Family

Verbenaceae.

Related Species

Vitex negundo L., V. trifoliate L., V. rotundifolia L., V. pediuncularis Wall., V. jeguado L. var cannabifolia . ¹

Parts Used

Fruit.

Common Forms

Dried or fresh ripe fruit for decoction.

• Tincture, Fluid Extract:   Of dried or fresh fruit, 50% to 70% alcohol.

• Standardized Extract:   6:1 to 12:1 standardized to casticin 0.6% (e.g., PreMens by Zeller AG).

Strategic Considerations

Vitex has an ancient reputation as a “galactogue” and long been considered to suppress sexual excitability. It was more recently popularized in Germany and approved by the Commission E in 1985 for menstrual irregularities. ^2,3Vitex is currently used primarily as a gynecological herb for cyclical problems, including dysmenorrhea, amenorrhea, oligomenorrhea, corpus luteum insufficiency (and infertility related to luteal insufficiency), hyperprolactinemia, premenstrual syndrome (PMS), acne, mastalgia and mastodynia, and lactation issues. The constituents of the fruit are complex, including diterpenes, irdoid glycosides, lipophilic flavonoids, triglycerides, and essential oil. The active constituents are poorly characterized, although the lipophilic components, especially diterpenoids such as rotundifuran, are thought to be important for its effects. Several significant research reports are in German; comprehensive reviews of the data have been published by the American Herbal Pharmacopoeia (AHP), ⁴ McKenna et al., ¹ and European Scientific Cooperative on Phytotherapy (ESCOP). ⁵

No interactions for vitex are documented; this was confirmed by a recent survey on the safety of the herb. ⁶ The authors confirmed, however, the cautionary note originating from the 1992 revised Commission E monograph, that because of recorded dopaminergic effects in animal experiments, vitex may interact with pharmaceutical dopamine receptor agonists. The Commission E also noted there were no reports of such interactions. ³ The dopamine-binding caution is now widely repeated in the derivative interactions literature, and some sources also suggest that interactions may occur with oral contraceptives (OCs) and hormone replacement therapy (HRT) or with monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and tricyclic antidepressants (TCAs). However, no interactions reports are associated with vitex. Reviewing the known pharmacology from an integrative perspective will contextualize these speculations.

The emerging consensus is that dopaminergic effects of vitex may be partly responsible for its prolactin-inhibiting actions. Several experimental studies using rodent striatum, calf striatum, and human recombinant dopamine D2receptors with two different ligand probes, sulpiride and spiroperidol, suggest that a variable degree of binding occurs between crude extracts and diterpene fractions of vitex. ^7,8However, reviews of all the data, including German unpublished material, suggest an order of magnitude variation (IC5040-500 µg/mL) in dose required for receptor binding for whole-plant extracts. ^1,4,5Additionally, isolated constituent studies for the diterpene rotundifuran (considered by some to be the most important dopaminergic compound in the crude herb) show an order of magnitude or more difference, with 100 micromolar (µM) rotundifuran about equivalent to 1 µM dopamine (data from Christoffel et al., 1999; reviewed by Upton ⁴ ). It is also unclear whether the receptor binding is in fact agonistic or antagonistic in vivo, and evidence suggests that dose-response kinetics are biphasic. Weak binding also takes place with other receptor subtypes, including mu (µ) and kappa (κ) opioid receptors, as well as to estrogen receptors. ^7,9,10In clinical practice, vitex seems to effect moderate prolactin inhibition and may be clinically appropriate in mild hyperprolactinemia, and the herb will have fewer adverse effects than bromocriptine for such indications. ¹¹

The D2family of receptors are also targets for neurological drugs (antiparkinsonian) and psychiatric (antipsychotic) drugs, such asL-dopa and haloperidol. This has given rise to more speculation on possible interactions between vitex and such psychopharmaceuticals. Clinically, the most typical prescribing patterns for vitex extracts by English-speaking herbal practitioners involve the use of small doses, 0.5 to 5.0 mL crude herb in a single dose, taken in the morning on rising. With this approach, the latency of herb effects on cyclical irregularities and related menstrual problems is extended, typically requiring at least three menstrual cycles to achieve a stable situation. ^12,13This is also seen in the results of clinical trials, where herb effects on both symptom reduction and prolactin secretion became significant over three cycles.

