codeine LD50, celing dose & is it codeine or codeine phosphate?

[Anon54]

Firstly the LD50 800mg for an anverage non-tolerant person seems obviously incorrect as the:

The lowest reported lethal dose is 12mg/kg

im looking for the website this was quoted from but can only find a BL thread atm.
so if a normal person weighs 75kg that's 900mg. but keep in mind that was the LOWEST reported death not half the ppl who have taken that dose & it was probably a female who only weight 50kg or so or was pretty old. It doesnt make sense that the lethal dose which kills half of an overage non-tolerant person is 800mg when the lowest reported lethal dose was 12mg/kg.

Next...

just found this, the equivalence between 4 Codeine salts:

From the stronger to the weaker:
-20mg Codeine Hydrochloride = 17,1mg Codeine
-20mg Codeine Phosphate Hemihydrate = 15,6mg Codeine
-20mg Codeine Phosphate = 14,7mg Codeine
-20mg Codeine Camsilate = 11,9mg Codeine

(I found that on a very reliable site)

So does this mean u have to drink u would hve to drink 600mg of codeine phosphate to acheive the ceiling codeine 450mg dose.

Im pretty sure the ceiling dose is for codeine phosphate. but just checking

Next I wanna talk about the ceiling dose. This is quoted from wikipedia:

Pharmacology

Codeine was once considered to be a morphine prodrug, since it was thought that its analgesia was due in large part to its O-demethylation to the much more powerful opiate, morphine. However, more recent research shows that 80% of codeine is conjugated with glucuronic acid to Codeine-6-glucuronide (C6G), which is the metabolite that is most responsible for codeine's analgesia. Only 5% of the dose is O-demethylated to morphine, which in turn is immediately glucuronidated at the 3- and 6-position and excreted renally.[9][10] A portion (~ 15%) of the codeine is N-demethylized to norcodeine.[11] It is less potent than morphine and has a correspondingly lower dependence-liability than morphine.[12] Like all opioids, continued use of codeine induces physical dependence and can be psychologically addictive. However, due to its low potency, the withdrawal symptoms are relatively mild compared to closely related opioids such as hydrocodone and oxycodone. As such, codeine has a lower physical dependence liability than most other opioids.[13]

A dose of approximately 200 mg (oral) of codeine must be administered to give analgesia approximately equivalent to 30 mg (oral) of morphine (Rossi, 2004). However, codeine in general isn't used in single doses greater than 60 mg (and no more than 240 mg in 24 hours).[14][15] When analgesia beyond 60 mg of codeine is required, stronger opioids such as hydrocodone or oxycodone are utilized.[16] When used to relieve dry coughs, codeine is used in doses ranging from 5-15 mg and is usually mixed as a syrup with other drugs such as promethazine[17] which is an antihistamine with strong sedative activity (some formulations come with different types of antihistamines),[18] guaifenesin which is an expectorant,[19] and other drugs. When codeine isn't effective in relieving stronger dry coughs, then the opioid hydrocodone is used instead.

Codeine is metabolized to C6G by uridine diphosphate glucuronosyl transferase UGT2B7, and, since only about 5% of codeine is metabolized by cytochrome P450 CYP2D6, the current evidence is that codeine-6-glucuronide (C6G) is the primary active compound.[20] Claims about the supposed "ceiling effect" of codeine doses seemed to rest on the assumption that high doses of codeine saturated CYP2D6, which prevented further conversion of codeine to morphine, which is simply incorrect since we now know that codeine-6-glucuronide (C6G) is the main metabolite responsible for codeine's analgesia.[9] There is also no evidence that CYP2D6 inhibition is useful in treating codeine dependence,[21] though the metabolism of codeine to morphine (and hence further metabolism to glucuronide morphine conjugates) does have an effect on the abuse potential of codeine.[22] However, CYP2D6 has been implicated in the toxicity and death of neonates when codeine is administered to lactating mothers, particularly those with increased 2D6 activity ("ultra-rapid" metabolisers).[23][24]

So it it 5% or 10% that's converted to morphine & why doesnt it add to the abuse potential?
if there is a celiling dose does that only apply to the conversion the morphine meaning u can still up the dose for the other active metabolites?

I might add to this thread later on Im just interested in ppl helping me search on the net of the ceiling dose of codeine, not codeine phosphate. Also whether the ceiling dose is a myth & if it's true & u do go over the ceiling dose if the other active metabolites are still active atleast.

