The drug itself is fairly nontoxic, but that's not where the damaging effects of drugs start from.
It's the stress. A lot of people will take drugs be it mdma, lsd, amphetamines, even weed, and have a "bad trip", or some will even have a very good time, While the drug itself is relatively non toxic that is not what causes all the problems, drugs like MDMA, especially in a rave setting, very little food or drink, dancing past the point of normal exhaustion is EXTREMELY stressful on the body. People take the drugs and then think "it must have caused brain damage and that's what's causing my problems" but that's not really the case.
It's the high stress that is caused to the body. This throws the body out of homeostasis. When your body and your stress response system, your hpa axis, are driven too far from resting point it becomes very hard for your body to return to normal. Not only this but once it's driven too far out of balance it becomes a negative cycle because your body becomes even more sensitive to stress. Most people's stress responses are robust and can recover from it but then there are many others that aren't. The same thing can, and I've seen it happen with other types of highly stressful situations. A person has a traumatic experience, rape, loss of loved one, victim in war etc..
If you look up HPA axis dysfunction you'll find lots of information on it.
Hpa axis dysfuntion you will feel very apathetic, usually hyper-vigilant but at the same time very tired. Most have anxiety and derealization and depression. Your HPA axis is the center for your emotional well being and happiness, every time you are excited or experience a positive feeling or emotion, your hpa axis is activated. When this is thrown out of balance the world can seem very black and white and you'll feel almost a detached feeling to the world around you.
There's also some speculation of amygdala trauma, but I won't go into that.
Pretty much to get your body's stress response back to normal, you need to cut out all forms of stress and keep stress to a minimum. Try your very best to get up and go to sleep the same time every day, get a good amount of exercise, don't overdue yourself. Avoid stressful situations or scary situations, Eat well, balanced meals. Meals should be:
1) Eat before 10:00 a.m.
2) Eat frequent, small meals: 6-8 am (breakfast), 12 noon (lunch), Snacks - 10am, 3pm and Bedtime
3) Eat 30-40% whole grains, 30-40% Vegetables (50% should be raw), 10-15% Beans, seeds & nuts, 10-20% animal foods, 5-10% fruits
Of course avoid all drugs, unless you can't sleep and need to take something for sleep.
Also.. try to get a good magnesium supplement, preferably citrate, NEVER oxide. As well as a high quality omega 3, like krill oil.
I would also avoid foods like milk and gluten. Other things that could help are low dose hydrocortisone, or licorice.
If you follow these things for a few weeks and I KNOW you will feel better. It may take some time to feel 100% better, but I know that you will feel a great deal better.
If your stress system(s) are out of wack - there' two new nootropic/longevity peptides that can help with that: Semax (ATCH Fragment - sounds contraindicated but it's explained below why despite being an ACTH fragment - it actually has anti-anxiety properties as well as cognitive enhancement (much subtler than an AMPAkine or Racetam's - but the changes are on the epigenetic/mRNA level, fixing the homeostasis of your dopamine and serotinogic systems (without activating them surprisingly - it potentiates d-amphetamine but has no dopaminergic activity on its own, same with serotonin and serotinergic system (through activating the TrKb Receptor - among other things). It's really helped me alot, recovering from MDMA mind you - which I am atm so I know how you feel - but in general with my anxiety, PTSD, depression and overall quality of life
SmarterNootropics said:
Semax is a heptapeptide developed by the Institute of Molecular Genetics, Russian Academy Of Science (IMG RAS)[1]. Semax was likely first developed in the 1980’s to early 1990’s and received authorization for marketing in 1994.[1]. In Russia, Semax is used to treat stroke, brain damage following ischemia, optic nerve disease and as a treatment for various cognitive disorders[2]. Additionally Semax has been shown in one human study to directly enhance cognitive function and favorably alter EEG bands.
Structure
Structurally, Semax is an analog of adrenocorticotropic hormone 4-10 (ACTH 4-10), a fragment of ACTH known for its neurological effects and absence of hormonal effects. While ACTH 4-10 sequence of amino acids is Met-Glu-His-Phe-Arg-Trp-Gly, Semax is slightly different; Met-Glu-His-Phe-Pro-Gly-Pro.
