Is guarana good for you?

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guarana

What is Guarana

Guarana also known as Brazilian cocoa or Paullinia cupana is a climbing evergreen vine with small fruits that is native to the Amazon region 1, 2, 3, 4, 5, 6). Guarana contains caffeine. Caffeine is also obtainable from various sources, including coffee beans, cacao beans, kola nuts (used to flavor soft drink colas), tea leaves and yerba mate. The Paullinia cupana seeds contain a high concentration of caffeine (up to 5.3% of caffeine) 7, 8, 9, far higher than in coffee beans (1% to 3% caffeine) 10 and dark chocolate (0.08% of caffeine) 11. Guarana is produced by shelling and washing the seeds, followed by drying or roasting. Guarana seeds are then pulverized into a powder that can be used as a food favoring, to prepare tea or as a component in energy drinks or multiingredient dietary supplements. Caffeine works by stimulating your central nervous system (brain and spinal cord), heart, and muscles 12, 13.

Guarana also contains theophylline and theobromine, which are chemicals similar to caffeine 14, 15, 16. In addition to a relatively high concentration and bioavailability of theophylline and theobromine, guarana also contains flavonoids (e.g., catechins, epicatechins) and pro-anthocyanidins, which may have other potential positive impacts on human health 7, 17. These include a range of health outcomes associated with reductions in chronic fatigue in cancer patients 18, 19, short-term weight and fat loss 20, and potentially protective effects against metabolic disorders in elderly subjects in habitual consumers 21. The anti-inflammatory, antioxidant, anticancer, and hypocholesterolemic effects of guarana have also been demonstrated 7. However, a recent meta-analysis established that chronic supplementation of guarana did not reduce perceived fatigue in cancer patients and the quality of experimental evidence was rated as low 22. People take guarana by mouth for obesity, athletic performance, mental performance, to increase energy, and for many other reasons, but there is no good scientific evidence to support these uses 4, 3, 23. Guarana can also be unsafe when taken long-term in large amounts.

Guarana is a common ingredient of energy drinks and can be unsafe in large amounts. Guarana is also used in weight-loss supplements 24. Guarana seed extracts have been used in traditional medicine as stimulants, aphrodisiacs (a substance that increases libido or sexual desire) and tonics (substance that strengthens, invigorates, or improves overall well-being) 2, 25. Guarana seeds high caffeine content and stimulating properties make Guarana particularly attractive in weight-loss supplements since it helps increase the metabolic rate and can improve thermogenesis (a metabolic process during which body burns calories to produce heat). Guarana (Paullinia cupana) containing products are popular among athletes because of their ergogenic (used to enhance athletic performance) and “fat burning” effects 26. Some studies have shown that Guarana (Paullinia cupana) positively affects fat metabolism 1, enhances weight loss 27, 28, and increases basal metabolic rate (amount of energy your body needs to maintain basic life functions like breathing, heart function, brain activity, and hormone production at rest) 15, 29. Moreover, several studies have also shown Guarana (Paullinia cupana) to have antioxidant and cardioprotective effects 15, 26, 30, 31.

Most energy drinks in the U.S. have the total amount of caffeine from all sources, such as other ingredients that may have caffeine, like guarana, listed on the label 32. Caffeine is also present in various over-the-counter products, including appetite suppressants, stimulants, exercise supplements, decongestants, bronchodilators, and mental stimulants, making unintentional overdose common 33, 34, 35. The U.S. Food and Drug Administration (FDA) estimates toxic effects, like seizures, can be observed with rapid consumption of around 1,200 milligrams of caffeine, or less than 1/2 teaspoon of pure caffeine 32. Pure and highly concentrated caffeine products can have serious health consequences, including death 32. Consumers should exercise caution when using caffeine products. Consuming up to 400 mg of caffeine a day is safe for most adults — some energy drinks contain over half this amount in a single can. Lethal doses of caffeine have been reported at blood concentrations of 80 to 100 mcg (microgram)/mL, which can result from ingesting approximately 10 g or more of caffeine 36, 37, 38, 39, 40, 41.

Too much caffeine can cause a variety of symptoms:

  • Fast heart rate (tachycardia)
  • Heart palpitations (arrhythmia)
  • High blood pressure (hypertension)
  • Insomnia (difficulty to fall asleep, stay asleep, or achieve restful sleep)
  • Anxiety
  • Jitters
  • Restlessness and shakiness
  • Upset stomach
  • Nausea
  • Headaches
  • Dizziness
  • Dehydration
  • Dependency, so you need to take more of it to get the same results.

Some people are more sensitive to the effects of caffeine than others. Lethal overdoses of caffeine in adults are rare and are commonly caused by an intentional overdose of medications 42, 43, 44. However, caffeine toxicity in children is typically caused by overconsumption of energy drinks 45. Toxic ingestions can occur after consuming energy drinks but are rarely observed in people who have consumed coffee or tea, secondary to the excessive amount of fluid required to reach toxic levels 46.

Complications of caffeine overdose include seizure, neurological changes, tachydysrhythmia, ECG changes, hypokalemia, hyperglycemia, and anion gap metabolic acidosis secondary to lactic acidosis. Severe cases can result in acute kidney injury, rhabdomyolysis, and even cardiac arrest 41, 47.

Each year, Poison Control Centers in the United States receive over 3,000 reports of caffeine-related exposures, with children and adult cases occurring at an equal ratio 48. On average, less than 2 of these reports typically end in death 48.

How does guarana work?

Guarana seeds contain large amounts of methylxanthines (caffeine, theophylline, and theobromine), saponins, and polyphenols, especially tannins, as well as trace concentrations of many other compounds 14, 15, 16. These constituents are probably responsible for the use of Guarana seed extract in popular medicine as a stimulant of your central nervous system (brain and spinal cord), in cases of physical and mental stress, and as an antidiarrheic, diuretic (substance that promotes diuresis or passing of urine), and antineuralgic (relieves the pain caused by damaged or irritated nerves) 16. Guarana seeds high caffeine content and stimulating properties make Guarana particularly attractive in weight-loss supplements since it helps increase the metabolic rate and can improve thermogenesis (a metabolic process during which body burns calories to produce heat). Guarana (Paullinia cupana) containing products are popular among athletes because of their ergogenic (used to enhance athletic performance) and “fat burning” effects 26. Some studies have shown that Guarana (Paullinia cupana) positively affects fat metabolism 1, enhances weight loss 27, 28, and increases basal metabolic rate (amount of energy your body needs to maintain basic life functions like breathing, heart function, brain activity, and hormone production at rest) 15, 29. Moreover, several studies have also shown Guarana (Paullinia cupana) to have antioxidant and cardioprotective effects 15, 26, 30, 31.

Caffeine is a competitive adenosine receptor antagonist that blocks adenosine receptors in the brain, therefore preventing the onset of drowsiness, caused by adenosine 12, 49. Being both fat- and water-soluble component, caffeine easily crosses the blood-brain barrier (BBB) and antagonizes all 4 adenosine receptor subtypes (A1, A2a, A2b, and A3) 12. The antagonism of the adenosine A2a receptor is particularly responsible for caffeine’s wakefulness effects 50, 35. Individuals who regularly consume caffeine have increased the number of adenosine receptors in their central nervous system (brain and spinal cord) and become more sensitive to the normal physiologic effects of adenosine. In classical drugs of abuse, such as amphetamines and cocaine, adenosine stimulates dopaminergic activity in the nucleus accumbens, thus producing dopamine-like effects in that part of the brain, which accounts for its addictive potential (Evans J, Richards JR, Battisti AS. Caffeine. [Updated 2024 May 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519490)), 49. However, caffeine does not induce a release of dopamine in the nucleus accumbens but leads to a release of dopamine in the prefrontal cortex, which is consistent with caffeine reinforcing properties. Caffeine also stimulates glucose utilization in a caudate nucleus, which mediates motor activity and regulates the sleep-wake cycle 51.

After oral ingestion, caffeine is rapidly and completely absorbed into the bloodstream, with peak blood levels reached in 30 min to 45 min. Caffeine is metabolized by the liver and is excreted by kidneys via urine. It is quickly eliminated, with a typical half-life of four to six hours 52.

Adenosine receptors are not limited to the central nervous system (brain and spinal cord) but are present throughout the body. Direct antagonism of adenosine A1 receptor in heart muscles results in positive inotropic effects by enhance the strength of heart muscle contractions, leading to an increased cardiac output. Likewise, adenosine receptor antagonism stimulates the release of catecholamines which are a group of hormones, including dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), produced by the adrenal glands and brain in response to stress, contributing to the systemic stimulatory effects of caffeine and further stimulating your heart’s contractions and heart rate. At the vascular level, caffeine undergoes complex interactions to control vascular tone, including direct antagonism of vascular adenosine receptors to promote widening of blood vessels (vasodilation) and stimulate endothelial cells to release nitric oxide, which further relaxes vascular smooth muscle cells.

This vasodilation is counteracted by increased sympathetic tone via catecholamine release and positive heart’s contractions and heart rate effects, promoting narrowing of the blood vessels (vasoconstriction). Multiple mechanisms of blood vessel constriction and dilation are at work, resulting in an individualized response dependent on caffeine dose, frequency of use, and comorbidities such as diabetes or hypertension. With infrequent use, caffeine appears to increase systolic blood pressure by approximately 5 to 10 mm Hg. However, little to no acute effect is observed in habitual consumers 53.

