Mandragora officinarum

Mandragora officinarum or mandrake is the type species of the plant genus Mandragora. As of 2015, sources differ significantly in the species they use for Mandragora plants native to the Mediterranean region. In the narrowest circumscription, M. officinarum is limited to small areas of northern Italy and the coast of former Yugoslavia, and the main species found around the Mediterranean is called Mandragora autumnalis, the autumn mandrake. In a broader circumscription, all the plants native to the countries around the Mediterranean sea are placed in M. officinarum, which thus includes M. autumnalis. The names autumn mandrake and Mediterranean mandrake are then used.^[2] Whatever the circumscription, Mandragora officinarum is a perennial herbaceous plant with ovate leaves arranged in a rosette, a thick upright root, often branched, and bell-shaped flowers followed by yellow or orange berries.

Because mandrakes contain deliriant hallucinogenic tropane alkaloids and shape of their roots often resemble human figures, they have been associated with a variety of superstitious practices throughout the history. They have long been used in magic rituals, today also in contemporary pagan traditions such as Wicca and Odinism.^[3] However, the so-called "mandrakes" used in this way are not always species of Mandragora let alone Mandragora officinarum; for example, Bryonia alba, the English mandrake, is explicitly mentioned in some sources.

Description

As of 2015, Mandragora officinarum has three or four different circumscriptions (see Taxonomy below). The description below applies to a broad circumscription, used in a 1998 revision of the genus, in which the name is used for all the plants native to Mediterranean region.^[1] Thus defined, Mandragora officinarum is a very variable perennial herbaceous plant with a long thick root, often branched. It has almost no stem, the leaves being borne in a basal rosette. The leaves are very variable in size and shape, with a maximum length of 45 cm (18 in). They are usually either elliptical in shape or wider towards the end (obovate), with varying degrees of hairiness.^[1]

The flowers appear from autumn to spring (September to April). They are borne in the axils of the leaves. The flower stalks (pedicels) are also very variable in length, up to 45 cm (18 in) long. The five sepals are 6–28 mm (0.2–1.1 in) long, fused together at the base and then forming free lobes to about a half to two-thirds of their total length. The five petals are greenish white to pale blue or violet in colour, 12–65 mm (0.5–2.6 in) long, and, like the sepals, joined together at the base with free lobes at the end. The lobes are between half as long as the petals to almost as long. The five stamens are joined to the bases of the petals and vary in length from 7 to 15 mm (0.3 to 0.6 in). The anthers of the stamens are usually yellow or brown, but are sometimes pale blue.^[1]

The fruit which forms in late autumn to early summer (November to June) is a berry, shaped like a globe or an ellipsoid (i.e. longer than wide), with a very variable diameter of 5–40 mm (0.2–1.6 in). When ripe, the fruit is glossy, and yellow to orange – somewhat resembling a small tomato. It contains yellow to light brown seeds, 2.5–6 mm (0.10–0.24 in) long.^[1]

Earlier, a different circumscription was used, in which Mandragora officinarum referred only to plants found in northern Italy and part of the coast of former Yugoslavia, most Mediterranean mandrakes being placed in Mandragora autumnalis.^[4][5] The description above would then apply to both species combined, with M. officinarum having greenish-white rather than violet petals, up to 25 mm (1 in) long rather than usually 30–40 mm (1.2–1.6 in) or longer, and a berry that is globose rather than ellipsoid.^[4] More recently, plants native to the Levant have been separated out as Mandragora autumnalis, leaving those found in the rest of the Mediterranean area as M. officinarum. One difference then is that the size of the seeds of M. officinarum is less than half the size of those of M. autumnalis.^[6]

Taxonomy

Mandragora officinarum was first described in 1753 by Carl Linnaeus in the first edition of Species Plantarum.^[7][8] It is the type species of the genus Mandragora.^[5] (Linnaeus later changed his mind and in 1759 placed M. officinarum in the genus Atropa as A. mandragora.^[9]) Linnaeus regarded M. officinarum as the sole species in the genus, at that time only known from the Mediterranean region. Jackson and Berry (1979)^[5] and Ungricht et al. (1998)^[1] have documented some of the subsequent confusion over the number of Mediterranean species of Mandragora and their scientific names. Ungricht et al. describe the confusion as "incredible" and a "morass".^[1]

The first confusion relates to the name "Mandragora officinalis Mill.", dated to 1768 in the eighth edition of Philip Miller's The gardener's dictionary. However, this work uses the epithet officinarum, not "officinalis".^[10] There is a reference to "Mandragora officinalis" as a synonym in the 9th edition of The gardener's dictionary of 1807. However, there was no such earlier use of the name, and Ungricht et al. say that "officinalis" is an orthographic error for the correct epithet officinarum, so that the name "Mandragora officinalis Mill." (and any subsequent uses of this epithet) have "no real nomenclatural standing".^[1]

The second confusion relates to the number of Mediterranean species of Mandragora (a confusion which continues). At different times, between one to five taxa have been recognized.^[1] Dioscorides was among those who distinguished between "male" and "female" mandrakes,^[5] a distinction used in 1764 when Garsault published the names Mandragora mas and Mandragora foemina. Flowering time was also used to distinguish species; thus in the 1820s, Antonio Bertoloni named two species as Mandragora vernalis, the spring-flowering mandrake, and Mandragora autumnalis, the autumn-flowering mandrake.^[1] Since the late 1990s, three main circumscriptions of Mandragora officinarum have been used and all three will be found in current sources.

