STORIES

What Happens when Scientists Give Psychedelics to Animals?

By Daniel Oberhaus on November 25, 2018

Art images by Anthony Ausgang.

For all its downsides, animal testing has historically been a fundamental part of the scientific process. Although it is decried by animal rights groups for its cruelty, many scientists see it as the price to be paid for increasing our knowledge of biology and saving human lives. Indeed, animals have been the pioneering subjects for everything from space exploration to cloning, but they’re also the unsung heroes (or martyrs, depending on your viewpoint) of psychedelic science.

“Experiments directed at these issues which employ human subjects are precluded for moral or ethical reasons, or because they require examination of tissue derived from living organisms,” psychiatrist Barry Jacobs wrote in a study in which he administered LSD to cats. “Therefore, we must turn to animal experiments for the answers to most of these questions.”

Over the last half century, a variety of animals have been dosed with cannabis, LSD, psilocybin, MDMA and other mind-altering chemicals. These experiments have given researchers deep insights into the effects of psychedelic drugs on human and animal cognition. Although many of these experiments were deeply unethical, they also served to reveal the profound similarities between human and animal brains and the mechanisms by which psychedelics induce their effects on us.

PRØHBTD compiled a brief history of psychedelic animal tests and what scientists learned from dosing our fellow passengers on spaceship Earth.

LSD

Perhaps the most notorious psychonaut involved with animal testing was John C. Lilly, who spent the better part of his career trying to figure out how to talk to dolphins. Lilly was a close friend of Carl Sagan, Timothy Leary, Allen Ginsberg and other LSD evangelists, and at the height of his career, he ran a dolphin research institute in the Caribbean. Here he used a variety of unorthodox research methods to try to crack the code of dolphin whistles, which he was sure constituted something approaching a full-fledged language. The story of Lilly’s research assistant Margaret Howe, who lived with a dolphin in a partially flooded house at the research institute and allegedly had a sexual encounter with one of the dolphins, is well known, but what is less well known is Lilly’s experiments with dolphins and LSD.

As Lilly detailed in a presentation at the 2nd International Conference on the Use of LSD in Psychotherapy and Alcoholism in 1967, Lilly had administered 100 microgram doses of LSD to several of his cetacean subjects. According to Lilly, he had administered the LSD in an attempt to facilitate meaningful communication with the dolphins. Although Lilly’s experiments didn’t accomplish this goal, he did note that the use of LSD made the dolphins far more vocal for hours after administering LSD.

Perhaps his biggest breakthrough, though, was establishing a connection with a dolphin that had undergone serious trauma. As Lilly detailed in his presentation, his research institute had taken in a dolphin that had been shot through the tail multiple times with a spear gun. When Lilly and his colleagues took this dolphin to the research institute, it would never get close to humans when they entered its pool. After administering LSD to the dolphin, however, it came over and interacted with Lilly in ways that he had never seen before. For Lilly, this was an indication that they had established a non-verbal communication that bordered on a sort of interspecies psychotherapy. 

Lilly wasn’t the only researcher pumping animals full of LSD in the '70s, however. Barry Jacobs, a professor at Princeton University’s Neuroscience Institute, spent a significant amount of his research time in 1976 and 1977 giving lucy to cats. In the first experiment, Jacobs sought to illuminate the mechanisms by which LSD induces its behavioral and perceptual effects in humans.

At the time, a leading theory for how LSD worked its magic involved the drug decreasing the activation rate of serotonin containing neurons in the brain. Based on this hypothesis, Jacobs argued that if LSD was combined with other serotonin blockers, such as p-chlorophenylalanine (PCPA), a tryptophan hydroxylase inhibitor, it should boost their effects. To test this, Jacobs administered 100 micrograms of LSD to 11 cats that had already been treated with PCPA.

As Jacobs discovered, LSD did seem to enhance the serotonin-blocking effects of PCPA in cats. In his reports on the experiments, Jacobs noted that “administration of LSD produced what appeared to be prominent hallucinatory-like behavior in which the cat continually scanned the cage, often stopping and staring for long periods, and made pawing movements at unseen objects.” Additionally, the LSD induced “aborted grooming,” paw flicking and a swaying of the head in the cats. According to Jacobs, these behaviors not only bolstered the theory that LSD suppresses serotonin transporters, it also served as good baseline metrics for further studying the effects of LSD since “these behaviors are quantifiable, easily scored and occur with very low frequency in normal cats.”

