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Psilocybin and Mood Regulation

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With their recent publication, Kraehenmann et al. (2014) have increased our understanding of the mechanism that is thought to underlie the potential effectiveness of psychedelic–assisted psychotherapy in relieving mood and anxiety related symptomology. Their results elaborate on earlier findings that the administration of psychedelics [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][1] in addition with psychotherapy reduces anxiety symptoms on a relatively short term (Gasser et al., 2014; Moreno, Wiegand, Taitano, & Delgado, 2006), with one study even showing a reduction of anxiety and an increase of positive mood six months after only a single dose of psilocybin (Grob et al., 2011).

These clinical observations are now complemented by the finding that psilocybin attenuates amygdala [2] reactivity in response to emotionally loaded pictures in healthy volunteers, and that these changes are associated with a positive mood change. The authors suggest that psilocybin might have the potential to normalize neurobiological systems that are dysregulated in individuals with a depressed mood state. In addition to the psychometric evidence and clinical observations that psilocybin-assisted psychotherapy improves mood within a clinical population, the results of the current study provide a possible neurobiological explanation for these effects. The questions that arise from this study relate to the degree to which these results can be generalized to a clinical population, and if and to what extent the acute changes in amygdala reactivity by themselves may account for long term changes in the processing of emotions.

According to the Trimbos Institute (2014) [3] there is a current prevalence of 4 – 10 % of people suffering from depression in Western society. Because of its high prevalence and devastating individual and societal consequences, depression is considered a major public health problem (Spijker, van Straten, Bockting, Meeuwissen, & van Balkom, 2013). The regular treatment options include psychotherapy, pharmacotherapy or a combination of the two, of which the latter is thought to establish the most favorable outcome. One of the added values of the study of Kraehenmann (2014) is the finding that psilocybin – with its pharmacological effect on amygdala reactivity – shares a neurobiological mechanism of action with selective serotonin reuptake inhibitors (SSRI’s), which are prescription drugs that are commonly deployed in the treatment of depression and other mood related disorders. What then, might be the necessity of exploring these psychedelic compounds as alternatives for customary treatment options?

The treatment of mood disorders with SSRI’s has several disadvantages, with probably the most prominent criticism being the modest response (47%) and remission rates (between 28 – 33%; Trivedi et al., 2006). Other disadvantages include a delayed therapeutic action (Stahl, 1998), withdrawal difficulties (Schatzberg, 1997), and the daily pharmacological treatment routine. Results from the psychedelic-assisted treatment sessions imply a prolonged uplift of mood after the pharmacological intervention, which is only implemented occasionally. These results are far too preliminary to abandon the extensively reviewed prescription drugs in the treatment of mood disorders and switch to less scientifically studied compounds that share some of the same neurobiological features, but it might be valuable to elucidate upon their therapeutical potential. What is it that psychologically distinguishes one type of drug with antidepressant properties from the other, and who are the people that might benefit from making this distinction? With one out of ten people suffering from depressive symptoms [4], the need for this kind of knowledge may not be underestimated.

[1] Red. classical psychedelics, which are isolated from a broader categorization of psychedelics by their pharmacological manifestation as serotonin 5-HT2A receptor agonists
[2] The amygdala is a structure in the limbic system that plays a major role in the processing of emotions and is therefore a key target for psychopharmacological interventions to treat mood and anxiety disorders (Phelps & LeDoux, 2005)
[3] The Trimbos Institute is a Dutch organization that serves as an information centre for matters related to mental health
[4] In Western societies (Trimbos Institute, 2014)
Gasser, P., Holstein, D., Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., & Brenneisen, R. (2014). Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases. The Journal of Nervous and Mental Disease, 00(00), 1. doi:10.1097/NMD.0000000000000113
Grob, C. S., Danforth, A. L., Chopra, G. S., Hagerty, M., McKay, C. R., Halberstadt, A. L., & Greer, G. R. (2011). Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Archives of General Psychiatry, 68(1), 71–8. doi:10.1001/archgenpsychiatry.2010.116
Kraehenmann, R., Preller, K. H., Scheidegger, M., Pokorny, T., Bosch, O. G., Seifritz, E., & Vollenweider, F. X. (2014). Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers. Biological Psychiatry, 1–9. doi:10.1016/j.biopsych.2014.04.010
Moreno, F. A., Wiegand, C. B., Taitano, E. K., & Delgado, P. L. (2006). Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder. The Journal of Clinical Psychiatry, 67(11), 1735–1740. doi:10.4088/JCP.v67n1110
Moreno, F. A., Wiegand, C. B., Taitano, E. K., & Delgado, P. L. (2006). Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder. The Journal of Clinical Psychiatry, 67(11), 1735–1740. doi:10.4088/JCP.v67n1110
Spijker, J., van Straten, A., Bockting, C. L. H., Meeuwissen, J. a C., & van Balkom, A. J. L. M. (2013). Psychotherapy, antidepressants, and their combination for chronic major depressive disorder: a systematic review. Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie, 58(7), 386–92. Retrieved from
Stahl, S. M. (1998). Mechanism of action of serotonin selective reuptake inhibitors. Serotonin receptors and pathways mediate therapeutic effects and side effects. Journal of Affective Disorders, 51(3), 215–35. Retrieved from
Trimbos Instituut (2014). Feiten en cijfers depressie. Reviewed on July 12, 2014 at
Trivedi, M. H., Rush, a J., Wisniewski, S. R., Nierenberg, A. a, Warden, D., Ritz, L., … Fava, M. (2006). Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. The American Journal of Psychiatry, 163(1), 28–40. doi:10.1176/appi.ajp.163.1.28[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

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