This proprietary Raintree product has not been the subject of any clinical research. A partial listing of third-party published research on each herbal ingredient in the formula is shown below. Please refer to the plant database files by clicking on the plant names below to see all available documentation and research on each plant ingredient.

Samambaia & Calaguala (Polypodium decumanum & Polypodium leucotomos)
Alvarez, X. A., et al. "Double-blind, randomized, placebo-controlled pilot study with anapsos in senile dementia: effects on cognition, brain bioelectrical activity and cerebral hemodynamics." Methods Find. Exp. Clin. Pharmacol. 2000; 22(7): 585-94.
Cacabelos, R., et al. "A pharmacogenomic approach to Alzheimer's disease." Acta Neurol. Scand. Suppl. 2000; 176: 12-19.
Alvarez, X. A., et al. "Anapsos improves learning and memory in rats with Beta-Amyloid (1-28) deposits in the hippocampus" Progress in Alzheimer's and Parkinson's Diseases, Ed. Fisher, A., Yoshida, M. and Hannin, I., Plenum Press, New York, 1998; pp. 699-703
Nikolov, R. "Alzheimer's disease therapy - an update." Drug News Perspect. 1998 May; 11(4): 248-55.
Alvarez, X. A., et al. "Anapsos reverses interleukin-1 beta overexpression and behavioral deficits in nbM-lesioned rats." Methods Find. Exp. Clin. Pharmacol. 1997; 19(5): 299-309.
Fernandez-Novoa, L., et al. "Effects of Anapsos on the activity of the enzyme Cu-Zn-superoxide dismutase in an animal model of neuronal degeneration." Methods Find. Exp. Clin. Pharmacol. 1997; 19(2): 99-106.
Quintanilla A. E., et al. "Pharmaceutical composition of activity in the treatment of cognitive and/or neuroimmune dysfunctions." U.S. patent no. 5,601,829; 1997.

Tamamuri (Brosimum acutifolium)
Takashima, J., et al. “Mururins A-C, three new lignoids from Brosimum acutifolium and their protein kinase inhibitory activity.” Planta Med. 2002; 68(7): 621-625.
Aksoy, E., et al. “Protein kinase C epsilon: A new target to control inflammation and immune-mediated disorders.” Int. J. Biochem. Cell Biol. 2004; 36(2): 183-8.
Stallings-Mann, M., et al. “A novel small-molecule inhibitor of protein kinase Ciota blocks transformed growth of non-small-cell lung cancer cells.” Cancer Res. 2006 Feb; 66(3):1767-74.
Cohen, E. E., et al. “Protein kinase C zeta mediates epidermal growth factor-induced growth of head and neck tumor cells by regulating mitogen-activated protein kinase.” Cancer Res. 2006 Jun; 66(12): 6296-303.

Catuaba (Erythroxylum catuaba)
Campos, M., et al. “Antidepressant-like effects of Trichilia catigua (Catuaba) extract: evidence for dopaminergic-mediated mechanisms.” Psychopharmacology. 2005 Oct; 182(1): 45-53.
Barbosa, N. R., et al. “Inhibition of platelet phospholipase A2 activity by catuaba extract suggests anti-inflammatory properties.” Phytother. Res. 2004; 18(11): 942-4.
Vaz, Z. R., et al. “Analgesic effect of the herbal medicine Catuaba in thermal and chemical models of nociception in mice.” Phytother. Res. 1997; 11(2): 101–6.

Muira puama (Ptychopetalum olacoides)
da Silva, A. L., et al. "Promnesic effects of Ptychopetalum olacoides in aversive and non-aversive learning paradigms." J. Ethnopharmacol. 2007 Feb; 109(3): 449-457.
da Silva, A. L., et al. "Memory retrieval improvement by Ptychopetalum olacoides in young and aging mice." J. Ethnopharmacol. 2004 Dec; 95(2-3): 199-203.
Siqueira, I. R., et al. "Neuroprotective effects of Ptychopetalum olacoides Bentham (Olacaceae) on oxygen and glucose deprivation induced damage in rat hippocampal slices." Life Sci. 2004 Aug; 75(15): 1897-906.
Siqueira, I. R., et al. "Ptychopetalum olacoides, a traditional Amazonian "nerve tonic," possesses anticholinesterase activity." Pharmacol. Biochem. Behav. 2003 Jun; 75(3): 645-50.
da Silva, A. L., et al. "Anxiogenic properties of Ptychopetalum olacoides Benth. (Marapuama)." Phytother. Res. 2002; 16(3): 223-6.
Siqueira, I. R., et al. "Psychopharamcological properties of Ptychopetalum olacoides Bentham (Olacaceae)." Pharmaceutical Biol. 1998; 36(5): 327–34.
Forgacs, P., et al. "Phytochemical and biological activity studies on 18 plants from French Guyana." Plant Med. Phytother. 1983; 17(1): 22–32.

Cat’s Claw (Uncaria tomentosa)
Jurgensen, S., et al. “Involvement of 5-HT2 receptors in the antinociceptive effect of Uncaria tomentosa.” Pharmacol. Biochem. Behav. 2005 Jul; 81(3): 466-77.
Kang, T. H., et al. “Pteropodine and isopteropodine positively modulate the function of rat uscarinic M(1) and 5-HT(2) receptors expressed in Xenopus oocyte.” Eur. J. Pharmacol. 2002 ay; 444(1-2): 39-45.
Mohamed, A. F., et al. “ Effects of Uncaria tomentosa total alkaloid and its components on xperimental amnesia in mice: elucidation using the passive avoidance test.” J. Pharm. Pharmacol. 001; 52(12): 1553–61.
Roth, B. L., et al. “Insights into the structure and function of 5-HT(2) family serotonin receptors eveal novel strategies for therapeutic target development.” Expert Opin. Ther. Targets 2001 Dec; (6): 685-695.
Castillo, G., et al. “Pharmaceutical compositions containing Uncaria tomentosa extract for treating Alzheimer's disease and other amyloidoses." Patent-Pct. Int. Paol. 1998; 00 33,659: 67pp.
Pilarski, R., et al. “Antioxidant activity of ethanolic and aqueous extracts of Uncaria tomentosa (Willd.) DC.” J. Ethnopharmacol. 2006 Mar; 104(1-2): 18-23.