• Identifying the spring-flowering mandrake as Linnaeus's M. officinarum, works such as Flora Europaea list two Mediterranean species of Mandragora: M. officinarum and M. autumnalis. On this view, the main Mediterranean species is M. autumnalis rather than M. officinarum, which is a rare species, confined to northern Italy and a small region of the coast of former Yugoslavia.^[4][5]

• Using statistical analysis of morphological characters, Ungricht et al. in 1998 found no distinct clusters among the specimens they examined and concluded that Linnaeus's M. officinarum is a single, variable species. They thus include M. autumnalis in M. officinarum, which on this view is the only Mediterranean mandrake.^[1]

• M. autumnalis was again separated from M. officinarum by Tu et al. in 2010 in a molecular phylogenetic study. They regard M. officinarum as the main species in the Mediterranean, but separate out plants native to the Levant as M. autumnalis, which was then shown to be more closely related to Mandragora turcomanica than to their circumscription of M. officinarum.^[6]

Distribution and habitat

In the circumscription in which Mandragora officinarum is the only Mediterranean species, it is native to southern Portugal and countries around the Mediterranean sea: Tunisia, Algeria and Morocco in north Africa; southern Spain, Italy, former Yugoslavia, Greece and Cyprus in southern Europe; southern Turkey; Syria, Lebanon, Israel, the Palestinian territories and Jordan in the Levant. It is usually found in open habitats, such as light woodland and disturbed sites, including olive groves, fallow land, waysides, railway embankments and ruins, from sea level to 1,200 m (3,900 ft).^[1]

When Mandragora autumnalis is regarded as the main Mediterranean species, M. officinarum is native only to north Italy and part of the coast of former Yugoslavia.^[4] Alternatively, M. officinarum is absent from the Levant, where it is replaced by M. autumnalis.^[6]

Toxicity

All species of Mandragora contain highly biologically active alkaloids, tropane alkaloids in particular. Hanuš et al. reviewed the phytochemistry of Mandragora species. More than 80 substances have been identified; their paper gives the detailed chemical structure of 37 of them.^[11] Jackson and Berry were unable to find any differences in alkaloid composition between Mandragora officinarum (using the narrowest circumscription of this species) and Mandragora autumnalis (viewed as the main Mediterranean species). Alkaloids present in the fresh plant or the dried root included atropine, hyoscyamine, scopolamine (hyoscine), scopine, cuscohygrine, apoatropine, 3-alpha-tigloyloxytropane, 3-alpha,6-beta-ditigloyloxytropane and belladonnines. Non-alkaloid constituents included sitosterol and beta-methylesculetin (scopoletin).^[5][11]

The alkaloids make the plant, in particular the root and leaves, poisonous, via anticholinergic, hallucinogenic, and hypnotic effects. Anticholinergic properties can lead to asphyxiation. Ingesting mandrake root is likely to have other adverse effects such as vomiting and diarrhea. The alkaloid concentration varies between plant samples, and accidental poisoning is likely to occur. Clinical reports of the effects of consumption of Mandragora officinarum (as Mandragora autumnalis) include severe symptoms similar to those of atropine poisoning, including blurred vision, dilation of the pupils (mydriasis), dryness of the mouth, difficulty in urinating, dizziness, headache, vomiting, blushing and a rapid heart rate (tachycardia). Hyperactivity and hallucinations also occurred in the majority of patients.^[12][13]

Folklore

Mandrake has a long history of medicinal use, although superstition has played a large part in the uses to which it has been applied. It is rarely prescribed in modern herbalism.

The root is hallucinogenic and narcotic. In sufficient quantities, it induces a state of oblivion and was used as an anaesthetic for surgery in ancient times.^[14] In the past, juice from the finely grated root was applied externally to relieve rheumatic pains.^[14] It was also used internally to treat melancholy, convulsions, and mania.^[14] When taken internally in large doses, however, it is said to excite delirium and madness.^[14]

In the past, mandrake was often made into amulets which were believed to bring good fortune, cure sterility, etc. In one superstition, people who pull up this root will be condemned to hell, and the mandrake root would scream as it was pulled from the ground, killing anyone who heard it.^[3] Therefore in the past, people have tied the roots to the bodies of animals and then used these animals to pull the roots from the soil.^[3]

In the Bible

Two references to דודאים (dûdã'im)—literally meaning "love plant"—occur in the Jewish scriptures. The Septuagint translates דודאים (dûdã'im) as μανδραγόρας (mandragoras), and Vulgate follows Septuagint. A number of later translations into different languages follow Septuagint (and Vulgate) and use mandrake as the plant as the proper meaning in both Genesis 30:14–16 and Song of Solomon 7:13. Others follow the example of the Luther Bible and provide a more literal translation.

