Hallucinogenic Plants

 Chapter 34 

Hallucinogenic Plants

INTRODUCTION

Hallucinogens are natural and synthetic (synthesized) substances that, when ingested (taken into the body), significantly alter one’s state of consciousness. Hallucinogenic compounds often cause people to see (or think they see) random colours, patterns, events and objects that do not exist. People sometimes have a different perception of time and space, hold imaginary conversations, believe they hear music and experience smells, tastes and other sensations that are not real. The other names of hallucinogens are Cartoon acid, Microdot, California sunshine, Psilocybin, Magic mushrooms.

Many types of substances are classified as hallucinogens, solely because of their capacity to produce such hallucinations. These substances are sometimes called ‘psychedelic’, or ‘mind-expanding’ drugs. They are generally illegal to use in the United States, but are sometimes sold on the street by drug dealers. A few hallucinogens have been used in medicine to treat certain disorders, but they must be given under controlled circumstances. Hallucinogens found in plants and mushrooms were used by humans for many centuries in spiritual practice worldwide. Unlike such drugs as barbiturates and amphetamines (which depress or speed up the central nervous system (CNS), respectively), hallucinogens are not physically addictive (habit forming). The real danger of hallucinogens is not their toxicity (poison level), but their unpredictability. The actual causes of such hallucinations are chemical substances in the plants. These substances are true narcotics. Contrary to popular opinion, not all narcotics are dangerous and addictive. A narcotic is any substance that has a depressive effect, whether slight or great, on the CNS. People have had such varied reactions to these substances, especially to lysergic acid diethylamide (LSD) that it is virtually impossible to predict the effect of a hallucinogen that will have on any given individual. Effects depend upon the person’s mood, surroundings, personality and expectations while taking the drug.

Natural hallucinogens are formed in dozens of psychoactive plants, including the peyote cactus, various species of mushrooms and the bark and seeds of several trees and plants. Marijuana and hashish—two substances derived from the hemp plant (Cannabis sativa)—are also considered natural hallucinogens although their potency (power) is very low when compared to others. Marijuana—a green herb from the flower of the hemp plant—is considered a mild hallucinogen. Hashish is marijuana in a more potent, concentrated form. Both drugs are usually smoked. Their effects include a feeling of relaxation, faster heart rate—the sensation that time is passing more slowly, and a greater sense of hearing, taste, touch and smell. 

A form of LSD was first produced in 1938, when Albert Hoffman, a Swiss research chemist at Sandoz Laboratories, synthesized many important ergot alkaloids (organic plant bases), including Hydergine, LSD-25 and psilocybin. The physical effects of hallucinogens are considered small compared to their effects on the mind. Death from an overdose of hallucinogens is highly unlikely, but deaths have resulted from accidents or suicides involving people under the influence of LSD. LSD is so powerful that a tiny amount can have a hallucinogenic effect.

MEDICAL USES OF HALLUCINOGENS

Hallucinogens have been studied for possible medical uses, including the treatment of some forms of mental illness, alcoholism and addiction to the drug opium. They have also been given to dying patients. Most of these uses have been abandoned, however. A synthetic form of the active chemical in marijuana, Tetra hydro cannabinol (THC) has been approved for prescription use by cancer patients, who suffer from severe nausea after receiving chemotherapy (treating cancer with drugs). THC is also used to reduce eye pressure in treating severe cases of glaucoma. Phencyclidine (PCP) is occasionally used by veterinarians as an anesthetic and sedative for animals. 

Hallucinogenic plants have played an important role in many developing cultures of the world, including our own. They have been used in healing, as entheogens, and as religious sacraments, as well as having recreational utility. It is only a recent development that use of all hallucinogens has been frowned upon. A vast amount of resources has been put into controlling common psychoactive substances (Marijuana, LSD, PCP, etc.), which may be turning curious experimenters back towards the use of plants and other unregulated substances as a means of getting ‘high’. There are many different species of hallucinogenic plants. Much information is available on many of them; yet, some are less studied than others. 

