The Effect of Using the Components of Cannabis and its Influence on the Severity and Progression of Anxiety Disorders in Adults

Introduction

Cannabis, also known as marijuana, is one of the most widely used drugs in many countries around the world. Cannabis use in North America is very high and the National Survey on Drug Use and Health (NSDUH) stated that around 49.6 million people aged 12 or older used cannabis in 2020 in the United States alone ^[1]. Additionally, in Europe around 27.4% of adults aged 15-64 have tried cannabis at least once according to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) ^[2]. Annually, 147 million people use cannabis, which makes up 2.5% of the total world population, according to the World Health Organization (WHO) ^[3]. As can be seen, cannabis is a drug that is used in many countries around the world. In Canada specifically, trends in cannabis use in the past 12 months have increased from 22% in 2018 to 26% in 2023 ^[4]. This drug use has been growing over the last few years and the importance of its use in medicine has become a topic of interest.

Cannabis is made up of 2 components namely Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). These two compounds have remarkably similar chemical structures yet vastly different effects on the brain ^[5]. When they bind to the same receptors, THC is psychoactive, which means it affects how the brain works and causes changes in mood, awareness, thoughts, feelings, or behaviour ^{[5] [6]}. On the other hand, CBD has antipsychotic properties which by definition manage psychosis including delusions, hallucinations, paranoia or disordered thought ^[5]. Cannabis has been associated with a range of psychological, social and physical health-related problems ^[7].

There has been substantial research exploring the effects of THC and CBD on the brain.

Additionally, many studies have covered the effects of Cannabis on pain and various psychological disorders such as Post-traumatic stress disorder (PTSD). However, only a few articles have examined how Cannabis affects individuals with anxiety disorders. Anxiety disorders are among the most prevalent mental health conditions, affecting millions of people worldwide. For some individuals, their anxiety has become so severe that it interferes with their daily lives and functioning which impairs their ability to perform simple everyday tasks, thus diminishing their overall quality of life. Given the increasing prevalence of anxiety disorders, we examined the effects of cannabis components on these conditions. This article aims to identify significant gaps in the existing literature.

While numerous studies have provided insight into the general effects of cannabis on mental health conditions, few articles have focused their main research on dissecting the distinct roles of THC and CBD in the context of anxiety. For this reason, the central research question for this article is to evaluate how the use of the components of cannabis influences the severity and progression of anxiety disorders (such as social anxiety and general anxiety) in adults. The long-term and short-term effects will be analyzed and this will provide a comprehensive understanding of how cannabis impacts anxiety over time and whether cannabis is anxiolytic (reduces anxiety) or anxiogenic (increases anxiety).

It is hypothesized that CBD, known for its non-psychoactive properties, will have long-term beneficial effects on reducing anxiety. CBD interacts with the endocannabinoid system (ECS), particularly the CB1 and CB2 receptors in the central nervous system, and is thought to exert its anxiolytic effects through indirect activation of serotonin 5-HT1A receptors, promoting serotonin release, which is critical for mood regulation ^[8]. By modulating serotonin signalling, CBD helps reduce anxiety and stress responses.

In contrast, THC, either alone or in combination with CBD, may exhibit negative effects on anxiety and potentially increase anxiety symptoms due to its psychoactive properties. THC primarily binds to CB1 receptors, leading to altered neurotransmitter release, particularly dopamine, which can induce psychoactive effects such as heightened anxiety ^[9]. Overstimulation of CB1 receptors by THC may disrupt normal ECS functioning, exacerbating anxiety and creating mood imbalances ^[10]. The differing effects of CBD and THC highlight the need to understand their impact on anxiety treatment. The next chapter will discuss previous discoveries made about cannabis.

Literature Review

There has been a lot of research done on Cannabis and its effects on certain disorders. Among these studies, one particular notable area of focus is the impact of cannabis on sleep disorders, specifically insomnia. Insomnia is a condition where it becomes difficult for an individual to fall asleep, stay sleeping or experience restorative sleep and it can lead to significant impairing in an individual's quality of life thus leading to various cognitive, emotional and physical health issues ^[12]. This study focused specifically on the CBD part of Cannabis and discovered through an experiment that individuals who took Cannabis only contained CBD had long-term sleep improvement ^[11]. A downside was mentioned in the study. Even though insomnia was improved long term, there was a small chance of addiction to Cannabis which could potentially lead to Cannabis Use Disorder ^[11].

