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John250

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  1. The entire amphetamine cascade is so complex it makes sense why it’s one of the most addictive drugs there is. After spending countless hours on wiki and selfdecode I pretty much got nowhere as the majority of things that help are changing gene expression. From what I’ve gathered you want to decrease expression of deltafosB while increasing expression of deltaJunD and the histone methyltransferase enzyme (EHMT2)(G9a) plus many other changes in gene expression. Of course that can’t be simple as it states: “Sufficiently overexpressing ΔJunD in the nucleus accumbens with viral vectors can completely block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB).” I spent 20 minutes looking up viral vectors and got nowhere lol ______________________________________________ *TAAR1 activation is supposed to be beneficial and of course there’s no practical TAAR1 agonists. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881156/ _____________________________________________ Although I will say the one substance that I’ve seen over and over on selfdecode that seem to properly increase and decrease expression in the genes you want and decrease expression in correct genes for counteracting amph’s addictive cascade is Depakote {Valproic Acid} (VA) I mean it seems like the closest thing you can get what are your thoughts about it? Side effects don’t outweigh the pros? My appointment with my new psychiatrist is tomorrow so I wanted to go over options. _______________________________________________ Links with VA and AMPH used together: *Reduced distractibility- https://www.ncbi.nlm.nih.gov/pubmed/9264079/ *Reduced Hyper Locomotion- https://www.sciencedirect.com/science/article/abs/pii/S030439400701261 *This is interesting. VA ameliorates AMPH induced cognitive impairment: https://www.researchgate.net/publication/51983635_Early_life_stress_exacerbates_cognitive_dysfunction_induced_by_D-amphetamine_Amelioration_by_valproic_acid _______________________________________________ This is in meth but it links VA to craving reduction https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025910/ ______________________________________________ More pro’s of VA as a means to reduce AMPH tolerance and sensitization- *HDAC Inhibitor *NMDA antagonist *GABA agonist- don’t remember the article but it found a strong linkage to depleted Gaba induced by amphetamine which is often dismissed as primary focus is mainly on DA/NE/SERT *MAO-A and MAO-B inhibitor: https://www.ncbi.nlm.nih.gov/m/pubmed/21775495/ https://www.hindawi.com/journals/bmri/2017/8124501/ *Increased expression of Tyrosine Hydroxylase and Tryptophan Hydroxylase: https://www.ncbi.nlm.nih.gov/pubmed/26512932/ *Increases expression of deltaJunD https://www.ncbi.nlm.nih.gov/pubmed/21427059/ *Increases expression of JUN (Jun proto-oncogene, AP-1 transcription factor subunit) https://www.ncbi.nlm.nih.gov/pubmed/27188386/ Same article for decreased expression of GSK3B *For FOS VA increases expression but decreases reaction not really sure if thats good or bad: https://www.ncbi.nlm.nih.gov/pubmed/8719796/ *Increases expression of G9a-EHMT2(Euchromatic histone lysine methyltransferase 2) https://www.ncbi.nlm.nih.gov/pubmed/17183730/ _______________________________________________ The following links were from selfdecode. •AMPH decreases PTN expression potentially inducing neurotoxicity but Valproic Acid increases PTN expression. 