Exercise as a Cognitive Enhancer: Learning & Memory
In a previous article, we explored how exercise can boost mood and reduce symptoms of anxiety and depression. But, exercise is not only beneficial for physical and emotional well-being, it can also enhance cognitive functioning and performance. I became interested in understanding more about the positive effects of exercise on the mind and brain, so have put together a bit of a summary of some of the things that I’ve been reading about recently. This is definitely one for the science nerds (like me) out there!
In this article, we will examine some of the mechanisms through which exercise at specific intensities can improve cognition and brain health by focusing on the upregulation of brain-derived neurotrophic factor (BDNF) via exercise and the endocannabinoid pathway. Then we will explore how this relates to improved learning and memory through promotion of neurogenesis and neuroplasticity. Finally, we will also look at some practical takeaways on utilising the knowledge of these mechanisms to your advantage when you’re studying or working, and even potentially to help reduce or prevent age-related cognitive decline.
Disclaimer: This article is intended for educational purposes only. Engaging in moderate to higher intensity exercise can increase the risk of injury. It is recommended that you consult your regular GP for a check-up and obtain medical clearance before commencing any new exercise program. Remember, safety is always the priority.
Mechanisms of Exercise-Induced Cognitive Enhancement
In response to exercise, people often report improved mood, a greater sense of well-being and calm, reductions in symptoms of anxiety or depression, and decreased sensations of pain (Dietrich & McDaniel, 2004; Raichlen et al., 2013). The underlying mechanisms which influence these outcomes can also positively influence the brain’s neurological receptiveness to learning and memory while providing additional neurological protective effects through the promotion of various growth factors (Voss et al., 2013; Costa et al., 2015; Kerling et al., 2017; Bosch et al., 2021; Chacur et al., 2023; Raji et al., 2024). Though there are several different factors that contribute to these effects, such as increased blood flow, alertness, motivation, and energy availability, this article will mostly focus on the endocannabinoid pathway, how endocannabinoid signalling contributes to BDNF production, and BDNF’s role in enhancing cognition and neural functioning.
The Endocannabinoid Pathway & Anandamide
Exercise induces the release of endocannabinoids (Sparling et al., 2003; Bosch et al., 2021; Weiermair et al., 2024), which are lipid-based neurotransmitters naturally synthesised in the body that are thought to play a role in the “runner’s high” phenomenon. When endocannabinoids are circulating in the bloodstream, they are suggested to be able to pass through the blood-brain barrier, where they can affect the brain in a variety of ways (Dietrich & McDaniel 2004; Glaser et al., 2006; Willoughby et al., 1997). There are many variables in this system, but endocannabinoids influence brain signalling (the electrical and chemical communication between neurons) and the body’s regulatory system, before they are rapidly broken down by enzymes to maintain a tightly regulated and controlled system (Dietrich & McDaniel, 2004; Glaser et al., 2006).
Endocannabinoids bind to specific cannabinoid receptors around the body, with two main subtypes identified, known as CB₁ and CB₂ (Matsuda et al., 1990; Gerard et al., 1991), though a third subtype has also been speculated (Dietrich & McDaniel, 2004; Joshi & Onaivi, 2019). CB₁ receptors are mostly located in the central nervous system, while CB₂ receptors are mostly located in peripheral tissues linked to the immune system. When activated, this broad distribution of endocannabinoid receptors modulate various things in the body, including the release of other neurotransmitters, cognitive and motor functions, mood, perception of pain, gut motility and appetite, energy metabolism, and immune and inflammatory responses (Munro, Thomas, & Abu-Shaar, 1993; Howlett et al., 2002; Joshi & Onaivi, 2019).
Of the endocannabinoids, anandamide was the first discovered and is the most frequently studied (Joshi & Onaivi, 2019). It acts primarily on the CB₁ receptor within the body’s existing homeostatic systems, where it triggers a cascade of biochemical events that modify cell behaviour and neural functioning by activating various intracellular signalling pathways.
