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.

Mulungu (Erythrina mulungu)
Hidalgo, A., et al. "Differential expression of glycans in the hippocampus of rats trained on an inhibitory learning paradigm." Neuropathology. 2006 Dec; 26(6): 501-7.
Ribeiro, M. D., “Effect of Erythrina velutina and Erythrina mulungu in rats submitted to animal models of anxiety and depression.” Braz. J. Med. Biol. Res. 2006; 39(2): 263-70.
Vasconcelos, S. M., et al. “Central activity of hydroalcoholic extracts from Erythrina velutina and Erythrina mulungu in mice.” J. Pharm. Pharmacol. 2004; 56(3): 389-93.
Onusic, G.M., et al. “Effects of chronic treatment with a water-alcohol extract from Erythrina mulungu on anxiety-related responses in rats.” Biol. Pharm. Bull. 2003; 26(11): 1538-42.
Onusic, G. M., et al. “Effect of acute treatment with a water-alcohol extract of Erythrina mulungu on anxiety-related responses in rats.” Braz. J. Med. Biol. Res. 2002; 35(4): 473–77.
Kittler, J. T., et al. “Mechanisms of GABA receptor assembly and trafficking: implications for the modulation of inhibitory neurotransmission.” Mol. Neurobiol. 2002; 26(2–3): 251–68.

Manacá (Brunfelsia uniflora)
Moon, P. D., et al. "Use of scopoletin to inhibit the production of inflammatory cytokines through inhibition of the IkappaB/NF-kappaB signal cascade in the human mast cell line HMC-1." Eur. J. Pharmacol. 2007 Jan; 555(2-3): 218-25.
Rollinger, J. M., et al. “Acetylcholinesterase inhibitory activity of scopolin and scopoletin discovered by virtual screening of natural products.” J. Med. Chem. 2004 Dec 2; 47(25): 6248-54.
Kim, H. J., et al. “Scopoletin suppresses pro-inflammatory cytokines and PGE2 from LPS-stimulated cell line, RAW 264.7 cells.” Fitoterapia. 2004 Jun; 75(3-4): 261-6.
Chiou, L. C., et al. "Chinese herb constituent beta-eudesmol alleviated the electroshock seizures in mice and electrographic seizures in rat hippocampal slices." Neurosci. Lett. 1997; 231(3): 171-74.
Ruppelt, B. M., et al. “Pharmacological screening of plants recommended by folk medicine as anti-snake venom–I. Analgesic and anti-inflammatory activities.” Mem. Inst. Oswaldo Cruz 1991; 86: 203–5.

Piri-Piri (Cyperus articulatus)
Rakotonirina, V. S., et al. “Sedative properties of the decoction of the rhizome of Cyperus articulatus.” Fitoterapia. 2001; 72(1): 22-9.
Bum, E. N., et al. “Ions and amino acid analysis of Cyperus articulatus L. (Cyperaceae) extracts and the effects of the latter on oocytes expressing some receptors.” J. Ethnopharmacol. 2004 Dec; 95(2-3): 303-9.
Bum, E. N., et al. “Extracts from rhizomes of Cyperus articulatus (Cyperaceae) displace [3H]CGP39653 and [3H]glycine binding from cortical membranes and selectively inhibit NMDA receptor-mediated neurotransmission.” J. Ethnopharmacol. 1996 Nov; 54(2-3): 103-11.
Bum, E. N., et al. “Effects of Cyperus articulatus compared to effects of anticonvulsant compounds on the cortical wedge.” J. Ethnopharmacol. 2003 Jul; 87(1): 27-34.
Bum, E. N., et al. “Anticonvulsant properties of the methanolic extract of Cyperus articulatus (Cyperaceae).” J. Ethnopharmacol. 2001 Jul; 76(2): 145-50.
Bum, E. N., et al. “Effect of the decoction of rhizomes of Cyperus articulatus on bicuculline-, n-methyl-d-aspartate- and strychnine-induced behavioural excitation and convulsions in mice.” J. Cameroon Acad. Sci. 2002; 2: 91-95.
Bum, E. N., et al. “Organic and water extracts of Cyperus articulatus (Cyperaceae)inhibited chemically and electrically-induced convulsions in mice.” J. Cameroon Acad. Sci. 2002; 2: 96-106.