I usually take 400mg of codeine phosphate like i did this morning with some valium
anyways the other night i was really tired & had 700mg & i can tell u it felt twice as strong as 400mg it was comparable to atleast 40mg of oxy IR. I was actually getting some euphoria. Maybe next time I'll try a gram with an antihistamine ofcourse

 

[NeighborhoodThreat]

I'm going to edit the title of this post to say "LD50" and not "LD0" - I did a double-take when I first read it haha

 

[SPC123]

This is taken from the codeine product information sheet:

7.2 Toxicity

7.2.1 Human data

7.2.1.1 Adults

The adult lethal dose is 0.5 to 1.0 g (Gosselin et al., 1984). This dose may cause convulsions and unconsciousness, and death from respiratory failure may result within 4 hours. Moffat (1986) estimated the minimum lethal adult dose at 800 mg.

Serum concentrations over 5 mg/L were detected in an adult who had self-administered 900 mg of codeine intravenously; he regained consciousness only after 3 days when serum levels reached 1.3 mg/L (Huffman & Ferguson, 1975).

Drug concentrations in codeine fatalities are approximately 2.8 mg/L in blood and 103.8 mg/L in urine (Baselt & Cravey, 1989).

The development of tolerance increases the potentially toxic doses. In volunteer studies individuals could tolerate up to 240 mg by mouth, 4 times daily (Reynolds, 1982).

7.2.1.2 Children

Doses over 5 mg/kg may cause serious respiratory depression.

Children may display signs of toxicity at 1/20 th of the minimum lethal dose of 800 mg (Moffat, 1986).

A cough syrup which contained 10 mg of codeine/5 mL, produced severe poisoning after two 5 mL doses in a prematurely born 3 month old baby (Wilkes et al., 1981).

7.2.2 Relevant animal data

Codeine

LD50 (oral) rat 427 mg/kg
LD50 (intravenous) rat 75 mg/kg
LD50 (subcutaneous) rat 229 mg/kg

Codeine phosphate

LD50 (oral) rat 266 mg/kg
LD50 (intravenous) rat 54 mg/kg
LD50 (subcutaneous) rat 365 mg/kg
LD50 (intramuscular) rat 208 mg/kg

(Sax & Lewis, 1989)

7.2.3 Relevant in vitro data

No relevant data available.

 

[SPC123]

Oh, the second question about codeine phosphate and ceiling dose... There is no ceiling dose. Codeines effects are not caused primarily by conversion to morphine in the liver as was once thought. As for the difference between salts, that's probably based on molecular weight. If you are taking codeine as a pill you are already taking codeine phosphate, and so if 600mg works for you then 600mg works for you. heh. The difference between the salts would only come up if you were comparing two different preparations containing different salts. In that case you might have to adjust accordingly.

 

[effie]

Codeine's metabolism is complex. 5-10% is converted to morphine but this varies from person to person - some people lack the enzyme for this step entirely, where as others metabolise it well. As you have stated, a different metabolic pathway metabolises it to codeine-6-glucuronide, which is now thought to be responsible for at least some of codeine's opioid effects. There may be other metabolites responsible as well. Subjectively, codeine does not have a ceiling for me - 800mg gets me higher than 600mgs.

Codeine phosphate is the most common salt in the UK, I am not sure about elsewhere. Preparations should state which salt it is.

 

[Anon54]

^^my question is does the so called ceiling dose stop the conversion to atleast morphine.
i know taking larger than the ceiling dose still converts to CG6 no matter what the dose but i wanna know if the conversion to morphine atleast stops at 400-500mg

 

[SPC123]

Yes, there is a ceiling for conversion to morphine. Once you saturate the CYP2D6 liver enzyme, no more will be available for additional metabolism.

 

[Anon54]

Can anyone find any info weather the ceiling dose of codeine is referring to codeine or codeine phosphate. because if it's referring to codeine only than the ceiling dose would be 600mg instead of 450mg if 450mg is the ceiling dose according to the codeine salts table.

