News Release

Treating mood disorders with psychoactive drugs

How do treatments for mood and anxiety disorders derived from psilocybin and cannabis exert their effects in the brain?

Reports and Proceedings

Society for Neuroscience

SAN DIEGO, CA — There is a need for new, effective treatments for mental illnesses like depression and anxiety. Researchers are expanding the field’s therapeutic toolbox by investigating the antidepressant and anxiolytic properties of drugs such as psilocybin and cannabis. The findings were presented at Neuroscience 2022, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health.

Mood disorders are among the most frequently diagnosed mental illnesses worldwide. Current drug treatments for these disorders, such as serotonin modulators and benzodiazepines, are slow to take effect, and when they do, they often bestow unwanted side effects. Additionally, many people with depression don’t respond at all to these medications. However, treatments derived from the psychedelic compound psilocybin and the psychoactive drug cannabis may be promising for a range of mental health disorders. Neuroscientists are probing how they work in the brain.

Today’s new findings show that:

  • The altered consciousness effects of psilocybin may not be necessary for it to produce anti-anxiety and anti-depressive effects in mice. (Katherine M. Nautiyal, Dartmouth College)
  • In male rats, symptoms of depression and anxiety following chronic stress may be improved by drugging a protein in the brain’s endocannabinoid system. (Steven R. Laviolette, University of Western Ontario)
  • Chronic cannabis use is associated with improvement in some cognitive functions in people with bipolar disorder. (Alannah Miranda, University of California, San Diego)

“As a field, we are thinking about psilocybin and cannabis in new ways and not only evaluating them for their potential therapeutic benefit but probing how they exert their effects in the brain,” says Lisa Monteggia, the Barlow Family Director of the Vanderbilt Brain Institute and professor pharmacology at Vanderbilt University, who studies mechanisms underlying antidepressant efficacy. “The research presented today is contributing to the growing evidence that these compounds may offer new avenues for symptom relief in many mental health conditions.”

This research was supported by national funding agencies including the National Institutes of Health and private funding organizations. Find out more about social behavior and the brain on BrainFacts.org.

Press Conference Summary
- Many people who take conventional drug treatments do not experience symptom relief.
- Researchers are investigating compounds such as psilocybin and cannabis to better understand how they produce anti-depressive and anti-anxiety effects.

Investigating Altered Consciousness and the Role of Serotonin Receptors in the Therapeutic Effects and Mechanisms of Actions of Psilocybin
Katherine M. Nautiyal, katherine.nautiyal@dartmouth.edu, Abstract 229.05

  • Psilocybin, the active psychedelic compound in “magic mushrooms,” has rapid and long-lasting benefits for those with depression and anxiety. However, the way it works and whether the compound’s therapeutic effects are independent of its effects on consciousness (i.e., hallucinations) is unknown.
  • Researchers injected mice with psilocybin under anesthesia. Afterward, the mice showed fewer anxiety-related behaviors, decreased anhedonia, and increased motivation for rewards, suggesting that the conscious experience of the drug may not be required for it to induce anti-depressive and anti-anxiety effects.
  • Researchers tested the role of the serotonin 1B receptor in psilocybin’s effects by administering psilocybin to genetically engineered mice lacking this receptor.

Inhibition of Fatty Acid Binding Protein-5 Stress-Induced Anxiety-Like and Depression-Like Psychopathology
Steven R. Laviolette, steven.laviolette@schulich.uwo.ca, Abstract 400.07

  • The brain’s endocannabinoid system is a promising target for treating mood and anxiety disorders because of its ability to regulate the brain’s emotion and anxiety circuits.
  • Researchers investigated the effects of inhibiting fatty acid binding protein-5 (FABP-5), a chaperone protein within the endocannabinoid system, on mood and anxiety symptoms in male rats.
  • Pharmacologically blocking the FABP-5 system resulted in an improvement in depressive and anxiety-related symptoms following chronic stress with no cognitive or addictive side effects. Signaling pathways within the limbic system appeared to mediate these improvements.
  • The findings identify a new brain target for treating depression and anxiety by safely altering the brain’s naturally occurring cannabinoid system without the side effects of traditional psychoactive drugs.

Normalization of Goal-Directed Behaviors Associated With Chronic Cannabis Use in Bipolar Disorder
Alannah Miranda, ahmirand@health.ucsd.edu, Abstract 562.06

  • Cannabis use is highly prevalent in people with bipolar disorder. Many report problems with motivation and cognitive functioning and that they use cannabis to cope.
  • Researchers found that chronic cannabis use is associated with a modest improvement in some cognitive functions in people with bipolar disorder. Cannabis use was also associated with a reduction of risky decision making and increased motivation in those with bipolar disorder, but not healthy participants.
  • While long-term negative effects such as on mood stability are possible, chronic cannabis use may have uniquely beneficial effects in people with bipolar disorder, potentially by reducing dopaminergic activity in the brain.

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