Most humans enjoy hanging with their buds. We share this trait with animals like dogs, but not with the California two-spot octopus. Octopus bimaculoides is an asocial creature, which means it avoids other octopuses whenever possible. Put it in a tank with another octopus, and it might become aggressive or squish itself shyly against a wall.
There’s one exception — during mating, this asocial behavior stops. Dölen figured that a neuromechanism was at play and wondered whether MDMA (3-4-Methylenedioxymethamphetamine, better known as ecstasy) could trigger that mechanism to switch the cephalopod into a more social animal.
This wasn’t wonder for its own sake. “There’s been a renaissance for looking at psychedelic drugs as possible therapeutics,” she said.
Robert C. Malenka, a professor of psychiatry and neuroscience at Stanford University, who was not involved with this study, called for increased study of MDMA in an influential Cell paper in 2016. MDMA has taboo associations with psychedelia and rave culture — it’s classified as Schedule 1, reserved for illegal drugs with high abuse potential. Nevertheless, it is being explored as a therapy for military veterans with PTSD.
Some people call MDMA “an empathogen,” because “it reduces inhibition, it reduces social anxiety, it reduces the fear of social interaction,” Malenka said. And because MDMA can curb hostility and anger, Malenka sees its value as a tool in neuroscience. “I passionately believe we need to understand” what makes social interactions positive, he said — nothing less than the “survival of our species” depends on it.
Enter other species. There is a long, and sometimes dubious, history of scientists dosing animals with psychoactive drugs. Tests in the 1950s demonstrated that spiders create chaotic webs when drugged with caffeine or mescaline. In 1962, in an experiment that went horribly awry, scientists at the University of Oklahoma injected an elephant named Tusko with a massive amount of LSD.
Toxicity tests funded by the National Institutes of Health and the Department of Defense exposed rabbits, monkeys and rodents to high doses of MDMA, said neuropharmacologist Allison A. Feduccia, who works at a Santa Cruz, Calif.-based organization called Multidisciplinary Association for Psychedelic Studies, or MAPS. MAPS donated the MDMA used in this study. The doses that the octopuses received were much more in line with what a human would take, she said. (This is also, to Feduccia’s knowledge, the first time the substance was given to an octopus.)
In the experimental trials, the authors placed an octopus for 30 minutes in a three-chambered tank set up like a house with separate rooms. The central room was empty. In the left room was a perforated container that held “Star Wars”action figures (a Chewbacca or a stormtrooper toy). In the right wing, a clear flowerpot flipped upside down held another octopus. The flowerpot container had holes so the octopuses could communicate by sight, touch and chemically, but the asocial animals could not hurt each other.
Sober octopuses spent most of their time away from the other animal — they scurried into the room with the “Star Wars” figures. But then the study authors dissolved MDMA in seawater and bathed the octopuses in the liquid for 10 minutes. They placed the drugged octopuses, males and females, back into the central chamber. And those octopuses spent significantly more time, on average 15 minutes, in the room with another male octopus.
The MDMA-drugged octopuses appeared to be “floaty and relaxed, hugging the flowerpot” that contained the other octopus, Dölen said.
"As far as the behavioral traits, the octopuses being more prosocial, it does support what we are seeing therapeutically,” said Feduccia, who is the author of a pilot trial of MDMA-assisted psychotherapy for social anxiety in adults with autism.
The authors observed even stranger behavior that they did not report in the study, Edsinger said. He was reluctant, even after extensive questioning, to further describe what the octopuses did, because the scientists could not be sure if the MDMA had induced these actions.
“They show that MDMA increases a particular type of social behavior in octopuses — namely, social approach and investigation of male unknown octopuses,” said Gillinder Bedi, a researcher at Melbourne University in Australia who was not involved with this work. “It is a little hard to call this ‘prosociality,’ but it does seem to be social interest at least.” Other lab animals exposed to MDMA also become more socially active, studies have shown.
MDMA binds to a receptor for the molecule serotonin, a neurotransmitter that affects our mood. The receptor is sort of like a vacuum at the end of a neuron that sucks up the serotonin molecules, Malenka said. MDMA flips the pump from a vacuum to a leaf blower, releasing more serotonin.
Octopus brains are organized totally differently than ours or a rodent’s. The animals have just a fraction of the neurons we do. Lacking a cortex, their brains are more similar to a snail’s than yours or mine. “Octopuses are special because they are separated from humans by over 500 million years of evolution, but they are able to do so many complex, interesting cognitive behaviors,” Dölen said.
They also appear to have something in their brains like the serotonin receptor in humans. Edsinger was part of the team that sequenced the California two-spot octopus genome in 2015. “If we look at the part of the gene that encodes the binding pocket of the receptor — it’s very similar,” Edsinger said.
Considering the hugging behavior and similar part of the gene, the authors say there’s evidence that “the neural mechanisms subserving social behaviors exist in O. bimaculoides.” Put another way, despite the 500 million years of separation between humans and octopuses, and our very different brains, what rewards us for social activity probably rewards octopuses, too.
Malenka, who called the approach in this report “very clever,” said he was not totally convinced that serotonin and its receptor explained this behavior. The genetic evidence is suggestive, but MDMA also interacts with neurotransmitters like dopamine, he pointed out.
“Without a test like blocking serotonin and then retesting the effects of MDMA you can’t be sure that this is the mechanism,” Bedi said. “However, I think that it is not an unreasonable hypothesis.”
Dölen said she would like to do more tests with more animals, like giving MDMA to an octopus at the same time as Prozac or a selective serotonin reuptake inhibitor that bind to the same receptor. And Edsinger said he plans to sequence two closely related octopus genomes — one species hangs out in groups, the other is a bunch of loners — to look for the source of social differences in their genes.