In Genesis 30:14, Reuben, the eldest son of Jacob and Leah finds mandrake in a field. Rachel, Jacob's infertile second wife and Leah's sister, is desirous of the דודאים and barters with Leah for them. The trade offered by Rachel is for Leah to spend that night in Jacob's bed in exchange for Leah's דודאים. Leah gives away the plant to her barren sister, but soon after this (Genesis 30:14–22), Leah, who had previously had four sons but had been infertile for a long while, became pregnant once more and in time gave birth to two more sons, Issachar and Zebulun, and a daughter, Dinah. Only years after this episode of her asking for the mandrakes did Rachel manage to become pregnant. The predominant traditional Jewish view is that דודאים were an ancient folk remedy to help barren women conceive a child.

¹⁴ And Reuben went in the days of wheat harvest, and found mandrakes in the field, and brought them unto his mother Leah. Then Rachel said to Leah, Give me, I pray thee, of thy son's mandrakes.

¹⁵ And she said unto her, Is it a small matter that thou hast taken my husband? and wouldest thou take away my son's mandrakes also? And Rachel said, Therefore he shall lie with thee to night for thy son's mandrakes.

¹⁶ And Jacob came out of the field in the evening, and Leah went out to meet him, and said, Thou must come in unto me; for surely I have hired thee with my son's mandrakes. And he lay with her that night.

—the Bible, King James Version, Genesis 30:14–16^[15]

A number of other plants have been suggested by biblical scholars, e.g., most notably, ginseng, which looks similar to the mandrake root and reputedly has fertility enhancing properties, for which it was picked by Reuben in the Bible; blackberries, Zizyphus lotus, the sidr of the Arabs, the banana, lily, citron, and fig. Sir Thomas Browne, in Pseudodoxia Epidemica, ch. VII, suggested the dudai'im of Genesis 30:14 is the opium poppy, because the word duda'im may be a reference to a woman's breasts.

The final verses of Song of Songs (Song of Songs 7:12–13), are:

לְכָ֤ה דֹודִי֙ נֵצֵ֣א הַשָּׂדֶ֔ה נָלִ֖ינָה בַּכְּפָרִֽים׃ נַשְׁכִּ֙ימָה֙ לַכְּרָמִ֔ים נִרְאֶ֞ה אִם פָּֽרְחָ֤ה הַגֶּ֙פֶן֙ פִּתַּ֣ח הַסְּמָדַ֔ר הֵנֵ֖צוּ הָרִמֹּונִ֑ים שָׁ֛ם אֶתֵּ֥ן אֶת־דֹּדַ֖י לָֽךְ׃

¹² Let us get up early to the vineyards; let us see if the vine flourish, whether the tender grape appear, and the pomegranates bud forth: there will I give thee my loves.

¹³ The mandrakes give a smell, and at our gates are all manner of pleasant fruits, new and old, which I have laid up for thee, O my beloved.

—the Bible, King James Version, Song of Songs 7:12–13^[16]

Magic and witchcraft

According to the legend, when the root is dug up, it screams and kills all who hear it. Literature includes complex directions for harvesting a mandrake root in relative safety. For example Josephus (circa 37–100 AD) of Jerusalem gives the following directions for pulling it up:

A furrow must be dug around the root until its lower part is exposed, then a dog is tied to it, after which the person tying the dog must get away. The dog then endeavours to follow him, and so easily pulls up the root, but dies suddenly instead of his master. After this, the root can be handled without fear.^[17]

Excerpt from Chapter XVI, "Witchcraft and Spells", of Transcendental Magic: Its Doctrine and Ritual by nineteenth-century occultist and ceremonial magician Eliphas Levi.

The following is taken from Paul Christian's The History and Practice of Magic:^[18]

Would you like to make a Mandragora, as powerful as the homunculus (little man in a bottle) so praised by Paracelsus? Then find a root of the plant called bryony. Take it out of the ground on a Monday (the day of the moon), a little time after the vernal equinox. Cut off the ends of the root and bury it at night in some country churchyard in a dead man's grave. For 30 days, water it with cow's milk in which three bats have been drowned. When the 31st day arrives, take out the root in the middle of the night and dry it in an oven heated with branches of verbena; then wrap it up in a piece of a dead man's winding-sheet and carry it with you everywhere.

In literature

In its more sinister significance:

• Machiavelli wrote in 1518 a play Mandragola (The Mandrake) in which the plot revolves around the use of a mandrake potion as a ploy to bed a woman.
• Shakespeare refers four times to mandrake and twice under the name of mandragora.

"... Not poppy, nor mandragora,

Nor all the drowsy syrups of the world,

Shall ever medicine thee to that sweet sleep

Which thou owedst yesterday."

Shakespeare: Othello III.iii

"Give me to drink mandragora ...

That I might sleep out this great gap of time

My Antony is away."

Shakespeare: Antony and Cleopatra I.v

"Shrieks like mandrakes' torn out of the earth."

