LD50, lethal dose 50

Terrence McKenna explains the concept of LD50.

"We want to take an excursion here and learn a little pharmacology. If you're going to talk about pharmacology, there is one concept that you should get straight, and that's called LD50. It means "lethal dose 50". What does this mean? Well, you have 20 rats and you give them a certain amount of, let's say, mescaline. When half the rats die, that dose, expressed as milligrams per kilogram of body weight, is called the LD50. And when pharmacologists assess the danger in a drug, they ask the following question, "what is the relation of the LD50 to the effective dose?", and if the LD50 of a drug is only 20 times the effective dose, that's considered an incredibly toxic, dangerous, and dubious drug. A good drug is a drug where the LD50 is 200 times more than the effective dose. In the case of LSD, the LD50 for man has never been determined. That's how safe LSD is. We're talking about lethality here, not you know. So people say, "Well are there unsafe psychedelics?" Well, yes, you just look up the LD50s, line them up, and see which ones have the better ratios. By that measurement, by that standard, LSD is the most desirable. But the LD50 of psilocybin is very impressive. You can take 100 times the effective dose of psilocybin and expect to live. Mescaline, not. Mescaline has a bad profile. As an amphetamine, if you took 20 times the effective dose of mescaline, you would probably die. Of course, an effective dose of mescaline is nearly a gram of pure material, 700 milligrams. If you took 20 times 700 milligrams you would be taking nearly 2/3 of an ounce of mescaline..." (Terrence McKenna)

The LD50 of LSD varies from species to species. Rabbit is the most sensitive species known, with LD50 of 0.3 mg/kg i.v. The LD50 for rats is ten times higher at 16.5 mg/kg i.v. Mice tolerate 46-60 mg/kg i.v. LSD (Passie et al, 2008). An intraperitoneal dose of LSD 5.0 mg/kg reportedly caused death in a rat within 30-45 minutes and was associated with cardiac irregularities and general rigidity of musculature (Sylar et al, 1971). A too high dose of LSD typically causes animals to expire by paralysis, bradycardia, or respiratory failure; these effects probably involve centers in the caudal brain stem.

In an experiment with Macacus rhesus, one animal received 240 ug/kg and the other 140 ug/kg, which are enormous doses of LSD. In terms of a 70 kg person, the animals received 168 and 98 hits of LSD. These doses did not produce an excited behavior in monkeys as small doses do, but instead produced sedation. The monkeys became quiet and more sluggish around the cage, and did not jump about the cage as they did before. The monkeys lived.


Reference

Passie, T., J.H. Halpern, D.O. Stichtenoth, H.M. Emrich and A. Hintzen 2008. The pharmacology of lysergic acid diethylamide: A review. CNS Neurosci. Ther. 14, 295-314.

Sklar, S., K.A. Nieforth and M. Malone 1971. Synthesis and preliminary screening of N-ethyltryptamine derivatives related to reserpine and lysergic acid. J. Pharm. Sci. 60, 304-306.