Perhaps you’ve been using Adderall as a study pill, whether you take it every day or during exam periods. Or maybe you have attention-deficit hyperactivity disorder (ADHD) and have been seeking treatment for years. In either case, you tried Adderall and felt like you found the right medication. But now, everything seems to be going wrong.
Adderall tolerance is a very real and distressing issue. Although you may feel amazing on Adderall, drug tolerance is your brain and liver’s way of protecting you from potentially harmful effects. So how does it happen, and what can we do to reverse it?
Key Takeaways: Adderall Tolerance
What Is Adderall Tolerance?
Adderall tolerance is an example of the biological process where a previously effective prescription medication becomes less effective over time. In some ways, it is in fact a normal, healthy response to taking a drug for a long period. However, a long-term lack of response could indicate serious issues.
What Causes Adderall Tolerance?
How Adderall works is through an increase of your levels of dopamine, noradrenaline, and certain other neurotransmitters, such as serotonin . Your body responds to this by turning down the production of these neurotransmitters. This is why missing a dose, or Adderall withdrawal, can leave you feeling terrible.
The vast majority of physiological processes are controlled by negative feedback loops. High levels of substances such as neurotransmitters or hormones will then turn their production down, so they don’t reach dangerously high concentrations. While it’s easy to feel like your body is betraying you, this is a protective response.
Additionally, with repeated exposure to certain substances, your liver ramps up detoxification. You may remember your first time trying alcohol, and how you were much more sensitive then than now. Or, if you don’t drink often, you’re more sensitive than your friends who drink regularly. This is because the parts of your liver cells that produce detoxification enzymes increase in number, as a specific response to Adderall .
Research suggests that tolerance is more likely with continuous doses of the drug, instead of occasional high doses. Shorter-term high doses are often used in animal research to test the effects of long-term Adderall use, but continuous smaller doses are more relevant to how we actually take the drug .
Why Is My Adderall Not Working Anymore?
A gradual, persistent loss of response to Adderall could indicate something more serious. Lab research points to the possibility that real-world doses of the drug may eventually damage dopaminergic neurons. Both dopamine and dopamine transporters significantly declined in primates taking realistic Adderall doses.
This could stop you from responding to the drug, as you aren’t making enough dopamine for it to work with. However, children seem to be better protected and may not build tolerance through this mechanism. As more children use Adderall than adults, we haven’t picked up this adverse effect yet .
Damage to the neurons may be partly caused by high levels of cortisol. If you miss a dose of Adderall, or worse, go through the Adderall crash, cortisol rises in response to the sudden fall in dopamine. Through oxidative stress, cortisol not only damages the neurons you already have but also impairs the growth and development of new ones  .
Research comparing amphetamined drugs (tested with MDMA), Ritalin, and modafinil found that, out of the three prescription stimulants, only the amphetamines raised cortisol.
While the placebo group’s cortisol levels were only 630nmol/L, those taking MDMA had an average cortisol concentration of 942nmol/L. MDMA is a stronger, illegal amphetamine, but Adderall may have a milder effect .
Adderall Tolerance Build Up: What To Know
Your body gets used to Adderall sooner than you think, but the most important thing is to stay safe.
How Long Does It Take for Adderall Tolerance?
The early signs of Adderall tolerance may even start within a few days. A study involving healthy men and women, with no ADHD or other disorder, showed the beginnings of tolerance after only three doses spread over five days. Just one dose significantly increased blinking rate, but after the third, this fell back to levels seen in the placebo group.
On the other hand, energy (measured as vigor) was higher after three doses than one alone. This means that while you develop a tolerance early, you are unlikely to see any negative effects of this for quite some time .
Noticeable Adderall tolerance can take weeks or months to appear. A study involving children with ADHD taking Ritalin, another stimulant, showed that the average child needed one or two dosage increases over the course of 10 months.
For children taking ADHD every day, there was an average of 1.79 dosage increases. However, having an “Adderall holiday” on the weekends reduced this down to 1.61 increases in their dose.
This means occasionally using the drug as a study pill, or reserving it for the most difficult periods of the semester, is less likely to cause tolerance. If you have ADHD, taking breaks could mean you will reach tolerance to your current dose a little slower, but use caution to avoid Adderall withdrawal symptoms .
What Adderall Dosage Works Best?
If you need stimulants for medical reasons, do not use larger doses of Adderall than what has been prescribed to you. The upper limit for the drug is set at 40 mg per day for ADHD symptoms, and up to 60 mg per day for narcolepsy. The right dose for you depends on how well you respond to Adderall. Only your doctor can determine this, as it is individual .
In research revealing tolerance through a loss of dopaminergic neurons, the response of the serotonin system was unchanged. One of the dangers of Adderall is therefore the perceived need to take higher doses because you could be at risk of serotonin syndrome.
