Thoughts from the void: Cannabis and the Liver

Paracetamol poisoning is the foremost cause of acute liver failure in the Western world, and accounts for most drug overdoses in the United States, the United Kingdom, Australia, and New Zealand.

- Wikipedia

- Nature

'Alcohol abuse and high-fat diet–induced liver diseases have been the most prevalent chronic liver diseases and the leading reasons for liver transplantation around the world. Cannabidiol (CBD) is a botanical component extracted from marijuana plants without psychoactive impact. In our previous reports, we found that CBD can prevent fatty liver induced by Lieber–DeCarli ethanol diet or non-alcoholic fatty liver disease (NAFLD) induced by high-fat high-cholesterol diet. The current work is a further study on whether CBD can alleviate liver injuries induced by ethanol plus high-fat high-cholesterol diet (EHFD), which is a model simulating heavy alcohol drinkers in a Western diet. A mice liver injury model induced by EHFD for 8 weeks was applied to explore the protective properties of CBD and the underlying mechanisms. We found that CBD prevented liver steatosis and oxidative stress induced by EHFD. CBD treatment inhibited macrophage recruitment and suppressed activation of NFB–NLRP3–pyroptosis pathway in mice livers. The hepatoprotective property of CBD in the current model might be a result of inhibition of inflammation via alleviating activation of the hepatic NFB–NLRP3 inflammasome–pyroptosis pathway by CBD.'

- Frontiers in Pharmacology

The liver, one of the key organs in our bodies, removes toxins present in what we consume. The more toxins we consume, the more damage to the liver. In today's world, the amount of toxins we consume has reached mind-numbing proportions. Hence, it is no surprise that liver diseases and liver failure account for a vast number of health issues world wide.

Let us examine some of the common sources of toxins that the liver needs to contend with on a near daily basis. There are petrochemical-based chemical pesticides and fertilizers in almost all the food and water we consume. Much of our food is unhealthy trans-fat based food. Many of us consume large amounts of alcohol. Then there is the cocktail of synthetic pharmaceutical drugs that many people take daily for long periods of time, vastly reducing the health providing capacity of the liver. While many studies have been conducted that examine the toxicity of one or two toxins present in our food, medicines, or alcohol, the sheer complexity of the combinations of toxins that act on our body today is beyond the means of any regulatory body to even understand, let alone investigate. As early as in the 1960s, Rachel Carson warned us about these combinations of toxins that amplified toxicity many times over. She wrote in Silent Spring - ' A few years ago a team of Food and Drug Administration scientists discovered that when malathion and certain other organic phosphates are administered simultaneously a massive poisoning results - up to 50 times as severe as would be predicted on the basis of adding the toxicities of the two. In other words, 1/100 of the lethal dose of each compound may be fatal when the two are combined. The discovery led to the testing of other combinations. It is now known that many pairs of organic phosphate insecticides are highly dangerous, the toxicity being stepped up or 'potentiated' through the combined action. Potentiation seems to take place when one compound destroys the liver enzyme responsible for detoxifying the other. The two need not be given simultaneously. The hazard exists not only for the man who must spray this week with one insecticide and the next week with another; it exists also for the consumer of sprayed products. The common salad bowl may easily present a combination of organic phosphate insecticides. Residues well within the legally permissible limits may interact.'

Studies indicate that cannabis is good for the liver. Cannabis is known to be beneficial for non-alcoholic fatty liver disease (NAFLD), a disease which affects many people because of the widespread consumption of unhealthy fatty foods dished out by our global fast food industry. Tandfonline reports that - 'Cannabis use is associated with a reduced risk of elevated fatty liver index in HIV-HCV co-infected patients. A study published in Frontiers in Pharmacology reports that 'Alcohol abuse and high-fat diet–induced liver diseases have been the most prevalent chronic liver diseases and the leading reasons for liver transplantation around the world. Cannabidiol (CBD) is a botanical component extracted from marijuana plants without psychoactive impact. In our previous reports, we found that CBD can prevent fatty liver induced by Lieber–DeCarli ethanol diet or non-alcoholic fatty liver disease (NAFLD) induced by high-fat high-cholesterol diet. The current work is a further study on whether CBD can alleviate liver injuries induced by ethanol plus high-fat high-cholesterol diet (EHFD), which is a model simulating heavy alcohol drinkers in a Western diet. A mice liver injury model induced by EHFD for 8 weeks was applied to explore the protective properties of CBD and the underlying mechanisms. We found that CBD prevented liver steatosis and oxidative stress induced by EHFD. CBD treatment inhibited macrophage recruitment and suppressed activation of NFB–NLRP3–pyroptosis pathway in mice livers. The hepatoprotective property of CBD in the current model might be a result of inhibition of inflammation via alleviating activation of the hepatic NFB–NLRP3 inflammasome–pyroptosis pathway by CBD.' PLOSONE says - 'We found that past marijuana users had lower odds of suspected NAFLD (non-alcoholic fatty liver disease) than non-users, which suggests that previous exposure to marijuana may affect the development of NAFLD.'