The following year, Jacobs published another paper that detailed an experiment he performed on cats that measured the occurrence of these behaviors relative to the amount of LSD administered to the animal. As he discovered, these abnormal behaviors—namely, paw flicking and aborted grooming—increased with LSD doses up to about 100 micrograms. Beyond this, their occurrence decreased dramatically. Notably, the cats didn’t increase their frequency of vocalizations, such as meowing or yowling, which indicated to Jacobs that they “never felt overly sick, anxious, or uncomfortable.” If anything, the LSD helped them relax, as indicated by a slight uptick in the frequency of kneading while under the influence of acid.

Not all LSD experiments ended so well, however. In the early 1960s, researchers from the University of Oklahoma injected Tusko, a 14-year-old elephant, with LSD to see how it would affect a behavioral quirk found exclusively in elephants. When male elephants reach maturity at around 12 years old, they begin exhibiting a mating behavior called “musth,” a seasonal type of “madness” that is generally characterized by high levels of irritability. As the University of Oklahoma researchers described it, musth causes an elephant to “run berserk for a period of about two weeks, during which time he may attack or attempt to destroy anything in his path,” which is “an almost unique phenomenon in nature.” According to the researchers, LSD was chosen because of its “well-known personality-disrupting effect upon humans and other animals.”

The researchers wanted to see if they could artificially induce musth in an elephant and so they decided to inject Tusko with 297 milligrams of LSD. This is about 1,000 times more LSD than humans need to feel the effects of the drug. This dosage was a best guess by the researchers, based on what was known about dosing requirements for other animals. For scientists, LSD doses are usually considered in terms of how much LSD is administered compared to the animal’s weight. For example, researchers learned that 6.5 milligrams of LSD per kilogram are needed to kill a cat. By comparison, Tusko was only administered 0.1 milligrams of LSD per kilogram, but because the elephant weighed several thousand pounds, this resulted in a large total quantity of LSD.

“If the elephant's sensitivity [to LSD] were of the order of that of a human being, this would represent a considerable overdose,” the researchers remarked in a report on the experiment. “However, if the elephant’s dose requirements in milligrams per kilogram were similar to those of other animals (including primates and cats), such a dose would at best be borderline effective.”

After receiving the injection, the researchers report that Tusko “began trumpeting and rushing around the pen” and “his restlessness appeared to increase for three minutes after the injection; then he stopped running and showed signs of marked incoordination.” Shortly thereafter, his mate, a 15-year-old elephant named Judy, came over to try to support Tusko as his knees began to buckle. Five minutes after receiving the injection, Tusko collapsed. The researchers noted that Tusko voided his bowels, his legs were held stiffly out in front of him, he began breathing rapidly and his pupils were “markedly dilated.” Within two hours, Tusko had died. 

It was unclear to the researchers what ultimately killed Tusko. One possibility they raised was that the LSD had not been distributed evenly throughout the elephant’s body and had “somehow rapidly concentrated in the nervous system,” resulting in Tusko’s death. In the conclusion of their report, the researchers noted that “it appears that the elephant is highly sensitive to the effects of LSD, a finding which may prove to be valuable in elephant-control work in Africa.”

Moreover, they extended this result to humans and noted that “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.” As such, the researchers concluded, “the possibility of suicide or even homicide by LSD cannot be ignored.”

Psilocybin

Psilocybin is the scientific name for the chemical compound that puts the “magic” in magic mushrooms. Researchers at Johns Hopkins University and elsewhere are currently exploring psilocybin as a potent form of therapy that can be used to treat depression, anxiety and especially trauma. These steps toward the medicinal use of shrooms wouldn’t have been possible without decades of animal research on the ways the fungus affects animal cognition. One of the most “shocking” experiments, so to speak, was conducted in 2013 by researchers from the University of South Florida.

In this experiment, researchers gave mice small doses of psilocybin and found that it eradicated fear in the mice. This suggested that the mushrooms could be a potent avenue for treating mental disorders such as PTSD. These results were part of a more wide-ranging investigation into how psilocybin affects short-term memories given that it binds with serotonin receptors in the hippocampus, the region of the brain that produces new neurons.

For their experiment, the researchers put mice in a cage and would then play a tone before delivering an electric shock to the mouse. Over time, the mice learned to link the tone with the shock so that when they heard the tone they would freeze in fear. Next, the researchers began to play the tone but didn’t deliver the electric shock to see how long it would take the mice to unlearn their fear response. This established a sort of baseline before the researchers brought psilocybin into the picture. Finally, the researchers began administering psilocybin to the mice. As they discovered, this drastically reduced the amount of time that it took for the mice to unlearn their fear response.

“Psilocybin enhanced forgetting of the unpleasant memory associated with the tone,” Juan Sanchez-Ramos, the lead researcher on the study, said in a statement. “The mice more quickly dissociated the shock from the stimulus that triggered the fear response and resumed their normal behavior.” 

Many researchers are now hoping that mushrooms can similarly reduce fear responses in humans, particularly those suffering from PTSD.