Research on cannabis and pain reveals mixed effects depending on the cannabis components and their combinations. One study found that THC combined with oxymorphone (OXM) or pentobarbital (PBL) amplified the sedative effects of OXM and induced hallucinations, anxiety, and cardiovascular changes when used with PBL ^[13]. Another study showed that THC and CBD together reduced pain intensity and anxiety when used with pain medication ^[14]. Zeeta Bawa et al. found that CBD alone reduced daily pain scores, improved grip strength, and enhanced quality of life measures related to fatigue and stiffness, with potential benefits to anxiety ^[15]. Overall, the role of different cannabis components in pain relief and anxiety reduction is still being studied.

The study of cannabis and its effects on anxiety gained momentum in the late 20th century, especially after the discovery of the endocannabinoid system in the 1990s, which highlighted the role of cannabinoids in mood regulation. More interest grew in the 2000s with increased support for medical cannabis and shifting legal frameworks that made research more accessible. While studies have since focused on CBD’s potential to reduce anxiety, research remains limited due to cannabis’ legal restrictions and the complexities of isolating its effects, dosage, and individual responses. This has left gaps in understanding that call for more rigorous studies.

A study by Cloutier et al. ^[16] found that people with anxiety tend to use more cannabis and alcohol compared to those without anxiety. Another study looked at the effects of CBD on anandamide levels in individuals with cannabis use disorder ^[17]. Anandamide is a naturally occurring cannabinoid neurotransmitter that is important in regulating mood, pain, appetite, and memory. It was discovered that when levels of anandamide were changed, it did not affect anxiety ^[17]. One article stated that cannabis is an effective coping method to help with social anxiety ^[18]. However, another article discovered that when participants strongly believed that cannabis could reduce their anxiety once they had taken it, it did reduce their anxiety ^[19]. This could have something to do with individuals' psychological thinking but more research is needed.

A 2022 study discovered that individuals with social anxiety tend to use cannabis and smoke more ^[20]. This study highlights that socially anxious individuals face more challenges in quitting smoking and are more likely to use substances like cigarettes and cannabis to cope with negative emotions than those who do not have social anxiety ^[20]. Building on the findings from previous research, the following method was employed to investigate the aim of the article which was to determine the effects of cannabis’s components on anxiety.

Methods

This study is a systematic review which aims to synthesize knowledge that already exists and provide a clearer understanding of the components of cannabis and its impact on anxiety.

Search Strategy

This study was a systematic review which aimed to understand the association between the components of cannabis, THC and CBD, and anxiety. A comprehensive search strategy was used to obtain information for this research from primary and secondary sources. These sources were gained through extensive searches on reputable databases such as Google Scholar and Pubmed.

The keywords that were used to find relevant studies were “THC”, “CBD” and “anxiety”.

Using these keywords gave a focused approach and ensured that the articles that came up were directly correlated with the research question of interest. The search provided a diversity of studies that examined the effects of THC and CBD on anxiety levels in participants. Google Scholar provided 31,500 articles on this topic and Pubmed provided 1,418 articles. Most of these articles were excluded since they did not fit the inclusion criteria.

Figure 1. (A) Google Scholar literature searches (2000-2024). Studies (mainly primary studies) were collected based on the inclusion criteria (B) PubMed Central literature searches (2000-2024). Studies (mainly primary studies) were collected based on the inclusion criteria.

Participants

The inclusion criteria were defined for this study to ensure the relevance of the findings. The participants had to be between aged 12 but below the age of 65. This age range was selected since it captures many adolescent, middle-aged and adult populations. At the same time, individuals who were too young and too old were excluded. All types of anxiety disorders were included such as general anxiety and social anxiety.

For this study, the method of cannabis consumption was not considered a significant variable. Whether it was through smoking or orally was deemed to be irrelevant to the primary objective which was to determine if cannabis, through its active components of THC and CBD, influenced anxiety. This decision was made to simplify the research and focus primarily on the potential anxiolytic or anxiogenic effects of cannabis instead of the way of consumption. Gender was also not specific in this study so both male and female individuals were included.

The exclusion criteria were any individuals outside of this age range. This helped maintain a focus on determining the desired results. Pregnant women were also excluded. This was due to other factors that could also have been involved in increasing anxiety, not just cannabis. Individuals who were cognitively impaired were also excluded in this study.

