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Chemically induced LTP?

ciltep pde4 forskolin ltp

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#811 Nootr

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Posted 04 October 2012 - 04:57 PM

Side effects

Due to the primary metabolites of L-amphetamine and L-methamphetamine, selegiline shares many side effects seen with these sympathomimetic stimulants. Minor side effects such as dizziness, dry mouth, difficulty falling or staying asleep, muscle pain, rash, nausea and constipation have been seen. More serious side effects such as severe headache, tachycardia, arrhythmia, hallucinations, or difficulty breathing should be investigated by health professionals immediately.
Selegiline is a selective inhibitor of MAO-B; MAO-B metabolizes dopamine and phenylethylamine.
What is phenylethylamine responsible for? Is it amphetaminic substance?

Edited by Dan Brown, 04 October 2012 - 05:00 PM.


#812 gbpackers

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Posted 05 October 2012 - 10:38 AM

I just realized there was some confusion on the last page about my pramiracetam and lsat score comments.

I have been studying for the LSAT for a very long time.. over 6 months.. and in that time my score went from a 149 cold diagnostic to an average of 165 to and average of 171.. with my highest score being 176. In that time I have been experimenting with various nootropics.. mainly the different racetams.. different combinations of oxi, prami, and pir. I am not sure how much of my score improvement is attributable to the nootropics because I have put in a shitload of time and effort in improving my score and learning the test. My main problem was that I have trouble focusing and understanding what I am reading and sometimes have to read the same thing twice for it to enter my brain. For the past couple months where my scores have been in the 169-178 range I have been using the following regimen:

creatine + beta alanine + DAA
Taurine
Theanine
Bacopa + Rhodiola (not sure if this combo is good to take before tests or just leave it for nighttime minus the rhodiola. I haven't taken it before every practice test)
Pramiracetam (300mg before the start of a practice test, 50mg during the middle break)
D-serine (1.5g at start, 1.0g middle break)
Pregnenolone spray (20 sprays)
Multivitamins

Edited by gbpackers, 05 October 2012 - 10:40 AM.


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#813 Nootr

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Posted 05 October 2012 - 11:32 AM

Phenethylamine, similar to amphetamine in its action, releases NE and dopamine. Abnormally low concentrations of endogenous phenethylamine are found in those suffering from attention-deficit hyperactivity disorder (ADHD), whereas abnormally high concentrations have been discovered to have a strong, positive correlation with the incidence of schizophrenia. Phenylethylamine's half-life is five to 10 minutes. It is metabolized by MAOA,MAOB, aldehyde dehydrogenase, and dopamine-beta-hydroxylase. When the initial phenylethylamine brain concentration is low, brain levels can be increased 1000-fold when taking an MAO inhibitor (MAOI), and by 3-4 times when the initial concentration is high.
So what selegiline does is it increases levels of natural amphetamin - phenethylamine. That is what produces energizing effect.

#814 stablemind

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Posted 05 October 2012 - 05:12 PM

Has anyone found MGT to be significantly synergistic to this stack? I've read that it can improve learning, but it be even noticeable when added to this stack?

#815 Nootr

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Posted 05 October 2012 - 07:54 PM

Folks, I have just found out that melatonin can be the cause of depression and I think that it neutralizes the action of all energy-producing drugs like selegiline, amphetamin and ciltep stack. I found out that it inhibits production of libido hormones and even the human growth hormone. But HG hormome is the best rejuvenating hormone. So melatonin does not stop ageing. On the contrary it may promote ageing. I have been melatonin user since 2005 and now i think that it contributed much to my depression and lack of energy. And the usual dose of melatonin in tablets is 3 mg while the normal dose of a grown-up is 30 microgram which means that the tablet contains 100 of normal doses. Also melatonin inhibits cAmp. I don't yet know if it is good or bad but since you say that ciltep stack increases cAMP, it should be bad coz cAMP is important for making us alert and motivated. I am gonna reduce melatonin dose to 300 microgram per night!

And what is also important is that melatonin increases GABA levels and seratonin levels which promote development of depression. GABA anxyolitics actually cause depression instead of supressing it.

Edited by Dan Brown, 05 October 2012 - 07:58 PM.


#816 Nootr

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Posted 05 October 2012 - 08:28 PM

At the same time:
Melatonin receptors appear to be important in mechanisms of learning and memory in mice,[73] and melatonin can alter electrophysiological processes associated with memory, such as long-term potentiation (LTP). Brain-derived neurotrophic factor (BDNF), its production stimulated by melatonin, is an braincell adaptogenic that helps prevent mental regression.

