The following study summary is a homework excerpt from Module 6: Endocannabinoid System, Lesson 1: Overview from the forthcoming Higher Learning LV course Cannabis Foundation: Part 1.
An August 2022 study entitled "A Systematic Review and Meta-Analysis on the Effects of Exercise on the Endocannabinoid System" that was published in the journal Cannabis and Cannabinoid Research investigated the relationship between exercise and the human endocannabinoid system (ECS).
More specifically, the researchers were curious if exercise may lead to improvements in the health, or tone, of the ECS that, in concert, may lead to improvements in disease states or conditions believed to result from deficiencies and problems in the ECS.
What is the ECS?
"The endocannabinoid system [ECS] plays a key role in maintaining homeostasis, including the regulation of metabolism and stress responses," reported the study, with a nod to the significant role played by the ECS in a number of bodily functions within humans and mammals.
Merriam-Webster defines homeostasis as "a relatively stable state of equilibrium or a tendency toward such a state between the different but interdependent elements or groups of elements of an organism, population, or group." In this case, that "group" is the endocannabinoid system.
"Chronic stress may blunt ECS signaling and disruptions in signaling have been linked to stress-related psychiatric disorders and physical health conditions, including anxiety, depression, post-traumatic stress disorder (PTSD), diabetes, and obesity."
ECS Disruptions Linked to Anxiety, Depression, & PTSD
"Chronic stress may blunt ECS signaling and disruptions in signaling have been linked to stress-related psychiatric disorders and physical health conditions, including anxiety, depression, post-traumatic stress disorder (PTSD), diabetes, and obesity," reported the research.
The study noted that the ECS "plays a key role in maintaining homeostasis throughout the brain and body, including regulating energy metabolism, cognition, sleep, inflammation, and stress responses."
CB1 & CB2 Receptors
It reported that CB1 receptors in the ECS are most dense in the limbic regions of the brain, including the prefrontal cortex, amygdala, and hippocampus—areas that are implicated "in stress and emotion regulation, reward processes, fear learning, and extinction." The research also reported that CB2 receptors in the ECS "are found on immune tissues and play an immunomodulatory role."
The study reported that research indicates that "nonpharmacological approaches—particularly exercise—can boost ECS signaling." It explained that the euphoric, analgesic (pain reducing), and mood-elevating effects of exercise (sometimes called "runner's high") previously were attributed to the endogenous opioid system and, more specifically, boosts in the human-produced opioid endorphin.
Runner's High Theory Debunked
"However, recent studies have challenged the role of endorphins in mediating the beneficial effects of exercise" for a variety of reasons, including evidence that "endorphins cannot cross the blood–brain barrier."
In addition, research has revealed that when endorphin signaling is blocked, this state does not prevent post-exercise "euphoric, analgesic, and anxiolytic effects," indicating that endocannabinoids such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are more likely the causal agents behind this long-misunderstood mechanism.
Research has revealed that when endorphin signaling is blocked, it does not prevent post-exercise "euphoric, analgesic, and anxiolytic effects," indicating that endocannabinoids such as anandamide and 2-AG are more likely the causal agents behind this long-misunderstood mechanism.
"Emerging data indicate that the ECS plays a pivotal role in mediating some of the well-documented effects of exercise, including reductions in pain and anxiety and improvements in cognitive functioning and mood," reported the study's authors. All reviewed studies indicated that "moderate-intensity exercise was associated with greater increases in [the endocannabinoid] anandamide as compared with less-intense exercise."
The study noted that "behavioral interventions" such as exercise "may be promising therapeutic approaches for the prevention and treatment of stress-related diseases" involving the ECS. "In this study, we perform a systematic review and the first meta-analysis to examine the impact of exercise on circulating endocannabinoid concentrations," explained the scientists.
The design of the study was that of a literature review that analyzed all prior studies (which had to meet a strict qualification criteria) regarding this topic. "We performed a review of the MEDLINE (PubMed) database for original articles examining the impact of exercise on [endocannabinoids] in humans and animal models," reported the study's authors. A total of 262 articles were screened for this study.
"The majority of [studies] that measured [the endocannabinoid] anandamide showed a significant increase in concentrations following acute exercise (74 percent increase), whereas effects on [the endocannabinoid] 2-AG were inconsistent," reported the study.
"The majority of [studies] that measured [the endocannabinoid] anandamide (AEA) showed a significant increase in anandamide concentrations following acute exercise."
The meta-analysis segment of the research "revealed a consistent increase in both [anandamide] and 2-AG following acute exercise across modalities (e.g., running, cycling), species (e.g., humans, mice), and in those with and without pre-existing health conditions (e.g., PTSD, depression)," reported the scientists.
The research reported that the data collected serve as "evidence to support the notion that acute exercise mobilizes endocannabinoids."
The study concluded that "acute exercise activates the ECS" and manifests as an increase in "circulating concentrations of endocannabinoids" such as 2-AG and anandamide. "Given that disruptions in ECS signaling are linked to several stress-related diseases (e.g., anxiety, depression, PTSD, obesity, and diabetes), exercise is a promising non-pharmacological approach for the prevention and treatment of stress-related psychopathology," summarized the researchers.
The anandamide molecule
If exercise leads to increased levels of endocannabinoids such as 2-AG and anandamide, what are the potential results of these increased endocannabinoid volumes? "Studies included in this review frequently report that elevations in endocannabinoids are associated with, or accompanied by, mood elevations, reductions in stress, anxiety, and pain, and enhanced cognitive functioning," reported the study. A slew of positive outcomes, no doubt.
"Elevations in endocannabinoids are associated with, or accompanied by, mood elevations, reductions in stress, anxiety, and pain, and enhanced cognitive functioning."
The research report noted that exercise also leads to increases in chemical compounds beyond endocannabinoids, including greater volumes of "circulating glucocorticoids, which may increase anandamide concentrations in the brain." It added that "other biomarkers" have been shown to be elevated following acute exercise and that this "may contribute (independently or in conjunction with endocannabinoids) to neuroplastic [indicating a potential role in diseases of aging such as Alzheimer's and Parkinson's] and antidepressant effects of exercise."
Need for Additional Research
The scientists reported that there is a critical need for additional research—particularly human clinical trials—that focus on five distinct issues related to exercise and the endocannabinoid system:
The usefulness of exercise as a probe for ECS functioning in disease or at-risk states
The shape of the ECS response and recovery following acute exercise
Factors that modify endocannabinoid response to exercise
Ability for chronic exercise to modulate basal endocannabinoid concentrations
Exercise as a preventive or therapeutic intervention
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