4 of the 13 phosphoproteins in the PTN are linked to Parkinson’s 1.) ANXA7 (Annexin A7) decreases expression by amph but increased expression by Valproic Acid https://www.ncbi.nlm.nih.gov/pubmed/23459167/ 2.) ALDH1A1 (Aldehyde dehydrogenase 1 family member A1) decreases expression by amph but increased expression by Valproic Acid. https://www.ncbi.nlm.nih.gov/pubmed/23179753/ The other 2 I didn’t find-COP9 signalosome subunit 5 (COPS5), and creatine kinase U-type (CKMT1). *Amphetamine decreases NYP (Neuropeptide Y)Valproic Acid increases NYP expression https://www.ncbi.nlm.nih.gov/pubmed/27188386/ And same article for decreases expression of CREBBP (CREB binding protein) 4.19 which I think is good since wiki stated: “Chronic use of amphetamine at excessive doses causes alterations in gene expression in the mesocorticolimbic projection, which arise through transcriptional and epigenetic mechanisms. The most important transcription factors that produce these alterations are Delta FBJ murine osteosarcoma viral oncogene homolog B (ΔFosB), cAMP response element binding protein (CREB), and nuclear factor-kappa B (NF-κB).[117] ΔFosB is the most significant VA and AMPH used together: ______________________________________________ *I believe VA is a protein kinase C activator which should make response to amph better by increased extracellular dopamine release so maybe just to be good or bad depending on if you don’t abuse it? It doesn’t increase all Calcium dependent proteins but it does increase expression in: •VA INCREASES expression in- *CAMK2N2 (Calcium/calmodulin dependent protein kinase II inhibitor 2) *PINK1 (PTEN induced putative kinase 1) *PRKCE (Protein kinase C epsilon) *PRKCA (Protein kinase C alpha) *No expression under(PRKCG or CAMK1G) https://www.ncbi.nlm.nih.gov/pubmed/23179753/ https://www.ncbi.nlm.nih.gov/pubmed/24935251/ https://www.ncbi.nlm.nih.gov/pubmed/27188386/ •VA DECREASES expression in- *Calcium-Dependent Protein Kinase Regulator Activity under gene- HMGB1 (High mobility group box 1) *CAMK2B (Calcium/calmodulin dependent protein kinase II beta) *CAMK4 (Calcium/calmodulin dependent protein kinase IV) https://www.ncbi.nlm.nih.gov/pubmed/15901671/ _______________________________________________ •Valproate increases expression of DRD4 and DRD1 https://www.ncbi.nlm.nih.gov/pubmed/17183730/ https://www.ncbi.nlm.nih.gov/pubmed/23665938/ _______________________________________________ 
  2. Thank you! Your a car fan I take it. Before my addiction I was into racing and tracking. I had a 2006 BMW M6 full bolt on around 575bph. Sold it when I opened a Nutrition store. In October I picked up another 2006 M6 and it had a 5.5l V10 13.2:1 high compression stroker on methanol put in. Rear diff went from a 3.62 to a 4.10. Carbon Fiber crankshaft, catless long tubes, fenders rolled to fit 315/30/20 drag radials,etc.. around 700bhp/600ft•lb/tq but hp/tq powerband on stock motor is around 6000-8250rpm. This powerband is 3000-7000rpm with redline at 8500. Haven’t even picked it up because of my addiction and it’s been ready since June. Very interesting about the Lateral Habenula playing a role in avoidance behaviors. Seems like there is lots of evidence backing it in that as well as it’s role in drug addiction. The 3rd article even states how Ibogain/18-MC improves the damaged LH regions. https://www.ncbi.nlm.nih.gov/pubmed/9365026/ https://www.nature.com/articles/npp2016286#ref31 https://www.frontiersin.org/articles/10.3389/fnhum.2014.00174/full
  3. Thanks guys. The psychiatrist works at UCSD Executive Mental Health department and works Saturdays so I moved my appointment to tomorrow morning. I’m extremely nervous but it has to be done.
