HEALTH A-Z & MARIJUANA NEWS

Cannabis and its components THC and CBD have a very low toxicity to humans.  The standard measure of toxicity is called the LD50

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Cannabis and its components THC and CBD have a very low toxicity to humans.  The standard measure of toxicity is called the LD50

Cannabis and its components THC and CBD have a very low toxicity to humans.  The standard measure of toxicity is called the LD50.

 

LD50 is an abbreviation for "lethal dose, 50%".   The value of LD50 for a substance is the dose required to kill half the members of a tested population. LD50 figures are used as a general indicator of a substance's toxicity. The lower the LD50, the more toxic the substance.  For example, a substance with an LD50 of 1 gram is less toxic than another with an LD50 of 1 mg.

 

THC, CBD and the cannabinoids are roughly 1 gram per Kilogram in rats. In a human, with body weight of 75 Kilogram (165lbs) the toxic dose - if humans respond similarly to rats - puts a toxic dose in the order of 75 grams.  

 

LD50 WEED

 

It should be noted that a lethal dose of THC has never been documented in humans.

 

THC, CBD and other cannabis components have extremely high LD50 ratings as compared to many other common drugs.  Particularly disturbing are the most common usage of some very toxic chemicals like sodium fluoride, which is meant to shore up fluoride supplies, however, this chemical is associated with a myriad of widespread toxic effects.  Interesting LD50 findings are that the opium derivative fentanyl is more toxic than both plutonium and sodium cyanide by weight.

 

LD50 OF COMMON DRUGS AND POISONS

Sodium chloride (table salt) rat, oral 3,000 mg/kg

Delta-9-tetrahydrocannabinol (THC) Synthetic  + Polysorbate 80 rat, oral 1,270 mg/kg

Cannabidiol (CBD) rat, oral[citation needed] 980 mg/kg

Psilocybin (from magic mushrooms) mouse, oral 280 mg/kg

Ketamine rat, intraperitoneal 229 mg/kg

Caffeine rat, oral 192 mg/kg

Cocaine mouse, oral 96 mg/kg

Methamphetamine rat, intraperitoneal 57 mg/kg
Sodium fluoride rat, oral 52 mg/kg

Heroin (diamorphine) mouse, intravenous 21.8 mg/kg

Nicotine human, oral mice, oral     6.5–13.0 mg/kg

Sodium cyanide rat, oral 6.4 mg/kg

Plutonium dog, intravenous 320 µg/kg

Fentanyl monkey 300 µg/kg


 


Substance      Reckoned Safety Ratio (Reddit Scientist)
----------------------------------------------------------------------------------------------------------------

 

Vitamin A      9637    percent mice oral:human oral 15 mg
LSD             4816    percent rodents iv:human oral 0.25 mg,averaged
5-MeO-DMT   958    percent mice intraperitoneal:human parenteral 6 mg
Psilocybin      641    percent rodents iv:human oral 16 mg,averaged
THC             420    percent rats inhaled:human smoked 5 mg
Aspirin         199    percent rodents oral:human oral 325 mg,averaged
DMT              91    percent mice intramuscular:human intramuscular 60 mg
Caffeine         84    percent rodents oral:human oral 150 mg,averaged
Acetaminophen    34    percent mice oral:human oral 500 mg
Nicotine         21    percent mice iv:human smoked 0.7 mg
VX  percent Nerve Gas    0    percent just a hunch

 

The higher the "Safety Ratio" is, the less toxic the drug is at normal dosages.
 

lethal dose of weed seems impossible

 

The so called "Safety Ratio" is based on the somewhat dubious assumption that humans have  the same LD50 as the lab animal in question; for the amounts to kill can vary up to an order of magnitude (10x) between say a mouse and a rabbit..   The assumption is that the margin of safety for a drug is proportional to the number of doses (common) a person would have to take in order to have a 50% chance of dropping dead, as if they were themselves a giant rodent.  
 

This "safety ratio" is roughly equivalent to the pharmacological measure known as the Therapeutic Index, which is a measure of the toxicity of a drug relative to its usual therapeutic dose.

