Adderall is a psychostimulant medication [of the phenethylamine classification] comprised of multiple amphetamine isomers: dextroamphetamine (~75%) and levoamphetamine (~25%). In medical settings, Adderall is frequently prescribed for the management of ADHD (attention-deficit/hyperactivity disorder) and narcolepsy. Less commonly, Adderall is utilized off-label as an adjunct in the management of refractory neuropsychiatric disorders such as: chronic fatigue syndrome; major depressive disorder; and atypical anxiety disorder.
Additionally, it is understood that Adderall and related psychostimulants are sometimes pursued for nonmedical purposes like recreational intoxication and performance enhancement (cognitive or athletic). When administered, the amphetamine isomers dextroamphetamine and levoamphetamine function predominantly via full agonism of TAAR1 receptors and modulation of VMAT2. The simultaneous action at TAAR1 and VMAT2 enhances catecholamine signaling throughout the central nervous system.
Due to this catecholaminergic effect, Adderall users generally report improvements in attention span and energy. In the event that you received a prescription of Adderall from a doctor to help manage symptoms of a medical condition, you may be curious as to how long it’ll take for the medication to “kick in” or facilitate a therapeutic effect. After all, you’re probably hoping that Adderall will help reduce your symptoms as quickly as possible.
How long does it take for Adderall to “kick in” or work?
It depends on the particular Adderall user. For a majority of users, the effect of Adderall will become noticeable within just 20 to 60 minutes following administration. This is because when Adderall is ingested, its amphetamine constituents are efficiently and rapidly metabolized, and distributed throughout the body. In both the central nervous system and peripheral nervous system, Adderall immediately begins modulating neurophysiologic targets such as: TAAR1 and VMAT2 (in the CNS) and adrenergic receptors (in the PNS).
This immediate modulation yields increased signaling from catecholamines like dopamine, norepinephrine, and epinephrine – as well as increased activation of the sympathetic nervous system. Assuming a healthy person takes Adderall as directed – and the medication is properly absorbed, metabolized, and distributed throughout the body – the medication will always start working in less than 1 hour (usually in under 30 minutes).
Although Adderall will always “kick in” or facilitate an effect in just minutes after administration, not all individuals will be consciously aware of this effect. Users who don’t notice its effect within an hour of administration may question whether the medication is really working. In most cases, two variables will be most influential in determining whether you’re able to consciously detect Adderall working: dosage administered and degree of tolerance (to psychostimulants).
Someone who exhibits high tolerance (to psychostimulants) and/or who ingests a tiny dose of Adderall – may have a difficult time detecting the effect of Adderall after administration. On the other hand, a person without any preexisting tolerance to psychostimulants and/or who ingests a high dose – may notice the medication “kick in” very rapidly. That said, just because you don’t consciously notice Adderall working does not mean that the medication hasn’t taken effect.
If you don’t notice Adderall working, variables such as: concurrent substance use; intestinal pH; preexisting medical conditions; and low self-awareness – might be to blame. Moreover, it’s reasonable to hypothesize that some individuals may not notice Adderall working on the first day – or even week of treatment due to: inadequate dosing and/or lack of medication-induced changes in neurophysiology (e.g. nerve growth) that are only attained with longer-term treatment.
In other words, some individuals may not notice Adderall working because they start treatment with too low of a dose – and need to titrate or increase the dosage to notice an effect. Additionally, neurophysiologic adaptations that can only be attained with longer-term use may need to occur for some individuals derive maximal therapeutic benefit from Adderall.
Note: It is important to mention that not everyone will derive therapeutic benefit from Adderall. Certain users may claim that the medication failed to manage unwanted symptoms of a medical condition (e.g. ADHD). Although Adderall sometimes won’t “work” for the management of medical symptoms, it always “works” in terms of exerting a neurophysiologic effect.
Why Adderall should “kick in” immediately or relatively quickly…
A majority of Adderall users will notice the medication working right away – or within 20 to 60 minutes of administration. Others may not fully notice the effect of Adderall on the first day of treatment, but might really notice that the medication has “kicked in” after several consecutive days of administration. Individuals who respond to Adderall on the first day of treatment are in the majority – rapidly responding to Adderall is considered normal.
