Historically, the prevailing view in neuroscience was that the adult brain was largely fixed in structure and function. The saying “You can’t teach an old dog new tricks” reflected this outdated notion, suggesting that the brain’s capacity to adapt or reorganise diminished significantly after childhood. However, recent research has overturned this belief, revealing that the adult brain remains highly plastic and malleable throughout our lives. This capacity to reorganise and change itself underpins our ability to learn new skills, adapt to new experiences, and recover from brain injuries8.
Neuroplasticity, the brain’s ability to form new neural connections, is essential for learning, memory, and recovery from brain injuries. This process involves various mechanisms, including neurogenesis (the birth of new neurons), dendritogenesis (the growth of dendrites), and synaptogenesis (the formation of synapses).
Brain-derived neurotrophic factor (BDNF) plays a crucial role in enhancing neuroplasticity by promoting the formation and strengthening of synapses. You can think of BDNF as “Miracle-Gro for the brain.” It binds to its receptor, TrkB, activating multiple signalling pathways essential for plasticity, such as the MAPK/ERK pathway4. For instance, lifestyle factors can influence BDNF levels and, thus, neuroplasticity.
When we discuss brain plasticity, it’s essential to understand the role of daily habits. Regular physical exercise, cognitive training, and dietary choices can boost BDNF levels, enhancing neuroplasticity. This insight is crucial for those considering lifestyle changes to improve brain health.
Psychedelics like LSD and psilocybin interact with the 5-HT2A receptors in the brain, which increases the release of glutamate, a neurotransmitter that enhances neural activity and communication between neurons12. The activation of AMPA receptors by glutamate further promotes the production of BDNF, fostering neuroplasticity6. This positive feedback loop ensures sustained neuroplasticity and explains why the effects of psychedelics on the brain can last long after the drug has left the body9.
Unlocking Neuroplasticity: How Psychedelics Enhance the Brain
The 5-HT2A receptor is a type of protein (“docking station”) found on the surface of specific brain cells. It’s part of a larger family of receptors that respond to serotonin, a neurotransmitter in the brain that influences mood, cognition, and perception13. When psychedelics like LSD or psilocybin enter the brain, they dock with these 5-HT2A receptors, much like a key fits into a lock14. This docking triggers a cascade of events inside the brain cells. One of the first things that happens is an increase in the release of glutamate, a major neurotransmitter that acts like a “supercharger” for the brain, kickstarting neural activity and encouraging increased communication between neurons12.
The AMPA receptor is another type of molecular “docking station” found on the surface of brain cells, functioning like an antenna that catches glutamate signals. When glutamate binds to the AMPA receptors, these receptors open up and let ions flow into the cell, strengthening the signals between neurons and enhancing their communication and growth10. When AMPA receptors are activated by glutamate, they also trigger the production of BDNF, which acts like fertiliser for the brain, encouraging the growth of new neurons and strengthening existing ones6.
BDNF binds to a receptor called TrkB. When BDNF binds to TrkB, it activates a pathway inside the neuron called mTOR, which further stimulates the production of more BDNF and promotes the activity of AMPA receptors10. This creates a self-reinforcing cycle: psychedelics activate 5-HT2A receptors, which increase glutamate release; glutamate activates AMPA receptors, leading to BDNF production; BDNF binds to TrkB, activating the mTOR pathway, which enhances BDNF and AMPA receptor activity 9. This positive feedback loop ensures that once the process of neuroplasticity kicks off, it can sustain itself and continue to promote growth and connectivity in the brain. This loop helps to explain why the effects of psychedelics on the brain can last long after the drug itself has left the body.
Insights from Animal Studies: How Psychedelics Spark Brain Adaptation
Animal studies have provided significant insights into how psychedelics promote neuroplasticity. Researchers have found that psychedelics like LSD, psilocybin, and DMT can increase the expression of genes related to synaptic plasticity and dendritic growth3. These genes are crucial because they help build and strengthen the connections between neurons, essential for learning and memory.
In these studies, animals treated with psychedelics show an increase in the growth of dendrites, the root-like extensions of neurons that receive signals from other neurons. They also show an increase in the formation of synapses, which are the connections between neurons. This increased growth and connectivity suggest that psychedelics can enhance the brain’s natural ability to reorganise and adapt, which is the essence of neuroplasticity10.