#817 Nootr

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Posted 05 October 2012 - 09:03 PM

Melatonin in combination with deprenyl significantly counteracts hydroxyl radical production associated with dopamine autoxidation in the brain, and the combination effect is significantly greater than the effect of either agent alone [JOURNAL OF PINEAL RESEARCH; Khaldy,H; 29(2):100-107 (2000)]. - Wow, it seems that melatonin synergizes with selegiline! So it is good!

Melatonin enhances memory consolidation under psychological stress [PSYCHOPHARMACOLOGY; Rimmele,U; 202(4):663-672 (2009)].

<a name="negative">For melatonin, more is not better. Blood concentrations which are ten times normal youthful levels can cleave heme molecules to liberate iron and induce oxidative stress [NEUROCHEMISTRY; Clapp-Lilly,KL; 12(6):1277-1280 (2001)]. Even higher levels of melatonin concentrations deplete reduced glutathione levels [LIFE SCIENCES; Osseni,RA; 502:127-131 (2001)].

Although supplement doses a hundred times the typical 3 mg per day have proven to be safe, higher doses may be unnecessary or even harmful. Doses in the 1 mg to 5 mg range should be safe and sufficient insofare as these doses produce blood levels 10 to 100 times higher than the usual nighttime peaks [THE NEW ENGLAND JOURNAL OF MEDICINE; Brzezinski,A; 336(3):186-195 (1997)].

So the dose of 1 mg is the optimal.

Edited by Dan Brown, 05 October 2012 - 09:14 PM.


#818 X_Danny_X

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Posted 06 October 2012 - 12:31 AM

Dan Brown, I am confused with your posts. First Melatonin is bad and now taking 1 to 5mg is good which also helps promote memory and learning along taking it with Selegiline. So you take Melatonin and Selegiline together at night or during the day?

Also I am wary of taking a stimulant which helps keep you awake and a sleeping agent at the sametime.

#819 golden1

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Posted 06 October 2012 - 02:48 AM

Benzodiazepine withdrawal apparently increases LTP.... lol... In a bad way though, from what I see.

#820 Nootr

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Posted 06 October 2012 - 03:07 AM

I was confused too. But now I have come to the conclusion that melatonin in the dose of 1 mg per night is OK and should not induce daily sleepiness and lack of energy. Moreover it sinergizes with selegiline acting stronger as anti-oxidant. And as mentioned above melatonin by itself promotes LTP by improving quality of sleeping and by great antioxydant and neuroprotevtive effect. Melatonin turned out to be the medium to prevent Alzgeimer's disease by prevening deposits of tau-protein. If taken during the day while physical exercises it promotes release of human growth hormone. While if taken at night it on the opposite inhibits production of human growth hormone - that's why NOT for teenagers. Dose of 1 mg of melatonin equals to 10 endogeniously produced doses of 20 year old person. So its still large but not large enough to cause daily sleepiness.
Selegiline was developed as psychistimulator combining both amphetamin and MAOI properties. It is even included in extasy pills.
I don't know what happened but today i had a burst of energy and insomnia now. I have never had insomnia like that before, only in cases of extreme smoking. SO i took dose of seleginiline of 1.25 mg a week ago. The effect still continues. I took bacopa each day before bed in 2 or fold dose. I took 1\4 of pill of nicotinic acid today and something happened. I feel energy through the body. My limbs seem to have a kind of hyper-tension. Seems I have found new biological stimuling stack. I dont know what it is. seems that selegiline + each day of melatonin + each day of bacopa + each day of coffee and finally + pill of nicotinic acid produce this energy and insomnia and energy. I hope I will fall asleep finally. I am afraid to have serotonin syndrome.

#821 Nootr

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Posted 06 October 2012 - 11:06 AM

Fell asleep at 6, got up at 13. Feeling of fully refreshed but veins on hands are protruding which is not typical of me because I have generally hypotension. Avoided coffee since morning. At night before falling asleep had twitching of limbs. Still feel the energizing effect. Have taken magnesium several times yesterday and today. Usually it lowers blood pressure but in this case I do not feel the effect. However it seemed to help me to fall asleep.
Ordered forskolin and artichoke. So will try ciltep stack in a couple of weeks and to compare against selegiline+bacopa+coffee+melatonin.

Have just measured blood pressure. Reads 100\67. So probably I have not had hypertension. But why do i feel energy in limbs and had twitching?

Edited by Dan Brown, 06 October 2012 - 11:18 AM.