The addition of the PGP sequence to the C-terminus of ACHT 4-10 is thought to be the reason Semax is so biologically active and possesses a more prolonged effect than ACHT 4-10 [3]. While the natural 4-10 fragment is degreaded into amino acids in the blood, Semax is degraded into a more stable intermediate peptide – Glu-His-Phe-Pro-Gly-Pro.
Benefits of Semax
Cognitive Enhancement
A 2 day study of Russian power plant workers tested the efficacy of Semax with a number memorization task.[4] In total the test lasted around 15 minutes and one was performed at the beginning and end of the workers’ shifts on days 1 and 2 respectively.
A dose of 1mg was given intranasally on day one around 1 hour prior to testing and on day two shortly after the morning’s tests. A placebo group was also requested to perform the same task.
Semax dramatically decreased the number of incorrect responses on days one and two while the placebo group’s error rate actually increased (see above). Semax also attenuated a decrease in correct performance scores compared to placebo.
Mood
Animal studies reveal Semax is a potential mood enhancer and anxiety reducing compound. A study of in rats revealed Semax to be capable of attenuating CCK-4 induced stress and depression, while not affecting rats administered placebo.[5]
CCK-4 is a potent neuropeptide capable of inducing anxiety in humans and animals, so much so, CCK-4 is used to induce panic attacks when researchers are searching for treatment options. Essentially this study demonstrated that rats given nothing or Semax were similar in mood states, while rats given CCK-4 were markedly more depressed and anxious during a forced swim and maze test.
The combination of both CCK-4 and Semax brought rats back to placebo levels in certain parameters of mood, suggesting Semax is capable of treating an anxious and depressed state, while leaving a “normal” state unchanged.
A study abstract featured in the international journal of psychophysiology discussed how both Semax and Selank were capable of producing sedative effects and relieving some effects of mental illness in primates. The full study doesn’t appear to be available online as of July 2014. [6]
Another abstract featured in the Journal for European Neuropsychopharmacology briefly discussed a study with Semax involving delirium following alcohol withdrawal. Semax was found to reduce the time of acute psychotic disturbances (1-5 days) compared to placebo (1-9 days) when administered at a dose of 0.6mg per day intranasally. [7] Following acute symptoms subsiding, Semax at 0.3mg/day was found to improve cognitive function and decrease asthenic disorders relative to placebo. No side effects were noted.
Migraines
A study conducted in 1995 sought to test the analgesic activity of Semax and if it could be suitable for headache and migrane relief. The study featured 3 groups of patients; group 1 was 12 individuals suffering from migraines, group 2 included 16 patients suffering with trigeminal neuralgia while group 3 included 9 patients suffering with dental plexalgia.
A single dose of 5mcg/KG Semax was found to be helpful for the severity and subjective perception of pain measured by the modified pain sensitivity test (MPST) for both dental plexalgia and migraine. Frequency of pain attacks was not reduced. Acute effects were noted in as little as 30 minutes with peak effects being found at 60-90 minutes.
Potentiation Of Stimulants
Semax has been found to directly enhance the dopamine release induced by dextroamphetamine in rodents: 20 pmol/ml extracellular DA vs 36-38 pmol/ml with Semax added.
Semax was also found to enhance dextroampethamine increased locomotor activity when compared to dextroampetamine alone (182% vs 261%).
Interestingly Semax alone did not alter locomotor or extracellular DA levels, suggesting a potentiation effect of the dopaminergic system rather than Semax being a direct stimulant.
Semax’s Mechanism Of Action
BDNF and NGF (Brain Derived Neurotrophin Factor & Nerve Growth Factor)
In glial cell cultures, both BDNF and NGF levels were increased 8 fold and 5 fold following exposure to Semax [8]. In rodents, Semax has been shown to increase BDNF and trkB levels by 1.4 and 1.6 fold respectively [9]. Further research has shown intranasal administration of Semax is able to increase BDNF in the rat brain [10].