  4. I actually have an appointment on Monday with a new psychiatrist with 30+ years experience who specializes in neurology. I think I’m going to just come clean about how much I take, how I snort it and just tell him everything and just ask him for help and take whatever advice he gives me. Something I can reflect on right now which is really odd is I’ve never fought so hard for anything in my life. But I fought all the wrong reasons. I’ve been fighting so damn hard for like a year trying to fix myself just taking more and more amph or doing different things and researching or adding this and that and it’s like I just didn’t give up but all in the wrong way. Countless 48 hours of staying awake fighting staying awake followed by sleeping 19hrs the next day, fighting feeling like complete shit everyday, fighting hiding shame, fighting knowing that I used to be an above average father and now I’m subpar if that , it’s like that saying “change happens when the pain of staying the same becomes more painful than changing.” I love that quote and it’s so odd how I’m able to fight so hard for the pain and not fight for change for some reason. Like take right now for example. My wife went to her moms for three days with the kids and I had a huge plan to finish my work and get caught up and I did nothing. They’ve been home sense yesterday and I haven’t seen them because I haven’t slept and I wont go home if I haven’t slept. I’m sitting in a parking lot right now in my car on my phone and I’m about to sleep in a fucking room I wasted $200 on at the Marriott 7 miles from my house. I would be better off just completely quitting my job and doing something else but then I think that would be so selfish to the kids if we had to move because I’m the sole provider but then I think it’s extremely selfish what I’m doing right now. And the frustrating part is I just can’t make a rational decision for the life of me. Hopefully this doctor on Monday help. I do appreciate all of your input. Thank you
  5. No that’s not what I’m saying. What I want to know is all of these horrible effects and downward path I want to know the mechanism causing it? Obviously it’s amphetamine because I was never this way before I started it and nothing else but what I’m curious on is what activity in my brain is causing this? Could this be depleted Serotonin? Imbalance of NE/DA (as my DBH gene shows I’m AA and I convert less NE and more DA. Or could my symptoms be from depleted dopamine since AMPH rapidly wears off and depleted DA and TH? I have a feeling it’s excessive DA in my mesolimbic pathway causing me to almost be manic. I’m definitely not hypomanic as my moods don’t fluctuate and hypomanics are typically functional and more productive than usual. I would say I’m more in a hypermanic state but I don’t fit that either. I took all the psy quizzes and I had some milds here and there but scored extremely high for major depression and moderate for ADHD. I guess my main question is even more so than what’s actually going on in my brain is,..it’s not that I don’t think I can get through the rest of my life without amph It’s just this one thing holding me back with my work. My entire day revolves around opening my freaking laptop to answer my emails and I just can’t do it! I’ve never been like that before I’ve never said I can’t do it especially something so trivial like this it’s extremely frustrating how it’s taken over my entire life. I just sit in my car and im on my phone all day. I make every single excuse and then when I finally get ready to start its like 2am and I kind of get a little anxiety because I know how much I have to do and then I’ll end up staying up all night on YouTube or something and the next day is ruined because I didn’t sleep and I’m out of it. So then I hope to do it the following day and then something happens then but this shit has been going on for like eight months now it’s insane. It’s like every night I think I’m losing more and more customers. This is a bad analogy but it’s almost like you have a Lamborghini and your wife put low octane fuel in it and she’s driving it and you’re on the phone trying to reach her saying pullover pullover stop stop like you know something bad going to happen any second that’s basically what I feel like. But it’s because it’s my freaking life and my career. I feel like if I stop and go off amph I won’t be able to work at all but at the same time I’m on and even when I use higher doses I still can’t work! I guess I’m honestly just afraid of what I’m going to feel like and how everything will go when I go off? But I’ve been so unproductive while on amph I wonder if I might even function better while being off because I’m not benefiting from anything it’s supposed to do and did for me years ago. In fact it’s the opposite. I feel like it has exacerbated every dormant negative trait/issue/quality I had many that would have never surfaced and it just brought it out like someone opened Pandora’s box.
  6. I keep seeing how Ibogaine works wonders for opiate and psychostimulant withdrawl. On selfhacked it states: “Inhibition of dopamine transporters: Ibogaine has the same effects on dopamine transporters, resulting in higher dopamine levels. Dopamine levels in addicted individuals are altered due to the excessive use of abused drugs, such as cocaine. Ibogaine can reset the dopamine levels to pre-addiction levels, without leading to a new addiction.” https://www.ncbi.nlm.nih.gov/pubmed/22451652/ The part that stands out the most is “Ibogaine can reset dopamine levels to pre addiction levels.” How many AMPH addicts have you heard say “if I could only just go back to how I was before ever using amph? Well,..I sure am one of them. Anyone know how much merit this holds though? If this was the case wouldn’t everyone addicted to amph microdose Ibogaine to completely reset dopamine? Seems too good to be true no? Thanks!
