Psychedelics have garnered attention for their ability to enhance neuroplasticity, offering promising therapeutic potential for emotional and cognitive health. Neuroplasticity is our brain’s remarkable ability to reorganise itself by forming new neural connections throughout life. This process is essential for learning, memory, and recovery from brain injuries. The capacity for neuroplasticity means that the brain can adapt to new experiences and recover from injuries, which is the basis for the therapeutic potential of psychedelics (Learn more about “Brain Plasticity and Psychedelic-Assisted Therapy).
Psychedelics induce significant structural changes in the brain, particularly in the prefrontal cortex (PFC) and hippocampus. The PFC is essential for higher cognitive functions such as decision-making, problem-solving, and emotional regulation. Psychedelics increase dendritic spine (“root”) density in the PFC, enhancing the strength and efficiency of neural connections, which enables increased cognitive flexibility and improved emotional regulation14.
Similarly, the hippocampus, vital for learning and memory, benefits from psychedelic-induced neurogenesis—the birth of new neurons. This process enhances memory formation, retrieval, and learning capabilities. Even a single dose of psilocybin has been shown to increase neuronal connections in the hippocampus, promoting long-term cognitive and emotional health12.
Beyond these structural changes, psychedelics also bring about functional changes in brain activity. One key area of impact is the amygdala, crucial for processing emotions and the centre of the “fight-and-flight response.” Psychedelics can modulate the amygdala’s responsiveness to negative stimuli, leading to improvements in emotional regulation. For example, psilocybin reduces the amygdala’s reactivity, increasing positive affect and reducing depressive symptoms 1,5. Enhanced connectivity between the PFC and other brain regions involved in cognitive control underpins better executive function and decision-making abilities, with benefits persisting for weeks post-treatment7.
The long-term benefits of psychedelic-induced neuroplasticity are significant and multifaceted. Enhanced synaptic connections and increased brain-derived neurotrophic factor (BDNF) levels contribute to sustained improvements in mood regulation and cognitive flexibility. Brain-derived neurotrophic factor (BDNF) is a protein that supports neurons’ survival, growth, and differentiation. You can think of it as “Miracle-Gro fertiliser” for the brain. BDNF plays a crucial role in enhancing neuroplasticity by promoting the formation and strengthening of synapses, thus aiding learning and memory.
Psychedelics reduce symptoms of depression and anxiety by inducing positive changes in neural circuits involved in emotion processing, such as the amygdala1. Furthermore, enhanced cognitive flexibility allows individuals to adapt to new information and switch tasks more efficiently, which is particularly beneficial for overcoming rigid thought patterns associated with mental health disorders7.
Thus, psychedelics promote long-term structural and functional changes in critical regions of the brain, most notably in areas like the prefrontal cortex and hippocampus, which are crucial for higher cognitive functions and memory. The persistence of these changes contributes to sustained improvements in cognitive and emotional health, highlighting the potential of psychedelics to enhance brain health and deliver long-term therapeutic benefits for various mental health conditions12.
Understanding the Neuroplasticity Phases
The duration of neuroplastic changes induced by psychedelics can be broken down into three distinct phases: Rapid Response, Growth Phase, and Maturation Phase.
Phase 1: Rapid Response (Hours to Days)
In the Rapid Response phase, psychedelics trigger immediate molecular and cellular changes. Plasticity-related genes and proteins such as brain-derived neurotrophic factor (BDNF) are upregulated within hours. Enhanced synaptogenesis, or the formation of new synaptic connections, can be observed within a day. For example, studies have shown significant increases in dendritic spine density (the “root system”) and synaptic activity within 24 hours after a single dose of DMT5.
Phase 2: Growth Phase (Days to Weeks)
During the Growth Phase, the initial synaptic changes continue to develop and take hold. Psychedelics promote the growth and branching of dendrites and the formation of new synapses, enhancing neural connectivity. Neurogenesis, the birth of new neurons (particularly in the hippocampus), occurs during this period. These new neurons integrate into existing neural networks, improving cognitive and emotional functions13,14.
Phase 3: Maturation Phase (Weeks to Months)
In the Maturation Phase, the newborn neurons and newly formed synapses undergo a process of maturation over several weeks to months. Full integration into the brain’s neural networks involves structural and functional maturation. It typically takes around four to six weeks for new neurons to mature and become functionally integrated into existing neural circuits (although some experts argue it may take up to ten to twelve weeks).
