cbd oil pill for anxiety

CBD Oil for Anxiety – March 2022

CBD has been known for its numerous health benefits , from helping reduce chronic pain to alleviating cancer symptoms (6 ) . There have also been other studies conducted to better understand the anxiolytic (anti-anxiety) characteristics of CBD.

CBD’s potential for anxiety relief is also linked to its ability to help with sleep problems, reduce stress, and manage depression.

Esther Blessing, Ph.D. of New York University, led a group of researchers in 2015 and investigated the benefits of CBD for anxiety. Their review of 49 studies yielded promising results (7 ) .

Researchers noted that animal studies conclusively demonstrated CBD’s efficacy in reducing anxiety behaviors linked to multiple disorders.

These disorders include panic disorder (PD) , generalized anxiety disorder (GAD), social anxiety disorder (SAD), obsessive-compulsive disorder (OCD) , and post-traumatic stress disorder (PTSD) .

Results of the animal studies were also supported by human experimental findings, which suggested CBD’s minimal sedative effects and excellent safety profile.

Unlike THC ( tetrahydrocannabinol ), another well-known compound of the cannabis plant , CBD is non-addictive. CBD does not get users high, making it an appealing option for most people dealing with anxiety.

However, the results could not confirm that CBD treatment would have comparable effects for those with chronic anxiety. Further tests are needed to determine the impact of prolonged CBD use on individuals.

Researchers of a 2019 study published in the Brazilian Journal of Psychiatry looked at the effects of cannabidiol on anxiety and stress.

The study demonstrated that CBD might help reduce the response to stressful environmental factors when given in optimal dosage (8 ) .

Orrin Devinsky, M.D., director of NYU Langone’s Comprehensive Epilepsy Center in New York City and a principal investigator in the Epidiolex trials, says there is growing evidence that CBD can ease anxiety.

In a study published in the Neuropsychopharmacology journal, a simulated public speaking test was conducted for participants with social anxiety disorder .

Results showed significant attenuation in anxiety scores relative to the placebo group in the group given clonazepam (drug used to prevent and control seizures) during the speech phase, and in the clonazepam and 300mg CBD groups in the post-speech phase (9 ) .

A review published in the Brazilian Journal of Psychiatry in 2019 yielded similar effects on healthy people in anxiety-inducing situations (10 ) .

Researchers are also exploring CBD as a means of soothing anxiety in people with an autism spectrum disorder (ASD).

According to a 2019 study published in Frontiers in Pharmacology , authors found an increase in the use of cannabidiol in children with ASD (11 ) .

Based on the parents’ reports, the findings suggest that CBD may help improve ASD symptoms, such as anxiety, aggression, and hyperactivity.

However, the authors also note that CBD’s efficacy and safety need large-scale clinical trials and further evaluation in children with ASD.

In another study published in the Brazilian Journal of Psychiatry, researchers suggested that the therapeutic benefits from the use of CBD oil may be attributed to its anti-anxiety and sleep-inducing effects (12 ) .

Results of an animal study published in the Neuropharmacology Journal in 2012 also had comparable results that supported CBD treatment.

The findings suggested that CBD might block anxiety-induced sleep disturbances through its anxiolytic effect on the brain (13 ) .

Meanwhile , a case report in The Permanente Journal noted CBD oil’s effectiveness for anxiety and insomnia related to post-traumatic stress disorder (PTSD) (14 ) .

The authors of the 2016 study found that CBD oil reduced anxiety and reduced the insomnia of a 10-year old girl.

The strength of this particular case is that the child was receiving no prescription medications other than the nonprescription diphenhydramine.

With only nutritional supplements and the CBD oil to control her symptoms, her scores on the sleep and anxiety scales consistently and steadily decreased over five months.

Ultimately, the child was able to sleep on most nights in her room, behave appropriately, and become less anxious at school and home.

A study published in Pharmaceuticals (Basel) in 2012 even compared CBD with a sleep aid called nitrazepam (16 ) .

The authors found that a high dose of 160 milligrams of CBD (equivalent to 0.16 milliliter of CBD) increased the subject’s duration of sleep.

Similarly, a 2017 study published in the Current Psychiatry Reports noted that at moderate to high doses of CBD, the compound might have therapeutic potential to treat insomnia (17 ) .

