Paullinia cupana



Guarana is a rainforest vine that was domesticated in the Amazon for its caffeine-rich fruits. Guarana has long been used as a tonic and to treat various disorders in Brazil. In the last two decades, guarana has emerged as a key ingredient in various sports and energy drinks. Some 60 plant species, from seven different plant families, contain caffeine, guarana seeds, however, contain more caffeine than any other plant in the world with levels ranging from 2 to 7.5%.1 Guarana contains about four times as much caffeine as coffee. Guarana was domesticated in the interfluvial forests (region of higher land between two rivers) in the Brazilian Amazon. The indigenous people, the Satere-Maue, who live along the Maue's river cultivate guarana extensively. Guarana is harvested by hand in the dry season. If the entire fruit bunch is ripe, it is either snipped off with scissors or small pruning shears, or broken off manually. If only a few berries are ripe, they are picked individually. Before roasting the seeds, the red skin must be removed. The fruits are skinned by hand, left to soak in water, or simply stored for several days until the skin softens. Guarana seeds are roasted and processed in a similar way to coffee beans. Guarana was transformed from an elixir and home-prepared beverage to a mass-produced soft drink in the early 20th century. In the last decade or so, guarana carts have begun appearing in some street markets in the Brazilian Amazon, selling guarana beverages prepared in a blender with crushed ice. The formula for the energy drink varies among vendors, but generally contains nuts, such as cashew, peanuts or Brazil nuts, powdered milk, various roots or barks and guarana powder or syrup. Some add fruit, such as avocado or raw quail eggs. Dozens of new energy drinks containing guarana are now promoted worldwide.2 Guarana was historically prescribed as a nerve tonic, diuretic, aphrodisiac, and for the treatment of headache, rheumatism, lumbago, diarrhoea and dysentery and it was included in the United States Pharmacopeia from 1880 through 1910.3


Guarana has been found to contain purine alkaloids, 3-10% caffeine, methylxanthine, <1% theophylline or theobromine, and 12% non-hyrolyzable tannins - catechin and epicatechin.7

Therapeutic activities

Guarana's stimulant properties have generally been assumed to due to the caffeine content. The psychoactive properties of guarana, however, may also be attributable to relatively high content of other potentially psychoactive components, including both saponins and tannins. After administration of single dosages of 37.5, 75, 150 and 300 mg of the same extract to 26 volunteers it has been shown that the 75 mg dose was the most effective in terms of behavioural modulation, with confirmation of the significant effects on the secondary memory measure. Mood was also improved, with all doses leading to increased 'contentedness' and the 300 and 75 mg doses increasing 'alertness' on two different subjective ratings scales.5 What is particularly interesting about the results across this study and an earlier study6 by the same authors, is that the 75 mg dose of guarana contained a level of caffeine (9 mg) generally considered to be too low to be functionally active, and that performance did not increase with dose, and therefore level of caffeine. This strongly suggests that the effects evinced were not attributable to guarana's caffeine content alone.7

The effects of caffeine but not guarana can be blocked by the adenosine agonist cyclopentyl adenosine suggesting a mechanism other than the adenosinergic system is responsible for the effects of guarana and may be indicative of the influence of components other than caffeine, within guarana.8 One possibility is therefore that the psychoactive properties evinced here are attributable to the several other potentially psychoactive components including the relatively high levels of saponins and tannins contained within guarana extracts.5

Antioxidant effects

Guarana has been shown to inhibit lipid peroxidation in vivo.9

Effects on mental performance

Single doses (3mg/kg and 30mg/kg) as well as chronic administration (0.3mg/mL) of guarana has been shown to reverse the amnesic effect of scopolamine in vivo.10 Guarana has also been shown to improve the mental performance in humans. The guarana extract used in this study contained only 11% to 12% caffeine, it seems unlikely that the potential maximum dose of under 10 mg caffeine could itself account for the performance effects observed. Furthermore, improved speed of task performance on all measures was still apparent at 6 hours. Caffeine, including when derived from guarana, has a half-life of approximately 6 hour in non-smoking humans, and would have presumably decayed to subactive levels by this time point. The suggestion that guarana's caffeine content alone does not account for all of its cognitive effects is also supported by observations in rodents. Doses of guarana with minimal total caffeine content were more beneficial than 10-fold doses of guarana (where the caffeine fraction may have been approaching pharmacological levels). Additionally, the lower doses were as effective as pure caffeine administered at a 16-fold higher dose (by caffeine content alone) on fatigue and memory tasks.11

Effects on hypertension and energy expenditure

A combination of green tea and guarana extract has been shown to increase the twenty-four hour energy expenditure by about 750 kilojoules compared to placebo. No effect on lipid oxidation was observed. The systolic and diastolic blood pressures increased by about 7 and 5 mmHg respectively compared to placebo although this increase was only significant for the 24-hour diastolic blood pressure.12