Furthermore, blocking adenosine receptors stimulates respiratory drive by increasing the medullary ventilatory response to carbon dioxide, enhancing central respiratory drive, and improving diaphragm contractility. Caffeine increases kidney blood flow, glomerular filtration, and sodium excretion, resulting in diuresis. Additionally, caffeine is a potent stimulator of gastric acid secretion and gastrointestinal motility 54, 55

Caffeine produces a variety of physiological effects on the cerebral vascular system, blood pressure, respiratory functioning, gastric and colonic activity, urine volume, and exercise performance. Low to moderate doses of caffeine (20 mg-200 mg) produce reports of increased well-being, happiness, energy, alertness, and sociability, whereas higher doses are more likely to produce symptoms of anxiety, jitteriness, and upset stomach 54, 56.

Caffeine has many effects on your body’s metabolism:

  • Caffeine stimulates your central nervous system, which can make you feel more awake and give you a boost of energy
  • Caffeine is a diuretic, meaning that it helps your body get rid of extra salt and water by urinating more
  • Caffeine increases the release of acid in your stomach, sometimes leading to an upset stomach or heartburn
  • Caffeine may interfere with the absorption of calcium in the body
  • Caffeine increases your blood pressure

Within one hour of eating or drinking caffeine, it reaches its peak level in your blood. You may continue to feel the effects of caffeine for four to six hours.

Caffeine is known to cross the placenta and decrease blood flow to the placenta, although the specific effects on a fetus are not known. It is also unknown, what effects caffeine withdrawal symptoms in a pregnant mother has on a fetus.

Guarana and weight loss

Many dietary supplements promoted for weight loss contain added caffeine or an herbal source—such as guarana (Paullinia cupana), kola (or cola) nut (Cola nitida), and yerba maté (Ilex paraguariensis)—that naturally contains caffeine. Caffeine increases energy expenditure and fat oxidation 57. However, the extent to which these effects affect weight loss is less clear, partly because clinical trials examining the effects of caffeine on weight loss have all been short and have used combination products. In one study, 167 participants with overweight or obesity (BMI 25–40) took a supplement containing kola nut (192 mg/day caffeine) and ma huang (90 mg/day ephedrine) or placebo 58. Participants were counseled to eat a normal diet except for limiting dietary fat to 30% of calories and to exercise moderately. After 6 months, those in the treatment group lost significantly more weight (mean weight loss 5.3 kg) than those in the placebo group (2.6 kg) and had significantly greater body fat reduction. A product containing caffeine plus glucosyl hesperidin (G-hesperidin, a flavonone glycoside found mainly in citrus fruits) reduced abdominal fat and BMI in a clinical trial in Japan 59. In this study, 75 healthy men and women who were overweight (BMI 24–30) received one of five treatments daily for 12 weeks while maintaining their regular lifestyle and eating habits 59. The five treatments were placebo and four formulations of 0, 25, 50, or 75 mg caffeine plus 500 mg G-hesperidin. The 75 mg caffeine plus G-hesperidin significantly reduced BMI by a mean of 0.56 versus 0.02 for placebo. The 50 or 75 mg caffeine plus G-hesperidin also significantly reduced abdominal fat compared to placebo, whereas the G-hesperidin alone or with only 25 mg caffeine did not significantly affect BMI or abdominal fat. These findings indicate that the higher doses of caffeine might be responsible for the observed effects 59.

In another study 60, 47 adults who were overweight (BMI 26–30) were randomized to take a combination product containing 336 mg yerba maté (1%–1.5% caffeine), 285 mg guarana (3%–6% caffeine), and 108 mg damiana (a botanical extract that contains essential oils, resins, and tannins but not caffeine) or placebo 15 minutes before each main meal for 45 days while maintaining their normal eating habits. At the end of the study, participants taking the herbal product lost a mean of 5.1 kg compared to 0.3 kg for those taking the placebo 60.

Data from a 12-year prospective observational study provide some insight into the long-term association between caffeine intake and body weight 61. In this study 61, researchers followed 18,417 healthy men and 39,740 healthy women enrolled in either the Nurses’ Health Study or the Health Professionals Follow-Up Study. On average, participants gained some weight during the study, but men who increased their caffeine intake during the 12 years of follow-up gained a mean of 0.43 kg less than those who decreased their caffeine consumption. For women, the corresponding mean difference in weight gain was 0.35 kg less. In a cross-sectional study 62, German adults who had lost weight and maintained the weight loss (n = 494) reported significantly higher consumption of coffee and other caffeinated beverages (mean intake 3.83 cups/day) than the general population (n = 2,129, mean intake 3.35 cups/day), suggesting that caffeine might help with weight loss maintenance. However, further research is needed to confirm this finding.

Is guarana safe?

Guarana (Paullinia cupana) is likely safe for most adults when taken in amounts commonly found in foods. Guarana is possibly safe when taken as medicine, short-term. When taken in high doses for a long time, Guarana is possibly unsafe. Guarana contains caffeine. For healthy adults, FDA and the European Food Safety Authority (EFSA) state that up to 400 mg/day caffeine does not pose safety concerns 32, 63, whereas the American Medical Association recommends a limit of 500 mg/day 64. Guarana doses containing more than 400 mg of caffeine daily have been linked to side effects. Side effects depend on the dose. At typical doses, the caffeine in guarana can cause insomnia, nervousness, stomach irritation, vomiting, and many other side effects.

The FDA and the European Food Safety Authority (EFSA) have not set a safe level of intake for children, but the American Medical Association recommends that adolescents consume no more than 100 mg/day, and the American Academy of Pediatrics discourages children and adolescents from consuming caffeine and other stimulants 64, 65.

Caffeine can cause sleep disturbances and feelings of nervousness, jitteriness, and shakiness. Caffeine can be toxic at doses of 15 mg/kg (about 1,000 mg for a 150-lb adult), causing nausea, vomiting, tachycardia, seizures, and cerebral edema 66. Doses above 150 mg/kg (about 10,000 mg for a 150-lb adult) can be fatal. Combining caffeine with other stimulants, such as bitter orange and ephedrine, can potentiate these adverse effects. According to an analysis, 47% of calls to the California Poison Control System in 2006 reporting adverse effects or toxicities potentially caused by dietary supplements involved products containing caffeine 67.

Guarana (Paullinia cupana) extract from seed is approved in the United States as a food additive, flavoring agent and is considered a dietary supplement 14, 68. The Committee on Herbal Medicinal Products at the European Medicines Agency concluded that, on the basis of its long-standing use, Guarana seed can be used for the relief of symptoms of fatigue (tiredness) and weakness 69, 70. The Committee on Herbal Medicinal Products at the European Medicines Agency conclusions on the use of Guarana seed medicines for fatigue and weakness are based on their “traditional use” 69, 70, 71. This means that, although there is insufficient evidence from clinical trials, the effectiveness of Guarana (Paullinia cupana) herbal medicines is plausible and there is evidence that they have been used safely in this way for at least 30 years including at least 15 years within the European Union (EU) 69, 70. Moreover, the intended use does not require medical supervision 69, 70. At the time of the Committee on Herbal Medicinal Products at the European Medicines Agency assessment, no side effects had been reported with these medicines 69, 70. The Committee on Herbal Medicinal Products at the European Medicines Agency recommended that Guarana (Paullinia cupana) based herbal medicines should not be used in people with stomach and gut ulcers, overactive thyroid gland (hyperthyroidism) or heart and blood vessels diseases (cardiovascular problems), such as high blood pressure (hypertension) and heart rhythm problems (arrhythmias) 69, 70, 71.

Furthermore, Guarana seed extracts should only be used in adults 69, 70. If symptoms persist for longer than one week during the use of Guarana seed, a qualified healthcare practitioner should be consulted 69, 70.

Who should avoid or limit caffeine?

You should check with your doctor about whether you should limit or avoid caffeine if you:

  • Are pregnant, since caffeine passes through the placenta to your baby.
  • Are breastfeeding, since a small amount of caffeine that you consume is passed along to your baby.
  • Have sleep disorders, including insomnia.
  • Have migraines or other chronic headaches.
  • Have anxiety.
  • Have gastroesophageal reflux disease (GERD) or stomach ulcers.
  • Have arrhythmia (a problem with the rate or rhythm of your heartbeat).
  • Have high blood pressure.
  • Take certain medicines or supplements, including stimulants, certain antibiotics, asthma medicines, and heart medicines. Check with your doctor about whether there might be interactions between caffeine and any medicines and supplements that you take.
  • Are a child or teen. Children can be especially sensitive to the effects of caffeine. Children should not have as much caffeine as adults.

Guarana and pregnancy

Guarana is possibly safe during pregnancy when taken in amounts commonly found in foods. If you are pregnant, guarana should be taken with caution due to the caffeine content. Small amounts are probably not harmful. However, taking guarana in high doses by mouth is possibly unsafe. Consuming more than 300 mg of caffeine daily has been linked to an increased risk of miscarriage and other negative effects.

Some studies have suggested that high levels of caffeine of more than 300 mg per day might make it harder to get pregnant, but these findings are not proven 72. Less than 200 mg per day of caffeine to moderate (about 200-300 mg per day) caffeine consumption has not been proven to make it harder to get pregnant 72.

