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Placebo

Psilocybin

Psilocybin

Psilocybin potentiates a high degree of neuroplasticity and neurogenesis. Its molecular structure closely resembles that of a serotonin molecule and acts primarily on the 5-HT2A serotonin receptor, introducing entropy into the brain. This proverbial “shaking of the snow globe” helps to smooth out deeply grooved neural pathways that often play a role in compulsive behaviors and thought loops.

 

As connections are made between brain networks that don’t normally exist, psilocybin simultaneously downregulates the Default Mode Network in the brain—the area responsible for rumination, metacognition (thinking about thinking), self-reflection, mind-wandering, and “time travel” (projecting to the future, thinking to the past). As shown through years of research and a multitude of peer-reviewed studies, psilocybin can have a therapeutic effect on conditions such as depression, anxiety, OCD, addiction, eating disorders, and PTSD.

In the graphic above, the image of the brain on the left is a placebo. On the right, a brain on psilocybin. The nodes and colors represent different networks — not areas — of the brain. The normal-state brain is highly ordered — connections mainly occur within networks, or between networks but in limited, structured ways. On psilocybin, however, the cross-talk between previously unrelated networks is enormous.

References:

  1. Carhart-Harris RL, Roseman L, Haijen E, et al. (2016). Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry, 3(7), 619-627.

  2. Griffiths RR, Johnson MW, Carducci MA, et al. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of Psychopharmacology, 30(12), 1181-1197.

  3. Bogenschutz MP, Pommy JA. (2015). Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study. Journal of Psychopharmacology, 29(3), 289-294.

  4. Kometer M, Schmidt A, Jäncke L, et al. (2012). Activation of serotonin 2A receptors underlies the psilocybin-induced effects on alpha band EEG and visual hallucinations. Biological Psychiatry, 72(8), 553-560.

  5. Rosenbaum J, Carhart-Harris RL, Erritzoe D, et al. (2018). Serotonin 2A receptors and the neuropharmacology of psychedelic-induced altered states of consciousness. Frontiers in Neuroscience, 12, 815.

Psilocybin and PTSD

Post-Traumatic Stress Disorder (PTSD) is a mental health condition that can develop after a traumatic event, such as military combat, sexual assault, or a natural disaster. Research suggests that psychedelic substances, such as psilocybin (found in magic mushrooms) may help alleviate symptoms of PTSD by allowing patients to process traumatic experiences in a therapeutic and controlled setting, leading to a reduction of symptoms such as anxiety, depression, and flashbacks.

Studies have shown that psychedelics can produce a profound shift in perspective and help patients gain new insights into their experiences, leading to a reduction in the emotional intensity of traumatic memories. They also appear to increase neuroplasticity and the brain's ability to create new connections, which can help rewire the brain to reduce symptoms of PTSD.

  • Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T., Jerome, L., & Doblin, R. (2011). The safety and efficacy of ±3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Journal of Psychopharmacology, 25(4), 439-452.

  • Ross, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., ... & Schmidt, B. L. (2016). Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology, 30(12), 1165-1180.

  • Garcia-Romeu, A., Griffiths, R. R., & Johnson, M. W. (2017). Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Current Addiction Reports, 4(2), 132-139.

Psilocybin and Depression

Research on the use of psilocybin for treating Major Depressive Disorder (MDD) has shown promising results. Psilocybin is a naturally occurring psychoactive compound found in certain species of mushrooms that has been used for spiritual and therapeutic purposes for centuries.

Several studies have demonstrated that psilocybin can produce rapid and long-lasting reductions in depression symptoms in patients with MDD. For example, one pilot study found that a single dose of psilocybin significantly reduced depression symptoms and increased quality of life measures up to five weeks after treatment. A recent clinical trial found that a single dose of psilocybin, in conjunction with psychotherapy, produced rapid and sustained improvements in depression symptoms that persisted for up to 12 months in some patients. These results have generated significant interest in the potential therapeutic applications of psilocybin and other psychedelics, and have led to calls for further research in this field.

References:

  • Carhart-Harris, R. L., et al. (2016). Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry, 3(7), 619-627.

  • Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., ... & Klinedinst, M. A. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of Psychopharmacology, 30(12), 1181-1197.

Psilocybin and Anxiety

Recent research suggests that psilocybin can help reduce anxiety symptoms by inducing a state of heightened introspection and inducing changes in the brain's default mode network, which is associated with self-referential thinking and rumination.

In several clinical trials, patients who received psilocybin reported significant reductions in anxiety and depression symptoms, even several months after treatment. The results of these studies indicate that psilocybin may have a lasting therapeutic effect for individuals with anxiety.

However, it is important to note that the use of psilocybin for the treatment of anxiety is still in the early stages of research and more studies are needed to fully understand the therapeutic benefits of this substance and its safety and efficacy in treating anxiety. The use of psychedelics should only be under the supervision of a medical professional and should not be used outside of a clinical setting.

References:

  • 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.

  • Garcia-Romeu, A., Williams, L. T., & Griffiths, R. R. (2014). Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Current Drug Abuse Reviews, 7(3), 157-164.

  • MacLean, K. A., Johnson, M. W., & Griffiths, R. R. (2011). Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness. Journal of Psychopharmacology, 25(11), 1453-1461.

  • Roseman, L., Leech, R., Feilding, A., Nutt, D. J., & Carhart-Harris, R. L. (2018). Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression. Frontiers in Psychiatry, 9, 269.

Psilocybin and Addiction

Studies have shown that psilocybin can reduce cravings and drug use in individuals with substance use disorders, as well as increase the likelihood of long-term abstinence. This is thought to be due to the compound's ability to create a profound shift in perspective and help individuals gain new insights into their experiences, leading to a reduction in the emotional intensity of traumatic memories and negative patterns of behavior.

Some references supporting the therapeutic potential of psilocybin for addiction include a pilot study by Johnson et al. (2014) that found that a single dose of psilocybin significantly reduced tobacco use in 15 out of 15 participants and a study by Bogenschutz et al. (2015) that found that psilocybin-assisted therapy was associated with decreased alcohol dependence and increased abstinence.

Safety

David Nutt's harm scale is a widely cited ranking system that compares the harmfulness of various drugs based on a range of criteria, including physical harm, dependence, and social harm. According to this scale, alcohol and tobacco are ranked among the most harmful drugs, whereas psilocybin is ranked relatively low in terms of harm.

Regarding the safety profile of psilocybin compared to alcohol and tobacco, it is well established that both alcohol and tobacco have negative impacts on health and can cause a range of physical and mental health problems. In contrast, psilocybin has a relatively low risk of physical harm and a favorable safety profile when used under guidance.

  • Nutt, D. J., King, L. A., & Phillips, L. D. (2010). Drug harms in the UK: a multicriteria decision analysis. The Lancet, 376(9752), 1558-1565.

  • Smith, M. L., Ferris, J., & Staines, G. (2018). Acute safety and tolerability of psilocybin in healthy volunteers. The American Journal of Drug and Alcohol Abuse, 44(6), 668-676.

  • Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P., & Griffiths, R. R. (2014). Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. Journal of Psychopharmacology, 28(11), 983-992.

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