Effects of Psilocybin on the Amygdala's Response to Emotions

A study conducted by Roseman, Demetriou, Wall, Nutt, and Carhart-Harris (2018) sought to explore the antidepressant function of psilocybin on amygdala responsiveness to facial expressions. Using MRI techniques, the study mainly focused on the amygdala’s response to fearful vs. neutral faces. Their hypothesis suggested that the amygdala’s reactivity will be linked to the nature of the psychological experience under psilocybin use, as the amygdala in depressive patients has been shown to be hyperactive to negative emotions. Hence, the amygdala’s response to emotion must change after the use of psilocybin, improving depressive states in individuals. Roseman et al., (2018) included 20 patients with ages ranging from 27 to 64 in the study. The patients had to score over 16 in the 21-item Hamilton Depression Rating Scale (from moderate to severe depressive symptoms) and had to have no indication of improvement, following two antidepressant treatments that lasted over six weeks.

Consequently, patients were asked to be antidepressant-free two weeks prior to psilocybin consumption. Firstly, the patients followed an fMRI scanning before the administration of the dosages. Then, the patients underwent two non-directed, supportive psilocybin therapies. During the first therapy, patients were administered a low dose (10mg), which was aimed to familiarize the patients with the experience. The second therapy was performed a week later, when the therapeutic higher dose was administered (25mg). The post-administration fMRI was done the next morning after the therapeutic dosage at precisely the same time that the previous scan was undertaken. Moreover, the fMRI presented happy, fearful, and neutral faces to measure the reactivity of the brain to different emotions. The results of the fMRI analysis demonstrated significantly increased response in the right amygdala to happy and fearful faces. The amygdala was also highly responsive to fearful vs. neutral faces, which were predictive of clinical improvements post-high-dose psilocybin administration. Moreover, the majority of the participants exhibited a clinically meaningful decrease in depressive symptoms, as their stated depression score diminished more than 50%. Additionally, nine out of the twenty patients experienced no relapse after five weeks of treatment.

Roseman et al., (2018) were effective at demonstrating the positive effects of using psychoactive drugs for clinical purposes. In opposition, their results are controversial and need further analysis to explain the differences of the physiological effects between SSRIs and psilocybin, which are stated to improve depressive states.

Past studies have associated the decrease in the amygdala’s reactiveness to fearful and negative emotions to the administration of SSRIs. According to Murphy, Norbury, O’Sullivan, Cowen, and Harmer (2009), the administration of SSRIs revealed an immediate effect, as the SSRIs significantly reduced the amygdala’s response to fearful facial expressions compared to placebo. Furthermore, Harmer, Duman, and Cowen (2017) stated that depression is associated with increased responses in limbic areas (including the amygdala) to negative emotional stimuli. These results have been coupled with the over-reactivity of regulative and inhibitory regions in the brain, such as the dorsolateral and prefrontal cortex. Also, the study has shown that acute doses of SSRIs have displayed a decreased amygdala response to negative emotional stimuli, even after six weeks of SSRIs treatments, in which the amygdala was responsive to happy faces, and was less reactive to negative faces. The results of the Roseman’s et al., (2018) study are contradictory, as the fMRIs revealed that patients significantly improved in their depressive states, but that the reactivity of their right amygdala was increased to fearful versus neutral faces. Such opposite results lead to the conclusion that because SSRIs act mainly as a partial agonist in the 5-HT1A, perhaps, it can have a different effect on the amygdala.

After reassessing Roseman’s et al., (2018) study and comparing it to previous studies, it is clear that there needs to be further research to investigate if the difference in the amygdala’s responsiveness has to do with the immediate positive effects that psilocybin has on depressed individuals..

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Roseman, L., Demetriou, L., Wall, M. B., Nutt, D. J., & Carhart-Harris, R. (2018). Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression. Neuropharmacology, 142, 263-269.

Harmer, C. J., Duman, R. S., & Cowen, P. J. (2017). How do antidepressants work? new perspectives for refining future treatment approaches. The Lancet Psychiatry, 4(5), 409- 418.

Murphy, S. E., Norbury, R., O'Sullivan, U., Cowen, P. J., & Harmer, C. J. (2009). Effect of a single dose of citalopram on amygdala response to emotional faces. The British Journal of Psychiatry, 194(6), 535-540.