Some of the important plant hallucinogens are as follows: Belladonna (Atropa belladonna), Betel Nut (Areca catechu), the Brooms (misc. sp.), Cabeza de Angel (Calliandra anomala), Calamus (Acorus calamus), California Poppy (Eschscholzia californica), Catnip (Nepeta cataria) , Chicalote; Prickly Poppy (Argemone mexicana), Coleus (Coleus sp.), Colorines (Erythrina flabelliformis), Damiana (Turnera diffusa), Daturas (Datura sp.), Doñana (Coryphantha macromeris), Fennel (Foeniculum vulgare), Hawaiian Baby Woodrose (Argyria nervosa), Hawaiian Woodrose (Merremia tuberosa), Heliotrope (Valeriana officinalis), Henbane (Hyoscyamus niger), Hops (Humulus lupulus), Hydrangea (Hydrangea paniculata), Iochroma (Iochroma sp.), Kava Kava (Piper methysticum), Khat (Catha edulis), Lion’s Tail (Leonotis leonurus), Lobelia (Lobelia inflata), Madagascar Periwinkle (Catharanthus rosea), Mandrake (Mandragora officinarum), Maraba (Kaempferia galanga), Maté (Ilex paraguayensis), Mescal Beans (Sophora secundiflora), Mormon Tea (Ephedra nevadensis), Morning Glory (Ipomoea sp.), Nutmeg (Myristica fragrans), Ololuique (Rivea corymbosa), Passionflower (Passiflora incarnata), Pipiltzintzintli (Salvia divinorum), Psilocybe Mushrooms (misc. sp.), Rhynchosia (Rhynchosia phaseoloides), San Pedro (Trichocereus pachanoi), Sassafras (Sassafras albidum), Shansi (Coriaria thymifolia), Silvervine (Actinidia polygama), Sinicuichi (Heimia sp.), So’ksi (Mirabilis multiflora), Syrian Rue (Peganum harmala), Tobacco (Nicotiana tabaccum), Wild Lettuce (Lactuca virosa), Wormwood (Artemisia absinthium).  

BELLADONNA

• Atropa belladonna L.; Nightshade family (Solanaceae).

• A perennial branching herb growing to 5-feet tall, with 8-inch-long ovate leaves. The leaves in first-year plants are larger than those of older plants. The flowers are bellshaped, blue-purple or dull red, followed by a shiny, black or purple 0.5 inch berry. The plant is native of Europe and Asia. 

Constituents

• Atropine, Hyoscyamine, Atropamine, Belladonnine and Hyoscine.

Medicinal Uses

Belladonna can be fatal to most carnivorous animals and humans, but the same doses have very little effect upon most birds and plant-eating animals. Children are often poisoned by the berries, mistaking them for cherries or other sweet fruit. In large doses, belladonna acts upon the cerebrospinal system, as showing such symptoms as dilatation of the pupils (mydriasis), presbyopia, obscurity of vision, blindness (amaurosis), visual illusions (phantasms), suffused eyes, occasionally disturbance of hearing (as ringing in the ears, etc.), numbness of the face, confusion of head, giddiness and delirium. Belladonna has been and is being used as a recreational drug, diuretic, sedative, antispasmodic and mydriatic. It is used very successfully to treat eye diseases, because of its effect of dilating the pupil. Atropine, an extract of belladonna, is what an eye doctor uses when they put liquid in your eye before testing you for glasses. Atropine has also been used as an antidote to opium, Calabar bean and chloroform poisoning. 

BETEL NUT

• Areca catechu L.; Palm family (Palmaceae).

• A very slender, graceful palm that grows up to 100- feet tall with a 6-inch diameter trunk. This is topped by a crown of three 6-foot-long leaves that are divided into many leaflets. The fruits are the size and shape of a hen’s egg and are yellowish to scarlet with a fibrous covering. It is native to Malaysia.

Constituents

• Betel nut contains arecaine and arecoline alkaloids which are comparable to nicotine in its stimulating, mildly intoxicating and appetite-suppressing effects on the mind. It also contains the alkaloids arecaidine, arecolidine, guracine (guacine) and guvacoline.

Medicinal Uses

• Stimulant, stroke recovery, schizophrenia, anaemia, dental cavities, ulcerative colitis and saliva stimulant. It is also used as alcoholism, aphrodisiac, appetite stimulant, asthma, cough, digestive aid, diphtheria and as diuretic. The findings of a prior study indicating a therapeutic relationship between consumption of betel nut and symptoms of schizophrenia were tested. These findings have clinical significance in betel-chewing regions and broader implications for theory of muscarinic neurophysiology in schizophrenia. 

CABEZA DE ANGEL

• Calliandra anomala (Kunth) Macbride; Bean family (Leguminosae).