Miscarriage is common and can occur in any pregnancy for many different reasons. Researchers have not reported an association between under 200 mg levels of caffeine and an increased chance of miscarriage 72. Some studies suggest that the chance of miscarriage might be increased when people consume moderate (200-300 mg) or high (more than 300 mg) levels of caffeine 72. As there can be many causes of miscarriage, it is hard to know if an exposure or other factors are the cause of a miscarriage.

Birth defects can happen in any pregnancy for different reasons. Out of all babies born each year, about 3 out of 100 (3%) will have a birth defect. Scientists look at research studies to try to understand if an exposure, like caffeine, might increase the chance of birth defects in a pregnancy. Caffeine has not been shown to increase the chance of birth defects 72.

Most studies find no clear evidence that less than 200 mg to moderate (200-300 mg) of caffeine use during pregnancy can increase the chance of other pregnancy-related problems, such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth) 72. High doses of (more than 300 mg of caffeine are not well studied 72.

The use of caffeine during pregnancy can cause temporary symptoms in newborns soon after birth. These symptoms are sometimes referred to as caffeine withdrawal. Large amounts of caffeine could affect babies in the same way as it does adults. Some reports suggest that children exposed to more than 500 mg of caffeine per day in the third trimester of pregnancy were more likely to have faster heart rates, shaking, increased breathing rate, and spend more time awake in the days following birth 72. Not all babies exposed to caffeine will have these symptoms 72. It is important that your doctor know you are taking caffeine so that if symptoms occur your baby can get the care that is best for them.

Guarana and Breast-feeding

Caffeine passes into breast milk rapidly after maternal ingestion and can affect a nursing infant. Insufficient high-quality data are available to make good evidence-based recommendations on safe maternal caffeine consumption 73. Fussiness, jitteriness and poor sleep patterns have been reported in the infants of mothers with very high caffeine intakes equivalent to about 10 or more cups of coffee daily 74. It has been suggested to limit daily consumption to 300 mg/day or less while breastfeeding 72. Studies in mothers taking 5 cups of coffee daily found no stimulation in breastfed infants 3 weeks of age and older 74. A maternal intake limit of 300 to 500 mg of caffeine daily might be a safe level of intake for most mothers, although European authorities set a likely safe level at 200 mg 75, 76, 77. Maternal doses of caffeine greater than 130 mg daily may decrease weight gain in their exclusively breastfed infants, but this needs further confirmation 78. However, preterm and younger newborn infants breakdown caffeine very slowly and may have serum levels of caffeine and other active caffeine metabolites similar to their mothers’ levels, so a lower intake level preferable in the mothers of these infants 75, 79, 80. Other sources of caffeine, such as cola and energy drinks, yerba mate or guarana, will have similar dose-related effects on the breastfed infant. Coffee intake of more than 450 mL daily may decrease breastmilk iron concentrations and result in mild iron deficiency anemia in some breastfed infants 81.

Anxiety

The caffeine in guarana might make feelings of anxiety worse.

Bladder control problems

Guarana contains caffeine. The caffeine in guarana might reduce bladder control, especially in older adults. If you need to urinate often with high urgency, use guarana cautiously.

Bleeding disorders

There is some concern that the caffeine in guarana might make bleeding disorders worse. If you have a bleeding disorder, check with your healthcare provider before starting guarana.

Diabetes

Guarana contains caffeine. Some research suggests that caffeine may affect the way the body uses sugar and might worsen diabetes. If you have diabetes, use guarana with caution and monitor your blood sugar closely.

Diarrhea

Guarana contains caffeine. The caffeine in guarana, especially when taken in large amounts, can worsen diarrhea.

Glaucoma

The caffeine in guarana increases the pressure inside the eye (intraocular pressure). The increase occurs within 30 minutes and lasts for at least 90 minutes after drinking caffeinated beverages.

Heart disease

The caffeine in guarana might cause irregular heartbeat in certain people. Use with caution.

High blood pressure

Guarana contains caffeine. The caffeine in guarana might raise blood pressure. However, this effect might be less in people who consume caffeine regularly.

Irritable bowel syndrome (IBS)

Guarana contains caffeine. The caffeine in guarana, especially when taken in large amounts, can worsen diarrhea and might make diarrhea from irritable bowel syndrome (IBS) worse.

Seizures

Guarana contains caffeine. There is a concern that high doses of caffeine might cause seizures or decrease the effects of drugs used to prevent seizures. If you have seizures, talk to your doctor before using guarana.

Weak bones (Osteoporosis)

The caffeine in guarana can flush calcium out of the body through the kidneys. This calcium loss might weaken bones. If you have osteoporosis, don’t consume more than 300 mg of caffeine per day. Taking calcium supplements may also help to replace any lost calcium. If you are generally healthy and getting enough calcium from your food or supplements, taking up to 400 mg of caffeine per day doesn’t seem to increase the risk of getting osteoporosis.

Guarana interactions with medications

Do not take Guarana with ephedrine (a medication used to manage and treat clinically significant low blood pressure or hypotension) 82. Stimulant drugs speed up the nervous system. Caffeine contained in guarana and ephedrine are both stimulant drugs. Taking Guarana along with ephedrine might cause too much stimulation and serious side effects and heart problems 82.

Moderate interactions

Be cautious when taking Guarana with these drugs 82:

  • Adenosine (Adenocard). Guarana contains caffeine. The caffeine in guarana might block the affects of adenosine, which is often used by doctors to do a test called a cardiac stress test. Stop consuming guarana at least 24 hours before a cardiac stress test.
  • Carbamazepine (Tegretol). Carbamazepine is used to treat seizures. The caffeine in guarana might reduce the effects of carbamazepine. In theory, taking guarana with carbamazepine might reduce its effects and increase the risk of seizures in some people.
  • Cimetidine (Tagamet). Guarana contains caffeine. The body breaks down caffeine to get rid of it. Cimetidine can decrease how quickly your body breaks down caffeine. Taking cimetidine along with guarana might increase the chance of caffeine side effects including jitteriness, headache, and fast heartbeat.
  • Clozapine (Clozaril). Clozapine is used to treat severely ill patients with schizophrenia who have used other medicines that did not work well. It is also used to lower risk of suicidal behavior in patients with schizophrenia or schizoaffective disorder. The body breaks down clozapine to get rid of it. The caffeine in guarana seems to decrease how quickly the body breaks down clozapine. Taking guarana along with clozapine can increase the effects and side effects of clozapine.
  • Dipyridamole (Persantine). Dipyridamole is an antiplatelet agent. It is also a vasodilator that is FDA-approved for use as an add-on agent for the prevention of blood clots in those undergoing heart valve replacement and thallium-nuclear stress testing. Guarana contains caffeine. The caffeine in guarana might block the effects of dipyridamole, which is often used by doctors to do a test called a cardiac stress test. Stop consuming guarana at least 24 hours before a cardiac stress test.
  • Disulfiram (Antabuse). Disulfiram is a medication used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol. Disulfiram works by inhibiting the enzyme aldehyde dehydrogenase, causing many of the effects of a hangover to be felt immediately following alcohol consumption. Guarana contains caffeine. The body breaks down caffeine to get rid of it. Disulfiram can decrease how quickly the body gets rid of caffeine. Taking guarana along with disulfiram might increase the chance of caffeine side effects, including jitteriness, headache, and fast heartbeat.
  • Estrogens. Estrogens are female sex hormones which promote the development and maintenance of female characteristics of the body. Estrogens are also found in oral contraceptives or used to treat menopausal and menstrual disorders. Guarana contains caffeine. The body breaks down the caffeine to get rid of it. Estrogens can decrease how quickly the body breaks down caffeine. Taking guarana along with estrogens can increase the risk of caffeine side effects, including jitteriness, headache, and fast heartbeat.
  • Ethosuximide. Ethosuximide is an anticonvulsant medication that works in the brain tissue to stop absence (petit mal) seizures in people with epilepsy. Caffeine in guarana might reduce the effects of ethosuximide. In theory, taking guarana with ethosuximide might reduce its effects and increase the risk of seizures in some people.
  • Felbamate. Felbamate is an anticonvulsant medication primarily used to treat partial seizures in adults and both partial and generalized seizures associated with Lennox-Gastaut syndrome in children. Felbamate is often used as add-on therapy alongside other antiepileptic drugs. Caffeine in guarana might reduce the effects of felbamate. In theory, taking guarana with felbamate might reduce its effects and increase the risk of seizures.
  • Flutamide (Eulexin). Flutamide is a nonsteroidal antiandrogen that competitively binds androgen receptors throughout the body. This binding inhibits cell growth in prostate cancer by inhibiting testosterone’s stimulatory effects. The body breaks down flutamide to get rid of it. Caffeine in guarana might decrease how quickly the body breaks down flutamide. In theory, taking guarana along with flutamide might increase the effects and side effects of flutamide.
  • Fluvoxamine (Luvox). Fluvoxamine belongs to a group of medicines known as selective serotonin reuptake inhibitors (SSRIs). Selective serotonin reuptake inhibitors (SSRIs) medicines are thought to work by increasing the activity of a chemical called serotonin in the brain. Fluvoxamine is used to treat obsessive compulsive disorder (OCD). Guarana contains caffeine. The body breaks down the caffeine to get rid of it. Fluvoxamine can decrease how quickly the body breaks down caffeine. Taking guarana along with fluvoxamine might increase the risk of caffeine side effects, such as jitteriness, headache, and fast heartbeat.
  • Lithium. Lithium is a mood-stabilizing medicine used to treat some mental illnesses, such as bipolar disorder (BPD). Lithium may work by changing the levels of chemicals such as serotonin in your brain. The body naturally gets rid of lithium. The caffeine in guarana can increase how quickly the body gets rid of lithium. If you take products that contain caffeine and you take lithium, don’t change your dose of caffeine quickly. Stopping caffeine too quickly can increase the side effects of lithium. If you stop using caffeine, reduce the dose slowly.
  • Medications for asthma (Beta-adrenergic agonists). Beta adrenergic agonists or beta agonists are medications that relax muscles of the airways, causing widening of the airways and resulting in easier breathing. Beta-agonists most commonly are used to treat breathing conditions like COPD and asthma. Doctors also sometimes use them to treat conditions in your heart and other areas of your body. They work by attaching to beta-receptors that relax muscles in your lungs and other organs and stimulate your heart functions. Guarana contains caffeine. Caffeine can stimulate the heart. Some medications for asthma can also stimulate the heart. Taking caffeine with beta-agonists for asthma might cause too much stimulation and heart problems.
  • Monoamine oxidase inhibitors (MAOIs). Monoamine oxidase inhibitors {MAOIs) are a class of antidepressants that work by inhibiting the enzyme monoamine oxidase, which breaks down neurotransmitters like serotonin, norepinephrine, and dopamine. This leads to increased levels of these neurotransmitters in the brain, which can help alleviate symptoms of depression. Monoamine oxidase inhibitors {MAOIs) are the least commonly prescribed antidepressants due to safety concerns around food and drug interactions. Guarana contains caffeine. There is some concern that caffeine can interact with certain monoamine oxidase inhibitors {MAOIs). If caffeine is taken with certain monoamine oxidase inhibitors {MAOIs), it might increase the risk for serious side effects including fast heartbeat and very high blood pressure.
  • Medications that slow blood clotting (Anticoagulant / Antiplatelet drugs). Guarana might slow blood clotting. Taking guarana along with medications that also slow blood clotting might increase the risk of bruising and bleeding.
  • Nicotine. Stimulant drugs such as nicotine speeds up the nervous system. The caffeine in guarana might also speed up the nervous system. Taking guarana along with stimulant drugs might cause serious problems including increased heart rate and high blood pressure.
  • Pentobarbital or pentobarbitone (Nembutal). Pentobarbital or pentobarbitone is a short-acting barbiturate typically used as a sedative, a pre-anesthetic, and to control convulsions in emergencies. The stimulant effects of the caffeine in guarana can block the sleep-producing effects of pentobarbital.
  • Phenobarbital (Luminal). Phenobarbital is also a member of the barbiturate that is used to treat seizures, treatment for status epilepticus, and insomnia; it also plays a pivotal role in addressing benzodiazepine and alcohol withdrawal. Caffeine, in guarana might reduce the effects of phenobarbital. In theory, taking guarana with phenobarbital might reduce its effects and increase the risk of seizures.
  • Phenylpropanolamine. Phenylpropanolamine is a sympathomimetic agent structurally similar to pseudoephedrine, is used to treat nasal congestion and appetite suppressant. The caffeine in guarana can stimulate the body. Phenylpropanolamine can also stimulate the body. Taking guarana along with phenylpropanolamine might cause too much stimulation and increase heartbeat, blood pressure, and cause nervousness.
  • Phenytoin (Dilantin). Phenytoin is an anticonvulsant. Phenytoin works by decreasing abnormal electrical activity in the brain. Phenytoin is used to control certain type of seizures, and to treat and prevent seizures that may begin during or after surgery to the brain or nervous system. Caffeine in guarana might reduce the effects of phenytoin. In theory, taking guarana with phenytoin might reduce its effects and increase the risk of seizures.
  • Pioglitazone (Actos). Pioglitazone is an oral antidiabetic from the thiazolidinedione drug class, approved for treating type 2 diabetes mellitus in adults. The caffeine in guarana might increase the amount of pioglitazone that the body absorbs. Taking guarana might increase the effects and adverse effects of pioglitazone.
  • Riluzole (Rilutek). Riluzole is a medication used to treat motor neuron disease such as amyotrophic lateral sclerosis (ALS) and other motor neuron diseases. The body breaks down riluzole to get rid of it. Taking guarana can decrease how fast the body breaks down riluzole and increase the effects and side effects of riluzole.
  • Stimulant drugs such as amphetamines and cocaine, speed up the nervous system. By speeding up the nervous system, stimulant medications can increase blood pressure and speed up the heartbeat. Caffeine in guarana can also speed up the nervous system. Taking guarana along with stimulant drugs might cause serious problems including increased heart rate and high blood pressure.
  • Theophylline. Theophylline belongs to a group of medicines known as bronchodilators. Bronchodilators are medicines that relax the muscles in the bronchial tubes (air passages) of the lungs. Theophylline is used together with other medicines to treat the symptoms of asthma, bronchitis, emphysema, and other lung diseases. Guarana contains caffeine. Caffeine works similarly to theophylline. Caffeine can also decrease how quickly the body gets rid of theophylline. Taking guarana along with theophylline might increase the effects and side effects of theophylline.
  • Valproate (valproic acid, sodium valproate). Valproate are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those with absence seizures, partial seizures, and generalized seizures. Caffeine in guarana might reduce the effects of valproate. In theory, taking guarana with valproate might reduce its effects and increase the risk of seizures.
  • Verapamil (Calan, others). Verapamil is a calcium channel blocker. It works by affecting the movement of calcium into the cells of the heart and blood vessels. As a result, verapamil relaxes blood vessels and increases the supply of blood and oxygen to the heart while reducing its workload. Verapamil is used to treat high blood pressure and to control angina (chest pain). The body breaks down the caffeine in guarana to get rid of it. Verapamil can decrease how quickly the body gets rid of caffeine. Taking guarana along with verapamil can increase the risk of caffeine side effects including jitteriness, headache, and fast heartbeat.
  • Water pills (Diuretic drugs). Guarana contains caffeine. Caffeine can decrease potassium levels. “Water pills” can also decrease potassium levels. Taking guarana along with “water pills” might make potassium levels drop too low.

