Lightning-Nl
Bluelighter
- Joined
- Nov 11, 2012
- Messages
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Disclaimer: I am not a doctor. This guide is a summary and not meant to be used as a prescribing guide. I will not be held responsible if you harm yourself following these instructions. No tolerance reduction plan is ever perfect. Regular use of amphetamines will eventually lead to side effects and loss of efficacy. A healthy diet, exercise, and mentally enriching activities will also help tolerance be at a manageable level.
Also, much of our research and current understanding of how Amphetamines & stimulants in general affect the body and Central Nervous System are speculatory and haven't been proven yet. That doesn't mean we're wrong, as much of our understanding and how we believe these drugs affect the human body fits perfectly into what we already know. However, due to this fact, the information in this guide is subject to change as we learn more about how these drugs affect us everyday. I will try to keep this guide up to date, and encompasses as much of the information as I can, as soon as it becomes available.
Amphetamine tolerance reduction mini FAQ
originally by SwampFox56, revisions by sekio, continually being updated by both.
Background info – What are amphetamines?
Amphetamines are a class of drugs that are derived from alpha-methyl-phenethylamine (US name: amphetamine or UK name: amfetamine). The first drug of the class to be discovered was amphetamine itself, in the late 1800s. Derivatives like methamphetamine were invented later, in the search for drugs that had more suitable effects, different durations or less potential for dependence. Extended release formulations for once-a-day dosing have also been devloped.
Amphetamines are prescribed for attention-deficit disorder, ADHD, narcolepsy, and sometimes used in the military to keep people awake. The two most popular formulations of amphetamine are Dexedrine, and Adderall. In Europe, amphetamine is sold on the street, whereas in North America, Asia, and Australia, methamphetamine is more popular. Methamphetamine is actually sold under the brand name Desoxyn in many countries, as a drug for narcolepsy and ADD when other treatments fail. Desoxyn, Dexedrine, and Adderall are also used to treat chronically obese patients that have been unable to lose weight any other way.
Typical effects from amphetamine use are euphoria, increased energy, increased confidence, rapid heart rate, increases in blood pressure and pupil diameter, increased metabolic rate, decongestion, and increased executive functioning. Adverse effects are common with long-term or high-dose use and include jitteriness, paranoia, racing thoughts, numbness in the extremities from vasoconstriction, headaches, low blood sugar from not eating, inablility to sleep, psychosis, heart attack, and compulsive behaviour.
Prescription Amphetamines are always found in the form of a pill or sometimes in the form of a transdermal patch. Amphetamines are usually taken by mouth, but can be smoked, snorted, rectally administered, or injected, especially if they are in "raw" form. Eating amphetamines produces a slightly slower onset, and longer duration, than any other method. Other methods of ingestion can lead to compulsive use, and greater risk of overdose.
The effects of amphetamine are thought to be due to its ability to release neurotransmitters in nerve cells, and to prevent the breakdown of released neurotransmitters as well. In addition to being a monoamine releasing agent, amphetamines have also been proven to stop the reuptake of monoamines. Normally, after neurotransmitters are released when a cell sends a signal, they are either destroyed in the synapse by special enzymes like monoamine oxidase, or they are pumped back into the cell by “reuptake transporters”. Amphetamines are thought to reverse the effect of these transporters. Other stimulants, like methylphenidate/Ritalin, simply block the pumps from working for some time, producing a more mild stimulating effect.
Related compounds like cocaine and methylphenidate are not amphetamines, but produce effects in a similar fashion by increasing monoamine levels in the synapse. Methylphenidate was developed as an analogue of cocaine without the local anesthetic properties (responsible for the cardiotoxicity of coke), and is now used as an ADD drug, and candestinely in much the same way amphetamine is.
Background Information - Neurotransmitters
Amphetamines build up tolerance quickly in the body. When amphetamines enter the central nervous system, they have a substantial effect on one or more of four very important neurotransmitters. These neurotransmitters are dopamine, norepinephrine, epinephrine, and serotonin. They are also known as monoamines, because they have a single amine group in them. Dopamine, norepinephrine, and adrenaline are phenethylamines, derived from the amino acid phenylalanine, and serotonin is a tryptamine, derived from tryptophan.
Dopamine is a neurotransmitter that plays a major role in the brain system that is responsible for reward-driven learning & survival activities. It is a phenethylamine and is biosynthesized from tyrosine, phenylalanine, or L-DOPA. Dopamine is commonly thought of as the “reward chemical”, but curiously research suggests dopamine is responsible for expectation of reward moreso than reward itself. Mice that are given food every time they depress a lever release less dopamine than mice that only recieve food 50% of the time. This explains why dopamine-stimulating drugs can sometimes cause behaviours like compulsive gambling, shopping, or sexual activity. Hence, dopamine is commonly assumed to be responsible for feelings of well-being, and sometimes euphoria. Dopamine also plays roles in motor control, sexual desire, horomonal regulation, and regulation of blood pressure.