Melanocortin Receptor Interactions
The melanocortin system is involved with a diverse number of functions in the body, including energy balance, food intake, immunomodulation and cardiovascular function[11]. Additionally the MC4 receptor is thought to play a role in emotional behavior and the stress response. [12]
ACHT 4-10, the fragment that Semax is based upon, is a melanocortin 4 (MC4) agonist[13] and is considered anxiogenic. Semax has been considered to be an antagonist of the mc4 receptor given its anxiolytic effects[14][15]. These anxiolytic effects may be related to activation of the serotonergic system.
Serotonin
A study involving two groups of animals (mice and rats), measured striatal and hypothalamic levels of dopamine, serotonin and their respective metabolites following Semax injection.
A rise in hypothalamic and striatal 5-HIAA levels were noted both 30 and 120 minutes following Semax injection in the mice group indicating an increase of serotonin turnover.
The second group, involving rats, noted a clear increase of striatum 5-HIAA, with 0.6mg/kg being more pronounced than 0.15mg, but both being statistically significant. Researchers speculated that the effects of Semax on the serotoninergic system may be related to melanocortin receptor antagonism.
A study of rodents being administered CCK-4, a panic inducing; anxiogenic peptide demonstrated Semax was able to attenuate the stressor effects of the compound. Given that this is traditionally done with SSRI drugs and a reduction in serotonin turnover typically gives rise to anxiety and depression the authors speculated that Semax operates to reduce anxiety by enhancing serotonin turnover. [5]
Alpha Brain Waves
Semax has been shown to alter EEG in humans during both a cognitive test and a hyperventilation challenge. During a cognitive test, Semax significantly reduced delta brainwave activity and increased the relative power of alpha and beta brain rhythm (4). Image below.
During a hyperventilation challenge, Semax prevented negative EEG changes (4). The placebo group experienced an increase in delta and theta brainwaves and a decrease in alpha 1 and 2 brainwaves and the administration of Semax 45 minutes prior nearly totally prevented the negative brainwave changes.
Safety
Semax would appear to be safe and nontoxic. In Russia, Semax is included in the list of vital and essential drugs (VED) [16], where it Is approved for a number of medical conditions including stroke, cognitive disorders and migraine.
In Russia, Semax has been tested extensively and has featured in a number of human clinical trials and has been reported to be free of side effects and hormonal activity. [1] [4][8].
References
[1]
http://old.img.ras.ru/Semax1-e.htm
[2]
http://www.ncbi.nlm.nih.gov/pubmed/11569188
[3]
http://www.ncbi.nlm.nih.gov/pubmed/16212268
[4]
http://onlinelibrary.wiley.com/doi/...9609)19:2<115::AID-NRC171>3.0.CO;2-B/abstract
[5]
http://www.ncbi.nlm.nih.gov/pubmed/20387390
[6]
http://www.deepdyve.com/lp/elsevier...of-Semax-and-selank-in-primates-at-gHqfNvoDEw
[7]
http://www.researchgate.net/publication/247138403_P.6.020_
Use_of_the_neurometabolic_drug_Semax_for_complex_treatment_of_alcohol_delirium
[8]
http://www.scirp.org/journal/PaperInformation.aspx?PaperID=40560#.U9VYWfldVWg
[9]
http://www.sciencedirect.com/science/article/pii/S0006899306022955
[10]
http://link.springer.com/article/10.1023/A:1025177812262
[11]
http://ajpendo.physiology.org/content/284/3/E468.long
[12]
http://www.ncbi.nlm.nih.gov/pubmed/15740781?dopt=Abstract
[13]
http://www.ncbi.nlm.nih.gov/pubmed/21629206
[14]
http://link.springer.com/article/10.1023/B:DOBS.0000017114.24474.40
[15]
http://www.ncbi.nlm.nih.gov/pubmed/7895772
[16]
http://mashkovsky.ru/tiki-index.php?page=Семакс
and the other peptide is Selank (from the same Russian Institute of Molecular Biology) an analog of Tuftsin (a naturally occouring peptide in the human body that controls macrophages and the like, the garbage compactors of human biology (macrophages is only one I forget the others atm)
Which also just passed the final trials (Semax is already prescribed in russian and the ukraine) Selank is just waiting mass production I beleive.
SmarterNootropics said:
Selank
Other names
Selank Peptide: L-threonyl-L-lysyl-L-prolyl-L-arginyl-L-prolylglycyl-L-Proline
Important Information
Dosage Guide
Generally 250-500mcg taken 1-2 times per day.