For example, studies have shown that psychedelics upregulate immediate early genes (IEGs) and BDNF. IEGs are the first genes activated in response to neural activity, and they play a critical role in initiating the process of neuroplasticity. BDNF, as mentioned earlier, acts like fertiliser for the brain, promoting the growth and strengthening of neurons and synapses6.
However, the impact of psychedelics on neurogenesis, or the birth of new neurons, varies. Some studies have shown that psilocybin may reduce neurogenesis, while DMT can increase it2,11. This variability suggests that different psychedelics may have distinct effects on the brain’s ability to generate new neurons.
These findings support the observation that psychedelic-assisted therapy can enhance the brain’s capacity for adaptation and change. However, more research is needed to understand these mechanisms fully and how they translate to humans.
Observations from Human Studies: The Proof of Psychedelic-Mediated Brain Change
Human studies, although more limited than animal research, have provided compelling evidence that psychedelics can influence neuroplasticity. One key area of focus has been measuring BDNF levels as a neuroplasticity marker. For instance, a study found that a single dose of ayahuasca (a brew containing DMT) increased BDNF levels in both mentally healthy individuals and those suffering from depression 2. These findings support the notion that psychedelics can enhance neuroplasticity in humans, which would explain their long-term therapeutic effects.
Neuroimaging studies have also shown that psychedelics like psilocybin can alter brain connectivity. Increased connectivity between the prefrontal cortex and other brain areas, including the limbic system, has been observed, correlating with reductions in negative emotions and anxiety1.
These changes in brain connectivity can last several weeks, indicating that the neuroplastic effects of psychedelics are not just immediate but have a lasting impact. It is worth noting that increased connectivity between the executive and limbic brain regions is strongly correlated with resilience, i.e., an individual’s capacity to positively deal with and grow through adversity.
Further, studies involving LSD have shown that even low doses can acutely increase BDNF levels, pointing to its potential for promoting neuroplasticity7. However, results can vary, and not all studies have observed significant changes in BDNF levels following psychedelic administration, highlighting the need for more research to understand the specific conditions and mechanisms involved5.
These studies provide evidence that psychedelics can induce neuroplastic changes in humans. Increased BDNF levels and altered neural connectivity are associated with improvements in mood, anxiety, and cognitive function, suggesting that psychedelics hold promise for enhancing mental health. Nonetheless, the variability in findings highlights the need for further research to fully understand these effects and the implications for therapeutic application.
The Transformative Potential of Psychedelic-Assisted Therapy
Psychedelic-assisted therapy, once restricted by stringent policies, has recently become more accessible, offering new hope to those suffering in silence. For decades, three groups have had limited options: those suffering without a clinical diagnosis, those for whom conventional treatments take too long or fail to provide relief, and those seeking personal and spiritual growth. Now, with the easing of restrictions and increasing research support, psychedelics are emerging as powerful tools for all these individuals.
However, with this newfound accessibility comes the risk of retreat organisers and marketers jumping on the bandwagon without a deep understanding of the underlying neurobiological changes. It’s crucial to recognise that psychedelic-assisted therapy is not just a trendy solution; it involves profound changes in the brain that can lead to lasting improvements in mood, cognition, and resilience.
As a therapist, I have witnessed firsthand how psychedelics can transform lives by enhancing the brain’s ability to reorganise and adapt. These changes are not just imagined or transient; they are real, measurable shifts in brain function. Psychedelic-assisted therapy leverages the brain’s natural capacity for neuroplasticity, creating new neural pathways and strengthening existing ones.
The benefits of increased brain connectivity and elevated BDNF levels are well-documented. These changes facilitate better emotional regulation, enhanced cognitive flexibility, and greater resilience. However, achieving these profound benefits requires more than just taking a psychedelic substance. It demands a structured, comprehensive approach that includes preparation, integration, and ongoing support.
Preparation involves educating clients about what to expect, setting intentions, addressing fears, and creating a safe environment. The psychedelic session itself is conducted under the guidance of trained professionals who provide support and intervention as needed. The integration phase is crucial, where the insights and experiences from the session are processed and incorporated into daily life. This phase often involves additional therapy sessions, journaling, and other practices to solidify the changes.
Without proper guidance and support, the potential benefits of psychedelics can be diminished or even lead to adverse outcomes. This is why it is essential to work with professionals who understand the complexities of psychedelic-assisted therapy and can provide the necessary support throughout the entire process.