•   This plant is tall and evergreen shrub. Leaves are bipinnate, rachis covered with dense brown hairs. Pinnae 15 pairs or more; leaflets 30–60 pairs, densely crowded and oblong. Pods are 7.5–10 cm long and 1.2–1.8 cm wide, densely villous with red hairs.

Constituents

• Mainly contains triterpenoidal saponins. Three triterpenoidal saponins were identified by FAB-MS spectrum, viz. calliandra saponin M, N and O. Six triterpenoids like calliandra saponins: G(1), H(2), I (3), J(4), K(5) and L(6) were isolated from the branches of Calliandra anomala.

Medicinal Uses

• Formerly it was used by Aztecs. Cut the bark and collect resin for several days; dry, pulverize, mix with ash and used as snuff. It acts as hypnotic, often induces sleep. 

CALAMUS

• Acorus calamus L.; Arum family (Araceae).

• A vigorous perennial herb growing up to 6-feet tall, composed of much long, slender, grasslike leaves up to 0.75 inch wide rising from a horizontal rootstock. The flowers are minute and greenish-yellow in colour, occurring on a 4-inch-long spike resembling a finger. The fruit is berrylike. It is native to eastern North America, Europe and Asia. 

Constituents

• Both triploid and tetraploid calamus contain asarone. Monoterpene hydrocarbons, sequestrene, ketones, (transor Alpha) Asarone (2,4,5-trimethoxy-1-propenylbenzene), and Beta-asarone (cis- isomer) contained in the roots essential oils. 

Medicinal Uses

• It is use as an analgesic for the relief of toothache or headache, for oral hygiene to cleanse and disinfect the teeth, to fight the effects of exhaustion or fatigue and to help cure/prevent a hangover. Also used to treat a cough, made a decoction as a carminative and as an infusion for cholic. The ethyl acetate fraction of the Acorus calamus extract (ACE) was found to enhance adipocyte differentiation as did rosiglitazone. The results of further fractionation of ACE indicated that the active fraction does not consist of beta-asarone, which is a toxic component of this plant. This finding suggests that ACE has potential insulin-sensitizing activity like rosiglitazone, and may improve type 2 diabetes. The in vitro acetylcholinesterase (AChE) inhibitory potential of the hydroalcoholic extract and of the essential oil from Acorus calamus (AC) rhizomes and that of its major constituents were evaluated based on the Ellman’s method. 

CATNIP

• Nepeta cataria L.; Mint family (Labiatae).

• A hardy, upright, perennial herb with sturdy stems bearing hairy, heart-shaped, grayish-green leaves. The flowers are white or lilac, 0.25 inch long, and occur in several clusters towards the tips of the branches. Native of Eurasia, naturalized in North America. 

Constituents 

• Daucosterol (beta-sitosterol 3-O-beta-D-glucoside) was isolated from the plant, in addition to small amounts of beta-sitosterol, campesterol, alpha-amyrin and beta-amyrin was also isolated.

Medicinal Uses

• It is used as a household herbal remedy, being employed especially in treating disorders of the digestive system and, as it stimulates sweating, it is useful in reducing fevers. The herb’s pleasant taste and gentle action makes it suitable for treating colds, flu and fevers in children. It is more effective when used in conjunction with elder  flower (Sambucus nigra). The leaves and flowering tops are strongly antispasmodic, antitussive, astringent, carminative, diaphoretic, slightly emmenagogue, refrigerant, sedative, slightly stimulant, stomachic and tonic.

CHICALOTE, PRICKLY POPPY

• Argemone mexicana L.; Poppy family (Papaveraceae).

• It is an annual herb, 1–3 feet high with prickly stems, leaves and capsules. The flowers are yellow or orange, up to 2.5 inches across, and followed by an oblong seed capsule. The leaves are white-veined and 4–6 inch long. It is native to tropical America. 

Constituents

• The plant contains alkaloids as berberine, protopine, sarguinarine, optisine, chelerythrine, etc. The seed oil contains myristic, palmitic, oleic, linoleic acids, etc.

