Giving lab rats illicit psychedelic drugs may help scientists uncover how it can be used to treat anorexia in humans.
Psychedelics, including psilocybin — the psychoactive compound produced by ‘magic mushrooms’ — show promise in treating the eating disorder anorexia nervosa. But they don’t work for everyone.
Anorexia nervosa is a mental health disorder that causes people to reduce the amount of food they eat over fear of gaining weight due to a distorted body image. It’s hoped that psilocybin can help ‘break down’ these ingrained patterns of thoughts and behaviour.
But not all people have clinically significant improvements after psilocybin treatments, curiously, particularly those with anorexia nervosa. The reason behind this is still unknown and so scientists are hoping to better understand the biological reasons why psychedelics might be beneficial for some but not others.
Laboratory animal studies can help scientists understand both the drug’s effects on our bodies and how they can change behaviour. Animals that act as a model for humans let scientists examine brain function at a detailed level not possible in human studies. For example, they can precisely link changes in the release of brain chemicals called neurotransmitters with specific aspects of learning behaviour.
People participating in trials of drugs are often not told whether they are receiving the drug or a fake, placebo dose — they are ‘blinded’. But existing expectations can lead them to claim a positive experience. Animal studies can avoid these issues, which is particularly important for psychedelic studies because it is not possible to ‘blind’ them to the intense subjective effects of psychedelic drugs.
Researchers at Monash University are trying to understand the specific biology and chemistry of psilocybin relevant to anorexia nervosa, using the most well-established animal model of the condition, known as activity-based anorexia.
The experimental protocol was developed in the 1960s and relies on allowing animals unlimited access to a running wheel paired with time-limited (but not quantity-limited) access to food. Bizarrely, rats or mice will choose to exercise instead of eat even when they reach extremely low body weights. Animals without access to a running wheel quickly learn to adapt to the scheduled food access and eat enough food in the time window to maintain body weight. But the animals with a running wheel who compulsively exercise appear to have some kind of failure in their learning processes — they never learn to adapt to the feeding schedule. Monash University researchers have also shown a specific neural circuit linking weight loss with inflexible learning in rats.
Given both anorexia in humans and the anorexia rat model are both based on inflexible thinking, Monash University researchers are investigating the effects of psilocybin on adaptive learning in rats and mice. The studies are hoping to discover how changes in learning are driven by changes in brain function. The researchers are particularly interested in the function of neurotransmitters dopamine and serotonin.
The animal models have shown that psilocybin has some interesting effects on reward learning that could explain how it can be useful to treat people with anorexia nervosa. It offers hope for the range of psychiatric conditions that are also characterised by impaired flexible behaviour, such as depression, anxiety and PTSD .
Psilocybin-induced changes in both serotonin and dopamine signalling in the brain need to be far better understood before psychedelics can become integrated into mental health treatments. But a drug-affected rat on a wheel may uncover more about the human brain than such an unconventional experiment may suggest.
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Dr Claire Foldi is a Senior Research Fellow at the Monash Biomedicine Discovery Institute where she leads the Anorexia and Feeding Disorders Group. She also co-leads the Workforce Development stream of the National Centre for Eating Disorders Research and is a member of the Monash Centre for Consciousness and Contemplative Studies (M3CS) and the Monash Neuromedicines Discovery Centre (NDC).
The study is funded by the National Health and Medical Research Council of Australia (NHMRC).
Dr Foldi is on the Scientific Advisory Board for Octarine Bio (Denmark) a synthetic biology company developing novel psychedelic compounds.