How Does Stress Affect the Endocannabinoid System?

Stress impacts the endocannabinoid system

Whether you’re about to have a job interview or are running from a mountain lion, stress can have an impact on your endocannabinoid system (ECS).

The ECS is part of your central nervous system that interacts with weed to get you high or produce therapeutic benefits. The endocannabinoid system governs all sorts of physiologic functions from sleep to appetite to mood.  

Read our full article on why weed gives you the munchies.

“ECB signaling is an important regulatory system in the brain that largely functions to buffer against many of the effects of stress and that dynamic changes in this system contribute to different aspects of the stress response,” states a 2016 study in Neuropsychopharmacology.

Researchers didn’t thoroughly document the endocannabinoid system until the 1990s, and they’re still trying to determine exactly how your endocannabinoid system works in response to stress, but evidence shows it’s crucial. Experiments with altered levels of ECS neurotransmitters (check out our article on anandamide) and artificially blocked ECS neuroreceptors have shown the ECS not only helps kick off your stress response, but it also helps you form memories about stressful situations and fine-tune your behavior and physical response over long periods of repeated stress so you’re not constantly in panic mode.

As a result, scientists are scrambling to understand all the intricacies of the ECS’s involvement in stress response. The hope is this study will lead to cannabis-based or other types of pharmaceuticals that target the ECS to treat all sorts of psychiatric disorders related to stress and trauma.

This is a schematic illustration of all the most important neurochemicals in the endocannabinoid system and how they interact with each other, as well as how they affect other neurochemical signaling systems. For a full description, visit the article in Nature Reviews Neuroscience, which provided this image.

How does your body respond to stress?

Human beings can get used to anything — maybe our greatest strength and greatest weakness. For example, say you’re an apprentice metalworker, and you have to strap in and hang off the side of a half-finished skyscraper for the first time. Your palms sweat, your heart races, you can’t catch your breath and your stomach drops. You can barely force yourself to go through with it.

A year later, however, you’re walking along iron girders 20 stories in the sky as if you’re strolling out your front door to get the mail.

The stakes haven’t changed — you’re still going to be a puddle of guts if you fall off that girder. YOU have changed, not only in your knowledge and expertise, but on a chemical level as your nervous system becomes conditioned to the dangerous conditions you spend eight hours a day braving.

And it’s your endocannabinoid system that helped turn you into a cool-headed steeplejack instead of the sweating, bug-eyed newbie the union guys ragged on all day.

This is a schematic illustration of how the ECB regulates the inhibitory and excitatory nerve responses within a synapse, or space between neurons. For a full explanation of this illustration, visit the journal Nature Reviews Neuroscience, which provided this image.

The reason you have those physiologic stress symptoms is to prepare your body to throw a punch or get the hell out — you need sweat to cool you off as your heart rate jumps in preparation for physical activity, flooding your muscles with oxygenated blood and making your lungs work overtime. Readers may be familiar enough to know this alludes to the famous “fight or flight” phenomenon.

When you perceive stress, the neuroendocrine subsystem called the hypothalamus-pituitary-adrenal axis kicks into overdrive. The stressful concept — that is, your perception of your physical height at a given moment and your knowledge of what happens to bodies when they hit the pavement — crystalizes in your hypothalamus. The hypothalamus is the part of your brain that regulates the pituitary gland, automatic functions like breathing and sleep, and the emotional fear response, among other functions.

hypothalamus has endocannabinoid receptors for stress

Your frightened hypothalamus revs up your pituitary gland, which among other functions, tells your adrenal glands (which sit on top of your kidneys) to squirt out adrenaline/epinephrine. Adrenaline is a super stimulant that primes your muscles to, for instance, lift a car off your baby, to use the old trope.

“Stress exposure also provokes a shift in many neurobehavioral processes, such as anxiety/vigilance, memory, reward salience, pain sensitivity, and coping behaviors,” states the Neuropsychopharmacology study. “Collectively, these changes in biological function produce coordinated and highly adaptive responses that are conducive to survival in response to a threat.”

