Study finds LSD reverses the deficiency in avoidance learning in impaired rats

New research suggests that LSD — known as the psychedelic drug “acid” — has antidepressant effects that appear to be linked to the serotonergic system in the brain.

Recent research has found that LSD can reduce the anxiety associated with life-threatening diseases such as cancer. But scientists are still relatively ignorant about the effects of LSD in the brain.

“Although early and extensively recognised for an ability to facilitate certain strategies of psychotherapy, particularly in the context of anxiety neuroses and/or depressive reactions, the therapeutic potential of serotonergic hallucinogens has hardly been considered pharmacologically,” Tobias Buchborn and his colleagues at the Otto-von-Guericke University in Germany explained in their study.

The study, published in April 30 in the Journal of Psychopharmacology, used an animal model to examine how LSD-induced changes in brain chemistry and behavior could be related to depression.

Removal of the olfactory bulbs from rodents — a surgery known as a bulbectomy — causes a reorganization of the brain and induces behavior that resembles clinical depression. Antidepressant medications have been shown to reverse many of the changes that occur in rodents after a bulbectomy.

In the study, bulbectomized rats were administered either LSD or a saline solution for 11 days. Another group of rats received a “sham” surgery. All of the rats completed an experiment designed to measure their ability to learn to actively avoid unpleasant stimuli, a cognitive process called avoidance learning that is impaired by bulbectomies.

The researchers found that the daily administration of LSD “largely reverse[d]” the deficiency in avoidance learning in the bulbectomized rats. The rats who had been given LSD “caught up” to the rats who were not bulbectomized, and “significantly differed” from the bulbectomized rats given saline, they wrote.

The researchers also found that LSD altered the function of serotonin receptors in an area of the brain known as the hippocampus.

“As the avoidance learning deficits after bulbectomy are reversible by drugs classified as antidepressant only, we infer that LSD’s behavioural effect in this model can be considered antidepressant-like. Our inference is strengthened by the fact that LSD specifically helps bulbectomized, but not sham-operated, rats.”

LSD appeared to have an antidepressant-like effects in the study, but the psychedelic substance should not be confused with the antidepressant class of drugs. Antidepressants and LSD are quite different, despite their similar effects on avoidance learning.

“Exploratory evidence suggests that serotonergic hallucinogens – when psychotherapeutically embedded – might be of assistance in the treatment of neurotic-type depression, or emotional distress associated with advanced stages of cancer,” Buchborn and his colleagues wrote. “However, as their acute effects on affection are highly variable and critically dependent on the pre-existing mood, hallucinogens should not be (mis-)conceptualised as acute mood-enhancers or antidepressants in a literal sense. Instead, they might rather be seen as a tool for psychotherapy to facilitate access to emotion-salient cognitions (e.g. memory) and work on the inherent biases that negatively prime the patient’s affective mindset.”