Another useful as a point of reference is the uncritical.NIOSH Registry of Toxic Effects of Chemical Substances also lists most published LD50 measurements.


 

LD50 THC CBD


 

DISCUSSIONS ABOUT LD50

 

kissI get that the author used quite well known toxins, but I would love to have the real toxic stuff on it.

kissBotulinum toxins are in the range of 1 nanogram/Kilogram, which is 2 000 000 times more toxic than strychnine.

kissThese are all natural and isolated in the 19th century, but yes, I agree too

kissIt looks like the author was only including small organic molecules. Most of the other really toxic things are proteins....and inorganic crap

kissI was a bit upset botulinum toxin wasn't mentioned, but I might be a bit biased here; see username.

kissIt's the most potent by at least an order of magnitude. It's just a protein, not small molecule, so it gets excluded by some pedantic natural product chemists.

kissMuscarine comes to mind too, from poisonous mushrooms.

kissWhich, unlike botulinum toxin, is actually a small molecule like the rest of these.

kissWell yes, it just said natural so I just went all the way with the example.

kiss"Can't wait to inject some of that shit in my face"


frownWhat about aflatoxin?

frownThis is not accurate, at minimum for nicotine. It says the numbers are all in milligrams/Kilogram, and then gives nicotine a value of 50. From https://www.news-medical.net/health/Nicotine-Toxicology.aspx

frownNicotine is a highly toxic chemical. While in rats, a dose of 50 milligrams per Kilogram is lethal, in mice the median lethal dose is around 3 milligrams per Kilogram weight. In humans, the median lethal dose is 0.5 to 1.0 milligrams/Kilogram or around 40 to 60 milligrams in an average human.

frownThe number given should be 0.5milligrams or 1.0 milligrams.

frownYeah, this chart is definitely not accurate for humans. The opioid dosages are about 150-200 x higher than the lethal dose for an opioid-naive person.

frownThe chart says rats or mice.

frownhmmm.....the more you know. I guess I should just avoid nicotine all together.

frownI am sure most of these are inaccurate...or at best just good estimates. I think we all know that animal studies are not perfectly reflective of behavior in humans. However, many times they give us a good estimate. Alternatively, human trials to determine LD50s are frowned upon currently.

frownSeems like they took the rat LD50 by mistake

frownIt's rat/mice LD50. Say so on the blurb at the top. Doesn't say human anywhere.

frownI've always been interested in the chemistry and biological pathways of poisons and toxins. My parents would say i'm going to kill myself by extracting nicotine from chewing tobacco, or scopolamine from my neighbors angels trumpet. In fact, when I started my major in chemistry I hoped to get a job related to this field in a research or military environment.

frownScopolamine from my neighbors angels trumpet

frownWhat on earth are you going to do with that?

frown"Yeah, I just casually extracted one of the most potent date rape drugs from my neighbor's garden. Oh no, I'm just applying it transdermally for seasickness, I swear."

frownNeeds more marine biotoxins. Here, have some 0.3 milligrams/Kilogram tetrodotoxin

frownSaxitoxin is around 4-10 ug/Kilogram. much scarier.

coolMy postdoc was developing a method for measuring that stuff :/ Edit: It's always super-fun when your analyte is a scheduled substance due to chemical weapons treaties.

coolHuh? We just extract it all ourselves, standards aren't easy to come by. I saw the bottle we have of solid stx the other day. About 1.5 inches in diameter, 5 inches tall, half full of saxitoxin. Hah, enough to kill all of the US quite easily i bet. I'm just finishing up a new way to screen samples for it + congeners.

coolSo you're telling me I can switch out my usual two cups of coffee for about 3 and a half cups of opium every morning??

coolPro-med just now sent me an email on a current story with a natural poison in it:

lethal dose of poison
 

PLANT POISON ASSASSINATION - UK: 2012, SUSPECTED

Police are combing the guest records of one of the world's most famous and expensive hotels in search of the alleged assassin who poisoned a Russian financier.