MDMA

Octopuses may not look much like us, but when it comes to how they handle their MDMA, it turns out we’re quite similar. At least this was the conclusion of a study conducted this year by researchers at Johns Hopkins University, who dosed octopuses with MDMA to see if it would induce the same kind of prosocial effects that the drug has on humans. At first blush, octopuses seem like an odd choice for replicating human behavior, but as it turns out, they share the gene for a neurotransmitter that allows MDMA to do its thing in humans. This led the Johns Hopkins researchers to suspect that the drug might induce similar effects in octopuses, despite their evolutionary lineage being separated from our own by more than 500 million years.

To test this theory, the researchers first gauged natural octopus behavior by placing the animal in an aquarium divided into three connected sections. In one section there was a toy underneath a cage, in the second was an empty “room,” and in the third there was another octopus inside a cage. Octopuses are generally solitary and pretty antisocial, a characterization that was borne out by these baseline metrics. Next, the researchers placed the octopuses in a bath of MDMA for 10 minutes before putting them back in the tank. The change in the octopuses' temperaments was dramatic.

The octopuses wanted to interact with the caged octopuses far more while under the influence than when they were sober. This included a lot of tentacle touching, a behavior that would be considered highly unusual for an octopus that wasn’t rolling. In addition to showing the researchers that MDMA can induce prosocial behavior in other species, the tests also demonstrated that the molecular mechanisms behind the serotonin transporters work similarly in octopus brains and human brains.

Other animal research on MDMA led to less benign conclusions—at least on the surface. In the early 2000s, George Ricaurte, a researcher with Johns Hopkins University, injected three squirrel monkeys with what he claimed was MDMA to see the drug’s effect on the monkeys’ brains. The drug was administered to the monkeys three times at three hour intervals, a dosage that Ricaurte claimed was equal to one “heavy party night’s” dosage.

What Ricaurte and his colleagues found was shocking. According to the researchers, this dose of MDMA led to permanent brain-damage that resembles Parkinson’s disease in humans. When they repeated the test with baboons, the results were much the same.

“We’ve long known that repeated ecstasy use damages serotonin brain cells,” Alan Leshner, a former director of the National Institute for Drug Abuse (NIDA), told The Guardian following the study. “This study shows that even very occasional use can have long-lasting effects on many different brain systems. It sends an important message to young people—don’t experiment with your brain.”

There was just one problem: The research was totally bogus.

The following year, Ricaurte retracted his paper from the prestigious journal Science after it was discovered that he was injecting the monkeys with methamphetamine, not MDMA. According to Ricaurte, the mix up was due to incorrect labels placed on bottles in his laboratory. When he later tried to replicate the findings after publishing the study, he found that the levels of brain damage in the primates weren’t the same, which led him to investigate the substances in the bottles and discover that the drugs were not the same as what was on their labels.

Although Ricaurte claimed that more evidence was needed to determine whether MDMA was as highly neurotoxic as it seemed at first, today things are looking a lot clearer. A pioneering effort by the Multidisciplinary Association for Psychedelic Studies (MAPS) has brought MDMA to the third and final stage of FDA trials. Should it pass this milestone, MDMA will likely become legal to prescribe to humans who suffer from PTSD. Although Ricaurte’s primate experiments almost derailed these efforts, in this case the mechanism of peer review acted just as it should have and saved MDMA from a preemptive ban.

DMT

As anyone who has ever taken psychedelics knows all too well, tripping is not without its unpleasant side effects. Many substances taste bitter, can induce nausea and vomiting, or lead to hallucinations and paranoia. For many psychonauts, these side effects are a small price to pay for the manifold benefits of a psychedelic experience. For animals who encounter psychoactive substances such as psilocybin or cannabis in the wild, however, these side effects are usually warning signs that suggest the plant they’re munching on isn’t food.

Although there are examples of animals ingesting intoxicating substances, these are more the exception than the rule. In the early '80s, however, two psychiatrists from UCLA set out to discover under what conditions a non-human animal would self-administer a psychedelic substance.

For this experiment, the researchers used three rhesus monkeys that had been trained to smoke lettuce cigarettes. The selection of rhesus monkeys was intentional. Not only had these monkeys been shown to self-administer hashish in a lab in the '70s, but they had also self-administered arylcyclohexylamines, a class of drugs with hallucinogenic properties that includes PCP. Moreover, previous research indicated that monkeys deprived of stimuli by being placed in an opaque box would quickly learn a task in order to earn a peek outside of the box.

This raised a question for the UCLA psychiatrists: “If isolated monkeys will work to earn access to a window in their box, what would happen if the only window available was a hallucinogenic drug window?”

