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RESEARCH

 

  • Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial (Davis et al., 2021). 

    • Sample size of 24, control was an 8-week delayed intervention group

    • 2 separate psilocybin facilitation sessions given a mean of 1.6 weeks apart in combination with 11 hours of psychotherapy

    • Primary assessment measure was the GRID-Hamilton Depression Rating Scale (GRID-HAMS), secondary was Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR) 

    • 71% of participants showed a clinically significant response (>50% reduction in GRID-HAMS) at week 1 and week 4, 58% at week 1 and 54% at week 4 were considered to be in remission 

    • QIDS-SR scores showed a rapid, large decrease in mean depression score which persisted throughout the 4 week intervention/assessment period

    • “Low potential for addiction and a minimal adverse event profile” (p. 486). 





 

  • Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial (Raison et al., 2023)

    • Double-blind RCT, placebo control group received Niacin 

    • 104 participants, 50 to intervention group and 54 to placebo group

    • Primary assessment measure was Montgomery-Asberg Depression Rating Scale (MADRS)

    • Psilocybin group had a statistically and clinically significant reduction in depressive symptoms compared to placebo group

    • These improvements were maintained over a 6-week period

 

  • A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy (Luoma et al., 2020). 

    • 9 placebo-controlled studies conducted on 211 people examining MDMA, psilocybin, ayahuasca, and LSD

    • “80% probability that a randomly selected patient undergoing psychedelic-assisted therapy will have a better outcome than a randomly selected patient receiving a placebo” (p. 295). 

    • Efficacy reported in the treatment of PTSD, anxiety/depression associated with life-threatening illness, unipolar depression, and social anxiety among autistic adults


 

  • Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomized clinical trial (von Rotz et al., 2023). 

    • 54 participants, 26 receiving psilocybin and 26 in placebo (mannitol) group along with psychological counselling 

    • Montgomery-Åsberg Depression Rating Scale (MADRS) and Beck’s Depression Inventory (BDI) used for assessment 

    • One-time administration of a moderate dose lower than most other studies 

    • At 14 days post intervention, psilocybin group had treatment response in 58% per MADRS and 54% per BDI, compared to 16%/12% in placebo group

 

  • Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies (Studerus et al., 2010). 

    • No full text available, the following was taken from the abstract: 

    • “…analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1–4 oral doses of psilocybin (45–315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.”

 

  • Cessation and reduction in alcohol consumption and misuse after psychedelic use (Garcia-Romeu et al., 2019)

    • No full text available, the following was taken from the abstract:

    • “343 respondents, mostly White (89%), males (78%), in the USA (60%) completed the survey. Participants reported seven years of problematic alcohol use on average before the psychedelic experience to which they attributed reduced alcohol consumption, with 72% meeting retrospective criteria for severe AUD. Most reported taking a moderate or high dose of LSD (38%) or psilocybin (36%), followed by significant reduction in alcohol consumption. After the psychedelic experience 83% no longer met AUD criteria. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced alcohol misuse.”


 

  • Psilocybin with psychological support for treatment-resistant depression: six-month follow-up (Carhart-Harris et al., 2017). 

    • 20 participants (19 who completed the intervention) with treatment-resistant depression received 2 doses of psilocybin (10mg and 25mg) 7 days apart, with psychological support consisting of preparation, acute support, and integration

    • Patients had failed a medium number of 4 medications in the treatment of depression in the past, with the maximum being 11

    • Assessed by Quick Inventory of Depressive Symptoms, Self-Report (QIDS-SR16) with ratings collected 1-3 and 5 weeks, and 3 and 6 months post-treatment

    • Marked reduction in depressive symptoms at week 1 and 5. 

    • Continued positive results at 3 and 6 months, but interpretation of this was confounded by multiple patients using other treatment methods such as medication or CBT

    • Rapid onset of action provides an edge over traditional antidepressant medications which require more time to take effect 

    • No serious adverse events 

 

  • Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: prospective 12-month follow-up (Gukasyan et al., 2022)

    • 24 (13 in immediate group, 11 in delayed treatment group) patients who received 2 doses of psilocybin (20mg/70kg and 30mg/70kg) spaced 2 weeks apart with follow-up at 1 day and 1 week following each administration and then at 1, 3, 6, and 12 months following the second session. 

