LSD affects spinal cord activity in salamander

The behavior of fish is altered in a characteristic way when LSD is dissolved in the tank water. Instead of swimming around the tank, the fish hold still at the surface of the water. Likewise, salamanders exhibit statue-like postures and slow movements when injected abdominally with 0.7-0.8 mg/g LSD.

From LSD salamander

Rather large doses of LSD were utilized in these studies. Unless a mistake was made reporting the units, the dose given to salamanders was 0.7 mg/g of body weight, or 700,000 ug/kg. Typically, 25 ug/kg in cat or 100 ug in a person of average weight 85 kg (1.1 ug/kg) is all that is needed to elicit an LSD reaction. During the peak of drug action the salamander moved slowly and allowed its limbs to be moved by researchers. Peters wrote,

“Within 5 to 15 minutes after the injection of LSD-25 the salamander, when placed in water, shows disturbances of equilibrium during which the animal slowly writhes, comes to rest on its side, back, or belly, and assumes statue-like postures representing some stage in standing or walking. These floating postures are interrupted by slow movements of trunk or limbs as if the salamander were attempting to maintain its balance. The trunk and limbs are not limp, but have the firmness of soft wax, so that the animal allows itself to be moved passively, especially in water. During this phase of drug action, tactile stimuli applied to the tip of the tail are followed by ambiguous results, i.e. they may evoke a prompt escaping reaction as vigorous as that of an untreated animal, or a slow response delayed 5 to 10 seconds, or no response at all.” (J. J. Peters, 1956)

EEGs were recorded from the brain and spinal cord of salamander. Activity at the electrode over the brain was somewhat unchanged by LSD, but the electrode over spinal cord showed much more high voltage activity compared to untreated salamander. Spinal cord EEGs showed a sustained discharge of waves of high frequency and amplitude (figure below), even though the salamander appeared quiet and motionless. The results suggest a more pronounced drug effect on electrical activity in the spinal cord rather than the brain.

From LSD salamander

The powerful mental effects of LSD have led many researchers to suspect that the mechanism of LSD is to affect firing of neurons of the brain, but in the case of salamander the electrical activity of spinal cord was specifically affected. It may be an important hypothesis to consider - that LSD does not necessarily exert its effects on higher order centers of the brain.


Reference

PETERS J. J. and A. R. VONDERAHE (1956). Behavior of the salamander under the influence of LSD-25 and Frenquel, and accompanying electrical activity of brain and spinal cord. J. Nerv. Ment. Dis. 124, 69-73.

LSD dose

The effective dose of LSD varies enormously among species. In salamander, the effective LSD dosage is 700,000 ug/kg. Intracranial injections of 300 ug/kg in goldfish produce the characteristic LSD fish surfacing reaction. In mouse the effective dose is 180 ug/kg of body weight. With LSD behavioral changes are discernible in rat at 80-160 ug/kg but in the cat at 25 ug/kg. A 20 ug/kg LSD affects pigeons' performance in learned discrimination tasks. In rabbit the effective dose is 15 ug/kg. In man, where we have the advantage of verbal reporting, the effective dose is less than 1 ug/kg. According to Albert Hofmann, the effective human dose of LSD is 0.5 ug/kg.

A flat dosage of 100 ug per person is used commonly in human LSD research. This dosage quantity is convenient to remember because it doesn't take body weight in kilograms into consideration. A dosage of 100 ug per person typically results in dramatic symptoms, but the threshold for activity generally is placed at 20 ug LSD per person.

Very low doses of LSD (4-40 ug per person) were tested in human volunteers by Greiner and colleagues in 1958. Psychic changes were established by way of interviews and measurement of pupil size, heart rate, and galvanic skin response. The data below showed that mood and psychomotor effects were detectable in human volunteers at dosages as low as 4 ug LSD per person, which is approximately 0.05 ug/kg of body weight, or 10 times less than the effective dose according to E. Rothlin and Hofmann. The objective measures showed that the galvanic skin response was activated after only 7 ug LSD per person. There was a dose-dependent increase in pupil size, heart rate, and other parameters.

From LSD dose

The researchers observed sudden shifts in affect in the volunteers after 4 ug, 7 ug, or 12 ug of LSD per person, but no significant changes in thought process or content. This data puts the threshold dose for LSD intoxication at about 20 ug per person.

LSD is one of the most potent drugs known to man. Whereas most drugs are administered at doses of tens or hundreds of milligrams, LSD is active at tens or hundreds of micrograms. The potency of LSD is best compared to other drugs on a log scale, as shown in Figure 1 below. It can be seen that the concentration of an active dose of alcohol is about a million times as great, expressed in terms of weight, as the concentration of LSD.

From LSD dose

Of course, the effective dose of LSD depends highly on the person, set, and setting. The dose threshold may be lower for people who are generally inexperienced with drugs, and higher for alcoholics and drug addicts.

“Familiarity with other drugs which produce psychological changes is also relevant. Alcoholics and drug addicts seem better able to cope with the LSD experience than normal subjects. I have had more difficulty with anxiety and panic in normal subjects than in patients who have had long experience with drugs.” (A. Hoffer, 1965)

Fasting or not can change the effective LSD dose too. Plasma concentrations of orally ingested LSD were twice as much on an empty stomach. The amount of the meal as well as the pH of the stomach will influence LSD absorption.


References

GREINER T., N. R. BURCH and R. EDELBERG. (1958). Psychopathology and psychophysiology of minimal LSD-25 dosage; a preliminary dosage-response spectrum. AMA Arch.Neurol.Psychiatry. 79, 208-210.

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.