Psilocybin

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This section does not replicate the other information on this topic but provides additional details or context most relevant to professionals.

Considerations for therapeutic use of psilocybin

In June 2023, the U.S. Food and Drug Administration published a new draft guidance › to highlight fundamental considerations to researchers investigating the use of psychedelic drugs for potential treatment of medical conditions, including psychiatric or substance use disorders. This is the first FDA draft guidance that presents considerations to industry for designing clinical trials for psychedelic drugs.

The context of psilocybin treatment is essential for successful outcomes. “Spiritual, existential, religious, and theological topics’ integration in psychedelic-assisted therapy is needed to ensure culturally competent, evidence-based treatment aligned with the highest standards of clinical care.”¹Palitsky R, Kaplan DM et al. Importance of integrating spiritual, existential, religious, and theological components in psychedelic-assisted therapies. JAMA Psychiatry. 2023 Jul 1;80(7):743-749. Making group therapy a part of psilocybin-assisted therapy (PAT) may improve the experience for patients: “First, the groups contributed to increase participants’ sense of safety and preparedness as they were engaging in the therapy; and second, the groups fostered a sense of connection and of belonging, which served to enrich and deepen the meaning of participants’ experience, ultimately opening a dimension of self-transcendence and compassion.”²Beaussant Y, Tarbi E et al. Acceptability of psilocybin-assisted group therapy in patients with cancer and major depressive disorder: qualitative analysis. Cancer. 2024 Apr 1;130(7):1147-1157.

Modes of action

Research results suggest that hallucinogens increase introspection and positive mood by modulating brain activity in the fronto-temporo-parieto-occipital cortex.³Dos Santos RG, Osório FL, Crippa JAS, Hallak JEC. Classical hallucinogens and neuroimaging: a systematic review of human studies: hallucinogens and neuroimaging. Neuroscience and Biobehavioral Reviews. 2016 Dec;71:715-728; Mertens LJ, Wall MB et al. Therapeutic mechanisms of psilocybin: changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression. Journal of Psychopharmacology. 2020 Feb;34(2):167-180.

“Psilocybin binds with high affinity to 5-HT2A [5]. 5-HT serotonin receptors are densely located in areas of the brain that are responsible for the mediation of mood and anxiety disorders such as the pre-frontal cortex. Molecular mechanisms of action have not yet been elucidated.”⁴Lowe H, Toyang N et al. The therapeutic potential of psilocybin. Molecules. 2021 May 15;26(10):2948.

Preclinical evidence

Notable preclinical evidence is presented here; clinical evidence is summarized in How can psilocybin help you? What the research says ›

Inflammation

“Activation of 5-HT_2A receptors produces potent anti-inflammatory effects in animal models of human inflammatory disorders at sub-behavioural levels.”⁵Flanagan TW, Nichols CD. Psychedelics as anti-inflammatory agents. International Review of Psychiatry. 2018 Aug;30(4):363-375.

Helpful links for professionals

Brooks M. Psychedelic therapy: what meaningful informed consent looks like. Medscape. April 30, 2024.

Rosa WE, Sager Z et al. Top ten tips palliative care clinicians should know about psychedelic-assisted therapy in the context of serious illness. Journal of Palliative Medicine. 2022 Aug;25(8):1273-1281.

Reynolds LM, Akroyd A et al. Cancer healthcare workers’ perceptions toward psychedelic-assisted therapy: a preliminary investigation. International Journal of Environmental Research and Public Health. 2021 Aug 2;18(15):8160.

Bossis AP. Psilocybin, spirituality, and palliative care: research and implications. Alternative and Complementary Therapies. 2021:27(1):14-17.

Hicks M. Is psychedelic therapy integrative medicine? Journal of Psychedelic Psychiatry. 2021 Jun;3(2):4-9.

MacCallum CA, Lo LA, Pistawka CA, Deol JK. Therapeutic use of psilocybin: practical considerations for dosing and administration. Frontiers in Psychiatry. 2022 Dec 1;13:1040217.

Seybert C, Cotovio G et al. Psychedelic treatments for mental health conditions pose challenges for informed consent. Nature Medicine. 2023 Sep;29(9):2167-2170.

Lowe H, Toyang N et al. The therapeutic potential of psilocybin. Molecules. 2021 May 15;26(10):2948.