Graviola (Annona muricata)
Padma, P., et al. “Effect of Annona muricata and Polyalthia cerasoides on brain neurotransmitters and enzyme monoamine oxidase following cold immobilization stress.” J. Natural Remedies 2001; 1(2): 144–46.
Hasrat, J. A., et al. “Screening of medicinal plants from Suriname for 5-HT 1A ligands: Bioactive isoquinoline alkaloids from the fruit of Annona muricata.” Phytomedicine. 1997; 4(20: 133-140.
N’gouemo, P., et al. “Effects of ethanol extract of Annona muricata on pentylenetetrazol-induced convulsive seizures in mice.” Phytother. Res. 1997; 11(3): 243–45.
Padma, P., et al. “Effect of alcohol extract of Annona muricata on cold immobilization stress induced tissue lipid peroxidation.” Phytother. Res. 1997; 11(4): 326-327.
Hasrat, J. A., et al. “Isoquinoline derivatives isolated from the fruit of Annona muricata as 5-HTergic 5-HT1A receptor agonists in rats: unexploited antidepressive (lead) products.” J. Pharm. Pharmacol. 1997; 49(11): 1145–49.
Bourne, R. K., et al. “A preliminary study of the sedative effects of Annona muricata (sour sop).” West Indian Med J. 1979 Jun; 28(2): 106-10.

Catuaba (Erythroxlyum catuaba)
Campos, M. M., et al. “Antidepressant-like effects of Trichilia catigua (Catuaba) extract: evidence for dopaminergic-mediated mechanisms.” Psychopharmacology (Berl). 2005; 182(1): 45-53.
Antunes, E., et al. “The relaxation of isolated rabbit corpus cavernosum by the herbal medicine Catuama and its constituents.” Phytother. Res. 2001; 15(5): 416-21.
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.
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.

Iporuru (Alchornea castaneifolia)
Manga, H. M., et al. “In vivo anti-inflammatory activity of Alchornea cordifolia (Schumach. & Thonn.) Mull. Arg. (Euphorbiaceae).” J. Ethnopharmacol. 2004 Jun; 92(2-3): 209-14.
Osadebe, P. O., et al. “Anti-inflammatory effects of crude methanolic extract and fractions of Alchornea cordifolia leaves.” J. Ethnopharmacol. 2003 Nov; 89(1):19-24.
Tona, L., et al. “Antiamoebic and spasmolytic activities of extracts from some antidiarrhoeal traditional preparations used in Kinshasa, Congo.” Phytomedicine. 2000 Mar; 7(1): 31-8.
Dunstan, C. A., et al. “Evaluation of some Samoan and Peruvian medicinal plants by prostaglandin biosynthesis and rat ear oedema assays.” J. Ethnopharmacol. 1997; 57: 35–56.
Ogungbamila, F. O., et al. “Smooth muscle–relaxing flavonoids from Alchornea cordifolia.” Acta Pharm. Nord. 1990; 2(6): 421–22.

Ubos (Spondias mombin)
Ayoka, A., et al. "Studies on the anxiolytic effect of Spondias mombin L. (Anacardiaceae) extracts." J. Trad. CAM. 2005: 2(2): 153-165.
Ayoka, A., et al. "Sedative, antiepileptic and antipsychotic effects of Spondias mombin L. (Anacardiaceae) in mice and rats." J. Ethnopharmacol. 2006 Jan; 103(2): 166-75.