In a study published in The Permanente Journal in 2019, researchers measured sleep and anxiety scores in human subjects and found that CBD could hold benefits for anxiety-related disorders (18 ) .

A 2018 study published in the Frontiers in Immunology Journal demonstrated CBD as a potential remedy to depression (19 ) .

In the study, researchers examined the experimental and clinical use of CBD . They found that CBD showed anti-anxiety, anti-epileptic, and antipsychotic properties that might help reduce depression linked to stress.

CBD is a Cannabis sativa constituent with great psychiatric potential, including uses as an anxiolytic -like and an antidepressant -like compound, as suggested by a 2014 study published in CNS and Neurological Disorders – Drug Targets (20 ) .

In one study, results showed that CBD could induce rapid-acting antidepressant -like effects and enhance neurotransmission (21 ) . Neurotransmission is the process of communication between nerve cells.

How CBD Works to Help With Anxiety

To fully understand how CBD works to help with anxiety, one must understand how the endocannabinoid system (ECS) works.

The therapeutic effects of cannabinoids , such as CBD, are realized by their interaction with the body’s ECS and its specialized cannabinoid receptors .

The ECS, integral to the body’s physiologies, is responsible for regulating a wide range of body functions. They include pain sensation, immune response, anxiety, sleep, mood, appetite, metabolism, and memory.

The body produces endocannabinoids, which are neurotransmitters that bind to cannabinoid receptors in the nervous system .

CB1 and CB2 are the two main types of receptors found in specific parts of the human body. These receptors each have particular roles in the ECS.

CB1 receptors are mostly located in the brain and central nervous system . However, they are also found in the reproductive organs, gastrointestinal and urinary tracts, liver, lungs, and retina (22 ) .

CB1 receptors play a role in motor regulation, memory processing, appetite, pain sensation, mood, and sleep (23 ) . The activation of CB1 receptors has also been related to neuroprotective responses.

This activity suggests the cannabinoids with a higher affinity for CB1 receptors could help in the treatment and prevention of neurodegenerative conditions, such as Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis.

Meanwhile, CB2 receptors are primarily situated on cells in the immune system and its associated structures.

When CB2 receptors are triggered, they stimulate a response that fights inflammation, reduces pain, and minimizes damage to tissues.

These anti-inflammatory responses are useful for treating inflammation-related conditions, such as chronic inflammatory demyelinating polyneuropathy (CIDP), Crohn’s disease, arthritis, and inflammatory bowel syndrome (24 ) .

CBD acts indirectly against cannabinoid agonists. Agonists are substances that attach to a receptor and cause the same action as the substances that typically bind to the receptor .

CBD also interacts with several other receptors in the body. These receptors include 5-HT1A, which is linked to serotonin , a neurotransmitter found to contribute to feelings of well-being.

Through their interaction with receptors , cannabinoids promote healing and balance (25 ) .

A 2005 research published in the Neurochemical Research Journal indicated that cannabidiol could inhibit serotonin ‘s reuptake in the brain, making serotonin more available for the body (26 ) .

Serotonin occurs throughout the body, and it impacts a variety of body and psychological functions. In the brain, serotonin influences levels of anxiety, mood, and happiness.

The researchers believe that with better regulation of serotonin , CBD could help stabilize mood and reduce anxiety. Many pharmaceutical antidepressants work directly on serotonin pathways.

A study demonstrated CBD’s ability to trigger the ECS in the body to produce more of its natural cannabinoids , including anandamide, which regulates emotions (27 ) . Results showed that anandamide levels were higher in subjects exposed to CBD.

The ECS plays a vital role in the human body due to its ability to maintain homeostasis or a state of balance, as explained in a 2018 research published in the Journal of Young Investigators (28 ) .

According to a 2019 study published in the Journal of Neuroscience, increased anandamide production in the brain is believed to guard against the effects of stress while reducing behavioral signs of anxiety and fear (29 ) .

In another 2019 study published in the journal Current Psychiatry Reports , results indicated that CBD might have the potential to help elevate anandamide levels for anxiety treatment in the future (30 ) .

Studies in the journal Cannabis and Cannabinoid Research showed that CBD might stimulate the hippocampus, a part of the brain important for memory, to regenerate neurons (nerve cells) (31 ) .

