Anxiety is a normal human reaction when one is faced with trials or difficulties. But once the problem is resolved, the anxiousness should disappear. For people suffering from an anxiety disorder, the feelings of fear, anxiety, and worry do not go away and typically worsen over time, affecting daily activities and interfering with their quality of life.
Almost everyone who has smoked marijuana in the past has occasionally experienced anxiety or, in some cases, full-blown panic attacks as a result. Therefore, many are very surprised to learn that a compound found in the cannabis plant, Cannabidiol (CBD), may be an incredibly effective treatment for anxiety.
Understanding Anxiety Disorder
According to the National Institute of Mental Health, 40 million adults in the United States suffer from an anxiety disorder, making it the most common mental illness in the U.S. Some of the most common anxiety disorders include:
- Panic Disorder: feelings of fear arise suddenly, without reason or warning, causing the person to feel terrified, anxious, and jittery.
- Generalized Anxiety Disorder: causes constant nervousness, extreme anxiety, and excessive worry about everyday life. Individuals worry and feel anxious about almost everything — personal relationships, health, financial status, work, and school.
- Phobias: phobias are an extreme, unreasonable fear of a particular thing or situation which can be triggered without its actual presence. Merely mentioning a trigger can cause exaggerated feelings of fear and anxiety.
- Social Anxiety Disorder: an exaggerated sense of fear, anxiety, and distress about speaking or interacting with other people. Classic examples include fear of speaking in public, fear of criticism, and fear of going out.
Pathophysiology of Anxiety
Anxiety disorders are caused by abnormalities in the brain, specifically an imbalance in neurotransmitters. The neurotransmitters1 most responsible for anxiety symptoms are:
- Serotonin and gamma-aminobutyric acid (GABA): inhibitory neurotransmitters which are responsible for mood stability and balancing the effects of excitatory neurotransmitters.
- Dopamine: functions as an excitatory and an inhibitory neurotransmitter.
- Norepinephrine: an excitatory neurotransmitter which excites and stimulates the brain.
- Corticotropin-releasing factor (CRH): a hormone and neurotransmitter secreted by the hypothalamus when a stressor is present.
- Orexin or hypocretin: a hypothalamic neuropeptide2 that plays a role in wakefulness, arousal, and appetite; and also plays a role in panic attacks3.
When we experience anxiety, the amygdala is triggered4 by a stimulus or stressor. The amygdala is the part of the brain where anxiety symptoms originate. Although it doesn’t trigger feelings or thoughts, it dictates how the body reacts. Its primary function is managing fear and our response to situations that we view as potentially dangerous.
The amygdala causes the heart and respiratory rate to rise by sending distress signals to the medulla oblongata, which is responsible for the body’s fight or flight response.
The amygdala also activates the hypothalamus, sending distress signals to activate the adrenal medulla which releases adrenaline, causing the brain to release more excitatory neurotransmitters.
In a perfectly functioning brain, inhibitory neurotransmitters modulate the body’s response5 to the stimulus.
However, in anxiety disorders, a neurotransmitter imbalance6 causes disruption in modulation and regulation, resulting in low serotonin and GABA, excessive norepinephrine and CRH, and high glutamate levels.
With inhibitory neurotransmitters depressed, anxiety and nervousness are heightened and intensified by excessive excitatory neurotransmitters, and CRH helps to enhance negative emotions.
Signs and Symptoms of Anxiety
During a panic attack, heart and respiratory rate increase causing palpitations and shortness of breath because the brain needs more oxygen to prepare for the flight and fight response. Anxiety and panic symptoms7 include nausea, chest pain, trembling, tingling, choking, lightheadedness, and loss of control.
Predicting a panic attack is impossible, and the anticipation alone can worsen symptoms.
Anxiety Disorder: Common Causes and Risk Factors
Several factors cause anxiety disorders:
- Stressors and Triggers — life events like health, financial, work, or personal problems, objects, and memories which trigger the attacks.
- Medical Conditions:
- Hyperthyroidism8, or high thyroid hormone levels, trigger the body’s fight or flight response.
- Diabetes9, specifically hypoglycemia, can cause anxiety by triggering an adrenaline release and the fight or flight response.
- Heart diseases10 cause irregularities and abnormalities in heart function including palpitations, dizziness, and shortness of breath which could trigger an anxiety attack.
- Lung problems like asthma and chronic obstructive pulmonary disease (COPD)11 can trigger anxiety.
- Brain tumors or cancers can cause anxiety by causing overproduction of hormones responsible for fight or flight response. Pheochromocytoma or paraganglioma12, tumors of the adrenal gland, cause higher adrenaline production.
- Traumatic brain injury13 and stroke14 can cause anxiety.
- Chronic pain.
- Drug or alcohol abuse, or withdrawal symptoms due to dependence.
- Genetic predisposition.
Current Treatment for Anxiety Disorders
Anxiety disorders treated with medication and therapy aim to “change” the reaction to the stimulus and teach coping techniques to lessen the effects of anxiety.
Common Medications for Anxiety Disorders
Conventional drugs for anxiety disorders include:
- Selective Serotonin Reuptake Inhibitors15 (SSRIs) inhibit reabsorption of serotonin canceling the effects of excitatory neurotransmitters.
- Benzodiazepines16 enhance neurons’ GABA receptors, making them more receptive to GABA and less excitable to excitatory neurotransmitters.
- Tricyclic Antidepressants17 inhibit reabsorption of serotonin and norepinephrine. Too little norepinephrine can cause depression18 which typically accompanies anxiety disorders.