Making a Selank Nasal Spray
This can be done easily enough with a metered nasal spray.
A great guide is found here.
Selank is not orally bio-available, as it’s a peptide which would be hydrolyzed and broken into it’s constituent amino acids in the gut. As such, the two methods of administration are intranasal and subcutaneous injection. If you purchase lyophilised / freeze dried selank powder. it’s generally stable for 3 months, though we’d advise refrigeration where possible.
Lyophilised selank will require reconstitution with bacteriostatic water before being suitable for injection or intranasal administration.
Background Information
Selank is an anxiolytic heptapeptide drug produced by the Institute of Molecular Genetics of the Russian academy of sciences (IMG RAS). It is considered to be an anxiolytic or a substance with anti-anxiety effect.
Selank is a synthetic analog of the endogenously produced peptide Tuftsin and is known to be capable of improving and positively altering the immune system, which classifies selank as immunomodulatory [1].
Semax, another heptapeptide nootropic that was also developed by researchers at the IMG RAS, is a drug closely related to Selank that has been approved for human use in both Ukraine and Russia. There have been many reports from researchers and users that indicate that Selank is a more effective alternative than Semax. Selank however, has recently completed stage III clinical trials in Russia and is awaiting to get the green light for release to human use.
Selank’s Method of Action
Immunomodulatory
From a purely pharmacological standpoint, selank mimics a lot of the effects of tuftsin which is the endogenous peptide it is based upon. These effects include the balance of T helper cells and the modulation of the expression of Interleukin-6. (4)
Additionally, there is evidence that suggests selank may modulate the expression of brain-derived neurotropic factor (BDNF) (3).
Serotonin, Noradrenaline and Dopamine Modulation
Selank’s mechanism of action is suspected to be related to the increase of serotonin. Serotonin influence’s appetite, supports a positive mood, and regulates the sleep and wake cycle. It is also well established that a serotonin deficient state can lead to depression, difficulty sleeping, and lack of an appetite.
A study on mice to unveil the effects of selank on neurotransmitter monomines and their metabolites showed significant differences in the content of dopamine, serotonin, norepinephrine, and in the levels of their hypothalamus, hippocampus, and frontal cortex (1). Further research supports selank’s serotonin raising ability (2) (6).
Selank and tuftsin were also shown to support serotonin levels despite rats being pre-treated with the serotonin synthesis inhibitor p-chlorophenylalanine. Serotonin metabolism was enhanced within 30 minutes of selank administration, however tuftsin was unable to raise 5-HT levels. (8).
Rodents exposed to 6-hydroxydopamine, a neurotoxin which damages the catecholaminergic system, had cognitive processes restored with selank (7).
Selank Benefits
Antidepressive Effects (Animal Study)
A study of mice genetically bred to suffer with depression demonstrated selank’s ability to fight adhedonia and restore pleasure seeking behaviors. Administration of selank increased sucrose self administration and reduced immobility during a forced swim test (9).
Anxiolytic / Anxiety Reducing
One study involving 62 patients with generalised anxiety disorder (GAD) sought to compare selank to a benzodiazepine treatment. 30 patients were treated with selank, while 32 with benzodiazepines, Remarkably, efficacy for both drugs was similar, however researchers noted selank carried anti-fatigue effects. (5). Full details on this study are difficult to obtain, as it was conducted in Russia and only the abstract has been indexed in pubmed.
Another study tested the immunomodulatory effects of selank, given that it’s endogenous “cousin” peptide, tuftsin, is primarily related to immune function. Selank was administered to patients with generalised anxiety disorder for 14 days, after which, it was noted that selank supressed IL-6 levels of patients with depression, while leaving healthy control subjects unaffected. T-helper cell (Th1/Th2) cytokines were also modulated in patients with GAD (4)
Selank as a Nootropic / Cognitive Enhancer
One animal study tested selank vs saline placebo during a food reward task that involved learning and memory. While specific study details are unclear, as the research was conducted in Russia, the researchers concluded that selank increased memory consolidation and this was primarily though to occur through a serotonin increase (2).