Alexander Perepilichnyy, a businessman who had turned supergrass [informer], died at his home in Surrey on the day he returned from a secretive trip to Paris.

British detectives had ruled out foul play, but -- to their embarrassment -- French investigators have taken up the case. They believe Mr Perepilichnyy, 44, can have been poisoned in Paris up to 48 hours before his death.

A post mortem examination found traces of Gelsemium elegans, a slow-acting poisonous plant said to be favoured by Russian and Chinese assassins, in his stomach. Police have now established Mr Perepilichnyy checked into the prestigious Bristol Hotel in Paris for 3 nights before his death. Police are now examining the Bristol's records to see who else was staying there when Mr Perepilichnyy was in Paris. He died on 10 Nov 2012, at his rented home on the high security St George's Hill estate in Weybridge, Surrey.

It is understood French officials have also made a request to British police to secure his mobile phone records for the period up to and during his stay in the French capital.  Mr Perepilichnyy, a father of 2, came to the UK in 2010, apparently in fear of his life, and brought with him a series of damning documents that exposed a massive fraud perpetrated in Moscow.

On the day of his death, he had complained to his wife he was feeling ill after arriving at his home and had gone for a jog to shake off the effects. He then collapsed and died. Despite serious concerns about his death, Surrey police ruled out murder in June 2013, despite not being able to determine the cause of death!!

The examination showing traces of Gelsemium were only found by a specialist plant expert at Kew Gardens, carrying out tests on behalf of the victim's life insurance company. An inquest in May 2015 was postponed and is due to resume in September 2015.

Concerns over the man's death were first raised by Bill Browder, an Anglo-American financier. Hermitage Capital, which Mr Browder founded and which now operates from London, had its Moscow branch raided by police in 2007 and it is alleged USD 230 million worth (GBP 148 million) of assets was stolen from the fund. Sergei Magnitsky, a lawyer working for Mr Bowder who exposed corruption at senior levels, was subsequently arrested in Moscow and beaten to death in a prison cell in November 2009.

Eight months later, Mr Browder approached [the Hermitage Capital financier's] lawyers with documents that claimed tax officials in Moscow had gone on a multi-million-pound spending spree on kickbacks earned from the Hermitage fraud.

 

"It beggars belief that the British police continue to refuse to reopen the investigation, given the evidence he could have been poisoned and given that French police have now opened their own murder investigation. What are they waiting for?" - Mr Browder


It is understood Mr Perepilichnyy booked 2 hotel rooms in Paris; one at the Bristol and another at an as yet unknown 3-star hotel. One possibility is he stayed at the cheaper hotel and paid for a representative of the Russian gang to stay at the Bristol in an attempt to broker a peace deal that would keep the gang from going after him. Surrey police declined to comment.

Gelsemium is a plant. Some people call it "woodbine", which can be confusing because American ivy and honeysuckle are also known as "woodbine." If you want gelsemium, look for its scientific name, which is Gelsemium sempervirens, Gelsemium nitidum, or Bignonia sempervirens.

Despite serious safety concerns, the root and underground stem (rhizome) of gelsemium are used to make medicine. Gelsemium is used as a painkiller for migraine headaches and for face pain caused by certain facial nerves (trigeminal neuralgia). It is also used for asthma and other breathing problems.

Morphine (an by extension codeine, which is a prodrug of Morphine) doesn't really work this way. In the presence of pain, extreme amounts can be administered. Alternatively, an opioid naive patient could die from a very small dose.