Preclinical studies have shown some evidence suggesting that the pro-neurogenic action of CBD through the hippocampus might trigger its anxiolytic (anti-anxiety) effects (32 ) .

CBD Oil vs. Alternative Treatments for Anxiety

Some of the alternative treatments for anxiety include yoga and massage.

According to an article posted by Harvard Health Publishing of the Harvard Medical School of Harvard University, yoga functions like other self-soothing techniques, such as relaxation, exercise, meditation, or even socializing with friends (33 ) .

By decreasing levels of perceived stress and anxiety, yoga modulates stress response systems. It consequently leads to a decreased heart rate , reduced blood pressure , and natural respiration.

Self-soothing methods also include massages or other types of tactile treatments, which represent different kinds of relationships with other living beings, like pets.

Oxytocin, a hormone produced in the brain, is released in response to several kinds of massage (34 ) .

According to a 2015 study published in the journal Frontiers in Psychology , oxytocin is linked to increased levels of social interaction, well-being, and anti-stress effects (35 ) .

Although using oxytocin to treat mental health conditions has not yet been studied sufficiently, low oxytocin levels have been linked to depression, says the Endocrine Society (36 ) .

The benefits of aromatherapy and essential oils include reducing anxiety and depression symptoms and improving sleep, according to a 2012 study (37 ) .

CBD used in aromatherapy and massage takes advantage of the cannabis plant ’s terpenes used to create an essential oil.

Terpenes are responsible for the flavors and aroma of cannabis and influence its effects by interacting with cannabinoids .

When combined with other essential oils, CBD stimulates one’s sense of smell and heightens the soothing benefits of a massage.

When applied topically, CBD oil gets absorbed into the skin and targets cannabinoid receptors found in the skin’s mast cells and nerve fibers.

The reaction gives a calming, anti-inflammatory effect with localized benefits all over the skin and muscles.

Massages are used as a wellness and healing practice, and with an infusion of pure CBD hemp extract , the therapeutic benefits may increase.

Studies have found that massage can also help relieve pain in people with cancer, as it helps relieve anxiety, fatigue, and stress (38 ) .

Meanwhile, according to an article published by the American Massage Therapy Association (AMTA), the potential value of massage therapy for individuals with depression comes from interrupting the pattern of symptoms regularly (39 ) .

CBD Dosage for Anxiety

Several factors determine the appropriate dose of CBD for an individual, including body weight, the amount of CBD is in each product, and the desired results.

However, the correct CBD dose guidelines for specific medical conditions , like anxiety, are still unclear.

The U.S. Food and Drug Administration ( FDA ) has not approved cannabidiol as a supplement (40 ) .

Researchers of the 2016 study published in The Permanente Journal say they have no foundation to suggest doses of CBD based on the data from their studies (41 ) .

However, in their experience, the CBD supplement given in different dosages of 12mg to 25 mg of CBD once daily appears to offer relief from anxiety and sleep problems, with nominal side effects .

Notably, the subject of their study did report any complaints or discomfort from the use of CBD . Further large scale prospective studies are necessary to generalize CBD dosing to the general population.

While CBD is considered generally safe, as the 2011 review in the Current Drug Safety Journal suggested, the long-term effects are yet to be examined further (42 ) .

How to Take CBD Oil for Anxiety

CBD oil capsules and edibles, such as brownies, gummies, and lozenges, provide a straightforward way to take CBD oil, especially for beginners.

Meanwhile, CBD oil tinctures or drops may be a practical option for those seeking fast results and maximum dosage control.

CBD oil tinctures may be directly discharged under the tongue by using a dropper, allowing the oil to be absorbed into the bloodstream.

Sublingual (under the tongue) absorption is an efficient way of consuming CBD tinctures . According to studies, CBD oil has a sublingual bioavailability of 13% to 19%, with some studies putting it as high as 35% (43 ) .

Bioavailability is the extent and rate to which a compound or an active drug ingredient is absorbed and becomes readily available for the body to use (44 ) .

When taken sublingually, CBD gets into one’s system in about 10 to 15 minutes (45 ) .

According to a 2010 review published in the International Journal of Pharmacy and Pharmaceutical Sciences , when most substances are given sublingually, effects are faster than when those same substances are ingested orally (46 ) .

For those who find the taste of pure CBD hemp extract unappealing, there are CBD gummies that come in many delicious flavors.

