Fear and anxiety are important adaptive responses that have helped our species survive. However, excessive or chronic fear can become maladaptive and lead to disability. The symptoms of an excessive fear response or anxiety can be found in a variety of psychiatric conditions such as generalized anxiety disorder (GAD), social anxiety disorder (SAD), panic disorder (PD), obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD).

These disorders are associated with a decreased sense of well-being, high levels of unemployment or underemployment, relationship dissolution and increased risk of suicide. The United States has a lifetime prevalence of anxiety-related psychiatric disorders of 29%, which results in a significant social and economic burden.

The pharmacological treatment options we currently have available such as antidepressants, benzodiazepines, anticonvulsants, and atypical antipsychotics have been shown to have limited response rates and side-effects which have a negative impact of tolerability and adherence among patients.

The high prevalence of these conditions, coupled with the limitations of the treatments we currently have, results in the need to continue our research and efforts to develop new pharmaceutical drugs.

CBD and THC

Cannabis sativa, a species of the Cannabis flowering plant, is commonly associated with Western Culture with illicit recreational drug use. With that being said, in recent years, both scientists and policymakers have become more open to the idea of studying the plant for its potential medical use.

The two most widely known cannabinoid constituents of the Cannabis plant are THC or tetrahydrocannabinol, which is the psychotropic cannabinoid responsible for the euphoria and psychomotor effects, and CBD which has been shown to lack psychotropic properties.

CBD has been regarded with increased interest in recent years because research has found it to have a wide range of potential therapeutic applications in a number of conditions, including psychiatric disorders with symptoms of anxiety. Furthermore, studies done when developing the drug Epidiolex, an FDA-approved seizure treatment, have demonstrated that CBD is well tolerated even at very high dosages of 1500 mg per day with no negative impact on vital signs, psychomotor function or mood.

Regarding its anxiolytic effects, even though THC has been known to increase levels of anxiety and paranoia in some cases, CBD interacts differently with the endocannabinoid system and seems to help regulate the fear response and related behaviors.

The Endocannabinoid System and Anxiety

A 1988 study led by Allyn Howlett and William Devane from the Saint Louis University School of Medicine found that the mammalian brain has specialized receptors that respond to cannabinoids. This finding further resulted in the discovery of the endocannabinoid system or ECB. After more research, we discovered that this system plays an important role in regulating a multitude of physiologic functions including emotional behavior through the effects it has on synaptic plasticity which determines learned responses to emotionally aversive events.

There are two major cannabinoid receptors: CB1 and CB2. The first type of receptors, CB1, is mostly found in the brain, peripheral nervous system, thyroid gland, liver, and bone tissue. The CB2 receptors which were discovered later can also be found in the brain and peripheral nervous system, but to a lesser extent than CB1. They are predominantly expressed in the immune system, gastrointestinal system, and spleen.

Activation of CB1 receptors seems to produce anxiolytic effects in unconditioned fear models. When it comes to conditioned fear, such as the case with phobias, the effect is more complex. Symptoms of anxiety can be increased or decreased depending on where in the brain CB1 receptors are activated. It could, however, potentially prevent fear consolidation (such as with conditions like PTSD) and enhance fear extinction.

Chronic stress seems to cause impairment in ECB signaling in the amygdala and hippocampus, which results in elevated levels of anxiety. Patients suffering from PTSD show signs of this impairment.

THC produces its psychotropic effects by directly binding to CB1 receptors and affecting the parts of the brain which regulate motor function, cognition, memory and pain perception. This high affinity to CB1 receptors might also explain why THC can also increase anxiety and paranoia.

CBD, on the other hand, does not bind to CB1 receptors directly. It works by stimulating the body’s endogenous cannabinoids such as anandamide and 2-arachidonoylglycerol which promotes homeostasis in the endocannabinoid system. This might be the reason why it’s not psychoactive, and it’s well-tolerated at such high dosages. These are promising findings because they might mean that we can use CBD to develop drugs that address specific neuropsychiatric disorders.

The Rising Trend of Smoking Hemp Buds

Despite smoking and vaping being mostly associated with recreational cannabis use, it appears that smoking hemp buds high in CBD content such as Organic CBD Nugs have become a very popular phenomenon.

This trend really took off after the Farm Act from 2018, which made it legal for U.S. farmers to grow hemp. Even in the states with strict marijuana laws, the cultivation and consumption of hemp that contains no more than 0.3% THC are federally legal.

This preference might be due to the fact that the bioavailability of CBD depends significantly on the method of administration. When consumed orally, such as in the form of CBD oil or capsules, only a small percentage of the cannabinoid (between 6% and 15%) manages to pass into the bloodstream after being processed by the stomach and liver. When it’s absorbed through the lungs, an impressive 40% of CBD reaches the bloodstream which might mean that consumers prefer this option as it leads to faster and stronger anxiolytic effects, especially right before events that might trigger a fear response such as giving a speech, going to an important meeting or job interview.

Another reason might be the “entourage effect” which refers to the theory that several chemical compounds in cannabis work together to produce a stronger therapeutic effect compared to isolate products.

Until now smokable hemp represented only a small segment of the CBD market, but, with increased interest from consumers, more cultivators might become motivated to experiment and create hybrids with different flavors, cannabinoid profiles, and physiological effects.