Medicinal Uses

•  The whole plant is analgesic, antispasmodic, possibly hallucinogenic and sedative. The fresh yellow, milky, acrid sap contains protein-dissolving substances and has been used in the treatment of warts, cold sores, cutaneous affections, skin diseases, itches, etc. It has also been used to treat cataracts. The sensitivity of two Gram positive (Staphylococcus aureus and Bacillus subtilis) and two Gram negative (Escherichia coli and Pseudomonas aeruginosa) pathogenic multidrug resistant bacteria was tested against the crude extracts (cold aqueous, hot aqueous and methanol extracts) of leaves and seeds of Argemone mexicana L. (Papaveraceae) by agar well diffusionmethod. Though all the extracts were found effective, yet the methanol extract showed maximum inhibition against the test micro-organisms followed by hot aqueous extract and cold aqueous extract.

COLORINES

• Erythrina flabelliformis Kearny; Bean family (Leguminosae).

• A shrub or small tree growing up to 10-feet high with spiny branches and leaves composed of fan-shaped leaflets. The flowers are bright scarlet, in short crowded racemes. The pods are up to 1-foot long, containing bright scarlet oval seeds. It is native to southern Arizona, New Mexico and Mexico. 

Constituents

• The first compounds isolated from Erythrina were alkaloids, i.e. β–Erythroidine. Homoerythrina alkaloids were also isolated.

Medicinal Uses

• Erythrina has been used in folk medicine for treatment of insomnia, malaria fever, venereal disease, asthma and toothache. South American Indians used Erythrina as a fish poison. In addition, there are reports of its use as a narcotic and antihelmintic, anticancer and relaxant in Mesoamerica.

DAMIANA

• Turnera diffusa; Turnera family (Turneraceae).

• A small shrub with smooth inch long, pale green leaves which have dense hairs on the underside. The flowers are yellow, rising from the leaf axils, followed by a one-celled capsule, which splits into three pieces. This plant is native to the Southwest and Mexico. 

Constituents

It contains Arbutin, volatile oil, Tetraphyllin B, resins, gums, starch and tannins.

Medicinal Uses

• It is used as stimulant, mild diuretic, mild laxative, testosteromimetic action, nervous restorative, antidepressant, urinary antiseptic anxiety and depression. It also is used as sexual inadequacies with a strong psychological or emotional element and to establish normal menstruation at puberty. A phytochemical investigation of Turnera diffusa afforded 35 compounds, comprised flavonoids, terpenoids, saccharides, phenolics and cyanogenic derivatives, including five new compounds (1–5) and a new natural product (6).

DATURAS 

Nightshade family (Solanaceae).

This genus has 15–20 species ranging from annual and perennial herbs to shrubs and trees, with trumpet-shaped flowers. All of these are hallucinogenic.

Datura fastuosa L., formerly known as D. metel: It is an annual herb, 4–5 feet tall, with ovate 7- to 8-inch leaves. The flower is 7-inch long, white inside, violet and yellowish outside, with a purple calyx. The fruit is a 1.25 inch diameter spiny capsule. There are also double-flowered and blue-, red- and yellow-flowered varieties. It is native to India and naturalized in the tropics of both hemispheres.

 D. inoxia Mill: It is a low-growing, spreading perennial with hairy 2- to 4-inch leaves. The flowers are white, 6–7 inch long, 10-lobed. The fruit is spiny, 2-inch or more in diameter. It is native to Mexico and the Southwest.

ameter. It is native to Mexico and the Southwest. D. meteloides DC: It is an erect perennial herb with 2–5 inch leaves. The flowers are white, 8-inch long, often tinged with rose or violet, fragrant. The capsule is intensely spiny, 2 inches in diameter. It is native to the Southwest and Mexico.

D. stramonium L. ‘Jimson weed’: It is a green-stemmed, hairless annual, 2–4 feet tall, with few branches and two 8-inch-long ovate leaves. The flowers are white, 4-inch long. The capsule is egg-shaped, 2-inch long, filled with many black seeds. In D. Stramonium var. tatula, the flower is violet-purple or lavender; the stems are purple. They are easily grown from seeds, which sprout quickly even without bottom heat. It does well in rich soil in a dry, sunny location. Thin out all but the healthiest plant after sprouting.

D. chlorantha Hook: It is a hairless, perennial shrub, occasionally reaching 10-feet tall, with almost triangular, wavy-margined leaves. The flowers are yellow, drooping, followed by a prickly capsule. This is not a true tree datura although it occasionally reaches similar heights. 