Included below are reasons as to why Adderall should facilitate a noticeable effect on the first day of administration. Such reasons include: efficient absorption, metabolism, and distribution – as well as immediate neurochemical action of amphetamine salts within the CNS and PNS. It’s also likely that Adderall: changes in neural connectivity and alters cerebral blood flow to facilitate a rapid onset of effect.
Efficient absorption and distribution
When ingested, amphetamine constituents of Adderall (dextroamphetamine and levoamphetamine) are rapidly absorbed within the gastrointestinal tract, exhibiting respective bioavailabilities of approximately 75%. Next, dextroamphetamine and levoamphetamine are distributed throughout bodily tissue, with highest concentrations entering the brain and cerebrospinal fluid.
Rapid CNS modulation
Once Adderall reaches the brain, it immediately begins modifying the user’s neurochemistry. Although the amphetamine constituents of Adderall (dextroamphetamine and levoamphetamine) interact with the same neurochemical targets, the potency of each varies depending on the specific target. After reaching the brain, dextroamphetamine and levoamphetamine agonize TAAR1 and modulate VMAT2.
Agonism of TAAR1 causes neuronal membrane-bound monoamine transporters to: cease transport of monoamines OR transport monoamines out of neurons. Amphetamine-mediated modulation of VMAT2 facilitates monoamine release from synaptic vesicles – into intraneuronal fluid. The net result of these actions is heightened signaling from stimulatory neurotransmitters like norepinephrine, dopamine, and epinephrine – and increased CNS activation.
Other specific actions of amphetamines within the brain include: inducing the release of norepinephrine via adrenergic receptors; inducing dopamine release via mesocorticolimbic system and nigrostriatal dopamine system; agonizing serotonin receptors; and inhibiting monoamine oxidase. In any regard, it is the immediate neurochemical action of Adderall within the CNS that causes most users to notice its effect within 20 to 60 minutes of administration.
Rapid PNS modulation
In addition to quickly modifying activation within the central nervous system, Adderall rapidly exerts an effect within the peripheral nervous system (PNS). The amphetamine constituents of Adderall (dextroamphetamine and levoamphetamine) interact with adrenergic nerve terminals; alpha-adrenergic receptors; and beta-adrenergic receptors in the peripheral. These interactions bolster activation of the sympathetic nervous system, which in turn, increases physical energy and performance.
Additionally, activation of the sympathetic nervous system can cause a “fight-or-flight”-like response characterized by: blood vessel constriction; pupil dilation; perspiration (i.e. sweating); increased heart rate; palpitations; and/or high blood pressure. Even if you don’t notice Adderall providing an immediate effect in reducing your medical symptoms, you may notice it “working” based on side effects consistent with increased activation of the sympathetic nervous system.
Rapid alteration of cerebral blood flow, neural connectivity, neuroelectrical activity
Another reason Adderall might “kick in” rapidly could be related to its modulation of numerous aspects of brain activation, including: cerebral blood flow; neural connectivity; and neuroelectrical activity (i.e. brain waves). For example, research by Russo, Hall, Chi, et al. (1991) suggests that amphetamine administration substantially increases cerebral blood flow in rats.
Specifically, average cerebral blood flow significantly increases in areas of the brain such as: the cortex, basal ganglia, pons, and medulla. It’s possible that the increase in cerebral blood flow to the brain – or particular regions – can alter consciousness, improve attention, and increase cognitive endurance.
Additionally, neuroimaging research by Schrantee, Ferguson, Stoffers, et al. (2016) discovered that acute exposure to dextroamphetamine significantly reduces functional connectivity in the cortico-striatal-thalamic network, default mode network, and salience-executive networks. It’s likely that alterations in connectivity (even if mediated by neurotransmitter changes) help explain the immediate action of Adderall.
What’s more, it is understood that neuroelectrical activity undergoes change as a result of psychostimulant medications. Due to the stimulatory effect of Adderall, brain waves are thought to undergo a shift from lower frequencies (e.g. alpha and theta) to higher ones (e.g. beta). Perhaps shifts in neuroelectrical activation post-Adderall administration aids in the facilitation of its rapid action.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/1905179
- Source: https://www.ncbi.nlm.nih.gov/pubmed/26149196
Placebo-like effect on Adderall (?)
