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Former featured article Caffeine is a former featured article. Please see the links under Article milestones below for its original nomination page (for older articles, check the nomination archive) and why it was removed.
Main Page trophy This article appeared on Wikipedia's Main Page as Today's featured article on September 16, 2006.

Edit Request: Add information on LD50 in the table at the right corner, justa like in German[edit]

Recently looked at LD50 of caffeine to assure safety on its use in higher doses. To acquire this information I had to resort to German wikipedia, as this information was not only more complete but clearly displayed at the first table in the right corner. I've got concerned with this lack of clarity as recently a few people died of caffeine overdose. Could somebody give me permission to edit this page or edit it for me? Also, why is this page protected? Diogopell (talk) 23:55, 1 July 2014 (UTC)

What do you wish to add to this page / change the text to? Doc James (talk · contribs · email) (if I write on your page reply on mine) 00:20, 2 July 2014 (UTC)

Edit request: Change incorrect information "antagonist" to "agonist"[edit]

In the Pharmacology section, "an antagonist of the ryanodine receptors (RYR1, RYR2, and RYR3)". The cited reference [116] says that caffeine is an agonist at RyRs. — Preceding unsigned comment added by (talk) 17:47, 12 February 2015 (UTC)

You have a sharp eye. Thank you: will review. This is not an area in which I have expertise, so will need to do a bit of self-education. (How did this new section get inserted between two July 2014 sections?) - IiKkEe (talk) 11:29, 18 February 2015 (UTC)
Wow! - 19 minutes after I wrote the above, Seppi333 swept in and nailed it, and with a reference: It is both an antagonist and agonist (activator). Sweet. - IiKkEe (talk) 12:15, 18 February 2015 (UTC)

Citation 169 "caffeine poisoning in dogs" is broken[edit]

Link sends me to > — Preceding unsigned comment added by (talk) 13:35, 24 July 2014 (UTC)

Broken infobox[edit]

There is an awful lot of data provided to the infobox that is not appearing on the page - safety data, CAS number, physical properties, etc. It looks like the article formerly used Template:Chembox for the infobox, which supported all the chemical data, but that template was eliminated and redirected to Template:Infobox drug, which does not support chemical data. I imagine a separate chembox would now be required to restore the missing data to the article. Not exactly as simple as a standard edit request, but would someone either refactor the unsupported infobox fields into a separate chembox or remove them to reduce the potential for confusion? (talk) 13:35, 10 August 2014 (UTC)

FixedSeppi333 (Insert  | Maintained) 17:55, 10 August 2014 (UTC)

Edit Request: Change "Expresso" to "Espresso" in the fourth paragraph[edit]

Fairly sure this is a simple misspelling. (talk) 15:32, 17 December 2014 (UTC)

Update reference[edit]

Reference [169] currently redirects to a porn site.

A replacement reference that supports the assertion "While safe in humans, caffeine is considerably more toxic to various animals, such as dogs" can be found here:

Jmh02001 (talk) 04:11, 12 September 2014 (UTC)

Thanks, fixed and welcome. Doc James (talk · contribs · email) (if I write on your page reply on mine) 07:44, 12 September 2014 (UTC)

Edit request on November, 1, 2014[edit]

Please correct the internal link where it says:

Caffeine is a receptor antagonist at all adenosine receptor subtypes (A1, A2A, A2B, and A3 receptors)."

"A1" is leading to "Alpha 1 adrenergic receptor" when it should actually link to "Adenosine A1 receptor".

Thanks. --Igorhb (talk) 16:17, 1 October 2014 (UTC)

Fixed Thanks for pointing it out. Seppi333 (Insert  | Maintained) 16:21, 16 October 2014 (UTC)

Caffeine melting point is correct in the info box, wrong in the body of the article; also sublimation point is highly misleading[edit]

There are two conflicting values given for the melting point of caffeine. The value in the info box is correct, according to the Merck Index (12th ed) and my own personal experience as an organic chemist: 235-238C. However, in the body of the article under the Chemical properties and biosynthesis section, the MP is incorrectly stated as 225-228C. I think this must be a simple typo.

Also, there is a serious error under boiling point in the info box (or a series of errors):

First, the boiling point is listed as: 178C (sublimes). First of all, the normal boiling point (the BP at 1 atm pressure) can NOT be lower than the normal melting point (the MP at 1 atm). It must be higher. There are no substances with normal boiling points lower than their normal melting points.

Second, if this is a sublimation point, it should NOT be listed under "boiling point" - sublimation is a totally different process than boiling, and the two should not be conflated. Caffeine does not have a normal boiling point because it decomposes soon after melting at around 238C.

Third, while caffeine can sublimate, it does not have a "normal sublimation point" -- that is, there is no temperature at 1 atm pressure in which the solid/gas equilibrium favors the gas phase. We know this is true because it has a normal melting point. Therefore, the triple point pressure for caffeine must be above 1 atm. If the triple point lies above 1 atm, there is no temperature at which it spontaneously sublimes at 1 atm. If you look at a phase diagram, you will see that this has to be true. Carbon dioxide's triple point is something like 5 atm, so it has a normal sublimation point (but not a normal melting point). It is impossible to have both a [normal] sublimation point and a [normal] melting point. I'm sure that caffeine sublimes at 178C at SOME pressure (below 1 atm), but it's critical to include pressure information here, otherwise it's very misleading (in the absence of pressure data, we usually assume 1 atm). So unless there is pressure data for the 178C value, that number should be removed.