Suma (Pfaffia paniculata)
Marques, L. C., et al. "Psychopharmacological assessment of Pfaffia glomerata roots (extract BNT-08) in rodents." Phytother. Res. 2004 Jul; 18(7): 566-72.
de-Paris, F., et al. "Psychopharmacological screening of Pfaffia glomerata Spreng. (Amarathanceae) in rodents." J. Ethnopharmacol. 2000 Nov; 73(1-2): 261-9.
Mendes, F. R., et al. "Brazilian plants as possible adaptogens: An ethnopharmacological survey of books edited in Brazil." J. Ethnopharmacol. 2006 Sep 1;
Mazzanti, G., et al. "Analgesic and anti-inflammatory action of Pfaffia paniculata (Martius) Kuntze." Phytother. Res. 1994; 8(7): 413-16.
Mazzanti, G., et al. "Anti-inflammatory activity of Pfaffia paniculata (Martius) Kuntze and Pfaffia stenophylla (Sprengel) Stuchl." Pharmacol. Res. 1993; 27(1): 91–92.
de Oliveira, F. G., et al. "Contribution to the pharmacognostic study of Brazilian ginseng Pfaffia paniculata." An. Farm. Quim. 1980; 20(1–2): 277–361.

Guarana (Paullina cupana)
Haskell, C. F., et al. "A double-blind, placebo-controlled, multi-dose evaluation of the acute behavioural effects of guarana in humans." J. Psychopharmacol. 2007; 21(1): 65-70.
Kennedy, D. O., et al. “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.
Espinola, E. B., et al. ”Pharmacological activity of Guarana (Paullinia cupana Mart.) in laboratory animals.” J. Ethnopharmacol. 1997 Feb; 55(3):223-9.
Galduróz, J. C., et al. “The effects of long-term administration of guaraná on the cognition of normal, elderly volunteers.” Rev. Paul. Med. 1996; 114(1): 1073–78.
Benoni, H., et al. “Studies on the essential oil from guaraná.” Z. Lebensm. Unters. Forsch. 1996; 203(1): 95–8.
Galduróz, J. C., et al. “Acute effects of the Paulinia cupana, ‘guaraná,’ on the cognition of normal volunteers.” Rev. Paul. Med. 1994; 112(3): 607–11.

Nettle (Urtica dioica)
Toldy, A., et al. “The effect of exercise and nettle supplementation on oxidative stress markers in the rat brain.Brain Res. Bull. 2005 May 30; 65(6): 487-93.
Barneoud, P., et al. “Brain neocortex immunomodulation in rats.” Brain Res. 1988 Dec; 474(2): 394-8.
Rau, O., et al. “Screening of herbal extracts for activation of the human peroxisome proliferator-activated receptor.” Pharmazie. 2006; 61(11):952-6.
Kanter, M., et al. “Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats.” World J. Gastroenterol. 2005; 11(42): 6684-8.
Gullcin, I., et al. “Purification and characterization of polyphenol oxidase from nettle (Urtica dioica L.) and inhibitory effects of some chemicals on enzyme activity.” J. Enzyme Inhib. Med. Chem. 2005 Jun; 20(3): 297-302.
Gullcin, I., et al. “Antioxidant, antimicrobial, antiulcer and analgesic activities of nettle (Urtica dioica L.).” J. Ethnopharmacol. 2004 Feb; 90(2-3): 205-15.

Sarsaparilla (Smilax sp)
Jeon, S. Y., et al. "Beta-secretase (BACE1)-inhibiting stilbenoids from Smilax Rhizoma." Phytomedicine. 2006 Nov 2
Ban, J. Y., et al. "Catechin and epicatechin from Smilacis chinae rhizome protect cultured rat cortical neurons against amyloid beta protein (25-35)-induced neurotoxicity through inhibition of cytosolic calcium elevation." Life Sci. 2006 Nov; 79(24) :2251-9.
Ren, L. X., et al. "Antidepressant-like effects of sarsasapogenin from Anemarrhena asphodeloides BUNGE (Liliaceae)." Biol. Pharm. Bull. 2006 Nov; 29(11): 2304-6.
Ban, J. Y., et al. "Protection of amyloid beta protein (25-35)-induced neurotoxicity by methanol extract of Smilacis chinae rhizome in cultured rat cortical neurons." J. Ethnopharmacol. 2006 Jun; 106(2): 230-7.
Barraclough , P., et al. "5-beta-sapogenin and pseudosapogenin derivatives and their use in the treatment of dementia." United States Patent 7,138,427: November 21, 2006.
Hu, Y., et al. "A new approach to the pharmacological regulation of memory: Sarsasapogenin improves memory by elevating the low muscarinic acetylcholine receptor density in brains of memory-deficit rat models." Brain Res. 2005 Oct; 1060(1-2): 26-39.
Xia, Z. et al. Steroidal sapogenins and their derivatives for treating Alzheimer's disease." United States Patent 6,812,213; November 2, 2004.