Gastrointestinal effects

Pre-treatment with 50 and 100mg/kg guarana orally has been shown to significantly reduce the severity of ethanol-induced gastric lesions in a manner similar to caffeine (20 and 30mg/kg orally). Higher doses were also shown to be effective against indomethacin-induced gastric ulceration whereas the tested dosage of caffeine was not. Guarana and caffeine have both been shown to significantly reduce the volume of gastric secretions as well as total acidity in animal models. The gastrointestinal transit time was not significantly affected.13

Hyperglycemic effects

A water extract of guarana (500 mg/kg) has been shown to significantly increase the blood glucose level (p<0.001) and decrease liver glycogen 60 minutes after oral maltose administration (p<0.05). The study also showed that guarana significantly suppressed exercise-induced hypoglycaemia (p<0.05). The guarana extract, however, did not affect the blood glucose in noradrenalin-induced glycogenolytic mice.14

Anti-inflammatory effects

Guarana extract has been shown to inhibit platelet aggregation, thromboxane and arachidonic acid in vitro.15, 16

Thermogenic effects

Methylxanthines isolated from guarana and combined with ephedrine induce a thermogenic response in obese mice, increasing their daily energy expenditure.17

Other effects extrapolated from activities related to caffeine

The mechanism of action of guarana is related to its significant caffeine content. Caffeine acts as a central nervous system stimulant, increases heart rate and contractility, increases blood pressure, inhibits platelet aggregation, stimulates gastric acid secretion, induces diuresis, and relaxes bronchial smooth muscle. The following trials have been carried out with caffeine. Their outcome therefore cannot be directly related to guarana4 but it is likely that guarana will have similar effects. Caffeine acts as a catecholamine inhibitor, thereby prolonging cyclic adenosine monophosphate (cAMP) in some cells. Caffeine has diuretic effects. Acute caffeine ingestion may induce a rise in mean adrenaline levels, an effect that is lost with sustained intake. Caffeine has also been shown to enhance dopamine release during an initial two-hour interval but to ultimately decrease total dopamine turnover during a three to four hour study period (biphasic response).4


Stimulant, thermogenic, anti-inflammatory, antioxidant.

Traditional usage

Guarana has long been esteemed for its energetic and curative properties. In the late 17th century, for example, a Jesuit missionary noted that the Satere-Maue valued guarana as much as Europeans did gold because the drink gave them so much energy, that they could hunt for a day without feeling hungry. Another missionary noted that guarana was drunk to diminish fevers and cure headaches, and also served as a powerful diuretic. During the colonial period, guarana was sold variously as a fortifier, stimulant, tonic, antidote to fever, a preventive against hardening of the arteries and to treat migraines. Guarana was deemed especially effective in treating diarrhoea and dysentery.2



Moderate consumption of drinks containing caffeine may alleviate drowsiness for a while, but it cannot replace the need for sleep. Short term use only.

Mental fatigue

A double-blind, placebo-controlled, cross-over study assessed the psychoactive effects of single doses of guarana in healthy adults. The study found that 75 mg guarana extract, administered to 28 healthy young participants, was capable of producing improvements in composite scores reflecting secondary memory performance and the speed of performing attentional tasks, as well as improving performance on serial subtraction mental arithmetic tasks.4

A double-blind, randomised, placebo-controlled, parallel groups study assessed the acute effects of either a guarana and multivitamin and mineral supplement or placebo drink in 129 healthy young adults (18-24 years). Participants completed a 10 min version of the Cognitive Demand Battery (comprising: Serial 3s and Serial 7s subtraction tasks, a Rapid Visual Information Processing (RVIP) task, 'mental fatigue' scale). Thirty minutes following their drink participants made six consecutive completions of the battery (i.e. 60 min). The guarana and multivitamin combination resulted in improved task performance, in comparison to placebo, in terms of both increased speed and accuracy of performing the RVIP task throughout the post-dose assessment. The increase in mental fatigue associated with extended task performance was also attenuated by the supplement. This research supports previous findings demonstrating guarana's cognition enhancing properties and provides evidence that its addition to a multi-vitamin-mineral supplement can improve cognitive performance and reduce the mental fatigue associated with sustained mental effort.5

In a previous study18 the effects of three different doses of caffeine (33, 38, and 46 mg) in combination with glucose was studied. Whilst the effects were somewhat similar to those from guarana, it is notable that the pattern of significant effects was less marked, with significant improvement only seen on the accuracy (but not speed) as measured by the Rapid Visual Information Processing examination, and with the relief of mental fatigue dissipating towards the end of the extended period of the task. However, one notable similarity between the caffeine and the guarana study is the lack of any significant effect on the Serial subtractions tasks. The two tasks require markedly different cognitive resources. The RVIP task could be described as a classic vigilance task (predominantly requiring attention), while Serial subtraction task introduces elements of working memory, and 'executive' function. Given that the investigational products in both studies contained caffeine, and that caffeine has not previously been shown to modulate tasks of this nature19 it seems likely that to the naturally occurring caffeine in guarana is responsible for the effect but that other constituents possibly modify the magnitude of the effect.5 The vitamin and minerals may also have contributed to the observed effects in the guarana study, however, as it was a single dose, this is unlikely.