Each gummy also comes in a fixed dosage, making it a convenient way to give CBD, even to kids with anxiety.

CBD oil can also be mixed with other foods and beverages. However, keep in mind that oil and water do not mix.

Given that CBD is a highly lipophilic (soluble in lipids or oils) molecule, it may dissolve in the fat content of food, increasing its solubility and absorption, according to a 2018 study published in the journal Frontiers in Pharmacology (47 ) .

An additional fat, like milk, may be necessary for the oil to bind and completely dissolve while maintaining the smooth consistency of the drink.

CBD may also be used in massage therapies or applied as a lotion, cream, balm, or salve. However, there is limited absorption through the skin with topical CBD oil.

Labels on topical products may mention nanotechnology, encapsulation, or micellization of CBD. These words indicate that their solution can carry CBD through the dermal layers, rather than staying on the skin.

Meanwhile, vape pens or oils are some of the quickest ways to get CBD into the body since it enters the bloodstream through the lungs without going through the digestive system.

However, vaping is not for everyone. Side effects of vaping include coughing, dry mouth and throat, and shortness of breath (48 ) .

A study also showed vape use is associated with lung diseases and injuries, such as collapsed lung and lipoid pneumonia (49 ) .

Possibilities include chemical irritation or allergic or immune reactions to various chemicals or other substances in the inhaled vapors (50 ) .

Before buying or taking CBD for the first time, individuals must proceed with caution and seek medical advice from a doctor experienced in cannabis use.

The Pros and Cons of CBD Oil for Anxiety

The Pros

  • Multiple studies have shown that CBD oil might be beneficial in alleviating anxiety, stress, and depression (51 ) .
  • Unlike the commonly prescribed medications for anxiety, such as selective serotonin reuptake inhibitors (SSRIs), serotonin -norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and benzodiazepines, CBD may be purchased without a prescription in locations where it is legally available.
  • CBD is non-addictive, says Nora Volkow, director of the National Institute on Drug Abuse (NIDA), in a 2015 article (52 ) . This characteristic makes CBD an appealing option for people with anxiety.
  • According to a critical review by the World Health Organization (WHO), CBD “is generally well-tolerated with a good safety profile (53 ) .”
  • In a 2017 review published in the CannabisandCannabinoidResearch Journal , the authors found CBD to be well-tolerated at doses of up to 1,500mg per day (54 ) .

The Cons

  • Studies are too limited to determine whether or not CBD is an effective treatment for various health conditions. The FDA has approved only Epidiolex, a drug for seizures with CBD as its main ingredient (55 ) .
  • As with the use of any natural chemical compound, there are risks involved in using CBD. Side effects of CBD use include diarrhea, fatigue, changes in appetite and weight, and potential interaction with certain medications (56 ) .
  • The CYP450 family of enzymes is responsible for breaking down several phytocannabinoids , including CBD (57 ) . Thus, taking CBD in combination with medications that have a “grapefruit warning” is not recommended (58 ) .
  • CBD products marketed online and in dispensaries are mostly unregulated, making it difficult to determine whether CBD products contain the amount of CBD the product labels claim (59 ) .
  • A 2017 review published in the Journal of the American Medical Association revealed labeling inaccuracies among CBD products (60 ) . Some products had less CBD than stated, while others had more.

A Close Look at Anxiety Disorders

Anxiety is the body’s natural way of reacting to stress and alerting the individual of potential danger. People with anxiety may have mild or severe, pathologic feelings of unease, worry, fear, or nervousness.

In the United States , anxiety disorders are the most common mental illness that affects 40 million adults or 18.1% of the population every year (61 ) .

Anxiety disorders may develop from a complex set of risk factors, such as brain chemistry, genetics, personality, and life events (62 ) .

The U.S. Department of Health & Human Services lists five significant types of anxiety disorders (63 ) :

Generalized Anxiety Disorder (GAD)

GAD is characterized by exaggerated worry, chronic anxiety, and tension, even when there is little or nothing to provoke it. This anxiety disorder affects 6.8 million adults or 3.1% of the U.S. population (64 ) .