Constituents

•  One steroidal constituent, daturasterol and a tricyclic diterpene, daturabietariene, have been isolated for the first time from the stem bark of Datura metel Linn. along with beta-sitosterol and atropine. The structures of the new compounds have been elucidated as 24-beta-methylcholest4-ene-22-one-3alfa-ol and 15-, 18-dihydroxyabietatriene, respectively, on the basis of the spectral data analyses and chemical reactions.

Medicinal Uses

• The whole plant, but especially the leaves and seed, is anaesthetic, anodyne, antiasthmatic, antispasmodic, antitussive, bronchodilator, hallucinogenic, hypnotic and mydriatic.

DONANA

Coryphantha macromeris (Engl.) Lem.; Cactus family (Cactaceae)

• A low, cylindrical cactus to 8-inch-tall branching at the base, covered with several inch long, soft, spine-tipped tubercles. The flowers are purple, 5 inches across. It is native to Mexico and West Texas. 

Constituents

• Mainly it contains macromerine, normacromerine. It also contains phenethylamines, normacromerine (N-methyl-3- ,4-dimethoxy-beta-hydroxyphenethylamine) abundantly.

Medicinal Uses

• It is a strong narcotic or hallucinogenic drug.

FENNEL

Foeniculum vulgare Mill; Carrot family (Umbelliferon).

• It is a perennial herb growing to 5-feet high, with bluegreen stems and leaves. The leaves are finely divided into threadlike leaflets. The flower cluster is a large umbel, composed of 15–20 yellow flowers. This plant is native of southern Europe; naturalized in the Western United States. 

Constituents

• The major biologically active constituent of Foeniculum fruit oil was characterized as (+)-fenchone and (E)-9- octadecenoic acid. It also contains anethole, methyl chavicol, D-apenine, camphene, etc.

Medicinal Uses

• The plant is analgesic, antiinflammatory, antispasmodic, aromatic, carminative, diuretic, emmenagogue, expectorant, galactogogue, hallucinogenic, laxative, stimulant and stomachic. The essential oil is bactericidal, carminative and stimulant. Pectin’s from Foeniculum vulgare were extracted under acidic conditions. The obtained pectins were mainly composed of uronic acid but also contained traces of rhamnose, galactose, and arabinose. Extracted pectin’s were used as a carbohydrate source to prepare biopolymer films in the absence and in the presence of phaseolin protein. The antiulcerogenic and antioxidant effects of aqueous Foeniculum vulgare (FVE) extract was studied on ethanol-induced gastric lesions in rats. It was found that pretreatment with FVE significantly reduced ethanol-induced gastric damage. 

HAWAIIAN BABY WOODROSE

Argyrias nevosa Bojer; family (Convolvulaceae).

• A large, perennial climbing vine with heart-shaped leaves up to 1 foot across backed with silvery hairs. The flowersare 2–3 inch long, rose-colored, on 6-inch stalks. Pods dry to a smooth, dark brown, filbert-sized capsule containing one to four furry brown seeds. The capsule is surrounded by a dry calyx divided into five petal-like sections. It is native to Asia. 

Constituents

• It contains argyroside, a new steroidal glycoside, (24R)-ergost-5-en-11-oxo-3beta-ol-alpha-D-glucopyranoside. It also contains ergoline alkaloids and D-lysergic acid amide. 

Medicinal Uses

• Used as psychotropic agent; in India, it is an Ayurvedic medicinal plant.

HELIOTROPE

Valeriana officinalis L.; Valerian family (Valerianaceae).

•  It is a perennial herb, 2–5 feet high with pinnately divided leaves and clusters of small, whitish, pinkish or lavender flowers. This plant is native of Europe and N. Asia.

Constituents

• It is of complex composition, containing valerianic, formic and acetic acids. The alcohol is known as borneol and pinene. The root also contains two alkaloids—Catarina and Valerianine.

Medicinal Uses

• Valerian is a powerful nervine, stimulant, carminative and antispasmodic. It has a remarkable influence on the Cerebro-spinal system and is used as a sedative to the higher nerve centers in conditions of nervous unrest. The effect of valerian extract preparation (BIM) containing valerian extract, golden root (Rhodiola rosea L.) extract and L-theanine (gamma-glutamylethylamide) on the sleep-wake cycle using sleep-disturbed model rats in comparison with that of valerian extract. A significant shortening in sleep latency was observed with valerian extract and the BIM at a dose of 1,000 mg/kg. 

