Stress affects millions of people worldwide. The endocannabinoid system plays a role in stress regulation by interacting with the HPA axis and the amygdala, a significant modulator of stress and relaxation responses. Medicinal cannabis, particularly CBD, may have a beneficial effect on stress relief.

We all experience stress at some point in our lives, whether due to work pressure, family responsibilities, or personal challenges.  But have you ever wondered what really happens to our bodies when we’re stressed?  And is there anything we can do to manage stress more effectively?

Stress is the body’s physiological response to substantial or unusual demands, which can initiate the “Fight or Flight” response.  The body’s stress response is regulated by the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS).  When the body perceives a threat or challenge, the hypothalamus releases corticotropin-releasing hormone (CRH), initiating a cascade that will ultimately lead the adrenal glands to release cortisol, the known body’s stress hormone.  The SNS also plays a role in the stress response by releasing adrenaline and noradrenaline, which increase heart rate, blood pressure, and respiration rate, among other physiological changes.  The stress response is a fundamental evolutionary adaptation that has enabled survival in challenging environments.

Even though our threats or stressors have changed, our bodies are still wired that way.  Nowadays, stress is a global issue that affects millions of people worldwide.  Apart from societal issues such as deprivation of basic life needs (food, shelter, security), our modern lifestyle with constant demands, expectations, and deadlines creates a stressful environment.  According to the World Health Organization, stress is the leading cause of disability worldwide, and it is estimated that stress-related illnesses cost the global economy $1 trillion each year.  Chronic stress has been linked to a range of health problems, including cardiovascular disease, diabetes, and depression.

Exposure to stressful circumstances can lead to headaches, tense muscles, insomnia, and other symptoms.  Stress can also alter memory function, immune function, metabolism, and disease susceptibility.  In fact, about 450 million people suffer from a mental or behavioral disorder due to stress, according to a WHO report.

The currently available scientific data clearly implicates the endocannabinoid system (ECS) in the central modulation of both physical and mental-emotional stress (both acute and chronic).  Endocannabinoids play a role in adaptation to stress and regulate the release of glucocorticoids in stressed and unstressed conditions.  The ECS interacts with the HPA axis in response to stress, and research suggests that endocannabinoid signaling plays an inhibitory role in regulating HPA axis activity and cortisol release.  Under basal conditions, endocannabinoid signaling suppresses HPA axis activity through concerted actions within the prefrontal cortex, amygdala, and hypothalamus.

Regarding the use of cannabis, various studies have examined the plant’s impact on the body’s stress-coping mechanisms.  Some results have been inconclusive, but recent studies have begun to resolve the apparently contradictory findings.  These lie in the differences between the use of cannabis-based therapeutics consisting of different ratios of CBD and THC, which is a major determining factor in realizing potential therapeutic or adverse effects.

Pre-clinical research has suggested that the endocannabinoid system (ECS)  plays a role in the stress recovery response.  A 2022 study found a relation between endocannabinoid level changes from pre-to-post-acute stress and the stress response, suggesting that targeting 2-AG  could be promising in finding treatments in the immediate aftermath of traumatic events. A 2022 systematic review of pre-clinical studies published in Translational Psychiatry found that cannabinoids may be a viable treatment option for stress-related psychopathologies such as depression and anxiety.

A lot of the research on ECS, cannabis, and stress has been developed within a PTSD framework.  A study found that the endocannabinoid 2-arachidonoyl glycerol (2-AG) was elevated in the cerebrospinal fluid of PTSD-phenotype rats in comparison to other groups and was inversely correlated with corticosterone urinary secretion.  This suggests that the ECS may be involved in the development of PTSD by regulating cortisol levels in response to stress, representing a therapeutic opportunity.

A 2021 study published in JAMA found that CBD reduced the symptoms of emotional exhaustion, anxiety, and depression among frontline healthcare professionals working during the COVID-19 pandemic.

There are still many underexplored areas and exciting therapeutic possibilities on the horizon.  Besides the direct involvement of the ECS exposed above, there is a whole body of research on the use of cannabis-based therapeutics to address conditions linked to chronic stress exposure, such as depression, insomnia, anxiety, diabetes, and cardiovascular issues.

It is important to stress (no pun intended) that cannabis does not operate miracles: managing stress effectively involves an integrative approach.  Here are a few tips: 

  • Practicing mindfulness meditation: Mindfulness meditation is a powerful tool that can help you manage stress.  It involves focusing on the present moment and accepting it without judgment.  This practice can help you calm your mind and reduce stress levels.
  • Engaging in regular physical exercise: Exercise is a great way to reduce stress.  It can help you release endorphins, which are natural mood boosters.  Regular exercise can also help you sleep better and improve your overall health.
  • Getting enough sleep: Lack of sleep can make you feel more stressed and anxious.  It is essential to get enough sleep to allow your body to recover from stress.  Aim for at least 7-8 hours of sleep each night.
  • Connection with others: Social support is an essential aspect of managing stress.  Talking to friends or family can help you feel more connected and reduce stress. 

In conclusion, stress is a complex physiological response affecting millions worldwide.  The endocannabinoid system plays a role in stress regulation by interacting with the HPA axis and the amygdala, a significant modulator of stress and relaxation responses.  Cannabis-based therapeutics can greatly aid in stress management, but it is essential to integrate strategies like regular exercise and quality sleep (and here, cannabis can help as well) to manage stress more effectively.


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