• Amphetamine Withdrawal

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    • #246048

      AlbaGuBrath
      Member

      10mg daily to start, increased in 10mg increments as needed and with close monitoring up to 60mg daily.

      Thanks Brooklyn Juice. Quick follow ups:

      Is that 60mg a Maximum daily dosage for an adult?

      And how is that 60mg usually split up…i.e…20mg three times a day or 15mg four times a day or even 10mg six times a day? I could see the latter being the case as the regular Dexedrine tabs (not the spansules) are rather short acting. Thanks again.

      AGB

      #246283

      Novick
      Member

      Amineptine will definitely knock out any signs of amphetamine withdrawal, but it’s a bit more risky than most options as it will have definite appeal for those with a taste for amphetamine like stimulants.

      Also, don’t foget about the importance of the 5-HT system in managing withdrawal of all types. 5-HTP or a chronic low dose regimen of SSRI’s could be very helpful.

      5-HTP works well for me in cutting down on impulsive cravings for lots of things, including stimulants.

      Another option, (and a great drug that is woefully underused) is tranylcypromine. Tranylcypromine, from a structural point of view, is extremely close to amphetamine (the carbons coming off the benzene ring are cyclic instead of in a straight chain). It’s an unselective irreversible MAOI, so you need to stay away from guacamole and the whatnot, but it should get rid of any signs of amphetamine withdrawal or depression within a matter of days.

      #246334

      SlateDrake
      Member

      Another option, (and a great drug that is woefully underused) is tranylcypromine.  Tranylcypromine, from a structural point of view, is extremely close to amphetamine (the carbons coming off the benzene ring are cyclic instead of in a straight chain).  It’s an unselective irreversible MAOI, so you need to stay away from guacamole and the whatnot, but it should get rid of any signs of amphetamine withdrawal or depression within a matter of days.

      guacamole?

      Sorry, I know I’m missing something obvious here…but can you help out in why to limit the guac?

      (and lord knows I love my quac…)

      #246447

      Novick
      Member

      [quote name=’Novick’ date=’Feb 29 2004, 11:01 PM’] Another option, (and a great drug that is woefully underused) is tranylcypromine.  Tranylcypromine, from a structural point of view, is extremely close to amphetamine (the carbons coming off the benzene ring are cyclic instead of in a straight chain).  It’s an unselective irreversible MAOI, so you need to stay away from guacamole and the whatnot, but it should get rid of any signs of amphetamine withdrawal or depression within a matter of days.

      guacamole?

      Sorry, I know I’m missing something obvious here…but can you help out in why to limit the guac?

      (and lord knows I love my quac…)

      anytime you irreversibly inhibit MAO-A in the gut, you need to watch how much tyramine you take in. guacamole is usually considered a food to stay away from while on MAOI’s due its tyramine content.

      #246621

      AlbaGuBrath
      Member

      Bump for Dexedrine dosing.

      #246890

      Dopamine
      Member

      The various forms of amphetamine have a well-known ability to decrease the activity of the rate-limiting enzyme tyrosine hydroxylase, which is involved in the conversion of L-Dopa to Dopamine. So, supplementing high doses of the amino acid L-Tyrosine and/or D,L-Phenylalanine while in the symptomatic state of tyrosine hydroxylase deficiency wouldn’t be very effective in treating catecholamine depletion. This seems to be a critical dimension to increasing catecholamine stores in a post-amphetamine use phase.

      One supplement that caught my attention was NADH (nicotinamide adenine dinucleotide), which is reported to “indirectly supply reducing equivalents to the rate-limiting, tyrosine hydroxylase-catalysed step of dopamine synthesis” (Drugs Aging 1998 Oct; 13(4):263-8). Perhaps co-supplementing L-Tyrosine and/or D,L-Phenylalanine with NADH would increase dopamine production to a greater degree than the pre-cursors alone.