  7. Can someone explain this? I’ve seen this before when discussing therapeutic options for reducing drug cravings: “Tamoxifen has demonstrated some efficacy has a therapeutic for bipolar mania and is believed to exert these effects through inhibition of protein kinase C (PKC). As the symptoms of amphetamine treatment in rodents are believed to mimic the symptoms of a manic episode, many of the preclinical studies for this indication have demonstrated that tamoxifen inhibits amphetamine action. The amphetamine-induced increase in extracellular dopamine which gives rise to the ‘manic’ effects is due to interaction of amphetamine with the dopamine transporter. We and others have demonstrated that PKC reduces amphetamine-induced reverse transport through the dopamine transporter. In this review, we will outline the actions of tamoxifen as a SERM and further detail another known action of tamoxifen—inhibition of PKC. We will summarize the literature showing how tamoxifen affects amphetamine action. Finally, we will present our hypothesis that tamoxifen, or an analog, could be used therapeutically to reduce amphetamine abuse in addition to treating mania.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332479/ So they are saying by inhibiting the extracellular dopamine it’s effective for inhibiting amphetamine addiction. Now wouldn’t the inhibition of dopamine just cause amphetamine to work less? I would think this would just make the user take more and more? Or does it still give you the desired effects and you can take less? I mean something like Naltexone and similar drugs makes you sick if you take opiates with it? So what would the difference be vs just not taking opiates? Less withdrawal? Is this the mechanism going on with Tamoxifen and Amphetamine? I just done get the mechanism of “how decreases extracellular DA improves amph addiction?” Thanks!
  8. Thanks everyone. No FMLA I run a private business{IFBB/Npc diet/training prep,etc..}. Hard to explain but I have many competitors and a few who were friends that know about my situation took advantage of it and basically stole a lot of my customers throughout my absence. Literally 10 hours total of work would catch me back up to where I could make an excuse to all my clients like I’m taking a 2 week vacation or something along those lines so I could detox but until I get those 10hrs caught up if I went to detox for 2 weeks on top of already being behind I would probably lose my entire business or most of it. Im not greedy I don’t buy fancy things but at the same time I would not want to have to re-locate housing and move my kids to different schools and cities, etc. Basically in the past I used to work about 4-5 hours a day and it was no problem but now like I mentioned before I just can’t seem to do it however usually at night maybe 10-11 PM I get a little boost of energy and Im able to knock out an hour but then being so behind it pretty much just sets me right back so I’m not getting more behind but I’m also not getting caught up. It sounds so simple it’s like just sit down and do your shit but if it was that simple I would’ve done it. Tomorrow I’m going to have my wife type for me and maybe help me a little so that might be something that could be beneficial. Our relationship has taken a toll so maybe working together and spending some time like that might be beneficial in multiple ways. I think at least 50% of this is mental like I constantly need to feel like I’m in the “right mood” before I work. I’ll tell myself “ ok you’re going to start in 30 minutes after you eat.” Then before I start I’ll tell myself “well just check your emails first, or check the forums first, etc.