  • Restlessness and irritability
  • Fatigue
  • Difficulty concentrating
  • Muscle tension
  • Sleep problems

Obsessive-Compulsive Disorder (OCD)

OCD is characterized by recurrent, unwanted thoughts or obsessions, and repetitive behaviors or compulsions. This anxiety disorder affects 2.2 million adults or 1.0% of the U.S. population (66 ) .

Repetitive behaviors, like hand washing and counting, are often done in the hope of making them go away. However, doing these so-called rituals provides only temporary relief, while not performing them increases anxiety.

People with OCD may also have other mental disorders, such as depression, anxiety, and body dysmorphic disorder (a condition where a person believes a part of their body is abnormal) (67 ) .

Panic Disorder (PD)

Panic disorder is described by unexpected and repeated episodes of intense fear. This anxiety disorder affects 6 million adults or 2.7% of the U.S. population (68 ) .

People with panic disorder sometimes worry about when the next attack can happen and try to prevent future attacks by avoiding certain places, situations, or behaviors they link to the panic attacks .

Worrying about panic attacks and exerting too much effort to avoid attacks cause significant problems in various aspects of life.

  • Heart palpitations or an accelerated heart rate
  • Trembling or shaking
  • Sweating
  • Sensations of shortness of breath or choking
  • Feelings of impending doom and being out of control

Post-Traumatic Stress Disorder (PTSD)

PTSD may develop after exposure to a terrifying ordeal or event in which severe physical harm occurred. This anxiety disorder affects 7.7 million adults or 3.5% of the U.S. population (70 ) .

Traumatic events that can trigger PTSD also include violent personal assaults, natural or human-caused disasters, accidents, or military combat (71 ) .

Anyone can develop PTSD at any age. Those at risk include war veterans, children, and people who have been through a physical or sexual assault, abuse, accident, and disaster.

According to the National Center for PTSD, 7 or 8 out of every 100 people experience PTSD at some point in their lives (72 ) .

Women are more likely to have PTSD than men. Also, some genes can make some people more likely to develop PTSD than others.

However, not everyone with PTSD has experienced a dangerous event. Some people may develop PTSD after a friend or family member experienced harm or danger.

The unexpected or sudden passing of a loved one can also lead to PTSD.

Social Anxiety Disorder (SAD) or Social Phobia

SAD is characterized by overwhelming anxiety and excessive self-consciousness in everyday social situations (73 ) .

Social phobia may be limited to one type of situation, such as a fear of speaking during formal situations or eating in front of others.

In its most severe form, a person with SAD may experience symptoms almost anytime they are around other people.

FAQs on CBD

How Is CBD Different From THC?

CBD is non- psychoactive , contrasting with THC (delta-9- tetrahydrocannabinol ), another primary cannabinoid . THC is the most significant factor contributing to the high associated with using cannabis .

Consuming CBD without any THC does not produce those effects, which means that nearly everyone should be able to function as they usually do when taking CBD.

The lack of high lets one continue with work, school, and other commitments without a decrease in performance.

The absence of psychoactive effects also makes CBD oil safe to take, even for those who must pass regular or random drug tests.

CBD products must not contain any THC for CBD not to induce psychoactive effects. Products containing broad-spectrum CBD and CBD isolates do not have THC , while full-spectrum CBD oil products do.

The full spectrum of cannabinoids , terpenes , fatty acids, and essential oils extracted from the plant all work together in synergy.

This synergy magnifies the therapeutic benefits of individual cannabinoids and produces a phenomenon known as the “ entourage effect .”

When buying any CBD product , an individual must pay attention to the percentage of THC . This information can be obtained from a third-party lab test result.

What Is the Difference Between CBD Oil and Hemp Oil?

CBD is one of more than 100 cannabinoids that occur naturally within hemp plants . The common methods used in extracting CBD are carbon dioxide (CO 2 ) and ethanol.

Hemp oil is produced by extracting the oil from hemp. CBD oil is extracted from the stem, stalk, leaves, and flowers of the hemp plants.

Although some people refer to “ hemp extract ” as hemp oil , the term “ hemp oil ” is is not be confused with “hempseed oil.”

Strictly speaking, hempseed oil is extracted from hemp seeds. Hempseed oil is abundant in nutrients, such as omega-3 and omega-6 fatty acids, making it ideal for digestion. However, hemp seeds do not have CBD.

The extraction of this oil involves pressing, processing, and refining of seeds before being bottled.

Does CBD Show Up on a Drug Test?