Shakespeare: Romeo and Juliet IV.iii

"Would curses kill, as doth the mandrake's groan"

King Henry VI part II III.ii

• John Donne refers to it in the second line of his song, 'Go and catch a falling star', as an example of an impossible task,

"Get with child a mandrake root"

• Alraune (German for Mandrake) is a novel by German novelist Hanns Heinz Ewers published in 1911.
• It is in Samuel Beckett's Waiting For Godot, too. "Let's hang ourselves immediately!" "It'd give us an Erection!" "An Erection!" "With all that follows—where it falls, Mandrakes grow, that's why they shriek when you pull them up. Did you not know that?"
• In Harry Potter by J.K. Rowling, mandrakes can be found in the Hogwarts greenhouses. When pulled out of the earth, they resemble humans, and just as in the mythology, the cry is fatal. The mandrake can also revive those who have been petrified.
• In The Winter of Our Discontent by John Steinbeck, Ethan Hawley mentions both the form and legend of the mandrake root in chapter eight when describing a collection of "worthless family treasures" as follows: "We even had a mandrake root—a perfect little man, sprouted from the death-ejected sperm of a hanged man ..."
• In Pan's Labyrinth by Guillermo del Toro, the Fawn, Pan, explains that a mandrake root is "A plant that dreamt of being human", and it can have healing powers if instructions are followed.
• In Equal Rites by Terry Pratchett, a reference to the mandrake is made, describing a plant that lets out a supersonic scream when it is uprooted.
• In Sir Arthur Conan Doyle's The Adventure of the Devil's Foot (contained in the Sherlock Homes collection His Last Bow) a crystalline extract of "Devil's Foot Root", also called mandrake, is at the root, so to speak, of two bizarre and related murders.
• In Neil Gaiman's "The Ocean at the End of the Lane" Lettie Hempstock trades a Mandrake for a shadow-bottle to attempt to send Ursula Monkton away "Mandrakes are so loud when you pull them up, and I didn't have earplugs"
• In The Republic by Plato, mandrake is used in an image whereby men use it to drug a ship captain, and take control of the ship (488 c4).

References

Further reading

• Heiser, Charles B. Jr (1969). Nightshades, The Paradoxical Plant, 131-136. W. H. Freeman & Co. SBN 7167 0672-5.
• Thompson, C. J. S. (reprint 1968). The Mystic Mandrake. University Books.

External links

Wikimedia Commons has media related to Mandragora officinarum.

Wikispecies has information related to: Mandragora officinarum

• Erowid Mandrake Vault
•  Chisholm, Hugh, ed. (1911). "Mandrake". Encyclopædia Britannica (11th ed.). Cambridge University Press. 
• Translation of Grimm's Saga No. 84 The Mandrake
• Mandragora in Wildflowers of Israel

Hypnotics/sedatives (N05C) GABAA Alcohols 2M2B Chloralodol Ethanol Alcohol Ethchlorvynol Methylpentynol Trichloroethanol Barbiturates Allobarbital Amobarbital Aprobarbital Barbital Butabarbital Butobarbital Cyclobarbital Ethallobarbital Heptabarb Hexobarbital Mephobarbital Methohexital Pentobarbital Phenallymal Phenobarbital Propylbarbital Proxibarbal Reposal Secobarbital Talbutal Thiamylal Thiopental Vinbarbital Vinylbital Benzodiazepines Brotizolam Cinolazepam Climazolam Doxefazepam Estazolam Flunitrazepam Flurazepam Flutoprazepam Haloxazolam Loprazolam Lormetazepam Midazolam Nimetazepam Nitrazepam Quazepam Temazepam Triazolam Carbamates Carisoprodol Emylcamate Ethinamate Hexapropymate Meprobamate Methocarbamol Phenprobamate Procymate Tybamate Neuroactive steroids Acebrochol Allopregnanolone Alphadolone Alphaxolone Eltanolone Hydroxydione Minaxolone Progesterone Nonbenzodiazepines Eszopiclone Indiplon Lirequinil Necopidem Pazinaclone Saripidem Suproclone Suriclone Zaleplon Zolpidem Zopiclone Phenols Fospropofol Propofol Piperidinediones Glutethimide Methyprylon Pyrithyldione Piperidione Quinazolinones Afloqualone Cloroqualone Diproqualone Etaqualone Mebroqualone Mecloqualone Methaqualone Methylmethaqualone Nitromethaqualone Volatiles/gases Acetophenone Acetylglycinamide chloral hydrate Centalun Chloral hydrate Paraldehyde Others Bromide Lithium bromide Potassium bromide Sodium bromide Chloralose Clomethiazole Dichloralphenazone Etomidate Gaboxadol Loreclezole Metomidate Petrichloral Sulfonmethane Triclofos Valerenic acid Valerian GABAB 1,4-Butanediol Aceburic acid GABOB GHB (sodium oxybate) GBL GVL H1 Antihistamines Captodiame Cyproheptadine Diphenhydramine Doxylamine Hydroxyzine Methapyrilene Pheniramine Promethazine Propiomazine Antidepressants Tricyclic antidepressants Amitriptyline Doxepin Trimipramine, etc. Tetracyclic antidepressants Mianserin Mirtazapine, etc. Antipsychotics Typical antipsychotics Chlorpromazine Thioridazine, etc. Atypical antipsychotics Olanzapine Quetiapine Risperidone, etc. α2-Adrenergic Clonidine Detomidine Dexmedetomidine Lofexidine Medetomidine Romifidine Tizanidine Xylazine 5-HT2A Antidepressants Trazodone Tricyclic antidepressants Amitriptyline Doxepin Trimipramine, etc. Tetracyclic antidepressants Mianserin Mirtazapine, etc. Antipsychotics Typical antipsychotics Chlorpromazine Thioridazine, etc. Atypical antipsychotics Olanzapine Quetiapine Risperidone, etc. Others Niaprazine Melatonin Agomelatine Melatonin Ramelteon Tasimelteon Orexin Almorexant Filorexant Suvorexant Others Acecarbromal Apronal Bromisoval Cannabidiol Cannabis Carbromal Diethylpropanediol Embutramide Evoxine Fenadiazole Gabapentin Kavalactones Kava Mephenoxalone Metaglycodol Niaprazine Opioids Oxycodone Morphine Opium), etc. Passion flower Phenaglycodol Scopolamine Mandrake UMB68 Valnoctamide Index of psychology and psychiatry Description Mental processes Disorders Mental and behavioral ADHD OCD Tourette's Mood Developmental pervasive dyslexia and specific Substance-related alcohol Emotional and behavioral Symptoms and signs eponymous Evaluation and testing Treatment Psychotherapy CBT Drugs depression antipsychotics anxiety dementia hypnotics and sedatives psychostimulants, ADHD and nootropics