Degrys (talk) 22:30, 15 October 2014 (UTC)Hans de Grys

I've fixed the MP in the body of the article, referenced the MP in the drugbox, and deleted the BP. These[1][2] were the references for those values - I've quoted them below. Seppi333 (Insert  | Maintained) 01:23, 16 October 2014 (UTC)


  1. ^ "Caffeine". Pubchem Compound. NCBI. Retrieved 16 October 2014.
    Boiling Point
    178 deg C (sublimes)
    Melting Point
    238 DEG C (ANHYD)
  2. ^ "Caffeine". ChemSpider. Royal Society of Chemistry. Retrieved 16 October 2014. Experimental Melting Point:
    234-236 °C Alfa Aesar
    237 °C Oxford University Chemical Safety Data
    238 °C LKT Labs [C0221]
    237 °C Jean-Claude Bradley Open Melting Point Dataset 14937
    238 °C Jean-Claude Bradley Open Melting Point Dataset 17008, 17229, 22105, 27892, 27893, 27894, 27895
    235.25 °C Jean-Claude Bradley Open Melting Point Dataset 27892, 27893, 27894, 27895
    236 °C Jean-Claude Bradley Open Melting Point Dataset 27892, 27893, 27894, 27895
    235 °C Jean-Claude Bradley Open Melting Point Dataset 6603
    234-236 °C Alfa Aesar A10431, 39214
    Experimental Boiling Point:
    178 °C (Sublimes) Alfa Aesar
    178 °C (Sublimes) Alfa Aesar 39214

Thanks - I've traced almost all the references I could find about the "178C sublimed" data back to the Merck Index - which does list this info, but without a pressure and without a reference. The next sentence is "Fast sublimation is obtained at 160-165C under 1 mm press." It seems dubious to me that normal sublimation (1 atm) would occur at 178C, while sublimation occurs only 13-18C cooler at 1 mm Hg. I will continue to search for primary literature about caffeine sublimation and associated pressure. Degrys (talk) 14:49, 16 October 2014 (UTC)Hans de Grys

Borked formatting[edit]

@IiKkEe: Your changes to the article lead layout violate MOS:LEAD - it should be at most 4 paragraphs. You've made it 9. One sentence paragraphs are also undesirable - it's simply bad writing. Please keep the article formatted correctly per the WP:Manual of style when you edit it. Seppi333 (Insert  | Maintained) 15:19, 9 November 2014 (UTC)

Seppi333:Thanks for educating me about the 4 paragraph limit. I have followed many of your edits on articles we were both editing in the past, and am always impressed with your contributions. On a related subject: I believe this lead is too long, it contains too much detail that is also covered in the article itself. Would you take a look at my shorter lead once I have completed some deletions, and tell me if I have removed items you believe should be retained? Thanks.

IiKkEe (talk) 23:42, 9 November 2014 (UTC)

To many issues in these edits [1][edit]

  1. The addition of primary sources [2] when we should be using secondary sources
  2. Dependency and tolerance is not a mild overdose
  3. Not sure why "Sources and consumption" was changed to "Amount Consumed" as it also deals with sources
  4. Many of the changes made the language more complicated. For example "antagonize adenosine receptors" replaced "counteract a substance called adenosine"

Doc James (talk · contribs · email) 03:58, 10 November 2014 (UTC)

Looking at it further. Most looks good and thus restored most of it. Doc James (talk · contribs · email) 05:37, 10 November 2014 (UTC)

Fixed citation mistakes and edited a part of the lead[edit]

I fixed some errors in the citations in the lead text, then removed the statement about caffeine not causing dehydration as it is discussed in detail in the "effects on kidneys" section. The latter was probably not a constructive edit? I would love some feedback. Hvaara TC 02:29, 17 November 2014 (UTC)

Your edits in my view are spot on.

IiKkEe (talk) 15:54, 29 November 2014 (UTC)

Section headings[edit]

We have a MOS for section headings here which states "The provisions in Article titles generally apply". The recommendations for article titles are here and include:

  • "Do not use A, An, or The as the first word". The word "on" would also be included.
  • Per WP:MEDMOS we use "other animals" or "other organisms"
  • Titles should normally be noun phrases.
  • Also per here "The title is no longer than necessary"

Doc James (talk · contribs · email) 05:37, 28 November 2014 (UTC)

The metabolite theobromine[edit]

Theobromine is identified incorrectly as a vasoconstrictor in the third paragraph of this article, when it is a vasodilator. In the separate page for theobromine, it is listed as a vasodilator. Later in the article on caffeine, it is listed as a vasodilator. I can't fix this, but someone should. — Preceding unsigned comment added by Reklaws 13 (talkcontribs) 01:43, 1 December 2014 (UTC)

Thank you for pointing out my error. Have fixed.