Norepinephrine - also known as noradrenaline - is a neurotransmitter that is very similar to adrenaline in function and structure. Norepinephrine effects parts of the brain where attention and responses are controlled - which is why release of norepinephrine causes increases in attention, euphoric feelings, and an increase in executive functioning. Norepinephrine levels are increased by almost every stimulant, save for caffeine. Norepinephrine has a primary role in making stimulants "feel good" - blockade of the norepinephrine transporter severely reduces the effects of drugs like MDMA.
Epinephrine - more commonly known as Adrenaline - is a neurotransmitter that is responsible for the regulation of your heart beat. It is also very important for regulating the diameter of blood vessels, nasal & air passages, as well as metabolic shifts. Epinephrine is also a crucial component of the fight-or-flight response used by the body when a threat is detected. Epinephrine is not euphoric on its own, and has strong peripheral effects that can feel very unpleasant. It is used as a fast-acting treatment for severe allergic reactions, until antihistamines can be administered.
Serotonin is a neurotransmitter that is - like dopamine - thought to be a contributor to feelings of well-being and happiness. Also known as 5-hydroxytryptamine, it is commonly abbreviated 5HT. It also has a major role in the intestine, and in blood vessels (which is what it was named for). However, serotonin's mechanism of action is almost entirely different and effects different areas of the body than dopamine. Serotonin has been proven to be a regulator of mood, appetite, and sleep. Serotonin release can be euphoric; but drugs that increase only serotonin levels are generally considered less euphoric than broad-spectrum stimulants. Drugs that mimic the effect of serotonin at some receptors can be hallucinogens (5HT2 receptors), anti-nauseants (5HT3 blockers) or even anti-anxiety drugs (5HT1a agonists).
In addition to these neurotransmitters, Amphetamines appear to to affect many others. For instance, Amphetamines appear to heighten levels of other neurotransmitters such as Beta-Endorphin and Acetylcholine. The mechanism behind this is speculative, however, the heighten levels of these neurotransmitters also contribute to the effects felt and seen by users of Amphetamines.
How tolerance happens
Amphetamine tolerance is thought to be caused by excess calcium ion influx through the NMDA receptor in the brain. The NMDA receptor is thought to be associated with learning and pasticity in the brain. Taking a chemical, drug or medication that can slow down or stop the excess flow of Ca++ into neurons is therefore observed to decrease tolerance to amphetamines and their relatives. By preventing excess Ca++ influx into the neuron an NMDA antagonist will help prevent associated brain alterations and damage in most cases. Most, if not all, monoamine-releasing, or reuptake inhibiting stimulants will produce tolerance in this manner.
The theory behind using a NMDA antagonist with a stimulant, is that reducing the activation of the NMDA receptor will stop your brain from trying to adjust its equilibrium. The most common use case is taking the NMDA antagonist at a low enough dose it does not produce psychological effects, but maintains a steady blood level when you have amphetamine in you. The NMDA antagonist and the stimulant should be taken together, or the NMDA antagonist shortly before the stim, for maximum effects.
In addition, some effects of tolerance can likely be attributed to the released dopamine over activating dopamine receptors, for instance.
Drugs that Cause Tolerance
Other The Counter medications that can cause a tolerance to Amphetamines are (but not limited to)...
Illegal drugs that can cause a tolerance to Amphetamines are (but not limited to)...
The most common way to slow development to tolerance, or possibly reverse it, is the use of NMDA receptor antagonists. However, there are many other ways to increase the effects of amphetamines - thus making the effects more noticeable, even with tolerance. This guide is really only meant for people who can't go a day without taking their medication because of some medical issue they have - such as narcolepsy or extremely severe forums of ADHD. I will start by listing what can help increase the effects of an amphetamine by listing them in the order they appear on this page.
Lowering Tolerance - Stopping All Use
By far the easiest and safest way of lowering tolerance to anything is by stopping all use of that substance for an extended period of time. I understand that isn't an option for some people. But for everyone taking amphetamines recreationally, this is by far the most effective way. The only downside is it takes time.
Potentation - Alkalization & Bio-Availability
Taking an alkalizing agent with an Amphetamine - when you take it orally - will help increase its effects by allowing more of it to be absorbed by your stomach. Potentiating your dose by alkalising your stomach will not reduce tolerance, as you are actually increasing the amount of amphetamine that is making it to your brain. Ampheatmine is less well absorbed in strongly acidic conditions than neutral or basic conditions. Taking something like Tums, Rolaids or baking soda should increase its effects a little bit more by causing an increase in bio-availability. However baking soda tastes awful. I recommend Tums or some other calcium carbonate tablets if you can't handle the taste. But if you can somehow take baking soda without puking from the horrid taste, I recommend that more since the alkalising effects of Tums only last for 30 minutes or so.