For example, when CB₁ receptors located on afferent (sensory) nerve endings are activated they can inhibit the release of the chemical messengers that would normally send the signal responsible for alerting the potential presence of pain to the central nervous system, thereby reducing the perception of pain (Ahluwalia et al., 2000; Morisset et al., 2001; Agarwal et al., 2007). These effects have even been suggested to rival the potent effects of morphine (for a summary of research in animal models, see Dietrich & McDaniel, 2004), although the concentration of receptor activation and type of pain stimuli appears to modify the analgesic effect (Morisset et al., 2001; Agarwal et al., 2007).
Research has also shown that exercise-inducted increases in circulating endocannabinoids, such as anandamide, are associated with greater hippocampal neurogenesis (Palazuelos et al., 2006; Hill et al., 2010) which is the formation and proliferation of new functional neurons from adult neural stem cells/precursors (Costa et al., 2015). This is relevant as the hippocampus is a region of the brain directly implicated in memory and learning, which has lead to the presence of anandamide being described as essential for this process to occur (Aguado et al., 2005, 2006; Raichlen et al., 2013; Costa et al., 2015). Not only does this contribute to exercise’s effects on mood regulation, but also to other key outcomes of interest here, increasing cognitive functioning and the expression and release of neurotropic growth factors like BDNF (Aguado et al., 2005, 2006; Heyman et al., 2012; Costa et al., 2015; Bosch et al., 2021).
What this means, is that exercise-induced increases of endocannabinoids and BDNF can lead to more neurons being developed which facilitates more, and, stronger connections in the brain. When these physical connections are enhanced through this process, it can then help support various cognitive abilities, such as processing information, learning, memory, logical reasoning, judgement, inhibition, and decision-making.
CB₁ receptors are mostly found in the central nervous system, including in the hippocampus, cortex, cerebellum, and basal ganglia. However, CB₁ receptors are also expressed in various peripheral tissues including the lungs, liver, and kidneys.
CB₂ receptors are located in some parts of the brain, but are mostly found on cells of the immune system in peripheral tissues, including the spleen, tonsils, lymph nodes, immune cells, gastrointestinal tract, liver, and adipose tissue.
Ferrets are unreliable. Interestingly, the endocannabinoid effects in response to exercise have also been shown in to occur in dogs, possibly functioning as a ‘reward’ to motivate engaging in exercise due to its survival benefits (Raichlen et al., 2012). Amusingly, when trying to determine if other animals not adapted for endurance exercise shared this effect by testing for it in ferrets, Raichlen and colleagues (2012) lamented that they couldn’t get the ferrets to walk consistently on treadmills at any speed, despite using positive reinforcement to attempt to encourage them!
Brain-Derived Neurotrophic Factor Production & the Hippocampus
BDNF is a protein that underpins the development, growth, and survival of neurons (Maisonpierre et al., 1991; Bosch et al., 2021). BDNF stimulates neurogenesis and additionally provides protective effects to different stressors in the brain, such as when there is too much nerve activity, poor blood flow, low blood sugar, or exposure to toxins (Maisonpierre et al., 1991; Cotman & Berchtold, 2002; Raji et al., 2024). BDNF also supports synaptic plasticity which relates to the changes in the strength and efficiency of synaptic connections between neurons; and, is a key component of neuroplasticity which is to the brain’s ability to adapt and reorganise itself by forming new neural connections (Cotman & Berchtold, 2002). This remodelling of the brain is an automatic process that you have probably experienced without realising, like when you slowly get better at doing things with your non-dominant hand after unfortunately having your other arm in a cast for several weeks. These processes are fundamental for learning and memory, including in contributing to long-term potentiation, by helping to create an environment for the brain that supports continued neuronal development (Chen et al., 2007; Bosch et al., 2021). BDNF is also widely considered to protect from age-related cognitive decline (Cotman & Berchtold, 2002; Erickson et al., 2011), such as the estimated 1-2% annual decreases in hippocampus volume in older adults (Raz et al., 2005) which increases the risk of developing cognitive impairment (Jack et al., 2010).
