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Fitoterapia : plantas com efeito na ansiedade

Paula Vias Jos de Felippe Junior

Existem dois tipos de ansiedade: a normal e a generalizada. A ansiedade normal se restringe a uma determinada situao, e nos faz pensar sobre como resolver os problemas e enfrenta los da melhor forma. Essa ansiedade nos acompanha desde os tempos da caverna, onde funcionava como sinalizador de perigo. Os principais sintomas da ansiedade so: inquietao, dificuldade de relaxar, irritabilidade, cansar se com facilidade, problemas gastro intestinais, dificuldade em adormecer ou sono insatisfatrio, palpitaes e falta de ar. A ansiedade generalizada diagnosticada quando esses sintomas tornam se constantes e a preocupao injustificvel. Portanto, o trabalho inicial do mdico est em avaliar cada um desses sintomas e excluir outras doenas que possam se parecer com a ansiedade generalizada. Quando a ansiedade generalizada aguda e intensa o paciente tem a sensao de morte iminente, taquicardia, suores profusos e medo intenso. Esse quadro denominado Sndrome do Pnico. Para tratar a ansiedade o mdico pode indicar o uso de apoio psicolgico ou tratamento medicamentoso sendo os mais usados os benzodiazepnicos. Eles facilitam a ligao do GABA, um neurotransmissor que causa sedao, ao seu stio de ligao. A seguir vamos enunerar alguns trabalhos cientficos retirados da literatrura mdica de bom nvel, sobre plantas que ajudam a controlar a ansiedade. Elas podem ser usadas para o conforto do paciente at que o fator causal seja afastado.

Plantas em geral Plants and the central nervous system. Pharmacol Biochem Behav;75(3):501-12, 2003 Jun. Carlini EA Resumo: This review article draws the attention to the many species of plants possessing activity on the central nervous system (CNS). In fact, they cover the whole spectrum of central activity such as psychoanaleptic, psycholeptic and psychodysleptic effects, and several of these plants are currently used in therapeutics to treat human ailments.Among the psychoanaleptic (stimulant) plants, those utilized by human beings to reduce body weight [Ephedra spp. (Ma Huang), Paullinia spp. (guaran), Catha edulis Forssk. (khat)] and plants used to improve general health conditions (plant adaptogens) were scrutinized.Many species of hallucinogenic (psychodysleptic) plants are used by humans throughout the world to achieve states of mind distortions; among those, a few have been used for therapeutic purposes, such as Cannabis sativa L., Tabernanthe iboga Baill. and the mixture of Psychotria viridis Ruiz and Pav. and Banisteriopsis caapi (Spruce ex Griseb.) C.V. Morton. Plants showing central psycholeptic activities, such as analgesic or anxiolytic actions (Passiflora incarnata L., Valeriana spp. and Piper methysticum G. Forst.), were also analysed.Finally, the use of crude or semipurified extracts of such plants instead of the active substances seemingly responsible for their therapeutic effect is discussed. Prof.Dr.Elisaldo Carlini.Um dos maiores conhecedores de psicofarmacologia no Brasil. Capim limo (Cymbopogon citratus ) Muito usada no Brasil como calmante. No estudo a seguir no foram detectados efeitos ansiolticos. Pharmacology of lemongrass (Cymbopogon citratus Stapf). III. Assessment of eventual toxic, hypnotic and anxiolytic effects on humans. J Ethnopharmacol;17(1):75-83, 1986 Jul. Leite JR; Seabra Mde L; Maluf E; Assolant K; Suchecki D; Tufik S; Klepacz S; Calil HM; Carlini EA Resumo: A herbal tea (called an abafado in Brazil) prepared from the dried leaves of lemongrass was administered to healthy volunteers. Following a single dose or 2 weeks of daily oral administration, the abafado produced no changes in serum glucose, urea, creatinine, cholesterol, triglycerides, lipids, total bilirubin, indirect bilirubin, GOT, GPT, alkaline phosphatase, total protein, albumin, LDH and CPK. Urine analysis (proteins, glucose, ketones, bilirubins, occult blood and urobilinogen) as well as EEG and EKG showed no abnormalities. There were slight elevations of direct bilirubin and of amylase in some of the volunteers, but without any clinical manifestation. These results taken together indicate that lemongrass as used in Brazilian folk medicine is not toxic for humans. The eventual hypnotic effect of lemongrass was investigated in 50 volunteers who ingested samples of lemongrass and a placebo under double-blind conditions. The parameters (i.e. sleep induction, sleep quality, dream recall and rewakening) did not show any effect of lemongrass as compared to the placebo. Eighteen subjects with high scores of trait-anxiety were submitted to an anxiety-inducing test following taking lemongrass or placebo under double-blind conditions. Their anxiety levels were similar, indicating that the abafado of the plant does not have anxiolytic properties. It is concluded that lemongrass, one of the most popular Brazilian herbal medicines, used for its alleged CNS-depressant effects, is atoxic but lacks hypnotic or anxiolytic properties. Ginseng da ndia ou Ashwangadha (Withania somnifera ) um ansioltico com ao semelhante ao GABA cujos efeitos finais so os dos benzodiazepnicos. Ashwangadha conhecida como o Ginseng da ndia porque exerce as mesmas atividades do Panax Ginseng. Ashwangadha tem sido usada na medicina Ayurverdica por mais de 2500 anos. Segundo Mehta AK, et al. (trabalho cientfico abaixo) o extrato de W. somnifera contm um princpio ativo que possui a mesma atividade do GABA. In vivo and in vitro Study : A methanolic extract of W. somnifera root stimulated the specific binding of GABA and TBPS and enhanced the binding of flunitrazepan to their receptor sites. Additional studies indicated the W. somnifera extract contains an ingredient

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which has a GABA mimetic activity (Mehta AK, et al. Pharmacological effects of Withania somnifera root extract on GABA receptor complex. Ind J Med Res 94 (B):312-5, 1991). Experimental Controlled Study : A formulation containing primarily Ashwagandha was used in the treatment of 34 diagnosed cases of anxiety neurosis. After 12 weeks of therapy, a significant reduction in 5 hydroxytryptophan levels was observed. Circulating monamine oxidase and GABA showed an increasing trend along with decrease glutamic acid levels after treatment. Psychological complaints were considerably decreased after 12 weeks. (Upadhaya L et al. Role of an indigenous drug Geriforte on blood levels of biogenic amines and its significance in the treatment of anxiety neurosis. Acta Nerv Super 32(1):1-5,1990) Panax Ginseng Enfermeiras de planto que tomam o Panax ginseng so mais objetivas, mais competentes e apresentam melhor humor. Experimental Double Blind Study: Nurses who had switched from day to night duty rated themselves for competence, mood, and general well being, and were given an objective test of psychophysical performance, blood counts, and blood chemistry. The group administered ginseng demonstrated higher scores in competence , mood parameters, and objective psychophysical performance when compared with those receiving a placebo. (Hallstrom C et al. Effect of ginseng on the performance of nurses on night duty. Comp Med East West 6:277-82,1982) A atividade ansioltica do Panax ginseng semelhante a dos benzodiazepnicos . Animal Experimental Study:The anxiolytic activity of Panax ginseng root was investigated in rats and mice using a number of experimental paradigms of anxiety and compared with diazepam. The effects produced by ginseng were comparable to those induced by diazepam. (Bhattacharya SK and Mitra SK. Anxiolytic activity of Panax ginseng roots: an experimental study. J Ethnopharmacology 34:87-92,1991)

Kava-kava (Piper mythysticum) um ansioltico que no causa dependncia e no diminui a memria e a concentrao. Kava-kava (Piper methysticum G. Forster) has been used in social and ceremonial life in the Pacific islands from ancient times for the soporific and narcotic effects. Today several extracts standardized in the biologically active constituents kavalactones are marketed both as herbal medicinal products for anxiety disorders and as dietary supplements to improve stress disorders, nervous tension and restlessness. Unlike other substances used for these purposes, kava-kava has been shown to have minimal negative effects, and possibly positive effects, on reaction time and cognitive processing. Furthermore, it decreases anxiety without the loss of mental acuity. Although kava-kava has been found to be very effective, well tolerated, and non-addictive at therapeutic dosages, potential side effects can occur when very high doses are taken for extended periods. In addition, in the last two years unexpected high liver toxicity has been reported in two patients. Until now no studies support the liver toxicity of kavalactones and it is unknown which compound could have provoked the liver disease. On the other hand, it should be possible that unknown or unexpected constituents are the responsible or contributed to the liver toxicity. (Bilia AR; Gallon S; Vincieri FF Kava-kava and anxiety: growing knowledge about the efficacy and safety. Life Sci;70(22):2581-97, 2002 Apr 19)