    • Primary outcome was GRID-HAMD, as well as QIDS and the Beck Depression Inventory II (BDI-II)

    • Response across all follow-up points for all 3 assessment scales was between 6-83%; remission across all scales/follow-up points was between 54-75% (great tables/graphs on page 154)

 

  • Long-term follow-up of psilocybin-facilitated smoking cessation (Johnson et al., 2016)

    • 15 participants who smoked on average 19 cigarettes per day for a mean of 31 years with a mean of 6 prior quit attempts

    • 15-week combination treatment including CBT, mindfulness training, and guided imagery in addition to a moderate dose of psilocybin at week 5 (20mg/70kg) and a high dose at week 7 (30mg/kg). An option 3rd high-dose psilocybin session was offered at week 13. 

    • Week 5 served as the target quit date (TQD), participants had follow-up meetings at 6 and 12 months post-TQD

    • At 12-month follow-up, 10 participants (67%) were biologically confirmed as smoking abstinent by breath and urine testing

    • At an extended follow-up (mean of 30 months post-TQD), 9 participants (60%) were biologically confirmed as smoking abstinent. This is a significant improvement from the most effective existing smoking cessation medications which “typically demonstrate less than 31% abstinence at 12 months post-treatment (p. 59). 

    • Patients also completed a Persisting Effects Questionnaire in which negative persisting effects received 3.2-8.1% of total possible score, and positive persisting effects received 53-64% of total possible score 

 

  • Emotions and brain function are altered up to one month after a single high dose of psilocybin (Barrett et al., 2020). 

    • 12 participants received a single 25mg/70kg dose of psilocybin 

    • Multiple measures were completed at one day before, one week after, and one month after administration (Profile of Mood Sates, State and Trait Anxiety inventory, the Positive and Negative Affect Schedule, the Depression, Anxiety, and Stress Scale, and the Dispositional Positive Emotion Scale). Participants also underwent fMRI measurements at these same time points, during rest and during completion of 3 emotional processing tasks

    • Negative affect decreased at week 1, returned to baseline at 1 month

    • Global increases in functional connectivity at 1 week and 1 month; may reflect increased neuroplasticity

    • Sustained decreases in negative affect states/traits, and increases in positive affect states/traits

  • Psychotherapy with Psilocybin for depression: Systematic Review (Dawood Hristova & Pérez-Jover, 2023)

    • Systematic review of eight studies that investigated the use of psilocybin for depression; five RCTs three of which were double-blind, and three open-label studies

    • “The results of all studies showed a significant reduction in depressive symptoms after treatment with one or two doses of psilocybin” (p. 297). Improvement persisted up to 6, 8, and 12 months post-treatment. 

    • In one comparative treatment between psilocybin and escitalopram, no significant differences were found at the 6 week point. 

    • Adverse effects included headaches, dizziness, nausea, and tachycardia, which occurred occasionally and with mild or moderate intensity. No cases of addiction to the substance were reported after treatment. 

 

  • Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression (Stroud et al., 2017). 

    • 17 patients with treatment-resistant depression completed emotional face recognition task at baseline and 1 month after 2 doses of psilocybin with psychological support; a control group of 16 completed the same task over the same time frame without receiving psilocybin. 

    • The intervention group displayed faster emotional recognition at follow-up compared to baseline and to the control group. Patients in the intervention group also displayed a reduction in anhedonia over the same time period

  • Sub-Acute Effects of Psilocybin on Empathy, Creative Thinking, and Subjective Well-Being (Mason et al., 2019). 