Regular exercise stimulates the hippocampus however, and has been associated with increased BDNF levels, improved memory and cognitive flexibility, enhanced physical performance, and greater brain structure volumes in both young and elderly populations (Kramer et al., 1999; Erickson et al., 2011; Costa et al., 2015; Bosch et al., 2021; Hola et al., 2024; Raji et al., 2024). Other mechanisms, though independent to the endocannabinoid upregulation of BDNF via a receptor-mediated signalling effect, also work to raise levels of BDNF in the brain as well. For example, the body produces higher amounts of another molecule (β-hydroxybutyrate) during exercise which crosses the blood brain barrier to change gene expression and also increase BDNF production through a metabolic and epigenetic effect (Sleiman et al., 2016).
When the process of neuron formation in the hippocampus is decreased or disrupted however, such as due to low levels of BDNF, it can potentially lead to difficulties with mood regulation, cognitive deficits, altered brain structure, memory impairments, and challenges in social and cognitive development. This is suggested to link hippocampal neurogenesis to underlying biological processes in a wide range of disorders, including depression, schizophrenia, age-related memory impairment, and some neuronal developmental disorders such as autism spectrum disorder (Costa et al., 2015; Kerling et al., 2017). Frequent high stress has also been correlated with atrophy of the hippocampus (Sapolsky, 1996).
On a similar note, research suggests that approximately 20-30% of Caucasians have a genetic mutation that reduces activity-dependant BDNF secretion (Shimizu et al., 2004; Egan et al., 2003; Chen et al., 2004) and is also connected to reduced memory functioning, and increased risk of Alzheimer’s disease, depression, and anxiety-related disorders (Shimizu et al., 2004; Sen et al., 2003; Verhagen et al., 2010; Soliman et al., 2010). Additionally, low levels of BDNF are associated with neurodegenerative conditions, such as Parkinson’s disease, multiple sclerosis, and Huntington’s disease (Bathina & Das, 2015).
Fortunately, exercise has been shown to help naturally increase endocannabinoid, BDNF, and other growth factor levels, especially when conducted at specific intensities which can help promote and maintain brain functioning and plasticity, including if commenced later in life (Cotman & Berchtold, 2002; Erickson et al., 2011; Sleiman et al., 2016; Bosch et al., 2021). Even when not assessing for BDNF changes, single 10-minute bouts of moderate-intensity running have been found to produce greater cortical activation of the prefrontal subregions of the brain, while boosting mood and executive functioning (Damrongthai et al., 2021).
Long-term potentiation is the process by which neurons strengthen their connections to each other with frequent activation. Over time, this enhances efficiency of communication and forms the primary cellular mechanism for learning and memory.
Hippo-campus. An easy way to remember the roles of the hippocampus (or at least how I remember it) is to break the word down into hippo and campus, then conjure an image of both to mind. Hippos are like elephants, and ‘elephants never forget’, suggesting an excellent memory. And, when you’re at a school or university campus, you’re (hopefully) learning. Hence, the hippocampus is responsible for memory and learning.
Suggested Exercise Intensity
Moderate intensity exercise, in the range of 70-80% of age-adjusted maximum heart rate has been found to provide significant changes in circulating endocannabinoid levels (Raichlen et al., 2013) which also has a contributory and independent effect BDNF production..
Note that to specifically obtain an upregulation in circulating endocannabinoid levels, Raichlen and colleagues (2013) suggest that the exercise intensities experienced during walking may not be sufficient. However, this finding was in the context of their research participants all self-identifying as ‘fit, healthy, regular runners’ with an average age of ~32 years old, who could run continuously for 30-mintues. Similarly, in a seminal study by Sparling and colleagues’ (2003), research participants were ‘trained male college students’ with an average age of ~24 years, who had been training for minimum 2-hours/week for the past 6-months. As such, in individuals who are older or not as highly trained, personal responses to exercise such as walking may provide the moderate exercise intensity suggested in the literature, while also being an approachable starting point.
