Unlearning to Relearn: How Psychedelics Disrupt Depression

Last update: February 21, 2024
Reading time: 3 minutes
By Brain Matters

Have you ever attempted to drive on the left side of the road when you usually drive on the right? Or tried to learn a friend’s new phone number but kept recalling their old one? You might accidentally slide into the wrong lane or mix up the numbers. This is a common experience called proactive interference, and it happens when your ability to learn new information is hindered by the old. 

When it comes to learning, unlearning can be equally important. Psychedelics have been discovered to be a possible means of catalysing this process. You may have heard of psychedelics like LSD and psilocybin in the context of recreational use, but these powerful psychoactive compounds can actually help treat mental illnesses, such as treatment-resistant depression.

Depression is often characterised by a self-reinforcing thought pattern called rumination, where negative thoughts and feelings repeat over and over, becoming more ingrained each time. Due to the repeated firing of this negative circuit, these thought processes become a default setting, or as we know from neuroplasticity, neurons that “fire together, wire together.” These ruminating thoughts become efficient, but unhelpful.

Cognitive behavioural therapy (CBT) is a possible solution to alleviating negative thought processes such as rumination. Through CBT, an individual can learn to identify and challenge determinantal thoughts and behaviours. But in some cases, it’s not always enough, and patients are unable to achieve remission. This is where psychedelics (could potentially) come into play.

Psychedelics can induce a mental environment conducive to unlearning negative thought patterns by introducing one key factor: entropy. In physics, entropy is a measure of the degree of disorder or randomness in a system. In the context of neurodynamics, entropy refers to the amount of randomness or unpredictability in the activity of neuronal networks.

But what are these neuronal networks, and why are they important? Neural networks are interconnected groups of neurons that work together to carry out specific brain functions. You can imagine the connectivity between these networks as paths on a ski slope. A healthy brain has many ski paths to choose from, which are scattered and random. But in a depressed brain, the paths are limited and deep due to repetitive use, which makes them difficult to change. Psychedelics are like fresh snow on these paths, giving you easier access to new slopes. The randomness of these paths reflects the brain’s ability to balance different functional networks and access different modes of thought and emotion. This is ideal for healthy emotional processing, but maybe not so much for skiing.

In summary, the connectivity between brain networks is often disrupted in depression, especially the connectivity involved in emotional regulation and reward processing. As a result, individuals with depression may have decreased entropy or randomness in certain brain regions, which causes a reduced capacity for cognitive flexibility and adaptation. The introduction of cortical entropy through psychedelics with a combination of CBT can disrupt this rigid thinking, which leads to emotional release, environmental sensitivity, and overall greater well-being.

In this case, unlearning negative thought patterns can be just as, if not more, important than learning new ones. While psychedelics may not help you forget your friend’s old telephone number, they offer a hopeful new avenue for the treatment of mental illness and give new insights into how we feel, think, and behave.

Author: Jenelle Rofe


  • Carhart-Harris, Robin L, and Guy M Goodwin. “The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future.” Neuropsychopharmacology, vol. 42, no. 11, 2017, pp. 2105–2113., https://doi.org/10.1038/npp.2017.84.
  • Carhart-Harris, Robin L., et al. “The Entropic Brain: A Theory of Conscious States Informed by Neuroimaging Research with Psychedelic Drugs.” Frontiers in Human Neuroscience, vol. 8, 2014.
  • Nejad, Ayna Baladi, et al. “Self-Referential Processing, Rumination, and Cortical Midline Structures in Major Depression.” Frontiers in Human Neuroscience, vol. 7, 2013, https://doi.org/10.3389/fnhum.2013.00666.
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