IiKkEe (talk) 10:51, 5 December 2014 (UTC)

Section ordering[edit]

Unless there is a good reason not to we should typically follow the order of sections at WP:MEDMOS. Thus reverted [3] Doc James (talk · contribs · email) 06:41, 10 December 2014 (UTC)

Edit Request: Change "Expresso" to "Espresso" in the fourth paragraph[edit]

Fairly sure this is a simple misspelling. (talk) 15:32, 17 December 2014 (UTC)

Yes check.svg Done Deli nk (talk) 16:39, 17 December 2014 (UTC)
I wish I could say it was a misspell. Not being a coffee drinker, when I looked up the three methods of making coffee, I actually thought the word was "expresso". So it was a misreading on my part, not a misspelling. I thought maybe it was the fastest way! I talked to the manager of a coffee house, and he said half the people who order it pronounce it "expresso". Thanks for fixing the Page. IiKkEe (talk) 07:17, 26 December 2014 (UTC)

Does caffeine not also cause the release of dopamine?[edit]

I was under the impression (And the "Health effects of caffeine page" seems to confirm) that caffeine also indirectly caused an increase in dopamine levels in the brain, which is partially responsible for the feel-good factor from drinking coffee and other energy drinks. Is the health effects page incorrect, or should this not be included in the main page as well?

It is odd that this is not signed or dated. I have never seen an entry without those identifiers. Will look into question and add to article if verifiable.
IiKkEe (talk) 13:09, 22 December 2014 (UTC)
This section was added on Dec 20 by an IP editor -- they often are not aware of how to sign and date a comment. Anyway, caffeine via its effects on adenosine probably alters nearly everything in the brain to some degree. The question is whether its effects on dopamine have drawn substantial attention in the literature. Looie496 (talk) 17:58, 23 December 2014 (UTC)


We state "It can be used to treat asthma"

This study makes no mention of its use to treat asthma.[4] It is a total of 75 people. Its use is not mentioned in treatment guidelines as far as I am aware. It is commented on as "People may need to avoid caffeine for at least four hours prior to lung function testing, as caffeine ingestion could cause misinterpretation of the results." Doc James (talk · contribs · email) 08:45, 24 December 2014 (UTC)

Nevertheless, caffeine has the same action as theophylline, a closely related molecule,and there is evidence from many studies that it similarly relaxes airways. It's not used clinically that way, but there's not much doubt that it has somewhat the same effect. See PMID 20091514. That's probably enough for a short mention in this article, so long as it doesn't suggest that doctors use caffeine routinely as a drug for asthma. SBHarris 04:00, 25 December 2014 (UTC)
Yes it can be mentioned in the body of the article. Were I was opposed to it being mentioned was in the lead. Doc James (talk · contribs · email) 09:34, 25 December 2014 (UTC)

Citation to support statements in lead request[edit]

A cup (7 ounces) of coffee contains 80–175 mg. of caffeine, depending on what "bean" (seed) is used and how it is prepared: by drip, percolation, or espresso. I always thought there were 8 ounces in a cup but coffee is often served in smaller than 8 ounces containers, expresso in thumbnail containers. Citation please. The citation for Cardiovascular disease such as coronary artery disease and stroke is less likely with 3-5 cups of coffee per day but more likely with over 5 cups per day does not state what size cup which really makes me wonder how reliable the citation is.1archie99 (talk) 18:53, 28 December 2014 (UTC)

Both good points. I remember reading somewhere that that 7 ounces was an "official" definition of a cup of coffee, and it did not reach my consciousness at that moment that that violates the standard definition of a cup as being 8 ounces. Will look into this and alter Page as needed. Also, the citation you refer to was a meta-analysis: I will look into whether it is possible to find out whether every study analyzed defined what the size of a cup was. I suspect it was based on self-reporting via subject interviews. For now, will add a cautionary "One meta-analysis concluded...", and look into it further. Thanks for raising these questions. Regards, IiKkEe (talk) 17:31, 3 January 2015 (UTC)

Weird question in the first section[edit]

The question "How much caffeine is in your daily habit?" is just sitting in the first section without any relation to the surrounding sentences. Should probably just be removed. — Preceding unsigned comment added by (talk) 16:00, 29 December 2014 (UTC)


We have a section on sources of caffeine. Products that contain caffeine are by definition sources. Synthesis of caffeine is also a source. Thus IMO these heading should go as subheadings of sources. Doc James (talk · contribs · email) 12:54, 2 January 2015 (UTC)

User:IiKkEe I would appreciate you commenting on the talk page. Coffee and tea are biological sources. We even have a see also caffeinated drink under the previous sources heading. Doc James (talk · contribs · email) 13:12, 2 January 2015 (UTC)
Good point. I have altered TOC according to your suggestion: Sources is main topic with 3 subtopics. Looks good! Regards. IiKkEe (talk) 13:53, 2 January 2015 (UTC)
Thanks :-) Doc James (talk · contribs · email) 21:00, 2 January 2015 (UTC)

I find this source confusing. It does not list what the abbreviations in the tables are for. Perhaps we need a better citation.1archie99 (talk) 22:04, 4 January 2015 (UTC)

... Erowid isn't a suitable source for any drug article. Seppi333 (Insert  | Maintained) 06:33, 5 January 2015 (UTC)
Seconded. Perhaps we should make a bot that looks for "erowid" or "sciencemadness" between <ref> tags :)
Riventree (talk) 08:26, 19 January 2015 (UTC)

Semi-protected edit request on 12 January 2015[edit]

It is found in the seeds, nuts, or leaves of a small number of plants native to South America. The most well known source of caffeine is the seed (commonly incorrectly referred to as the "bean") of the coffea arabica coffee plant.

