A groundbreaking new study shows that octopuses seemed to exhibit uncharacteristically social behavior when given MDMA, the psychedelic drug commonly known as ecstasy.
- Octopuses, like humans, have genes that seem to code for serotonin transporters.
- Scientists gave MDMA to octopuses to see whether those genes translated into a binding site for serotonin, which regulates emotions and behavior in humans
- Octopuses, which are typically asocial creatures, seem to get friendlier while on MDMA, suggesting humans have more in common with the strange invertebrates than previously thought
It may seem like octopuses and humans have nothing in common.
After all, octopuses separated from humans on the evolutionary family tree nearly 500 million years ago, and with their eight arms, three hearts and sharp beaks, they bare little resemblance to primates. The venomous cephalopods possess extraordinarily large brains whose neurons, unlike humans, are distributed mostly throughout their arms, composing a uniquely complex nervous system. Octopuses also wield strange, alien-like abilities: They can taste what they touch, paralyze prey with saliva, change their skin color to use camouflage, and blind enemies with jets of ink.
But one thing octopuses and humans have in common is intelligence.
Thought to be among the planet's first intelligent creatures, octopuses have been observed to play, navigate mazes and even collect coconut shells to build shelter, an example of tool use. They also display an uncanny ability to escape from human captivity. In 2016, a young octopus at New Zealand's National Aquarium was able to squeeze himself through a tiny gap at the top of his tank, flop to the floor, slither down a long drainpipe, and plop into the ocean, never to be seen by aquarium staff again.
A crucial difference
Despite this cognitive sophistication, many scientists have long thought octopuses and other invertebrates lack the neural requirements needed to experience emotion or practice social behaviors in the ways mammals do.
However, a new study published in the journal Current Biology challenges that long-held presumption by showing that administering MDMA to octopuses seems to elicit social behavior in them, suggesting that the architecture for experiencing such phenomena extends farther back in evolutionary history than previously thought.
All five of the octopuses that completed this part of the experiment spent far more time in the room with the toy, though both male and female octopuses did tentatively explore the other room when a female was in the cage.
The researchers then conducted this experiment again, but this time, each octopus was bathed in water containing MDMA before entering the three-zone tank. Unlike before, the octopuses on MDMA seemed far more interested in the room with the octopus, at times touching it in an exploratory manner, instead of the room with the lifeless toy.
The three-zone tank used in the experiment. Cage with toy on left, cage with octopus on right.
(Eric Edsinger, Gül Dölen)
An eight-armed hug
"They were very loose," Dölen said. "They just embraced with multiple arms."
It's impossible to know what the octopuses were experiencing, but Dölen offered her own personal observation (as anecdotal evidence, not scientific) to Inverse: the octopuses acted like humans do when they're on ecstasy.
On high doses, the octopuses breathed intensely and turned white. But on lower doses, the octopuses seemed to display more typical behavior of someone on a psychedelic: one became very interested in minor sounds and scents, another spent some time doing flips in the tank, and one octopus "looked like it was doing water ballet," swimming around with its arms extended.
In humans, MDMA acts on the brain mainly by stimulating activity of the neurotransmitter serotonin. The California two-spot octopus also possesses a serotonin transporter to which MDMA can bind. However, the researchers weren't sure whether this ancient feature was active in the octopuses.
"We needed to check the genome to make sure that the genes that encode the serotonin transporter, which is the protein that MDMA binds to, was still a binding site in octopuses even despite the fact that so much evolutionary time had passed," Dölen told Inverse.
"We performed phylogenetic tree mapping and found that, even though their whole serotonin transporter gene is only 50 to 60% similar to humans, the gene was still conserved. That told us that MDMA would have a place to go in the octopus brain and suggested it could encode sociality as it does in a human brain."
Although they are about as alien from human life as it gets, Dölen's study shows that octopuses share some important characteristics with humans.
(FRED TANNEAU/AFP/Getty Images)
Familiar behavior in strange brain structures
The idea that octopus behavior might be regulated by serotonin, which largely controls human emotion, is especially interesting because of how different the creatures are from humans.