Taking too much baking soda can cause excess sodium in the blood, and can possibly cause severe gas or bloating, as well as causing diarrhea.
Taking baking soda and calcium carbonate may have a constipating effect if you take too much.
Potentiation - Stimulant + Stimulant
Taking a stimulant, with another stimulant is also an effective way at increasing the effects. For instance, taking methylphenidate with dextroamphetamine will increase the effects of both stimulants. Since taking a scheduled stimulant with another scheduled stimulant isn't practical since both of those are going to - or should - be strong enough on their own, you should consider taking over the counter stimulants to help increase prescription stimulant effects.
Obviously, combining 2 stimulants with a common mode of action won't decrease your tolerance.
Combining stimulants increases the potential for adverse effects like paranoia, anxiety, panic, high blood pressure, etc. and should always be done with care
The two OTC stimulants most people will have access to are caffeine, or ephedrine/pseudoephedrine.
Caffeine - Caffeine does an okay job at helping to increase the effects of a prescription stimulant. However, since many people also have a considerable tolerance to caffeine (I know I do!), you may have to take a higher dose of Caffeine than your used to. Purchasing some caffeine pills at your local GNC or any other nutrition store should give you 100mg or 200mg pills. I personally don't like Caffeine since it makes me shaky at higher doses. But if you don't have a problem with that, then go for it!
Pseudoephedrine & Ephedrine (original trade name; Sudafed) – the ephedrines are amphetamines that are from the Ephedra genus of plants. They are less centrally active than amphetamine is, and produce effects primarily by releasing norepinephrine and mimicking adrenaline at receptors. Ephedrine is more potent than pseudopehedrine by a factor of 8 to 10 times. The ephedrines are primarily used as stimulating decongestants. Overuse of ephedrine and pseudoephedrine can cause hypertension (high blood pressure) and sometimes rebound congestion.
Levmetamfetamine - (original trade name; Vicks Vapo Inhalers - Levmetamfetamine is the levorotatory enantiomer of Methamphetamine and is found in Vicks Vapo Inhalers. Levmetamfetamine is a synonym by the drug companies used to hide the fact that one of the active ingredients is "Levomethamphetamine." Methamphetamine has recreational value, however, the Levorotatory isomer of Methamphetamine is CNS inactive. This means it does no have any effect on the Central Nervous System or brain. Due to this fact, it will not give you a high like Methamphetamine does. It does have some Norepinephrine effects outside of the CNS and therefore is a mild stimulant.
Levmetamfetamine can be used to increase the effects of a CNS active stimulant. However, caution should be used when using Levmetamfetamine due to it's ability to cause hypertension and anxiety. Also, it should be noted that, even though Levmetamfetamine is, technically, Methamphetamine - there is no recreational value to abusing it. I've tried and it does provide mild stimulation, however, the amount required for mild stimulation is the same amount that can give you bad anxiety and cause hypertension. Caution is advised when dosing.
Propylhexedrine (original trade name; Benzedrex - Propylhexedrine is very similar to Methamphetamine. It's molecular structure is exactly the same as Methamphetamine. The only way the two differ is; Propylhexedrine has a cyclohexyl group (cyclohexane) where Methamphetamine would have a Benzene ring. Propylhexedrine has pharmacology similar to that of Amphetamine. It's able to cross the blood-brain barrier and inhibits DAT, NET and SERT through TAAR1 agonism (speculated) just like Amphetamine does.
Propylhexedrine, therefore, may have potential recreational value. However, it's vastly less potent than Amphetamine or Methamphetamine is, and therefore is used in the same way levmetamfetamine is - nasal decongestion via nasal inhalation. The same warnings apply to Propylhexedrine as Levmetamfetamine - the amount required for mild stimulation is the same amount that can give you bad anxiety and cause hypertension. Caution is advised when dosing.
Bupropion (Wellbutrin) - Bupropion is a stimulant-like antidepressant that stops the reuptake of Dopamine and Norepinephrine just like most other stimulants. It is related to the cathinones, and has a mild stimulating effect even though it does not reliably produce euphoria. Combining buproprion with amphetamines may increase the risk of seizure, especially at high doses of buproprion. It is also disputed whether or not bupropion will help increase the effects of Amphetamine. Some users report it does, and some report it doesn't. Pharmacology doesn't help us determine this either. Try a low dose and decide for yourself
Vitamin supplements - Vitamins + Stimulant potentiation
L-Tyrosine, L-DOPA The aforementioned chemicals are precursors to Dopamine. By taking L-Tyrosine or L-DOPA, the body will absorb it and use it to synthesize Dopamine. Therefore - any stimulant that has dopaminergic effects will have an increase in Dopamine levels on top of the stimulants effects on Dopamine. What this means is; besides the increase in dopamine levels that the stimulant will produce, L-Tyrosine or L-DOPA will also increase Dopamine levels on top of that due to the fact that the body will turn it into Dopamine.
(Will add more tomorrow)
NMDA antagonists for tolerance reduction
For the average person, the best option is to take between 30 and 60 mg of DXM, once or twice a day (first alongside your amphetamine dose, then halfway through the day). Get a bottle of magnesium supplements as well, and take the recommended dose in the morning. Eating healthy and excercising will also help.
If you can find some, memantine or amanitidine are good replacements because they lack the SNRI "antidepressant" effect of DXM They used to be used as influenza antivirals before every strain of the flu developed resistance. Now they are used to help treat neurodegenerative diseases.
OTC NMDA Antagonists
Wikipedia: Amphetamine, methamphetamine, methylphenidate.
Erowid: Amphetamines, methylphenidate
Bluelight: NMDA antagonists for tolerance (part 2), Amphetamine FAQ, Amphetamine Neurotoxicity and Tolerance Prevention (part 2, part 3)
Also, much of our research and current understanding of how Amphetamines & stimulants in general affect the body and Central Nervous System are speculatory and haven't been proven yet. That doesn't mean we're wrong, as much of our understanding and how we believe these drugs affect the human body fits perfectly into what we already know. However, due to this fact, the information in this guide is subject to change as we learn more about how these drugs affect us everyday. I will try to keep this guide up to date, and encompasses as much of the information as I can, as soon as it becomes available.
Amphetamine tolerance reduction mini FAQ
originally by SwampFox56, revisions by sekio, continually being updated by both.
Epsilon Alpha said:
Background info – What are amphetamines?
Amphetamines are a class of drugs that are derived from alpha-methyl-phenethylamine (US name: amphetamine or UK name: amfetamine). The first drug of the class to be discovered was amphetamine itself, in the late 1800s. Derivatives like methamphetamine were invented later, in the search for drugs that had more suitable effects, different durations or less potential for dependence. Extended release formulations for once-a-day dosing have also been devloped.
Amphetamines are prescribed for attention-deficit disorder, ADHD, narcolepsy, and sometimes used in the military to keep people awake. The two most popular formulations of amphetamine are Dexedrine, and Adderall. In Europe, amphetamine is sold on the street, whereas in North America, Asia, and Australia, methamphetamine is more popular. Methamphetamine is actually sold under the brand name Desoxyn in many countries, as a drug for narcolepsy and ADD when other treatments fail. Desoxyn, Dexedrine, and Adderall are also used to treat chronically obese patients that have been unable to lose weight any other way.
Typical effects from amphetamine use are euphoria, increased energy, increased confidence, rapid heart rate, increases in blood pressure and pupil diameter, increased metabolic rate, decongestion, and increased executive functioning. Adverse effects are common with long-term or high-dose use and include jitteriness, paranoia, racing thoughts, numbness in the extremities from vasoconstriction, headaches, low blood sugar from not eating, inablility to sleep, psychosis, heart attack, and compulsive behaviour.
Prescription Amphetamines are always found in the form of a pill or sometimes in the form of a transdermal patch. Amphetamines are usually taken by mouth, but can be smoked, snorted, rectally administered, or injected, especially if they are in "raw" form. Eating amphetamines produces a slightly slower onset, and longer duration, than any other method. Other methods of ingestion can lead to compulsive use, and greater risk of overdose.
The effects of amphetamine are thought to be due to its ability to release neurotransmitters in nerve cells, and to prevent the breakdown of released neurotransmitters as well. In addition to being a monoamine releasing agent, amphetamines have also been proven to stop the reuptake of monoamines. Normally, after neurotransmitters are released when a cell sends a signal, they are either destroyed in the synapse by special enzymes like monoamine oxidase, or they are pumped back into the cell by “reuptake transporters”. Amphetamines are thought to reverse the effect of these transporters. Other stimulants, like methylphenidate/Ritalin, simply block the pumps from working for some time, producing a more mild stimulating effect.
Related compounds like cocaine and methylphenidate are not amphetamines, but produce effects in a similar fashion by increasing monoamine levels in the synapse. Methylphenidate was developed as an analogue of cocaine without the local anesthetic properties (responsible for the cardiotoxicity of coke), and is now used as an ADD drug, and candestinely in much the same way amphetamine is.
Background Information - Neurotransmitters
Amphetamines build up tolerance quickly in the body. When amphetamines enter the central nervous system, they have a substantial effect on one or more of four very important neurotransmitters. These neurotransmitters are dopamine, norepinephrine, epinephrine, and serotonin. They are also known as monoamines, because they have a single amine group in them. Dopamine, norepinephrine, and adrenaline are phenethylamines, derived from the amino acid phenylalanine, and serotonin is a tryptamine, derived from tryptophan.