Minor interactions

  • Alcohol (Ethanol). The body breaks down the caffeine in guarana to get rid of it. Alcohol can decrease how quickly the body breaks down caffeine. Taking guarana along with alcohol might increase the risk for caffeine side effects, such as jitteriness, headache, and fast heartbeat.
  • Antibiotics (Quinolone antibiotics). The body breaks down caffeine from guarana to get rid of it. Some drugs can decrease how quickly the body breaks down caffeine. Taking these drugs along with guarana might increase the risk of caffeine side effects including jitteriness, headache, and fast heartbeat.
  • Birth control pills (oral contraceptive drugs). Guarana contains caffeine. The body breaks down caffeine to get rid of it. Birth control pills can decrease how quickly the body breaks down caffeine. This might increase the risk for caffeine side effects, such as jitteriness, headache, and fast heartbeat.
  • Fluconazole (Diflucan). Fluconazole is an antifungal drug used to treat serious fungal or yeast infections, including vaginal candidiasis, oropharyngeal candidiasis (thrush, oral thrush), esophageal candidiasis (candida esophagitis), other candida infections. Guarana contains caffeine. The body breaks down caffeine to get rid of it. Fluconazole might decrease how quickly the body gets rid of caffeine. Taking guarana along with fluconazole might increase the risk of caffeine side effects such as jitteriness, headache, and fast heartbeat.
  • Medications for diabetes (Antidiabetes drugs). Guarana might lower blood sugar levels. Taking guarana along with diabetes medications might cause blood sugar to drop too low. Monitor your blood sugar closely.
  • Medications that decrease the breakdown of other medications by the liver (Cytochrome P450 1A2 (CYP1A2) inhibitors). Guarana is changed and broken down by your liver. Some drugs decrease how quickly the liver changes and breaks down guarana. This could change the effects and side effects of guarana.
  • Metformin (Glucophage). Metformin is used to treat high blood sugar levels that are caused by type 2 diabetes. Guarana contains caffeine. The body breaks down caffeine to get rid of it. Metformin can decrease how quickly the body breaks down caffeine. Taking metformin along with guarana might increase the risk of caffeine side effects. such as jitteriness, headache, and fast heartbeat.
  • Methoxsalen (Oxsoralen). Methoxsalen is a medication used to treat psoriasis, eczema, vitiligo, and some skin lymphomas in conjunction with exposing the skin to ultraviolet light from lamps or sunlight. Guarana contains caffeine. The body breaks down caffeine to get rid of it. Methoxsalen can decrease how quickly the body breaks down caffeine. Taking methoxsalen along with guarana might increase the risk of caffeine side effects, such as jitteriness, headache, and fast heartbeat.
  • Mexiletine (Mexitil). Mexiletine is a medication used to treat abnormal heart rhythms (arrhythmias), chronic pain, and some causes of muscle stiffness. Guarana contains caffeine. The body breaks down caffeine to get rid of it. Mexiletine can decrease how quickly the body breaks down caffeine. Taking mexiletine along with guarana might increase the risk of caffeine side effects, such as jitteriness, headache, and fast heartbeat.
  • Phenothiazines. Phenothiazines are first-generation antipsychotic medications, known for their ability to antagonize dopamine receptors. Phenothiazines are used to treat various conditions, including schizophrenia, bipolar disorder, nausea, and vomiting. Guarana contains caffeine. The body breaks down caffeine to get rid of it. Phenothiazines can decrease how quickly the body breaks down caffeine. Taking phenothiazines along with guarana might increase the risk of caffeine side effects, such as jitteriness, headache, and fast heartbeat.
  • Terbinafine (Lamisil). Terbinafine is an antifungal medication used to treat various fungal infections, including nail infections (onychomycosis), ringworm (tinea corporis, tinea cruris), and athlete’s foot (tinea pedis). Guarana contains caffeine. The body breaks down caffeine to get rid of it. Terbinafine can decrease how fast the body gets rid of caffeine and increase the risk of caffeine side effects such as jitteriness, headache, and fast heartbeat.
  • Tiagabine (Gabitril). Tiagabine is an anticonvulsant medication that is used in the treatment of epilepsy. It is also used in the treatment for panic disorder. There is some concern that caffeine can reduce the effects of tiagabine. But studies show that tiagabine still works even when taken with caffeine.
  • Ticlopidine (Ticlid). Ticlopidine is a platelet aggregation inhibitor that reduces the chance that a harmful blood clot will form, by preventing certain cells in the blood from clumping together. This effect of ticlopidine may also increase the chance of serious bleeding in some people. Guarana contains caffeine. The body breaks down caffeine to get rid of it. Ticlopidine can decrease how fast the body gets rid of caffeine. In theory, taking guarana along with ticlopidine might increase the risk of caffeine side effects, such as jitteriness, headache, and fast heartbeat.
  • Bitter orange. Bitter orange and its extracts are used in Traditional Chinese Medicine (TCM) to treat indigestion, diarrhea, dysentery, and constipation. Guarana contains caffeine. Taking bitter orange along with herbs that contain caffeine, such as guarana, can increase blood pressure and heart rate in people who otherwise have normal blood pressure. This might increase the chance of developing problems with the heart and blood vessels.
  • Caffeine-containing herbs and supplements. Guarana contains caffeine. Taking it along with other supplements that contain caffeine might increase caffeine side effects. Examples of supplements that contain caffeine include black tea, coffee, green tea, and yerba mate.
  • Calcium. High caffeine intake from foods, beverages, and herbs including guarana increases how much calcium the body loses in the urine. This might lower calcium levels.
  • Creatine. Creatine is a compound that comes from three amino acids. Creatine is found mostly in your body’s muscles as well as in the brain. Creatine supplementation primarily boosts energy production in muscles, leading to increased strength, power, and muscle growth. There is some concern that taking caffeine with creatine might reduce the beneficial effects that creatine has on athletic performance.
  • Danshen. Danshen also known as red sage, redroot sage, Chinese sage, or danshen, is commonly used in Traditional Chinese Medicine (TCM). Guarana contains caffeine. The body breaks down caffeine to get rid of it. Danshen might decrease how quickly the body breaks down caffeine. Using danshen with guarana might increase the risk of caffeine side effects.
  • Echinacea. Guarana contains caffeine. The body breaks down caffeine to get rid of it. Echinacea might decrease how quickly the body breaks down caffeine. Using echinacea with guarana might increase the risk of caffeine side effects.
  • Ephedra. People use ephedra for weight loss and athletic performance. It’s also used for allergies, nasal congestion, asthma, common cold, headache, and many other ailments. Stimulants speed up the nervous system. Caffeine (contained in guarana) and ephedra are both stimulants. Taking guarana along with ephedra might cause too much stimulation and serious side effects and heart problems.
  • Genistein-containing herbs and supplements. Guarana contains genistein. Genistein might decrease how quickly the body breaks down caffeine. Taking guarana with caffeine might increase caffeine levels and side effects. Examples of supplements that contain genistein include cumin, dyer’s broom, kudzu, red clover, and soy.
  • Herbs and supplements that might slow blood clotting. Guarana might slow blood clotting and increase the risk of bleeding. Taking it with other supplements with similar effects might increase the risk of bleeding in some people. Examples of supplements with this effect include garlic, ginger, ginkgo, nattokinase, and Panax ginseng.
  • Kudzu also called Japanese arrowroot or Chinese arrowroot. Guarana contains caffeine. The body breaks down caffeine to get rid of it. Kudzu might decrease how quickly the body breaks down caffeine. Using kudzu with guarana might increase the risk of caffeine side effects.
  • Magnesium. High caffeine intake from foods, beverages, and herbs including guarana increases how much magnesium the body loses in the urine. This might lower magnesium levels.
  • Melatonin. Melatonin is a hormone produced by the pineal gland in the brain. Its level varies throughout the day and night to control your body clock. Melatonin helps regulate your sleep cycle and other body functions. Guarana contains caffeine. Taking caffeine along with melatonin supplement can increase melatonin levels. In theory, taking guarana with melatonin supplement might increase melatonin effects and side effects.

Guarana side effects

Most energy drinks in the U.S. have the total amount of caffeine from all sources, such as other ingredients that may have caffeine, like guarana, listed on the label 32. Caffeine is also present in various over-the-counter products, including appetite suppressants, stimulants, exercise supplements, decongestants, bronchodilators, and mental stimulants, making unintentional overdose common 33, 34. The U.S. Food and Drug Administration (FDA) estimates toxic effects, like seizures, can be observed with rapid consumption of around 1,200 milligrams of caffeine, or less than 1/2 teaspoon of pure caffeine 32. Pure and highly concentrated caffeine products can have serious health consequences, including death 32. Consumers should exercise caution when using caffeine products. Consuming up to 400 mg of caffeine a day is safe for most adults — some energy drinks contain over half this amount in a single can. Lethal doses of caffeine have been reported at blood concentrations of 80 to 100 mcg (microgram)/mL, which can result from ingesting approximately 10 g or more of caffeine 36, 37, 38, 39, 40, 41.

Too much caffeine can cause a variety of symptoms:

  • Fast heart rate (tachycardia)
  • Heart palpitations (arrhythmia)
  • High blood pressure (hypertension)
  • Insomnia (difficulty to fall asleep, stay asleep, or achieve restful sleep)
  • Anxiety
  • Jitters
  • Restlessness and shakiness
  • Upset stomach
  • Nausea
  • Headaches
  • Dizziness
  • Dehydration
  • Dependency, so you need to take more of it to get the same results.

Some people are more sensitive to the effects of caffeine than others. Lethal overdoses of caffeine in adults are rare and are commonly caused by an intentional overdose of medications 42, 43, 44. However, caffeine toxicity in children is typically caused by overconsumption of energy drinks 45. Toxic ingestions can occur after consuming energy drinks but are rarely observed in people who have consumed coffee or tea, secondary to the excessive amount of fluid required to reach toxic levels 46.

Complications of caffeine overdose include seizure, neurological changes, tachydysrhythmia, ECG changes, hypokalemia, hyperglycemia, and anion gap metabolic acidosis secondary to lactic acidosis. Severe cases can result in acute kidney injury, rhabdomyolysis, and even cardiac arrest 41, 47.

Each year, Poison Control Centers in the United States receive over 3,000 reports of caffeine-related exposures, with children and adult cases occurring at an equal ratio 48. On average, less than 2 of these reports typically end in death 48.

Caffeine overdose management

There is no established standard of care or treatment plan for caffeine overdose, but consulting poison control is highly recommended when managing these cases. The primary treatment for minor caffeine ingestion is supportive care, including advanced cardiac life support or pediatric advanced life support as needed 83. Hydration may be oral for minor cases. Patients with severe caffeine toxicity benefit from intravenous hydration 83. Beta-blockers such as esmolol or metoprolol are effective for treating tachycardia 83. Procainamide, lidocaine, or bicarbonate have also been used to treat tachydysrhythmias 84. Adenosine and electrical cardioversion in cases of caffeine toxicity have not been shown to have any sustained effect on cardiac dysrhythmias 85, 86. Vasopressors, such as norepinephrine or phenylephrine, can help maintain a goal arterial pressure greater than 65 mm Hg without worsening tachycardia 87. Activated charcoal can bind caffeine if the ingestion is recent, and repeated doses can help diminish serum levels through enterohepatic circulation 83.

Orogastric lavage using a standard nasogastric tube has also been reported to help aspirate caffeine contents, but only if initiated within 1 hour of ingestion 83. If the patient develops symptomatic hypokalemia, then potassium should be replaced 83. Hemodialysis has been effective in severe, life-threatening caffeine ingestions 83. The first-line treatment for seizures includes benzodiazepines, such as lorazepam, diazepam, and midazolam 83. Phenobarbital and propofol may be used to treat refractory seizures. Both phenytoin and fosphenytoin are not recommended for the treatment of seizures related to caffeine toxicity in response to case reports of increased mortality in animal models with methylxanthine toxicity 88. Caffeine exhibits ideal characteristics for dialysis, including low protein binding (36%), low molecular size (194 kDa), and a small volume of distribution (0.6 to 0.8 L/kg) 83. Dialysis can be discontinued when clinical improvement is observed or when the serum caffeine concentration is less than 15 mg/L 89. Imminent cardiac arrest in caffeine toxicity should prompt intralipid therapy to scavenge the free serum caffeine 90, 91. Extracorporeal membrane oxygenation (ECMO) can be considered for patients who are resistant to treatment and are hemodynamically unstable 92, 93.