Kava-kava and anxiety: growing knowledge about the efficacy and safety. Life Sci;70(22):2581-97, 2002 Apr 19. Bilia AR; Gallon S; Vincieri FF Resumo: Kava-kava (Piper methysticum G. Forster) has been used in social and ceremonial life in the Pacific islands from ancient times for the soporific and narcotic effects. Today several extracts standardized in the biologically active constituents kavalactones are marketed both as herbal medicinal products for anxiety disorders and as dietary supplements to improve stress disorders, nervous tension and restlessness. Unlike other substances used for these purposes, kava-kava has been shown to have minimal negative effects, and possibly positive effects, on reaction time and cognitive processing. Furthermore, it decreases anxiety without the loss of mental acuity. Although kava-kava has been found to be very effective, well tolerated, and non-addictive at therapeutic dosages, potential side effects can occur when very high doses are taken for extended periods. In addition, in the last two years unexpected high liver toxicity has been reported in two patients. Until now no studies support the liver toxicity of kavalactones and it is unknown which compound could have provoked the liver disease. On the other hand, it should be possible that unknown or unexpected constituents are the responsible or contributed to the liver toxicity.

A systematic review of the safety of kava extract in the treatment of anxiety. Drug Saf;25(4):251-61, 2002. Stevinson C; Huntley A; Ernst E Pas de publicao: New Zealand Resumo: This paper systematically reviews the clinical evidence relating to the safety of extracts of the herbal anxiolytic kava (Piper methysticum). Literature searches were conducted in four electronic databases and the reference lists of all papers located were checked for further relevant publications. Information was also sought from the spontaneous reporting schemes of the WHO and national drug safety bodies and ten manufacturers of kava preparations were contacted. Data from short-term post-marketing surveillance studies and clinical trials suggest that adverse events are, in general, rare, mild and reversible. However, published case reports indicate that serious adverse events are possible including dermatological reactions, neurological complications and, of greatest concern, liver damage. Spontaneous reporting schemes also suggest that the most common adverse events are mild, but that serious ones occur. Controlled trials suggest that kava extracts do not impair cognitive performance and vigilance or potentiate the effects of central nervous system depressants. However, a possible interaction with benzodiazepines has been reported. It is concluded that when taken as a short-term monotherapy at recommended doses, kava extracts appear to be well tolerated by most users. Serious adverse events have been reported and further research is required to determine the nature and frequency of such events. Evaluation of combining kava extract with hormone replacement therapy in the treatment of postmenopausal anxiety. Maturitas;39(2):185-8, 2001 Aug 25. De Leo V; la Marca A; Morgante G; Lanzetta D; Florio P; Petraglia F Pas de publicao: Ireland Resumo: OBJECTIVE: to evaluate the efficacy of combining kava extract with hormone replacement therapy in the treatment of

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menopausal anxiety. MATERIALS AND METHODS: HAMA score was evaluated before and after therapy in four groups of women in menopause (duration of menopause ranged from 1 to 12 years). The groups were treated with hormone replacement therapy (with and without progestogens) and kava extract or placebo for 6 months. RESULTS: A significant reduction in HAMA score was observed in all four groups of women. The reduction was more significant in groups taking kava extract than in groups on hormones only. DISCUSSION: The combined use of hormone replacement therapy and kava extract seems to be effective against menopausal anxiety. Kava extract accelerates resolution of psychological symptoms while hormone therapy safeguards against osteoporosis and cardiovascular disease. Phytochemicals as means to induce sleep Phytopharmaka als Mittel zur Schlaffrderung.. Z Arztl Fortbild Qualitatssich;95(1):33-4, 2001 Jan. Volz HP Pas de publicao: Germany Resumo: Phytopharmacons are widely used in Germany. Whereas St. John's wort extracts are prescribed for the treatment of mild forms of depression and kava-kava for unspecified anxiety syndromes, hop, balm, lavender, passiflora and valerian are traditionally administered against nervousness and sleep disturbances. Controlled clinical trials are only available for valerian. However, no sleep inducing potential of valerian was observed, only a certain positive effect on daytime mood. Therefore, the mentioned phytopharmacons cannot be recommended for the treatment of sleep disturbances. Treatment of perioperative anxiety in suspected breast carcinoma with a phytogenic tranquilizer Zentralbl Gynakol;122(11):561-5, 2000. Neuhaus W; Ghaemi Y; Schmidt T; Lehmann E Pas de publicao: Germany Resumo: OBJECTIVE: The present study examined the anxiolytic effect of the herbal preparation Kavosporal forte in 20 patients with situationally induced anxiety. MATERIAL AND METHODS: The degree of anxiety was acute in that the patients were waiting for the results of a histopathological diagnosis, carried out on account of suspect mammary findings, and therefore feared they were suffering from a mammary carcinoma. RESULTS: A significant reduction of anxiety compared with the placebo control was seen after a week's treatment with Kavosporal forte, levels of anxiety being measured a priori from the combined scores of two self-rating scales and one observer-rated scale. In addition, a significant increase was noted in alertness and a lessening of fatigue, introverted behavior and excitability as well as a reduction in levels of depression under the real therapeutic agent over the observation period. In none of the cases examined did any undesirable side effects occur, and the overall tolerance was also consistently good. CONCLUSIONS: It could therefore be concluded that the preparation under investigation is well suited of amelioration of the anxiety that arises regularly in connection with a mammary biopsy. Assessment of the association of Kava-Kava extract and hormone replacement therapy in the treatment of postmenopause anxiety Minerva Ginecol;52(6):263-7, 2000 Jun. De Leo V; La Marca A; Lanzetta D; Palazzi S; Torricelli M; Facchini C; Morgante G Pas de publicao: ITALY Resumo: BACKGROUND: Anxiety is one of the main symptoms in menopause. The aim of this study was to evaluate the efficacy of the association of Kava-Kava extracts with hormone replacement therapy (HRT) and to compare it with HRT alone in the treatment of postmenopausal anxiety. METHODS: Forty women in physiological or surgical menopause for the past 1 to 12 years were enrolled in the study. Patients in physiological menopause were randomly assigned to one of the following protocols: TTS natural estrogens 50 micrograms/day with progestin and Kava-Kava extract at a dose of 100 mg (HRT + K, no. = 13); TTS natural estrogens 50 micrograms/day with progestin and a placebo product (HRT, no. = 9). Patients in surgical menopause were randomly assigned to one of the following protocols: TTS natural estrogens 50 micrograms/day and Kava-Kava extract at a dose of 100 mg (ERT + K, no. = 11); TTS natural estrogens 50 micrograms/day and a placebo product (ERT, no. = 7). Each treatment cycle lasted for 6 months. The outcome of the study was to evaluate changes in the HAMA score. RESULTS: A significant reduction in the HAMA score was observed after 3 and 6 months' treatment in all four groups of women studied. The groups treated with the therapeutic association (HRT + K, ERT + K) showed a greater reduction in the HAMA score compared to patients in the groups treated with hormones alone. CONCLUSIONS: The results of this study