Cannabis is one of the most potent medications for cancer, and this includes liver cancer. Wiley Online Library reports the use of hemp seed flour and its benefits in treating liver cancer - 'Hemp peptides (HP) generated by controlled hydrolysis of hemp proteins have a number of health benefits and are of pharmaceutical value. In the present study, we produce small molecular weight HP from hemp seed and investigate its anticancer properties in Hep3B human liver cancer cells. We demonstrate that HP treatment increased apoptosis, reduced cell viability, and reduced cell migration in Hep3B human liver cancer cells without affecting the normal liver cell line L02. We correlate these phenotypes with increased cellular ROS levels, upregulation of cleaved caspase 3 and Bad, and downregulation of antiapoptotic Bcl-2. HP treatment led to increased Akt and GSK-3ß phosphorylation, with subsequent downregulation of ß-catenin, suggesting ß-catenin signaling modulation as a critical mechanism by which HP exhibits anticancer properties. Our findings suggest HP are of potential therapeutic interest for liver cancer treatment.'

Looking at it from another perspective, alcohol is one of the primary causes of liver disease. Liver cirrhosis, caused by alcohol abuse is wide spread, and ever increasing. Where cannabis has been legalized, it is growing in popularity, with many consumers preferring cannabis over alcohol. Even people who prefer alcohol over cannabis, say that consuming cannabis brings down the amount of alcohol that they would otherwise consume, often quite significantly. These instances where cannabis is substituting alcohol, or reducing alcohol intake, can be seen as ways in which liver health can be improved across individuals through the harm reduction alternative that cannabis presents over alcohol. Science Direct reports that - 'In summary, medicinal cannabis is associated with improved patient and hospital outcomes in cirrhotics'. The same applies to tobacco, as well as the illegal synthetic drugs heroin, cocaine, methamphetamine, etc,. Studies that specifically study if cannabis damages the liver have shown that it does not seem to directly cause any damage to it.

Then there are the synthetic pharmaceutical drugs. Especially in older populations, prolonged usage of synthetic pharmaceutical drugs on a daily basis, for the treatment of high blood pressure, diabetes, pain, nausea, insomnia, cancer, indigestion, fevers, etc., takes a heavy toll on the liver. Wikipedia says that - 'Paracetamol poisoning is the foremost cause of acute liver failure in the Western world, and accounts for most drug overdoses in the United States, the United Kingdom, Australia, and New Zealand.' Cannabis as an analgesic, sedative, anti-inflammatory, anti-nausea drug, as well as its anti-carcinogenic properties, ability to keep diabetes and obesity in check, appetite building abilities and ability to improve digestive health means that a vast array of toxic synthetic pharma drugs can be replaced thus vastly improving liver health. NORML reports that - 'Investigators concluded: “In this large-sample study, self-dosing [with] CBD was not associated with an increased prevalence of elevation of LT [liver tests] or low levels of TT [total testosterone] in men. Furthermore, CBD administration decreased DD [daytime drowsiness] and was associated with a lower prevalence of low testosterone levels in older men as compared to age-adjusted population norms. … [I]n those over 45 years of age, the prevalence of type 2 diabetes was significantly lower than that of the general population.”' Many older persons in places that have legalized cannabis for medical and/or recreational use, are switching from prescription pharmaceutical drugs to cannabis for their medication. Cannabis has been approved for the treatment of more than 30 medical conditions in US states where medical cannabis has been legalized.