    • 22 participants completed tests of creative thinking and empathy at baseline, the morning after taking psilocybin, and 7 days after taking psilocybin

    • Participants were tested on convergent thinking, divergent thinking, cognitive empathy, emotional empathy, and satisfaction with life scale (SWLS)

    • Results demonstrated increased subjective well-being both morning after and 7 days after; convergent thinking enhanced after 7 days

    • Divergent thinking was enhanced on day 1 and returned to baseline by day 7; DT “can enhance psychological flexibility by allowing individuals to generate new, more effective strategies that facilitate adaptive interpretations and coping abilities” (p. 130), which provides therapeutic potential for patients to process trauma in the sub-acute phase of psilocybin ingestion. 

 

  • Exploring the Use of Psilocybin Therapy for Existential Distress: A Qualitative Study of Palliative Care Provider Perceptions (Mayer et al., 2021). 

    • 5 interdisciplinary palliative care providers were given semi-structured interview

    • All expressed several current barriers to properly addressing existential distress in end-of-life care. Reported that very few treatment options are currently available for existential distress, and the struggle of Western medicine focusing on avoidance of death


 

  • Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls (Rootman et al., 2022). 

    • 953 microdosers and 180 non-microdosers were observationally investigated for 30 days; baseline assessments were complete at study onset and follow-up assessments completed 22-35 days later

    • Microdosers displayed greater improvements across measures of depression, anxiety, and stress. 

    • Older adults displayed improved psychomotor performance 

 

  • Embedding existential psychology within psychedelic science: reduced death anxiety as a mediator of the therapeutic effects of psychedelics (Moreton et al., 2019). 

    • Theorization of the underlying cause of psychedelics alleviating death anxiety

    • Ego death, mystical experiences, death transcendence

    • Reduced focus on the self, shifting meta-physical beliefs, amplified religious faith, increased feelings of connectedness and meaningfulness of life 

 

  • Psilocybin for treating psychiatric disorders: A psychonaut legent or a promising therapeutic perspective? (Coppola, Bevione, & Mondola, 2022). 

    • The use of plant-extracted psychedelics by humans has been documented for 5700 years (northeastern Mexico). 

    • “generally considered to be well tolerated and low in toxicity” (p. 45). 

    • Reports of psychosis in healthy adults with no history of psychotic disorder are rare

    • “Psilocybin does not directly affect the mesolimbic dopaminergic pathway involved in the reward system; consequently, it does not induce craving, addiction or withdrawal” (p. 46). 

    • Cites multiple studies demonstrating reduced death anxiety in patients with life-threatening cancer.

 

  • Analysis of Psilocybin-Assisted Therapy in Medicine: A Narrative Review (Ziff et al., 2022)

    • Use of mescaline identified by archeologists to have occurred 5700 years ago per radiocarbon dating

    • The metabolite of psilocybin (psilocin, which is what psilocybin becomes after ingestion) closely resembles serotonin, and is thus able to activate 5HT receptors

    • Downregulation of 5HT receptors leads to a compensatory upregulation in metabotropic glutamate (MGluR2/3) receptors due to their inverse relationship; this is significant as MGluR2/3 receptors play a role in the mediation of craving and addiction; those with alcoholism have been found to have deficiency in mGluR2 pathways in the prefrontal cortex 

    • Effects at 5HT-2A receptors lead the striatum to release increased levels of dopamine, leading to improved regulation of defective reward pathways in patients with depression or suicidal ideation

    • Low abuse potential; no signs of physical dependence or withdrawal have been documented; associated with few adverse effects; Half-life of 2.5-3 hours 

    • Demonstrated potential for addiction, depression, end-of-life mood disorders

  • The Therapeutic Potential of Psilocybin (Lowe et al., 2021). 

    • Up to 1 billion people worldwide are estimated to be affected by a mental health or substance use disorder, with anxiety disorders affecting an estimated 284 million people as of 2018 and depression affected 264 million. Also as of 2018, 107 million were effected by alcohol-use disorders are 71 million were affected by drug-use disorders excluding alcohol. An estimated 800,000 people die by suicide annually. 

    • Psilocybin has also demonstrated efficacy in the treatment of chronic pain, including cluster headaches and intractable phantom limb pain. 

    • University of California, Los Angeles began clinical trials on psilocybin in 2004, initiating what some consider the ‘third psychedelic renaissance.’ 