This period is crucial for stabilising and consolidating the new neural connections formed during the psychedelic experience6.
Understanding these phases helps optimise therapeutic strategies by aligning interventions with periods of highest neuroplastic potential, ensuring that the new neural pathways formed during and after psychedelic therapy lead to positive and lasting changes.
Challenges in Psychedelic Therapy and Neuroplasticity
Drug Interactions: Medications That Block Psychedelic Benefits
Certain prescription drugs, particularly those often prescribed for common mental health conditions, can interfere with the neuroplastic effects of psychedelics, posing significant challenges in psychedelic-assisted therapy.
Selective serotonin reuptake inhibitors (SSRIs), commonly used to treat depression, can blunt the effects of psychedelics by altering serotonin receptor activity. This interaction can lead to reduced therapeutic benefits as the psychedelics’ ability to promote neuroplasticity is diminished4,10.
Monoamine oxidase inhibitors (MAOIs), used for depression and other psychiatric disorders, present another risk. When combined with psychedelics, MAOIs can increase the risk of serotonin toxicity, a potentially life-threatening condition that also disrupts the expected neuroplastic effects11.
Antipsychotics such as risperidone and haloperidol, which block dopamine and serotonin receptors, can similarly reduce both the subjective and neuroplastic effects of psychedelics, limiting their therapeutic potential11.
Lithium, used to treat bipolar disorder, poses a risk for seizures and serotonin toxicity, which not only diminishes the quality of psychedelic experiences but also interferes with neuroplasticity11.
Additionally, benzodiazepines, commonly prescribed for anxiety and insomnia, can mute the effects of psychedelics, thereby reducing the intensity of the experiences and potentially limiting the neuroplastic benefits11.
The Cortisol Dilemma: How Stress Limits Neuroplasticity
High cortisol levels, a hormone associated with stress, can significantly inhibit neuroplasticity. Chronic stress leads to persistently elevated cortisol levels, negatively impacting the brain’s capacity to form new neural connections.
In the hippocampus, high cortisol can cause the dendrites, the root-like extensions of neurons, to shrink, reducing the number of dendritic spines essential for synaptic connections and neural communication8. Additionally, elevated cortisol levels can reduce the proliferation of neural progenitor cells in the hippocampus, impairing the brain’s ability to adapt and form new memories9. Cortisol also decreases the expression of BDNF, the “fertiliser” vital for supporting neuron growth and synaptic plasticity. Lower BDNF levels hinder the brain’s capacity to form and maintain critical neural connections9. Chronic stress can also lead to the atrophy of neurons in the prefrontal cortex, resulting in decreased cognitive flexibility and poorer emotional control2. Chronic stress shrinks the hippocampus, which is associated with cognitive decline and impaired memory.
The Dark Side of Plasticity: Risks of Negative Reinforcement
The enhanced neuroplasticity enabled by psychedelics can also reinforce negative behaviours and adaptations unless properly managed. For instance, if an individual returns to addictive habits shortly after a psychedelic experience, the heightened state of neuroplasticity can strengthen these behaviours, exacerbating the addiction. Furthermore, psychedelics promote rapid and extensive synaptic growth, which, if not carefully integrated and managed, can lead to chaotic or maladaptive neural connections. This uncontrolled synaptic growth might result in cognitive and emotional disturbances rather than the anticipated and desired therapeutic benefits2,3,4.
Grieving the Loss of Connection Post-Psychedelic Ceremony
The aftermath of a psychedelic ceremony can be an emotionally intense period marked by a profound sense of connection to oneself and others and a greater source of existence. This transformative experience reveals our true essence as collaborative and generous beings. However, reintegrating into a society that values disconnection and competition can cause this sense of unity to fade, leading to a significant and painful grieving process.
Western capitalist ideology promotes individualism and competition, perpetuating the belief that human nature is fundamentally selfish and separate. This perspective is detrimental, undermining our intrinsic collaborative tendencies. During a psychedelic ceremony, participants often experience a deep connection to their authentic selves, shattering the illusion of separation and competition. This experience highlights a reality where interdependence and unity are fundamental truths.