Worldwide, the deaths due to alcohol, chronic pharmaceutical drug usage, as well as non-alcohol related fatty liver diseases runs in huge numbers. Most people who would prefer to use cannabis instead of alcohol, synthetic pharma drugs, or junk fatty food, do not have a choice as cannabis is prohibited and inaccessible, whereas alcohol, synthetic pharma drugs and fatty foods are freely available the world over to people of all age groups. The legalization of cannabis worldwide for adult recreational use should be one of the worldwide strategies to combat and reduce liver disease since it is extremely easy to implement and very affordable. It is important for health organizations and policy makers to recognize this and make the necessary changes to cannabis laws. This will of course mean taking a stance that the alcohol industry, pharmaceutical industry, medical industry, petrochemical based chemical pesticide and fertilizer industry, food and beverage industries, and other big businesses opposed to cannabis may not be very happy with.

The following list of articles taken from various media speak about the above subject. Words in italics are the thoughts of yours truly at the time of reading the article.

'Researchers affiliated with the University of Chicago and with Tarleton University in Texas assessed the daily use of CBD in a cohort of over 1,000 adults. Most of the study’s participants reported having consumed full-spectrum CBD tinctures for at least one year.

Investigators concluded: “In this large-sample study, self-dosing [with] CBD was not associated with an increased prevalence of elevation of LT [liver tests] or low levels of TT [total testosterone] in men. Furthermore, CBD administration decreased DD [daytime drowsiness] and was associated with a lower prevalence of low testosterone levels in older men as compared to age-adjusted population norms. … [I]n those over 45 years of age, the prevalence of type 2 diabetes was significantly lower than that of the general population.”

Several population-based studies have reported that cannabis consumers typically possess lower BMI and other favorable indices related to diabetic control. Observational studies have also shown that the past use of cannabis is significantly associated with lower odds of diabetes in adults.

Data published in 2021 similarly determined that the repeated use of oral CBD products is not associated with liver abnormalities, such as the elevated production of the enzyme alanine transaminase.'

https://norml.org/news/2023/04/06/study-daily-use-of-cbd-tinctures-associated-with-decreased-daytime-drowsiness-no-increased-risk-of-liver-disease/

Smoke that joint (the natural one with the right balance of THC and CBD not synthetic skunk with predominantly THC) when you drink to protect your liver..

"In conclusion, we demonstrate that CBD treatment significantly attenuates liver injury induced by chronic plus binge alcohol in a mouse model and oxidative burst in human neutrophils. CBD ameliorates alcohol-induced liver injury by attenuating inflammatory response involving E-selectin expression and neutrophil recruitment, and consequent oxidative/nitrative stress, in addition to attenuation of the alcohol-induced hepatic metabolic dysregulation and steatosis. These beneficial effects, coupled with the proven safety of CBD in human clinical trials and its current orphan drug approval by FDA for various indications suggest that it may have therapeutic potential in liver disease associated with inflammation, oxidative stress, metabolic dysregulation and steatosis."

https://www.nature.com/articles/s41598-017-10924-8

'Results: Among the 3706 patients in the study population, 50.8% had central obesity, 34.7% overweight, and 14.4% obesity. After multivariable adjustment, current cannabis use was associated with a 59% lower risk of central obesity compared with no lifetime use (adjusted odds ratio [95% CI]: 0.41 [0.24 to 0.70]). It was also associated with a 54% and 84% lower risk of overweight (adjusted relative risk ratio [95% CI]: 0.46 [0.27 to 0.76]) and obesity (0.16 [0.04 to 0.67]), respectively.

Conclusions: Cannabis use was associated with lower risks of overweight and obesity in patients with HBV chronic infection. Future studies should test whether these potential benefits of cannabis and cannabinoid use translate into reduced liver disease progression in this high-risk population.'

https://www.liebertpub.com/doi/10.1089/can.2021.0094

NSAIDs for inflammation such as aspirin, ibuprofen, naproxen increase risk of a range of gastrointestinal (GI) problems, kidney disease and adverse cardiovascular events. Large doses of NSAIDs significantly suppress the production of immune cells. By inhibiting physiological COX activity, all NSAIDs increase the risk of kidney disease and through a related mechanism, heart attack.

Higher doses of analgesics like paracetamol may lead to toxicity, including liver failure. Paracetamol poisoning is the foremost cause of acute liver failure in the Western world, and accounts for most drug overdoses in the United States, the United Kingdom, Australia, and New Zealand. There is a consistent association of increased mortality as well as cardiovascular (stroke, myocardial infarction), gastrointestinal (ulcers, bleeding) and renal adverse effects with taking higher dose. Acetaminophen(paracetamol) treats pain mainly by blocking COX-2 and inhibiting endocannabinoid reuptake almost exclusively within the brain, but not much in the rest of the body.

Besides this, prolonged use of all opioids and NSAIDs cause multi-organ failure.