Although Adderall generally induces a noticeable effect within minutes of administration, its initial effect may be enhanced by and/or partly attributable to preexisting expectation that it’s going to work – or a placebo-like effect. It is well-understood that if a person strongly believes his/her medication will “work” or facilitate an effect, this strong belief can alter neurophysiology to induce an effect.
In other words, a subset neurophysiologic alterations occurring while under the influence of Adderall could be attributable to user expectation, thereby generating a placebo-like effect. Though we know that amphetamine constituents within Adderall are predominantly what facilitate a noticeable effect, it’s possible that there might be synergistic influence from a placebo-like effect in a subset of users.
For example, someone may expect that Adderall will start working within 30 minutes of administration – and this expectation may modify aspects of neurophysiology to induce a rapid effect. Moreover, perhaps the combination of expectation-mediated neurophysiologic changes plus Adderall-mediated neurophysiologic changes could explain prominent and/or noticeable effects in the early stages of treatment.
Nevertheless, whether a placebo-like effect may contribute to rapid onset of Adderall action is debatable. It’s fair to assume that a placebo-like effect may play no role whatsoever in a subset of rapid responses to Adderall, whereas it might augment the effect of Adderall in another subset.
Why Adderall may “kick in” later than you expect…
If you don’t notice Adderall working on the very first day of treatment, there are several possible reasons. Reasons that Adderall may take longer than you expect to “kick in” include: inadequate dosing; poor absorption (e.g. due to atypical intestinal pH); concurrent substance use; and lack of long-term neurophysiologic adaptations.
Assuming you aren’t using other medications with Adderall and you don’t have a medical condition (or abnormal intestinal pH) that might interfere with its absorption, the medication should take effect within 20 to 60 minutes of administration. However, if you’re using an extremely low dose (especially relative to preexisting tolerance) and/or have low self-awareness, you may not consciously notice its effect until the dosage is increased.
Moreover, in order to reap maximal therapeutic benefit from Adderall, you may need to take it regularly for several weeks or months. Although Adderall is a fast-acting medication, it is understood that longer-term use can induce favorable neurophysiologic adaptations that do not emerge in the short-term. Perhaps these longer-term neurophysiologic adaptations are what provide a therapeutic effect in a subset of users.
Low or inadequate Adderall dose
Though many people can detect the effect of Adderall on the first day of treatment, even with a low dose, others may not notice any effect as a result of low dosing. In other words, someone who is prescribed a low starting dose of Adderall may report feeling no different than before using Adderall. In this case, a medical doctor may need to gradually titrate or adjust the Adderall dosage to a level that facilitates a noticeable effect.
For adults with ADHD, the therapeutic dosage range of Adderall is 5 mg to 40 mg per day, whereas for adults with narcolepsy, the therapeutic dosage range is 5 mg to 60 mg per day. If you start at 5 mg per day and don’t notice the medication working – it’s likely that the dose was too low. As you gradually increase the dosage from 5 mg to 10 mg or 20 mg – you should begin noticing a pronounced stimulatory effect.
Persons with high preexisting tolerance to psychostimulant substances and/or low self-awareness may be least likely to notice an effect from low Adderall doses. Individuals with high psychostimulant tolerance exhibit neurophysiologic adaptations to large doses of psychostimulants, such that when a low dose is administered, it may not facilitate a noticeable or therapeutic effect.
Adderall-mediated neuroplastic changes take time
While most individuals will benefit from Adderall within days or weeks of treatment, some individuals may report that Adderall works best when administered consistently for several months. Research suggests that long-term Adderall treatment induces neuroplastic changes throughout the brain that do not emerge with short-term use.
For example, a meta-analysis of neuroimaging studies conducted by Hart, Radua, Nakao, et al. (2013) reported that long-term treatment with psychostimulants may modify and normalize brain activity among persons with ADHD. Specifically, the meta-analysis noted that long-term psychostimulant treatment favorably modifies activation within the right caudate nucleus.
