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Towards an understanding of psychedelic-induced neuroplasticity

Recent decades have seen renewed scientific interest in classic psychedelics, which include lysergic acid diethylamide (LSD),psilocybin, 2,5-dimethoxy-4-iodoamphetamine (DOI), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and N,N-dimethyltryptamine

(DMT), the psychedelic compound in the Amazonian ayahuasca brew.


Classic psychedelics have been shown to catalyze relatively long-lasting improvements in mental health after a small number of doses, especially when combined with psychotherapy.


In patients suffering from depression, anxiety disorders, and addiction, the benefits of psychedelic-assisted psychotherapy can last for many months or years. Additionally, healthy subjects report increased well-being up to a year after administration of psychedelics in a safe and supportive setting.


One leading theory of psychedelics’ lasting effects categorizes them as “psychoplastogens” which rapidly stimulate a period of enhanced neuroplasticity, as well as enduring neuroplastic changes. Neuroplasticity denotes the nervous system’s

ability to reorganize its structure and function and adapt to its dynamic environment. Throughout the lifespan, neuroplasticity is essential for learning, memory, and recovery from neurological insults, as well as adapting to life experiences.


The theory that psychedelics open a window of neuroplasticity would explain how long-term effects outlast the drug’s presence in the body, and it is also attractive because disruptions in neuroplasticity are present in mood disorders and addiction.


Neuroplasticity can be investigated at multiple levels of analysis. At the molecular level, it comprises changes in gene and protein expression, as well as post-translational modifications. Of particular importance is brain-derived neurotrophic factor (BDNF),

a neurotrophin that regulates neuronal growth and synaptic plasticity. Changes in gene and protein expression give rise to morphological changes, including the formation and modification of synapses and dendrites.


In particular regions, most notably the hippocampus, neuroplasticity also comprises neurogenesis. These processes modify neural circuits, ultimately manifesting

in learning, memory, and changes in adaptive behavior.


Neuroplasticity is crucially activity-dependent at the cellular level, which translates into experience-dependence at the level of cognition and behavior: people learn both passively and actively from their experiences, adjusting patterns of thought, emotion, and behavior accordingly.


In order to effectively harness the potential of psychedelics, it is imperative to understand how they affect neuroplasticity, as well as the clinical relevance of these effects. In the present review, we first evaluate the available evidence concerning whether psychedelics enhance neuroplasticity.


We then discuss where in the brain this likely happens, what doses are capable of this, how long the effects may last, and whether they have meaningful consequences

for emotion, cognition, and behavior, as well as therapeutic use.


Finally, we discuss the advantages and challenges that psychedelic-induced neuroplasticity presents and identify important directions for future research.


We have included more information in the attached pdf for your reference which you are welcome to download.



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