Abstract
Due to an increasing number of depression diagnoses and limited effective treatments, researchers continue to explore novel therapeutic strategies for this disorder. Recently, interest has revolved around the use of serotonergic psychedelics to reduce the symptoms of depression. In this systematic review, we summarize the currently available knowledge on the safety and efficacy of psychedelic substances for the treatment of depression. A literature search of the PubMed/MEDLINE database identified 14 clinical trials from the last 10 years that examined the use of psilocybin, MDMA, DMT, or LSD for the treatment of depression symptoms. Some psychedelics, especially psilocybin, demonstrated an ability to reduce depressive symptoms as measured by several psychological scales, which was often sustained for months after the last psychedelic session. Moreover, one study revealed that psilocybin has comparable efficacy to escitalopram in the treatment of depression. None of the studies reported any serious adverse events associated with psychedelic administration. The reviewed studies suggest that psychedelics have great potential in depression therapy and, after addressing and overcoming the current study limitations, may be used as a novel method of treating depression in the future.
Highlights
The results showed that psilocybin reduced amygdala reactivity to negative and neutral stimuli and improved the mood of healthy volunteers, as confirmed by the Positive and Negative Affect Schedule (PANAS) scores
These findings suggest that psilocybin may normalize the amygdala hyperactivity and negative mood states associated with depression [29]
It is important to mention that none of the clinical trials included in this review revealed any serious adverse events occurred during the psychedelic administration period and afterwards, researchers detected some cases of serious adverse events caused by serotonergic substances, foremost MDMA, such as serotonin syndrome [66], hallucinogen persisting perception disorder (HPPD) [67], exogenous psychosis [68], fatal hyperthermia [69], rhabdomyolysis, and renal failure [70]
Summary
Some factors are strongly associated with a higher risk of developing depression, including environmental factors like emotional, physical, and sexual abuse; genetic and epigenetic factors; and organic changes in the central nervous system, especially in the hippocampus. These factors can affect the neurobiological stressresponsive systems, resulting in neuroinflammation and altered neurotransmission [3]. The biological dysfunctions produced by these factors can have a great impact on physical health and are associated with a higher risk of developing various conditions, such as heart disease, disability, diabetes mellitus, obesity, and cancer [4]. The most pressing clinical concern is suicide, a direct cause of death in patients with depressive disorders, as the pooled lifetime prevalence of suicide attempts in depressed patients is estimated to be 27–34%, which is almost 20 times greater than in general population [1,5]
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