“Magic” psilocybin-containing mushrooms are currently being studied for their therapeutic potential for a host of mental health conditions. Regarding treatment-resistant depression, psilocybin is of particular interest, and is now displaying some very promising results.


Once viewed as dangerous and shrouded in mystery, magic mushrooms are now being decriminalised in several American cities and explored by scientific researchers for their therapeutic potential. Although still categorised as a Schedule I drug (or equivalent) in most countries, governing bodies have started to grant legal access to researchers, and the Centre for Psychedelic Research at Imperial College London has been given the go-ahead to investigate them.

The “magic” in these mushrooms is derived from a psychotropic prodrug molecule known as psilocybin. This molecule acts on serotonin receptors in the brain, and in doing so can cause altered sensory experiences such as synaesthesia. Small doses of the psilocybin-containing fungi can result in elevated mood and emotional experiences, whereas large doses are associated with full-blown psychedelic states.

Researchers investigating psilocybin have encountered some interesting effects that suggest therapeutic use in conditions such as addictive behaviour, psychological distress, obsessive-compulsive disorder (OCD), and cluster headaches. Psilocybin has also been explored for its effects on depression, and has displayed some interesting and promising results herein.



Depression is a common mental disorder defined by feelings of severe despondency and dejection. As opposed to temporary feelings of sadness or unhappiness that accompany certain life events, depression is a persistent and chronic state of deep sadness that has no single cause.

According to a World Health Organisation report, depression is reaching epidemic proportions worldwide, affecting more than 300 million individuals of all ages, with the disorder manifesting more frequently in women than men. Depression is now recognised as the leading cause of disability across the world. In some people, depression causes feelings and sensations that can lead to reclusive behaviour and inactivity, yet in others, symptoms can become so severe that they lead to suicidal behaviour.


Symptoms Of Depression

The symptoms of depression can vary from person to person, as the condition affects individuals differently.

Common symptoms include:

  • Anxiety and agitation
  • Changes in appetite and bodyweight
  • Anger and frustration
  • Persistent feelings of sadness, emptiness, and tearfulness
  • Issues with thinking, concentrating, and cognitive tasks
  • Unexplained back pain and headaches
  • Suicidal thoughts and behaviour
  • Loss of interest in activities, hobbies, and work
  • Reduced libido
  • Feelings of worthlessness and guilt
  • Personality changes


There is no single determining cause of depression. The disorder can arise due to certain triggers, including life-changing events such as the loss of a loved one, giving birth, or being fired from a job. Genetics can also play a role in the development of depression, and having a relative with the disorder is recognised as a risk factor.

Biological differences in brain structure are also associated with depression, with findings indicating physical changes in the brains of depressed individuals. Alterations in nerve cell connections, nerve cell growth, and nerve circuit function could all contribute to depression.


Neurotransmitters, The Brain, And Depression

Neurotransmitters are chemical messengers released by neurons to transmit signals across synaptic spaces. Research shows a relationship between neurotransmitters dopamine, norepinephrine, and serotonin and symptoms of depression. Symptoms are associated with increases and decreases in the levels of these neurochemicals.

For example, low levels of serotonin have been linked to depression. Serotonin is involved in regulation of mood, social behaviour, appetite, sleep, and memory. This has led to the prescription of selective serotonin reuptake inhibitors (SSRIs) to block serotonin from being reabsorbed into neurons.


Treatment for depression varies depending on the severity of symptoms. Mild depression may respond to lifestyle changes such as increasing levels of aerobic exercise. This can increase concentrations of neurotransmitters like dopamine and endocannabinoids like anandamide, which are both associated with increased mood.

In cases of mild to moderate depression, psychotherapy, cognitive behavioural therapy, and counselling may be provided to help individuals identify the root cause of associated behaviours, actions, and thought patterns.

Treatment for moderate to severe depression includes cognitive behaviour therapy, interpersonal therapy, psychodynamic therapy, and the prescription of antidepressant medications such as SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), atypical antidepressants, and monoamine oxidase inhibitors (MAOIs). These medications can be effective in some people, however, they are associated with side effects such as anxiety, dizziness, flu-like symptoms, and gastrointestinal irritation.

Below is a collection of scientific literature that reviews the effects of psilocybin on depression, possibly suggesting the future therapeutic use of the substance following further investigation and clinical trials.

Disclaimer: The following is not advice or an endorsement of magic mushroom use for as a treatment. Research is still very early and requires investigation on a much


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