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Psychedelic Research
Psychedelics and the Brain
Neuroplasticity
Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics
"Studies show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment. Findings from the current review demonstrate that psychedelics induce molecular and cellular adaptations related to neuroplasticity and suggest those run parallel to the clinical effects of psychedelics, potentially underlying them."
https://www.frontiersin.org/articles/10.3389/fpsyt.2021.724606/full
Immunomodulation
Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities
"Classical psychedelics... besides their psychopharmacological activity, have also been shown to exert significant modulatory effects on immune responses by altering signaling pathways involved in inflammation, cellular proliferation, and cell survival via activating NF-κB and mitogen-activated protein kinases. Recently, several neurotransmitter receptors involved in the pharmacology of psychedelics, such as serotonin and sigma-1 receptors, have also been shown to play crucial roles in numerous immunological processes. This emerging field also offers promising treatment modalities in the therapy of various diseases including autoimmune and chronic inflammatory conditions"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500993/
Psilocybin
Mood & General Mental Health
Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls
"Using a naturalistic, observational design, we followed psilocybin microdosers... and non-microdosing comparators... for approximately 30 days and identified small- to medium-sized improvements in mood and mental health that were generally consistent across gender, age and presence of mental health concerns"
https://www.nature.com/articles/s41598-022-14512-3
Depression
Major Depressive Disorder (MDD)
Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up
"Treatment response and remission were 75% and 58%, respectively, at 12 months."
https://journals.sagepub.com/.../10.1177/02698811211073759
Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial
"documented a rapid decrease in mean depression score from baseline to day 1 after session... which remained statistically significantly reduced through the week 4 follow-up... In the overall sample, 17 participants (71%) at week 1 and 17 (71%) at week 4 had a clinically significant response to the intervention... and 14 participants (58%) at week 1 and 13 participants (54%) at week 4 were in remission"
https://jamanetwork.com/.../jamaps.../fullarticle/2772630...
Post-Traumatic Stress Disorder (PTSD)
An Interpretative Phenomenological Analysis of the use of psilocybin by veterans with symptoms of trauma
"All participants who had used psilocybin reported immediate and long-term improvements in their symptomatology. The study suggests that some perceive current treatments as ineffective and/or inaccessible, leading to the consideration of alternatives, such as psilocybin. The immediate and long-term symptom reductions reported suggest it may be a viable treatment option for symptoms of trauma for some."
https://journals.sagepub.com/doi/full/10.1177/20503245221124117
Chronic Pain
Chronic pain and psychedelics: a review and proposed mechanism of action
"Qualities of psychedelics have been attributed, through serotonin 2A (5-HT2A) receptor agonism, to ’reset’ areas of functional connectivity (FC) in the brain that play prominent roles in many central neuropathic states. Psychedelic substances have a generally favorable safety profile, especially when compared with opioid analgesics. Clinical evidence to date for their use for chronic pain is limited; however, several studies... have shown potential analgesic benefit in cancer pain, phantom limb pain and cluster headache. While the mechanisms by which the classic psychedelics may provide analgesia are not clear, several possibilities exist given the similarity between 5-HT2A activation pathways of psychedelics and the nociceptive modulation pathways in humans. Additionally, the alterations in FC seen with psychedelic use suggest a way that these agents could help reverse the changes in neural connections seen in chronic pain states."
https://tryptherapeutics.com/assets/documents/pdf/Tryp-Therapeutics_Pain-and-Psychedelics_Castellanos_2021-10-02-221023_huug.pdf
Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin
"Over the 2-week period measured after single administration, the reduction in weekly migraine days from baseline was significantly greater after psilocybin... than after placebo... This exploratory study suggests there is an enduring therapeutic effect in migraine headache after a single administration of psilocybin."
https://link.springer.com/article/10.1007/s13311-020-00962-y
Functional Neurological Disorders
Psychedelic treatment of functional neurological disorder: a systematic review
"In most cases, patients received a course of psychotherapy with variable adjunctive administration of psychedelics.. with protocols varying between studies. Of those treated, 69% (n = 18) were found to have made at least some recovery on heterogeneous and subjective clinician-rated criteria.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225815/
Psychedelic‐assisted therapy for functional neurological disorders: A theoretical framework and review of prior reports
"An in‐depth discussion of prior published cases detailing the use of psychedelics for psychosomatic conditions, analyzing therapeutic outcomes from a contemporary neuroscientific vantage as informed by several recent neuroimaging studies on psychedelics and FNDs."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719191/
5-HT2A Agonists: A Novel Therapy for Functional Neurological Disorders?
"Recent studies have shown that these agents induce changes in neural activity that disrupt hierarchical brain dynamics and modulate networks subserving self-related processing. Converging evidence suggests they may hold unique therapeutic potential in functional neurological disorders."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417053/