Becky: Page is Locked so let the wiki experts deal with it. Is this really indicative of a level-4 vital article in Science for Wikipedia? If you do not understand my comments about Caffeine being a plant based xanthine alkaloid found in OLD World and NEW World plants, then let someone else read my comments and make the changes needed to keep the article somewhat factually accurate. The caffeine entry is tiresomely verbose and factually inaccurate at the same time. Why devote a paragraph to S American sources of caffeine when Coffee and Tea are number 1 and 2 sources of this alkaloid for human commerce by more than a thousand fold over all other sources of caffeine combined. Coffee bean harvest = 6-7 Bil metric tons vs Tea 5-6 Bil metric tons harvested 2012 source: Statista top coffee producers worldwide), assuming 2% w/w caffeine content in this 2012 harvest, that is more than 120 million tons of caffeine harvested as coffee beans for 2012. And drop that oddity Coffee seed used throughout the article.

-while use of the word bean to refer to the seed of the Coffea arabica plant is botanically incorrect, it is also common English usage, just as we commonly refer to a cucumber as a vegetable and not a fruit although botanically speaking it contains seeds so is a fruit.

Multiple problems. Coffea arabica natural growth range is in Yemen, Ethiopia, not a S. American native plant although widely commercially CULTIVATED in S. America, it is not native to that continent, thereby refuting statement that it is a new world alkaloid. Camellia sinensis is the black and green tea plant and is the most widely consumed source of caffeine. Please note this plant originated in China and is not cultivated or otherwise found in S. America. Coffea and Tea are the two most widely known and consumed caffeine containing plants and NEITHER is a native to S. America, so refuting the statement that the sole source of these alkaloids is S. American vegetation.

Also note that purine metabolism in man is a complex subject and many diseases can result from metabolically damaged purine pathways including gout and others(source wikipedia page on purine metabolism Symptoms can include gout, anaemia, epilepsy, delayed development, deafness, compulsive self-biting, kidney failure or stones, or loss of immunity). This is a more important link to health related issues than pointing out that the guanine and adenine purines are found in RNA, which although true is but of little significance to understanding the role caffeine and theophylline metabolism and pharmacology play when consumed on a daily basis by much of humanity. Sweedld (talk) 05:51, 12 January 2015 (UTC)

Red question icon with gradient background.svg Not done: it's not clear what changes you want to be made. Please mention the specific changes in a "change X to Y" format.  B E C K Y S A Y L E 06:03, 12 January 2015 (UTC)
Red information icon with gradient background.svg Not done: please establish a consensus for this alteration before using the {{edit semi-protected}} template. Sam Sing! 21:37, 15 January 2015 (UTC)

IUPAC name question[edit]

The IUPAC name for this looks weird to me: "1,3,7-Trimethylpurine-2,6-dione". The 7 for the third methyl and the 6 for the second dione look like they're using a different coordinate system. I had expected to find them on adjacent carbons, yet they are not. If I'm counting the carbons wrong, I'm sorry, but I thought someone should double-check this.

Riventree (talk) 05:40, 14 January 2015 (UTC)

Anyone? Bueller?

Riventree (talk) 08:32, 19 January 2015 (UTC)

Semi-protected edit request on 21 January 2015[edit]

Typo in Effects -> Kidney: "airline assengers" should probably be "airline passengers" Lancer827 (talk) 19:10, 21 January 2015 (UTC)

Yes check.svg Done Thanks for pointing that out - Arjayay (talk) 19:13, 21 January 2015 (UTC)

Caffeine article typo[edit]

Just a minor typo in the caffeine article that I want to point out. The typo is in the first paragraph of the subheading "Undesired". Below I have highlighted it in bold as it appears in the article. "n" should read "in". That is all. Thanks.

Undesired Minor undesired symptoms from caffeine ingestion not sufficiently severe to warrant a psychiatric diagnosis are common, and include mild anxiety, jitteriness, insomnia, and interference with co-ordination in athletes.[21] The caffeine-induced disorders recognized n the "The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition American Psychiatric Association (2013).[22] (DSM-5) are: caffeine-induced anxiety disorder, caffeine-induced sleep disorder, caffeine intoxication, caffeine withdrawal and caffeine-related disorder not otherwise specified.