Therefore, as much of the research has used trained individuals, if someone was new to exercising they could calculate their own 70-80% suggested target heart rate range, then review their individual response to exercises where they can maintain a steady heart rate. To make this easy, most smartwatches have built in heart rate monitors, but if this is inaccessible, counting a pulse on the wrist or one side of the neck for 6 seconds, then multiplying this number by 10 to give approximate beats per minute provides a quick estimate. As a rough guide, Sparling and colleagues (2003) describe that moderate intensity exercise should not be easy, but not exhausting either.
To create a more objective calculation of moderate intensity exercise, calculating specific target heart rates to use as a guide (as untrained individuals tend to show greater inaccuracy when rating exercise intensity) that take into account individual variations in age (being older theoretically lowers maximum heart rate) and resting heart rate (as a proxy for fitness level) with heart rate calculators can be useful.
Heart Rate Calculator
Please enter your age and, if known, your normal resting heart rate below. This calculator uses the Tanaka and colleagues (2001) formula to estimate your maximum heart rate and, if you provide your resting heart rate, applies the Karvonen method (Karvonen et al., 1957) to calculate your target heart rate range at 70–80%. Including your resting heart rate helps tailor the calculation to your individual fitness level.
Modifying Exercise to Support Memory & Learning
1) Aim for moderate intensity, aerobic exercise where you can maintain a steady state heart rate guided by your personal ~70-80% heart rate range.
Aerobic training, rather than resistance training seems to have the most evidence for providing the effects discussed. Exercises targeting major muscle groups through locomotion (moving your whole body around) are utilised in the research, most frequently with running, but also with cycling, hiking, and rowing, with some attempts to include swimming (Sparling et al., 2003; Dietrich & McDaniel 2004; Rasmussen et al., 2009; Feuerecker et al., 2012; Heyman et al., 2012). There are some suggestions however that running, as a more involved locomotive process, elicits stronger promotion of cognitive and mood enhancing effects (Damrongthai et al., 2021).
2) Start with durations of at least ~10 minutes and increase to be within a ~20-60 minute window.
This follows the typical durations utilised in much the research identified here. Keep in mind however, that session duration varies a lot and is likely heavily influenced by personal overall fitness levels and format of exercise, so adjust this depending on your own personal tolerance.
3) Try to maintain a regular and consistent exercise regime distributed throughout work/study (preferably before engaging with learning exposure), then a high quality sleep routine after learning exposure.
This might be something that you engage with every day in some small way or every other day, while actively focusing on engaging with the material you are trying to take in. There is some research starting to examine the influence exercise frequency exerts on post-exercise circulating endocannabinoid levels (Weiermair et al., 2024), though this requires further examination and replication.
4) Potentially most importantly, try to be selective with the type of both intended and unintended stimulation that the brain receives.
The brain is constantly learning from the environment and encoding experiences in attempts to increase adaptive functioning for the future. This means that just because the brain has been primed for receptivity of learning and long-term potentiation, that it is going to magically encode useful information by itself (anybody else got a whole bunch of old TV show quotes in their brain?). The aim is to pair neural receptivity with beneficial behaviours and exposure to the type of content that you are wishing to engage with and encode into memory. This might include utilising evidence-based studying techniques (like the principles from contextual interference combined with self-testing), focusing on mastering or refining processes at work, or while establishing healthy behavioural habits. If the brain in this state is exposed to ‘fast food-esq’ sources of un-focused information, like scrolling endlessly through short-format videos or reality TV shows, the resulting implications on the neural networks could be less then ideal, potentially leading to development of what I like to think of as ‘Type 2 ADHD’ (an almost pseudo-ADHD developed from ineffective lifestyle and behavioural factors).