Caffeine overdose prognosis

There are relatively few deaths reported from caffeine overdose; however, caffeine overdose prognosis largely depends on how quickly treatment is implemented 46. In cases of severe caffeine overdose, the prognosis is directly correlated with the timeliness of caffeine removal from the bloodstream using hemodialysis or intralipid emulsion therapy 90.

Caffeine withdrawal

Caffeine is a central nervous system (brain and spinal cord) stimulant and is one of the most widely used drugs in the world 49. If you have been consuming caffeine on a regular basis and then suddenly stop, you may have caffeine withdrawal. Symptoms can include:

  • Headaches
  • Drowsiness
  • Irritability
  • Nausea
  • Trouble concentrating

These symptoms usually go away after a couple of days.

Multiple studies have demonstrated that caffeine-withdrawal syndrome is a clinically relevant entity and is included in the Diagnostic and Statistical Manual of Mental Disorders (DSM 5th edition), a American Psychiatric Association’s professional reference book on mental health and brain-related conditions that help clinicians and researchers define and classify mental disorders 94, 95.

  1. Lima WP, Carnevali LC, Jr., Eder R, Costa Rosa LFBP, Bacchi EM, Seelaender MCL. Lipid metabolism in trained rats: effect of guarana (Paullinia cupana Mart.) supplementation. Clinical Nutrition. 2005;24(6):1019–1028. doi: 10.1016/j.clnu.2005.08.004[↩][↩][↩]
  2. de Oliveira Campos MP, Riechelmann R, Martins LC, Hassan BJ, Casa FBA, Giglio AD. Guarana (Paullinia cupana) improves fatigue in breast cancer patients undergoing systemic chemotherapy. The Journal of Alternative and Complementary Medicine. 2011;17(6):505–512. doi: 10.1089/acm.2010.0571[↩][↩]
  3. Hack B, Penna EM, Talik T, Chandrashekhar R, Millard-Stafford M. Effect of Guarana (Paullinia cupana) on Cognitive Performance: A Systematic Review and Meta-Analysis. Nutrients. 2023 Jan 14;15(2):434. doi: 10.3390/nu15020434[↩][↩]
  4. Gurney T, Bradley N, Izquierdo D, Ronca F. Cognitive effects of guarana supplementation with maximal intensity cycling. Br J Nutr. 2023 Jul 28;130(2):253-260. doi: 10.1017/S0007114522002859[↩][↩]
  5. Schimpl FC, da Silva JF, Gonçalves JF, Mazzafera P. Guarana: revisiting a highly caffeinated plant from the Amazon. J Ethnopharmacol. 2013 Oct 28;150(1):14-31. doi: 10.1016/j.jep.2013.08.023[↩]
  6. Silva FA, Liotti RG, Boleti APA, Reis ÉM, Passos MBS, Dos Santos EL, Sampaio OM, Januário AH, Branco CLB, Silva GFD, Mendonça EAF, Soares MA. Diversity of cultivable fungal endophytes in Paullinia cupana (Mart.) Ducke and bioactivity of their secondary metabolites. PLoS One. 2018 Apr 12;13(4):e0195874. doi: 10.1371/journal.pone.0195874[↩]
  7. Torres E., Pinaffi-Langley A., Figueira M.S., Cordeiro K.S., Negrão L.D., Soares M.J., da Silva C.P., Alfino M.C.Z., Sampaio G.R., de Camargo A.C. Effects of the consumption of guarana on human health: A narrative review. Compr. Rev. Food Sci. Food Saf. 2022;21:272–295. doi: 10.1111/1541-4337.12862[↩][↩][↩]
  8. Kennedy DO, Haskell CF, Wesnes KA, Scholey AB. Improved cognitive performance in human volunteers following administration of guarana (Paullinia cupana) extract: comparison and interaction with Panax ginseng. Pharmacol Biochem Behav. 2004;79(3):401–411. doi: 10.1016/j.pbb.2004.07.014[↩]
  9. Haskell CF, Kennedy DO, Wesnes KA, Milne AL, Scholey AB. A double-blind, placebo-controlled, multi-dose evaluation of the acute behavioural effects of guarana in humans. J Psychopharmacol. 2007;21(1):65–70. doi: 10.1177/0269881106063815[↩]
  10. Coffee, espresso. https://fdc.nal.usda.gov/food-details/1104140/nutrients[↩]
  11. Chocolate, dark, 70-85% cacao solids. https://fdc.nal.usda.gov/food-details/170273/nutrients[↩]
  12. Evans J, Richards JR, Battisti AS. Caffeine. [Updated 2024 May 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519490[↩][↩][↩]
  13. Nehlig A, Daval JL, Debry G. Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Brain Res Rev. 1992 May-Aug;17(2):139-70. doi: 10.1016/0165-0173(92)90012-b[↩]
  14. Heard CM, Johnson S, Moss G, Thomas CP. In vitro transdermal delivery of caffeine, theobromine, theophylline and catechin from extract of Guarana, Paullinia cupana . International Journal of Pharmaceutics. 2006;317(1):26–31. doi: 10.1016/j.ijpharm.2006.02.042[↩][↩][↩]
  15. Costa Krewer C, Ribeiro EE, Ribeiro EA, et al. Habitual intake of guaraná and metabolic morbidities: an epidemiological study of an elderly Amazonian population. Phytotherapy Research. 2011;25:1367–1374. doi: 10.1002/ptr.3437[↩][↩][↩][↩][↩][↩]
  16. Klein T, Longhini R, de Mello JC. Development of an analytical method using reversed-phase HPLC-PDA for a semipurified extract of Paullinia cupana var. sorbilis (guaraná) Talanta. 2012;88:502–506. doi: 10.1016/j.talanta.2011.11.023[↩][↩][↩]
  17. Santana AL, Macedo GA. Health and technological aspects of methylxanthines and polyphenols from guarana: a review. J Funct Foods. 2018;47:457–468. doi: 10.1016/j.jff.2018.05.048[↩]
  18. Campos M.P.D.O., Riechelmann R., Martins L.C., Hassan B.J., Casa F.B.A., Del Giglio A. Guarana (Paullinia cupana) Improves Fatigue in Breast Cancer Patients Undergoing Systemic Chemotherapy. J. Altern. Complement. Med. 2011;17:505–512. doi: 10.1089/acm.2010.0571[↩]
  19. del Giglio A.B., Cubero D., Lerner T.G., Guariento R.T., de Azevedo R.G.S., Paiva H., Goldman C., Carelli B., Cruz F.M., Schindler F., et al. Purified dry extract of Paullinia cupana (guaraná) (PC-18) for chemotherapy-related fatigue in patients with solid tumors: An early discontinuation study. J. Diet. Suppl. 2013;10:325–334. doi: 10.3109/19390211.2013.830676[↩]
  20. Boozer C.N., Nasser J.A., Heymsfield S.B., Wang V., Chen G., Solomon J.L. An herbal supplement containing Ma Huang-Guarana for weight loss: A randomized, double-blind trial. Int. J. Obes. Relat. Metab. Disord. 2001;25:316–324. doi: 10.1038/sj.ijo.0801539[↩]
  21. Krewer C.D., Ribeiro E.E., Ribeiro E.A., Moresco R.N., de Ugalde Marques da Rocha M.I., Montagner G.F.F.S., Machado M.M., Viegas K., Brito E., da Cruz I.B.M. Habitual intake of guaraná and metabolic morbidities: An epidemiological study of an elderly Amazonian population. Phytother. Res. 2011;25:1367–1374. doi: 10.1002/ptr.3437[↩]
  22. de Araujo D.P., Pereira P.T.V.T., Fontes A.J.C., Marques K.D.S., de Moraes B., Guerra R.N.M., Garcia J.B.S. The use of guarana (Paullinia cupana) as a dietary supplement for fatigue in cancer patients: A systematic review with a meta-analysis. Support. Care Cancer. 2021;29:7171–7182. doi: 10.1007/s00520-021-06242-5[↩]
  23. Kennedy DO, Wightman EL. Mental Performance and Sport: Caffeine and Co-consumed Bioactive Ingredients. Sports Med. 2022 Dec;52(Suppl 1):69-90. doi: 10.1007/s40279-022-01796-8[↩]
  24. Rodrigues M, Alves G, Lourenço N, Falcão A. Herb-Drug Interaction of Paullinia cupana (Guarana) Seed Extract on the Pharmacokinetics of Amiodarone in Rats. Evid Based Complement Alternat Med. 2012;2012:428560. doi: 10.1155/2012/428560[↩]
  25. Marques LLM, Ferreira EDF, de Paula MN, et al. (2019) Paullinia cupana: a multipurpose plant-a review. Rev Bras Farmacognosia 29, 77–110[↩]