--Wickyyutch (talk) 23:05, 23 January 2015 (UTC)

Fixed - thanks for pointing it out. Seppi333 (Insert  | Maintained) 01:18, 29 January 2015 (UTC)

Alternative to the addiction glossary template[edit]

@Doc James: I just incorporated the associated definitions/concepts from the glossary directly into the text; I actually sort of agree with you that in this particular article, the (truncated) glossary wasn't very useful. I'd like to know how do you feel about including coverage of the addiction/dependence-related concepts in articles in this manner as opposed to transcluding {{addiction glossary}} – is it preferable to you? Seppi333 (Insert  | Maintained) 01:13, 29 January 2015 (UTC)
Mildly tangential: my talk page is probably more appropriate for this discussion, but I think John Blackburne is a dick and I don't want his 2¢. Seppi333 (Insert  | Maintained) 01:15, 29 January 2015 (UTC)

I think that is reasonable if done to a limited extent. We also need to work to write in simpler language. I have simplified some. Doc James (talk · contribs · email) 01:30, 29 January 2015 (UTC)
@Doc James: There are some articles with a transcluded glossary that I think would be just as accessible if the glossary were replaced with in-text descriptions. The only two ways that I can think of doing this are parenthetical descriptions and reference group tooltips (e.g., "note"[note 1] references), both of which I used in my recent edits in this article. I know you don't like the addiction glossary, so do you have a preference for either method if I decide to replace glossary transclusions? Seppi333 (Insert  | Maintained) 03:29, 29 January 2015 (UTC)
Prefer in-text descriptions rather than notes. Many times; however, simply a wiki link is good enough. Doc James (talk · contribs · email) 06:28, 29 January 2015 (UTC)

Pharmacology section[edit]

The issue with the pharmacology content is that there are errors in pharmacodynamics and there are literally 2 different pharmacokinetics sections in the pre-revert version: -- Seppi333 (Insert  | Maintained) 13:12, 11 February 2015 (UTC)


Guaranine redirects here, but is not explained in the article. -- Beland (talk) 22:00, 13 February 2015 (UTC)

Crystal Clear action edit add.png Added to drugbox synonyms. Seppi333 (Insert  | Maintained) 19:43, 17 February 2015 (UTC)

Section on overdose[edit]

One sentence in the "Overdose" section reads "Though achieving lethal dose of caffeine is difficult with coffee, it is easily achieved with seventy 200 milligram caffeine pills."

I think this information is unnecessary and not encyclopedic, and therefore I suggest that it should be deleted. The number of coffee cups is much more relevant as a comparison and is already listed. Thoughts anyone?

(even if it stays I think "easily" should be edited out and the qualification "for a 70 kg person" should be added.)

Kmonkmon (talk) 05:50, 19 February 2015 (UTC)

I agree the whole sentence is inappropriate, so I have removed it. Deli nk (talk) 14:41, 19 February 2015 (UTC)
Spot on. IiKkEe (talk) 14:25, 22 February 2015 (UTC)

Inaccurate Half-Life[edit]

Under Pharmacokinetics, the half-life is stated as being "roughly 6 hours". It includes a reference to this page. However, the reference page states the half-life is 3-7 hours, which is a wide range, nothing like "roughly 6 hours".

I've been trying to find studies related to the half-life of caffeine in healthy adults. The only one I could find was this one which did detect and average of 5.7 hrs, which is roughly 6, but only has a sample size of 3 people. I can't find any documentation to support even a 3-7 hour half-life, much less a "roughly 6 hours".

Until better documentation can be provided, this should be changed either to match the cited page (3-7 hours) or removed entirely. — Preceding unsigned comment added by (talk) 14:08, 12 March 2015 (UTC) Fixed Seppi333 (Insert  | Maintained) 17:06, 12 March 2015 (UTC)

Thanks for your continued dedication to accuracy. IiKkEe (talk) 13:20, 15 March 2015 (UTC)

Semi-protected edit request on 18 March 2015[edit]

Third, caffeine can enhance the reward memory of pollinators such as honey bees, thus increasing the numbers of its progeny. This is very interesting, if true. I would like to see a citation. Rikki-Tikki-Tavi (talk) 16:45, 18 March 2015 (UTC)

The statement was added to both the lead and the main article in this diff by User:Jpgordon on 8 March 2013. As you can see from the diff, the statement was correctly referenced:-
Caffeine has also been found to enhance the reward memory of honeybees, improving the reproductive success of the plant.[1]
The article has been edited about 1200 times since then, the statement in the lead has been moved down, but the citation is still there (currently No 171) in this section - Arjayay (talk) 18:16, 18 March 2015 (UTC)


  1. ^ Wright, G.A. (2013). "Caffeine in Floral Nectar Enhances a Pollinator's Memory of Reward". Science (6124): 1202–1204.  Unknown parameter |vol= ignored (|volume= suggested) (help)

"Small number of plants native to South America"[edit]

In the Introduction it is stated that caffeine is contained in the parts of a small number of plants native to South America." This seems to suggest that caffeine is only found in South-American plants, and that the number of species of such plants is small. For the second claim (the small number) no evidence or citation is given. For the first claim, it is wrong, as the tea plant Camilla sinensis which is native to East Asia, also contains caffeine. (talk) 09:44, 13 April 2015 (UTC)