I have a feeling that taking 800mg of codeine would be stronger than 400mg. Im still very curious about the answer to my above post ^^

like i said before even if the conversion to morphine stops at 400mg-600mg well i says nothing about CG6 which apparently gives codeine the majority of its effects. not morphine. I think hydromorphone is another metabolite. yes u heard right. hydromorphone.

taking an antihistamine with I got a really good high the other night from 700mg. i mean it was much better than 400mg. Im curious to try over a gram as long as i have an antihistamine.

now theres alot of controversy weather the sedating AHs potentiate codeine or not. can someone enlighten me. otherwise i'll still with zyrtec or something. its suppose to be the best AH for allergies and histamine release.

c'mon. there has to be some other ppl out there that can confirm that taking over a gram of codeine is considerably stonger than it's so called ceiling dose

 

[SPC123]

Both effie and I have told you there is no ceiling. As well the wikipedia article you quoted says there is no ceiling. Also it has been discussed plenty here. The only ceiling is in the conversion to morphine, which isn't where codeine gets the majority of its kick. The morphine conversion ceiling is at about 450mg codeine phosphate, but it varies from person to person. As effie said, some can't metabolize it to morphine at all, others are very rapid metabolizers which has caused death in some cases due to OD.

As for the antihistamine, a first generation like diphenhydramine can increase CNS depression which will have an additive effect on the nod, but also the respiratory depression of opiates. The newer second generation antihistamines are less likely to have any additive effect. Technically there is no potentiation per se (you won't get more euphoria by adding either a first or second gen antihistamine) but the first generation antihistamines do induce sedation, which has a synergistic effect with codeine.

 

[Anon54]

that was a good answer spc123 thanks.
now....

Does anyone know if the ceiling dose for conversion to morphine applies to codeine or codeine phosphate? (As this would make the difference of which the ceiling dose is approx 450mg or 600mg if using codeine phosphate.)

it must be on the internet somewhere. can anyone help me look. be good to know i can get more morphine outta codeine that i didnt even know about.
i said before i have 700mg after being really tired the other night & it was like the first time ive had codeine & it was really relazing & thee effected were pretty pronounced

 

[SPC123]

Hrm, interesting. You can clearly write reasonable English, but you don't seem to read it too well.

As I said in my previous post, the morphine conversion ceiling is at about 450mg codeine phosphate, but it varies from person to person.

 

[Anon54]

^^yeah firefox has a built in spell checker
yeah im one of a kind. i actually jogged the furthest ive ever jogged without stopping to walk (18km) while i was on 8mg of xanax & 200mg (could have been 250mg or 150mg) of tramadol (I find this to be the sweet spot any more was to stimulating cuz of the SNRI effect)
if i were to drink a 6 beers i would be way more fucked up than 150mg of valium & i wouldnt even be able to run 2kg. (ppl can notice when ive only drank like 4 beers. but i feel completely straight even after mixing 80mg of oxy & 120mg of valium. (I suffer from GAD so i dont get fucked up from stuff like that. it makes me feel more normal & productive)
I took tramadol for 4.5 months. the dr was actually giving it to me for depression believe it or not. & it was the best SNRI ive ever tried. it SHOULD be prescribed as an AD. its opoid effect is weaker than codeine. pitty its prescribed for pain cause apap is probably a better pain killer.
im actually more energetic on benzos.
the only time i got tired from benzos is when i stupidly mixed xanax with alcohol.
xanax is the only one that's capable of effecting my mood noticeably.

 

[SPC123]

Agreed on the Tramadol. It's more like and AD with an added pain killer than a pain killer with an AD. Personally I never got any pain relief from Tramadol but when I'd take it I'd skip my Effexor or Cymbalta dose for the day and it seemed to work for my anxiety at least as good as those.

 

[KickStand]

I can confirm that over a gram of codeine is much stronger than what people are saying the ceiling dose is, as I took over 3,000mg, 3g, in a period of 5-10 minutes. being, I barely survived, but am currently doing research just trying to figure out what the LD50 of it is, and getting caught up in reading all the input.

 

[KickStand]

Also, I'd like to add that I'm looking for some input from people who personally have used benzos (FOR GAD OR RELATED DISAGNOSIS). I was on clonazepam for about 4 months, but my doctor took me far from serious. And what I was prescribed was barely enough to get me to leave my house, unless it was the middle of the night, even for food. I also suffer from shizoaffective disorder, and looking for what the recommended benzo to try would by? I've learned Kolonopin, valium, or diazepam, from personal experience. But, being younger, I don't want to sound like a full blown pharmacologist to my doctor, and red flag her into thinking I'm med seeking for fun, and not for actual help with coping with my mental health. Thank you.
EDIT - also, I would like to add that my doctor also took me off the clonazepam for a miniscule amount of THC in my system, and no benzos in my urine, even though I took one the day of my test. This was a red flag to me that she far from understood what someone with my diagnosis can suffer from. Let alone the fact that she herself said "it looks as if you've been given about every diagnosis in the book". But, to her, it was a flag I was selling them, instead of taking them, which I have never given away a single in my life... Why give/sell something I need?