Passionflower (Passiflora sp.)
Miyasaka, L., et al. "Passiflora for anxiety disorder." Cochrane Database Syst Rev. 2007 Jan 24; (1): CD004518.
Coleta, M., et al. "Neuropharmacological evaluation of the putative anxiolytic effects of Passiflora edulis Sims, its sub-fractions and flavonoid constituents." Phytother. Res. 2006 Dec; 20(12): 1067-73.
Lolli, L. F., et al. "Possible involvement of GABA(A)-benzodiazepine receptor in the anxiolytic-like effect induced by Passiflora actinia extracts in mice." J. Ethnopharmacol. 2006 Nov 26;
Gramowski, A., et al. "Functional screening of traditional antidepressants with primary cortical neuronal networks grown on multielectrode neurochips." Eur. J. Neurosci. 2006 Jul; 24(2): 455-65.
Reginatto, F. H., et al. "Evaluation of anxiolytic activity of spray dried powders of two South Brazilian Passiflora species." Phytother. Res. 2006 May; 20(5): 348-51.
Ernst E. "Herbal remedies for anxiety - a systematic review of controlled clinical trials." Phytomedicine. 2006 Feb; 13(3): 205-8.
Wheatley, D. “Medicinal plants for insomnia: a review of their pharmacology, efficacy and tolerability.” J. Psychopharmacol. 2005 Jul; 19(4): 414-21.
Shinomiya, K., et al. “Hypnotic activities of chamomile and passiflora extracts in sleep-disturbed rats.” Biol. Pharm. Bull. 2005; 28(5): 808-10.
Dhawan, K., et al. “Attenuation of benzodiazepine dependence in mice by a tri-substituted benzoflavone moiety of Passiflora incarnata Linneaus: a non-habit forming anxiolytic.” J. Pharm. Pharm. Sci. 2003 May-Aug; 6(2): 215-22.
Dhawan, K., et al. “Comparative anxiolytic activity profile of various preparations of Passiflora incarnata Linneaus: a comment on medicinal plant’s standardization.” J. Altern. Complement. Med. 2002; 8(3): 283-91.
Dhawan, K., et al. “Suppression of alcohol-cessation-oriented hyper-anxiety by the benzoflavone moiety of Passiflora incarnata Linneaus in mice.” J. Ethnopharmacol. 2002; 81(2): 239-44.
Dhawan, K., et al. “Anxiolytic activity of aerial and underground parts of Passiflora incarnata.” Fitoterapia. 2001; 72(8): 922-6.
Akhondzadeh, S., et al. “Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam.” J. Clin. Pharm. Ther. 2001; 26(5): 363-7.
Dhawan, K., et al. “Correct Identification of Passiflora incarnata Linn., a Promising Herbal Anxiolytic and Sedative.” J. Med. Food. 2001 Autumn; 4(3): 137-144.
Wolfman, C., et al. “Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea.” Pharmacol. Biochem. Behav. 1994; 47(1): 1-4.
Maluf, E., et al. “Assessment of the hypnotic/sedative effects and toxicity of Passiflora edulis aqueous extract in rodents and humans.” Phytother. Res. 1991; 5(6): 262-266.

Chamomile (Matricaria chamomilla)
Reis, L. S., et al. "Matricaria chamomilla CH12 decreases handling stress in Nelore calves." J. Vet. Sci. 2006 Jun; 7(2): 189-92.
McKay, D. L., et al. "A review of the bioactivity and potential health benefits of chamomile tea (Matricaria recutita L.)." Phytother. Res. 2006 Jul; 20(7): 519-30.
Wheatley, D. “Medicinal plants for insomnia: a review of their pharmacology, efficacy and tolerability.” J. Psychopharmacol. 2005 Jul; 19(4): 414-21.
Shinomiya, K., et al. “Hypnotic activities of chamomile and passiflora extracts in sleep-disturbed rats.” Biol. Pharm. Bull. 2005; 28(5): 808-10.
Gomaa, A., et al. “Matricaria chamomilla extract inhibits both development of morphine dependence and expression of abstinence syndrome in rats.” J. Pharmacol. Sci. 2003 May; 92(1): 50-5.
Larzelere, M., Wiseman, P. “Anxiety, depression, and insomnia.” Prim. Care. 2002; 29(2): 339-60.
Avallone, R, et. al. “Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla.” Biochem. Pharmacol. 2000; 59(11): 1387-94.
Paladini, C, et al. “Flavonoids and the central nervous system: from forgotten factors to potent anxiolytic compounds.” J. Pharm. Pharmacol. 1999; 51(5): 519-26.
Cauffield, J. S, et al. “Dietary supplements used in the treatment of depression, anxiety, and sleep disorders.” Lippincotts Prim. Care. Pract. 1999; 3(3): 290-304.
Viola, H., et al. “Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects.” Planta Med. 1995; 61(3): 213-6.

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.
Siqueira, I. R., et al. “Ptychopetalum olacoides, a traditional Amazonian "nerve tonic", possesses anticholinesterase activity.” Pharmacol. Biochem. Behav. 2003; 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 olachoides Bentham (Olacaceae)." Pharmaceutical Biol. 1998; 36(5): 327-34.
Paiva, Laf, et al. "Effects of Ptychocepalum olacoides extract on mouse behaviour in forced swimming and open field tests." Phytother. Res. 1998; 12(4): 294-96.
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.