The 'Natural occurrence section' states it is found in about sixty plants. I don't believe this is a small number so I've altered the text accordingly. East Asian plants are now noted in the lead. Sizeofint (talk) 17:13, 13 April 2015 (UTC)

caffeine decreases heart rate?[edit]

I don't think so. agonists at the adenosine receptors reduce heart rate and are used in supraventricular tachyarrythmias by slowing conduction through the atrioventricular node. it seems at least counterintuitive and more likely flat out wrong that it "reduces" heart rate, it increases it. can this be changed or am i mistaken? — Preceding unsigned comment added by (talk) 08:36, 22 April 2015 (UTC)

The source says it promotes bradycardia and also says there are heart rate increasing effects as well. It seems reasonable that there are competing effects. I have added a sentence regarding the increase in heart rate. Sizeofint (talk) 18:04, 22 April 2015 (UTC)

Overdose caused by powered caffeine supplements[edit]

I have added some information about the overdose potential of powdered caffeine supplements, sourced to a New York Times article. (The cited source shows up as a blog, but a shorter version of this appeared in the print edition.) This seems like information that our article ought to have, given that a number of fatalities have occurred. Looie496 (talk) 13:14, 19 May 2015 (UTC)


With respect to caffeine addiction our current text appears to take one side in the debate.

  • This 2015 pyschiatry textbook descibes "continued caffeine use despite knowledge of a persistent or recurrent pyschological or physical problem caused or exacerbated by caffeine" [5]
  • This paper from 2014 discusses the controversy ""Academics and clinicians, however, have not yet reached consensus about the potential clinical importance of caffeine addiction (or ‘use disorder’1) [1]. The DSM-5 designated caffeine withdrawal as a formal disorder, an important step towards recognizing the potential to develop clinically significant problems related to caffeine use [2]. Moreover, caffeine use disorder was included in Section III (conditions for further study), acknowledging the merit of the condition while conveying the need for further research before an official designation. Of note, the World Health Organization (WHO) has long included caffeine on its list of psychostimulants that produce withdrawal or dependence disorders in the ICD-10."[6]
  • This review speaks about an effect on dopamine systems "Through these interactions, caffeine is able to directly potentiate dopamine neurotransmission, thereby modulating the rewarding and addicting properties of nervous system stimuli." [7]
  • This 2013 review states "an increasing number of clinical studies are showing that some caffeine users become dependent on the drug and are unable to reduce consumption despite knowledge of recurrent health problems associated with continued use" [8]

Now of course others do say it is not addictive. We should likely present both. Doc James (talk · contribs · email) 01:12, 11 July 2015 (UTC)