      In the framework of tyrosine hydroxylase activity, Selegiline arises once again as an effective treatment for dopamine depletion. One study reports after the administration of selegiline:

      The tyrosine hydroxylase activity and tyrosine hydroxylase content increased in hypothalamus and hypophysis (P < 0.05). In the hypophysis the increase in tyrosine hydroxylase activity was consistent with the increase in tyrosine hydroxylase amount.

      Source: Eur J Pharmacol 1997 May 30; 327(2-3):215-20

      Does anyone know of any other supplement/nootropic/drug which increases the amount and/or activity of tyrosine hydroxylase?

      #247833

      Novick
      Member

      Selegiline works, but only in low doses to increase tyrosine hydroxylase. (i’ll go into further detail in my upcoming article about this)

      nicotine increases tyrosine hydroxylase as well.

      nicotine is a good option to help amphetamine withdrawal because of its different mechanism of action (nicotinic ACh receptors), thereby increasing dopaminergic activity more indirectly.

      With amphetamines we’ve already downregulated dopamine function by attacking a single pathway (the DAT causing release and re-uptake inhibition), so in order to upregulate dopamine function, it might make sense to attack a seperate pathway in order to cirumvent negative feedback mechanisms. The nicotinic receptors are one. GABA is another, although GABA might not work as well to ameliorate the acute symptoms of amphetamine withdrawal.

      #250693

      Dopamine
      Member

      The various forms of amphetamine have a well-known ability to decrease the activity of the rate-limiting enzyme tyrosine hydroxylase, which is involved in the conversion of L-Dopa to Dopamine. So, supplementing high doses of the amino acid L-Tyrosine and/or D,L-Phenylalanine while in the symptomatic state of tyrosine hydroxylase deficiency wouldn’t be very effective in treating catecholamine depletion. This seems to be a critical dimension to increasing catecholamine stores in a post-amphetamine use phase.

      One supplement that caught my attention was NADH (nicotinamide adenine dinucleotide), which is reported to “indirectly supply reducing equivalents to the rate-limiting, tyrosine hydroxylase-catalysed step of dopamine synthesis” (Drugs Aging 1998 Oct; 13(4):263-8). Perhaps co-supplementing L-Tyrosine and/or D,L-Phenylalanine with NADH would increase dopamine production to a greater degree than the pre-cursors alone.

      In the framework of tyrosine hydroxylase activity, Selegiline arises once again as an effective treatment for dopamine depletion. One study reports after the administration of selegiline:

      The tyrosine hydroxylase activity and tyrosine hydroxylase content increased in hypothalamus and hypophysis (P < 0.05). In the hypophysis the increase in tyrosine hydroxylase activity was consistent with the increase in tyrosine hydroxylase amount.

      Source: Eur J Pharmacol 1997 May 30; 327(2-3):215-20

      Does anyone know of any other supplement/nootropic/drug which increases the amount and/or activity of tyrosine hydroxylase?

      #251613

      Novick
      Member

      Selegiline works, but only in low doses to increase tyrosine hydroxylase. (i’ll go into further detail in my upcoming article about this)

      nicotine increases tyrosine hydroxylase as well.

      nicotine is a good option to help amphetamine withdrawal because of its different mechanism of action (nicotinic ACh receptors), thereby increasing dopaminergic activity more indirectly.

      With amphetamines we’ve already downregulated dopamine function by attacking a single pathway (the DAT causing release and re-uptake inhibition), so in order to upregulate dopamine function, it might make sense to attack a seperate pathway in order to cirumvent negative feedback mechanisms. The nicotinic receptors are one. GABA is another, although GABA might not work as well to ameliorate the acute symptoms of amphetamine withdrawal.

      #252635

      Dopamine
      Member

      Has anyone had any experience with the antidepressant Moclobemide? It is a reversible MAO-A inhibitor, with effects lasting no longer than 24 hours. Supposedly, you’re not supposed to combine Moclobemide with amphetamines, but perhaps it would be a good, fast-acting anti-depressant for the days of amphetamine abstinence. Any thoughts?