Dopamine is a neurotransmitter that plays a major role in the brain system that is responsible for reward-driven learning & survival activities. It is a phenethylamine and is biosynthesized from tyrosine, phenylalanine, or L-DOPA. Dopamine is commonly thought of as the “reward chemical”, but curiously research suggests dopamine is responsible for expectation of reward moreso than reward itself. Mice that are given food every time they depress a lever release less dopamine than mice that only recieve food 50% of the time. This explains why dopamine-stimulating drugs can sometimes cause behaviours like compulsive gambling, shopping, or sexual activity. Hence, dopamine is commonly assumed to be responsible for feelings of well-being, and sometimes euphoria. Dopamine also plays roles in motor control, sexual desire, horomonal regulation, and regulation of blood pressure.
Norepinephrine - also known as noradrenaline - is a neurotransmitter that is very similar to adrenaline in function and structure. Norepinephrine effects parts of the brain where attention and responses are controlled - which is why release of norepinephrine causes increases in attention, euphoric feelings, and an increase in executive functioning. Norepinephrine levels are increased by almost every stimulant, save for caffeine. Norepinephrine has a primary role in making stimulants "feel good" - blockade of the norepinephrine transporter severely reduces the effects of drugs like MDMA.
Epinephrine - more commonly known as Adrenaline - is a neurotransmitter that is responsible for the regulation of your heart beat. It is also very important for regulating the diameter of blood vessels, nasal & air passages, as well as metabolic shifts. Epinephrine is also a crucial component of the fight-or-flight response used by the body when a threat is detected. Epinephrine is not euphoric on its own, and has strong peripheral effects that can feel very unpleasant. It is used as a fast-acting treatment for severe allergic reactions, until antihistamines can be administered.
Serotonin is a neurotransmitter that is - like dopamine - thought to be a contributor to feelings of well-being and happiness. Also known as 5-hydroxytryptamine, it is commonly abbreviated 5HT. It also has a major role in the intestine, and in blood vessels (which is what it was named for). However, serotonin's mechanism of action is almost entirely different and effects different areas of the body than dopamine. Serotonin has been proven to be a regulator of mood, appetite, and sleep. Serotonin release can be euphoric; but drugs that increase only serotonin levels are generally considered less euphoric than broad-spectrum stimulants. Drugs that mimic the effect of serotonin at some receptors can be hallucinogens (5HT2 receptors), anti-nauseants (5HT3 blockers) or even anti-anxiety drugs (5HT1a agonists).
In addition to these neurotransmitters, Amphetamines appear to to affect many others. For instance, Amphetamines appear to heighten levels of other neurotransmitters such as Beta-Endorphin and Acetylcholine. The mechanism behind this is speculative, however, the heighten levels of these neurotransmitters also contribute to the effects felt and seen by users of Amphetamines.
How tolerance happens
Amphetamine tolerance is thought to be caused by excess calcium ion influx through the NMDA receptor in the brain. The NMDA receptor is thought to be associated with learning and pasticity in the brain. Taking a chemical, drug or medication that can slow down or stop the excess flow of Ca++ into neurons is therefore observed to decrease tolerance to amphetamines and their relatives. By preventing excess Ca++ influx into the neuron an NMDA antagonist will help prevent associated brain alterations and damage in most cases. Most, if not all, monoamine-releasing, or reuptake inhibiting stimulants will produce tolerance in this manner.
The theory behind using a NMDA antagonist with a stimulant, is that reducing the activation of the NMDA receptor will stop your brain from trying to adjust its equilibrium. The most common use case is taking the NMDA antagonist at a low enough dose it does not produce psychological effects, but maintains a steady blood level when you have amphetamine in you. The NMDA antagonist and the stimulant should be taken together, or the NMDA antagonist shortly before the stim, for maximum effects.
In addition, some effects of tolerance can likely be attributed to the released dopamine over activating dopamine receptors, for instance.
Drugs that Cause Tolerance
Other The Counter medications that can cause a tolerance to Amphetamines are (but not limited to)...
- Ephedrine
- Pseudoephedrine
- Phenethylamine
- Levmetamfetamine
- Propylhexedrine
- Adderall (Racemic mixture of different Amphetamine isomers)
- Concerta, Metadate, Ritalin, Methylin (Methylphenidate) - Not an amphetamine, but is a potent Norepinephrine Dopamine Reuptake Inhibitor
- Desoxyn (DextroMethamphetamine)
- Dexedrine (Dextroamphetamine)
- Didrex (Benzphetamine)
- Adipex-P (Phentermine) - A Phenethylamine derivative stimulant that has effects and pharmacology similar to Amphetamine. It is currently used for weight loss.