The biggest problem here is that non-research models do not define an addiction consistently or use an evidence-based definition to define that pathology. The second biggest problem is that, thanks to the file drawer effect, no one has bothered to publish a negative finding of caffeine-induced ΔFosB induction in D1-type neurons in nucleus accumbens compared to control drugs (or maybe no molecular biologist cares enough to conduct a single study to confirm a caffeine addiction model, since that finding is really all it would take). The first problem goes back to the whole diagnostic models of addiction don't have an actual pathophysiological basis or evidence to support their "labels". While I think it's perfectly fine to indicate that some literature asserts that caffeine is associated with an "addiction", it should be clear that this statement does not imply a contradiction with the research model unless the evidence for that statement is based upon the research model (e.g., any of the following would be sufficient evidence to assert that caffeine is addictive: clear reward system activation + activation of the mesolimbic pathway in particular in human neuroimaging studies, the presence of a drug/nautral reward cross-sensitization effects in animals, evidence that it is self-administrated in a manner similar to other addictive drugs in animal models, evidence of dopamine/calcium signaling in D1-type MSNs in animals, or evidence of ΔFosB induction in D1-type MSNs in animals). I just spent the past 5 hours looking for evidence of any of this and the strongest evidence I could find is that D1 receptors are activated in a part of the nucleus accumbens in animals from high-dose caffeine; however, this effect only occurs during acute use, but not chronic use, due to an adenosine A1 receptor desensitization effect which attenuates the agonist-like action on dopamine D1 receptors caused by caffeine-induced adenosine A1 receptor antagonism (in plain English: a form of drug tolerance occurs with repeated caffeine use).
I did read the paper on children that you linked above a few hours ago, but that doesn't say that it activates the reward system; the language it uses is that it modulates the rewarding properties of addictive stimuli, which need not involve the D1-type MSN pathway (it also doesn't preclude inhibitory effects by caffeine, as some other papers suggest with chronic use - mentioned in 1 of the linked PMIDs below). That modulatory effect could occur in any dopaminergic signaling pathway that interacts with the D1-type MSN pathway as a downstream effect. Some of the cell signaling literature that I read over the past few hours mentioned the a modulatory effect between caffeine and other drugs (cocaine), and suggested that it involved D2-type receptors (which it effects through adenosine A2 antagonism) and the desensitization effect between adenosine/dopamine A1 and D1 that I mentioned above (covered in PMID 18088379 PMID 17532111). It does indicate a that it isn't compulsively and increasingly self-administered like other addictive stimulants though: "Caffeine and drugs of abuse are both considered reinforcing and are both self administered in naturalistic settings and in the laboratory. In animal models of self-administration, caffeine is administered irregularly, is typically observed after prolonged caffeine exposure followed by abstinence, and is not seen under the same conditions which reliably produce cocaine or amphetamine self-administration"
The strongest clinical evidence I've found against an addiction model is this evidence of SPECT neuroimaging of the nucleus accumbens in humans and associated cell signaling evidence in animals at high doses:
  • textbook[1] cites this paper on humans[2]
The strongest nonclinical evidence that I've come across against an addiction model is that it isn't consistently self-administered like other addictive drugs in animals, it doesn't continue to produce an agonist-like effect on D1-type receptor with chronic use due to tolerance (meaning that if it is addictive, then unlike other psychostimulants, dopamine receptors don't play a significant role in producing an addiction), and there's a fairly large amount of evidence that it is markedly less rewarding in animals compared to other stimulants. The following covers the relative lack of drug reward compared to other stimulants:
This review[3] cites the following primary source[4] - these papers indicate that its (weakly) rewarding properties are not due to activation of dopamine receptors in D1-type NAcc MSNs, or in any other dopamine pathway for that matter.
TL;DR: I'm fine with indicating that some sources say that caffeine is addictive, so long as we make a clear distinction between the models/definitions which identify "addiction" using an arbitrary cluster of symptoms and the model which actually involves the use of a biomarker and signal transduction pathways to study a real disease. Seppi333 (Insert ) 04:35, 11 July 2015 (UTC)
"Real disease" is not appropriate terminology. Most of psychiatry is studied based on symptoms and signs not neurimaging and biochemistry. And we do not typically state they are not diseases. Caffeine either has no addiction or low addiction and that information is useful. The literature does not agree that ΔFosB must be present first. Doc James (talk · contribs · email) 04:45, 11 July 2015 (UTC)
When you say "the literature does not agree that ΔFosB must be present first", are you referring to the hand-wavy bullshit pushed out by diagnostic classification systems? In any event, can you show me the literature you're referring to which supports that claim? I have never read any papers asserting that. Seppi333 (Insert ) 05:03, 11 July 2015 (UTC)
Yes I am referring to the "hand-wavy bullshit" diagnostic systems that form the basis of psychiatric diagnosis. The DSM5 is an example. Mental illnesses are not diagnosed based on lab tests or medical imaging. Doc James (talk · contribs · email) 16:20, 11 July 2015 (UTC)
By the way we at Wikipedia should simply state the major positions on a topic. We are not here to advocate a single position or world view. You comments above seem to imply that the biological model of mental illness is the only one worth mentioning. It however is not. Doc James (talk · contribs · email) 16:28, 11 July 2015 (UTC)

──────────────────────────────────────────────────────────────────────────────────────────────────── it's not the only one worth mentioning IMO. All 3 models are notable, hence they should be covered. The evidence-based model is just the only correct model of an addiction, by any definition, because it's the only evidence-based model. I vocalize my opinion on talk pages, but I seldom act on my biases when I edit articles; e.g., yesterday I added coverage of the DSM-5 and ICD-10 in that section. Seppi333 (Insert ) 17:47, 11 July 2015 (UTC)

You are welcome to your opinion that the biological model is the "only correct model of an addiction". There are many forms of evidence out their. And some of the other models are based on non laboratory based evidence. Doc James (talk · contribs · email) 18:47, 11 July 2015 (UTC)
That "opinion" is me paraphrasing the National Institute of Mental Health director's statement (about all current diagnostic models of any/all mental health disorders, not just addictions), which is apparently why he supports the Research Domain Criteria system.[5]

While DSM has been described as a “Bible” for the field, it is, at best, a dictionary, creating a set of labels and defining each. The strength of each of the editions of DSM has been “reliability” – each edition has ensured that clinicians use the same terms in the same ways. The weakness is its lack of validity. Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure. In the rest of medicine, this would be equivalent to creating diagnostic systems based on the nature of chest pain or the quality of fever.