  26. Bulku E, Zinkovsky D, Patel P, et al. A novel dietary supplement containing multiple phytochemicals and vitamins elevates hepatorenal and cardiac antioxidant enzymes in the absence of significant serum chemistry and genomic changes. Oxidative Medicine and Cellular Longevity. 2010;3(2):129–144. doi: 10.4161/oxim.3.2.7[↩][↩][↩][↩]
  27. Boozer CN, Nasser JA, Heymsfield SB, Wang V, Chen G, Solomon JL. An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial. International Journal of Obesity. 2001;25(3):316–324. doi: 10.1038/sj.ijo.0801539[↩][↩]
  28. Opala T, Rzymski P, Pischel I, Wilczak M, Woźniak J. Efficacy of 12 weeks supplementation of a botanical extract-based weight loss formula on body weight, body composition and blood chemistry in healthy, overweight subjects—a randomised double-blind placebo-controlled clinical trial. European Journal of Medical Research. 2006;11(8):343–350.[↩][↩]
  29. Bérubé-Parent S, Pelletier C, Doré J, Tremblay A. Effects of encapsulated green tea and Guarana extracts containing a mixture of epigallocatechin-3-gallate and caffeine on 24 h energy expenditure and fat oxidation in men. British Journal of Nutrition. 2005;94(3):432–436. doi: 10.1079/bjn20051502[↩][↩]
  30. Bydlowski SP, Yunker RL, Subbiah MTR. A novel property of an aqueous guarana extract (Paullinia cupana): inhibition of platelet aggregation in vitro and in vivo. Brazilian Journal of Medical and Biological Research. 1988;21(3):535–538.[↩][↩]
  31. Bydlowski SP, D’Amico EA, Chamone DAF. An aqueous extract of guarana (Paullinia cupana) decreases platelet thromboxane synthesis. Brazilian Journal of Medical and Biological Research. 1991;24(4):421–424.[↩][↩]
  32. Spilling the Beans: How Much Caffeine is Too Much? https://www.fda.gov/consumers/consumer-updates/spilling-beans-how-much-caffeine-too-much[↩][↩][↩][↩][↩][↩][↩]
  33. Wikoff D, Welsh BT, Henderson R, Brorby GP, Britt J, Myers E, Goldberger J, Lieberman HR, O’Brien C, Peck J, Tenenbein M, Weaver C, Harvey S, Urban J, Doepker C. Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food Chem Toxicol. 2017 Nov;109(Pt 1):585-648. doi: 10.1016/j.fct.2017.04.002[↩][↩]
  34. Tran NL, Barraj LM, Bi X, Jack MM. Trends and patterns of caffeine consumption among US teenagers and young adults, NHANES 2003-2012. Food Chem Toxicol. 2016 Aug;94:227-42. doi: 10.1016/j.fct.2016.06.007[↩][↩]
  35. Fisone G, Borgkvist A, Usiello A. Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci. 2004 Apr;61(7-8):857-72. doi: 10.1007/s00018-003-3269-3[↩][↩]
  36. Ciszowski K, Biedroń W, Gomólka E. Acute caffeine poisoning resulting in atrial fibrillation after guarana extract overdose. Przegl Lek. 2014;71(9):495-8. [↩][↩]
  37. Cappelletti S, Piacentino D, Fineschi V, Frati P, Cipolloni L, Aromatario M. Caffeine-Related Deaths: Manner of Deaths and Categories at Risk. Nutrients. 2018 May 14;10(5):611. doi: 10.3390/nu10050611[↩][↩]
  38. Holmgren P, Nordén-Pettersson L, Ahlner J. Caffeine fatalities–four case reports. Forensic Sci Int. 2004 Jan 6;139(1):71-3. doi: 10.1016/j.forsciint.2003.09.019[↩][↩]
  39. Winek CL, Wahba W, Williams K, Blenko J, Janssen J. Caffeine fatality: a case report. Forensic Sci Int. 1985 Nov-Dec;29(3-4):207-11. doi: 10.1016/0379-0738(85)90114-8[↩][↩]
  40. Kerrigan S, Lindsey T. Fatal caffeine overdose: two case reports. Forensic Sci Int. 2005 Oct 4;153(1):67-9. doi: 10.1016/j.forsciint.2005.04.016[↩][↩]
  41. Campana C, Griffin PL, Simon EL. Caffeine overdose resulting in severe rhabdomyolysis and acute renal failure. Am J Emerg Med. 2014 Jan;32(1):111.e3-4. doi: 10.1016/j.ajem.2013.08.042[↩][↩][↩][↩]
  42. Bioh G, Gallagher MM, Prasad U. Survival of a highly toxic dose of caffeine. BMJ Case Rep. 2013 Feb 8;2013:bcr2012007454. doi: 10.1136/bcr-2012-007454[↩][↩]
  43. Bonsignore A, Sblano S, Pozzi F, Ventura F, Dell’Erba A, Palmiere C. A case of suicide by ingestion of caffeine. Forensic Sci Med Pathol. 2014 Sep;10(3):448-51. doi: 10.1007/s12024-014-9571-6[↩][↩]
  44. Forman J, Aizer A, Young CR. Myocardial infarction resulting from caffeine overdose in an anorectic woman. Ann Emerg Med. 1997 Jan;29(1):178-80. doi: 10.1016/s0196-0644(97)70326-3[↩][↩]
  45. Bigard AX. Dangers des boissons énergisantes chez les jeunes [Risks of energy drinks in youths]. Arch Pediatr. 2010 Nov;17(11):1625-31. French. doi: 10.1016/j.arcped.2010.08.001[↩][↩]
  46. Gummin DD, Mowry JB, Spyker DA, Brooks DE, Fraser MO, Banner W. 2016 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 34th Annual Report. Clin Toxicol (Phila). 2017 Dec;55(10):1072-1252. doi: 10.1080/15563650.2017.1388087. Epub 2017 Nov 29. Erratum in: Clin Toxicol (Phila). 2017 Dec;55(10):1256. doi: 10.1080/15563650.2017.1415423[↩][↩][↩]
  47. Wilson RE, Kado HS, Samson R, Miller AB. A case of caffeine-induced coronary artery vasospasm of a 17-year-old male. Cardiovasc Toxicol. 2012 Jun;12(2):175-9. doi: 10.1007/s12012-011-9152-9[↩][↩]
  48. Gummin DD, Mowry JB, Beuhler MC, Spyker DA, Rivers LJ, Feldman R, Brown K, Pham NPT, Bronstein AC, DesLauriers C. 2023 Annual Report of the National Poison Data System® (NPDS) from America’s Poison Centers®: 41st Annual Report. Clin Toxicol (Phila). 2024 Dec;62(12):793-1027. doi: 10.1080/15563650.2024.2412423[↩][↩][↩][↩]
  49. Sajadi-Ernazarova KR, Hamilton RJ. Caffeine Withdrawal. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430790[↩][↩][↩]
  50. Ferré S. An update on the mechanisms of the psychostimulant effects of caffeine. J Neurochem. 2008 May;105(4):1067-79. doi: 10.1111/j.1471-4159.2007.05196.x[↩]
  51. O’Callaghan F, Muurlink O, Reid N. Effects of caffeine on sleep quality and daytime functioning. Risk Manag Healthc Policy. 2018 Dec 7;11:263-271. doi: 10.2147/RMHP.S156404[↩]
  52. Meredith SE, Juliano LM, Hughes JR, Griffiths RR. Caffeine Use Disorder: A Comprehensive Review and Research Agenda. J Caffeine Res. 2013 Sep;3(3):114-130. doi: 10.1089/jcr.2013.0016[↩]
  53. Echeverri D, Montes FR, Cabrera M, Galán A, Prieto A. Caffeine’s Vascular Mechanisms of Action. Int J Vasc Med. 2010;2010:834060. doi: 10.1155/2010/834060. Epub 2010 Aug 25. Erratum in: Int J Vasc Med. 2019 Nov 20;2019:7480780. doi: 10.1155/2019/7480780[↩]
  54. Addicott MA. Caffeine Use Disorder: A Review of the Evidence and Future Implications. Curr Addict Rep. 2014 Sep;1(3):186-192. doi: 10.1007/s40429-014-0024-9[↩][↩]
  55. Boekema PJ, Samsom M, van Berge Henegouwen GP, Smout AJ. Coffee and gastrointestinal function: facts and fiction. A review. Scand J Gastroenterol Suppl. 1999;230:35-9. doi: 10.1080/003655299750025525[↩]
  56. Evans SM, Griffiths RR. Caffeine withdrawal: a parametric analysis of caffeine dosing conditions. J Pharmacol Exp Ther. 1999 Apr;289(1):285-94.[↩]
  57. Harpaz E, Tamir S, Weinstein A, Weinstein Y. The effect of caffeine on energy balance. J Basic Clin Physiol Pharmacol. 2017 Jan 1;28(1):1-10. doi: 10.1515/jbcpp-2016-0090[↩]
  58. Boozer CN, Daly PA, Homel P, Solomon JL, Blanchard D, Nasser JA, Strauss R, Meredith T. Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial. Int J Obes Relat Metab Disord. 2002 May;26(5):593-604. doi: 10.1038/sj.ijo.0802023[↩]
  59. Ohara T, Muroyama K, Yamamoto Y, Murosaki S. Oral intake of a combination of glucosyl hesperidin and caffeine elicits an anti-obesity effect in healthy, moderately obese subjects: a randomized double-blind placebo-controlled trial. Nutr J. 2016 Jan 19;15:6. doi: 10.1186/s12937-016-0123-7. Erratum in: Nutr J. 2017 May 12;16(1):28. doi: 10.1186/s12937-017-0253-6[↩][↩][↩]
