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As yet we do not know the biochemical mechanisms through which LSD exerts its psychic effects. Investigations of the interactions of
LSD with brain factors like serotonin and dopamine, however, are examples of how LSD can serve as a tool in brain research, in the
study of the biochemical processes that underlie the psychic functions. 



How Toxic Is LSD? 

The toxicity of LSD has been determined in various animal species. A standard for the toxicity of a substance is the LDso, or the

median lethal dose, that is, the dose with which 50 percent of the treated animals die. In general it fluctuates broadly, according to the

animal species, and so it is with LSD. The LDso for the mouse amounts to 50-60 mgtkg i.v. (that is, 50 to 60 thousandths of a gram

of LSD per kilogram of animal weight upon injection of an LSD solution into the veins). In the rat the LDso drops to 16.5 mg/kg, and

in rabbits to 0.3 mg/kg. One elephant given 0.297 g of LSD died after a few minutes. The weight of this animal was determined to be

5,000 kg, which corresponds to a lethal dose of 0.06 mg/kg (0.06 thousandths of a gram per kilogram of body weight). Because this

involves only a single case, this value cannot be generalized, but we can at least deduce from it that the largest land animal reacts

proportionally very sensitively to LSD, since the lethal dose in elephants must be some 1,000 times lower than in the mouse. Most

animals die from a lethal dose of LSD by respiratory arrest. 


The minute doses that cause death in animal experiments may give the impression that LSD is a very toxic substance. However, if one

compares the lethal dose in animals with the effective dose in human beings, which is 0.0003-0.001 mg/kg (0.0003 to 0.001

thousandths of a gram per kilogram of body weight), this shows an extraordinarily low toxicity for LSD. Only a 300- to 600-fold

overdose of LSD, compared to the lethal dose in rabbits, or fully a 50,000- to 100,000fold overdose, in comparison to the toxicity in

the mouse, would have fatal results in human beings. These comparisons of relative toxicity are, to be sure, only understandable as

estimates of orders of magnitude, for the determination of the therapeutic index (that is, the ratio between the effective and the lethal

dose) is only meaningful within a given species. Such a procedure is not possible in this case because the lethal doge of LSD for

humans is not known. To my knowledge, there have not as yet occurred any casualties that are a direct consequence of LSD

poisoning. Numerous episodes of fatal consequences attributed to LSD ingestion have indeed been recorded, but these were accidents,

even suicides, that may be attributed to the mentally disoriented condition of LSD intoxication. The danger of LSD lies not in its

toxicity, but rather in the unpredictability of its psychic effects. 


Some years ago reports appeared in the scientific literature and also in the lay press, alleging that damage to chromosomes or the

genetic material had been caused by LSD. These effects, however, have been observed in only a few individual cases. Subsequent

comprehensive investigations of a large, statistically significant number of cases, however, showed that there was no connection

between chromosome anomalies and LSD medication. The same applies to reports about fetal deformities that had allegedly been

produced by LSD. In animal experiments, it is indeed possible to induce fetal deformities through extremely high doses of LSD,

which lie well above the doses used in human beings. But under these conditions, even harmless substances produce such damage.

Examination of reported individual cases of human fetal deformities reveals, again, no connection between LSD use and such injury.

If there had been any such connection, it would long since have attracted attention, for several million people by now have taken LSD.


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LSD in Animal Experiments and Biological
Research

	Before a new active substance can be investigated in systematic clinical trials with human subjects, extensive data on its effects and

side effects must be determined in pharmacological tests on animals. These experiments must assay the assimilation and elimination of

the particular substance in organisms, and above all its tolerance and relative toxicity. Only the most important reports on animal

experiments with LSD, and those intelligible to the layperson, will be reviewed here. It would greatly exceed the scope of this book if

I attempted to mention all the results of several hundred pharmacological investigations, which have been conducted all over the world

in connection with the fundamental work on LSD in the Sandoz laboratories. 

Animal experiments reveal little about the mental alterations caused by LSD because psychic effects are scarcely determinable in lower

animals, and even in the more highly developed, they can be established only to a limited extent. LSD produces its effects above all in

the sphere of the higher and highest psychic and intellectual functions. It is therefore understandable that speciflc reactions to LSD can

be expected only in higher animals. Subtle psychic changes cannot be established in animals because, even if they should be

occurring, the animal could not give them expression. Thus, only relatively heavy psychic disturbances, expressing themselves in the

altered behavior of research animals, become discernible. Quantities that are substantially higher than the effective dose of LSD in

human beings are therefore necessary, even in higher animals like cats, dogs, and apes. 


While the mouse under LSD shows only motor disturbances and alterations in licking behavior, in the cat we see, besides vegetative

symptoms like bristling of the hair (piloerection) and salivation, indications that point to the existence of hallucinations. The animals

stare anxiously in the air, and instead of attacking the mouse, the cat leaves it alone or will even stand in fear before the mouse. One

could also conclude that the behavior of dogs that are under the influence of LSD involves hallucinations. A caged community of

chimpanzees reacts very sensitively if a member of the tribe has received LSD. Even though no changes appear in this single animal,

the whole cage gets in an uproar because the LSD chimpanzee no longer observes the laws of its finely coordinated hierarchic tribal

order. 

Of the remaining animal species on which LSD was tested, only aquarium fish and spiders need be mentioned here. In the fish,

unusual swimming postures were observed, and in the spiders, alterations in web building were apparently produced by kSD. At very

low optimum doses the webs were even better proportioned and more exactly built than normally: however, with higher doses, the

webs were badly and rudimentarily made. 



LSD from the Black Market 

Nonmedicinal LSD consumption can bring dangers of an entirely different type than hitherto discussed: for most of the LSD

offered in the drug scene is of unknown origin. LSD preparations from the black market are unreliable when it comes to both

quality and dosage. They rarely contain the declared quantity, but mostly have less LSD, often none at all, and sometimes even too

much. In many cases other drugs or even poisonous substances are sold as LSD. These observations were made in our laboratory

upon analysis of a great number of LSD samples from the black market. They coincide with the experiences of national drug

control departments.