- Focalin (Dexmethylphenidate)
- Vyvanse (Lisdexamphetamine) - a chemically time-released amphetamine that is not active itself, but is metabolized by the body into Dextroamphetamine which is active
- Nuvigil (Armodafinil) - Not an amphetamine, but is an NMDA receptor agonist (not antagonist), & dopamine reuptake inhibitor
- Provigil (Modafinil) - Not an amphetamine, but is an NMDA receptor agonist (not antagonist), & dopamine reuptake inhibitor
- Wellbutrin (Bupropion), a cathinone-derivative that is a mild Norepinephrine Dopamine Reuptake Inhibitor and is therefore used as an antidepressant
Illegal drugs that can cause a tolerance to Amphetamines are (but not limited to)...
- Crystal Meth (Street Methamphetamine) - Amphetamine Stimulant that has no set milligram, so there is no way of knowing how much you're taking. Pharmaceutical grade Methamphetamine - trade name Desoxyn - has proven to be much safer than street meth.
- Ecstasy (methylenedioxymethamphetamine, aka MDMA, Molly, Ecstacy, X) – a serotonin-releasing entheogenic stimulant.
- Khat (Cathinone) - A naturally occurring plant that contains a potent amphetamine-like stimulant called "cathinone"
- Methcathinone - Methcathinone is a methylated derivative of cathinone. Just like Methamphetamine, it has proven to be more powerful than its precursor - cathinone - and is therefore also illegal. It is commonly manufactured from pseudoephedrine, especially in Eastern Europe, due to the ease of synthesis. Heavy metals used in the synthesis can cause posioning and brain damage.
- Mephedrone, and related cathinones. Mephedrone is 4-methylmethcathinone, and became popular in the early 2000s as a replacement for drugs like ecstacy, cocaine, and the amphetamines.
- MDPV, or methylenedioxypyrovalerone, a very potent cathinone derivative sold as a “research chemical”. It is a powerful dopamine and norepinephrine reuptake inhibitor.
- Cocaine.
- MDA and analogues
The most common way to slow development to tolerance, or possibly reverse it, is the use of NMDA receptor antagonists. However, there are many other ways to increase the effects of amphetamines - thus making the effects more noticeable, even with tolerance. This guide is really only meant for people who can't go a day without taking their medication because of some medical issue they have - such as narcolepsy or extremely severe forums of ADHD. I will start by listing what can help increase the effects of an amphetamine by listing them in the order they appear on this page.
- Cessation of use – this is obvious, stopping amphetamine use will let your body regain equilibrium again after some time.
- Alkalizing agents (i.e. Bicarbonate, calcium carbonate) - This helps increase the absorption & bio-availability of an amphetamine if taken orally, and decreases the amount excreted in the urine.
- Combining stimulants - As described above, taking two stimulants together help potentate the effects of each other.
- Taking Vitamin supplements - This is sort of the same idea as stimulant + stimulant potentiation. However taking vitamin supplements to increase a stimulants effects is different.
- NMDA receptor antagonists - This causes reduced tolerance by decreasing the flow of calcium ions through the NMDA receptor, slowing the development of tolerance.
Lowering Tolerance - Stopping All Use
By far the easiest and safest way of lowering tolerance to anything is by stopping all use of that substance for an extended period of time. I understand that isn't an option for some people. But for everyone taking amphetamines recreationally, this is by far the most effective way. The only downside is it takes time.
Potentation - Alkalization & Bio-Availability
Taking an alkalizing agent with an Amphetamine - when you take it orally - will help increase its effects by allowing more of it to be absorbed by your stomach. Potentiating your dose by alkalising your stomach will not reduce tolerance, as you are actually increasing the amount of amphetamine that is making it to your brain. Ampheatmine is less well absorbed in strongly acidic conditions than neutral or basic conditions. Taking something like Tums, Rolaids or baking soda should increase its effects a little bit more by causing an increase in bio-availability. However baking soda tastes awful. I recommend Tums or some other calcium carbonate tablets if you can't handle the taste. But if you can somehow take baking soda without puking from the horrid taste, I recommend that more since the alkalising effects of Tums only last for 30 minutes or so.
Taking too much baking soda can cause excess sodium in the blood, and can possibly cause severe gas or bloating, as well as causing diarrhea.
Taking baking soda and calcium carbonate may have a constipating effect if you take too much.
Potentiation - Stimulant + Stimulant
Taking a stimulant, with another stimulant is also an effective way at increasing the effects. For instance, taking methylphenidate with dextroamphetamine will increase the effects of both stimulants. Since taking a scheduled stimulant with another scheduled stimulant isn't practical since both of those are going to - or should - be strong enough on their own, you should consider taking over the counter stimulants to help increase prescription stimulant effects.