A literature review by Spencer, Brown, and Seidman, et al. (2013) documented that long-term administration of psychostimulant medications (at therapeutic doses) improves brain development and corrects structural and functional abnormalities in persons with ADHD. Individuals with ADHD who remain untreated and/or haven’t used psychostimulants like Adderall for a lengthy duration tend to exhibit abnormal neural activity.
Frodl and Skokauskas (2012) conducted a meta-analysis of MRI studies that examined persons with ADHD. Results suggested that long-term treatment with psychostimulant medications (e.g. Adderall) favorably improves brain structure among persons with ADHD, whereas lack of treatment yields deleterious structural changes.
Specifically, it was noted that ongoing psychostimulant use protected against volume abnormalities within various regions, including the: right globus pallidus, putamen, caudate, anterior cingulate cortex, and amygdala. Researchers concluded that psychostimulant treatment has positive effects on brain structure.
Moreover, preliminary evidence suggests that ongoing amphetamine administration (at therapeutic doses) may increase BDNF and promote neurogenesis – or nerve growth within the brain. Because Adderall-mediated neuroplastic changes may only occur with consistent long-term administration – it’s possible that some individuals may notice the medication working better after longer-term use (e.g. months).
- Source: https://www.ncbi.nlm.nih.gov/pubmed/23247506
- Source: https://www.ncbi.nlm.nih.gov/pubmed/24107764
- Source: https://www.ncbi.nlm.nih.gov/pubmed/22118249
Variables that influence the onset of Adderall action
There are many variables that could influence how long it’ll take Adderall to “kick in” – or for a person to notice that the medication is working. Variables that likely impact how long it takes to notice the effect of Adderall include: the dosage administered; degree of stimulant tolerance; genetics; concurrent substance use; and preexisting medical diagnoses. Other variables such as: how Adderall is administered and the self-awareness of the user might influence whether someone notices the medication working.
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Initial Adderall dose (5 mg to 60 mg)
The starting dose of Adderall that’s prescribed could influence how quickly someone notices the medication “working.” Generally speaking, the higher the dose of Adderall that is administered to start treatment, the more likely a user will notice the medication working right away – within 20 to 60 minutes of administration. If lower Adderall doses are administered to start treatment, there’s a chance that the dosage end up being too low for certain users to notice its effect – or derive therapeutic benefit.
If you were to initiate treatment with a low dose of Adderall (e.g. 5 mg per day), you might struggle to detect its effect. Comparatively, if you were to initiate treatment with a moderate dose of Adderall (e.g. 20 mg per day), you’d be far more likely to notice the medication working. Because high doses of Adderall modulate neurophysiology to a greater extent than low doses – the psychostimulant effect derived from higher doses will be more pronounced or noticeable to the user.
Specifically, 40 mg of Adderall will interact with neurochemical targets such as TAAR1, VMAT2, and adrenergic receptors to a greater extent than 10 mg. This will yield greater stimulatory neurotransmission from dopamine, norepinephrine, epinephrine, etc. – than the lower dose. Predictably, it’ll be more obvious that you’re under the influence of Adderall – or that the drug is working when you initiate treatment with a higher dose.
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Degree of psychostimulant tolerance
If you have a history of regularly administering stimulatory substances, regardless of the type (e.g. prescription medications; over-the-counter agents; illicit drugs; or dietary supplements) – this could’ve lead to the development of stimulant tolerance. If you have preexisting psychostimulant tolerance, this may interfere with your ability to notice Adderall working – or “kicking in.”
More specifically, the significance of your psychostimulant tolerance relative to your dose of Adderall may determine whether you’ll be able to notice its effect. For example, someone with a history of using cocaine or methamphetamine at high doses use may not notice much of any effect following the administration of clinically-dosed Adderall due to high preexisting psychostimulant tolerance.
Even if you have a history of using Adderall for a long-term, you could develop “Adderall tolerance” such that the medication no longer works as well as it once did. Psychostimulant tolerance means that neurophysiology has undergone adaptation to the regular ingestion of psychostimulants and may be evidenced by: abnormal densities of neurochemical receptors; altered endogenous neurotransmitter production; or modified gene expression – to compensate for the regular presence of stimulant drugs.
