[I'm starting a new series here at Retrospectacle, called 'Science Vault,' of which this post is the first. Pretty much I'm just going to dig back into the forgotten and moldering annuls of scientific publications to find weird and interesting papers that very likely would never be published today (and perhaps never should have.) I'll probably try to do it once a week (and if you have suggestions, please do email me with them.)]
Most of you read the title and thought I was kidding, right? I mean, who in their right mind would give a huge dose of a psychotropic substance to an elephant, just to see what happened? Well, the year was 1962, and someone did just that. And, as icing on the cake, they got a Science paper out of it.
The history of LSD is a fascinating one, but rather lengthy so I’ll just brush over a few points for context. Before the 1960s, lysergic acid diethylamide (LSD) was seen as a compound which had promise as a therapeutic agent, specifically in psychiatric therapy. Until 1966, the lab which originally invented LSD (Sandoz Labs) provided LSD for free to interested researchers. The US military became quite interested in LSD during the Cold War as an aid in interrogation, and the CIA conducted many tests with LSD (now destroyed) before moving on to other drugs. Widespread abuse of LSD eventually led to the US government to ban it for recreational and medical uses in 1967, despite very positive results from ‘LSD psychotherapy.’
However, when this paper was published in 1963, the LSD still flowed to researchers. The three authors were from the University of Oklahoma, one of which (Louis West) was a CIA collaborator. The proposed point of the experiment was to determine whether an injection of LSD would induce “musth,” a mysterious pachydermian state where elephants become violent which lasts about 2 weeks. Elephants have been known to kill their handlers when in “musth.”
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The authors saw this unique temporary madness as an opportunity for research. During musth, elephants release a sticky brown substance from a gland near their temples. No one really knew what it was, and whether there was an internal correlate which triggered musth somehow. The authors wanted to try to induce musth artificially, and theorized that the mystery musth-substance may be chemically similar to LSD. Specifically they decided to introduce to an elephant (not in musth) a “behavioral aberration that might resemble the phenomenon of going on musth.” That ‘aberration’ would be a huge dose of acid. They would then observe if the temporal glands began producing the brown substance, and collect it.
Now, to me, this seems a stretch to connect the dots “LSD produces changes in psychological state in humans” and “LSD induces violent and uncontrollable behavioral state in elephants.” But, I mean, it seems silly to pick out one incongruity in a paper full of them, so on we march.
The subject was a 14-year-old male Indian elephant named Tusko being housed at the Lincoln Park Zoo. As previous research had suggested that high doses to LSD were needed to get perceivable effects in “lower animals,” they decided to start with a 0.1 mg/kg dose of LSD for Tusko. That came to about 297 milligrams (in 5 mL of water, injected intramuscularly) of LSD for 7000 pound Tusko. The injection was delivered via a pressurized CO2 dart gun. For comparison, the threshold dosage for an effect in people is around 20-30 micrograms and a recreational 3+ hour dose would be around 100-200 micrograms.
“Tusko began trumpeting and rushing around the pen, a reaction not unlike the one he had shown the day before (during the placebo shot). However, this time his restlessness appeared to increase for 3 minutes after the injection; then he stopped running and showed signs of marked incoordination. He began to sway, his hindquarters buckled, and it became increasingly difficult for him to maintain himself upright. Five minutes after the injection he trumpeted, collapsed, fell heavily on his right side, defecated, and went into status epilepticus.”
The researchers were understandable quite surprised and distressed by the elephants seriously bad reaction to the LSD (they theorized that elephants were actually quite resistant to psychotropic substances). They tried to alleviate the seizures by administering promazine hydrochloride (Thorazine, 2800 mg!), which had a modest effect in reducing the spasms but did nothing for Tusko’s overall state. A last ditch effort to save the animal by injection of pentobarbitol sodium was also unsuccessful, and Tusko died 1 hour and 40 minutes after the LSD dose.
Necropsy illuminated the cause of death as strangulation secondary to laryngeal spasms. The authors were really just grasping at straws as to *why* the elephant died, and so quickly, and tossed out theories from “autosensitization” (because Tusko had been in musth before, and if LSD was similar to whatever made the elephants go crazy…..) to accidental intravenous injection (unlikely in a muscle). They also deigned it appropriate to wax moral and suggest what to do in a human overdose:
“Despite efforts by its manufacturer to prevent misuse of the drug, LSD has been increasingly and sometimes irresponsibly administered to humans as a putative adjunct to psychotherapy. The possibility of suicide or even homicide by LSD cannot be ignored. Treatment of an individual in extremis from LSD poisoning would be symptomatic but a possible emergency requirement for anticonvulsant medication, and for a muscle relaxant such as succinylcholine, is suggested from the results of this single experiment.”
Well, it doesn’t seem reasonable to me to extrapolate anything about human reactions to LSD (or really, anything of scientific merit) from this ‘experiment.’ Unsurprisingly, a controversy appeared shortly after the paper was published, questioning whether it was actually the LSD that was lethal, rather than the high doses of Thorazine and pentobarbitol. Also, why would the researchers attempt to give the elephant so high a dose of a substance that they had no idea what effect it would have? Wouldn’t the prudent thing to do be to give a small dose, and give more later, if necessary? As Erowid points out:
If a human model had been used to determine the dose of LSD for the elephant, the dose would be in the neighborhood of 0.003 mg/kg. For a 60 – 100kg human, doses of .2mg (200 micrograms) is enough to cause substantial clinical effects. Based on this, the calculated dose for an elephant of Tusko’s size (3000 kg) would be about 9mg of LSD. West et al.’s choice to inject Tusko with 297mg was more than 30 times the effective oral dose for a human of Tusko’s weight. If the dosage had been chosen by metabolic rate, the amount would have been around 3.9mg and if based on brain size (elephants have brains about 3 times the size of human brains) only .64 mg. (Schmidt-Nielsen, 1972) Interspecies scaling of dosages can be extremely complicated and variations in enzymes and metabolism can completely invalidate any type of calculated scaling.
Another strange detail is the use of a valuable zoo animal (which had a mate who was in the pen at the time) for a dangerous chemical experiment–an animal which the authors themselves tout as intelligent and social. This certainly makes me quite glad to be in science during a time where much, much more care and justification is required to undertake risky (or even not risky) animal experimentation.
West LJ, Pierce CM, Thomas WD. (1962). Lysergic acid diethylamide: Its effects on a male Asiatic elephant. Science, 138, 1100-1102. PDF