Depending on the severity, serotonin syndrome can involve anything from a faster heart rate and rest under medical supervision, to organ damage and intensive care .
How To Make Adderall Work Again: 6 Simple Tips
If you’re missing the benefits of Adderall, there are simple ways to make your ADHD drugs work better for you again without turning to Adderall abuse. You may have been eating foods that impair absorption, leading to an easy misunderstanding that the stimulant medications have stopped working.
On the other hand, there is hope if your dopaminergic systems have been burnt out by stimulant medication use. While impaired dopamine responses have been documented up to three years after quitting the drug, they slowly improve even without intervention .
1. Stay Hydrated
Dehydration can make you feel terrible and increase cortisol levels . The discomfort of dehydration may paint a higher dose of Adderall in a more tempting light, while cortisol contributes to brain cell damage. What’s more, a tall glass of water alongside Adderall can dilute your stomach acid, which aids absorption .
2. Avoid Citrus Juice
Dietary acids, such as citric acid, are known to reduce the absorption of amphetamines from the intestines and into the bloodstream. All citrus fruits are particularly rich in these, so it’s best to avoid them and even more so around the time when you take your medication .
3. Don’t Miss Breakfast
It doesn’t matter how busy you are; don’t skip meals, including breakfast. Taking Adderall on an empty stomach may reduce its absorption as your digestive system’s pH is more acidic.
Some nutrients can aid neurotransmitter systems too. For example, choline may increase your levels of dopamine receptors in the reward system . Eggs are one of the best natural sources of choline, whether they are fried, scrambled, or boiled.
4. Avoid Vitamin C in the Evenings
The technical term for vitamin C is ascorbic acid—yes, it’s an acid too! Like citric acid, it can impair the absorption of amphetamines such as Adderall. Do not take vitamin C near your dose of Adderall; if you need both, separate them by a few hours .
5. Develop Healthy Sleep Patterns
Healthy sleeping patterns keep your levels of cortisol within the correct rhythms. This protects your brain against damage in the long term and can assist in the restoration of neurotransmitter systems as a result.
What’s more, you are likely to feel better mentally. A common psychological cause of taking Adderall is a lack of coping skills and self-care, as stimulant drugs may be seen as all you need . Making healthy lifestyle choices now could improve your overall wellbeing and prevent Adderall addiction to fill the gaps.
6. Know When To See a Doctor
If your ADHD symptoms are returning to their pre-medication state, and you’re still taking Adderall at the recommended dose, it’s best to see a doctor. It may be tempting to experiment with higher doses, but this can be dangerous, especially without medical supervision.
Sometimes, it may be best for you to have a break from taking Adderall (and possibly other stimulant medication) or change over to other drugs entirely. Adderall is often recommended for shorter-term use only due to potential long-term effects .
Adderall Tolerance Reset Supplements
If you want to prevent Adderall tolerance or take low doses instead, there are nootropic supplements that can help increase dopamine and noradrenaline. This means they can prevent you from developing tolerance, compensate for falling Adderall efficacy, or even replace the drugs altogether. As a result, they are often described as OTC Adderall, or natural Adderall.
Many people who abuse Adderall also prefer to transition onto nootropics to benefit neurological health and prevent future substance abuse as they are not addictive. If this is you, a medically supervised tapering program may still be necessary, especially if you take a high dose.
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Some, such as Bacopa monnieri, assist in the production of dopamine and noradrenaline . Citicoline is a safer supplemental version of choline, which helps to increase dopamine receptor counts . These benefits can help prevent tolerance to Adderall and keep you at your original dose, or soothe withdrawal symptoms if you want to quit abusing Adderall.
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Phosphatidylserine can help you recover from Adderall misuse or other stimulant drug abuse by assisting the repair of neurons . Maritime pine bark is a potent antioxidant, able to end the cycle of oxidative stress and cell damage seen with high cortisol or neurotransmitter toxicity .
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What are the most important things we need to know about Adderall tolerance?
Does Adderall Become Less Effective Over Time?
ADHD medications, including Adderall, begin losing their potency within a few days. This will likely begin as reduced severity of side effects, but it is common to need an increased dose after several weeks or months.
Does Adderall Cause Drug Tolerance?
Both normal physiological processes and Adderall itself cause you to develop a tolerance. The same mechanisms of liver detoxification that make you more able to handle alcohol can also cause you to metabolize Adderall faster. By dialing down dopamine signaling and potentially causing neurotoxicity, taking the drug every day for long periods leads to tolerance too.
Can You Build a Tolerance To Amphetamines?
Research described above has demonstrated a tolerance through the dopaminergic pathways, but the serotonergic system does not necessarily follow. With a partial tolerance, you may still be vulnerable to serotonin syndrome symptoms if you increase your dose without supervision or past the safe range.