#822 hephaestus

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Posted 06 October 2012 - 07:22 PM

I believe the shakiness is caused by the stimulants effecting greater glutamate release than your GABA can keep up with. Theanine and picamilon both help when I am shaky, as does drinking water and eating usually. It is sometimes accompanied by anxiety, but only rarely as I am generally a very calm person. I was reading a thread the other day about someone trying to treat benzodiazepine withdrawal and it was mentioned that ashwagandha, bacopa, valerian root, and gotu kola all contain gaba agonists, or increase gaba production, so any of them might help.

Some people get strong blood pressure rebound effects after coming down from stimulants.

Edited by hephaestus, 06 October 2012 - 07:32 PM.


#823 X_Danny_X

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Posted 06 October 2012 - 11:30 PM

so you take 1 melatonin table with selegiline during the day and you get a stronger effect.

#824 dreth7

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Posted 07 October 2012 - 04:44 AM

So is Magnesium Theonate recommended with this stack?

#825 Nootr

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Posted 07 October 2012 - 03:06 PM

I did not mean that it is compulsory to take melatonin with selegiline. I just came across the facts that
1) melatonin is effective against Alzgeimer
2) if taken at daytime it increases human growth hormone
3) it induces LTP due to protection of neurons if taken at bedtime
4) scientists claim it does not effect alertness if taken at day but i would avoid taking at day time

And do not take more than 1 mg of melatonin per day. Otherwise it inhibits iron circulation in organism thus making some harm.

Selegiline on its own is the best stimulator and mood improver. I have not taken adderall or ciltep stack to compare. Just it immediately stops depression for me and the effects last more than a week. So selegiline is very cheap as compared to other drugs if not taking into account its side effects which I still don't know how to overcome.
3mg of melatonin induced depresseion and lack of energy and this effect was so strong that it lead to the following:
1) difficulty to see vivid dreams due to too deep sleep or to remember them
2) lack of energy at daytime which is bad for career
3) inhibition of honadotropes resulting in lowering libido

Endogenous melatonin peaks at the age of 6. The dose of 1 mg is 5 times greater than endogenious peak. That should be quite enough to use its antioxidant and anti-ageing properties.

As selegiline is at the same time amphetamin and IMAO it is quite enough to make you energetic and more contect with life. I notice such effects as more sharp vision, euphoria, almost absence of negitive thoughts. Ability to concentrate on the subject and not caring for the bad things that surround you in the social environment.
So instead of taking tranquilizesrs and antianxyety drugs which cause sedation and finally depression and encephalopathia I am going to take psychostimulators and neural-protective means which at present are selegiline (1mg per weak), bacopa (before bed), melatonin (before bed), coffee in the morning, and probably afobazole (for one month) to restore GABA receptors after spoiling them by phenibut. I think that is quite enough to enjoy life.
And if you are taking selegiline, don't take MB because it will spoil selegiline's effect. Also avoid any other antidepressant supplements. I noticed that any additional supplements can diminish selegiline's effects. As for nootropics I am not sure if they combine well with selegiline. However GOOD MOOD is the best nootropic ever existing.

An interesting fact that I have read is that people with deficit of concentration (depressive people) suffer from lack of endogenious fenethylamine (natural amphetamin) while people with shizophrenia have too much of endogenious fenethylamine. Due to selegiline's ability to be turned in the body into fenethylamine and MAOI which also protect fenethylamine from decay, the level of fenethylamine normalizes and even becomes closer to that of shizophrenics which changes your levels or energy and creates a protective shield and such a wonderful property as impulsiveness. So it restores feelings and emotions and helps to eliminate feeling of emptyness.

#826 hephaestus

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Posted 07 October 2012 - 04:46 PM

The racetams potentiate stimulants pretty well in my experience.

#827 Nootr

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Posted 07 October 2012 - 06:30 PM

And what about noopept? Have you tried it with stimulants?

#828 golden1

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Posted 07 October 2012 - 07:44 PM

Selegiline was nothing special for me, it had effects but none were really useful.. unless you were quitting amphetamine or such, then it helps with the withdrawal very well. my experience.

Noopept adds to stimulants, but in my experience aniracetam or piracetam were the most potentiating.

Edited by golden1, 07 October 2012 - 07:45 PM.


#829 hephaestus

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Posted 07 October 2012 - 08:57 PM

Yeah noopept seems to work well too, I find it pretty stimulating on its own even.

#830 stablemind

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Posted 07 October 2012 - 09:09 PM

So is Magnesium Theonate recommended with this stack?


Yes it's been said that it's recommended however there aren't many anecdotes showing it's synergy. By itself, however, there are plenty of anecdotes.

#831 gizmobrain

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Posted 07 October 2012 - 09:21 PM

Earlier in this thread, I recommended Magnesium L-Threonate as part of a night time recuperation stack. It should help with any NMDA down-regulation caused by whatever stimulant you use as part of the stack (especially those that use any amphetamine based stimulants).