    • The Center for Psychedelic and Conscious Research was established at Johns Hopkins University in 2006, “which has since published over eighty peer-reviewed articles on psychedelic research” (p. 2948). 

    • Multiple institutions have been awarded the status of ‘breakthrough therapy’ for psilocybin-based depression treatments by the USFDA. 

    • Nearly 550 grants have been awarded to research institutes performing psychedelic research between 2015 and 2020. 

    • Also being studied at many name-recognition institutions; Harvard, Yale. 

    • Interaction with serotonergic and mesolimbic dopaminergic systems 

    • Low toxicity, low abuse potential, safe response, and no associated persisting adverse effects during or after use. This excludes those with a history of psychotic disorders, which is currently considered a contraindication to psilocybin use. 

  • Psychedelics: Alternative and Potential Therapeutic Options for Treating Mood and Anxiety Disorders (Lowe et al., 2022). 

    • Therapeutic administration of psychedelics has been demonstrated to produce anti-depressive, anxiolytic, anti-addictive, and anti-suicidal properties 

  • Psychedelic drug psilocybin shows promise treating anorexia in early trials (Wade, 2023) news article

    • University of California, San Diego reporting promising results in early trials

    • 45% reduction in severity of anorexia nervosa

    • 90% of participants reported feelings more optimistic about their life 3 months post-treatment, and 70% reported overall improved quality of life

    • 2 additional trials completed by Imperial College London and Columbia University in New York also reporting improvements in treatment of anorexia nervosa using psilocybin 








 

References

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Carhart-Harris, R. L., Bolstridge, M., Day, C. M., Rucker, J., Watts, R., Erritzoe, D. E., Kaelen, M., Giribaldi, B., Bloomfield, M., Pilling, S., Rickard, J. A., Forbes, B., Feilding, A., Taylor, D., Curran, H. V., & Nutt, D. J. (2017). Psilocybin with psychological support for treatment-resistant depression: Six-month follow-up. Psychopharmacology, 235(2), 399–408. https://doi.org/10.1007/s00213-017-4771-x 

Coppola, M., Bevione, F., & Mondola, R. (2022). Psilocybin for treating psychiatric disorders: A psychonaut legend or a promising therapeutic perspective? Journal of Xenobiotics, 12(1), 41–52. https://doi.org/10.3390/jox12010004 

Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., & Griffiths, R. R. (2021). Effects of psilocybin-assisted therapy on major depressive disorder. JAMA Psychiatry, 78(5), 481. https://doi.org/10.1001/jamapsychiatry.2020.3285 

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Garcia-Romeu, A., Davis, A. K., Erowid, F., Erowid, E., Griffiths, R. R., & Johnson, M. W. (2019). Cessation and reduction in alcohol consumption and misuse after psychedelic use. Journal of Psychopharmacology, 33(9), 1088–1101. https://doi.org/10.1177/0269881119845793 

Gukasyan, N., Davis, A. K., Barrett, F. S., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., & Griffiths, R. R. (2022). Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Journal of Psychopharmacology, 36(2), 151–158. https://doi.org/10.1177/02698811211073759 

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Mayer, C. E., LeBaron, V. T., & Acquaviva, K. D. (2021). Exploring the use of psilocybin therapy for existential distress: A qualitative study of palliative care provider perceptions. Journal of Psychoactive Drugs, 54(1), 81–92. https://doi.org/10.1080/02791072.2021.1916659 

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Rootman, J. M., Kiraga, M., Kryskow, P., Harvey, K., Stamets, P., Santos-Brault, E., Kuypers, K. P., & Walsh, Z. (2022). Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls. Scientific Reports, 12(1). https://doi.org/10.1038/s41598-022-14512-3 

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Stroud, J. B., Freeman, T. P., Leech, R., Hindocha, C., Lawn, W., Nutt, D. J., Curran, H. V., & Carhart-Harris, R. L. (2017). Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression. Psychopharmacology, 235(2), 459–466. https://doi.org/10.1007/s00213-017-4754-y 

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