show that the association of HRT and Kava-Kava extract may represent an excellent therapeutic tool for the treatment of women in stabilized menopause, in particular those suffering from anxiety and depression, given that Kava-Kava therapy accelerates the resolution of psychological symptoms without diminishing the therapeutic action of estrogens on organic disease, such as osteoporosis and cardiovascular disease. Efficacy of kava extract for treating anxiety: systematic review and meta-analysis. J Clin Psychopharmacol;20(1):84-9, 2000 Feb. Pittler MH; Ernst E Resumo: Synthetic anxiolytic drugs are effective for treating anxiety, but they are burdened with adverse effects. Constraints on resources and time often render therapies such as psychologic interventions impracticable. Thus, an effective oral medication with few adverse effects would be a welcome addition to the therapeutic repertoire. This systematic review and meta-analysis was aimed at assessing the evidence for or against the efficacy of kava extract as a symptomatic treatment for anxiety. Systematic literature searches were performed in the computerized databases MEDLINE, EMBASE, BIOSIS, AMED, CISCOM, and the Cochrane Library (all from their respective inception to June 1998). The search terms used were kava, kawa, kavain, Piper methysticum, and Rauschpfeffer (German term for Piper methysticum). Experts on the subject were contacted to provide further information. There were no restrictions regarding the language of publication. Double-blind, randomized, placebo-controlled trials of oral kava extract for the treatment of anxiety were included. All publications were blinded before assessment by a person not involved in the study. Data were extracted in a standardized, predefined fashion independently by the two reviewers. The methodologic quality of all trials was assessed. Superiority of kava extract over placebo was suggested by all seven reviewed trials. The meta-analysis of three trials suggests a significant difference in the reduction of the total score on the Hamilton Rating Scale for Anxiety in favor of kava extract (weighted mean difference, 9.69; 95% confidence interval, 3.54-15.83). These data imply that kava extract is superior to placebo as a symptomatic treatment for anxiety. Therefore, kava extract is an herbal treatment option for anxiety that is worthy of consideration. Efeitos colaterais do Kava-kava Hepatitis associated with Kava, a herbal remedy for anxiety. BMJ;322(7279):139, 2001 Jan 20. Escher M; Desmeules J; Giostra E; Mentha G

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Valeriana (Valeriana officinalis L ) Quarenta pacientes portadores de sintomas leves de ansiedade e distrbios de tenso emocional foram randomizados em dois grupos, um tratado com dois comprimidos de 50 mg de valeriana duas vezes ao dia e o outro com placebo, ambos durante 21 dias. A valeriana mostrou-se estatisticamente superior ao placebo. Os resultados clnicos e a ausncia de efeitos colaterais confirmam a segurana e a atividade da droga no tratamento da tenso emocional. (Delsignore, R; Orlando, S; Costi, D; Baroni, M. C; Butturini, U. Avaliao clnica comparativa com placebo de um extrato estabilizado de valeriana Folha Md; 104(5):191-6, maio 1992. tab) Angelica Esse trabalho mostra que o leo essencial de angelica possui efeito ansioltico semelhante ao diazepan The effects of angelica essential oil in three assays predictive of anxiolytic activity in male mice were studied, with diazepam as a positive anxiolytic control. In the elevated plus-maze test, compared to the positive control diazepam, angelica essential oil (30.0 mg/kg, PO) had a modest anxiolytic-like effect (increased the percentage of open-arm time and reduced the percent protected head dips). In the light/dark test, angelica essential oil (30.0 mg/kg) prolonged the time spent in the light area without altering the locomotor activity of the animals. In the stress-induced hyperthermia test, 60 and 70 min after drug administration, rectal temperature was measured twice, angelica essential oil at the dose of 30.0 mg/kg inhibited stress-induced hyperthermia. Thus, these findings indicate that angelica essential oil, as does diazepam, exhibits an anxiolytic-like effect. Further studies will be required to assess the generality of the present findings to other species and behavioural paradigms.