To answer this question, the researchers laced lettuce cigarettes with 50 milligrams of DMT and then provided them to the monkeys, each of which was isolated in a sensory deprivation chamber. These cigarettes were placed in a steel smoking apparatus that the monkeys could suck on to ignite the cigarettes and inhale the smoke. After the monkeys were placed in the sensory deprivation chambers, the researchers monitored their behavior using infrared cameras.

The monkeys were placed in the sensory deprivation chambers for a stretch of 20 consecutive days. During their stay in the chambers, the monkeys had unlimited food and water, but only one DMT-laced cigarette was made available each hour. The first monkey didn’t smoke any DMT-laced cigarettes until the third day, and the second monkey didn’t smoke any DMT-laced cigarettes until the eighth day. “Interestingly,” as the researchers noted, “once DMT smoking was initiated in isolation, it continued at steady rates throughout the isolation sessions.”

The exception to this was the third monkey, which smoked a DMT-cigarette on its second day and then did not smoke any more for the remainder of its time in the isolation tank. The reason for this, the researchers speculated, is because the monkey got far too high and began convulsing, making it afraid to return to the smoking tube.

When the monkeys smoked the DMT-laced lettuce cigarettes, the researchers noticed a dramatic uptick in their movements. One monkey kept falling backwards and another began crawling around its cage. According to the researchers, one monkey “repeatedly moved his hands over the cage floor, following them with his eyes—movements virtually identical to those observed in the tracking of real objects.” Taken together, this suggested that the DMT was inducing hallucinations in the researchers’ primate subjects.

What did the researchers learn from their bizarre experiment? The main takeaway was that the monkeys will self-administer DMT when they are isolated and sensory deprived, even though they avoided dosing themselves with DMT when in a normal laboratory setting.

“The drug-taking behavior here was dramatically facilitated by the change in environmental conditions that motivate similar drug self-administration in man,” the researchers concluded. “That the aversive consequences of such drug use can be overshadowed by contextual environmental stimuli is not only evident, it is enlightening.”

If you’ve ever taken DMT, the thought of smoking the stuff while sitting in a dark box for days on end probably sounds horrifying. Fortunately, not all monkey experiments with DMT have been so horrific. Earlier this year, researchers in Brazil gave marmosets ayahuasca, a potent psychedelic brew made by shamans in the Amazon whose main psychoactive chemical is DMT, and found that it helped their depression.

To induce a state of depression in their primates, the researchers isolated the monkeys for eight weeks, which caused the younger monkeys to exhibit behaviors indicative of stress, such as excessive sleepiness, scratching and weight loss. Furthermore, the researchers measured the monkeys' cortisol levels, a hormone associated with stress reactions, during the eight weeks. Next, they administered ayahuasca provided by a religious organization called Barquinha. Each monkey received a dose of ayahuasca containing about 50 micrograms of DMT.

According to the researchers, the ayahuasca produced a notable uplifting effect on the mood of the monkeys based on the reduction of behaviors indicative of stress. According to the researchers, these mood-altering effects were noticeable for up to two weeks after giving the monkeys the brew. Even more amazing, however, was how these results compared to a similar study done by the researchers last year in which monkeys were given nortriptyline, a tricyclic antidepressant. According to the results of these studies, ayahuasca produced faster and more notable antidepressant effects.

These are but a few of the dozens of scientific studies that involve dosing animals with psychedelic compounds. Although many of these studies are ethically troubling, especially those that were undertaken in the '60s and '70s, they also provided profound insights into the way hallucinogens affect our brain. For now, doing research on humans that involves psychedelic compounds remains prohibitively difficult due to the illegal nature of the substances involved. This means that many of these studies are the most accurate scientific data we have on some of the most potent mind-altering chemicals on Earth. This will hopefully change in the future, but in the meantime, be sure to give your pet some extra love to thank them for their contribution to psychedelic science.

The Rise of Psychedelic Psychotherapy

Dear Culturalist: Am I Ready to Try Acid?

Hearing Food and Tasting Color with Psychedelics

How an All-Time Great Guitarist Opened his Mind with Acid

Alcoholics Anonymous: How LSD Almost Became the 13th Step

LSD-Assisted Hypnosis Might Become a Thing

Dropping Acid Might Improve White House Job Security

Kick Depression's Ass with Shrooms!

Johns Hopkins Suggests Reclassifying Psilocybin as Schedule IV

Why Researchers Are Getting Zebrafish High AF

Psilocybin Makes People Feel Better and Smoke Less

I Hosted a “Brieing” Party Where Middle-Aged Women Ate MDMA-Laced Cheese

Is Ketamine Replacing Other Club Drugs?

Speech Tool Might Help Identify Candidates for Shroom Therapies

These Cops Might Benefit from Taking MDMA