Returning to everyday life can be disorienting. The societal structures and norms we navigate daily do not align with the interconnected reality experienced during the ceremony. This dissonance can lead to a profound sense of loss and grief as the reconnection to our true selves diminishes. It is crucial to recognise and understand this grieving process as a natural part of integration.
Neuroscience offers insights into this phenomenon. As we established in the earlier chapters, the brain releases BDNF, a protein that supports neuron growth and neuroplasticity, during a psychedelic experience. This neuroplasticity facilitates deep emotional and cognitive shifts, allowing profound insights and reconnection to our true nature.
However, the same neuroplastic processes that enable these transformative experiences can also entrench feelings of loss and disconnection post-ceremony. Individuals may struggle to reconcile their insights with societal demands without conscious effort and support, leading to disconnection and competition. The initial sense of unity can be overshadowed by societal pressures, resulting in deep grief and longing.
An intentional integration process is essential to navigate this grieving period. This involves acknowledging the inevitability of this sense of loss and preparing for it with adequate support structures. Integration should include ongoing therapeutic support, community connections, and practices reinforcing the insights gained during the ceremony. Regular mindfulness practices, maintaining connections with supportive individuals, and creating environments that nurture the sense of unity experienced during the ceremony can help mitigate the loss.
Understanding the grieving process and its neurobiological underpinnings empowers individuals to approach integration with greater awareness and compassion. It’s not enough to merely undergo a psychedelic experience; the actual work lies in integrating these insights into daily life within a disconnected society, maintaining a connection to our authentic selves despite societal pressures.
The post-ceremony grieving process is a critical aspect of psychedelic integration. Society’s reinforcement of disconnection contrasts with the profound sense of unity experienced during psychedelic ceremonies. By understanding the role of neuroplasticity and being conscious of the grieving process, we can better prepare for reintegration challenges. Proper support and intentional practices can help preserve the transformative insights gained during the ceremony, fostering a more profound and lasting connection to our true, collaborative, and generous nature. This journey is essential to becoming conscious, whole, and free.
Embracing the Future of Mental Health and Personal Growth with Psychedelic Therapy
Psychedelic-assisted therapy offers a liberating path for those seeking real, lasting change in their mental health and personal growth. As a therapist, I’ve witnessed the profound transformations that psychedelics can bring. These treatments don’t just offer temporary relief—they create lasting, meaningful changes in the brain, enhancing emotional resilience and cognitive flexibility.
Psychedelic-assisted therapy facilitates dramatic changes in the brain that can lead to profound positive outcomes. However, these changes require the right conditions to truly take hold. Certain medications and high-stress levels can hinder the effects of psychedelics. This is why a structured, personalised approach to preparation and integration is crucial. Your therapist must understand your medical history to create a comprehensive plan. Many seeking this therapy worry about being turned away and might withhold crucial information, but doing so undermines the process. Personalised care ensures your unique needs are met, fostering a supportive and effective therapeutic experience.
Imagine a therapy that not only alleviates symptoms but also fosters personal and spiritual growth. This is the promise of psychedelic-assisted therapy. By working with professionals who understand the intricacies of this approach, you can unlock your brain’s potential to reorganise and adapt, leading to sustained improvements in mood and overall well-being.
For instance, a client who struggled with severe anxiety and had tried numerous conventional treatments found significant relief through a carefully structured psychedelic therapy program. With the proper guidance, they were able to navigate the challenges and achieve lasting positive changes in their mental health.
If you’re struggling with mental health challenges that conventional treatments haven’t addressed, or if you’re on a journey of personal and spiritual growth, psychedelic-assisted therapy could be the key to unlocking the next level of growth for you. This is more than just taking psychedelics in an informal setting—it’s a transformative experience that can lead to a brighter, more adaptable future.
For more insights into the phases of neuroplasticity and the potential benefits of psychedelic therapy, see my detailed discussion in the article Brain Plasticity And Psychedelic-Assisted Therapy: What You Need to Know. Explore strategies for optimising therapeutic outcomes with psychedelic therapy in Effective Strategies for Enhancing Neuroplasticity in Psychedelic-Assisted Therapy.