“ I almost feel like since I never had true ADHD and was prescribed amphetamines they almost “gave me ADHD” if that makes sense. It’s made me hyper focused on everything other than I’m supposed to. It’s been almost 5 years and I would say for the better part I would consider myself a “functioning addict” but the past six months I would consider myself “on the verge” of becoming a “non functioning addict.” I know what I need to do. I know I need to go off of it and just suffer through a few weeks and I make every excuse in the book when realistically when I’m caught up on work all my other excuses do not hold any other merit. Today was my second rTMS therapy. It’s 5 days/wk fir 6weeks so I’m going to stick with that and hopefully at least get caught up with in that timeframe and if there is no improvements then I’m just going to bite the bullet and either go to rehab or stay at my dads house a few hours away with my brother who just beat a benzodiazepine/alcohol addiction(he went to rehab and they gave them a shit ton of stuff to help like gabapentin, buspar, clonidine,etc..) What sucks is they don’t give you shit for amphetamines in fact he said a few people were in there for amphetamines and they just gave them Xanax sometimes. He was a completely different person after only 10 days of rehab. I was always optimistic for him but I was thinking he probably feels fine from all the meds they have him on and once he’s off the gabapentin and other meds is when he’s going to feel the true withdrawl but it’s been about a month since that and he’s doing great he has zero cravings he’s like a complete different person and wants me to stay with him through my detox so I think that’s the plan if I can’t beat this through TMS. At the TMS they are having me do CBT therapy with a psychologist as it’s important to do it “during” and after the treatment and also I’m seeing a nurse practitioner(PH.d) who specializes in changing medications you are on, tapering off meds, adding meds if need be,etc.. I was hesitant at first but it’s $16,000 (my insurance covered 90%) and they all have great credentials everyone either graduated from Harvard or the Mayo Clinic, etc. so we will see how that goes I guess.
  9. Unfortunately I’m already in that situation and have been about 4yrs now. I was prescribed up to 110mg/day Adderall in 2014 due to my size and metabolism but it was still negligent on the Dr’s part. I never even took it all I averaged about 60mg/day the first year and 1/2 then had a bad 4-6 months of 80-90mg. I developed a bad habit of snorting it which is good in a sense that I lost a good 25% of the drug but bad for the other obvious reasons. I went to new Dr. and came clean about the misuse and he switched me to 70mg Vyvanse which was rough as that’s only 28mg amphetamine so the jump from 90-28 I was like bed ridden tired for a week then sluggish another week then was fine and we tapered down each month until I got to 20mg Vyvanse and then I just went off as 20mg is a measly 8mg Amph. I stayed off about 6mo and was fine but opened a new business and felt like I needed it again but could be responsible. That was a mistake. The past 2yrs I averaged about 60-80mg/day(still about 50%+ intranasal) but the past 4-6mo lately I’ve pretty much hit rock bottom. The drug no matter what dosage does gives no energy, cognitive clarity or help with anything. But without it I’m a zombie who can barely get out of bed. I started developing bad habits like smoking, terrible diet and completely stopped all exercise. I have debilitating procrastination with my job which is email based and I’m months behind. I made the mistake of thinking I could just up the dose and knock out what I was behind in, then crash and taper off again so I used 120-140mg/day which was supposed to be for just a few days but it’s been a few weeks now. And the worst part is it didn’t help at all with my work it almost made it worse. For the life of me I can’t answer my emails I’ll literally do everything else but that in despite of knowing I’m using my savings and risk losing my family. I started TMS today and go 5days/week for the next 6weeks. I’m hoping it will help with some of my issues and let me taper off easier but I can’t taper off until I catch up on work which would only take a few days but I just can’t seem to do it. And I can’t cold turkey or detox because then I’ll be beyond the point of behind and lose my job. I’m in a viscous downward spiral for sure right now and a big predicament.
  10. Yes I see what you are saying but I’m not necessarily referring to only increasing dopamine to get the benefits.i meant compounds that synergize that aren’t harmful themselves. Like the addition of theanine to caffeine,etc.. I have a bottle of Guanfacine from irc I got a long time ago but was afraid to use it because I’ve read several reports of fatigue being a big side effect of Guanfacine. Have you tried it and if so what did you notice, dosage, etc.?