Data Extractions

These selected studies were reviewed to gather key information on THC and CBD's effects on anxiety. There was a total of 34 articles between both Pubmed and Google Scholar however duplicates were removed. The articles were then narrowed to 23 primary studies and 5 secondary sources. The collected details on study characteristics, cannabis component concentrations, methodology, number of participants, and anxiety measures were recorded. Results of each study, whether indicating anxiolytic or anxiogenic effects, were recorded.

Data Analysis

The extracted data were organized into a table for analysis. The overall impact of THC and CBD on anxiety was assessed, looking for patterns in the results. A thorough evaluation of each study allowed the research question to be analyzed.

Anxiety from these studies was measured in a few different ways such as through self-reported questionnaires (State-Trait Anxiety Inventory (STAI), Beck Anxiety Inventory (BAI), and Generalized Anxiety Disorder-7 (GAD-7)), experimental tasks (Simulated Public

Speaking Test (SPST)), physiological measures (heart rate and blood pressure), interviews and neuroimaging (fMRI to observe brain activity). These methods helped researchers assess both the subjective and objective impacts of THC and CBD on anxiety.

Study Comparisons

Studies were compared based on THC and CBD concentrations, the number of participants, and the length of the study. The goal was to identify common trends or differences in findings. This comparison highlighted reliable results and pointed out areas needing further research. The results of the data analysis will follow.

Results

The studies reviewed focused on the impact of CBD on anxiety, with two studies reporting specific dosages. A study used 300mg of CBD over eight months and found an anxiety reduction compared to a placebo group, without any impairment in cognitive functions ^[21]. A 2015 study, that used 200mg, 400mg, and 800mg of CBD over 28 days, also reported a decrease in anxiety symptoms, emphasizing the role of anandamide in mood regulation ^[22]. Several studies highlighted the reduction of social anxiety through CBD treatment, including one in which individuals who had not received prior treatment for social anxiety experienced a decrease in anxiety after a single administration of CBD ^{[23] [26] [27]}. Another study showed that the effects of CBD on anxiety were influenced by participants' beliefs, with those expecting CBD to reduce anxiety experiencing a greater reduction ^[24]. Additionally, CBD was found to help individuals overcome past fears and contribute to the treatment of anxiety disorders ^[25]. Repeated administration of CBD was associated with a significant decrease in anxiety, and studies also reported benefits in treating anxiety-related disorders ^{[28] [29]}.

Table 1: Studies That Analyzed the Impact of CBD on Anxiety

Figure 2. The average of the different dosages (mg) of CBD and their effect on reducing anxiety as a percentage [21] [22] [23] [25] [26] [27] [28].

The articles in Table 2 only analyzed the THC component of cannabis. One study evaluated an individual’s use of THC and the effects it has on the amygdala which is a region in the brain that is responsible for emotional processing ^{[30] [33]}. They discovered that THC can alter the functional connectivity in the amygdala in response to social threats and thus can reduce anxiety ^{[30] [33]}. However, it was also mentioned that this is context-dependent and that THC cannot decrease anxiety in every situation and setting ^[30].

On the other hand, several studies reported that the use of the THC component of cannabis can increase anxiety ^[31]. Another study analyzed the effects of THC on individuals who have depression ^[31]. They discovered that when these individuals used THC for 30 days, instead of their depression decreasing, it increased due to anxiety levels and suicidal thoughts increasing thus leading to impaired everyday functioning ^[31]. It was discovered that the THC is dosage dependent that is when given at a low dose it can decrease anxiety (7.5mg) but when given at a high dose (12.5mg) it can increase anxiety ^[32]. Another study also looked at the dosage of THC and discovered that at higher dosages of THC, there were more pronounced symptoms of anxiety ^[34]. It was also stated that THC induced a range of psychosis-like symptoms such as paranoia, hallucinations and cognitive distortions ^[34]. Zvolensky et al. focused on panic attacks which is a type of anxiety disorder and examined what THC’s impact would be to individuals with panic attacks ^[35]. It was noted that individuals who use marijuana (which is part of the plant Cannabis sativa that contains substantial amounts of tetrahydrocannabinol (THC)) more frequently have an increased likelihood of having a panic disorder ^{[35] [37]}. It was stated that individuals who had a pre-existing vulnerability factor, such as having a history of anxiety disorders or who have a sensitivity to anxiety symptoms would have more pronounced symptoms of anxiety and panic attacks when given THC ^[35]. Additionally, a study that only looked at women, reported that when oral THC was given, anxiety levels increased and autonomic cardiac activity was altered such as heart rate increases and heart rate variability decreased ^[36]. This indicates that when THC was given it increased anxiety and affected physiological responses ^[36].

