CBD as a Potential Treatment for Anxiety and PTSD

Anxiety is an emotion filled with worry, tension, and the uncomfortable feeling of helplessness to do anything about those worries. Experiencing occasional anxiety is a normal part of life. However, people with anxiety disorders typically have repeated bouts of terror or fear, sometimes coming on suddenly, as in panic attacks, and sometimes more prolonged as in generalized anxiety disorders. Nevertheless, such disorders are often socially and economically crippling since anxiety affects every parameter of one’s existence. 

Post-traumatic stress disorder (PTSD) previously was classified as an anxiety disorder and although characterized by high levels of anxiety, is now classified as its own diagnosis, and consists of a subset of symptoms of which anxiety is only one. Other symptoms include re-experiencing a traumatic event, emotional numbness, and avoidance of anything that reminds the person of the trauma, along with difficulty sleeping, feeling irritated and jumpy with heightened states of arousal. PTSD sufferers also typically experience bad dreams and reenactments of stressful events in dreams.

Both disorders tend to last 6 months or more, tend to be chronic and persistent and share high rates with other anxiety disorders, mental illnesses, and physical problems such as high blood pressure.

How Prevalent are Anxiety/PTSD Disorders?

It is estimated that 40 million people in the United States alone and about 1 in 13 people worldwide suffer from an anxiety disorder. Anxiety disorders are the most diagnosed mental disease in the world. About 7-8% of the population will suffer from PTSD at any point in their lives. Anxiety disorders represent the most prevalent mental illness in the world.

The plethora of anxiety disorders include generalized anxiety disorder (GAD), social anxiety disorder (SAD, or social phobia), specific phobia, panic disorder and agoraphobia (a fear of leaving one’s house).

 The prevalence of anxiety disorders is double in females as opposed to males. Subjects in clinical trials are overly represented by males, a study limitation. Females also tend to exhibit an increased severity of symptoms, comorbidity, and burden of illness.

PTSD can develop in anyone after a traumatic event whether it is in combat or a life-threatening or frightening event.

How are Anxiety and PTSD Currently Treated?

Psychological treatments are popular but are often limited or temporary in their effectiveness. These include cognitive behavioral therapy, exposure therapy and cognitive processing therapy.

Medications typically used include antidepressants, benzodiazepines, mood stabilizers, anticonvulsants, and antipsychotics. These drugs lead to widespread patient dissatisfaction along with a high rate of adverse side-effects. There are currently no satisfactory treatment options for anxiety or PTSD making CBD an attractive consideration for use.

Is there a Future for CBD in Mental Health Disorders?

CBD may be an effective treatment modality in PTSD and related depression, anxiety disorders, social anxiety disorder (SAD), generalized anxiety disorder (GAD), obsessive-compulsive disorders and panic disorder. While pre-clinical evidence is positive relative to CBD’s anxiety relieving effects, it is well recognized that the field needs much more study with large scale placebo controlled clinical trials.

CBD use in Acute vs. Chronic Anxiety

Current studies have been fairly limited in scope to acute anxiety with chronic long-term situations remaining to be studied. Several studies are currently underway in the area of chronic anxiety but have not been completed to date.

One clinical trial on the effectiveness of CBD compared with a benzodiazepine found that both the benzodiazepine and CBD had significant effects on the reduction of anxiety but only the benzodiazepine showed sedative effects.

Another human trial showed that pretreatment with 600 mg CBD prior to a speaking engagement statistically reduced the social anxiety disorder symptoms of anxiety, cognitive impairment, and discomfort in speech performance. The placebo group that received no medication exhibited statistically significantly higher scores on the same parameters.

A 2019 study on 37 Japanese teenagers given 300 mg CBD oil for SAD for  3-4 weeks exhibited a decrease in their symptoms providing relief comparable to Paxil, an antidepressant drug used in mood control. Some of these teenagers were also able to overcome the stigma associated with their anxiety and seek additional psychotherapeutic treatment.

In a retrospective study of 47 volunteers who expressed having anxiety, 25 mg of CBD was given over the course of 3 months and 79.2% of the respondents reported an improvement in anxiety scores after only one month of treatment with most reporting further improvement at 2 months.

A Potential Benefit of CBD in PTSD therapy

For CBD to be effective in PTSD, it must play a role in memory, recall and possibly even dreams. Since depression is often a comorbid condition, it should act as an antidepressant as well. Recent studies have confirmed the ability of CBD to alter specific portions of bad memories and lessen their retention. CBD is known to affect the 5-HT1A receptor that is also involved in the mechanism of action of antidepressant medications.