In any event, I wouldn't make an assertion like that simply based upon my perception of one model being more correct than another. That line of thinking is fairly retarded IMO. Seppi333 (Insert ) 19:12, 11 July 2015 (UTC)
I am not saying that psychiatry is not different than the rest of medicine. The majority of the clinical research done is based on the DSM and ICD diagnostic criteria. Doc James (talk · contribs · email) 19:16, 11 July 2015 (UTC)
Add: I didn't notice your first reply; my argument wasn't relevant to diagnosing addiction, rather it was about whether or not "caffeine addiction" was supported by some form of evidence w.r.t. the neuroscience (NAcc neuroimaging), psychology (self administration), molecular biology (ΔFosB), or pharmacological (dopamine/glutamate/other receptor/ion channel activation in D1-type NAcc MSNs) component of the addiction model.
FWIW, while a brain biopsy could actually be used to diagnose an addiction using the evidence-based model, I doubt anyone would opt to have a hole drilled into their skull for the sake of that particular diagnosis. That's really not even necessary to identify an addiction using this model though - anyone with a drug addiction and a working knowledge of operant conditioning (this is extensively covered in all high school/college level introductory psychology courses) should be able to recognize that their compulsion is being driven by positive reinforcement. Recognizing the difference between drug addiction and drug dependence is as simple as asking oneself whether one's drug use behavior has been associated with removing something "bad", which is negative reinforcement (i.e., drug use occurred in response to withdrawal symptoms or any other undesirable stimulus), or the addition of something "rewarding" or "approachable", which is positive reinforcement (i.e., drug use begets more drug use). There are no other possible drug-induced compulsive disorders because any compulsion is just a pathologically (positively and/or negatively) reinforced behavior; so, I really have no clue why current diagnostic models don't just follow that framework which predates both the first edition of the DSM and ICD. Seppi333 (Insert ) 19:12, 11 July 2015 (UTC)

Underlying mechanism[edit]

In the text we have some research that does not conclude their is a mechanism and other research that does. We need to balance both. Doc James (talk · contribs · email) 21:25, 22 July 2015 (UTC)

You have research saying that it modulates reward. Electrolytes modulate reward. Are sodium chloride and magnesium addictive? No. Do they affect drug reward? Yes. It is not indicative That the addiction mechanism exists. Seppi333 (Insert ) 08:58, 23 July 2015 (UTC)
It's disappointing to see an editor I respect so much ignoring WP:BRD. Looie496 (talk) 16:01, 23 July 2015 (UTC)

This review speaks about an effect on dopamine systems "Through these interactions, caffeine is able to directly potentiate dopamine neurotransmission, thereby modulating the rewarding and addicting properties of nervous system stimuli." [9]. I have not seen the same said about taking sodium chloride. We should not ignore part of the literature. Doc James (talk · contribs · email) 19:57, 23 July 2015 (UTC)

Aside from its well-known effects on sleep and arousal, which are primarily mediated by antagonism of the adenosine A1 receptor, caffeine is also known to interact with the dopamine system to exert some of its behavioral effects (Cauli and Morelli, 2005; Fredholm and Svenningsson, 2003). These actions are likely mediated through inhibition of the adenosine A2A receptor, which is primarily localized to dopamine rich areas of the brain (Fredholm, 1999). Adenosine A2A receptors are co-localized with dopamine D1 and D2 receptors (Kudlacek et al., 2003) and have been shown to form heterodimers (Fuxe et al., 2003). In addition, activation of adenosine A2A receptors decreases dopamine binding at the D2 receptor (Salim et al., 2000). Through these interactions, caffeine is able to directly potentiate dopamine neurotransmission, thereby modulating the rewarding and addicting properties of nervous system stimuli... In rats, caffeine administration leads to increased locomotor activity (Nehlig et al., 1992), which can be blocked by administration of dopamine receptor antagonists (Garrett and Holtzman, 1994); (Kuribara and Uchihashi, 1994). Caffeine can also induce rotational behavior in rats with unilateral lesions of the nigrostriatal dopamine cells in a manner that mimics dopamine (Garrett and Holtzman, 1995; Herrera-Marschitz et al., 1988). Finally, caffeine can potentiate the effects of dopamine on rotational behavior in animals with this same lesion (Jiang et al., 1993). When taken together, these studies suggest that caffeine interacts with the dopaminergic system to produce some of its behavioral effects.

Greater text Doc James (talk · contribs · email) 20:00, 23 July 2015 (UTC)

We cannot put in Wikipedia's voice stuff that is directly refuted by other high quality sources [10] Doc James (talk · contribs · email) 20:07, 23 July 2015 (UTC)
Wherein the above do you think you read a "biomolecular mechanism of addiction"? It says it affects the dopamine system, i.e., the VTA and nigrostriatal dopamine nuclei through A2A-D2 and A1A-D1 heterodimers. Not once does it suggest that it exerts chronic DA stimulation in the nacc through this effect. What you're writing in the article is WP:OR. Seppi333 (Insert ) 20:46, 23 July 2015 (UTC)
It clearly states that there are potential mechanisms by which it affect the DA system. Thus "directly potentiate dopamine neurotransmission" Doc James (talk · contribs · email)
This is a bit too complex to explain in simple terms, so I'll just elaborate on it in the pharmacodynamics section at some point. I pointed out before that chronic stimulation of A1A-D1 heterodimers produces tolerance to the effect in neurons. That's a key point, as D1-type MSNs in the NAcc shell are what mediate drug reward, and these A1A-D1 receptors (and not the A2A-D2 heterodimers) would be prevalent heterodimer in D1-type neurons. Zinc is a perfect example of something that potentiates dopamine neurontransmission without being addictive. I wrote about it a while back in dopamine transporter. In any event, I don't really care about this anymore - it's wrong and it's misleading, but it's just one article. Seppi333 (Insert ) 16:17, 26 July 2015 (UTC)