How does psychedelic therapy work?

    Last Updated: October 25, 2023

    The mechanisms underpinning psychedelic therapy’s effects are being actively researched, but they likely involve a combination of psychological and biological changes. Psychologically, psychedelic therapy seems to increase insight, enhance emotional processing, and promote psychological flexibility (the ability to adapt our thoughts, emotions, and behaviors when faced with challenging or new situations).[1] This could create an opportunity to shift negative core beliefs and maladaptive thought patterns.[2] Interestingly, having a spiritual or mystical experience during the psychedelic session has repeatedly been found to predict a sustained psychological benefit.[2][3] This can be assessed by researchers using a questionnaire and generally involves positive feelings of oneness/interconnectedness with the world and an intuitive understanding of some aspect of life.[3]

    At a biological level, psychedelic therapy may induce structural and functional changes in the brain. Classic psychedelics primarily activate serotonin 2A (5-HT2A) receptors in the brain, which produces an altered state of consciousness and also seems to activate neurobiological pathways that lead to changes in neuroplasticity—the ability of the brain to change in both structure and function. Preclinical trials in mice have found that a single dose of psychedelics increases the expression of genes and proteins related to plasticity, including brain-derived neurotrophic factor (BDNF); induces cellular changes (the density/number of neurons and dendrites); and increases learning behaviors. Only a few studies have been performed in humans and the results are less clear, but preliminary neuroimaging studies report shifts in functional connectivity that are sustained after the drug has worn off.[4][5] For a deeper dive into these mechanisms, check out our study summary.

    References

    1. ^Ko K, Kopra EI, Cleare AJ, Rucker JJPsychedelic therapy for depressive symptoms: A systematic review and meta-analysis.J Affect Disord.(2023-Feb-01)
    2. ^Rosenblat JD, Husain MI, Lee Y, McIntyre RS, Mansur RB, Castle D, Offman H, Parikh SV, Frey BN, Schaffer A, Greenway KT, Garel N, Beaulieu S, Kennedy SH, Lam RW, Milev R, Ravindran AV, Tourjman V, Ameringen MV, Yatham LN, Taylor VThe Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: Serotonergic Psychedelic Treatments for Major Depressive Disorder.Can J Psychiatry.(2023-Jan)
    3. ^Aday JS, Mitzkovitz CM, Bloesch EK, Davoli CC, Davis AKLong-term effects of psychedelic drugs: A systematic review.Neurosci Biobehav Rev.(2020-Jun)
    4. ^Cato M H de Vos, Natasha L Mason, Kim P C KuypersPsychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of PsychedelicsFront Psychiatry.(2021 Sep 10)
    5. ^Frederick S Barrett, Manoj K Doss, Nathan D Sepeda, James J Pekar, Roland R GriffithsEmotions and brain function are altered up to one month after a single high dose of psilocybinSci Rep.(2020 Feb 10)