Exposure to traumatic stress is necessary for the formation of PTSD and exposure to CBD is an effective way of reducing both the cardiovascular responses and the anxiety-producing effects precipitated by stress.

A case study of a 10-year old child who had been sexually traumatized since age 5 and unresponsive to conventional treatments responded positively to 12-25 mg of full-spectrum CBD oil once per day with predominant symptoms resolving and nighttime sleep restored within several weeks of CBD only treatment.

High CBD Strains for Anxiety

The following strains are known for their CBD content:

CBD Products for Anxiety

Hemp Extract Oil, Full Spectrum CBD Oil, CBD Gummies and CBD Distillates may all be used for various forms of anxiety and PTSD and can be found here.

How Does CBD Combat Anxiety and PTSD?

Science is just beginning to unravel the mysteries behind the CBD molecule and its many functions. The human body has many “receptors” which are protein-based structures attached to cells that receive signals from a variety of stimuli and produce different neurotransmitters and chemicals in response to stimulation. While CBD interacts with many receptors and has many functions, 3 primary areas stand out.

CBD, Serotonin, and 5-HT

There are 14 receptors associated with the neurotransmitter serotonin. CBD interacts with serotonin receptor 5-HT1A, the receptor most associated with anxiety and panic reduction.  The 5-HT1A receptor is also involved with the mechanism of action of antidepressants. It has been suggested that CBD activates this receptor in several brain regions. Serotonin is the chemical involved in mood regulation occasionally being called the “happy” chemical. Serotonin sends signals throughout the nervous system with imbalances leading to depression, anxiety, and mood swings.

In preclinical studies, CBD oil had anti-anxiety and anti-depressant effects in an animal model associated with 5-HT1A activation. The 5-HT1A receptor is involved in serotonin production. Low serotonin levels have been associated with anxiety and depression.

CBD and the Endocannabinoid System (ECS)

The endocannabinoids are fatty acid derivatives that are synthesized upon demand in response to cellular changes. Two of the body’s endocannabinoids are anandamide (AEA) and 2—arachidonoyl glycerol (2-AG). The endocannabinoid system is essential to learning and emotionally stable responses to stimuli. CBD is thought to act via indirect action on the CB1 and CB2 cannabinoid receptors in the ECS showing little direct affinity for these receptors.

Other receptors important to the endocannabinoid signaling process include the vanilloid type 1 (TRPV1), the G protein-coupled 55 (GPR55) and the peroxisome proliferator-activated receptor-gamma. It is via TRPV1 and CB1 that CBD regulates the anxiety-producing effects sometimes experienced with THC use.

CBD’s involvement in the endocannabinoid system is thought to mediate the effects seen on anxiety disorders, sleep, emotional responses, and fear management. 

CBD, Endocannabinoids, and PTSD

People with PTSD show reduced peripheral AEA and reduced endocannabinoid tone. CBD can reverse this effect on tone by making more AEA available through inhibition of the enzyme that breaks AEA down, fatty acid amide hydrolase (FAAH). They also exhibit reduced 2-AG which has recently been implicated in the regulation of fear and anxiety. Essentially AEA operates as a natural antidepressant and can impair recall of adverse memories as well. CBD has the potential to do the following in PTSD patients:

• Restore restful sleep
• Regulate stress hormones
• Block flashbacks
• Improve extinction learning (reprogramming of the brain’s response to stimuli)

CBD and Neural Regeneration

In a rat model, CBD was shown to stimulate neurogenesis in the hippocampus. The hippocampus is involved in learning and memory.

Chronic stress and anxiety are known to impact the brain-damaging neurological circuitry. CBD has demonstrated in animal models it can repair damage in vulnerable parts of the brain and increase AEA levels in the hippocampus. CBD may also encourage neurogenesis in the aging process through the actions of related receptors.

How Much CBD Oil Should I Take for Anxiety?

How much CBD oil or product you should take is individual and depends on the type of product chosen whether CBD isolates or full/broad-spectrum and the amount of time you want to take to see an effective response.

One thing to remember is that most CBD studies have been carried out in animal models at dosage levels based on weight. The problem with this is that animals absorb more CBD than humans do, and the dose translation may need to be exaggerated from those used in animals due to the high bioavailability in the animal model. This makes dosage extrapolation even more difficult. And, in those studies done on humans, many were done on healthy volunteers, were of small sample size and lacked adequate controls such as formulation type.