How a Psychologist Can Help
Now that we have hopefully learnt a bit about how exercise influences brain health and functioning, it’s time to talk about some of the things that a psychologist can help you work on in therapy to influence the mind.
Exercise is helping to provide the warm-up for the engine, but we also want to make sure that the path you are taking the vehicle down is the right one. This metaphor is supposed to communicate that the brain can be primed to be in a more receptive state to optimally take in information, but the mind can easily take us wandering off course or in an unintended direction, and this is where talk therapy can come into it.
Talk therapy is just that, therapy that is done by talking about some of the different mental processes that occur in your mind and depending on therapeutic orientation, this might include unhelpful automatic thoughts, maladaptive beliefs about things, how you have come to understand others/the world, perceptions of relationships in your life, and ineffective patterns in behaviour. Any of the things that may not necessarily be taking you in the most helpful direction, often without you realising. Just like it is easy to find yourself lost when driving in an unknown area, with lots of unnecessary turns down side streets (to continue the metaphor), a psychologist can help you recognise and overcome problems with these things and provide tools to navigate back towards a more efficient pathway to help increase the probability of achieving your goals.
So, if you would like to learn more about how some therapy sessions or how seeing a psychologist could help you, consider getting in touch today.
Key Takeaways
Exercise can make you feel better emotionally and can also be an effective tool to improve brain health and functioning.
Exercise partly achieves this by increasing endocannabinoid and BDNF levels in the brain through various pathways.
These increases and changes can improve the brain’s neuroplasticity, growth of new neurons, and neural connectivity.
Improved neural functioning can benefit memory and learning processes but also overall cognitive abilities.
Moderate intensity exercise at ~70-80% age-adjusted maximum heart rate appears most effective for boosting endocannabinoid levels.
References
Agarwal, N., Pacher, P., Tegeder, I., Amaya, F., Constantin, C. E., Brenner, G. J., Rubino, T., Michalski, C. W., Marsicano, G., Monory, K., Mackie, K., Marian, C., Batkai, S., Parolaro, D., Fischer, M. J., Reeh, P., Kunos, G., Kress, M., Lutz, B., Woolf, C. J., … Kuner, R. (2007). Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors. Nature Neuroscience, 10(7), 870–879. https://doi.org/10.1038/nn1916
Aguado, T., Monory, K., Palazuelos, J., Stella, N., Cravatt, B., Lutz, B., ... & Galve‐Roperh, I. (2005). The endocannabinoid system drives neural progenitor proliferation. The FASEB Journal, 19(12), 1704-1706. https://doi.org/10.1096/fj.05-3995fje
Aguado, T., Palazuelos, J., Monory, K., Stella, N., Cravatt, B., Lutz, B., ... & Galve-Roperh, I. (2006). The endocannabinoid system promotes astroglial differentiation by acting on neural progenitor cells. Journal of Neuroscience, 26(5), 1551-1561. https://doi.org/10.1523/JNEUROSCI.3101-05.2006
Ahluwalia, J., Urban, L., Capogna, M., Bevan, S., & Nagy, I. (2000). Cannabinoid 1 receptors are expressed in nociceptive primary sensory neurons. Neuroscience, 100(4), 685–688. https://doi.org/10.1016/s0306-4522(00)00389-4