We' class='bbc_url' title='External link' rel='nofollow external'>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749993/]We examined the turnover and trafficking of NMDA receptors and found that chronic exposure to the psychostimulant amphetamine (AMPH) induced selective downregulation of NMDA receptor NR2B subunits in the confined surface membrane pool of rat striatal neurons at synaptic sites. This downregulation was a long-lived event and was a result of the destabilization of surface-expressed NR2B caused by accelerated ubiquitination and degradation of crucial NR2B-anchoring proteins by the ubiquitin-proteasome system. The biochemical loss of synaptic NR2B further translated to the modulation of synaptic plasticity in the form of long-term depression at cortico-accumbal glutamatergic synapses. Behaviorally, genetic disruption of NR2B induced and restoration of NR2B loss prevented behavioral sensitization to AMPH. Our data identify NR2B as an important regulator in the remodeling of excitatory synapses and persistent psychomotor plasticity in response to AMPH.

→ source (external link)


' class='bbc_url' title='External link' rel='nofollow external'>http://www.ncbi.nlm.nih.gov/pubmed/20152124']
Learning and memory are fundamental brain functions affected by dietary and environmental factors. Here, we show that increasing brain magnesium using a newly developed magnesium compound (magnesium-L-threonate, MgT) leads to the enhancement of learning abilities, working memory, and short- and long-term memory in rats. The pattern completion ability was also improved in aged rats. MgT-treated rats had higher density of synaptophysin-/synaptobrevin-positive puncta in DG and CA1 subregions of hippocampus that were correlated with memory improvement. Functionally, magnesium increased the number of functional presynaptic release sites, while it reduced their release probability. The resultant synaptic reconfiguration enabled selective enhancement of synaptic transmission for burst inputs. Coupled with concurrent upregulation of NR2B-containing NMDA receptors and its downstream signaling, synaptic plasticity induced by correlated inputs was enhanced. Our findings suggest that an increase in brain magnesium enhances both short-term synaptic facilitation and long-term potentiation and improves learning and memory functions.

→ source (external link)

Edited by zrbarnes, 07 October 2012 - 09:27 PM.


#832 Nootr

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Posted 07 October 2012 - 10:29 PM

Will magnesium acetate work like Magnesium L-Threonate in restoring receptors?

#833 gizmobrain

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Posted 07 October 2012 - 10:41 PM

Will magnesium acetate work like Magnesium L-Threonate in restoring receptors?


The Mg2+ ion is what is inhibiting NMDA receptors. This alone may be responsible for NMDA upregulation, however, the l-threonate molecule is not inert. It is a metabolite of ascorbic acid (vitamin C), which has inhibitory functions within the brain:

Because' class='bbc_url' title='External link' rel='nofollow external'>http://www.pnas.org/content/97/4/1891.full']Because ascorbic acid (AA) is concentrated in synaptic vesicles containing glutamic acid, we hypothesized that AA might act as a neurotransmitter. Because AA is an antioxidant, it might therefore inhibit nitric oxidergic (NOergic) activation of luteinizing hormone-releasing hormone (LH-RH) release from medial basal hypothalamic explants by chemically reducing NO. Cell membrane depolarization induced by increased potassium concentration [K+] increased medium concentrations of both AA and LH-RH. An inhibitor of NO synthase (NOS), NG-monomethyl-l-arginine (NMMA), prevented the increase in medium concentrations of AA and LH-RH induced by high [K+], suggesting that NO mediates release of both AA and LH-RH. Calcium-free medium blocked not only the increase in AA in the medium but also the release of LH-RH. Sodium nitroprusside, which releases NO, stimulated LH-RH release and decreased the concentration of AA in the incubation medium, presumably because the NO released oxidized AA to dehydro-AA. AA (10&minus;5 to 10&minus;3 M) had no effect on basal LH-RH release but completely blocked high [K+]- and nitroprusside-induced LH-RH release. N-Methyl-d-aspartic acid (NMDA), which mimics the action of the excitatory amino acid neurotransmitter glutamic acid, releases LH-RH by releasing NO. AA (10&minus;5 to 10&minus;3 M) inhibited the LH-RH-releasing action of NMDA. AA may be an inhibitory neurotransmitter that blocks NOergic stimulation of LH-RH release by chemically reducing the NO released by the NOergic neurons.

→ source (external link)


Does the L-threonate metabolite work the same as ascorbic acid? Probably not, but since I can't find any studies on Magnesium Acetate causing NMDA upregulation, I can't really answer your question.

#834 nidhogg

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Posted 09 October 2012 - 02:12 PM

Noone mentioned nicotine?