HENBANE

Hyoscyamus niger L.; Nightshade family (Solanaceae).

• An annual or biennial herb, to 2.5-feet high, with hairy, 3- to 8-inch-long leaves. The flowers are 1 inch across, greenish yellow with purple veins; they grow in spikes from June to September. The seed capsule is filled with many pitted seeds. 

Constituents

• The main constituents are hyoscyamine, hyoscine, scopolamine and hyoscipicrin. 

Medicinal Uses

• It causes deranged vision, headache, giddiness, dilated pupils, dry throat, hoarseness, weakness of the lower limbs, spasms, cramps, paralysis, loss of speech, or loquacious delirium with hallucinations, followed by a dreamy sleep, according to the dosage. The cDNA from Nicotiana tabacum encoding Putrescine N-methyltransferase (PMT), which catalyses the first committed step in the biosynthesis of tropane alkaloids, has been introduced into the genome of a scopolamine-producing Hyoscyamus niger mediated by the disarmed Agrobacterium tumefaciens strain C58C1, which also carries Agrobacterium rhizogenes Ri plasmid pRiA4, and expressed under the control of the CaMV 35S promoter. 

HOPS

Humulus lupulus L.; Hemp family (Cannabinaceae).

• A perennial twining vine growing from 15- to 30-feet long with oval three- to five-lobed leaves having coarsely toothed edges. Male and female flowers occur on separate plants. It is native to Eurasia. 

Constituents

• It contains up to 1% volatile oil (humulene, myrcene, caryophyllene, fremescence); 15–25% resinous bitter principles and phloroglucinol derivatives known as alpha acids (humulone, cohumulone, adhumulone, valerianic acid) and beta acids (lupulone, colupulone, adlupulone); condensed tannins and phenolic acids, flavonoid glycosides (astralagin, quercitin, rutin), fats, amino acids, unidentified oestrogenic substances, choline, asparagine. The oil and bitter resins together are known as lupulin.

Medicinal Uses

• Hops are an aromatic bitter and hence may be useful in atonic dyspepsia. By many they are believed to have a sedative effect on the nervous system and are used in hysteria, restlessness, insomnia. It also used as sedative, soporific, visceral spasmolytic, aromatic bitter, digestive tonic, hypnotic, astringent, diuretic. The in vivo and in vitro effect of hop beta-acids on CNS function was investigated. Oral administration of beta-acids (5–10 mg/kg) in rats produced an increased exploratory activity in the open field, a reduction in the pentobarbital hypnotic activity and a worsening of picrotoxin-induced seizures.

• Xanthohumol (XN) is a prenylated chalcone with antimutagenic and anticancer activity from hops. A nonaqueous reverse polarity capillary electrophoretic method forthe determination of XN in hop extract was developed and validated. 

HYDRANGEA

Hydrangea paniculata Sieb. var. grandiflora; family (Saxifragaceae).

• This is the commonest hardy hydrangea in cultivation. It is a treelike shrub 8–30 feet high, with 3- to 5-inch-long oval leaves. The flowers are whitish, in dense clusters 8–15 inch long. The flowers sometimes change to pink and purple with age. It is native to China and Japan. 

Constituents

• It contains flavonoids, a cyanogenic glycoside (hydrangein), saponins, and a volatile oil.

Medicinal Uses

• It is helpful in the treatment of kidney and bladder stones. It is also used in genitourinary system, including cystitis, urethritis, enlarged prostate, and prostatitis. 

KAVA KAVA

• Piper methysticum Forst.; Pepper family (Piperaceae). It is a perennial, soft-wooded shrub growing 8–10 feet tall, with 8-inch ovate to heart-shaped leaves. The flower spikes are opposite to the leaves; male and female flowers occur on separate plants. This plant is native to the Pacific Islands. 

Constituents

• Kava pyrones (including kavalactones kawahin, yangonin, methectic) and Mucilage. It also contains pipermethystine, a kava alkaloid obtained from leaves. 

Medicinal Uses

• It is used as diuretic, urinary antiseptic, circulatory stimulant antispasmodic, analgesic, an aesthetic (topically), anaesthetic effect in the gastric mucosa and bladder mucosa, mental stimulant in small doses depressant in large, Rubefacients (topically) and as antifungal. Serial plasma concentration time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. The current study compared short-term toxic effects of pipermethystine in F-344 rats to acetone-water extracts of kava rhizome (KRE)