The trouble is, being terrified all the time is really hard on your body. If you couldn’t get used to stressful situations, your body would be flooded with adrenaline and glucocorticoids (the body’s own steroids) every time you were exposed to the same stressor.

As a high-rise construction worker who could never get used to the height, the wear and tear on your organs and mood would be similar to taking methamphetamines every day.

As anyone who has panic disorder, spent time in prison, worked in high finance or is a combat veteran can tell you, that’s not a great place to be. Luckily, evolution has equipped us with the endocannabinoid system, referred to by one prominent neuroscientist as “the traffic cop of the nervous system.”

Your endocannabinoid system changes its neurotransmitter production levels in such a way as to tell your hypothalamus to take it easy — “it seems scary now, but as long as you watch where you step, you’re not going to fall.” As a result, your pituitary ratchets down its activity. Your adrenaline levels return to relatively normal — not, like, sitting-on-the-couch-watching-Simpsons-reruns normal, but not panic-level.

This schematic shows how the endocannabinoid regulates synaptic transmission in synapses where three neurons meet. In the lower half of the image, the center cell is an astrocyte, a star-shaped type of brain neuron that provides nutrients to other neurons and helps regulate electrical activity in the brain. For a full explanation, visit Nature Reviews Neuroscience, which provided this image.

In this, your endocannabinoid system is like the boxing cornerman for your hypothalamus, feeding it water, massaging its shoulders, giving strategic tips between rounds.

“ECB signalling seems to determine the value of fear-evoking stimuli and to tune appropriate behavioural responses, which are essential for the organism’s long-term viability, homeostasis and stress resilience; and dysregulation of eCB signalling can lead to psychiatric disorders.” states a 2018 study published in Nature Reviews Neuroscience. “The endocannabinoid system has emerged as a central integrator linking the perception of external and internal stimuli to distinct neurophysiological and behavioural outcomes (such as fear reaction, anxiety and stress-coping), thus allowing an organism to adapt to its changing environment,”

How does the endocannabinoid system regulate stress response?

“ECS signalling (has) long been known to regulate the hypothalamic-pituitary-adrenocortical (HPA) axis, which is the major neuroendocrine stress response system of mammals,” according to a meta analysis published in the European Journal of Pharmacology. “However, how the ECS could modify the stress hormone secretion is not fully understood.’

The human endocannabinoid system comprises two main neuroreceptors — molecules with a specifically shaped hole in the middle that sit on a neuron’s membrane and act as a keyhole to unlock functions. There are two types of these endocannabinoid receptors we know of, called CB1 and CB2, and they’re in nerve cells throughout your brain, gut and to a lesser degree, throughout your nervous system.

CB1 and CB2 activate — kicking off a cascade of physiological effects that govern sleep, mood, perception and a host of other vital functions — when they connect with your naturally produced cannabinoid (endocannabinoid) neurotransmitters called anandamide (AEA) and 2-arachidonoylglycerol (2-AG). These neurotransmitters are the keys (ligands) to the CB1 and CB2 locks.

These neurotransmitters are similar in structure and properties to Delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD), which are the two most potent cannabinoids the marijuana plant produces. As a result, the phytocannabinoids (phyto meaning “plant” in Greek) partially activate CB1 and CB2, leading to the shift in mood and perception characterized as the marijuana high.

stress impacts the endogenous cannabinoid system

Researchers have measured how the endocannabinoid system reacts to stress mostly in rodents, whose neurology has many of the same properties as ours. The data show the ECS is responsible for both activating the HPA axis to produce the stress response (specifically through elevated levels of 2-AG) and for habituating the brain response and higher-order behavior in the face of repeated stress.

The ECS is also crucial in forming emotional memories in periods of high stress — that is, your memory of the fear or terror you experienced during a stressful event. This is why it’s such a promising target for treatment of post-traumatic stress disorder and other trauma-related psychiatric issues.

About Adam Townsend 50 Articles
Adam Maxwell Townsend has been a journalist for 15 years. His reporting has covered science, technology and medicine. Currently, he edits and writes medical and pharmaceutical articles for consumer websites, including WoahStork.

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