Vanessa Denny

Psilocybin is a compound found in over 200 species of mushrooms, and is colloquially known as “Magic Mushrooms.” The research behind the therapeutic benefits have recently gained popularity. They were discussed in the Netflix-original documentary Fantastic Fungi, in Michael Pollan’s book How To Change Your Mind, as well as on the state level after it was legalized in Oregon for therapeutic use at the end of last year [1].

Before the war on drugs, psychedelics were making big waves in the therapeutic market of the 60s and 70s. However, the compounds were classified as Schedule 1 drugs by the DEA in 1968, putting them back on the shelf for nearly three decades. At the turn of the century, interest in the potential medical benefits, and hard work by advocates, brought the drugs back into the spotlight [2]. Today, we are seeing the first government-funded study for psychedelic’s potential therapeutic effects in over fifty years. Johns Hopkins Center for Psychedelics and Consciousness was awarded nearly four million dollars by the National Institute on Drug Abuse to see how effective psilocybin can be in the cessation of smoking [3].

Things are beginning to change in the world of medicine, but what does it all mean? How can a mushroom be used for mental health? In order to understand the effects of this drug on the brain, we’ll look at its pharmacology. Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamin e) is known as a “classic” psychedelic. It is a tryptamine-based compound where it acts as a Serotonin 5-HT2A agonist, meaning it binds with the 2A neuroreceptor in the brain [4]. This is different from your typical selective serotonin reuptake inhibitor (SSRI), that works on the presynaptic neuron, by blocking the reuptake of serotonin and allowing more of the chemical to stay in the pathway [5].

A study led by Robin L. Carhartt-Haris at the Imperial College of London published in 2012 sought to look at the effects of psilocybin when going from a normal waking state to the psychedelic state. They measured brain activity using arterial spin labeling (ASL) perfusion and blood-oxygen level-dependent (BOLD) measures of functional MRI. After intravenous administration of a moderate dose of psilocybin they saw effects begin seconds after. Their results found decreased cerebral blood flow and BOLD signals. This led to a significant result in the decrease of the positive coupling between the medial prefrontal cortex and the posterior cingulate cortex. This led them to conclude that the subjective effects of the drug were caused by this decoupling which leads to “unconstrained cognition.” They also measured other subjective effects such as visual changes in the environment, changes in your experience of time, and experiencing a dreamlike state, which had much higher ratings during the psilocybin stage vs. the placebo [6].

In 2013 the Lieber Institute for Brain Development looked at how psilocybin impacts neurogenesis and hippocampal-dependent learning. After conditioning mice with shock, they were able to induce a fear response, freezing, to an associated tone. After being injected with small amounts of psilocybin they were able to extinguish the fear conditioning. They concluded this had to do with diminished neurogenesis and alterations in hippocampal neurotransmission. They found these results to be promising for the treatment of post-traumatic stress disorder [7].

Psilocybin has since been designated as a break-through therapy for treatment-resistant depression (in 2018), and for major depressive disorder (in 2019). This status came after the non-profit company Usona Institute found a single dose of psilocybin to be effective in treatment of depression. In a statement, the company noted that “Psilocybin potentially offers a novel paradigm in which a short-acting compound imparts profound alterations in consciousness and could enable long-term remission of depressive symptoms [8].” 

More recently, a study done at Yale University has been gaining a lot of attention in the media. In July of this year they published their findings on psilocybin-induced growth of dendritic spines in the frontal cortex of mice. A single dose of psilocybin led to a 10% increase in the spine’s size and density, and saw this effect to happen both quickly and persisted a month later. They found this rapid rewiring to potentially be the mechanism for the anti-depressant effects [9]. 

Results such as these have left scientists to wonder if this breakthrough therapy could also have potential benefits for patients with Alzheimer’s Disease (AD). A review published in Frontiers, found that both psilocybin and lysergic acid diethylamide (LSD), which also acts as 5HT2A agonist, could have promising results. The hippocampus is a key player in both learning and memory, and being able to retain long-term neuroplasticity and neurogenesis is one of the best ways to combat the effects of dementia. Consequently, the hippocampus is one of the first places to be affected by the pathology of AD. 

They also covered micro-dosing in their review, which is the practice of taking a very small dose of a psychedelic in order to achieve cognitive enhancement. While this idea has gained popularity in places such as Silicon Valley and on psychedelic news sites such as Double Blind and the Psychedelic Society, the science is still lacking there. Animal testing models have found that low does have demonstrated hippocampal neurogenesis, whereas higher doses did not have the same results. However, it is unknown just how that would translate in human studies. Anecdotally, the practice has had great results, but the placebo effect here cannot be ruled out. 

The review concluded that both psychedelic compounds LSD and psyilocybin’s ability to stimulate neurogenesis, enhance cognitive function, and reduce inflammation make it a viable potential treatment, either at micro or macro doses, for a disease where a breakthrough treatment has been long overdue [10].

 

This article has been approved and reviewed by the scientific writing team lead of Esurgi: Ishtiak Ahmed Chowdhury

Sources:

  1. Acker L. Oregon becomes first state to legalize psychedelic mushrooms. oregonlive. https://www.oregonlive.com/politics/2020/11/oregon-becomes-first-state-to-legalize-psychedelic-mushrooms.html. Published November 4, 2020. Accessed November 1, 2021. 
  2. Willliams L. Human psychedelic research: A historical and sociological analysis. MAPS. https://maps.org/index.php?option=com_content&view=article&id=5468. Accessed November 1, 2021. 
  3. Johns Hopkins Medicine receives first federal grant for psychedelic treatment research in 50 Years. Johns Hopkins Medicine Newsroom. https://www.hopkinsmedicine.org/news/newsroom/news-releases/johns-hopkins-medicine-receives-first-federal-grant-for-psychedelic-treatment-research-in-50-years. Published October 18, 2021. Accessed November 1, 2021. 
  4. Passie T, et al. The pharmacology of psilocybin – maps. https://maps.org/research-archive/w3pb/2002/2002_Passie_22704_1.pdf. Published 2002. Accessed November 1, 2021. 
  5. Chu A. Selective serotonin reuptake inhibitors. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK554406/. Published May 10, 2021. Accessed November 1, 2021. 
  6. Carhart-Harris RL, Erritzoe D, Williams T, et al. Neural correlates of the psychedelic state as determined by fmri studies with psilocybin. Proceedings of the National Academy of Sciences of the United States of America. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277566/. Published February 7, 2012. Accessed November 1, 2021. 
  7. Catlow B.J., Song S., Paredes D.A., et al. Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning. Experimental brain research. https://pubmed.ncbi.nlm.nih.gov/23727882/. Accessed November 1, 2021. 
  8. FDA grants Breakthrough therapy designation to usona institute’s psilocybin program for major depressive disorder. Business Wire. https://www.businesswire.com/news/home/20191122005452/en/FDA-grants-Breakthrough-Therapy-Designation-Usona-Institutes. Published November 22, 2019. Accessed November 1, 2021. 
  1. Xiao Shao L, Liao C, Gregg I, et all. Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo. Neuron. https://pubmed.ncbi.nlm.nih.gov/34228959/. Accessed November 1, 2021. 
  2. Vann Jones SA, O’Kelly A. Psychedelics as a treatment for alzheimer’s disease dementia. Frontiers in synaptic neuroscience. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472664/. Published August 21, 2020. Accessed November 1, 2021.