The inverted U-shaped response curve for CBD isolate

The dosage for CBD is an inverted U-shaped curve where there is a “sweet spot” that works for everyone. Some studies have shown results with 600 mg and others have had results with 12-25 mg/day. When analyzing the differences between the studies a striking difference was observed as to the CBD product used in the study. An inverted U shaped dose-response curve is typical of CBD isolate where one study found 300 mg to be effective against anxiety when doses of 100, 300, 600 and 900 mg were given.

A linear dose-response curve for CBD with full-spectrum oil 

The standard recommendation is to start low and go slow. This is especially true with full or broad-spectrum oil where the inverted U shaped dose-response curve turns linear. With each escalating dose, an increase in effect is seen. Thus, a lower dose theoretically is possible to achieve the desired effect in a reasonable timeframe.

It was observed in the speaking engagement study that the onset of benefits of the CBD isolates at a dosage of 600 mg was effective almost immediately whereas in the case study of the child it took several months for a full spectrum dose to be successful. The dose-response time seems to be related to both the type of product chosen and the dosage given. Again, more research is needed.

Dosing Strategies for Anxiety and PTSD

Low Dose= 15-25 mg/day

Medium Dose= 35-75 mg/day

High Dose = 100+ mg/day

CBD dosage is individualized according to age, sex, metabolism, health status and endocannabinoid tone in addition to product type.

How Much CBD Oil Should I Take for PTSD?

In a study of 11 patients with PTSD, a dose of 25-50 mg/day controlled the symptoms of 91% of the participants. CBD also offered relief to a set of patients who reported nightmares as part of their syndrome. Other human studies using doses of 25-75 mg per day of an oral or sublingual spray across different PTSD populations all showed effective anxiety reduction effects

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What About CBD Edibles?

Although CBD products are available nationally,  CBD infused edibles are illegal at this time. CBD is now in drug form and has not gone through regulatory clearance to be added to food or supplements. The 2018 Farm Bill legalized hemp, but it left CBD in limbo. Under the Federal Food Drug and Cosmetic Act, a manufacturer may not introduce into commerce a food or dietary supplement containing an active ingredient that is in an FDA-approved drug or for which substantial clinical investigations have been conducted. Epidiolex is a CBD pharmaceutical introduced to control specific seizure types approved in 2018, thus substantial clinical investigations have been conducted placing CBD in an awkward legal position.

Is CBD Addictive?

No. CBD does not create tolerance or addiction. Once an effective dose is established there is no reason to increase it. There is no direct effect on CB receptors. THC has direct effect on both the CB1 and CB2 receptors thus creating tolerance.

CBD’s Effect on Other Medications

CBD is a potent inhibitor of some of the drug metabolism pathways in the P-450 cytochrome oxidase system. CBD may increase the concentrations of benzodiazepines, opiates, warfarin, antidepressants, antihistamines, beta-blockers, and antipsychotics to name a few. Be sure your doctor knows you are taking CBD. 

What Quality Concerns Should Be Looked at for CBD Oil?

Look for and consider:

• It is better to use a Full-spectrum product
• Organically grown hemp plants
• Preferably CO2 extracted
• CBD isolate has higher dosing problems and lack of entourage effect
• CBD isolate is usually extracted from industrial hemp using harsh solvents and contains no terpenes, flavonoids, or other cannabinoids
• CBD isolates offer a quick and accurate way of dosing, especially high doses 
• Is there a Certificate of Analysis?
• Does what is on the Certificate of Analysis match the product label?

Final Words

Animal models have paved the way with some interesting and intriguing potential therapeutic models for treating conditions such as anxiety and PTSD that have no viable and effective treatment options. Pharmacological management of the endocannabinoid signaling system at the level of the receptors, transporters and degradative enzymes is a probable strategy for targeting PTSD therapy.

We need studies that compare CBD with anxiolytics. We need to study the effects of CBD on chronic anxiety, not just acute anxiety in human subjects of all ages and sex. Only one pediatric case study was found. Pediatrics is an understudied group. Treatment formula type should be identified in study literature to sort out the effects of isolated vs. full-spectrum products.

Most of all, we need large scale, randomized, human clinical trials to tease out the effects of the cannabis plant on human physiology, chronic disease and particularly, the role of CBD, dosages, and therapeutic indications.

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