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Cannabis Compound Said To "Halt Cancer"

Posted by kdawson on Tue Nov 20, 2007 07:58 AM
from the afraid-of-what-we-represent dept.
h.ross.perot informs us of research out of the California Pacific Medical Center Research Institute suggesting that a compound found in cannabis may stop breast cancer from metastasizing. Cannabidiol, or CBD, could develop into a non-toxic alternative to chemotherapy some years down the road, if animal and human trials bear out its effectiveness. The article notes that smoking cannabis will not deliver significant quantities of CBD.
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  • by mrjb (547783) on Tuesday November 20 2007, @08:00AM (#21419039)
    Maybe this [smoothhigh.co.uk] will do the trick then.
        • by holysin (549880) on Tuesday November 20 2007, @10:21AM (#21420599) Homepage
          It's just really hard to estimate doseage. As it all depends on the quality of the herb, the effects the user wants, etc. Personally I'm a fan of chronic olive oil (VICS [thevics.com] has a good recipe). Basically, experiment with what you have and see what works for you. Some people swear by using "vapour poo" for making olive oil/butter. Others grow their own and chop up the male plants for making butter/oil.

          Generally speaking, don't just sprinkle herb on your food unless you have a high tolerance for food that tastes strongly of pot (yuck). Making olive oil (or corn oil, whatever oil you want really) is the easiest method for most people to have some good thc laced treats, and it makes some damn good enchiladas/pasta :) Butter is a bit harder to make (majorly labour intensive) but you can end up with a killer batch of brownies that last a long time due to the potency (the freezer is your friend). One note, eating cannabis is very different from smoking it, you can easily eat too much, and sadly, you can't un-eat it. So start slow, and give it an hr or two before trying another piece of cake/whatever. Note: I'm not advocating you break the law of wherever you live, I'm just giving suggestions so if you do ingest cannabis you'll do so with your eyes open, and maybe won't run into oncoming traffic.

          If you're really experimental there are ways to infuse thc into alchohal for use at clubs and places where using "breath drops" would be acceptable. But that is even more of a headache than making butter. Search for "cannabis tincture" if you're so inclined. If you live in SoCal and are a MMJ patient you can buy cannabis oil, cannabis tincture, and other assorted ready made foods from your local MMJ dispensary. YMMV.
          • I do advocate smoking ganja.

            BTW, THC is much more soluble in fat than in EtOH. This Erowid article [erowid.org] has good information on chemically extracting THC. I don't advocate that unless you know what the fuck you are doing. You know, something more than HS chemistry. Acetone is poisonous.

            Anyway, I really do advocate that you (yes, you) smoke the sensimillia till yu eyes turn red certain. A fi bun mi sensi!
  • The article notes that smoking cannabis will not deliver significant quantities of CBD
    There you've ruined my ingenious punchline.
    • All it says is that you need to use more and stronger canabis.
        • by Anonymous Coward on Tuesday November 20 2007, @09:35AM (#21419985)
          here [swissinfo.ch] is some new data on cannabis related emphysema:

          The tests were unable to show which substances had caused the lung damage, but cannabis fibres were found in the tissue samples and can constitute the starting point for inflammation.(...) There were also no cases of emphysema in the control group, even though it included 74 regular smokers.

          • Bad study (Score:4, Insightful)

            by bpkiwi (1190575) on Tuesday November 20 2007, @03:36PM (#21425969)
            Have you read that study? They took 17 people with collapsed lungs or emphysema, all of whom smoked on average six joints a day over a period of more than eight years and also consumed cigarettes on a daily basis for nearly 12 years. They then said that tests were unable to show which substances had caused the lung damage.
        • by caffeinemessiah (918089) on Tuesday November 20 2007, @10:41AM (#21420885) Journal

          No worries, you will still get emphysema which is almost as unpleasant and tourchers you for longer. By the way, this explains why Cannabis has a ratio of emphysema to lung cancer that is quite different from cigarettes which is something that has been suspected for a while (hard to get good data because people generally smoke both).