Chronic consumption of paracetamol may result in a drop in hemoglobin level indicating possible gastrointestinal bleeding and abnormal liver function tests. There is a consistent association of increased mortality as well as cardiovascular (stroke, myocardial infarction), gastrointestinal (ulcers, bleeding) and renal adverse effects with taking higher dose of paracetamol. The drug may also increase the risk of developing hypertension.

The recommended maximum daily dose for an adult is three to four grams. Higher doses may lead to toxicity, including liver failure. Paracetamol poisoning is the foremost cause of acute liver failure in the Western world, and accounts for most drug overdoses in the United States, the United Kingdom, Australia, and New Zealand.

Source Wikipedia

'Hemp peptides (HP) generated by controlled hydrolysis of hemp proteins have a number of health benefits and are of pharmaceutical value. In the present study, we produce small molecular weight HP from hemp seed and investigate its anticancer properties in Hep3B human liver cancer cells. We demonstrate that HP treatment increased apoptosis, reduced cell viability, and reduced cell migration in Hep3B human liver cancer cells without affecting the normal liver cell line L02. We correlate these phenotypes with increased cellular ROS levels, upregulation of cleaved caspase 3 and Bad, and downregulation of antiapoptotic Bcl-2. HP treatment led to increased Akt and GSK-3ß phosphorylation, with subsequent downregulation of ß-catenin, suggesting ß-catenin signaling modulation as a critical mechanism by which HP exhibits anticancer properties. Our findings suggest HP are of potential therapeutic interest for liver cancer treatment.'

https://onlinelibrary.wiley.com/doi/10.1002/fsn3.1976

'Cannabis use is associated with a reduced risk of elevated fatty liver index in HIV-HCV co-infected patients. Further research is needed to confirm whether and how cannabinoids may inhibit the development of hepatic steatosis or other metabolic disorders in high-risk populations.'

https://www.tandfonline.com/doi/abs/10.1080/14787210.2021.1884545?journalCode=ierz20

'Results: As a result, body weight gain, epididymal, and perirenal adipose tissue decreased in the CSSF (Cannabis sativa seed Flour) group in both doses (100 mg/kg and 200 mg/kg) compared to the HCD. CSSF lowered serum glucose level elevated by HCD. For lipid profiles, total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, and triglycerides (TG) significantly decreased in the CSSF group. The histopathological results of this study showed a regenerative effect of CSSF on the kidney and liver tissues.

Conclusion: It is concluded from the present study that CSSF can be used as a natural anti-obesity agent.'

https://www.researchgate.net/profile/Bouarfa_Mouna2/publication/345396297_ANTI-OBESITY_EFFECT_OF_CANNABIS_SATIVA_SEED_FLOUR_FROM_KHLALFA_OF_TAOUNATE_REGION_NORTHERN_OF_MOROCCO_IN_HIGH_CALORIC_DIET-INDUCED_OBESE_MICE/links/5fa6f00092851cc2869d76ec/ANTI-OBESITY-EFFECT-OF-CANNABIS-SATIVA-SEED-FLOUR-FROM-KHLALFA-OF-TAOUNATE-REGION-NORTHERN-OF-MOROCCO-IN-HIGH-CALORIC-DIET-INDUCED-OBESE-MICE.pdf

'Conclusion
In summary, medicinal cannabis is associated with improved patient and hospital outcomes in cirrhotics, but yields mixed results in the reduction of hospital admission for hepatic decompensation, specifically those with hepatic encephalopathy. Improvement in outcomes is noted after the legalization of cannabis, when patients are more likely to be taking consistent, regulated doses. While an association in improved short-term outcomes is demonstrated, the long term effects of cannabis use and subsequent complications in transplant patients remain unclear at this time. Additional research in the form of prospective trials should be performed to further clarify the effect of medicinal cannabis on liver disease prior to the acceptance of this as an appropriate intervention.'

https://www.sciencedirect.com/science/article/pii/S1665268120302052?via%3Dihub

'Hepatitis C-infected subjects who use cannabis possess a lower risk of diabetes, according to data published in the Journal of Viral Hepatitis.