Hallucinogens Psychedelics 5-HT2AR agonists Lysergamides AL-LAD ALD-52 BU-LAD IP-LAD Diallyllysergamide Dimethyllysergamide Ergometrine ETH-LAD LAE-32 LPD-824 LSA LSD LSD-Pip LSH LSM-775 2-Butyllysergamide LSZ 3-Pentyllysergamide Methylergometrine Methylisopropyllysergamide Methysergide MLD-41 PARGY-LAD PRO-LAD Phenethylamines Aleph 2-Methyl-MDA 2C-B 2C-B-AN 2C-B-Dragonfly 2C-B-FLY 2CB-Ind βk-2C-B 2C-C 2C-C-FLY 2C-CP 25C-NBOMe 25CN-NBOH 25CN-NBOMe 25D-NBOMe 2C-D 2C-D-FLY 2C-E 2C-E-FLY 25E-NBOMe 2C-EF 2C-F 25F-NBOMe 2C-G 25G-NBOMe 25H-NBOMe 2C-I βk-2C-I 2C-iP 2C-I-FLY 2C-N 25N-NBOMe 2C-O 2C-O-4 2C-P 2C-T 2C-T-2 2C-T-3 2C-T-4 25T4-NBOMe 2C-T-7 2C-T-7-FLY 25T7-NBOH 2C-T-8 2C-T-13 2C-T-15 2C-T-16 2C-T-17 2C-T-19 2C-T-21 2C-T-21.5 2C-T-22 2C-T-27 2C-T-28 2C-TFE 2C-TFM 25TFM-NBOMe 2C-V 2C-YN 2CBCB-NBOMe 2CBFly-NBOMe 2CD-5EtO 25B-NBOMe 25B-NBOH 25C-NBOH 25I-NBMD 25I-NBOH 25I-NBF 25I-NBOMe 25P-NBOMe 3C-AL 3C-DFE 3C-E 3C-P 3C-TFE 4C-B 4C-D 5-APB 5-APDB 5-APDI 5-Methyl-MDA 6-APB 6-APDB 6-Methyl-MDA Br-DFLY Difluoroescaline Difluoromescaline DESOXY DMBMPP DMMDA DMMDA-2 DOB DOB-FLY DOC DOEF DOET DOF DOI DOM DOM-FLY DON DOPR DOTFM DOYN BOB BOD BMB Escaline Fluoroproscaline Ganesha HOT-2 HOT-7 HOT-17 Isoproscaline Jimscaline Lophophine Macromerine MDA MDEA MDMA Mescaline Mescaline-NBOMe Methallylescaline MMA MMDA MMDA-2 MMDA-3a MMDMA Proscaline TCB-2 TFMFly Trifluoroescaline Trifluoromescaline TMA Piperazines pFPP TMFPP mCPP Tryptamines 1-Me-5-MeO-DiPT 2,N,N-TMT 4,5-DHP-α-MT 4,5-DHP-DMT 4-AcO-DALT 4-AcO-DET 4-AcO-DiPT 4-AcO-DMT 4-AcO-DPT 4-AcO-MiPT 4-HO-5-MeO-DMT 4-HO-DBT 4-HO-DPT 4-HO-MET 4-HO-MPMI 4-HO-MPT 4,N,N-TMT 4-Propionyloxy-DMT 5,6-diBr-DMT 5-AcO-DMT 5-Bromo-DMT 5-Me-MIPT 5-MeO-2,N,N-TMT 5-MeO-4,N,N-TMT 5-MeO-α,N,N-TMT 5-MeO-α-ET 5-MeO-α-MT 5-MeO-DALT 5-MeO-DET 5-MeO-DiPT 5-MeO-DMT 5-MeO-DPT 5-MeO-EiPT 5-MeO-MET 5-MeO-MiPT 5-MeO-MPMI 5-N,N-TMT 7,N,N-TMT α-ET α-MT α,N,N-TMT Aeruginascin Baeocystin Bufotenin DALT DBT DCPT DET DIPT DMT DPT EiPT Ethocin Ethocybin Ibogaine Iprocin MET Miprocin MiPT Norbaeocystin Noribogaine PiPT Psilocin Psilocybin Voacangine Others AL-38022A ALPHA Dimemebfe M-ALPHA RH-34 Dissociatives NMDAR antagonists Adamantanes Amantadine Memantine Rimantadine Arylcyclohexylamines 3-MeO-PCP 4-MeO-PCP Dieticyclidine Esketamine Ethketamine Eticyclidine Gacyclidine Ketamine Methoxetamine Methoxyketamine PCPr Phencyclidine Rolicyclidine Tenocyclidine Tiletamine Morphinans Dextrallorphan Dextromethorphan Dextrorphan Racemethorphan Racemorphan Others 2-MDP 8A-PDHQ Aptiganel Dexoxadrol Diphenidine Dizocilpine