Hemp-derived CBD products sold online and in retail stores are not supposed to contain THC over 0.3%. THC is the compound abundant in marijuana that can get the user high and may be detectable on a drug test.

However, sometimes, CBD products contain more THC than the amount printed on the label, says Barry Sample, senior director of science and technology at Quest Diagnostics, the largest administrator of drug tests in the U.S. (74 ) .

It is also possible that, eventually, the trace amounts of THC allowed in CBD products could accumulate in the body to detectable levels, Sample explains.

THC is fat-soluble, adds Norbert Kaminski, Ph.D., professor of pharmacology and toxicology at Michigan State University in East Lansing. Thus, THC that is not immediately broken down by the body is stored in fat tissues (75 ) .

Over time, THC and THC metabolites (substances made when the body breaks down chemicals) are slowly released. As a result, it is possible to test positive for THC and not pass a drug test, even after one has stopped taking the product.

What Are the FDA-Approved Drugs That Contain CBD and Synthetic Cannabinoids?

CBD is used in the treatment of some types of epilepsy , such as Dravet’s Syndrome, a complex disorder in children that is associated with a high rate of mortality and drug-resistant seizures.

Epidiolex ( cannabidiol ) oral solution is the first drug approved by the FDA for the treatment of seizures in individuals two years of age and older (76 ) .

The scientific study of cannabinoids has led to two FDA -approved drugs, dronabinol and nabilone. These medications contain THC in pill form (77 ) .

What Are the Safety Considerations of CBD?

Possible adverse effects of CBD may include fatigue, diarrhea, nausea, drowsiness, dry mouth, and irritability (78 ) .

Although the World Health Organization says that CBD is safe and well-tolerated (79 ) , it is not clear how much to take or how often a person should use it for any particular problem.

Higher doses of CBD may interact with other medications, such as blood thinners, antidepressants , and immune suppressors (80 ) .

CBD may also intensify the level of the blood thinner coumadin in the bloodstream and raise levels of certain drugs or medications in one’s system.

Another significant safety concern with CBD is that it is primarily marketed and sold as a supplement, not as a medication (81 ) . Currently, the FDA does not regulate the purity and safety of dietary supplements.

Thus, consumers cannot know for sure that the product they are buying has active ingredients at the dose printed on the label. The product, as with any other non-FDA-regulated substance, may also contain other unknown elements.

Is CBD Legal?

CBD is readily obtainable in many parts of the United States , although its exact legality continually changes.

In December 2015, the FDA eased the regulatory stipulations to allow researchers to conduct CBD investigations and trials. Currently, many people are able to get CBD online without a medical cannabis license (82 ) .

The 2018 Farm Bill legalized industrial hemp and hemp-derived products at the federal level, removing them from the jurisdiction of the Drug Enforcement Administration (DEA) (83 ) .

Since hemp is no longer categorized under controlled substances, it is now the job of the United States Department of Agriculture (USDA) to regulate the crop as it does other agricultural commodities.

The law defined “agricultural hemp” as cannabis strains that contain less than 0.3% THC . Additionally, the Farm Bill explicitly legalized the “extracts, cannabinoids , and derivatives” of hemp.

Many states and Washington, D.C., have passed cannabis -related laws, making medical marijuana with high levels of THC legal. Still, marijuana may require a prescription from a licensed physician (84 ) .

Also, several states have made recreational use of marijuana and THC legal. One should be able to buy CBD in states where marijuana is legal for recreational or medical purposes.

For a complete list of legal medical marijuana states and D.C., including the corresponding laws, fees, and possession limits, click here (85 ) .

Individuals who possess cannabis -related products in a state where they are illegal or do not have a medical prescription in states where the products are legal for medical treatment could face legal penalties.

To get more information on state laws and penalties, click here (86 ) .

Conclusion

In recent years, CBD has shown potential therapeutic efficacy in reducing both physiological and behavioral measures of stress and anxiety.

Small clinical trials have also suggested CBD’s benefits in helping reduce symptoms of anxiety with few or no adverse effects.

Research on CBD oil is still in its infancy. However, there has been mounting scientific evidence to suggest that it can help provide anxiety relief or reduce anxiety symptoms .

Still, the long-term side effects of CBD are unknown, and longitudinal scientific research is still significantly lacking.