Psychedelics.com Team
PART I: Summary
📖 What’s This Paper About?
This paper explores the potential use of psilocybin as a treatment for depression, particularly for treatment-resistant cases. The research analyzes recent studies showing that psilocybin, the active compound in “magic mushrooms,” may provide significant benefits for patients who don’t respond to conventional antidepressants by acting on serotonin receptors in the brain.
Why This Matters
According to WHO statistics, more than 260 million people worldwide suffer from clinical depression, with 15-33% experiencing treatment-resistant depression. This creates an urgent need for novel therapeutic approaches for patients who don’t respond to currently available medications.
- Treatment-resistant depression represents a significant unmet medical need
- Psychedelic compounds like psilocybin offer a different mechanism of action than traditional antidepressants
- Recent clinical trials show promising results with rapid and sustained effects
Top 5 Takeaways
1. Mechanism of Action
Psilocybin is dephosphorylated to psilocin, which crosses the blood-brain barrier and acts as a serotonin receptor (5-HT2A) agonist with higher affinity than serotonin itself.
2. Neural Response
Psilocybin increases amygdala activation during positive emotional stimuli while decreasing activation during negative emotional stimuli, potentially explaining its positive emotional effects.
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3. Comparable Efficacy
One study found no substantial difference in antidepressant effects between psilocybin and escitalopram (a selective serotonin reuptake inhibitor), suggesting comparable therapeutic potential.
4. Rapid Response
The COMPASS Pathways study showed significant improvements in approximately one-third of participants by the end of the third week, indicating a relatively quick onset of action.
5. Safety Profile
Psilocybin has a favorable safety profile with common side effects including headache, nausea, fatigue, and insomnia. Only 1.5% is excreted unchanged in urine, making it safe for patients with renal insufficiency.
The Bigger Picture
The research on psilocybin represents a paradigm shift in psychiatric treatment. Unlike traditional antidepressants that require daily administration for weeks before showing effects, psilocybin may offer rapid relief with just a few doses. Additionally, some studies suggest psychedelics can enhance brain-derived neurotrophic factor (BDNF), positively affecting synaptic plasticity. These findings point toward a future where psychedelic therapy could become an established treatment option for depression, especially treatment-resistant cases.
Final Thought
While psilocybin therapy for depression is still in the research phase, current evidence shows significant promise for addressing one of the most challenging mental health conditions, offering hope to millions who don’t respond to conventional treatments.
PART II: Complete English Translation
THE USE OF PSILOCYBIN AS A TREATMENT FOR DEPRESSION
Darbinyan R.G., Kravtsov A.P.
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Scientific advisor: Professor Rusanovsky V.V., MD
Department of Pharmacology, St. Petersburg State Pediatric Medical University
Email: ra**************@***il.com
According to WHO statistics, more than 260 million people worldwide suffer from clinical depression, with treatment-resistant depression affecting 15 to 33% of them. This necessitates new treatment methods for those who do not respond to currently used medications. Recent results have shown that psychedelic drugs may play a role in treating depressive symptoms. One such drug could be psilocybin, which has been studied in recent years as a possible treatment for depression.
Keywords: psilocybin, depression, psilocin, serotonin
Research Relevance
According to WHO statistics, more than 260 million people worldwide suffer from clinical depression, with treatment-resistant depression affecting 15 to 33% of them. This necessitates new treatment methods for those who do not respond to currently used medications. Recent results have shown that psychedelic drugs may play a role in treating depressive symptoms. One such drug could be psilocybin, which has been studied in recent years as a possible treatment for depression.
Research Objective
Analysis of literature data on the use of psilocybin for the treatment of depression.
Materials and Methods
Review of scientific literature
Results
Psilocybin is dephosphorylated to psilocin, which is its active form and crosses the blood-brain barrier [1]. Psilocin acts as an agonist of serotonin receptors (5-HT2A) and has a higher affinity for them than serotonin itself [1, 2].
It is also assumed that psilocybin indirectly increases dopamine activity by increasing serotonin input, as there is a high correlation between the serotonergic and dopaminergic systems. Evidence for this is the reduction of psilocybin activity by haloperidol, which is a dopamine antagonist [1]. Additionally, it has been found that psilocybin increases the activation of the amygdala during the stimulation of positive emotions and decreases it during the stimulation of negative emotions [1]. Through such mechanisms, it apparently induces positive emotions [1].
One study showed no significant difference in antidepressant effects between psilocybin and escitalopram (a selective serotonin reuptake inhibitor) in a group of patients being treated for depression. In a recently completed study conducted by COMPASS Pathways, psilocybin treatment led to a response and significant improvement in approximately one-third of participants by the end of the third week. The most common adverse reactions were headache, nausea, fatigue, and insomnia [1]. Some studies have shown that psychedelics can improve brain-derived neurotrophic factor (BDNF), having a positive effect on synaptic plasticity [2].
Friederike Holze et al. in their study noted that the duration and length of psilocybin’s effect depended on the dose but did not depend on body weight [3]. Of great importance is the intensive metabolism of psilocin, in which only 1.5% is excreted unchanged in urine, making it safe for patients with renal insufficiency [3].
Conclusions
Psilocybin has an antidepressant effect comparable to currently used antidepressants. Unlike the latter, it is effective in addressing treatment-resistant depression, and moreover, with a rapid effect, it does not have pronounced side effects. However, psilocybin therapy in combination with professional support in treating depression is still at the research stage, but it is clear that significant hopes are placed on it.
This is informational, not medical advice.
Read the Original Russian Version
This translation is based on the original Russian academic paper. Access the source document to see the scholarly work in its native language.
Sources
1. Á. Jóhannesdóttir and E. Sigur sson, "The use of psilocybin for treatment-resistant depression," Laeknabladid, vol. 108, no. 9, pp. 403–410, 2022, doi: 10.17992/lbl.2022.09.706.
2. R. A. Al-Naggar, H. Alshaikhli, and G. Erlam, "Effectiveness of psilocybin on depression: A qualitative study," Electron. J. Gen. Med., vol. 18, no. 3, 2021, doi: 10.29333/ejgm/10862.
3. F. Holze, A. M. Becker, K. E. Kolaczynska, U. Duthaler, and M. E. Liechti, "Pharmacokinetics and Pharmacodynamics of Oral Psilocybin Administration in Healthy Participants," Clin. Pharmacol. Ther., no. January 2023, 2022, doi: 10.1002/cpt.2821