Obviously, combining 2 stimulants with a common mode of action won't decrease your tolerance.
Combining stimulants increases the potential for adverse effects like paranoia, anxiety, panic, high blood pressure, etc. and should always be done with care
The two OTC stimulants most people will have access to are caffeine, or ephedrine/pseudoephedrine.
Caffeine - Caffeine does an okay job at helping to increase the effects of a prescription stimulant. However, since many people also have a considerable tolerance to caffeine (I know I do!), you may have to take a higher dose of Caffeine than your used to. Purchasing some caffeine pills at your local GNC or any other nutrition store should give you 100mg or 200mg pills. I personally don't like Caffeine since it makes me shaky at higher doses. But if you don't have a problem with that, then go for it!
Pseudoephedrine & Ephedrine (original trade name; Sudafed) – the ephedrines are amphetamines that are from the Ephedra genus of plants. They are less centrally active than amphetamine is, and produce effects primarily by releasing norepinephrine and mimicking adrenaline at receptors. Ephedrine is more potent than pseudopehedrine by a factor of 8 to 10 times. The ephedrines are primarily used as stimulating decongestants. Overuse of ephedrine and pseudoephedrine can cause hypertension (high blood pressure) and sometimes rebound congestion.
Levmetamfetamine - (original trade name; Vicks Vapo Inhalers - Levmetamfetamine is the levorotatory enantiomer of Methamphetamine and is found in Vicks Vapo Inhalers. Levmetamfetamine is a synonym by the drug companies used to hide the fact that one of the active ingredients is "Levomethamphetamine." Methamphetamine has recreational value, however, the Levorotatory isomer of Methamphetamine is CNS inactive. This means it does no have any effect on the Central Nervous System or brain. Due to this fact, it will not give you a high like Methamphetamine does. It does have some Norepinephrine effects outside of the CNS and therefore is a mild stimulant.
Levmetamfetamine can be used to increase the effects of a CNS active stimulant. However, caution should be used when using Levmetamfetamine due to it's ability to cause hypertension and anxiety. Also, it should be noted that, even though Levmetamfetamine is, technically, Methamphetamine - there is no recreational value to abusing it. I've tried and it does provide mild stimulation, however, the amount required for mild stimulation is the same amount that can give you bad anxiety and cause hypertension. Caution is advised when dosing.
Propylhexedrine (original trade name; Benzedrex - Propylhexedrine is very similar to Methamphetamine. It's molecular structure is exactly the same as Methamphetamine. The only way the two differ is; Propylhexedrine has a cyclohexyl group (cyclohexane) where Methamphetamine would have a Benzene ring. Propylhexedrine has pharmacology similar to that of Amphetamine. It's able to cross the blood-brain barrier and inhibits DAT, NET and SERT through TAAR1 agonism (speculated) just like Amphetamine does.
Propylhexedrine, therefore, may have potential recreational value. However, it's vastly less potent than Amphetamine or Methamphetamine is, and therefore is used in the same way levmetamfetamine is - nasal decongestion via nasal inhalation. The same warnings apply to Propylhexedrine as Levmetamfetamine - the amount required for mild stimulation is the same amount that can give you bad anxiety and cause hypertension. Caution is advised when dosing.
Bupropion (Wellbutrin) - Bupropion is a stimulant-like antidepressant that stops the reuptake of Dopamine and Norepinephrine just like most other stimulants. It is related to the cathinones, and has a mild stimulating effect even though it does not reliably produce euphoria. Combining buproprion with amphetamines may increase the risk of seizure, especially at high doses of buproprion. It is also disputed whether or not bupropion will help increase the effects of Amphetamine. Some users report it does, and some report it doesn't. Pharmacology doesn't help us determine this either. Try a low dose and decide for yourself
Vitamin supplements - Vitamins + Stimulant potentiation
L-Tyrosine, L-DOPA The aforementioned chemicals are precursors to Dopamine. By taking L-Tyrosine or L-DOPA, the body will absorb it and use it to synthesize Dopamine. Therefore - any stimulant that has dopaminergic effects will have an increase in Dopamine levels on top of the stimulants effects on Dopamine. What this means is; besides the increase in dopamine levels that the stimulant will produce, L-Tyrosine or L-DOPA will also increase Dopamine levels on top of that due to the fact that the body will turn it into Dopamine.
(Will add more tomorrow)
NMDA antagonists for tolerance reduction
For the average person, the best option is to take between 30 and 60 mg of DXM, once or twice a day (first alongside your amphetamine dose, then halfway through the day). Get a bottle of magnesium supplements as well, and take the recommended dose in the morning. Eating healthy and excercising will also help.
If you can find some, memantine or amanitidine are good replacements because they lack the SNRI "antidepressant" effect of DXM They used to be used as influenza antivirals before every strain of the flu developed resistance. Now they are used to help treat neurodegenerative diseases.