Etoxadrol Ibogaine Methoxphenidine Midafotel NEFA Neramexane Nitrous oxide Noribogaine Perzinfotel Remacemide Selfotel Xenon Deliriants mAChR antagonists Atropine Benactyzine Benzatropine Benzydamine Biperiden BRN-1484501 Brompheniramine BZ CAR-226,086 CAR-301,060 CAR-302,196 CAR-302,282 CAR-302,368 CAR-302,537 CAR-302,668 Chloropyramine Chlorphenamine Clemastine CS-27349 Cyclizine Cyproheptadine Dicycloverine Dimenhydrinate Diphenhydramine Ditran Doxylamine EA-3167 EA-3443 EA-3580 EA-3834 Elemicin Flavoxate Hyoscyamine JB-318 JB-336 Meclozine Mepyramine Myristicin Orphenadrine Oxybutynin Pheniramine Phenyltoloxamine Procyclidine Promethazine Scopolamine Tolterodine Trihexyphenidyl Tripelennamine Triprolidine WIN-2299 Miscellaneous Cannabinoids CB1R agonists Phytocannabinoids Cannabinol THC (Dronabinol) THCV (Cannabidiol has different mechanism of action) Synthetic 4-HTMPIPO 5F-PB-22 AB-001 AB-005 A-836,339 AB-CHMINACA AB-FUBINACA AB-PINACA ADB-FUBINACA ADB-PINACA ADBICA AM-630 AM-679 AM-694 AM-1220 AM-1221 AM-1235 AM-1241 AM-1248 AM-2201 AM-2232 AM-2233 APICA APINACA CB-13 CP 47,497 CP 55,244 CP 55,940 DMHP HU-210 HU-308 JWH-007 JWH-015 JWH-018 JWH-019 JWH-030 JWH-073 JWH-081 JWH-098 JWH-116 JWH-122 JWH-149 JWH-167 JWH-182 JWH-193 JWH-198 JWH-200 JWH-203 JWH-210 JWH-250 JWH-251 JWH-398 JWH-424 JTE 7-31 JTE-907 Levonantradol MAM-2201 MDA-19 MN-25 NESS-0327 NESS-040C5 Nabilone Nabitan Org 28611 Parahexyl QUCHIC QUPIC RCS-4 RCS-8 SDB-006 STS-135 THC-O-acetate THC-O-phosphate UR-144 WIN 55,212-2 XLR-11 D2R agonists Apomorphine Aporphine Bromocriptine Cabergoline Lisuride Memantine Nuciferine Pergolide Piribedil Pramipexole Ropinirole Rotigotine Also indirect D2 agonists, such as dopamine reuptake inhibitors (cocaine, methylphenidate), releasing agents (amphetamine, methamphetamine), and precursors (levodopa). GABAAR agonists Eszopiclone Gaboxadol Ibotenic acid Muscimol Zaleplon Zolpidem Zopiclone Inhalants Mixed MOA Aliphatic hydrocarbons Butane Gasoline Kerosene Propane Aromatic hydrocarbons Toluene Ethers Diethyl ether Enflurane Haloalkanes Chlorofluorocarbons Chloroform κOR agonists 2-EMSB 2-MMSB Alazocine Bremazocine Butorphanol Cyclazocine Cyprenorphine Dextrallorphan Dezocine Enadoline Herkinorin HZ-2 Ibogaine Ketazocine LPK-26 Metazocine Nalbuphine Nalorphine Noribogaine Pentazocine Phenazocine Salvinorin A Spiradoline Tifluadom U-50488 U-69,593 MAO inhibitors Harmaline Harmine Tetrahydroharmine Yohimbine σR agonists DMT Dextrallorphan Dextromethorphan Dextrorphan Noscapine Others Glaucine Isoaminile Pukateine

