the big scripts. People are looking at this as solely the stim effect, but it's so much more than that.
5. Caffeine: Most should know the MOA of this and assume/predispose it's synergy. However, it may be important to note its specific effects on fatty acids and those effects' similarity to TMG's effects on fatty acids
Now lets connect the dots.
TMG and PEA have yet to be combined in effective doses and isomers in any other product (that I could find). I've already explained the synergy there.
NMT hasn't been heavily thought of as an MAO-b inhibitor , yet, mainly a stim. It'll INCREASE stim affects as an alpha-2 receptor antagonist (note MAO-B inhibitor is not the same as alpha-2 receptor antagonist but generally (if not always) if a compound is one, it is the other as well). But it also has its own stimulant activity, also again, a significant MAO-B inhibitor. So this is good for PEA as it's metabolized by MAO in a rather quick time frame.
BUT if we inhibit MAO-B effectively enough (and we’re coming to the conclusion that NMT does) then MAO synthesis has to occur in order for the drug reactions to be metabolized, otherwise their effects will still be in process. This is why taking say deprenyl and PEA together will yield hours of fun rather than just 30 minutes or so of PEA alone. Also note a powerful MAO-B such as deprenyl doesn’t have to be taken daily as its effect on MAO lasts multiple days due to it being an irreversible inhibitor. IIRC, somewhere along the lines of 3-5 days depending on dose and environment. So even if NMT is not a full blown IR inhibitor, it seems strong enough to have multiple hours of inhibiting effects. Also, being an A2 antagonist, norep will be readily released, even MORE neuro action. Could this be too much of a good thing?
Now as to why there should be some concern for this product…
APA action of it seems greatly emphasized. Sure it may give great pumps and blood flow, but in result, we have our possible side effects. There is such a thing as having too much APA where our INR reaches the whole number 5 area. There are reports of just simple daily servings of garlic raising INR enough over time to indicate bleeding. The most common place for that bleeding to occur in general for reference is the brain, thus explaining the reports of dizziness, blackouts, headaches, etc. Obviously we can look at a drug like warfarin and we have to be very careful as that causes MAJOR bleeding, but there are different levels of bleeding that don't cause as much “damage”, but cause the side effects and possibly over consistent usage cause short term/long term issues. That being said, it is entirely possible that this product has the ability to raise INR to the point of worry. With NMT and b-pea (and all the other pea's) being lumped in with aspirin in writings of studies on their effect on APA, plus caffeine, not to mention the darkhorse dendrobium who's majority stem extracts showed very promising APA affinity in vitro. So who's to say it can't do what garlic can do with daily use in itself with all those different compounds? Some of which, we know very little about. We don’t know what else is even in dendrobium stems, it's extracts were patented so quickly that everything about it is vague.
Dendrobium has been described as an analgesic multiple times. It's not directly stated anywhere, but the comparisons between the (still unknown) possible MOA's of say acetaminophen (remember, those effect the cannabinoid receptors.) Now we know the effect on the ECS of aspirin for instance is not drastic and we aren't even sure of the location of the analgesic effects specifically, but that's a possible MOA of that class of drug. is it possible in synergy or one of these compounds individually effects the ECS? We wouldn’t know as we cant even figure out if aspirin does or not and we have been studying it for how long? No one seems to have drawn this conclusion, but it's VERY possible considering the similarities between the compounds overall actions and the very little known about almost all the ingredients in this product. Maybe it's a derivative of the class of analine analgesics? Maybe it just has a similar MOA or overall effect? This is the most effective away to explain the pain killing effect and it ties together with all the other conclusions.
Another conclusion to piggy back off that and maybe add some substance to it, THC increases the effect of PEA 4 fold. Keep that in mind and in connection.
Now we look at the INCREDIBLE output of norep, dopamine, seratonin (to be specific and standard to what the studies point out). PEA specifically successfully releases norep and dopamine and will continue to do so until MOA is reestablished. PEA acts also very similar to amphetamines which also release NT's such as dopamine. Now too much of a good things is in fact, too much. Here comes the scary part.
Schizophrenia has yet to be completely understood, but a common treatment is dopamine agonists. It’s thought that dopamine agonists misfire and causes PART of the schizo issues (PEA also can be a hallucinogen. So antipsychotics have been noted to agonize the receptors and block them. Now as said earlier, PEA and amphetamines act on NT"s very similarly and when used they cause a sensitivity to dopamine. It’s referred to as supersensitivity to dopamine and a marked rise in the number of dopamine D2 receptors in the high-affinity state for dopamine. High affinity receptors coupled with incredible output of NT"s by the synergy of craze, COULD lead to dopamine misfiring, even chronically or short term after use is extinguished. If you tie all this together, it's a possibility that it could do SOMETHING due to this products aimed nature. The fact that vaughn described it as cocaine which is obviously similar to lidocaine, and lidocaine was mentioned in studies of NMT and the connections coke has with NT's like amphetamines, makes the conclusion make sense. Now, this isn’t saying normal use of pea and APA's will make you go schizo, this also isn’t saying abusing Craze will, but looking at how this product is formulated, how well it works syngeristically, how studies compare the different compounds to script drugs that have been extensively studied, we must at least take caution
Its alpha2 agonist abilities (a2 receptor binds to NT's and adrenaline, agonize the receptor and it can’t bind, therefore releasing adrenaline and its effects) obviously cause vasodilation, but if craze as a whole has any significant affect at all on b2 receptors (which was noted in some possible effects of the DR constituents if discerned correctly, and also possibly an effect of NMT) then that in turn would cause coronary vasoconstriction which would still increase the output of the heart and the energy it must expend to keep up with all the other effects of craze and pump enough blood. Not sure what effect this may have, but may raise heart rate to a significant degree, which also has been reported.
As you know, NT misfirings will affect mental productivity at different levels. We’ve explained the issue of nausea and cramping by acute bleeding, stimulants in general will obviously have their individual normal expected side effects so those are accounted for.
Some users have reported blurred vision or simply impaired vision. MAO Inhibitors may cause this effect (as we see above, lots of mao inhibition with Craze) and thus can lead to orthostatic hypotension.
So in conclusion, we’ve accounted for the "pain killer" claim. We’ve accounted for the few hours of feeling amazing and then the crash (typical of the actions we’ve described), and we’ve covered the withdrawal possibilities and we’ve accounted for the vision problems. Now everything above isn’t being stated as fact, but none of this was in their write up or thus far explanations of why they chose these compounds. This product is extremely effective because it's extremely synergistic. The problem is it may be TOO effective, causing TOO many reactions in sync with TOO many risks.