  60. Andersen T, Fogh J. Weight loss and delayed gastric emptying following a South American herbal preparation in overweight patients. J Hum Nutr Diet. 2001 Jun;14(3):243-50. doi: 10.1046/j.1365-277x.2001.00290.x[↩][↩]
  61. Lopez-Garcia E, van Dam RM, Rajpathak S, Willett WC, Manson JE, Hu FB. Changes in caffeine intake and long-term weight change in men and women. Am J Clin Nutr. 2006 Mar;83(3):674-80. doi: 10.1093/ajcn.83.3.674[↩][↩]
  62. Icken D, Feller S, Engeli S, Mayr A, Müller A, Hilbert A, de Zwaan M. Caffeine intake is related to successful weight loss maintenance. Eur J Clin Nutr. 2016 Apr;70(4):532-4. doi: 10.1038/ejcn.2015.183[↩]
  63. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2015. Scientific Opinion on the safety of caffeine. EFSA Journal 2015;13(5):4102, 120 pp. doi:10.2903/j.efsa.2015.4102[↩]
  64. Torpy JM, Livingston EH. JAMA patient page. Energy drinks. JAMA. 2013 Jan 16;309(3):297. doi: 10.1001/jama.2012.170614. Erratum in: JAMA. 2013 Feb 6;309(5):442.[↩][↩]
  65. Committee on Nutrition and the Council on Sports Medicine and Fitness. Sports drinks and energy drinks for children and adolescents: are they appropriate? Pediatrics. 2011 Jun;127(6):1182-9. doi: 10.1542/peds.2011-0965[↩]
  66. Yen M, Ewald MB. Toxicity of weight loss agents. J Med Toxicol. 2012 Jun;8(2):145-52. doi: 10.1007/s13181-012-0213-7[↩]
  67. Haller C, Kearney T, Bent S, Ko R, Benowitz N, Olson K. Dietary supplement adverse events: report of a one-year poison center surveillance project. J Med Toxicol. 2008 Jun;4(2):84-92. doi: 10.1007/BF03160960[↩]
  68. GUARANA, GUM (PAULLINIA CUPANA HBK). https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-172/subpart-F/section-172.510[↩]
  69. Guarana seed. https://www.ema.europa.eu/en/documents/herbal-summary/guarana-seed-summary-public_en.pdf[↩][↩][↩][↩][↩][↩][↩][↩]
  70. Paulliniae semen – herbal medicinal product. https://www.ema.europa.eu/en/medicines/herbal/paulliniae-semen[↩][↩][↩][↩][↩][↩][↩][↩]
  71. Addendum to Assessment report on Paullinia cupana Kunth (syn. Paullinia sorbilis Mart.), semen. https://www.ema.europa.eu/en/documents/herbal-report/addendum-assessment-report-paullinia-cupana-kunth-syn-paullinia-sorbilis-mart-semen_en.pdf[↩][↩]
  72. Caffeine. https://mothertobaby.org/fact-sheets/caffeine-pregnancy[↩][↩][↩][↩][↩][↩][↩][↩][↩][↩]
  73. McCreedy A, Bird S, Brown LJ, Shaw-Stewart J, Chen YF. Effects of maternal caffeine consumption on the breastfed child: a systematic review. Swiss Med Wkly. 2018 Sep 28;148:w14665. doi: 10.4414/smw.2018.14665[↩]
  74. Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006-. Caffeine. [Updated 2024 Jan 15]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501467[↩][↩]
  75. James J, Lawrence R. Can consuming caffeine while breastfeeding harm your baby? An interview with Ruth Lawrence, PhD. J Caffeine Res 2011;1:192-4. doi:10.1089/caf.2011.1212[↩][↩]
  76. EFSA Panel on Dietetic Products Nutrition and Allergies (NDA). Scientific opinion on the safety of caffeine. EFSA J 2015;13:4102. doi:10.2903/j.efsa.2015.4102[↩]
  77. Ryu JE. Effect of maternal caffeine consumption on heart rate and sleep time of breast-fed infants. Dev Pharmacol Ther. 1985;8(6):355-63. doi: 10.1159/000457060[↩]
  78. Elenberg-Alter Y, Batcir R. Caffeine consumption influence among lactating mothers on babies’ growth parameters during first 6 months of life -a prospective study. J Pediatr Gastroenterol Nutr 2023;76:1049-50. doi:10.1097/MPG.0000000000003823[↩]
  79. McNamara PJ, Abbassi M. Neonatal exposure to drugs in breast milk. Pharm Res. 2004 Apr;21(4):555-66. doi: 10.1023/b:pham.0000022401.14710.c5[↩]
  80. Oo CY, Burgio DE, Kuhn RC, Desai N, McNamara PJ. Pharmacokinetics of caffeine and its demethylated metabolites in lactation: predictions of milk to serum concentration ratios. Pharm Res. 1995 Feb;12(2):313-6. doi: 10.1023/a:1016207832591[↩]
  81. Muñoz LM, Lönnerdal B, Keen CL, Dewey KG. Coffee consumption as a factor in iron deficiency anemia among pregnant women and their infants in Costa Rica. Am J Clin Nutr. 1988 Sep;48(3):645-51. doi: 10.1093/ajcn/48.3.645[↩]
  82. Guarana. https://medlineplus.gov/druginfo/natural/935.html[↩][↩][↩]
  83. Murray A, Traylor J. Caffeine Toxicity. [Updated 2025 Feb 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532910[↩][↩][↩][↩][↩][↩][↩][↩][↩]
  84. Kapur R, Smith MD. Treatment of cardiovascular collapse from caffeine overdose with lidocaine, phenylephrine, and hemodialysis. Am J Emerg Med. 2009 Feb;27(2):253.e3-6. doi: 10.1016/j.ajem.2008.06.028[↩]
  85. Li SF, Edwards L, Nguyen V. Treatment of caffeine toxicity with metoprolol. Am J Emerg Med. 2019 Mar;37(3):562.e5-562.e10. doi: 10.1016/j.ajem.2018.11.038[↩]
  86. Cabalag MS, Taylor DM, Knott JC, Buntine P, Smit D, Meyer A. Recent caffeine ingestion reduces adenosine efficacy in the treatment of paroxysmal supraventricular tachycardia. Acad Emerg Med. 2010 Jan;17(1):44-9. doi: 10.1111/j.1553-2712.2009.00616.x[↩]
  87. Holstege CP, Hunter Y, Baer AB, Savory J, Bruns DE, Boyd JC. Massive caffeine overdose requiring vasopressin infusion and hemodialysis. J Toxicol Clin Toxicol. 2003;41(7):1003-7. doi: 10.1081/clt-120026526[↩]
  88. Blake KV, Massey KL, Hendeles L, Nickerson D, Neims A. Relative efficacy of phenytoin and phenobarbital for the prevention of theophylline-induced seizures in mice. Ann Emerg Med. 1988 Oct;17(10):1024-8. doi: 10.1016/s0196-0644(88)80439-6[↩]
  89. Ishigaki S, Fukasawa H, Kinoshita-Katahashi N, Yasuda H, Kumagai H, Furuya R. Caffeine intoxication successfully treated by hemoperfusion and hemodialysis. Intern Med. 2014;53(23):2745-7. doi: 10.2169/internalmedicine.53.2882[↩]
  90. Muraro L, Longo L, Geraldini F, Bortot A, Paoli A, Boscolo A. Intralipid in acute caffeine intoxication: a case report. J Anesth. 2016 Oct;30(5):895-9. doi: 10.1007/s00540-016-2198-x[↩][↩]
  91. Schmidt M, Farna H, Kurcova I, Zakharov S, Fric M, Waldauf P, Ilgova Z, Pazout J, Pachl J, Duska F. Succesfull treatment of supralethal caffeine overdose with a combination of lipid infusion and dialysis. Am J Emerg Med. 2015 May;33(5):738.e5-7. doi: 10.1016/j.ajem.2014.11.002[↩]
  92. Kohara S, Kamijo Y, Kyan R, Yoshizawa T, Takahashi T, Shin K, Hasegawa E. Severe caffeine poisoning with mexiletine successfully treated by extracorporeal methods. Am J Emerg Med. 2024 Dec;86:190.e5-190.e7. doi: 10.1016/j.ajem.2024.09.034[↩]
  93. Kato Y, Kuriyama A, Hata R, Ikegami T. Extracorporeal Membrane Oxygenation for Hypokalemia and Refractory Ventricular Fibrillation Associated with Caffeine Intoxication. J Emerg Med. 2020 Jan;58(1):59-62. doi: 10.1016/j.jemermed.2019.09.023[↩]
  94. Heard CM, Johnson S, Moss G, Thomas CP. In vitro transdermal delivery of caffeine, theobromine, theophylline and catechin from extract of Guarana, Paullinia Cupana. Int J Pharm. 2006 Jul 6;317(1):26-31. doi: 10.1016/j.ijpharm.2006.02.042[↩]
  95. Harstad E, Sideridis G, Sherritt L, Shrier LA, Ziemnik R, Levy S. Concurrent Validity of Caffeine Problems and Diagnostic Criteria for Substance Use Disorders. J Caffeine Res. 2016 Dec 1;6(4):141-147. doi: 10.1089/jcr.2016.0006[↩]

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