          This is righteous bullshit. Allow me to elaborate:

          • Cannabis studies have a history of being stooped in politics, alternating between pro and con. If you're talking about the ratio of emphysema to lung cancer, I'd be interested in how the population was sampled. Was it a random sampling of cannabis users? Was it people who showed up in a clinic with emphysema, and were then entered into the study? Consider the next point.
          • Suppose there are two equal-sized populations of cigarette smokers and cannabis smokers. Each population has exactly the same emphysema/lung cancer ratio. We'll assume that cannabis smokers don't smoke cigarettes for now, although if they did it would only make the study more dubious. If everyone reported accurately if there were a cannabis smoker or just cigarette smoker, we'd find approximately equal ratios. On the other hand, if some healthy cannabis smokers, out of fear of law enforcement or privacy reasons, reported themselves as cigarette smokers, the emphysema/lung cancer ratio in the sampled cannabis 'group' would appear to be much higher. I'd also doubt non-cannabis smokers reporting themselves as cannabis smokers.
          • The final point. You don't actually need to smoke cannabis, thereby removing all risk of emphysema and associated respiratory disorders. THC is fat-soluble, and so can be cooked or baked into anything that requires the use of fat or oil. Popular recipes include pasta and confectioneries, and I'm pretty sure none of those give you cancer. If you do choose to smoke cannabis, a vaporizer is often advocated in the Netherlands. I don't know what the health risks are, but they certainly seem to have a lot lower concentration of particulate matter (hence the name).
          • Re: (Score:3, Insightful)

            It's good to see so many people have done research to make sure that pot smokers can get high safely. Now if only we had time for those poor sods with *real* diseases...
            • by caffeinemessiah (918089) on Tuesday November 20 2007, @02:09PM (#21424379) Journal

              You just fired off a bunch of things that COULD be wrong with the studies. That's like me saying that your parents could have been the ones who assasinated JFK. Its not really based in fact

              In science, if something *plausible* COULD be wrong with a study, it deserves to be analyzed before the study is assumed to be rigorous. This also applies to studies on the other side, i.e. the ones which claim marijuana cures death and stops global warming. In your analogy, you can't possibly give me any plausible evidence that my parents killed JFK. I pointed out a rather common methodological flaw (check the literature) with using self-reporting in smoked marijuana studies.

              Look, I agree that people CAN cook cannabis and they SHOULD use a vaporizer if they want to smoke it. However plenty of people do smoke it in bowls. In fact I'd bet money that In the United States, most people smoke it without using a vaporizer. Even more people smoke it then cook it.

              Would you say there's an honest culture of information about cannabis in the United States? I wouldn't. I don't know if you're being sarcastic or not, but I'd be all for a campaign to educate people on the safe use of marijuana. In the Netherlands, most coffee shops stock a vaporizer and a lot of Dutch people I've talked to would prefer to use a vaporizer. Ultimately, people will probably still smoke cannabis because of the social bonding aspect, but they should be educated about the alternatives. After that, it's a choice you make for yourself.

              In case you were NOT being sarcastic, here are some websites that advocate safe marijuana use:
              safer choice [saferchoice.org], regulate [regulatemarijuana.org], marijuana uses [marijuana-uses.com] (not really an organization, but an emeritus harvard professor who's studying the positive uses of marijuana)

            • Re: (Score:3, Informative)

              For a drug to treat cancer it must be at toxic to at least cancer cells. And if a drug is used to treat cancer it is by definition chemotherapy.

              Not true. It doesn't have to be toxic, it just has to prevent the cancer from spreading for long enough for other treatments to do the killing.

              THC, for instance, has been demonstrated to prevent cancer cells from creating new blood vessels to feed themselves. Metastasizing isn't even growth, it's migration, where a cancer colony sends out cells to other parts of t
  • I volunteer (Score:5, Funny)

    by pklinken (773410) on Tuesday November 20 2007, @08:02AM (#21419063)
    Human trials!

    Too bad I don't have breasts ...
    • Re:I volunteer (Score:5, Informative)

      by sm62704 (957197) on Tuesday November 20 2007, @09:37AM (#21420019) Journal
      Google has failed me this morning. I remember reading in New Scientist (whose anti-drug propaganda I ranted about a couple of years ago) [mcgrew.info] that they did a study of baby boomers; the generation that started smoking ganja in their youth and are now geezers. They were trying to prove, as all these government studies from all the world's governments do, that pot is bad for you. The object of the study was to look at cancer rates in potheads vs non-potheads. They were certain that reefer causes cancer because there are carcinogens in it.