An animal study of adult rats showed Selank was able to compensate for hypoxia induced cognitive deficit and the subsequent lowering of serotonin and noradrenaline (6).
References
http://www.ncbi.nlm.nih.gov/pubmed/19093364
http://www.ncbi.nlm.nih.gov/pubmed/20919548
http://www.ncbi.nlm.nih.gov/pubmed/18841804
http://www.ncbi.nlm.nih.gov/pubmed/18577961
http://www.ncbi.nlm.nih.gov/pubmed/18454096
http://www.researchgate.net/publication/6422962
http://www.deepdyve.com/lp/springer-journals/effect-of-selank
http://www.ncbi.nlm.nih.gov/pubmed/19803361
http://www.ncbi.nlm.nih.gov/pubmed/18661785
The parts I bolded and italicized would directly help - hypoxia can be a side effect of too much MDMA (or an stimulant) esp. if you have pre-existing hypertension. And the first one is almost exactly what you're looking for - they used a potent neurotoxin that irrevocably damages your catecholamine system on the rats and within a few administrations of the peptide, Selank had reversed all damage.
Other ways to clear up your brain fog (might not be a good idea but maybe it is aslong as you get Citicholine or Alpha GPC) but Piracetam or another lower-level racetam like oxiracetam or perhaps Aniracetam might be best as its one with the most anti-anxiety properties aswell (not like pramiracetam or phenylpiracetam - and I certainly wouldn't mess with an AMPAkine like Sunifiram atm even though I happen to like Sunifiram)
Lots of potent antioxidants (I'm taking trans-resevatrol, melatonin at night to help restore serotonin levels and both act as potent anti-oxidants) Theres a theory that the crash/moody blues after wards is part of Oxidative Stress (aswell as emotional stress) so the more anti-oxidants the better (Vitamin C is a very easy to come by antioxidant). Aswell as my favorite multi-vitamin, multi-mineral, anti-oxidant, amino acids (including the EAA's and BCAA's), & more adaptogens/herbal complex. Ah other antioxidants and adaptogens (that will fix any internal organ damage and such - help adapt you to the increased stress responce)
I can reccomend are:
ALA - Alpha Lipoic Acid
Citrus Bioflavinoids (from the peel)
Coenzyme Q10
Eluethero (root)
Hawthorn (berry)
Inositol
Milk Thistle (seed)
Oriental Ginesing (root) - which will also help with circulation
PABA - Para-Aminobenzoic Acid
Pyridoxine alpha-Ketoglutarate
Carnitine
Choline (in some form - Choline CDP (Citicholine) and Alpha GPC being the most bioavailable, but even plain old Choline Bitarate will do, even if you decide against the Racetam's - it'll help clear up brain fog and improve your cognition)
Also, maybe try some Atarax/Vistaril (Hydroxyzine) as it antagonizes the receptors that MDMA activates, (and from what Ive heard anecdotally - can stop a MDMA trip dead in its tracks). Its commonly used for vertigo, motion sickness and anxiety (as an safer alternative to benzos and z-drugs). Could help regulate it or atleast deactivate any over-activation (if there is such a thing, my brain is mush atm)
Benzodiazeapines will help you relax, but if you wanna stay away from all drugs I feel you.
I'd check your Blood Pressure a few times, maybe you had preexisting hypertension or prehypertension and the MDMA exacerbated that. Which comes with all sorts of problems that Im sure you're aware of.
I recently found out I had HBP - now taking Micadis (Telmistartan) for it an ARB (Angiotensin Receptor Blocker) - feeling fantastic compared to any other BP med I've been on - seemingly no sides like beta blockers - I get energy from it not lose it, still clam/relaxed/controlled bp - which REALLY makes a difference (also has longevity properties, increases endurance, helps repair soft tissue, collagen and muscle damage as well as control your BP through the renin-angiotensin system (RAS) by antagonizing the Angiotensin II Receptor. Beta Blockers were contraindicated as I take Vyvanse (and adderal XR before that AND ritalin before that - basically my whole life, which I think caused the HBP (along with increased sedentary lifestyle due to slipped disc and bad diet) AND I noticed that the normal dosage range (I tested my MDMA it was pure) did not effect me NEARLY as much as I thought it would - which I attribute to them both being amphetamines - cross tolerance and my serotonin system always having been unbalanced (and I Don't do SSRIs, MAOIs - because of the amphetamine, TCAs, TeCAs, SNRIs or any of that crap).
