chemistry

Thujone

Thujone is a chemistry topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Thujone rather than just read about it. In short: Thujone ( ) is a ketone and a monoterpene that occurs predominantly in two diastereomeric (epimeric) forms: (−)-α-thujone and (+)-β-thujone. Though it is best known as a chemical compound in the spirit absinthe, it is only present in trace amounts and is unlikely to be responsible for the spirit's purported stimulant and psychoactive effects.

Key takeaways

Thujone belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Thujone to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Thujone from memory before moving on to harder problems.

Reference excerpt

Thujone ( ) is a ketone and a monoterpene that occurs predominantly in two diastereomeric (epimeric) forms: (−)-α-thujone and (+)-β-thujone. Though it is best known as a chemical compound in the spirit absinthe, it is only present in trace amounts and is unlikely to be responsible for the spirit's purported stimulant and psychoactive effects. Thujone acts on the GABAA receptor as an antagonist. As a competitive antagonist of GABAA receptor, thujone alone is considered to be convulsant, though by interfering with the inhibitory transmitter GABA, it may convey stimulating, mood-elevating effects at low doses. It is also found in perfumery as a component of several essential oils. In addition to the naturally occurring (−)-α-thujone and (+)-β-thujone, two other forms are possible: (+)-α-thujone and (−)-β-thujone. In 2016, they were found in nature as well, in Salvia officinalis.

Sources Alpha and beta thujones are found in a number of plants, such as arborvitae (genus Thuja, hence the derivation of the name), Nootka cypress, some junipers, mugwort, oregano, common sage (sage oil contain more than 20% from alpha and beta thujones), tansy, and wormwood, most notably grand wormwood (Artemisia absinthium), usually as a mix of isomers in a 1:2 ratio. It is also found in various species of Mentha (mint). The aroma of alpha and beta thujones are characteristically "thujonic".

Biosynthesis The biosynthesis of thujone is similar to the synthesis of other monoterpenes and begins with the formation of geranyl diphosphate (GPP) from dimethylallyl pyrophosphate (DMAPP) and isopentenyl diphosphate (IPP), catalyzed by the enzyme geranyl diphosphate synthase. Quantitative 13C NMR spectroscopic analysis has demonstrated that the isoprene units used to form thujone in plants are derived from the methylerythritol phosphate pathway (MEP). The reactions that generate the thujone skeleton in sabinene from GPP are mediated by the enzyme sabinene synthase which has GPP as its substrate. GPP (1) first isomerizes to linally diphosphate (LPP) (2) and neryl diphosphate (NPP) (3). LPP preferentially forms a delocalized allylic cation-diphosphate (4). The ion-pair intermediate then cyclizes in an electrophilic addition to yield the α-terpinyl tertiary cation (5).

The α-terpinyl cation (5) then undergoes a 1,2 hydride shift via a Wagner–Meerwein rearrangement, leading to the formation of the terpinen-4-yl cation (6). This cation undergoes a second cyclization to form the thujyl cation intermediate (7) before loss of a proton to form the thujone precursor, (+)-sabinene (8).

From (+)-sabinene (8), the proposed biosynthetic route to generate thujone follows a three-step pathway: (+)-sabinene is first oxidized to an isomer of (+)-sabinol (9-1, 9-2) by a cytochrome P450 enzyme, followed by conversion to (+)-sabinone (10) via a dehydrogenase. Finally, a reductase mediates the conversion to α-thujone (11-1) and β-thujone (11-2). The isomerism of the (+)-sabinol intermediate varies among thujone-producing plants; for instance, in the western redcedar (Thuja plicata), thujone is derived exclusively from the (+)-trans-sabinol intermediate (9-1) whereas in the common garden sage (Salvia officinalis), thujone is formed from the (+)-cis-sabinol intermediate (9-2).

Pharmacology

Based on a hypothesis that considered only molecular shape, it was speculated that thujone might act similarly to THC on the cannabinoid receptors; however, thujone failed to evoke a cannabimimetic response in a 1999 investigative study. Thujone is a GABAA receptor antagonist and, more specifically, a GABAA receptor competitive antagonist. By inhibiting GABA receptor activation, neurons may fire more easily, which can cause muscle spasms and convulsions. This interaction with the GABAA receptor is specific to alpha-thujone. Thujone is also a 5-HT3 antagonist. The median lethal dose, or LD50, of α-thujone, the more active of the two isomers, in mice, is around 45 mg/kg, with 0% mortality rate at 30 mg/kg and 100% at 60 mg/kg. Mice exposed to the higher dose have convulsions that lead to death within 1 minute. From 30 to 45 mg/kg, the mice experience muscle spasms in the legs, which progress to general convulsions until death or recovery. These effects are in line with other GABA antagonists. Also, α-thujone is metabolized quickly in the liver in mice. Pretreatment with GABA positive allosteric modulators like diazepam, phenobarbital, or 1 g/kg of ethanol protects against a lethal dose of 100 mg/kg. Attention performance has been tested with low and high doses of thujone in alcohol. The high dose had a short-term negative effect on attention performance. The lower dose showed no noticeable effect. Thujone is reported to be toxic to brain, kidney, and liver cells and could cause convulsions if used in too high a dose. Other thujone-containing plants such as the tree arborvitae (Thuja occidentalis) are used in herbal medicine, mainly for their alleged immune-system stimulating effects. Side effects from the essential oil of this plant include anxiety, sleeplessness, and convulsions, which confirms the central nervous system effects of thujone.

In absinthe Thujone is most commonly known for being a compound in the spirit absinthe. In the past, absinthe was thought to contain up to 260–350 mg/L thujone, but modern tests have shown this estimate to be far too high. A 2008 study of 13 pre-ban (1895–1910) bottles using gas chromatography–mass spectrometry (GC-MS) found that the bottles had between 0.5 and 48.3 mg/L and averaged 25.4 mg/L A 2005 study recreated three 1899 high-wormwood recipes and tested with GC–MS, and found that the highest contained 4.3 mg/L thujone. GC–MS testing is important in this capacity because gas chromatography alone may record an inaccurately high reading of thujone as other compounds may interfere with and add to the apparent measured amount.

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Thujone

Start with the simplest possible case. Write down what Thujone claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Thujone before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Thujone ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Thujone

In research: Thujone appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Thujone in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Thujone is common in secondary-school and first-year university syllabi. It links to neighbouring topics 5-HT3 antagonists, Absinthe, Bicyclic compounds, so understanding it makes those chapters shorter.
In everyday life: Look for Thujone outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Thujone in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Thujone means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Thujone out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Thujone in simple terms?

Why does Thujone matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Thujone?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Thujone.