A team of French investigators assessed the relationship between cannabis consumption and diabetes prevalence in a nationally representative sample of over 10,000 subjects with hepatitis C. Because chronic hepatitis C virus (HCV) infection is a risk factor of insulin resistance, HCV-infected patients are at a higher risk of developing diabetes than those in the general population.'

https://norml.org/news/2020/08/27/study-cannabis-use-associated-with-reduced-rates-of-diabetes-in-patients-with-hepatitis-c

'Chronic hepatitis C virus (HCV) infection is a risk factor of insulin resistance, and HCV-infected patients are at a high risk of developing diabetes. In the general population, research has shown the potential benefit of cannabis use for the prevention of diabetes and related metabolic disorders. We aimed to test whether cannabis use is associated with a lower risk of diabetes in chronic HCV-infected patients...In this large cross-sectional study of chronic HCV-infected patients, cannabis use was associated with a lower risk of diabetes independently of clinical and socio-behavioral factors. Further studies are needed to elucidate a potential causal link and shed light on cannabis compounds and mechanisms involved in this relationship.'

https://pubmed.ncbi.nlm.nih.gov/32810343/

'The full scope of the dangerous interaction of chemicals is as yet little known, but disturbing findings now come regularly from scientific laboratories. Among this is the discovery that that the toxicity of an organic phosphate can be increased by a second agent that is not necessarily an insecticide. For example, one of the plasticizing agents may act even more dangerously than another insecticide to make malathion more dangerous. Again, this is because it inhibits the liver enzyme that would normally 'draw the teeth' of the poisonous insecticide.

What of other chemicals in the normal human environment? What, in particular, of drugs? A bare beginning has been made on this subject, but already it is known that some organic phosphates (parathion and malathion) increase the toxicity of some drugs used as muscle relaxants, and that several others (again including malathion) markedly increase the sleeping time of barbiturates.'
- Silent Spring, Rachel Carson, 1962

"In conclusion, we demonstrate that CBD treatment significantly attenuates liver injury induced by chronic plus binge alcohol in a mouse model and oxidative burst in human neutrophils. CBD ameliorates alcohol-induced liver injury by attenuating inflammatory response involving E-selectin expression and neutrophil recruitment, and consequent oxidative/nitrative stress, in addition to attenuation of the alcohol-induced hepatic metabolic dysregulation and steatosis. These beneficial effects, coupled with the proven safety of CBD in human clinical trials and its current orphan drug approval by FDA for various indications suggest that it may have therapeutic potential in liver disease associated with inflammation, oxidative stress, metabolic dysregulation and steatosis."
https://www.nature.com/articles/s41598-017-10924-8

'Overall, pre-transplant marijuana use, past or current, does not appear to impact liver transplant outcomes; however, tobacco smoking remains detrimental.'
https://aasldpubs.onlinelibrary.wiley.com/doi/abs/10.1002/lt.25417

We found that past marijuana users had lower odds of suspected NAFLD (non-alcoholic fatty liver disease) than non-users, which suggests that previous exposure to marijuana may affect the development of NAFLD.

Against previous background of plausible harms from marijuana, metabolic risk estimates from current data suggest a protective effect. Recent studies report that marijuana use is associated with decreased risk of metabolic abnormalities such as obesity, diabetes, and metabolic syndrome.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186702

'Constituents of cannabis, such as cannabidiol and delta9-tetrahydrocannabinol, have shown anti-inflammatory, antioxidant, and hepatoprotective effects both in in vitro and clinical studies, and appear to have potential in the symptom management and treatment of various liver diseases that were previously considered difficult to manage conservatively.'
https://journals.lww.com/eurojgh/Abstract/publishahead/Cannabis_in_liver_disorders___a_friend_or_a_foe_.97980.aspx

'Our novel study to the best of our knowledge represents the largest population-based study to assess the effect of cannabis use on CLD associated with HCV infection. Our observations suggest cannabis use might have a positive impact in alleviating complications of portal hypertension, liver cancer and disease outcomes among HCV infected individuals. These novel findings require additional prospective and translational molecular research studies to decipher which specific active components of cannabis impact liver disease development during chronic HCV infection.'
https://www.hindawi.com/journals/cjgh/aip/9430953/

'Unfortunately for all of us, opportunities for this sort of thing to happen are legion. A few years ago a team of Food and Drug Administration scientists discovered that when malathion and certain other organic phosphates are administered simultaneously a massive poisoning results - up to 50 times as severe as would be predicted on the basis of adding the toxicities of the two. In other words, 1/100 of the lethal dose of each compound may be fatal when the two are combined.