If you have high psychostimulant tolerance relative to your Adderall dose, it may seem like the drug isn’t working or kicking in – even at reasonable doses. On the other hand, if you are psychostimulant-naïve or have no history of psychostimulant use, you’re more likely to notice Adderall working at a clinically recommended dose early in treatment due to lack of tolerance.
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Using substances with Adderall
Anyone who’s using substances with Adderall such as: pharmaceutical medications; dietary supplements, over-the-counter agents; or illicit drugs – could impact whether Adderall actually works, and if so, how long it takes to “kick in.” It is known that certain substances are not recommended to be administered with Adderall because they alter intestinal pH. Any concurrently-administered substances that increase acidification within the gastrointestinal tract will decrease Adderall absorption and prevent the medication from working as well as indented.
Oppositely, concurrently-administered substances that promote alkalization of the gastrointestinal tract might enhance Adderall absorption and expedite its onset of action. In addition to concurrent substances potentially altering pH to influence the onset of Adderall action, concurrent substances might either augment or counteract the neurochemical effect facilitated by Adderall.
For example, administration of a stimulatory substance with Adderall like caffeine might expedite the onset of Adderall’s action and/or make its effect more pronounced. On the other hand, administration of an inhibitory agent with Adderall – or a medication that counteracts a subset of its pharmacodynamic actions (e.g. an antipsychotic) might prevent delay the onset of Adderall’s action and/or make its effect less noticeable.
Moreover, because Adderall treatment induces neuroplastic changes within the brain, perhaps concurrently-administered agents that exert similar neuroplastic changes would expedite the onset of its therapeutic action in a subset of users who require neuroplastic changes to reap maximal therapeutic benefit. For this reason, you should reflect upon the substances that you’re using with Adderall – and consider that they could be reason as to why Adderall isn’t “kicking in” as quickly as usual.
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Adderall user genetics
The genetics of an Adderall user may determine the rate at which the medication “kicks in” or induces a noticeable effect after administration. It is known that genes can influence the pharmacokinetics (absorption, metabolism, distribution, etc.) of Adderall. Because Adderall and its metabolites undergo modest biotransformation via hepatic CYP450 enzymes such as CYP2D6, CYP1A2, and CYP3A4 – and genes predict hepatic CYP450 expression – atypical gene expression could influence the onset of Adderall’s action – or the significance of its effect.
If you are a CYP2D6 poor metabolizer (based on your genes), you may experience a more noticeable effect from Adderall as a result of greater systemic exposure (resulting from less efficient drug metabolism). Oppositely, if you are CYP2D6 rapid metabolizer, you may experience a less noticeable effect from Adderall due to lower systemic exposure (resulting from more efficient drug metabolism).
In addition to the potential impact of gene expression on Adderall pharmacokinetics, gene expression could influence its pharmacodynamics. More specifically, variants of genes that determine the activation of monoamine oxidase (MAO) or the densities of neurochemical targets (e.g. TAAR1, VMAT2, etc.) implicated in the effect of Adderall – might explain differences among users in the onset of Adderall action or the significance of its effect.
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Preexisting medical conditions
Any preexisting medical condition(s) with which you’ve been diagnosed could influence how long it takes Adderall to “kick in” – or whether you notice the medication working. For example, persons with severe forms of brain damage and/or neurodegeneration may require more time than average to respond to Adderall’s effect due to preexisting neural abnormalities.
It’s also possible that patients with forms of brain damage or neurodegeneration might never notice that they’re under influence of the medication – even if it’s working. Conversely, it’s possible that individuals with neuropsychiatric conditions like bipolar disorder may be highly sensitive to the effect of Adderall such that they respond at a faster rate than most users due to preexisting neurochemical sensitivities associated with their condition.
Other non-neuropsychiatric medical conditions that affect Adderall metabolism or elimination might influence how quickly it works – and its efficacy. For example, a gastrointestinal disorder that acidifies the GI tract might interfere with Adderall absorption and prevent the medication from working well – or exerting a noticeable effect. Evaluate your medical history and diagnoses if Adderall doesn’t seem to be working well.