Bathina, S., & Das, U. N. (2015). Brain-derived neurotrophic factor and its clinical implications. Archives of Medical Science : AMS, 11(6), 1164–1178. https://doi.org/10.5114/aoms.2015.56342
Bosch, B. M., Bringard, A., Logrieco, M. G., Lauer, E., Imobersteg, N., Thomas, A., ... & Igloi, K. (2021). A single session of moderate intensity exercise influences memory, endocannabinoids and brain derived neurotrophic factor levels in men. Scientific Reports, 11(1), 14371. https://doi.org/10.1038/s41598-021-93813-5
Chacur, M., Binda, K. H., & Real, C. C. (2023). Exercise and Parkinson’s disease: Linking in the cannabinoid type 1 (CB1) and type 2 (CB2) and mu-opioid receptors. In V. B. Patel, V. R. Preedy, & C. R. Martin (Eds.), Neurobiology and Physiology of the Endocannabinoid System (pp. 137–147). Academic Press. https://doi.org/10.1016/B978-0-323-90877-1.00028-0
Chen, K., Henry, R. A., Hughes, S. M., & Connor, B. (2007). Creating a neurogenic environment: The role of BDNF and FGF2. Molecular and Cellular Neuroscience, 36(1), 108-120. https://doi.org/10.1016/j.mcn.2007.06.004
Chen, Z. Y., Patel, P. D., Sant, G., Meng, C. X., Teng, K. K., Hempstead, B. L., & Lee, F. S. (2004). Variant brain-derived neurotrophic factor (BDNF)(Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. Journal of Neuroscience, 24(18), 4401-4411. https://doi.org/10.1523/JNEUROSCI.0348-04.2004
Costa, V., Lugert, S., & Jagasia, R. (2015). Role of adult hippocampal neurogenesis in cognition in physiology and disease: Pharmacological targets and biomarkers. In K. Kantak & J. Wettstein (Eds.), Cognitive Enhancement: Handbook of Experimental Pharmacology (pp. 99–155). Springer. https://doi.org/10.1007/978-3-319-16522-6_4
Cotman, C. W., & Berchtold, N. C. (2002). Exercise: A behavioural intervention to enhance brain health and plasticity. Trends in Neurosciences, 25(6), 295–301. https://doi.org/10.1016/S0166-2236(02)02143-4
Damrongthai, C., Kuwamizu, R., Suwabe, K., Ochi, G., Yamazaki, Y., Fukuie, T., ... & Soya, H. (2021). Benefit of human moderate running boosting mood and executive function coinciding with bilateral prefrontal activation. Scientific reports, 11(1), 22657. https://doi.org/10.1038/s41598-021-01654-z
Dietrich, A., & McDaniel, W. F. (2004). Endocannabinoids and exercise. British Journal of Sports Medicine, 38(5), 536-541. https://doi.org/10.1136/bjsm.2004.011718
Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., ... & Weinberger, D. R. (2003). The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal Function. Cell, 112(2), 257-269. https://doi.org/10.1016/s0092-8674(03)00035-7
Erickson, K. I., Voss, M. W., Prakash, R. S., Basak, C., Szabo, A., Chaddock, L., ... & Kramer, A. F. (2011). Exercise training increases size of hippocampus and improves memory. Proceedings of the National Academy of Sciences, 108(7), 3017-3022. https://doi.org/10.1073/pnas.1015950108
Feuerecker, M., Hauer, D., Toth, R., Demetz, F., Hölzl, J., Thiel, M., ... & Choukèr, A. (2012). Effects of exercise stress on the endocannabinoid system in humans under field conditions. European Journal of Applied Physiology, 112, 2777-2781. https://doi.org/10.1007/s00421-011-2237-0
Gerard, C. M., Mollereau, C., Vassart, G., & Parmentier, M. (1991). Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochemical Journal, 279(1), 129-134. https://doi.org/10.1042/bj2790129
Heyman, E., Gamelin, F. X., Goekint, M., Piscitelli, F., Roelands, B., Leclair, E., ... & Meeusen, R. (2012). Intense exercise increases circulating endocannabinoid and BDNF levels in humans—Possible implications for reward and depression. Psychoneuroendocrinology, 37(6), 844-851. https://doi.org/10.1016/j.psyneuen.2011.09.017
