Cannabinoid system versus fear and anxiety
Hashtag anxiety hits 13 million posts on @Instagram alone. Yet, many believe being stressed and being anxious is more or less the same. And, most importantly the outcome is on you. Willpower, or the power of positive thinking, exercising, healthy diet — all within your hands. Trust me, deep breathing only will not correct the dysregulation of the body’s physiological systems.
A routine blood test may reveal one’s thyroid hormone level, or vitamin D level is abnormal. I challenge that praying, meditating, or taking a relaxing bath would reset vitamin D or thyroid. However, everyone seems to have advice on how to treat anxiety. Try yoga, take a deep breath, relax, forgive yourself, go for a walk, meditate. Still no luck to be more chill? Meditate deeper, longer, ring a friend, reconnect with your family — millions of useful ideas. Approaches are indeed excellent to deal with occasional stress (a justified and temporary worry). Still, it does nothing to help a person who suffers from constant chronic and recurring anxiety when no threat presents itself on the horizon.
Stress as an occasional worry is a healthy survival mechanism. Anxiety, when no imminent danger presented, is a disorder. Strikingly, chronic anxiety may be a hypocannabinergic state of the endocannabinoid system (ECS). Severe anxiety, also known as post-traumatic stress disorder (PTSD) is an extreme reaction to terrifying events.
Lately, significant insight into the brain functioning and neuronal circuits regulating anxiety has been gained. A large body of data has emerged and published in highly respected medical reviews, pointing to a crucial role of the endocannabinoid system (ECS) in regulating the acquired fear, anxiety, and stress coping. The endocannabinoid system is a primary human system guarding us against fear, anxiety, and stress. The new theory is that chronic stress creates a chemical disbalance in the human body’s signaling — the so-called “hypocannabinergic state.” The inability to properly process and extinct fears as in PTSD is more or less a chemical disbalance.
A change of ECS may have occurred at birth ( genetic predisposition) or due to exposure to stressful events, or both.
In 2018 Health Canada gathered and published, available evidence suggesting an essential role for the ECS in PTSD. Fear-related memories change the brain in animals, for example. The altered brain further enhances fear-related behaviors. Evidence from human trials suggests that PTSD is distinguished by hyperresponsiveness of the amygdala, a brain region. And CB1 receptor (one of two receptors of ECS) plays a central role in fear extinction.
Fortunately, there is a possibility of manipulating the ECS and disrupt contextual fear memories. The human body creates molecules on demand to regulate and balance the endocannabinoid system, such as anandamide. And some of us are better genetically equipped to process fears and avoid disproportional anxiety.
Low-level anxiety as the anticipation of potential threats to avoid harmful situations is helpful. After all, anxiety-like behaviors (for example, avoidance, decreased motion, increased heart rate, and hypervigilance) within the normal range are essential for survival. However, when anxiety chronically exceeds the normal range and becomes disproportionate to the actual level of danger, you need a solution, not a well-meaning friend.
Scientists are getting better evidence supporting CB1 receptor agonists (for example, medical Cannabis) in alleviating persistent anxiety. Yet, no trials have looked into the genetic makeup of trial participants, the doses (low versus high), the pattern of consumption (acute versus chronic ), the way to administer (oral, vape, smoking), and the age and gender. And why? The stigma of Cannabis.
Individuals with PTSD have a lower level of circulating endocannabinoid and upregulation of brain CB1 receptors. Evidence exists micro-dosing medical Cannabis helps with anxiety. Ultra-low and low doses of partial agonist activity of cannabinoid receptor CB1 (THC) alleviate stress, but high doses are ineffective or potentially anxiety-provoking. Also, there is proof that humans (and mice) carrying a common variant of the FAAH gene have increased anandamide signaling and show reduced threat-related reactivity and enhanced fear extinction. A study of 16 healthy individuals looked at the effects of THC on amygdala reactivity — an ultra-low dose of human-made Cannabis correlates with reduced brain reactivity to a perceived threat and does not affect visual and motor function. To explore further, the participants have had functional magnetic resonance imaging (fMRI) of the brain while reexposed to the memory of the traumatic events — the amygdala showed decreased activity. The fear seemed to be successfully extinct from memory. Another randomized clinical study of 48 healthy participants found that CBD further enhanced the consolidation of fear abolition. That suggests that CBD may be a potential help to consolidate extinction-based therapies for anxiety disorders.
The authors of the 266 pages long detailed report from Canadian Health authorities highlighted that evidence is too limited to draw any definite conclusions. Clinical trials are urgently needed to determine the safety and efficacy of plant-based Cannabis for PTSD, anxiety disorder, and fear extinction.
Self-proclaimed “experts” and gurus believe that the choice is yours to worry about or not. But neuroscientists know: “Our current understanding, cultural, and social acceptance of anxiety disorder is incomplete. Our view of brain functioning only started to take shape since 1992 when ECS was discovered”.
Read more about the human Endocannabinoid system and the potential medical application of Cannabis-derived drugs.
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Anna Deveaux, M.Sc. is a learner, writer, biotech investor who is interested in research translation, drug development, genetics.