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Other user-specific variables
There are a several user-specific variables that may determine the amount of time it takes for Adderall to take effect. For example, the specific Adderall format; modality of administration; and administration details (timing and food vs. empty stomach) could determine the onset of Adderall’s effect. Additionally, the self-awareness of each Adderall user may modestly influence whether the effect of Adderall is noticed after administration.
Adderall format + administration: It is known that there are subtle differences between Adderall IR vs. XR. Some users may report that one format “kicks in” quicker or is subjectively more effective than the other. In addition to the format of Adderall being used, the mode of administration might affect how long the medication takes to facilitate a noticeable effect.
For example, some individuals claim that “snorting Adderall” yields a faster effect than oral administration. What’s more, the timing of Adderall administration could determine the onset of its action. It is possible that circadian biology may interact with Adderall via “chronopharmacodynamics” such that the medication may “kick in” slightly faster at certain times of day than other times.
Whether you take Adderall with food versus on an empty stomach could also affect the onset of its action – and how well it works. Furthermore, if you take Adderall with food – the specific foods that you eat could influence its efficacy. For example, consuming an acidifying food like an orange with Adderall will reduce the pH of your GI tract, which could interfere with Adderall absorption and onset of action.
On the other hand, consuming alkalizing foods with Adderall may increase the pH of your GI tract to enhance absorption and the potency of its effect. If you’re wondering why Adderall doesn’t always kick in at the same rate each time you use it – administration details should be examined.
Adderall user’s self-awareness: While Adderall will “kick in” (or alter neurophysiology) regardless of whether you’re aware of its action, most people don’t consider medications as “working” unless they subjectively notice an effect. If you have low self-awareness, it’s possible that you could struggle to detect or gauge the speed at which Adderall takes effect.
On the other hand, if you’re highly self-aware, you may have an easier time noticing exactly how long it takes for Adderall to kick in. Moreover, someone with high self-awareness may be able to detect the onset of Adderall action quicker than someone with low self-awareness – possibly explaining why some users report the medication kicking in at a faster rate than others.
How long did it take for Adderall to work for me?
20 to 30 minutes. Each time I’ve administered Adderall, I’ve noticed the medication working within 20 to 30 minutes of ingestion. Subjectively, in less than 30 minutes following administration, I experience a combination of: increased thought speed, heightened alertness, mood enhancement, and reduced anxiety. The effect of Adderall usually persists for 4 to 6 hours – or longer if I use the extended-release (XR) format.
In my case, Adderall was prescribed by a psychiatrist to be used “as needed” for the management of depression and comorbid attentional deficits. Because I want to avoid developing tolerance or dependence on psychostimulants, I only use Adderall on rare occasions. Furthermore, when I use Adderall, I administer very small doses – doses that most medical professionals would classify as “subtherapeutic” for an adult.
Yet, even at a dose of just 5 mg, I’m cognizant of a significant effect within around 20 minutes of administration. On several occasions, I’ve tried to test the threshold dose at which I’m no longer able to consciously detect that I’m under Adderall’s influence. Because I’m highly medication sensitive and self-aware, I was able to detect Adderall “kicking in” within 20 minutes even at doses of 2.5 mg and 1 mg.
How long does it take for you to notice Adderall “kicking in?”
If you’ve used Adderall, leave a comment below documenting how long it took for the medication to “kick in” following administration. Specifically, how long after ingesting Adderall did it take before you became cognizant that you were under its influence? If you noticed Adderall working on the first day of treatment, would you consider the early effect “therapeutic” – or did you require longer-term treatment to derive therapeutic benefit?
To help others better understand your Adderall use, mention things in your comment like: Adderall dose (e.g. 20 mg per day); Adderall format (e.g. extended-release); mode of administration (e.g. oral); and the total duration over which you’ve been using it. Also note: whether you use other substances with Adderall; whether you have medical conditions that might interfere with Adderall absorption or effectiveness; and your level of self-awareness.
In the event that you were unable to detect the effect of Adderall or found the medication to be ineffective, are there any logical explanations for this? Possibilities might include: using too low of a dose; having a high psychostimulant tolerance; exhibiting an abnormal intestinal pH; having a medical condition that interferes with Adderall absorption; or using other substances with Adderall that reduced its effectiveness.