The relation between this pattern of moderate vitex prescription and a slow modulation of cyclical irregularity (or prolactin level normalization) interacting with pharmaceutical agents is difficult to assess. A German report of a trial by Wuttke and colleagues in 1997 is discussed at length in the AHP monograph ⁴ ; measurable reductions of prolactin levels were achieved after 3 months with vitex preparations compared to placebo. However, metoclopramide-induced prolactin secretion did not differ between the treatment and placebo groups. A 2-week trial in 20 healthy males (presumed to lack the cyclical hormone fluctuations in women) found a biphasic response to thyrotropin-releasing hormone (TRH)–stimulated prolactin levels among three groups administered vitex extract at different doses. A low dose (120 mg/day) increased the area under curve (AUC) for prolactin, a high dose (240 mg/day) reduced AUC, but a median dose (240 mg/day) did not differ from controls. ¹⁴ Therefore, the simple view of vitex having a “bromocriptine”-like dopamine agonism apparently is inappropriate, and extrapolating interactions on the assumption that it is a pharmaceutical-level agent is not justifiable. Also, the pharmacology of the herb remains incompletely characterized. Emerging experimental data suggest that vitex extracts may act as agonists to the µ-opiate receptor, although the levels required to achieve median inhibition concentration (IC50) were higher than those likely to be attained in vivo; at this time a role for opiate receptor agonism for vitex in vivo cannot be considered established. ¹⁵

Given that the median age of onset for Parkinson's disease is 57 years, it is unlikely a significant population of female parkinsonian patients would present with typical gynecological indications for vitex. In the psychiatric category, the effects of various antipsychotics and neuroleptics on in vivo dopamine remains poorly understood. The “dopamine hypothesis” of schizophrenia is increasingly considered a controversial oversimplification. Because of the high frequency of pharmacokinetic and pharmacodymamic interactions exhibited by many classes of psychiatric medications, prudence would suggest monitoring usage of all coadministered herbs, and vitex interactions with neuroleptic agents having dopamine D2, D3, and D4subtypes must remain speculative at this time.

The currently known pharmacology of the herb suggests that the common interactions extrapolated from putative pharmacology between pharmaceuticals and vitex should be considered unproven, or overstated until substantial evidence becomes available.

• 1.McKenna D, Jones K, Hughes K, Humphrey S. Vitex. Botanical Medicines. 2nd ed. Binghamton, NY: Haworth Press; 2002:1039-1078.
• 2.Weiss R. Herbal Medicine. Meuss A, Translator. 6th ed. Beaconsfield, UK: Beaconsfield Publishers Ltd; 1988.
• 3.Blumenthal M, Busse W, Goldberg A et al. The Complete German Commission E Monographs. Austin, Texas: American Botanical Council: Integrative Medicine Communications; 1998.
• 4.Upton R. Chaste tree fruit. American Herbal Pharmacopoeia. Scotts Valley, Calif; 2001.
• 5.ESCOP. Agni casti fructus. ESCOP Monographs: the Scientific Foundation for Herbal Medicinal Products. 2nd ed. Exeter, UK: European Scientific Cooperative on Phytotherapy and Thieme; 2003:8-13.
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• 8.Jarry H, Leonhardt S, Gorkow C, Wuttke W. In vitro prolactin but not LH and FSH release is inhibited by compounds in extracts of Agnus castus: direct evidence for a dopaminergic principle by the dopamine receptor assay. Exp Clin Endocrinol 1994;102:448-454.View Abstract
• 9.Jarry H, Spengler B, Porzel A et al. Evidence for estrogen receptor beta-selective activity of Vitex agnus-castus and isolated flavones. Planta Med 2003;69:945-947.View Abstract
• 10.Liu J, Burdette JE, Xu H et al. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agric Food Chem 2001;49:2472-2479.View Abstract
• 11.Sliutz G, Speiser P, Schultz AM et al. Agnus castus extracts inhibit prolactin secretion of rat pituitary cells. Horm Metab Res 1993;25:253-255.View Abstract
• 12.Christie S, Walker A. Vitex agnus-castus L. (1) A review of its traditional and modern therapeutic use; (2) Current use from a survey of practitioners. Eur J Herbal Med 1997;3:29-45.
• 13.Romm A, Treasure J. Vitex agnus castus: AHG Professional Member Botanical Therapeutics Survey. J Am Herbalists Guild 2001;2:27-31.
• 14.Merz PG, Gorkow C, Schrodter A et al. The effects of a special Agnus castus extract (BP1095E1) on prolactin secretion in healthy male subjects. Exp Clin Endocrinol Diabetes 1996;104:447-453.View Abstract
• 15.Webster DE, Lu J, Chen SN et al. Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS. J Ethnopharmacol 2006.View Abstract
• 16.Tandon VR, Gupta RK. An experimental evaluation of anticonvulsant activity of Vitex negundo. Indian J Physiol Pharmacol 2005;49:199-205.View Abstract
• 17.Gupta RK, Tandon VR. Antinociceptive activity of Vitex negundo Linn leaf extract. Indian J Physiol Pharmacol 2005;49:163-170.View Abstract
• 18.Berger D, Schaffner W, Schrader E et al. Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS). Arch Gynecol Obstet 2000;264:150-153.View Abstract