 

LD50 CBD


coolIf you have a group of genetically identical animals and a certain dose of poison kills half of them, why do the members of the other half not die?

coolActually, they aren't genetically identical. Not all lab rats (or other animals) have exactly the same DNA. Similar, yes, but they are not identical clones. And since they are not all identical, small variations in metabolism or weight can make the difference between very sick and dead.

coolIt's like alcohol in humans. One person can have three drinks and feel nothing, while another has the same amount and is very tipsy or drunk.

coolOK. Suppose you had a cloned strain of laboratory animals reared identically and of identical weight. Would it be possible to find an LD50 using these animals or could you only get LD0 and LD100?

coolRandom mutation, epigenetics, environmental factors, and statistical and quantum mechanics prevent the existence of truly identical individuals.

coolWouldn't using identical animals always be a flaw, since you risk them being resistant or weaker to a certain compound and then ending up with a skewed dosage.

coolThe other answer was quite frankly not very good. They are right that in our tests, the lab rats are closely related (more so than human siblings), but not actually clones. However, even if we did make perfect clones and treated them as similarly as we possibly could, they would not all die if given the LD50.

surpriseThe reason for the variance in otherwise perfectly identical animals is random chance. In chemistry, a reaction can happen when two potentially reactive molecules (i.e. an acid and a base) collide in the proper orientation to cause a chemical reaction and have enough energy to react. There is a caveat though: just because they CAN react does not mean they will every single time. There is a probability that they will instead bounce off. I won't get into all the details, but know that quantum mechanics allows us to calculate these probabilities with great accuracy.

surpriseNow back to the animal scale. Toxins are deadly because they react with the molecules that the animal is composed of, but the body has a number of defense mechanisms to protect against these. Some are targeted and break down specific molecules or types of molecules. Others are simply alternate, less critical targets that the toxin can go for.

surpriseSo some animals will be less "lucky" and have the more necessary parts of their body impaired by the toxin before they can break it down, whereas other more "lucky" animals will scrape by due to the toxin either taking longer to affect its target (and allowing them to survive with reduced functionality for a time), due to the toxin being degraded, or due to the toxin affecting non-life-threatening molecules.

LD50 CBD


surpriseSo THC is obviously too dangerous to be on the chart. I'm guessing a -0.3

surprise30 milligrams/Kilogram if administered intravenously, which puts it slightly below nicotine, but this chart is somewhat useless as it doesn't have any info on the route of administration.

surpriseI probably don't drink more than 192 milligrams caffeine in a day. So glad to know I'd have to guzzle down more than a double shot / Kilogram at Starbucks to get there.

surprise192 milligrams/Kilogram though, so you would need around 15,000milligrams (or 15g) for the average human.

surpriseY'all need to cross-post this to data is beautiful. I like how it clearly explains what an LD50 is.

 

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FURTHER READING

 

Inhalation, parenteral and oral LD50 values of Δ9-tetrahydrocannabinol in Fischer rats

 

Inhalation, parenteral and oral LD50 values of D9THC in Fischer rats?

In order to resolve the differences in reported LD50 values for d9THC obtained with various vehicles and rat strains, the oral LD50 values of d9THC in a natural vegetable oil vehicle and in an aqueous emulsion were determined in the same rat strain. In addition an iv LD50 value obtained with the emulsion formulation was compared with an inhalation LD50.

 

The natural vegetable oil was pure sesame oil and the aqueous emulsion used orally was comprised of 13 percent sesame oil, 1 percent polysorbate 80 and isotonic saline. A similar emulsion (7 percent sesame oil and 0.5 percent polysorbate 80) was used to establish the iv and ip LD50 values. The young adult Fischer rat was used in all experiments and the polysorbate 80 concentrations in emulsion formulations was maintained below toxic levels for the rodent. Marijuana cuttings were impregnated with D9THC and formed into cigarettes which were smoked under controlled conditions of puff volume and duration in an automatic smoking machine to obtain an inhalation LD50.

 

It was demonstrated that behavioral and physiological responses to D9THC occurred sooner with the oral emulsion formulation than with the vegetable oil. The intragastric LD50 with the emulsion was 800 milligrams/Kilogram and with the sesame oil formulation, 1270 milligrams/Kilogram. The iv LD50 was 36–40 milligrams/Kilogram, similar to the inhalation dose when the latter was corrected for D9THC losses in the rodent nasal passages. The results from this study affirmed that the LD50 values obtained were reliable and that the vehicle did not contribute to the toxicity.