      What they found instead was that (IIRC) potsmokers who did not smoke tobacco had a 10% lower incidence of all cancers than nonsmokers. More striking, however, was the difference between cigarette smokers who also smoked hemp and buttheads who only smoked butts. The cancer incidence of those who smoked both marijuana and tobacco was half the number of those who only smoked cigarettes.

      So your study is done, the results are that cannibis prevents cancer.

      As I said, a google search for "marijuana boomer study" yielded only one hit (he he he said), to a site I'd never heard of. So I searched New Scientist and found some other interesting tidbits:
      Cannabis compound reduces skin allergies in mice [newscientist.com]
      Cannabis compound slows lung cancer in mice [newscientist.com]
      Cannabis extract shrinks brain tumours [newscientist.com]
      Cannabis can help MS sufferers [newscientist.com]
      Cannabis can protect the brain from damage from stroke [newscientist.com]

      So we have a substance that is non-addictive (habit forming but not addictive), non-lethal, fights cancer, helps MS sufferers, is the best anti-nausea agent known, stimulates appetite, yet it is illegal. So why is it illegal?

      Because it makes you lazy and forgetful, and what's worse for our corporate overlords, makes you think. You can forget about any substance that makes you think ever being legalized; thinking is the VERY last thing your government (wherever you may live) wants you to to do.

      Yes, I'm a geezer. No, I wasn't in the study. Yes, I've smoked dope. [kuro5hin.org]

      -mcgrew
      • Re:I volunteer (Score:5, Interesting)

        by twistedsymphony (956982) on Tuesday November 20 2007, @09:49AM (#21420201) Homepage

        So why is it illegal?
        The official reason why it was banned in the first place: [African American]s' satanic music, jazz, and swing, result from marijuana use. This marijuana causes white women to seek sexual relations with Negroes, entertainers and any others [wikipedia.org].

        ...Something tells me that excuse wouldn't hold up today.
        • The history channel has has on a good show about drugs. Their reason, while similar to the one from wikipedia, had to do with anti-mexicanism at the time. The mexicans were here working in the US (much like now) and smoking lots of pot. Well they blamed any bad mexican behavior on the pot and then eventually outlawed it. BTW, if you ever see the history of drugs on the history channel it's a great show. IIRC, cocaine was originally outlawed because of "crazed blacks" and your description.
              • I read a proposal at one point that said all laws would have a natural time limit based on the % of of the vote. That would not only require past laws to be re-evaluated but also give congress something useful to do instead of passing new law after new law just to keep themselves busy.

                It was something along the lines of 51% of the vote=2 years before re-eval, 65% of the vote =4 years before re-eval, 80% of the vote = 8 years before re-eval, unanimous=permanent unless some new law overturns it.
        • Re: (Score:3, Informative)

          Official reasons that sound like crap usually are crap. And crap is generally used to hide economic motives. I, for one, think it's really coincidental that marijuana was prohibited in the entire US in exactly the same year that the decorticator for hemp was invented - a device that sped up the processing of hemp a tenfold, thereby making it far superior to cotton for textile and far superior to woodpulp for paper.

          http://www.jackherer.com/popmech.html [jackherer.com]
      • Re:I volunteer (Score:5, Insightful)

        by Cajun Hell (725246) on Tuesday November 20 2007, @12:15PM (#21422499) Homepage Journal

        So why is it illegal?

        People will quote the special interests against it, but there's a bigger reason that dominates them all, and makes racism and the chemical company lobby fade into the background. That reason is: attitude about government.

        Americans still overwhelmingly think the purpose of government is to implement whatever good ideas come up, and solve our problems. That's why this particular article is political: people are talking about the presence of useful compounds inside the plant. People talk about how harmful it is, how harmful it isn't, etc, as though the utility of the plant, or its side-effects, actually matter.

        As long as you engage in discussion of the merits (or lack of merits) of the plant, in the context of whether or not it should be illegal, you lose. There will always be arguments against anything, whether its heroin or hydrogen hydroxide, that the material is harmful to the user. There's nothing on this earth that is provably safe.

        The debate should always be about who owns people, not the decisions that the owner makes. Is it the government's decision on what people should ingest, or the people's decision? People, stop citing the plant's advantages, and start talking about the real political issues. Don't ask "why is this illegal?" Ask, "How is does local gardening fall under the intent of the 'interstate commerce' clause?" Ask, "Why do voters in Texas have a say in Vermont citizens' health?"