#835 Nootr

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Posted 09 October 2012 - 03:23 PM

Nicotine is toxic and bad for skin. I would avoid it. What about hordenin? Has anyone tried it in ciltep stack as the stimulanting component?

Edited by Dan Brown, 09 October 2012 - 03:24 PM.


#836 nidhogg

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Posted 09 October 2012 - 05:29 PM

Nicotine is as bad for the skin as an equivilent dose of acetylcholine, if its the nAChR vasoconstricting effect you are refering to. Nicotine does not equal smoking
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#837 Nootr

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Posted 09 October 2012 - 09:20 PM

I mean that it results in splitting collagen apart and makes your skin age more quickly. That's why smokers have wrinkles. In addition to this is it a toxic substance 3 times more toxic than potassium cianide.

#838 Mr. Pink

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Posted 09 October 2012 - 09:46 PM

nicotine is also addictive which is one of the worst things for brain health long term, but as people here regularly take amphetamine as a cognitive enhancer, it's not a problem. addiction is not just genetic, it can be conditioned through repeated self administration of addictive substances. psychological addiction is much stronger and long lasting than physical tolerance/withdrawl. it's what causes relapse. you're not immune. /rant

Edited by Mr. Pink, 09 October 2012 - 09:47 PM.

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#839 nidhogg

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Posted 10 October 2012 - 12:51 PM

Im sorry but if you have an addictive personality i would advise you to refrain from using any nootropics, because those who actually work and make you feel enlightened in any sense will get you hooked. And once you stop you will develop psychological withdrawal

You'd think people on these forums had more sense but no, "nicotine is 3 times more toxic than potassium cyanide" LOL

The amount of random shit, with zero scientific research behind them, that people consume on these forums would make nicotine seem like a kid experimenting with chocolate

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#840 Ames

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Posted 10 October 2012 - 06:14 PM

Im sorry but if you have an addictive personality i would advise you to refrain from using any nootropics, because those who actually work and make you feel enlightened in any sense will get you hooked. And once you stop you will develop psychological withdrawal


It would be a large understatement to say that the term 'nootropics' is loosely defined, and so it certainly cannot be said that anything anyone considers a 'nootropic' should be avoided if you have an 'addictive personality' (another pseudo-clinical term with a very loose definition). I would be okay with the term 'nootropic' being thrown out, along with 'addictive personality', as they are both terms that are sourced from bro-science in my opinion.

What is a nootropic? An AMPA modulator? Something that improves LTP? Something that corrects an imbalance, temporary or permanent? Something that acts as a prophylactic against a large amount of predictable future neurophysical or emotional stress? A stimulant? Something that causes neurogenisis? Something that subjectively just makes you think better, or remember better without a clear explanation as to how it is accomplished? Something that specifically counteracts an addiction that was creating a loss in cognitive ability?

A nootropic will be something different for everyone, especially those with a specific pathology, like many/most on this board have, addiction included. Many substances here, that subectively/objectively act as nootropics for an individual, do so specifically by lessening addiction to, sub-optimal self medication with, or damage caused by other substances.

You'd think people on these forums had more sense but no, "nicotine is 3 times more toxic than potassium cyanide" LOL


It's not fair to lump "everyone" in to your admonishment in regard to a comment made by one person. Many people here are exceptionally reasonable, educated, and careful, even more so than most MDs (careful). I don't know of too many MDs, and I know more than a few personally, who take the time to read the full research regarding everything that they prescribe, especially in the context of other regulated or non-regulated options out there. Of course, there are exceptions and a select few fringe individuals on this board tend toward the reckless, choose to chase a nootropic buzz, or choose the shotgun approach without being aware of the science or the consequences. After all, the board itself is not password protected and is free to all to read who can use google. However, especially when the recklessness of modern commonly prescribed medications is taken into account, an example being long term adderall use amongst many others, then the approach by most here, who are attempting to find more sustainable and less long-term damaging solutions through a largely careful and responsible methodology, should escape your finger pointing.

The amount of random shit, with zero scientific research behind them, that people consume on these forums would make nicotine seem like a kid experimenting with chocolate


Addressed above, but also patently untrue (especially with the lazy accusation of "zero research being behind them"): the term 'random shit' being wholly non-specific. Again, "people" on these forums covers a lot of "people", most of whom don't deserve your rush to judgment or other wise blind categorization based on relative unfamiliarity with specific personalities here and your skimming the forum.

Persoanlly, I'd be a heck of a lot more sick/damaged/less functional than I am if it weren't for this forum. I'm able to live my life becasue of it.

Edited by golgi1, 10 October 2012 - 06:32 PM.

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