 

LD50 Median lethal dose

 

In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50 percent"), LC50 (lethal concentration, 50 percent) or LCt50 is a measure of the lethal dose of a toxin, radiation, or pathogen. The value of LD50 for a substance is the dose required to kill half the members of a tested population after a specified test duration. LD50 figures are frequently used as a general indicator of a substance's acute toxicity. A lower LD50 is indicative of increased toxicity.

 

The term semi lethal dose is occasionally used with the same meaning, in particular in translations from non-English-language texts, but can also refer to a sublethal dose; because of this ambiguity, it is usually avoided. LD50 is usually determined by tests on animals such as laboratory mice. In 2011, the U.S. FDA approved alternative methods to LD50 for testing the cosmetic drug Botox without animal tests.

 

The choice of 50 percent lethality as a benchmark avoids the potential for ambiguity of making measurements in the extremes and reduces the amount of testing required. However, this also means that LD50 is not the lethal dose for all subjects; some can be killed by much less, while others survive doses far higher than the LD50. Measures such as "LD1" and "LD99" (dosage required to kill 1 percent or 99 percent, respectively, of the test population) are occasionally used for specific purposes.

Lethal dosage often varies depending on the method of administration; for instance, many substances are less toxic when administered orally than when intravenously administered. For this reason, LD50 figures are often qualified with the mode of administration, e.g, "LD50 intravenous."

The related quantities LD50/30 or LD50/60 are used to refer to a dose that without treatment will be lethal to 50 percent of the population within (respectively) 30 or 60 days. These measures are used more commonly within Radiation Health Physics, as survival beyond 60 days usually results in recovery.

A comparable measurement is LCt50, which relates to lethal dosage from exposure, where C is concentration and t is time. It is often expressed in terms of milligrams-min/cubic meters. ICt 50 is the dose that will cause incapacitation rather than death. These measures are commonly used to indicate the comparative efficacy of chemical warfare agents, and dosages are typically qualified by rates of breathing (e.g, resting = 10 l/min) for inhalation, or degree of clothing for skin penetration. The concept of Ct was first proposed by Fritz Haber and is sometimes referred to as Haber's Law, which assumes that exposure to 1 minute of 100 milligrams/cubic meters is equivalent to 10 minutes of 10 milligrams/cubic meters (1 × 100 = 100, as does 10 × 10 = 100).

Some chemicals, such as hydrogen cyanide, are rapidly detoxified by the human body, and do not follow Haber's Law. So, in these cases, the lethal concentration can be given simply as LC50 and qualified by a duration of exposure (e.g, 10 minutes). The Material Safety Data Sheets for toxic substances frequently use this form of the term, even if the substance does follow Haber's Law.

For disease-causing organisms, there is also a measure known as the median infective dose and dosage. The median infective dose (ID50) is the number of organisms received by a person or test animal qualified by the route of administration (e.g, 1,200 org/man per oral). Because of the difficulties in counting actual organisms in a dose, infective doses can be expressed in terms of biological assay, such as the number of LD50's to some test animal. In biological warfare infective dosage is the number of infective doses per cubic metre of air times the number of minutes of exposure (e.g, ICt 50 is 100 medium doses - min/cubic meters).

Limitations - As a measure of toxicity, LD50 is somewhat unreliable and results can vary greatly between testing facilities due to factors such as the genetic characteristics of the sample population, animal species tested, environmental factors and mode of administration.

There can be wide variability between species as well; what is relatively safe for rats can very well be extremely toxic for humans (cf. paracetamol toxicity), and vice versa. For example, chocolate, comparatively harmless to humans, is known to be toxic to many animals. When used to test venom from venomous creatures, such as snakes, LD50 results can be misleading due to the physiological differences between mice, rats, and humans. Many venomous snakes are specialized predators on mice, and their venom can be adapted specifically to incapacitate mice; and mongooses can be exceptionally resistant. While most mammals have a very similar physiology, LD50 results can or can not have equal bearing upon every mammal species, such as humans, etc.






 

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