Hill, M. N., Titterness, A. K., Morrish, A. C., Carrier, E. J., Lee, T. T. Y., Gil‐Mohapel, J., ... & Christie, B. R. (2010). Endogenous cannabinoid signaling is required for voluntary exercise‐induced enhancement of progenitor cell proliferation in the hippocampus. Hippocampus, 20(4), 513-523. https://doi.org/10.1002/hipo.20647
Hola, V., Polanska, H., Jandova, T., Jaklová Dytrtová, J., Weinerova, J., Steffl, M., ... & Bartos, A. (2024). The Effect of Two Somatic-Based Practices Dance and Martial Arts on Irisin, BDNF Levels and Cognitive and Physical Fitness in Older Adults: A Randomized Control Trial. Clinical Interventions in Aging, 1829-1842. https://doi.org/10.2147/CIA.S482479
Howlett, A. C., Champion, D., Wilkenham, N., Mechoulam, R., & Pertwee, R. G. (2002). International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacological Reviews, 54(2), 161–202. https://doi.org/10.1124/pr.54.2.161
Jack Jr, C. R., Wiste, H. J., Vemuri, P., Weigand, S. D., Senjem, M. L., Zeng, G., ... & Alzheimer’s Disease Neuroimaging Initiative. (2010). Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer’s disease. Brain, 133(11), 3336-3348. https://doi.org/10.1093/brain/awq277
Joshi, N., & Onaivi, E. S. (2019). Endocannabinoid System Components: Overview and Tissue Distribution. In A. N. Bukiya (Ed.), Recent Advances in Cannabinoid Physiology and Pathology. Advances in Experimental Medicine and Biology (pp. 1-12). Springer. https://doi.org/10.1007/978-3-030-21737-2_1
Karvonen, M. J., Kentala, E., & Mustala, O. (1957). The effects of training on heart rate; A longitudinal study. Annales Medicinae Experimentalis et Biologiae Fenniae, 35(3), 307-315.
Kerling, A., Kück, M., Tegtbur, U., Grams, L., Weber-Spickschen, S., Hanke, A., ... & Kahl, K. G. (2017). Exercise increases serum brain-derived neurotrophic factor in patients with major depressive disorder. Journal of Affective Disorders, 215, 152-155. https://doi.org/10.1016/j.jad.2017.03.034
Kramer, A. F., Hahn, S., Cohen, N. J., Banich, M. T., McAuley, E., Harrison, C. R., ... & Colcombe, A. (1999). Ageing, fitness and neurocognitive function. Nature, 400(6743), 418-419. https://doi.org/10.1038/22682
Maisonpierre, P. C., Le Beau, M. M., Espinosa III, R., Ip, N. Y., Belluscio, L., de la Monte, S. M., ... & Yancopoulos, G. D. (1991). Human and rat brain-derived neurotrophic factor and neurotrophin-3: gene structures, distributions, and chromosomal localizations. Genomics, 10(3), 558-568. https://doi.org/10.1016/0888-7543(91)90436-I
Matsuda, L. A., Lolait, S. J., Brownstein, M. J., Young, A. C., & Bonner, T. I. (1990). Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature, 346(6284), 561-564. https://doi.org/10.1038/346561a0
Morisset, V., Ahluwalia, J., Nagy, I., & Urban, L. (2001). Possible mechanisms of cannabinoid-induced antinociception in the spinal cord. European Journal of Pharmacology, 429(1-3), 93–100. https://doi.org/10.1016/s0014-2999(01)01309-7
Munro, S., Thomas, K. L., & Abu-Shaar, M. (1993). Molecular characterization of a peripheral receptor for cannabinoids. Nature, 365(6441), 61–65. https://doi.org/10.1038/365061a0
Palazuelos, J., Aguado, T., Egia, A., Mechoulam, R., Guzmán, M. and Galve-Roperh, I. (2006), Non-psychoactive CB2 cannabinoid agonists stimulate neural progenitor proliferation. The FASEB Journal, 20, 2405-2407. https://doi.org/10.1096/fj.06-6164fje