      • Re:I volunteer (Score:4, Insightful)

        by Plutonite (999141) on Tuesday November 20 2007, @09:31AM (#21419937)

        I thik there was an episode of "Oz" where a mobster got breast cancer, and tried to keep it secret.
        That's friggin hilarious. Even more hilarious is the fact that you're using the mobster who got breast cancer in Oz as some sort of reference.

        I *heart* slashdot.
  • But... (Score:5, Funny)

    by Anonymous Coward on Tuesday November 20 2007, @08:03AM (#21419071)
    Have you ever stopped breast cancer from metastasizing...on weed???
  • Woo! Woo! Get on to the bandwagon fast. Kabul is going to be the Cancer Cure Capital of the World!!!
  • Um, using a cannabis-derived compound isn't an alternative to chemotherapy, it is chemotherapy [wikipedia.org], which literally means "treatment with chemicals." Just because a bunch of people have screwed up the meaning of the word like they did with 'hacker' vs. 'cracker', that doesn't make it right.

    • Re:Chemotherapy (Score:5, Informative)

      by Lloyd_Bryant (73136) on Tuesday November 20 2007, @08:27AM (#21419279)

      Um, using a cannabis-derived compound isn't an alternative to chemotherapy, it is chemotherapy, which literally means "treatment with chemicals." Just because a bunch of people have screwed up the meaning of the word like they did with 'hacker' vs. 'cracker', that doesn't make it right.
      Um, perhaps you should actually read the Wiki article, specifically the part about modern day usage meaning treatments using cytotoxic substances.

      By your definition, ANY drug-based treatment is "chemotherapy", while the general usage (including usage by the medical profession) refers to this specific class of drug treatments.

      The hacker/cracker screwup was a result of outsiders misinterpreting geek jargon. The meaning change of chemotherapy originated from the professionals *within* the medical field. Two entirely different issues.
  • by sherriw (794536) on Tuesday November 20 2007, @08:13AM (#21419161)
    My mom had breast cancer several years ago. The treatments are just horrible, but I'm thankful she's still with us. It seems however that once a year we hear about some potential breakthrough or another. Well, with the truckloads of donations going to 'breast cancer research', I'm getting a little sick of hearing about 'potential' breakthroughs. I want something we can start using right now. It's hard to be patient when people you care about are sick or dying. I hope some of these possibilities pan out soon.
    • Re: (Score:3, Insightful)

      The problem with what you hear is that 99% of these potentials fail some point along the way. Either they're too toxic in the human body, or not effective enough against cancers for their toxicity, or just not competitive with existing treatments(no niche to exploit).

      I heard once...

      It's very easy to kill cancer cultures in a dish. Matter of fact, much of the time the trick is keeping them alive.

      It's an entirely different matter to do it in the body.

      Makes sense to me. A little splash of bleach and that pe

    • Estimating Risk (Score:5, Insightful)

      by PIPBoy3000 (619296) on Tuesday November 20 2007, @08:58AM (#21419547)
      Basically everyone I've known who has died, has died of cancer. It drives me crazy that we're spending hundreds of billions of dollars to avenge the deaths of 3,000 people, while under four billion is spent on fighting cancer, which kills half a million people each year. It reminds me again how terrible people are at estimating risk [schneier.com].

      References:
      NCI budget [cancer.gov]
      Cost of Iraq war [msn.com]
      cancer deaths [forbes.com]
      • we could spend that money on education too, or healthcare for the middle class

        we don't. we think it's valuable to our security to get rid of saddam hussein and democratize iraq. is that right? is it wrong? certainly, it could be the stupidest thing the usa has ever done

        but therefore, you need to defeat the money spent on that operation based on that rationale alone, within the confines of the merits or lack thereof of that operation by itself

        but comparing the money spent on that to money to be spent on some
              • with all the waste a government system obviously means, it is still far better than an equally wasteful system, that only cares about profit, that doesn't insure everyone

                i am not stumping for universal healthcare as some sort of nirvana, i am saying it is the less worse of two evils

                all of the negatives you can throw at me about universl ahealthcare, i agree with you 100%

                and it's still better than what we have now
              • I tell you what, I'll vote for a socialized health-care system if you volunteer you and yours to always lose the treatment lotto for cancer patients.