OTC NMDA Antagonists
- Magnesium - Yup, that's right! Plain old magnesium is an NMDA antagonist and will help lower amphetamine tolerance. This is by far the safest one, but the least effective.
Magnesium supplements come in several forms, as pure magnesium is an indigestible metal. "Chelated" magnesium is any form of magnesium that is paired with a carbon-based acid, like magnesium citrate or magnesium glycinate. You will often hear people say "only get chelated magnesium", but realistically, any form will work. You can even just eat 1/2 gram of Epsom salts a day. The NIH recommends people don't eat more than 350mg of elemental magnesium a day. (i.e. 3.5 gm of magnesium citrate, or sulphate, both about 10% by weight Mg) because it can have a laxative effect and in rare cases can cause electrolyte imbalances. Magnesium is also reputed to reduce jaw grinding, clenching, and muscular twitching.
Magensium is even absorbed through the skin, if you bathe in water with a cup or so of epsom salts (magnesium suphate). - Zinc – Zinc supplementation can help NMDA receptor function
- Dextromethorphan (DXM) - This is the main anti-cough medication that is found in OTC drugs like Nyquil, Robotussin and Mucinex. Taking some of this everyday (commonly stated as 30 to 60mg a day) has been reported to lower tolerance. DXM is a serotonin and norepinephrine reuptake inhibitor as well, and may produce dependence if overused.
- Alcohol (Ethanol) – Alcohol is a NMDA antagonist, but its use for reducing amphetamine tolerance is discouraged. Regular use of alcohol can lead to dependence and liver damage.
- Memantine and amantidine - NMDA antagonists that are used as neuroprotectants. These are long-duration and have fewer side effects than e.g. PCP. they are probably your best choice, if you can get access to them.
- Ketamine – Developed as an analogue of PCP with a shorter duration and more tolerable side effects profile, ketamine is an anesthetic and dissociative hallucinogen that is commonly used in emergency/battlefield medicine, to anesthetise children or people with liver problems, and in veterinary usage. However, prescriptions for ketamine are extremely rare, and it is usually only ever used as a anesthetic for patients undergoing surgery. Sometimes it is formulated into a cream to be used as a topical painkiller. In recent years ketamine has been touted as a cure for depression. Overuse of ketamine is associated with bladder damage in some individuals. Its duration is likely too short for use preventing tolerance.
- Methoxetamine, 3-MeO-PCP, et cetera – these are analogues of ketamine and PCP sold as “research chemicals”. They have much longer durations than ketamine, and are suitable for use as tolerance reduction aids if the doses are kept very low - below "psychedelic" effect levels.
- Nitrous Oxide - Also know as a laughing gas, is used to render people insensible during dental work. Nitrous Oxide is also used to sedate people during surgeries. Nitrous Oxide is never given out in a prescription, but it can be found in whipping cream cans as well as “whippits” designed for whipped cream dispensers, because it provides more foaming action than air. Nitrous oxide has a very short duration, and so must be continually delivered as a mixture with oxygen in surgery. Used recreationally it produces a rapid and short-acting high, and is therefore not suitable for use to reduce tolerance. Overusage can cause oxygen deprivation and depletion of vitamin B12.
- Methadone - Methadone is an opioid that is used to help opioid addicts stabilise and detox. It has a long half life, and due to its potency is often very addictive itself. It is also used in chronic pain treatment. Methadone is more toxic than other opioids and has a high risk of overdose when combined with other depressants. It is not suitable for regular use unless you are opioid dependent.
- Tramadol – Tramadol is a moderately weak opioid with additional painkilling effects, used as a codeine replacement and in veterinary medicine. It is a weak NMDA antagonist and has a variety of other effects, making it unwise to use for tolerance reduction.
- Phencyclidine (PCP) – PCP was developed as an abnesthetic, but its long duration of action and tendency to produce hallucinations led to it being rebranded as a veterinary anesthetic, and eventually banned. It is used as a dissociative hallucinogen and commonly smoked on cigarettes or marijuana joints known as “dippers” or “sherm sticks”. It has a very long duration of action, and can be a powerful intoxicant, so must be used with care if you plan to use it for tolerance reduction... if at all.
- Ibogaine - a powerful hallucinogen that has a wide spectrum of effects, but is also a NMDA antagonist. It is too hallucinogenic and expensive for regular use, & can cause cardiac problems because it binds to a protien known as hERG.
- MK-801 - a "research chemical" and very potent NMDA antagonist.
Wikipedia: Amphetamine, methamphetamine, methylphenidate.
Erowid: Amphetamines, methylphenidate
Bluelight: NMDA antagonists for tolerance (part 2), Amphetamine FAQ, Amphetamine Neurotoxicity and Tolerance Prevention (part 2, part 3)
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