Cognitive enhancement

Guarana is often combined with Panax ginseng for their synergistic effects. Ginseng is currently consumed worldwide for its beneficial properties, which include positive effects on physical parameters, cognitive performance and well-being. In a double-blind, counterbalanced, placebo-controlled study,11 the cognitive and mood effects of separate single doses of: 75 mg of a dried ethanolic extract of guarana (approx 12% caffeine), 200 mg of Panax ginseng (G115), and their combination (75 mg/200 mg), were assessed in 28 healthy young (18-24) participants. In comparison to placebo, all three treatments resulted in improved task performance throughout the day. In the case of guarana, improvements were seen across the attention tasks (but with some evidence of reduced accuracy), and on a sentence verification task. While also increasing the speed of attention task performance, both ginseng and the ginseng/guarana combination also enhanced the speed of memory task performance, with little evidence of modulated accuracy. Guarana and the combination, and to a lesser extent ginseng, also led to significant improvements in serial subtraction task performance. These results provide the first demonstration in humans of the psychoactive effects of guarana, and confirmation of the psychoactive properties of ginseng. Given the low caffeine content (9 mg) of this dose of guarana extract, the effects are unlikely to be attributable to its caffeine content.4

Weight loss

Guarana is known to help stave off hunger and it is used in weight loss programmes. But almost all energy drinks with guarana as one of the ingredients also contain large amounts of high fructose corn syrup, a sure sign that the beverages are not particularly healthy and may lead to weight gain when taken on a regular basis.

Exercise performance

Guarana is also used to enhance athletic performance and to reduce fatigue. It has been used in the past as an aphrodisiac, diuretic, astringent, and to prevent malaria and dysentery, diarrhoea, fever, headache, and rheumatism.4

Mood enhancement

Caffeine may have positive effects on mood. Caffeine may increase alertness and feelings of well-being and improve performance on sustained attention tasks and simulated driving performance. Slow release caffeine consumption has been correlated with a decrease in calmness and an increase in sleep onset latency.4 Guarana may have similar effects.

Use in pregnancy

Guarana is not recommended in pregnancy or lactation due to lack of sufficient data. Excessive amounts of caffeine should be avoided although studies reports no adverse effects on the featus from drinking normal amounts of coffee. Avoid in breastfeeding women, as caffeine is rapidly transferred to breast milk and may produce effects such as irritability or anxiety in infants.4

Contraindications and cautions

Excessive consumption is associated with caffeine overdose and could lead to insomnia or dizziness.1 Guarana is generally regarded as safe when not combined with other stimulatory agents, such as ephedrine. The LD50 for mice for guarana is more than 500mg/kg (142), while the LD50 for caffeine in rats is 233mg/kg.4

Guarana is generally well-tolerated. A majority of information related to adverse effects of guarana is based in theory upon the adverse effect profile of caffeine. The effects of caffeine are likely more pronounced at age extremes, in the elderly and in children. The chronic use of caffeine, especially in large amounts, may produce tolerance, habituation, and psychological dependence. Abrupt discontinuation of caffeine can result in physical withdrawal symptoms including headache, irritation, nervousness, anxiety, and dizziness. "Burning in the stomach" was reported by four patients in a controlled study (three were on guarana, and one was on caffeine).4

Avoid or use guarana with care in the following situations4 (due to its caffeine content):

  • hypertension as caffeine may increase blood pressure
  • arrhythmias as caffeine may exacerbate this condition
  • breast disease due to possible association with fibrocystic breast disease
  • impaired kidney function, as guarana may produce a diuretic effect
  • diabetic patients, as caffeine may raise blood glucose level
  • pre-existing mitral valve prolapse, as intractable ventricular fibrillation has been reported in a case associated with high dosage caffeine consumption
  • individuals with iron deficiency due to possible association with development of anaemia
  • individuals with bleeding disorders, as caffeine may prolong bleeding time
  • glaucoma, drinking caffeinated products may increase intraocular pressure
  • osteoporosis, as caffeine may increase urinary excretion of calcium


Guarana may interact with the following drugs due to its caffeine content: Acetaminophen (caffeine combined with analgesics has been reported to increase the analgesic effect by 40%), ibuprofen (a clinical trial showed an increase in pain reduction of 2.6 times when ibuprofen was used in combination with caffeine compared to ibuprofen alone. The combination of ibuprofen and caffeine had a greater analgesic effect in women suffering from primary dysmenorrhoea, amphetamines (additive effect), anticoagulant/antiplatelet drugs (additive effect), benzodiazepines (guarana may attenuate the drowsy effects and mental slowness of benzodiazepines. Guarana may also reduce their sedative effect), beta-adrenergic agonists (concomitant use of guarana may increase the inotropic effects of beta agonists), CNS stimulants (concomitant use of CNS stimulants and caffeine may increase the risk of stimulant adverse effects). Caffeine may affect the bioavailability or metabolism of carbamazepine, cimetidine, ciprofloxacin, clozapine and theophylline.4

Administration and Dosage

Guarana (seeds) 1:1 liquid extract: 0.2 to 1.3 ml three times daily.