Side Effects of Anti-Anxiety Drugs
Medications help control symptoms of anxiety and panic attacks but come with an extensive list of side effects19 including:
- Dizziness and lightheadedness
- Incoordination and weakness
- Headaches and vertigo
- Dry mouth
- Blurry vision, sometimes with eye muscle spasms
- GI upset — Nausea, diarrhea or constipation
- Slurred speech
- Swelling (fluid retention)
- Sexual dysfunction
- Weight change
- Long-term damage to the heart, lungs, and kidneys
Cannabinoids: An Alternative Treatment for Anxiety Disorders
The endocannabinoid system (ECS)20, has two primary cannabinoid receptors in the central and peripheral nervous systems which respond to endocannabinoids (body-produced cannabinoids) and phytocannabinoids (cannabinoids from plants) to regulate pain, appetite, mood, and other physiological processes, like inflammation.
In recent years, researchers have begun to uncover the possibilities of using phytocannabinoids as an alternative treatment for a variety of illnesses and diseases, including anxiety disorders. In particular, Cannabidiol (CBD) has been shown to be an effective treatment for anxiety without generating any of the psychoactive effects typically associated with cannabis.
CBD Boosts Serotonin Receptors
Serotonin receptors are found all over the brain, including the amygdala. Serotonin activates these receptors, creating a cascade of signals21 which decrease the heart and respiratory rate, reduce body temperature, produce a calming effect, and decrease anxiety and aggression.
Antidepressants22 increase serotonin in the brain, but too much serotonin causes the brain to stop releasing serotonin, causing antidepressants to take longer to control anxiety symptoms.
On the other hand, CBD boosts serotonin receptors and inhibits signaling23 its receptors, causing the brain to continue to release serotonin and achieving the antidepressant effect much faster.
CBD Inhibits the Uptake of GABA
GABA24, an inhibitory neurotransmitter, decreases neuron excitability, creating a calming effect and relaxing muscle tone. Low GABA levels can lead to heightened anxiety symptoms. CBD inhibits the uptake25 of this neurotransmitter. By blocking the reabsorption of GABA, CBD helps control excitatory neurotransmitters.
CBD Inhibits Dopamine Release
Dopamine can be either an excitatory or inhibitory neurotransmitter depending on the part of the brain it acts on and the receptor site to which it binds. Playing a role in “pleasure and reward” feelings, dopamine is commonly referred to as the “feel good” neurotransmitter, creating motivation and energy.
In anxiety disorders, irregular dopamine levels affect how the amygdala interprets the importance of an event. Higher dopamine levels can increase anxiety symptoms26.
CBD activates adenosine receptors, which have an important role in regulating blood flow and heart rate27, and suppressing the release of excitatory neurotransmitters28 like dopamine. Activating these receptors with CBD decreases anxiety symptoms by inhibiting the release of dopamine, slowing down the heart rate, and normalizing blood pressure.
CBD Inhibits Glutamate Release
Glutamate, a major excitatory neurotransmitter29, plays a role in stress responses30, especially how we develop, retain, and prioritize fears.
Lab research31 on rodents shows that stress affects normal glutamate transmission, and disruption contributes to anxiety. Adenosine receptors regulate the release of glutamate32, and CBD activates these receptors, effectively blocking glutamate release.
CBD Reduces Hypothalamic Activity
The hypothalamus plays a role in stress and anxiety reaction by secreting higher levels of CRH and orexin, which affect arousal and wakefulness and increase anxiety symptoms.
A study showed CBD’s effects on regional cerebral blood flow heightened activity in the hypothalamus when a stressor was present. After the anxiolytic properties of CBD had taken effect, hypothalamic activity decreased33.
Studies on the Effectiveness of CBD for Treating Anxiety
Research and human clinical trials on CBD continue to demonstrate its effectiveness as an alternative treatment for anxiety. A few of the case studies worth noting include:
- A study in 201134 included 36 participants –12 individuals with no anxiety disorder and 24 with social anxiety disorder who were not being treated. All were asked to perform a simulated public speaking test. The 12 healthy individuals were not given anything before the trial, while the second group was divided – with half receiving CBD and half a placebo. Throughout the test, assessments were taken six times including subjective mood and self-assessment scales, as well as blood pressure, heart rate, and skin conductance. The group receiving CBD reported decreased stress and anxiety during the test, while those receiving a placebo treatment reported extreme stress and anxiety. In fact, the CBD group had a similar response to the healthy group.
- To further prove CBD’s anti-anxiety effects, a study35 conducted on ten patients suffering from generalized social anxiety disorder (SAD) used functional neuroimaging to examine the effects of CBD in the brain. In a double-blind procedure, groups were given CBD or a placebo while measuring resting regional cerebral blood flow and subjective ratings five times throughout the test. After a week, the procedure was repeated with a new drug. CBD significantly decreased anxiety and reduced the activity in the brain responsible for fear and anxiety. The study concluded that CBD might be an alternative treatment for generalized social anxiety disorder36.
- In 1995, CBD was given to a 19-year-old female patient suffering from schizophrenia37 who had been receiving medications for her disorder but suffering serious side effects. After a four-day cleanse, she received an increasing dosage of CBD for four weeks, then CBD was replaced with a placebo for four days and then followed by an increasing dosage of haloperidol. Assessing her symptoms throughout the trial revealed significant improvement on the days she had CBD and worsening symptoms while taking a placebo.
- In another lab study, after being subjected to stressors, mice were given CBD to assess its effectiveness in controlling stress and fear. The study showed CBD provided anti-anxiety effects38 and helped lower their heart rate when faced with the stressor.
These studies provide evidence that CBD is an effective alternative treatment for anxiety. Additionally, CBD acts quickly on the cellular level, is neuroprotective, and has none of the psychoactive effects of THC39.
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