                And how is that different than the current system? You are already "playing the lotto" that your HMO won't declare your cancer "a pre-existing condition" or the treatment that you need is "experimental".

                What good is a cure for cancer if your HMO won't pay for it and you can't afford it?

  • CBD (Score:5, Informative)

    by spazmolytic666 (549909) on Tuesday November 20 2007, @08:18AM (#21419195) Journal
    The article notes that smoking cannabis will not deliver significant quantities of CBD.

    Actually, you can get CBD from smoking cannabis, but most cannabis is optimized for the best high (most abount of THC).

    CBD is one of the two lesser psychoactive chemicals (CBN is the other) that THC breaks down to in the late life cycle of the cannabis plant. Most growers harvest when the plant is "ripe", when it has the most THC. If you wait a week or two after the peek harvest time, the THC will break down and have a higher percentage of CBD and CBN and a lesser percentage of THC.
  • Brain tumors, too (Score:5, Informative)

    by Scrameustache (459504) on Tuesday November 20 2007, @08:23AM (#21419237) Homepage Journal
    http://norml.org/index.cfm?Group_ID=6947 [norml.org]

    THC selectively decreases the proliferation of malignant cells and induces cell death in human GBM cell lines. Healthy cells in the study were unaffected by THC administration.

    Separate preclinical studies indicate that cannabinoids and endocannabinoids can stave off tumor progression and trigger cell death in other cancer cell lines, including breast carcinoma, prostate carcinoma, colectoral carcinoma, skin carcinoma, and pancreatic adenocarcinoma.
  • ohru. (Score:4, Funny)

    by drix (4602) on Tuesday November 20 2007, @08:24AM (#21419247) Homepage

    The article notes that smoking cannabis will not deliver significant quantities of CBD.
    Sounds like a challenge to me!

    --Cancer free since 1998.
  • by Junior J. Junior III (192702) on Tuesday November 20 2007, @08:42AM (#21419387) Homepage
    ... but it does get the cancer to mellow out and be cool and stop causing so many hassles.
  • by spectrokid (660550) on Tuesday November 20 2007, @08:42AM (#21419393) Homepage
    Cuban medicine has shown for years that mother nature provides all kinds of wonderful molecules for free. They even have a bio-version of Viagra. Problem is these things are not patentable. So a large medicinal company has to spend tons of money on trials and FDA approval, and the very next day half a dozen competitors can throw a "me too" version on the market without incurring those costs. Sorry for you if you have cancer, but don't hold your breath 'cause it ain't gonna happen.
    • look at taxol and the yew tree for breast cancer treatment

      what the pharma companies do is substitute a methyl group for a hydrogen somewhere, or mix the chemical with some other chemical, patent that, and call it vastly superior, even if it isn't

      just look at celebrex: it's just an NSAID. nothing that aspirin can't handle. but they modified the chemical slightly, patent that, the effects are slightly different, but the slight effects are relabelled massive and brilliant improvements in function, and you have
  • This study is quite obviously flawed. Cannabis, otherwise known as marijuana, is bad. It's just bad! Taking it is wrong! People who take marijuana are bad people.

    Marijuana cannot be used to stop cancer. Stopping cancer is good, and marijuana is bad; therefore marijuana cannot logically be used to stop cancer. It's a basic fact!

    Why are you promoting the use of this evil drug, when you know that it can only be used for bad not for good. Do you want children to smoke marijuana, and destroy their lives? Do you want them to commit murder and rape so they can feed their evil habits? Do you want them to think that bad things are good? That's just wrong!

    We need to defend our children and society from the scourge of drugs. Breast cancer is bad, but that does not mean we should use evil to fight it. Instead, I propose setting up a breast cancer awareness group where people can discuss how breast cancer has affected their lives. That's a real solution to this problem.

    We can hold meetings at the local bar, so people have a few drinks and a smoke afterwards.
  • by colourmyeyes (1028804) on Tuesday November 20 2007, @09:11AM (#21419685) Homepage
    Ah, I know my day is off to a good start when I the first tags that I see are "potheads" and "boobies."

    Smashing.
  • drugsarebad (Score:4, Funny)

    by bigsexyjoe (581721) on Tuesday November 20 2007, @09:17AM (#21419747)
    It would be better that we all died of cancer than ingested something derived from cannabis.
  • by BytePusher (209961) on Tuesday November 20 2007, @09:32AM (#21419945) Homepage

    Just a thought, but I wonder if it could be possible that humans are genetically disposed to loving cannabis? It has been a commonly used plant for a long, long time. The seeds have been used as food and seem to have the perfect balance of essential fats. Now it seems we've discovered it suppresses certain forms of common cancer. Certainly, there are people who abuse themselves with it, but maybe we want them to. In my experience, the people who overuse pot are the same people who have trouble restraining many of their impulses. One of my room mates seemed to actually became a human when he was high... otherwise he was intolerable. By taking these people's pot away, we don't make them better people, just angrier.

    Another thing to note is that, while cannabis is illegal now, if we are genetically disposed to love it, cannabis will win the legal battle eventually no matter what the logic for it's legalization is. People legalize things they love and suppress the things they hate ignoring all logic in the process. You can't fight your nature. :)

  • by kcdoodle (754976) on Tuesday November 20 2007, @09:57AM (#21420291)
    I used to think that it would be legal by the time I was thirty.

    I high school (circa 1977), at least 70% of the kids smoked regularly or occasionally.
    25% didn't care if anyone smoked it and only 5% were against it. (These numbers are all personal observation so take with a grain of salt.) The point is -- I was a geek, I occasionally did imbibe, I didn't care if anyone else smoked all day long.

    Fast forward a couple decades. Those same pot-heads are now republicans and swear that they never, ever smoked pot. In fact they believe it is immoral to do so. And anyone who does should be thrown in jail. Amazing how raising kids changes your perspective.

    I believe that alcohol is far worse than pot to your body and to society as a whole. BTW, I quit smoking pot years ago, but that doesn't mean you should.
    • by Scrameustache (459504) on Tuesday November 20 2007, @08:30AM (#21419293) Homepage Journal

      That weed is a magic cure for "X". A while back they where offering it for glaucoma then M.S. and now cancer. In the end it's still used mostly for getting high.
      I don't care what you do, but until there is a viable way to get all the positive herbal healing from it, don't sound the "smoke weed to cure [blah]" horns.
      It was listed by Hypocrates as a cure-all.
      It was prescribed by Queen Victoria's doctor.

      It was then made illegal under false pretenses, kept illegal "pending review", and kept illegal under new false pretenses once the scientific review proved it shouldn't be illegal. No honest, free-thinking, educated person wants this to be illegal.
        • by misanthrope101 (253915) on Tuesday November 20 2007, @11:41AM (#21421865)

          I'm just tired of it being presented as a snake oil cure for everything when it isn't.
          I'm tired of people claiming that medical marijuana proponents claim that marijuana cures everything, when in fact they don't. You're making a sensible, supportable position--that marijuana can help with a wide variety of conditions--and turning it into a caricature, then objecting to the caricature you've made as if it's the position people actually hold.

          Cue the tin foil hats about how this is a conspiracy from the government/Big Pharms.
          If people are working in concert to do something they shouldn't be doing, that meets the textbook definition of a conspiracy. Government used fraudulent data and scare tactics to ban marijuana, and "Big Pharma" supports them in this--that isn't "tin foil hat" material. You're caricaturing a reasonable position, one backed up by well-documented facts, and then spewing your contemptuous bile at your own caricature, once again pretending that it's the position people actually take.
    • Re: (Score:3, Insightful)

      I can't think of a single reason why it should be a crime to grow & smoke.

      You probably don't have a vested interest in tobacco production, pharmaceutical research, nutritional supplements, petroleum production/distribution, cloth manufacture... etc.

      A recent scientific study proved that it is not a so-called "gateway drug" that leads to e.g. heroin abuse.

      There you go, bringing your silly "facts" into the argument again. It's bad! End of discussion.

      George Washington grew it on his farm, what could be m

      • Re: (Score:3, Insightful)

        Problem is, almost no studies are done on this particular subject...good luck getting government funding to do so.

        Common sense states that your average pot smoker smokes a lot less pot than your average cigarette smoker smokes cigarettes, so there's a starting point. Further, a LOT of chemicals are used in the manufacture of your typical cigarette.

        There are a ton of starting points for reasonable research to be done, but alas, it won't be any time soon. Without doing research unfortunately, we simply can no