Researchers from McGill University have discovered how lysergic acid diethylamide (LSD) increases empathy and social behaviour. Their findings could help unlock the potential of LSD as a medical treatment for psychiatric disorders.
LSD is a potent hallucinogen and can alter a person’s perception of reality and vividly distort the senses. It can also produce feelings of happiness, trust and enhanced emotional empathy.
Originally derived from “ergot,” a fungus that grows on rye and other grains, the hallucinogenic effect of LSD was first discovered in 1943. Recreational use of LSD increased in the 1960s, and more recently ‘micro-dosing‘ has gained popularity as a way to enhance mood, creativity and relationships. At the same time, LSD and other psychedelic substances are seeing a clinical renaissance as potential mental health treatments, but only now are scientists starting to understand how LSD works.
To learn more about how LSD exerts its social and mood boosting effects, the McGill researchers administered low-dose LSD (or an inactive equivalent) to male mice either as a one-off, or as a daily dose given over the course of a week.
The team then examined the “sociability” of the mice using social interaction tests. When two mice are placed in the same space, they will normally investigate each other by sniffing and crawling over each other. Introduce a third, and mice will investigate the stranger more than their familiar counterparts. Using Direct Social Interaction and Three Chambers tests, researchers record and analyze the behaviour of mice under different conditions to determine sociability levels.
In this instance, they found that a single dose of LSD failed to increase sociability. However, repeat doses did have an effect. Mice given a daily dose spent more time interacting with strangers, seemingly without any unwanted side effects.
But the question remains, why does this happen?
The team used a cutting-edge technique called optogenetics. This uses genetic engineering to introduce light-sensitive proteins into select brain cells. Researchers can then use light signals to “turn on” these cells and monitor the resulting brain activity in different social environments. With this insight, they were able to describe the underlying mechanism for the social effects of LSD in rodents.
“Increased sociability occurs because the LSD activates the serotonin 5-HT2A receptors and the AMPA receptors — which is a glutamate receptor, the main brain excitatory neurotransmitters — in the prefrontal cortex and also activates a cellular protein called mTORC1,” explains Danilo De Gregorio, a postdoctoral fellow in the Neurobiological Psychiatry Unit at McGill and the study’s first author.
“These three factors, taken together, promote social interaction in mice, which is the equivalent of empathy and social behaviour in humans.”
Using optogenetics, the researchers also discovered that “turning off” LSD-related activity in the prefrontal cortex removed the social effects of the drug. This highlights the importance of the prefrontal cortex for the behavioural effects of LSD.
Next, the researchers plan to test LSD in mice displaying autism spectrum and social anxiety characteristics. Eventually, they hope to explore whether micro-doses of LSD could potentially be a viable and safe medical treatment for those with psychiatric and social disorders.
“Social interaction is a fundamental characteristic of human behaviour,” notes the co-lead author Dr. Gabriella Gobbi, Professor in the Department of Psychiatry at McGill and psychiatrist at the McGill University Health Centre.
“These hallucinogenic compounds, which, at low doses, are able to increase sociability may help to better understand the pharmacology and neurobiology of social behaviour and, ultimately, to develop and discover novel and safer drugs for mental disorders.”