The discovery led to the testing of other combinations. It is now known that many pairs of organic phosphate insecticides are highly dangerous, the toxicity being stepped up or 'potentiated' through the combined action. Potentiation seems to take place when one compound destroys the liver enzyme responsible for detoxifying the other. The two need not be given simultaneously. The hazard exists not only for the man who must spray this week with one insecticide and the next week with another; it exists also for the consumer of sprayed products. The common salad bowl may easily present a combination of organic phosphate insecticides. Residues well within the legally permissible limits may interact.'

- Silent Spring, Rachel Carson, 1962

'Marijuana use did not increase the prevalence or progression of hepatic fibrosis in HCV and HCV–HIV-coinfected patients. On the contrary, we noted a reduction in the prevalence of NAFLD (nonalcoholic fatty liver disease) in marijuana users. Future studies are needed to further understand the therapeutic impact of cannabidiol-based formulations in the management of NAFLD.'
https://journals.lww.com/eurojgh/Abstract/publishahead/Marijuana_is_not_associated_with_progression_of.97965.aspx

'We found that past marijuana users had lower odds of suspected NAFLD (non-alcoholic fatty liver disease) than non-users, which suggests that previous exposure to marijuana may affect the development of NAFLD.'
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186702

'Compared with those without medical cannabis recommendations, cannabis users with medical cannabis recommendations had 0.59 times fewer drinks/day, 0.44 times fewer occasions drinking 5+, and 0.78 times the average maximum number of drinks in one day (all ps < .05).'
https://www.ncbi.nlm.nih.gov/pubmed/30573025?dopt=Abstract

'Malathion, another of the organic phosphates, is almost as familiar to the public as DDT, being widely used by gardeners, in household insecticides, in mosquito spraying, and in such blanket attacks on insects as the spraying of nearly a million acres of Florida communities for the Mediterranean fruit fly. It is considered the least toxic of this group of chemicals and many people assume they may use it freely and without fear of harm. Commercial advertising encourages this comfortable attitude.

The alleged 'safety' of malathion rests on rather precarious ground, although - as often happens - this was not discovered until the chemical had been in use for several years. Malathion is 'safe' only because the mammalian liver, an organ with extraordinary protective powers, renders it relatively harmless. The detoxification is accomplished by one of the enzymes of the liver. If, however, something destroys this enzyme or interferes with its action, the person exposed to malathion receives the full force of the poison.'
- Silent Spring, Rachel Carson, 1962

'There are differences between how THC and CBD are absorbed orally than when inhaled. “The way the circulation works, the first place [ingested cannabis] is going to go to is the liver: it’s called first pass effect,” explains Dr. Carolina Landolt, rheumatologist at the Summertree Medical Clinic.

When smoked or vaporized, cannabinoids directly enter the bloodstream through the lungs. When ingested, THC and CBD pass through the liver and are metabolized by enzymes before entering the bloodstream. “The liver is what breaks down a lot of other medications,” said Landolt. “There’s something called the hepatic metabolism.”'
https://www.leafly.com/news/health/considerations-before-ingesting-edibles

'The fisheries of fresh and salt water are a resource of great importance, involving the interests and the welfare of a very large number of people. That they are now seriously threatened by the chemicals entering our waters can no longer be doubted. If we could divert to constructive research even a small fraction of the money spent each year on the development of even more toxic sprays, we could find ways to use less dangerous materials and to keep poisons out of our waterways. When will the public become sufficiently aware of the facts to demand such action? - Silent Spring, Rachel Carson, 1962

'This system, however - deliberately poisoning our food, then policing the result - is too reminiscent of Lewis Carroll's White Knight who thought of 'a plan to dye one's whiskers green, and always use so large a fan that they could not be seen.' The ultimate answer is to use less toxic chemicals so that the public hazard from their misuse is greatly reduced.' - Silent Spring, Rachel Carson, 1962

'In short the Department of Agriculture embarked on its program without even elementary investigation of what was already known about the chemical to be used - or if it investigated, it ignored the findings. It must also have failed to do the preliminary research to discover the minimum amount of the chemical that would accomplish its purpose. After three years of heavy dosages, it abruptly reduced the rate of application of heptachlor from 2 pounds to 1 and 1/4 pounds per acre in 1959; later on to 1/2 pound per acre, applied in two treatments of 1/4 pound each, 3 to 6 months apart. An official of the Department explained that 'an aggressive methods improvement program' showed the lower rate to be effective. Had this information been acquired before the program was launched, a vast amount of damage could have been avoided and the taxpayers could have been saved a great deal of money.' - Silent Spring, Rachel Carson, 1962

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