In our practice, we are committed to providing this level of structured support. Our approach is designed to maximise the therapeutic potential of psychedelics, ensuring that clients achieve the most significant and lasting benefits possible. With the right approach, psychedelic therapy can be a powerful tool for healing and transformation.
The promise of psychedelic-assisted therapy lies in its ability to foster genuine, lasting change. This is not just a fleeting experience but a profound shift in brain function, leading to improved mental health and well-being. If you are struggling with mental health challenges that conventional treatments have not addressed, or if you are seeking personal and spiritual growth, psychedelic-assisted therapy could be the key to unlocking your potential.
For more on how psychedelics enhance brain connectivity, see our detailed discussion in the article Harnessing Neuroplasticity: How Psychedelics Transform Your Brain and explore insights into 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:
1. Barrett, F. S., Doss, M. K., Sepeda, N. D., Pekar, J. J., & Griffiths, R. R. Emotions and brain function are altered up to one month after a single high dose of psilocybin. Sci. Rep. 10, 2214 (2020). https://doi.org/10.1038/s41598-020-59282-y
2. Catlow, B. J., Song, S., Paredes, D. A., Kirstein, C. L., & Sanchez-Ramos, J. Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning. Exp. Brain Res. 228, 481-491 (2013). https://doi.org/10.1007/s00221-013-3579-0
3. de la Fuente Revenga, M., Zhu, B., Guevara, C. A., Naler, L. B., Saunders, J. M., & Zhou, Z. Prolonged epigenomic and synaptic plasticity alterations following single exposure to a psychedelic in mice. Cell Rep. 37, 109836 (2021). https://doi.org/10.1016/j.celrep.2021.109836
4. 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
5. Holze, F., Ley, L., Müller, F. et al. Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects. Neuropsychopharmacol. 47, 1180–1187 (2022). https://doi.org/10.1038/s41386-022-01297-2
6. Horch, H., & Katz, L. BDNF release from single cells elicits local dendritic growth in nearby neurons. Nat. Neurosci. 5, 1177–1184 (2002). https://doi.org/10.1038/nn927
7. Hutten, N. R. P. W., Mason, N. L., Dolder, P. C., Theunissen, E. L., Holze, F., Liechti, M. E., Varghese, N., Eckert, A., Feilding, A., Ramaekers, J. G., & Kuypers, K. P. C. Low Doses of LSD Acutely Increase BDNF Blood Plasma Levels in Healthy Volunteers. ACS Pharmacol. Transl. Sci. 4, 461–466 (2020). https://doi.org/10.1021/acsptsci.0c00099
8. Kolb, B., & Gibb, R. Searching for the principles of brain plasticity and behaviour. Cortex 58, 251-260 (2014). https://doi.org/10.1016/j.cortex.2013.11.012
9. Ly, C., Greb, A. C., Vargas, M. V., Duim, W. C., Grodzki, A. C. G., Lein, P. J., & Olson, D. E. Transient Stimulation with Psychoplastogens Is Sufficient to Initiate Neuronal Growth. ACS Pharmacol. Transl. Sci. 4, 452–460 (2020). https://doi.org/10.1021/acsptsci.0c00065
10. Ly, C., Greb, A. C., Cameron, L. P., Wong, J. M., Barragan, E. V., Wilson, P. C., Burbach, K. F., Soltanzadeh Zarandi, S., Sood, A., Paddy, M. R., Duim, W. C., Dennis, M. Y., McAllister, A. K., Ori-McKenney, K. M., Gray, J. A., & Olson, D. E. Psychedelics Promote Structural and Functional Neural Plasticity. Cell Rep. 23, 3170–3182 (2018). https://doi.org/10.1016/j.celrep.2018.05.022
11. Morales-Garcia, J. A., Calleja-Conde, J., Lopez-Moreno, J. A., Alonso-Gil, S., Sanz-SanCristobal, M., Riba, J., & Perez-Castillo, A. N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca regulates adult neurogenesis in vitro and in vivo. Transl. Psychiatry 10, 331 (2020). https://doi.org/10.1038/s41398-020-01011-0
12. Muschamp, J. W., Regina, M. J., Hull, E. M., Winter, J. C., & Rabin, R. A. Lysergic acid diethylamide and [-]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex. Brain Res. 1023, 134–140 (2004). https://doi.org/10.1016/j.brainres.2004.07.044
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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.