(Chen SW; Min L; Li WJ; Kong WX; Li JF; Zhang YJ. The effects of angelica essential oil in three murine tests of anxiety. Pharmacol Biochem Behav;79(2):377-82, 2004 Oct) Indian Abies pindrow Anxiolytic activity of Indian Abies pindrow Royle leaves in rodents: an experimental study. Indian J Exp Biol;38(4):343-6, 2000 Apr. Kumar V; Singh RK; Jaiswal AK; Bhattacharya SK; Acharya SB Pas de publicao: India Resumo: Putative anxiolytic activity of ethanolic extract of Indian A. pindrow Royle leaf was investigated in rats using various experimental paradigms of anxiety viz. open field exploratory behaviour, elevated plus maze (EPM) and elevated zero maze (EZM) tests. Pilot studies indicated that single dose administration of extract had little to no acute behavioural effects, hence the extract was administered orally at different dose levels once daily for three consecutive days, while lorazepam (LR) (0.5 mg/kg, i.p.) was administered acutely. Ethanolic extract of A. pindrow (AP) leaves (50 and 100 mg/kg, p.o.) showed significant anxiolytic effects on all the paradigms of anxiety. The results indicate that AP and LR induced a significant increase in open field ambulation and slight increase in rearings and activity in center, whereas grooming and faecal droppings remain unchanged. In EPM, significant augmentation of open arm entries, and time spent on open arms was noted in AP treated rats. In EZM test, significant increase in time spent on open arms and entries in open arms was observed, whereas slight increase in head dips and stretched attend postures was also observed. The AP extract showed consistent and significant anxiolytic activity in all the tests. The effects induced by ethanolic extract of AP were less marked than those of lorazepam were. Tagetes minuta Anxiogenic-like effects of Tagetes minuta L essential oil on T-maze and tonic immobility behaviour in domestic chicks. Fundam Clin Pharmacol;12(4):426-32, 1998. Marin RH; Garcia DA; Martijena ID; Zygadlo JA; Arce A; Perillo MA Pas de publicao: FRANCE . Feito na Argentina Resumo: In a first experiment, four doses (ranging between 0.04 and 0.45 mg/kg of body weight) of the essential oil from Tagetes minuta L. were subcutaneously injected in two-day-old chicks and a dose-response curve assessed for escape performance in a T-maze test. The 0.1, 0.25 and 0.45 mg/kg doses impaired the first escape performance suggesting an anxiogenic-like effect of the essential oil. After 3 h the same chicks were tested for a second escape performance, without being injected again, and no differences were observed compared to controls, suggesting that the essential oil did not affect retention. Furthermore, the effects of the essential oil were observed in the three sections of the T-maze apparatus. So, the performance was impaired in the isolation chamber section, suggesting the induction of increased anxiogenic behaviour, and also in the mirror section, suggesting that the social reinstatement behaviour was modified by an increased anxiety level. Changes in the principal corridor section were not observed, suggesting that the locomotor activity was not affected by these oil doses. The second escape performance was not affected in any of the T-maze sections, confirming that these doses did not affect learning ability. In a second experiment, a middle dose of the essential oil (0.25 mg/kg) increased the tonic immobility reaction in 15 days old chicks similarly to an anxiogenic dose of FG 7142 (1 mg/kg), while an anxiolytic dose of diazepam (0.08 mg/kg) did not affect this behaviour. Taken together, the present results suggest that the essential oil from Tagetes minuta L. may exert a negative modulation on the GABAergic function without affecting the learning ability. Formula Chinesa : Suanzaorentang Studies on the suanzaorentang in the treatment of anxiety. Psychopharmacology (Berl);85(4):486-7, 1985. Chen HC; Hsieh MT; Lai E Pas de publicao: GERMANY, WEST Resumo: We studied the anxiolytic and psychomotor effects of the ancient Chinese formula of Suanzaorentang, and found that it improved mood, decreased the accompanying sympathetic symptoms and improved psychomotor performance during the day.

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