Ancient anaesthesia Plants / animals Aconitum (aconite) Atropa belladonna (belladonna) Cannabis medical use Castoreum Coca Conium (hemlock) Datura inoxia (thorn-apple) Datura metel (devil's trumpet) Hyoscyamus niger (henbane) Lactucarium Mandragora officinarum (mandrake) Opium Saussurea (saw-wort) Willow People Abulcasis Avenzoar Avicenna Celsus Dioscorides Galen Hippocrates Rhazes Sabuncuoğlu Sushrutha Theophrastus Zhang Compounds Aconitine Atropine Cocaine Coniine Δ9-THC Hyoscyamine Morphine Salicylate Scopolamine

Cholinergics   Receptor ligands mACh Agonists: 77-LH-28-1 AC-42 AC-260,584 Aceclidine Acetylcholine AF30 AF150(S) AF267B AFDX-384 Alvameline AQRA-741 Arecoline Bethanechol Butyrylcholine Carbachol CDD-0034 CDD-0078 CDD-0097 CDD-0098 CDD-0102 Cevimeline Choline cis-Dioxolane Ethoxysebacylcholine Itameline LY-593,039 L-689,660 LY-2,033,298 McNA343 Methacholine Milameline Muscarine NGX-267 Ocvimeline Oxotremorine PD-151,832 Pilocarpine RS86 Sabcomeline SDZ 210-086 Sebacylcholine Suberyldicholine Talsaclidine Tazomeline Thiopilocarpine Vedaclidine VU-0029767 VU-0090157 VU-0152099 VU-0152100 VU-0238429 WAY-132,983 Xanomeline YM-796 Antagonists: 3-Quinuclidinyl benzilate 4-DAMP Aclidinium bromide Anisodamine Anisodine Antihistamines (first-generation) (e.g., brompheniramine, chlorphenamine, cyproheptadine, dimenhydrinate, diphenhydramine, doxylamine, mepyramine (pyrilamine), phenindamine, pheniramine, promethazine, tripelennamine, triprolidine) Atropine Atropine methonitrate Atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine, zotepine) Benactyzine Benzatropine (benztropine) Benzydamine BIBN 99 Biperiden Bornaprine CAR-226,086 CAR-301,060 CAR-302,196 CAR-302,282 CAR-302,368 CAR-302,537 CAR-302,668 CS-27349 Cyclobenzaprine Cyclopentolate Darifenacin DAU-5884 Dimethindene Dexetimide DIBD Dicyclomine (dicycloverine) Ditran EA-3167 EA-3443 EA-3580 EA-3834 Etanautine Etybenzatropine (ethybenztropine) Flavoxate Himbacine HL-031,120 Ipratropium bromide J-104,129 Hyoscyamine Mamba toxin 3 Mamba toxin 7 Mazaticol Mebeverine Methoctramine Metixene N-Ethyl-3-piperidyl benzilate N-Methyl-3-piperidyl benzilate Orphenadrine Otenzepad Oxybutynin PBID PD-102,807 PD-0298029 Phenglutarimide Phenyltoloxamine Pirenzepine Piroheptine Procyclidine Profenamine RU-47,213 SCH-57,790 SCH-72,788 SCH-217,443 Scopolamine (hyoscine) Solifenacin Telenzepine Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin, mirtazapine) Tiotropium bromide Tolterodine Tricyclic antidepressants (e.g., amitriptyline, butriptyline, clomipramine, desipramine, dosulepin (dothiepin), doxepin, imipramine, lofepramine, nortriptyline, protriptyline, trimipramine) Trihexyphenidyl Tripitamine Tropatepine Tropicamide Typical antipsychotics (e.g., chlorpromazine, loxapine, thioridazine) WIN-2299 Xanomeline Zamifenacin nACh Agonists: 5-HIAA A-84,543 A-366,833 A-582,941 A-867,744 ABT-202 ABT-418 ABT-560 ABT-894 Acetylcholine Altinicline Anabasine Anatoxin-a AR-R17779 Butinoline Butyrylcholine Carbachol Choline Cotinine Cytisine Decamethonium Desformylflustrabromine Dianicline Dimethylphenylpiperazinium Epibatidine Epiboxidine Ethanol Ethoxysebacylcholine EVP-4473 EVP-6124 Galantamine GTS-21 Ispronicline Ivermectin Levamisole Lobeline MEM-63,908 (RG-3487) Morantel Nicotine (tobacco) NS-1738 PHA-543,613 PHA-709,829 PNU-120,596 PNU-282,987 Pozanicline Rivanicline RJR-2429 Sazetidine A SB-206553 Sebacylcholine SIB-1508Y SIB-1553A SSR-180,711 Suberyldicholine Suxamethonium (succinylcholine) TC-1698 TC-1734 TC-1827 TC-2216 TC-5214 TC-5619 TC-6683 Tebanicline Tropisetron UB-165 Varenicline WAY-317,538 XY-4083 Antagonists: 18-MAC 18-MC α-Bungarotoxin α-Conotoxin ABT-126 Alcuronium Allopregnanolone Amantadine Anatruxonium AQW051 Atracurium Barbiturates (e.g., pentobarbital, sodium thiopental) Bupropion Chandonium Chlorisondamine Cisatracurium Coclaurine Coronaridine