Diazepam and other benzoes shown to be mutagens; cause for concern?

[deruyityn]

If they are so widely prescribed, and in the case of diazepam, has been since the 60s, does that mean the issue must not be that much of a problem since if it were there would be a cancer epidemic now from the millions of users who have taken them since the 60s?

Quote:

Mutagenic activity of diazepam evaluated by in vivo cytogenetic tests. Abstract BACKGROUND: Diazepam, one of the benzodiazepine group of tranquilizers, is used as an adjunctive drug for sedation and for relief of anxiety in the treatment of epilepsy. Suspicion has been aroused of a possible mutagenic and teratogenic effect of this drug, thus the potential for cancer development. METHODS: To analyze the mutagenic effect of diazepam, the micronuclei and sister chromatid exchange (SCE) tests were performed by in vivo techniques in the bone marrow of Balb-C mice after intraperitoneal drug administration. Sixty mice, 30 males and 30 females, were classified as negative control (n = 12), positive control (n = 12), and three groups were treated with diazepam (n = 36). All groups were matched by sex, and each mouse received a single intraperitoneal injection. Negative control group was injected with physiological saline, positive control group with mitomycin-C at a dose of 0.5 mg/kg of body weight. Treated groups received diazepam, one at 0.1, the other at 0.2, and the last, at 0.4 mg/kg. RESULTS: The results showed a significant increase in the frequency of micronucleated polychromatic erythrocytes at all doses tested for whole population in relation to negative control. The polychromatic/normochromatic erythrocyte ratio showed a significant decrease at doses of 0.1 and 0.4 mg/kg in relation to negative control. The frequency of SCE was significantly higher at doses of 0.2 and 0.4 mg/kg in relation to negative control, the male mice being those affected. CONCLUSIONS: It is concluded that diazepam showed mutagenic and genotoxic effects on bone marrow cells of mice and that it might represent a human health risk.

Quote:

Genetic toxicology of four commonly used benzodiazepines: a review. Abstract Benzodiazepines are a group of drugs which have been extensively used for their activities as an anti-anxiety, sedative, muscle relaxant and anti-convulsant. Benzodiazepines at present are the most commonly prescribed drugs. Some of these drugs are teratogenic and also carcinogenic in experimental animals. The wide human exposure to this group of drugs throughout the world is of great concern for human health. In the present review, we have attempted to evaluate and update the mutagenic and genotoxic effects of four of the most commonly used benzodiazepines, i.e., chlordiazepoxide (CDZ), diazepam (DZ), nitrazepam (NZ) and oxazepam (OZ) based on available literature.

Regarding increased micronuclei, I read the wiki and got the general idea, does it mean that once those micronuclei are hanging around in your system are they like the seeds of cancer which will never go away or can your body clear them out to a certain extent?

 

[Product]

Wow, this post blows my mind. I have taken Valium, Xanax, and so on. If this is the case, It really worries me because ive been on xanax for 4-5 years and i hope that it doesn't hurt me with cancer in the long run. thanks for this post. I am just glad im not prescribed Val's and instead prescribed Xanax (cant be better im assuming). But to answer your final question i hope it does not linger in your system for the sake of your health. I hope all goes well. From: Product.

 

[deruyityn]

Well I don't take them regularly thankfully .

But as you say such information could certainly effect further usage. Which is why I was eager to put it out there for further discussion.

So I would like to get more info on this micronuclei stuff, and whether it does clear out; from what I read so far it seems like bad bad news.

 

[sekio]

doi:10.1089/gtmb.2008.0116 has soem info that apparently diazepam messes with human lymphocytes inducing sister chromatid exchanges.

does it mean that once those micronuclei are hanging around in your system are they like the seeds of cancer

I think it's the diazepam, not the micronuclei.

Does this mean that if you take diazepam you're doomed to die from cancer? Probably not. A certain amount of genetic damage is tolerated and amy in fact be neccesary for life.