  1. Beck HT. Caffeine, alcohol, and sweeteners. In: Prance GT (ed).The Cultural History of Plants. New York: Routledge, 2005, 173–90.
  2. Smith N, Atroch AL. Guarana's Journey from Regional Tonic to Aphrodisiac and Global Energy Drink.Evid Based Complement Alternat Med. 2007
  3. Morton, J. F. Widespread tannin intake via stimulants and masticatories, especially guarana, kola nut, betel vine, and accessories. Basic Life Sci. 1992;59:739-765
  4. Natural Standard Guarana Monograph. Accessed 1/10/08
  5. Haskell, C. F., Kennedy, D. O., Wesnes, K. A., Milne, A. L., & Scholey,A. B. (2007). A double-blind, placebo-controlled, multi-dose evaluationof the acute behavioural effects of guarana´ in humans. Journal of Psychopharmacology.
  6. Haskell, C. F., Kennedy, D. O., Wesnes, K. A., & Scholey, A. B. (2005).Cognitive and mood improvements of caffeine in habitual consumers and habitual non-consumers of caffeine. Psychopharmacology, 179,813–825.
  7. Kennedy DO, Haskell CF, Robertson B, Reay J, Brewster-Maund C, Luedemann J, Maggini S, Ruf M, Zangara A, Scholey AB.Improved cognitive performance and mental fatigue following a multi-vitamin and mineral supplement with added guaraná (Paullinia cupana).Appetite. 2008 Mar-May;50(2-3):506-13.
  8. Campos, A. R., Barros, A. I., Albuquerque, F. A., Leal, L. K., & Rao, V. S. (2005). Acute effects of guarana (Paullinia cupana Mart.) on mouse behaviour in forced swimming and open field tests. Phytotherapy Research, 19, 441–443.
  9. Mattei, R., Dias, R. F., Espinola, E. B., Carlini, E. A., and Barros, S. B. Guarana (Paullinia cupana): toxic behavioral effects in laboratory animals and antioxidants activity in vitro. J.Ethnopharmacol. 1998;60(2):111-116
  10. Espinola, E. B., Dias, R. F., Mattei, R., and Carlini, E. A. Pharmacological activity of Guarana (Paullinia cupana Mart.) in laboratory animals. J.Ethnopharmacol. 1997;55(3):223-229.
  11. 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 Nov;79(3):401-11.
  12. Berube-Parent S, Pelletier C, Dore J, and 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. Br J Nutr 2005;94(3):432-436
  13. Campos, A. R., Barros, A. I., Santos, F. A., and Rao, V. S. Guarana (Paullinia cupana Mart.) offers protection against gastric lesions induced by ethanol and indomethacin in rats. Phytother Res. 2003;17(10):1199-1202
  14. Miura, T., Tatara, M., Nakamura, K., and Suzuki, I. Effect of guarana on exercise in normal and epinephrine-induced glycogenolytic mice. Biol.Pharm.Bull. 1998;21(6):646-648.
  15. Bydlowski, S. P., Yunker, R. L., and Subbiah, M. T. A novel property of an aqueous guarana extract (Paullinia cupana): inhibition of platelet aggregation in vitro and in vivo. Braz.J.Med.Biol.Res. 1988;21(3):535-538
  16. Bydlowski, S. P., D'Amico, E. A., and Chamone, D. A. An aqueous extract of guarana (Paullinia cupana) decreases platelet thromboxane synthesis. Braz.J.Med.Biol.Res. 1991;24(4):421-424
  17. Dulloo, A. G. and Miller, D. S. The thermogenic properties of ephedrine/methylxanthine mixtures: human studies. Int J Obes. 1986;10(6):467-481
  18. Kennedy, D. O., & Scholey, A. B. (2004). A glucose-caffeine "Energy Drink" ameliorates subjective and performance deficits during prolonged cognitive demand. Appetite, 42, 331–333.
  19. Haskell, C. F., Kennedy, D. O., Wesnes, K. A., & Scholey, A. B. (2005). Cognitive and mood improvements of caffeine in habitual consumers and habitual non-consumers of caffeine. Psychopharmacology, 179, 813–825.