Adderall tolerance is the result of several biological processes where your detoxification ability speeds up, neurotransmitter production falls, and dopaminergic systems face potential damage. If your study success is falling back into a nightmare, nootropic supplements can be a safer, more effective alternative to the drug.
If you require stimulant medication, there are ways you can maintain the drug’s therapeutic effects. Through nootropic supplements, keeping healthy lifestyle habits, and managing stomach acidity around your Adderall doses, you can stay on top of your ADHD symptoms.
- U.S. Food and Drug Administration. “Adderall.” (2017) https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/011522s043lbl.pdf
- Tortora, Gerald J. & Derrickson, B. “Principles of anatomy & physiology.” Wiley (2011).
- Turner, Amy C et al. “Repeated intermittent oral amphetamine administration results in locomotor tolerance not sensitization.” Journal of psychopharmacology (Oxford, England) vol. 32,8 (2018): 949-954. doi:10.1177/0269881118763984
- Ricaurte, George A et al. “Amphetamine treatment similar to that used in the treatment of adult attention-deficit/hyperactivity disorder damages dopaminergic nerve endings in the striatum of adult nonhuman primates.” The Journal of pharmacology and experimental therapeutics vol. 315,1 (2005): 91-8. doi:10.1124/jpet.105.087916
- Bray, Brenna, et al. “Amphetamine withdrawal differentially affects hippocampal and peripheral corticosterone levels in response to stress.” Brain Research, 1644, (2016): 278–287. doi:10.1016/j.brainres.2016.05.030
- de Souza-Talarico, Juliana Nery et al. “Effects of stress hormones on the brain and cognition: Evidence from normal to pathological aging.” Dementia & neuropsychologia vol. 5,1 (2011): 8-16. doi:10.1590/S1980-57642011DN05010003
- Dolder, Patrick C et al. “Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects.” Psychopharmacology vol. 235,2 (2018): 467-479. doi:10.1007/s00213-017-4650-5
- Strakowski, S M et al. “Human response to repeated low-dose d-amphetamine: evidence for behavioral enhancement and tolerance.” Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology vol. 25,4 (2001): 548-54. doi:10.1016/S0893-133X(01)00253-6
- Pelham, William E, and James M Swanson. “Examining Tolerance to CNS Stimulants in ADHD.” Clinicaltrials.gov, 22 Jan. 2013, clinicaltrials.gov/ProvidedDocs/08/NCT02039908/Prot_SAP_000.pdf.
- Wang, Robert Z et al. “Serotonin syndrome: Preventing, recognizing, and treating it.” Cleveland Clinic journal of medicine vol. 83,11 (2016): 810-817. doi:10.3949/ccjm.83a.15129
- Hayley, Amie C et al. “Amphetamine-induced alteration to gaze parameters: A novel conceptual pathway and implications for naturalistic behavior.” Progress in neurobiology vol. 199 (2021): 101929. doi:10.1016/j.pneurobio.2020.101929
- Zaplatosch, Mitchell E, and William M Adams. “The Effect of Acute Hypohydration on Indicators of Glycemic Regulation, Appetite, Metabolism and Stress: A Systematic Review and Meta-Analysis.” Nutrients vol. 12,9 2526. 20 Aug. 2020, doi:10.3390/nu12092526
- Giménez, R et al. “Changes in brain striatum dopamine and acetylcholine receptors induced by chronic CDP-choline treatment of aging mice.” British journal of pharmacology vol. 104,3 (1991): 575-8. doi:10.1111/j.1476-5381.1991.tb12471.x
- Yanofski, Jason. “The Dopamine Dilemma-Part II: Could Stimulants Cause Tolerance, Dependence, and Paradoxical Decompensation?.” Innovations in clinical neuroscience vol. 8,1 (2011): 47-53.
- Aguiar, Sebastian, and Thomas Borowski. “Neuropharmacological review of the nootropic herb Bacopa monnieri.” Rejuvenation research vol. 16,4 (2013): 313-26. doi:10.1089/rej.2013.1431
- Friedman, Mendel. “Chemistry, Nutrition, and Health-Promoting Properties of Hericium erinaceus (Lion’s Mane) Mushroom Fruiting Bodies and Mycelia and Their Bioactive Compounds.” Journal of agricultural and food chemistry vol. 63,32 (2015): 7108-23. doi:10.1021/acs.jafc.5b02914
- Naftelberg, Shiran et al. “Phosphatidylserine improves axonal transport by inhibition of HDAC and has potential in treatment of neurodegenerative diseases.” Neural regeneration research vol. 12,4 (2017): 534-537. doi:10.4103/1673-5374.205082
- Malekahmadi, Mahsa et al. “The effect of French maritime pine bark extract supplementation on inflammation, nutritional and clinical status in critically ill patients with traumatic brain injury: A randomized controlled trial.” Phytotherapy research : PTR, 10.1002/ptr.7187. 12 Aug. 2021, doi:10.1002/ptr.7187