"This was such an incredible paper, with a completely unexpected and almost unbelievable outcome," said Judit Pungor, a postdoctoral researcher at the University of Oregon not involved in the study, in an interview with Gizmodo. "To think that an animal whose brain evolved completely independently from our own reacts behaviorally in the same way that we do to a drug is absolutely amazing."
To be sure, it's not exactly clear why the octopuses "opened up" while they were on MDMA. In addition to the study being limited by sample size, it's possible that the octopuses were more inclined to touch the other octopus because the drug made them more interested in touching in general, not necessarily social touching.
Still, Dölen said that the findings suggest that molecular and cellular genetic information, rather than anatomical data, are more important in deciding whether animals develop social behavior.
"Octopuses don't have the same parts of the brain that we think are important for social behavior, a region called the nucleus accumbens," Dölen told Inverse. "What we're arguing is that the brain regions don't matter. What matters is that they have the molecules, the neurotransmitters, and some configuration of neurons. They have the serotonin transporter and that's enough."
Studies and trials point to the potential of a rave drug becoming the newest antidepressant medication in decades.
A powerful anesthetic, used as an animal tranquilizer and an illicit club drug, has been receiving growing attention for its potential to treat depression. A number of studies point to the possibility that ketamine (known in the club scene as “special K”) can become the next big thing in anti-depressant medications.
While it’s not approved by the FDA for treating depression, numerous clinics have sprung up to treat patients “off-label”, with low doses of the drug, while drug manufacturers are ramping up research and development.
Yale professor of psychiatry Dr. Sanacora, who has used ketamine to treat hundreds of patients suffering from severe depression, said in a recent interview with NPR that he feels an obligation to use the drug.
"If you have patients that are likely to seriously injure themselves or kill themselves within a short period of time, and they've tried the standard treatments, how do you not offer this treatment?" said Sanacora.
He also says a survey of U.S. and Canada clinics showed that “over 3,000” patients have already been treated.
How effective can ketamine be? It has been shown to relieve the kind of depression that no other drugs can affect. It's lifted even suicidal depression in just hours. With studies into ketamine going on for over a decade, a recent statement from the American Psychiatric Association says there is “compelling evidence” that it works, although its effects have been described as “transient.”
There is definitely more research to be done, especially considering the absence of large-scale trials.
“We don't know how much or how often it should be given for it to be effective or safe,” said psychiatry and neuroscience Professor James Murrough, in a review of ketamine published in Nature Reviews Drug Discovery.
Murrough is concerned that we don’t know the long-term effects of taking the drug. It also tends to wear off, necessitating more to be taken. Another big issue — how to avoid the often-unpleasant “high” from the drug, leaving only its therapeutic qualities. Professor Sanacora shares those concerns:
“In a nutshell, I feel confident telling patients who have had little help from previous treatments that ketamine provides meaningful relief from some of their worst symptoms for at least a few days or even weeks,’’ said Dr. Sanacora. “But I can’t tell them with any degree of certainty how long the benefit can be sustained or how safe it is to repeatedly administer the medication over periods of months or years. "
But even with reasonable cautions, ketamine’s promise is very much real, as it can lead to a totally new kind of medication.
"There's warranted caution that's balanced with an optimism that says we've never had a new medication for depression since the era of Prozac," says Murrough.
While most current antidepressants target the neurotransmitters serotonin and noradrenaline, ketamine works on glutamate. Before ketamine was studied, the role of this pathway in depression was not known.
Will we see a ketamine drug soon?
A 2016 study on mice found that the compound hydroxynorketamine may be responsible for ketamine’s success in treating depression. The scientists involved are going to human trials next.
A compound formed from ketamine called esketamine is now in the final testing stage before being considered by the FDA. Other ketamine-like drugs are also in development.
When used in clubs, ketamine is usually injected or snorted to create strong feelings of detachment. The more it’s taken, leading down what’s called a “K hole,” the more feelings of disassociation it will cause. For that reason, it can also be dangerous, with potential to cause temporary amnesia, confusion, increased heart rate, aggression and impaired motor function. There have also been cases of ketamine overdosing leading to date rape (due its paralyzing effects) or even death. In other words - don’t try this at home and wait for the science to catch up.
Check out this Big Think interview with neurobiologist and psychiatric Dennis Charney, who explains how ketamine works differently than other antidepressants: