Written by Dr. Lindsay Mackay, MD, CCFP

Psilocybin research has been increasing rapidly over the last number of years, with many clinical trials in progress using psilocybin for a range of conditions including addictions, eating disorders, headaches, anxiety and depression. Psilocybin has also been evaluated for enhancing abilities like creativity and resilience. More studies have been published recently that improve our understanding of how a single dose of psilocybin works in the brain to facilitate long lasting positive benefits. One of the more interesting and promising ideas being discussed in the research world is the apparent ability for psilocybin to promote neuroplasticity. Neuroplasticity refers to the brain’s ability to change its structure and function over time, and in the case of psilocybin, adaptively to promote overall wellbeing and enhanced resilience. Below is a brief summary of interesting and promising research that has been published with psilocybin over the last one to two years from randomized clinical trials to naturalistic use surveys and animal studies.

A few quick notes on research terms:

  • Randomized refers to the process where study participants are assigned to a treatment group or placebo at random, with an equal chance at being in each group. This helps to make sure that differences between treatment and placebo groups are due to the treatment rather than differences in group characteristics.
  • Placebo controlled means the treatment (psilocybin in the below studies) is compared to a sham or fake treatment to help determine if any group differences are really due to the treatment or drug rather than some other factor.
  • Double blind refers to the technique where both the study participants and researchers are not aware if they are receiving placebo or treatment. This helps to reduce bias that may occur. For example, if a participant is expecting to feel better from a treatment, they may feel better just because they expect to rather than a true benefit from treatment. 

Trial of Psilocybin versus Escitalopram for Depression

  • Double-blind, placebo-controlled, randomized controlled trial with 60 participants with moderate-severe depression comparing psilocybin and antidepressants
  • The results indicated that two psilocybin-assisted therapy sessions showed the same benefit as antidepressant therapy over six weeks
  • A larger and longer trial is needed to determine if there are further differences between treatment

Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial

  • Randomized, waiting list-controlled trial using two psilocybin-assisted therapy sessions where 27 participants with major depression received immediate vs. delayed treatment (waitlist)
  • With psilocybin therapy, over half of participants went into full remission from depression and 71% had a significant improvement in their depression symptoms
  • These results are very promising compared to currently available depression treatments

Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer

  • Follow up study from a randomized, placebo-controlled trial that evaluated one psilocybin-assisted therapy session in participants with cancer-related distress
  • At 4.5 year follow up from their psilocybin experience, 60-80% of participants had significant reductions in anxiety, depression, hopelessness and death anxiety
  • Most participants attributed their positive life changes to the psilocybin experience and said it was one of the most personally meaningful and spiritually significant experiences of their lives

Spontaneous and deliberate creative cognition during and after psilocybin exposure

  • Double blind, placebo-controlled study with 60 participants using psilocybin vs. placebo to assess creativity
  • Under the effects of psilocybin, there were increased ratings of spontaneous creative insights, while task-based creativity (i.e., guessing the correct association between images) was decreased
  • One week after psilocybin was given, number of new ideas increased in the psilocybin group
  • It’s difficult to draw any firm conclusions that psilocybin increases creativity from this study; however, it shows potential

Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo

  • A single dose of psilocybin led to 10% increases in neuron spine size (part of the neuron that forms connections with other neurons) and density within 24 hours and this neuron growth was persistent one month later
  • These results support the neuroplasticity theory behind the long-term benefits achieved from psilocybin

Emotions and brain function are altered up to one month after a single high dose of psilocybin

  • 12 participants were given psilocybin and had brain imaging with a functional MRI to assess brain function before, one week after and one month after taking psilocybin
  • Negative emotions and brain response to negative facial expressions were reduced one week after psilocybin and anxiety was reduced at one month
  • The number of functional connections in the brain increased from before psilocybin to one week and one month after taking psilocybin.
  • These preliminary findings suggest that psilocybin may increase emotional and brain plasticity 

Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing

  • Online survey of 81 participants planning a psychedelic microdosing regimen
  • The survey found self-reported improved well-being, emotional stability and reductions in anxiety and depression symptoms
  • Other findings included increases in resilience, social connectedness, agreeableness, nature relatedness and aspects of psychological flexibility
  • One significant study drawback was positive expectancy scores prior to microdosing predicted improvements in well-being, suggesting the improvements could be due to the expectation of improvement rather than the microdosing itself (i.e., placebo response)

Psychedelic Communitas: Intersubjective Experience During Psychedelic Group Sessions Predicts Enduring Changes in Psychological Wellbeing and Social Connectedness

  • Communitas refers to a sense of togetherness and shared humanity, in this case during a psychedelic group ceremony
  • Online survey of almost 900 participants at multiple time points prior to and after a guided psychedelic experience
  • A positive relationship between participants and guides and emotional support facilitated the emergence of communitas
  • Communitas during ceremony was associated with increases in wellbeing and connectedness

Cross-Sectional Associations Between Lifetime Use of Psychedelic Drugs and Psychometric Measures During the COVID-19 Confinement: A Transcultural Study

  • Survey of almost 3000 participants during the height of covid lockdowns April-July 2020 found
  • that regular users of psychedelics experienced less stress during covid
  • Personality differences were found with regular psychedelic users compared to occasional and non-users
  • These results suggest that either regular psychedelic use might be a protective factor against stress or that people with certain personality traits that protect against stress are more likely to frequently use psychedelics


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