  11. I have. I tried 200mg and then a low dose of 50mg. Each time I tried it was a few hours after my morning Vyvanse dose and I found it just gave me some brain fog and reduced amps cognitive positives. I feel there was probably a cross tolerance like there is when you add Wellbutrin with amp as they compete for DAT. However I haven’t tried Modafinil “before” amphetamine so maybe that will help. It’s odd how different methamphetamine is from amphetamine I’m very greatful I’m not hooked on meth because in several trials they tried giving methamphetamine users dextroamphetamine to help with withdrawal and even that didn’t help,
  12. Well I guess if the person had no plans to quit it wouldn’t be worth it but during a taper it could be useful and speed it up. Say someone is used to needing 30mg amp to get up in the morning and function. Maybe with a PKC activator 20mg could let the person function the same. Or even if the end user didn’t plan to taper or quit they could reduce the dosage which would be overall less harmful. Like how let’s say 200mg caffeine+200mg theanine May give someone the same effects as 300-350mg caffeine. Your consuming less so less sides plus theanine is healthy. But unfortunately I think PKC activation is negative. I honestly know nothing about it. I guess it’s just about weighing the pro’s and cons of each situation. Tamoxifen isn’t necessarily healthy and it comes with its own host of side effects so even PKC inhibition in this case wouldn’t be worth it as it doesn’t really seem to offer much value for its role in amphetamines.
  13. So wouldn’t activating protein kinase C (PKC) increase the rewarding responses of amphetamines. Wouldn’t it make sense to find a PKC agonist or activator which would allow one to use less amphetamine yet reap the same rewarding effects?
  14. That makes sense. Here’s my problem with Amphetamine. There is no FDA withdrawl drug for it yet opiate users get methadone or suboxone, benzo’s get Gabapentin,etc.. all making the withdrawl easier yet nothing for amps. Amphetamine is also the easiest withdrawl of most drugs in terms of length of time and rare to have a risk of a seizure. But it’s by far the most debilitating fatigue and cognitive function leaving the user pretty much useless. However amphetamine, methamphetamine, coke and Nicotine all impact the brains main addiction pathway(deltafosB) far more than most other drugs. Probably why relapse rates are the worst. But... there is zero excuse why there is no the updated or perspective amphetamine withdrawl medication especially because doctors are handing it out like candy. Either the FDA doesn’t care because it’s a minimal risk of having a seizure or they don’t want something to come out as Big Pharma will lose $$ and wants you hooked. amphetamines rapidly deplete dopamine and tyrosine hydroxylase. Why is nobody looking more into compounds like Bromantane (restoration of tyrosine hydroxylase) and 9-Me-bc or BPC-157(restoration of pretty much the entire dopamine system). Why is there no explanation if this would be beneficial or if they could cause neurotoxic metabolites if used in conjunction with amphetamines? But its not just dopsmine. How about addressing deltafosB? HDAC inhibition has shown promise why is there no ongoing research for this. low dose naltrexone has shown some promise why is there no ongoing research on prevention of amp withdrawl via more research with the opioid pathway PDE4 inhibition has shown some promise(Ibudilast) (maybe Rolipram) why no ongoing research? And why only PDE4? PDE1, PDE2, PDE4, and PDE10 are highly expressed in the striatum and play a huge role in dopamine regulation yet you never hear of anything other than PDE4 for withdrawl? the dopamine system should be far easier to fix than many others like Serotonin and Gaba yet science seems to have those down yet withdrawl management for amphetamines is “behavioral therapy.” It’s disgusting. If you’re going to give somebody a drug that completely dysregulates specific brain regions then you damn well better have a drug to fix it. Im starting TMS next week as that seems to hold more merit than anything our worthless FDA has come out with. And the biggest problem is....if people on forums know this information there should be ZERO excuse why the FDA hasn’t fixed or addressed it.
  15. I’m probably reading this wrong but is it saying it reduces the dopamine and positives from amphetamines? If so I never understood why some studies would even list compounds that attenuated the “high” or positives of the drug. Like I read something about some NMDA antagonist that completely blocked all “positives” from amphetamines and it then said this antagonist could be useful for withdrawl. How? If your not feeling it your going to take more. You would think they would list compounds that synergize the drug not attenuate it.
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