Table 2: Studies That Analyzed the Impact of THC on Anxiety

STAI scale indicates anxiety. A score between 20 to 80 means that the individual is anxious. The higher number the individuals get on the STAI scale indicates more anxiety.

Figure 3. Comparing studies and if the THC used in the studies affected anxiety. 0 = no effect of the drug on anxiety, 1 = moderate reduction in anxiety, 2 = increase in anxiety, 3 = increased at higher dosages [30] [31] [32] [33] [34] [35] [36].

These studies which were reviewed in Table 3, analyzed the effects of cannabis with both of its components (CBD and THC). It was discovered that reducing cannabis in general, which includes both CBD and THC, would decrease anxiety ^[20]. Additionally, when cannabis products contained more CBD than THC, participants reported having less severe anxiety symptoms ^{[11] [20] [40]}. When the cannabis product contained more THC than CBD anxiety levels were reported to increase ^{[11] [39] [40]}. Sativex is a type of cannabis plant extract that delivers a balanced amount of both components ^[38]. It was discovered in one study that compared oral THC alone and Sativex that when oral THC was given to participants, anxiety levels increased and so did physical measures such as heart rate and blood pressure ^[38]. However, when Sativex was given, anxiety levels decreased and there were still some physiological measures that altered but were not as pronounced as when oral THC was given ^[38].

Furthermore, one study identified the effects of THC and CBD on neural activation ^[41]. It was reported that when THC was given to individuals, the neural activation in brain regions associated with emotional processing such as the amygdala, increased and this increase was linked to heightened anxiety ^[41]. On the other hand, when CBD was given, it had a more calming effect on neural activation since it reduced activation in the amygdala and other areas that are responsible for emotional processing, and this correlated with a reduction in anxiety ^[41]. The results mentioned above will be interpreted and discussed in the next section.

Table 3: Studies That Analyzed the Impact of a combination of THC and CBD on Anxiety

Discussion

The studies reviewed from search engines such as Pubmed and Google Scholar have provided significant insight into how cannabis components, specifically CBD and THC, influence the severity and progression of anxiety disorders in adults. The findings propose a clear divergence in the effect of these two component. CBD shows more anxiolytic (anxiety-reducing) properties whereas the impacts of THC are more dependent on the dosage and are context-specific, potentially heightening anxiety levels, especially at higher dosages ^[32].

Effects of CBD on Anxiety

From the results, it was found that 90% of the articles stated that CBD has a positive effect in reducing anxiety. For instance, 90% of articles stated that CBD effectively decreases anxiety in individuals with social anxiety disorder (SAD) and generalized anxiety, especially in acutely stressful situations, such as public speaking ^{[23] [26] [27] [28] [29]}. This indicates that CBD does have beneficial short-term effects. No side effects, such as addiction, were observed when CBD was given to participants ^{[23] [26] [27] [28] [29]}. Additionally, it can be noted that when 400 mg of CBD was administered, there was a reduction in anxiety without any impairment in cognitive or psychomotor functions which suggests that it is safe and can be a good therapeutic option for treating anxiety disorders ^[21]. Moreover, studies indicate that when CBD is administered repeatedly, it can significantly reduce symptoms of anxiety over time and thus can enhance therapeutic effects in long-term treatment ^[28].

An interesting finding from the research was the role of expectancy in the anxiolytic effects of CBD. Spinella et al. stated that participants who believed that CBD would reduce their anxiety, experienced a greater reduction in their anxiety symptoms than those who did not believe this and this illustrates the expectancy effects ^[24]. This suggests that while CBD can help reduce anxiety, the patient's beliefs and expectations about the treatment are also important and can affect how well it works. This links with the broader observations made clinically where a placebo effect plays a crucial role in the treatment of psychological disorders and thus highlights the importance of a patient's belief and support system in optimizing their treatment.

Effects of THC on Anxiety

When comparing CBD to THC, studies done on THC present a more complex and more negative picture. Lower dosages of THC (ex. 7.5mg) have been shown to have some potential to decrease anxiety ^{[32] [33]}. However, higher doses of THC (ex. 12.5mg) tend to increase symptoms of anxiety ^[34]. This reveals a dose-dependent response that can pose a risk for treating anxiety disorder. The impact THC has on anxiety is closely linked with its effects on the amygdala, which is a brain region that is responsible for processing fear and emotional responses. Several studies have shown that THC increases neural activity in the amygdala, especially in response to social threats which can heighten anxiety symptoms ^{[30] [33] [41]}. This proposes that while THC may reduce anxiety when individuals are in a controlled setting, its anxiogenic potential can increase when in an unpredictable or threatening situation.