Interested in learning more about safe and effective psychedelic practices? Book a 20-minute consultation with Paul today to explore how personalised psychedelic-assisted therapy can benefit your mental health and well-being.
Don’t wait to start your journey towards enhanced brain plasticity and emotional resilience – schedule your consultation now and take the first step towards a healthier, more balanced future.
References:
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2. Calder, A. E., & Hasler, G. Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 48, 104-112 (2022). https://doi.org/10.1038/s41386-022-01389-z
3. Cameron, L. P., Tombari, R. J., Lu, J., Pell, A. J., Hurley, Z. Q., Ehinger, Y., … & Olson, D. E. A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 589, 474-479 (2021). https://doi.org/10.1038/s41586-020-3008-z
4. Carhart-Harris, R. L., & Nutt, D. Serotonin and brain function: a tale of two receptors. J. Psychopharmacol. 31, 1092-1105 (2017). https://doi.org/10.1177/0269881117725915
5. De Vos, C. M. H., Mason, N. L., & Kuypers, K. P. C. Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. Front. Psychiatry 12, 724606 (2021). https://doi.org/10.3389/fpsyt.2021.724606
6. Denoth-Lippuner, A., & Jessberger, S. Formation and integration of new neurons in the adult hippocampus. Nat. Rev. Neurosci. 22, 223-236 (2021). https://doi.org/10.1038/s41583-021-00433-z
7. Doss, M.K., Považan, M., Rosenberg, M.D. et al. Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. Transl Psychiatry 11, 574 (2021). https://doi.org/10.1038/s41398-021-01706-y
8. McEwen, B. S. Physiology and neurobiology of stress and adaptation: Central role of the brain. Physiol. Rev. 87, 873-904 (2007). https://doi.org/10.1152/physrev.00041.2006
9. Pittenger, C., & Duman, R. Stress, Depression, and Neuroplasticity: A Convergence of Mechanisms. Neuropsychopharmacol. 33, 88–109 (2008). https://doi.org/10.1038/sj.npp.1301574
10. Psychedelic Passage. The Psilocybin-Blunting Effects of SSRIs and Antidepressants. (2023). https://www.psychedelicpassage.com/psilocybin-blunting-effects-of-ssris-and-antidepressants/
11. Psychedelic Support. Psilocybin and SSRIs: A Talk with Dr. Erica Zelfand, ND. (2023). https://psychedelic.support/resources/psilocybin-and-ssris/
12. PsyPost. New research provides evidence that a single dose of psilocybin can boost brain connections. (2021). Retrieved from https://www.psypost.org/new-research-provides-evidence-that-a-single-dose-of-psilocybin-can-boost-brain-connections/
13. Ribeiro, F. F., & Xapelli, S. An Overview of Adult Neurogenesis. Adv. Exp. Med. Biol. 1331, 77-94 (2021). https://doi.org/10.1007/978-3-030-74046-7_7
14. Sumner, R., & Lukasiewicz, K. Psychedelics and neural plasticity. BMC Neurosci. 24, 35 (2023). https://doi.org/10.1186/s12868-023-00809-0
Disclaimer:
The content provided in this article series by Mind Matters is for informational and educational purposes only and does not substitute professional medical advice or consultation with healthcare professionals. If you are seeking medical advice, diagnoses, or treatment, we advise you to consult a licensed medical professional or healthcare provider. Psychedelic-assisted therapy is not legalised in Malta; therefore, our services in Malta focus solely on preparation and integration. We do facilitate psychedelic-assisted therapy in collaboration with licensed therapists in jurisdictions where it is legal. We do not provide or facilitate the use of illegal substances. Please check the legal status of psychedelic substances in your jurisdiction, as legal frameworks are continuously evolving.
Paul Sinclair
Paul, Managing Director at Mind Matters, specialises in mental health, trauma, and psychedelic-assisted therapy. He has trained under Dr. Gabor Maté, a renowned expert in trauma and addiction, and has also undergone extensive training in psychedelic-assisted therapy. Paul's diverse background as an elite military unit member, top athlete, and successful entrepreneur informs his unique approach to transforming ingrained patterns of thought and behaviour. He has trained thousands of individuals, and over 20,000 development and mental health professionals follow his teachings on LinkedIn. Paul believes in the power of resilience and personal transformation, drawing from his journey to inspire and guide his clients.
