Psychedelics lead to long-lasting brain changes

September 8, 2020

Written by: Claudia Lopez-Lloreda

Psychedelics are able to change us. Specifically, they change the way people visually process the world as well as their emotional connections to it, even if it’s just for a moment. However, the degree to which psychedelics change us and how long this change lasts is just now being studied. Although previous studies looked at the brain of people administered with psilocybin, the active component in psychedelic mushrooms, a recent study observed people one month out from taking the drug and found a striking result: psilocybin led to long-lasting brain and emotional changes1.

Psilocybin is one of many psychedelics, which are also called hallucinogens for their ability to cause sensations or images that feel real2. It was LSD (D-lysergic acid diethylamide in chemist talk) created by Albert Hoffman in 1938 that sparked scientists’ interest in considering psychedelics as treatments. During the 1950 and 60s, LSD was used in clinical trials as a way to treat depression and substance use disorders. One meta-analysis, which looks at the results of many studies, found that a single dose of LSD was associated with reduced drinking in people with alcoholism3.

Decades later, some scientists still consider psychedelics, specifically psilocybin and LSD, to be a potential therapy for mood disorders such as depression and anxiety and for substance use disorders such as tobacco use disorder and alcohol use disorder. For example, one study found that psilocybin treatment reduced symptoms of depression and improved anxiety after one week, with some people having reduced depression scores for up to three months4.

One of the ways psychedelics can potentially help with depression is by reducing brain activity in areas known to be hyperactive in people with this condition. For example, dysfunction of certain brains areas related to affect, or the emotional experience, such as the amygdala and the anterior cingulate cortex has been related to this disorder. Studies had shown that psilocybin could reduce activity of the amygdala and other brains areas in healthy participants5,6. Another study in people with treatment-resistant depression also showed that psilocybin reduced amygdala activity and that this reduction was associated with a reduction in depressive symptoms, meaning that it can lead to meaningful short-term changes in the brain and behavior7. However, mood and substance use disorders are often chronic conditions that require treatment that can alter the brain in a more sustained manner.

For this reason, a group of scientists at Johns Hopkins set out to determine if brain changes after taking psilocybin lasted more than a week. In this study, they treated healthy individuals with a high dose of psilocybin (25 mg/70kg) and then analyzed the way they processed emotions, their levels of emotional distress, and how the activity and connectivity of the brain changed.

The researchers found that after one week of administering psilocybin, negative feelings such as anger, confusion, and tension decreased while positive feelings such as joy, pride, and awe increased. Consistent with previous studies, they saw that psilocybin decreased activity in the amygdala in response to viewing facial images after one week. The scientists also found that activity in cortical areas, which process higher order functions like cognition, were increased. However, after one month, amygdala activity and negative affect returned to their initial levels prior to psilocybin administration, while positive affect remained increased.

Additionally, scientists observed sustained differences in connections through the brain in a specific brain network. This network is a group of connections that are activated in the brain when a person is not focused on anything in particular, or in other words when they are cognitively “at rest”. This finding suggests that psilocybin induces a period of plasticity, a timeframe in which the strength of connections across the brain can change.

Scientists think that this general increase in connectivity means that psilocybin allows participants to perceive the world in new ways, while at the same time modulating brain areas that control feelings to allow for emotional plasticity. The researchers suggest then that psilocybin could be used as a way to treat patients with mood and substance use disorders. As a limitation, they note that the participants used in the study were healthy people. This means that long-lasting changes in the brain could be different in people with mood or substance abuse disorders than the brain alterations seen in this study. However, the study gives insight into the ways that psilocybin and psychedelics in general could be affecting the brain and consequently behavior in an enduring manner.

More studies will be needed to understand exactly how long these alterations remain and if they are different from other standard treatments for mood disorders such as serotonin-reuptake inhibitors and cognitive behavioral therapy. But as a Schedule I drug under the Controlled Substances Act, it is incredibly hard for researchers to obtain funding to study its effects on the brain and its capacity to help with psychiatric conditions. Therefore, it is necessary to start considering psychedelics as serious options and continue advocating for increased funding of this important research.  


Cover image: Pixabay.


  1. Barrett, F. S., Doss, M. K., Sepeda, N. D., Pekar, J. J., & Griffiths, R. R. (2020). Emotions and brain function are altered up to one month after a single high dose of psilocybin. Scientific Reports, 10(1).
  2. National Institute on Drug Abuse. (2020, July 6). Hallucinogens DrugFacts. National Institute on Drug Abuse.
  3. Krebs, T. S., & Johansen, P.-Ø. (2012). Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. Journal of Psychopharmacology, 26(7), 994–1002.
  4. Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M. J., Erritzoe, D., Kaelen, M., … Nutt, D. J. (2016). Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry, 3(7), 619–627.
  5. Kraehenmann, R., Preller, K. H., Scheidegger, M., Pokorny, T., Bosch, O. G., Seifritz, E., & Vollenweider, F. X. (2015). Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers. Biological Psychiatry, 78(8), 572–581.
  6. Carhart-Harris, R. L., Erritzoe, D., Williams, T., Stone, J. M., Reed, L. J., Colasanti, A., … Nutt, D. J. (2012). Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proceedings of the National Academy of Sciences, 109(6), 2138–2143.
  7. Carhart-Harris, R. L., Roseman, L., Bolstridge, M., Demetriou, L., Pannekoek, J. N., Wall, M. B., … Nutt, D. J. (2017). Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports, 7(1).

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