 

[Speed King]

Can you list a link or specific source for this information. I know it says wiki, but that doesn’t necessarily mean wikipedia. Don't want to search for hours looking this up.

 

[sekio]

you don't have to "search for hours", google the titles of the studies?

it's not like research is that hard in this day and age, i mean, you don't even have to go digging in library stacks any more.

 

[Speed King]

Thank's for the pointing out the ease of research.

 

[deruyityn]

I think it's the diazepam, not the micronuclei.

How do you mean? As I read it the ingestion creates/increases micronuclei.

Have any epidemiological studies been done as to the long term effects since they have a good 50-60 year + of data since benzoes first came on the market.

Like I say there are so many millions of people that use it that I imagine serious effects would have presented themselves by now no?

 

[LearntYoung]

This is from a 1998 article, bit outdated

 

[deruyityn]

This is from a 1998 article, bit outdated

So something ceases to be true as soon as a few years pass?

Do cigarettes no longer cause cancer either since they found that out in the early part of the last century.

Sound logic there.

 

[dopamimetic]

Does anybody know if this is related to the carcinogenic effects of the Z-drugs? Are in the end all of the GABA-A positive allosteric modulators more or less mutagenic? (If I remember it correctly, with the Z-drugs it has been speculated whether it's a direct effect / structurally related or from a general dampening of the immune system, opening doors for unwanted things- but this would be more infections than cancer, or?)

Ouch. Even when there are so many people, also elderly, taking these benzos daily for years without getting cancer. But then tell me one again that using arylcyclohexylamines against depression is 'taking incalculable risks'...!

 

[sekio]

Studies in rats, mice, and Salmonella sp. show that if diazepam is a carcinogen (it is not considered to be one), it's incredibly weak and would require the ingestion of multiple grams per kilogram of body mass on a routine basis.
[ref]

And yeah, like you said, it's been in usage for a looong time now. Technically every drug that is prescribed in the US is in a "phase 4" trial, the technical term for "the FDA still pays attention to weird effects like higher chances of cancer in those taking it".

So this is a case of "may interact with the genome on some level, but is not neccesarily damaging".

 

[paranoid android]

Me and my doctor where recently talking about this due to the fact that i have been on about 6mg's of Clonazepam a day for about a decade. He said given how long these drugs have been prescribed and how widely they are prescribed someone surely would have noticed a distinct link between Benzodiazepines and cancer if there was one. Plus since i smoke about a pack of Cigarettes a day Benzos are really one of the least likely things to cause cancer.

 

[LearntYoung]

So something ceases to be true as soon as a few years pass?

Do cigarettes no longer cause cancer either since they found that out in the early part of the last century.

Sound logic there.

Are they slowly eliminating cigarettes out of the accepted and legal phase? Yes. Are they doing so with benzodiazepines? No. There's a reason for it. One of the findings has been contradicted.

 

[Xzbtya]

Studies in rats, mice, and Salmonella sp. show that if diazepam is a carcinogen (it is not considered to be one), it's incredibly weak and would require the ingestion of multiple grams per kilogram of body mass on a routine basis.
[ref]

And yeah, like you said, it's been in usage for a looong time now. Technically every drug that is prescribed in the US is in a "phase 4" trial, the technical term for "the FDA still pays attention to weird effects like higher chances of cancer in those taking it".

So this is a case of "may interact with the genome on some level, but is not neccesarily damaging".

Having read through these types of studies numerous time, giving mice or rats enough of any drug will produce some sort of carcinogenic effect. Like you said, lots of things interact with the genome every day and cancerous cells are produced and destroyed in the body every day through apoptosis. Its the ones that don't that end up being the issue (obviously) and that's the real mechanism that should be being investigated by people. This was more than likely a case of "Hey I really need to get something published".

 

[Memantine]

I believe only oxazepam is a "possible" carcinogen. And oxazepam is a metabolite of diazepam and temazepam.

 

[Incunabula]

For christ sake, even bacon is a carcinogen now. Being alive is a dangerous thing, you can die from it.