      #252665

      Oracle5
      Member

      “Perhaps co-supplementing L-Tyrosine and/or D,L-Phenylalanine with NADH would increase dopamine production to a greater degree than the pre-cursors alone.”

      I have used NADH supplements for 3 years now, and IMO, supplementing with L-Tyrosine and/or D,L – Phenylalanine without at least 2.5mg/day of NADH –> will limit the potential benefits of these dopamine-“precursor” amino acid supplements to a LARGE degree…

      #252667

      Oracle5
      Member

      Biopterin is the folic-acid derivative that is most necessary along with copper in order for phenylalanine/tyrosine to be metabolized in the liver by the enzymes phenylalanine and tyrosine hydroxylase (which are almost identical in structure).

      Phenylalanine is also a constituent of mescaline, morphine, codeine, vasopressin, angiotensin II, and cholecystokinin.

      Some of these abstracts below shed some light on how different supplements can alter tyrosinase activity…

      hope this helps you out!

      Di Yi Jun Yi Da Xue Xue Bao. 2002 Nov;22(11):1017-9.

      [Effect of Tribulus terrestris L decoction of different concentrations on tyrosinase activity and the proliferation of melanocytes]

      [Article in Chinese]

      Deng Y, Yang L, An SL.

      Department of Traditional Chinese Medicine, First Military Medical University, Guangzhou 510515, China.

      OBJECTIVE: To study the effects of the decoction of Tribulus terrestris L on tyrosinase activity and melanogenesis. METHODS: MTT was employed to study the proliferation of human melanocytes cultured in vitro, and tyrosinase activity was estimated by measuring the rate of oxidation of DL-dopa, after the cells were treated with different concentrations of decoction of Tribulus terrestris L. RESULTS: The treatment with the decoction increased the amount of melanin at higher concentrations but act to the reverse effect at lower concentrations, with the best concentrations for promoting and inhibiting the cell growth being 1.5 mg/ml (P<0.05) and 0.5 mg/ml (P<0.05) respectively. At high concentrations the decoction enhanced the tyrosinase activity that was inhibited at low concentrations. The best concentrations for enhancing and inhibiting tyrosinase activity were 100 mg/ml (P<0.05) and 10 mg/ml (P<0.05) respectively. CONCLUSION: -->> “Tribulus terrestris L decoction exercises a two-way regulation on the activity of tyrosinase and the proliferation of melanocytes.”

      PMID: 12433636 [PubMed – indexed for MEDLINE]

      Exp Dermatol. 2003 Feb;12(1):61-70.

      Tyrosine hydroxylase isoenzyme I is present in human melanosomes: a possible novel function in pigmentation.

      Marles LK, Peters EM, Tobin DJ, Hibberts NA, Schallreuter KU.

      Clinical and Experimental Dermatology, Department of Biomedical Sciences, University of Bradford, West Yorkshire, BD7 1DP, UK.

      Both human epidermal melanocytes and keratinocytes have the full capacity for de novo synthesis of 6® L-erythro 5,6,7,8, tetrahydrobiopterin, the essential cofactor for the rate limiting step in catecholamine synthesis, via tyrosine hydroxylase. Catecholamine synthesis has been demonstrated in proliferating keratinocytes of the epidermis in human skin. This study presented herein identified for the first time the expression of tyrosine hydroxylase isozyme I mRNA within the melanocyte. The location of the enzyme was demonstrated in both the cytosol and melanosomes of human epidermal melanocytes, using immunohistochemistry and immunofluorescence double staining as well as immunogold electron microscopy. High-performance liquid chromatography (HPLC) analysis of pure melanosomal extracts from the human melanoma cell line, FM94, confirmed the production of L-dopa within these organelles. In addition, enzyme activities for both tyrosine hydroxylase and tyrosinase were measured in the same preparations, by following the catalytic release of tritiated water from L-[3,5-3H]tyrosine. The melanosomal membrane location of tyrosine hydroxylase together with tyrosinase implies a coupled interaction, where L-dopa production facilitates the activation of tyrosinase. Our results support a direct function for tyrosine hydroxylase in the melanosome via a concerted action with tyrosinase to promote pigmentation.