I've considered an SSRE (Selective Serotonin Reuptake Enhancer) like Stablon but no Rx for it yet and I just spent my money for the week (the rest is going towards my vacation to nashville to see Rifftrax Live)
Now finally getting it back in balance with Semax and Selank - the affects are cumulative and actually last because it fixes you on the genetic level. I really think now that were into Pharamcogenomics that medicine is going to slowly become much more effacious - Thank god.
Selank - I read in one study 33 genes had been expressed or change within 15 mins of intranasal administration and 20 more were the same way when they checked an hour later). I tried redosing but didn't work out too well (now Ive got the headache, brain fog, etc - but im sure that will clear up - sleep deprivation doesn't help either).
The other positive effects of Selank and Semax should help in all cases across the board, immunomodulatory, balancing serotonin, dopamine, epinephrine and norepinephrine system(s), etc. If you've been kind a stiff (you said heat helps with the aches? You could very well have hypertension - that'll cause oxygenated blood to not get to everywhere it needs to causing tighter, colder tendins, ligaments and muscles - and with it being winter here - I already wake up freezing and stiff - hot shower loosenes everthing up - if your still in pain (not stiff but pain) swtich the water to really COLD gradually - after taking a steaming hot shower then being hit with the really cold all of a sudden causes inflammation to go down alot (football players with injuries soak in a hot tub then jump in an icebath to do the same thing).
Cat's Claw might help (immune stimulant) but Im not sure if it would in this case. I just saw it in my pile'o supplements and mention it.
P.S. Coulracetam - is an Acetylcholine Reuptake Inhibitor and seems to work very fast if you find cholinergics/racetams to be helpful with the brain fog/mental decline. Also Huperazine A does a similar thing through a different mechanism of action (Coulracetam is more effacious IMHO)
Lions Mane Mushroom couldn't hurt (more expression of BDNF and NGF)
If your still using them, I'm not sure about 5-HTP but I know Melatonin is a huge neuroantioxidnt aswell as regulating your circadian rythm and regulating your serotonin levels - if you don't like 5-HTP (I know I didnt) - Try Melatonin - just make sure you take it at night or the daylight will just turn it into 5-HTP (and vice versa, if you use 5-HTP at night becomes Melatonin - I believe). If you're joints ache - try something like Move Right or Osteo-Biflex (Glucosamine, MSM, VitaminD3, Hyraluanic Acid, a certain type of Calcium and Chrondroiten) helps me - once the MDMA is fully out of your system an asprin (or if your all natural willow tree bark extract), another NSAID or Tylenol.
Also - lots of herbal teas and just regular green/white/black tea will help add adaptogens, healthy herbs and antioxidants.
Hope this helps, oh and don't get the Selank/Semax imported from Russia - its extremely expensive that way compared to just getting lypophized powder, bacteriostatic water and reconstitute the peptides yourself if you chose to try them. Not only do you save a whole helluva lot of money, but you get about 4x dosage wise, than what the nasal sprays imported from Russia does.
Nasal Sprays = 60-70% bio-available
Subcutaneous Injection = 100% bio-available.
Once most of it clears up - get a thyroid and hormone panel done at a specialist - because if your HPTA is out of wack, badly - you could probably use some hormonal treatment (either supplemented using herbal test boosters and the like or prescribed by the doctor) - same with your Thyroid.
Those are the only ROA's (theres a link showing you how to reconstitue Selank - and you can find articles on reconstituting Semax easily by google - its the same deal just different math/calculations to make to get the right dose per drop/spray, and mg per ml/cc that you want based off molecular weight and such things. If taken orally or sublingually - the stomach will break down the peptide into its respective amino-acids and have no effect.
Hope everything I wrote makes sense, I'm on 36 hours or more without sleep, crashed on mdma, among other things lol.
Get better my man; "No matter what you do; stay on the Bike" (Buck 65 lyric) and keep on keepin on' things will get better sooner than you think I'd bet.
Peace & Love
-AMKR