Cyclopropane Dacuronium Decamethonium Desflurane Dextromethorphan Dextropropoxyphene Dextrorphan Diadonium DHβE Dihydrochandonium Dimethyltubocurarine (metocurine) Dipyrandium Dizocilpine (MK-801) Doxacurium Encenicline Enflurane Esketamine Fazadinium Gallamine Halothane Hexafluronium Hexamethonium (benzohexonium) Hydroxybupropion Ibogaine Isoflurane Ketamine Kynurenic acid Laudexium (laudolissin) Levacetylmethadol Levomethadone Malouetine ME-18-MC Mecamylamine Memantine Methadone Methorphan (racemethorphan) Methyllycaconitine Metocurine Mivacurium Morphanol (racemorphan) Neramexane Nitrous oxide Pancuronium bromide Pempidine Pentamine Pentolinium Phencyclidine Pipecuronium Progesterone Promegestone Radafaxine Rapacuronium Reboxetine Rocuronium Sevoflurane Surugatoxin Thiocolchicoside Toxiferine Tramadol Trimetaphan camsilate (trimethaphan camsylate) Tropeinium Tubocurarine Vanoxerine Vecuronium Xenon   Transporter ligands CHT Inhibitors: Hemicholinium-3 (hemicholine) Triethylcholine Enhancers: Coluracetam VAChT Inhibitors: Vesamicol   Enzyme inhibitors ChAT 1-(-Benzoylethyl)pyridinium 2-(α-Naphthoyl)ethyltrimethylammonium 3-Chloro-4-stillbazole 4-(1-Naphthylvinyl)pyridine Acetylseco hemicholinium-3 Acryloylcholine AF64A B115 BETA CM-54,903 N,N-Dimethylaminoethylacrylate N,N-Dimethylaminoethylchloroacetate AChE Reversible: Carbamates: Aldicarb Bendiocarb Bufencarb Carbaryl Carbendazim Carbetamide Carbofuran Chlorbufam Chloropropham Ethienocarb Ethiofencarb Fenobucarb Fenoxycarb Formetanate Furadan Ladostigil Methiocarb Methomyl Miotine Oxamyl Phenmedipham Pinmicarb Pirimicarb Propamocarb Propham Propoxur; Stigmines: Distigmine bromide Eptastigmine Ganstigmine Neostigmine Phenserine Physostigmine Pyridostigmine bromide Quilostigmine Rivastigmine Terestigmine; Others: Acotiamide Ambenonium Donepezil Caffeine Edrophonium Galantamine Huperzine A Ipidacrine Minaprine Tacrine Zanapezil Irreversible: Organophosphates: Acephate Azinphos-methyl Bensulide Cadusafos Chlorethoxyfos Chlorfenvinphos Chlorpyrifos Chlorpyrifos-methyl Coumaphos Cyclosarin Demeton Demeton-S-methyl Diazinon Dichlorvos Dicrotophos Diisopropyl fluorophosphate Diisopropylphosphate Dimethoate Dioxathion Disulfoton EA-3148 Echothiophate Ethion Ethoprop Fenamiphos Fenitrothion Fenthion Fosthiazate GV Isofluorophate Isoxathion Malaoxon Malathion Methamidophos Methidathion Metrifonate Mevinphos Monocrotophos Naled Novichok agent Omethoate Oxydemeton-methyl Paraoxon Parathion Parathion-methyl Phorate Phosalone Phosmet Phoxim Pirimiphos-methyl Sarin Soman Tabun Tebupirimfos Temefos Terbufos Tetrachlorvinphos Tribufos Trichlorfon VE VG VM VR VX; Others: Demecarium Onchidal (Onchidella binneyi) BChE Cymserine Note: Many of the AChE inhibitors listed above also act as BChE inhibitors.   Others Precursors Choline (lecithin) Citicoline Cyprodenate Dimethylethanolamine Glycerophosphocholine Meclofenoxate (centrophenoxine) Phosphatidylcholine Phosphatidylethanolamine Phosphorylcholine Pirisudanol Cofactors Acetic acid Acetylcarnitine Acetyl-coA Vitamin B5 Others Acetylcholine releasing agents: α-Latrotoxin β-Bungarotoxin; Acetylcholine release inhibitors: Botulinum toxin (Botox); Acetylcholinesterase reactivators: Asoxime Obidoxime Pralidoxime Index of the central nervous system Description Anatomy meninges cortex association fibers commissural fibers lateral ventricles basal ganglia diencephalon mesencephalon pons cerebellum medulla spinal cord tracts Physiology neutrotransmission enzymes intermediates Development Disease Cerebral palsy Meningitis Demyelinating diseases Seizures and epilepsy Headache Stroke Sleep Congenital Injury Neoplasms and cancer Other paralytic syndromes ALS Symptoms and signs head and neck eponymous lesions Tests CSF Treatment Procedures Drugs general anesthetics analgesics addiction epilepsy cholinergics migraine Parkinson's vertigo other