Raichlen, D. A., Foster, A. D., Seillier, A., Giuffrida, A., & Gerdeman, G. L. (2013). Exercise-induced endocannabinoid signaling is modulated by intensity. European Journal of Applied Physiology, 113(4), 869–875. https://doi.org/10.1007/s00421-012-2495-5
Raichlen, D. A., Foster, A. D., Gerdeman, G. L., Seillier, A., & Giuffrida, A. (2012). Wired to run: Exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the ‘runner’s high’. Journal of Experimental Biology, 215(8), 1331-1336. https://doi.org/10.1242/jeb.063677
Raji, C. A., Meysami, S., Hashemi, S., Garg, S., Akbari, N., Ahmed, G., ... & Attariwala, R. (2024). Exercise-related physical activity relates to brain volumes in 10,125 individuals. Journal of Alzheimer’s Disease, 97(2), 829-839. https://doi.org/10.3233/JAD-230740
Rasmussen, P., Brassard, P., Adser, H., Pedersen, M. V., Leick, L., Hart, E., ... & Pilegaard, H. (2009). Evidence for a release of brain‐derived neurotrophic factor from the brain during exercise. Experimental Physiology, 94(10), 1062-1069. https://doi.org/10.1113/expphysiol.2009.048512
Raz, N., Lindenberger, U., Rodrigue, K. M., Kennedy, K. M., Head, D., Williamson, A., ... & Acker, J. D. (2005). Regional Brain Changes in Aging Healthy Adults: General Trends, Individual Differences and Modifiers. Cerebral Cortex, 15(11), 1676-1689. https://doi.org/10.1093/cercor/bhi044
Sapolsky, R. M. (1996). Why Stress Is Bad for Your Brain. Science, 273(5276), 749-750. https://doi.org/10.1126/science.273.5276.749
Sen, S., Nesse, R. M., Stoltenberg, S. F., Li, S., Gleiberman, L., Chakravarti, A., ... & Burmeister, M. (2003). A BDNF coding variant is associated with the NEO personality inventory domain neuroticism, a risk factor for depression. Neuropsychopharmacology, 28(2), 397-401. https://doi.org/10.1038/sj.npp.1300053
Shimizu, E., Hashimoto, K., & Iyo, M. (2004). Ethnic difference of the BDNF 196G/A (val66met) polymorphism frequencies: The possibility to explain ethnic mental traits. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 126B(1), 122–123. https://doi.org/10.1002/ajmg.b.20118
Sleiman, S. F., Henry, J., Al-Haddad, R., El Hayek, L., Abou Haidar, E., Stringer, T., ... & Chao, M. V. (2016). Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate. eLife, 5, e15092. https://doi.org/10.7554/eLife.15092
Sparling, P. B., Giuffrida, A., Piomelli, D., Rosskopf, L., & Dietrich, A. (2003). Exercise activates the endocannabinoid system. Neuroreport, 14(17), 2209-2211. https://doi.org/10.1097/00001756-200312020-00015
Tanaka, H., Monahan, K. D., & Seals, D. R. (2001). Age-predicted maximal heart rate revisited. Journal of the American College of Cardiology, 37(1), 153-156. https://doi.org/10.1016/S0735-1097(00)01054-8
Verhagen, M., van der Meij, A., van Deurzen, P. A. M., Janzing, J. G. E., Arias-Vasquez, A., Buitelaar, J. K., & Franke, B. (2010). Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: Effects of gender and ethnicity. Molecular psychiatry, 15(3), 260-271. https://doi.org/10.1038/mp.2008.109
Voss, M. W., Vivar, C., Kramer, A. F., & van Praag, H. (2013). Bridging animal and human models of exercise-induced brain plasticity. Trends in Cognitive Sciences, 17(10), 525-544. https://doi.org/10.1016/j.tics.2013.08.001
Weiermair, T., Svehlikova, E., Boulgaropoulos, B., Magnes, C., & Eberl, A. (2024). Investigating Runner’s High: Changes in Mood and Endocannabinoid Concentrations after a 60 min Outdoor Run Considering Sex, Running Frequency, and Age. Sports, 12(9), 232. https://doi.org/10.3390/sports12090232