      PMID: 12631248 [PubMed – indexed for MEDLINE]

      #252753

      NN_DMT
      Member

      Well I don’t know if this helps, but I had a friend who found she liked ritalin for help with schoolwork….

      I told her to try this stack and she said it gave her the same feeling when taken on an empty stomach and all three at the same time.

      Tyrosine, DMAE, & Gingko

      what about amineptine (survector = tricyclic antidepressant focused in on dopamine primarily….FDA had the drug squashed from existence)? if you can find it…..

      #254550

      Novick
      Member

      J Neurosci Res. 1995 Dec;42(5):684-91. Related Articles, Links

      Increase in dopamine turnover and tyrosine hydroxylase enzyme in hippocampus of rats fed on low selenium diet.

      Castano A, Ayala A, Rodriguez-Gomez JA, de la Cruz CP, Revilla E, Cano J, Machado A.

      Departamento de Bioquimica, Bromatologia y Toxicologia, Facultad de Farmacia, Universidad de Sevilla, Spain.

      We have studied the turnover of dopamine, noradrenaline, and serotonin and their metabolites in hippocampus of adult female rats that were fed control or selenium-deficient diets during 15 days. Under these circumstances, there was an increase of dopamine turnover (4-fold) in rats fed with selenium-deficient diet with respect to controls and also an increase in the tyrosine hydroxylase activity (75.8%), which was the result of the increase of the amount of the enzyme (2-fold), without significant change in the phosphorylation of the tyrosine hydroxylase. In addition the glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase activities have been studied. After selenium-deficient diet, the enzymatic activities of superoxide dismutase and catalase did not show change with respect to the controls; however glutathione reductase and glutathione peroxidase significantly decreased 15% and 29%, respectively. It is concluded that the increase in dopamine turnover seems to be associated with the induction of tyrosine hydroxylase enzyme. In these conditions the decrease in antioxidant capacity may produce a cascade of events, which accelerates the degenerative process, since the increase in dopamine turnover produces an increase in oxygen radical by monoamine oxidase activity.

      #257284

      Dopamine
      Member

      Selenium is one of those essential nutrients which are good in a small dose, but go toxic at higher ones. In my limited experience, I have found that more than 500 mcg of selenium has produced a general feeling of nausea and sickness. It frustrates me when I see all of these great formulas purporting to increase cognitive function adding in levels of selenium which, when taken with a standard multivitamin, could induce a toxic reaction. I don’t think a lot of these companies who put together these nutritional formulas quite understand that selenium is a heavy metal, and therefore toxic in high doses.

      #364083

      Bobby
      Member

      I wonder if something like Selegiline would help for dopamine depletion. As a MAO-B inhibitor, it preferentially prevents the breakdown of dopamine and phenethylamine (amphetamine is dl-alpha-methylphenethylamine). By taking Selegiline, you increase the time in which the…

      I find your reply remarkably complete. What whould be the aggregate catalysts to combat Opiate, Ecstasy, and alcohol and THC, particular to the ravaging effects on the liver for alcohol and the common acetaminophen load that many Vicodin users experience. I am curious what catalysts used with tryptophane or 5HTTP to convert to serotonon. Also the lipid properties of THC and the difficulty of flushing them out of the system.

      Bobby

      The level of determining Spiritual progress is inversley proportionate to continous thought.

      #364194

      Oracle5
      Member

      NAC, Taurine, SAM-e and many other supplements combined with sauna therapy etc can all go along way…

      #364381

      magister
      Member

      What is NAC ?

      #364419

      Oracle5
      Member

      What is NAC ?

      N-acetyl cysteine (NAC) is an altered form of the amino acid cysteine with many, many protective and detoxifying benefits for the liver, lungs, brain, etc…

      #364442

      Chairman_MAO
      Member

      The most effective remedy for amphetamine withdrawal I can think of is Parnate (tranylcypromine), 90-200mg/day.

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