Many studies also emphasize the risks linked with chronic THC use. When THC is consumed on a long-term basis, it is correlated with increased anxiety, panic attacks and symptoms that resemble psychosis such as paranoia, hallucinations and cognitive distortions ^{[31] [34] [35]}. Notably, these effects can be more prominent in individuals who have a pre-existing vulnerability to anxiety ^[35]. For instance, chronic users of cannabis products that had a rich component of THC in them showed a higher likelihood of developing anxiety disorders and experiencing panic attacks. This describes the potential dangers of consuming THC for long periods. Though gender differences were not focused on in this study, one study did analyze THC administration in only women, and it was noted that anxiety increased when THC was administered and autonomic cardiac responses were also altered, such as increased heart rates and decreased heart rate variability ^[36].

Effect of a Combination of THC and CBD on Anxiety

When analyzing the effects of both CBD and THC, studies suggest that CBD can alleviate some of the anxiety-inducing effects of THC. Cannabis products that contain higher levels of CBD than THC can decrease anxiety symptoms ^{[11] [20] [40]}. A study specifically looked at Sativex, which contains a balanced amount of both CBD and THC in a 1:1 ratio. It was found that Sativex decreased anxiety more effectively than oral THC alone and it also had fewer adverse physiological effects such as increased heart rate and blood pressure ^[38]. This suggests that CBD might have some counteractive effects to the anxiogenic properties of THC and thus this can offer a therapeutic advantage where both components of cannabis are present. These findings indicate the importance of considering the ratio of CBD to THC in cannabis products, especially when they are being used to manage anxiety disorders.

Furthermore, there has been evidence from neuroimaging studies that support the differential effects of CBD and THC on anxiety disorders. This study showed that THC increased neural activity in brain regions associated with processing emotion and this correlated to an increase in anxiety whereas CBD was found to have a more calming effect and thus decreased anxiety ^[41]. This highlights the complex interplay between these components and the neurobiological mechanisms that underlie anxiety and can provide insight into balanced formulation of both CBD and THC to optimize therapeutic outcomes to treat anxiety so the anxiolytic properties of CBD would increase whereas the potential anxiogenic effects of THC would decrease.

Relating these findings to the research question, it can be concluded that the hypothesis could be accepted. CBD does have short-term and long-term effects on anxiety as this was seen when looking at the articles. Most of the articles conducted their experiments for a day or two whereas others conducted their experiments for a few weeks or months. After this duration, whether it be a small duration (a few days) or a long duration (a few months), these articles reported the participants had reduced anxiety. From Figure 2 it was analyzed that a dosage of 400mg best reduced anxiety with an average of 53% reduction ^{[22] [26]}. On the other hand, 900mg of CBD reduced anxiety but not too much with only a 5% reduction ^[27]. Conversely, the hypothesis stated about THC was also correct. THC has a negative effect on anxiety since the articles stated that when only THC was given to the participants over 1 month, the severity of anxiety was increased ^[31].

Limitations and Future Studies

One limitation of this study was the age range. The age range was wide starting from age 12 to 65. Age is an important factor since cannabis can affect older adults more compared to younger individuals since older individuals have slower metabolisms, body compositions and overall health conditions, such as respiratory or cardiovascular problems, that can influence how their body processes THC and CBD, potentially leading to more intense effects. To overcome this a narrower age range should be used. Another limitation was that since this article used other primary sources instead of conducting its experiment, the methods that each primary article used were different, as some used the survey method whereas others used an experimental approach. The number of participants was also different and so was the length of each study. All these factors could play a significant impact on the data and should be focused on more in future studies.

More research can also be done to learn about the effects of cannabis on specific anxiety disorders such as social or general anxiety disorders. Another future study could look at the age component and determine if age plays a role in the effects of cannabis and anxiety disorders.

Cannabis use in different countries and its effects on anxiety disorders would also be a good research study to conduct in the future. Since gender was not focused on in this study, further research can be conducted to evaluate gender-specific responses to THC and CBD.

Conclusion

To summarize, the studies reviewed suggest that CBD plays an important role in reducing anxiety and this can be implicated in therapeutic applications and medications. THC on the other hand plays a negative role since it increases anxiety rather than decreasing it. More research needs to be conducted to determine the specific dosages of each component that are required to benefit patients with anxiety disorder.

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