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cannabis anxiety study

Marijuana can affect your body in many ways beyond just getting you high. The high feeling you may experience after smoking or ingesting marijuana is due to tetrahydrocannabinol (THC), the chemical compound that gives marijuana its psychoactive effects.

THC can raise your heart rate, which, if you have anxiety, may make you feel even more anxious. Using too much marijuana can also make you feel scared or paranoid.

Risks

Verywell / Cindy Chung

Working with a psychotherapist to manage your anxiety will give you a better handle on your condition in the long run.

This is paradoxical and can be difficult to diagnose, as marijuana has been used to decrease nausea and vomiting in cancer treatment. Sufferers sometimes find relief in hot baths and showers, but ultimately, abstinence from marijuana is necessary for long-term improvement.

Wright and her colleagues reviewed the current findings from both pre-clinical and clinical trials to shed light on the potential role of CBD in the treatment of anxiety.

“Preliminary evidence from human studies demonstrates that CBD may reduce anxiety in healthy participants and patients with social anxiety disorder. It is important to emphasize that this data is preliminary and more research is required.”

A new report published in the journal Cannabis and Cannabinoid Research presents an overview of the clinical findings concerning the effectiveness of cannabidiol (CBD) in the treatment of anxiety. While the report suggests that CBD may offer a safe and effective treatment for anxiety, the authors highlight the need for additional research among the female population.

“The rates of anxiety disorders are nearly doubled in females compared to males, there are differing anxiety-related symptoms and responses to psychotropic medications between the sexes, and CBD has different effects on the body in males and females,” Wright explained. “Therefore, it is important that future research examines sex and gender differences in the utility of CBD as a potential treatment for anxiety disorders.”

“There are still many questions that need to be addressed and rigorously studied,” Wright said. “The only human studies examining CBD as a treatment for anxiety have been conducted in patients with social anxiety disorder, therefore, research is needed in patients with other anxiety disorders, such as generalized-anxiety disorder and panic disorder. Secondly, much remains unknown about the use of CBD as a treatment for anxiety, such as the most effective route of administration, appropriate doses to be used, and its long-term safety and efficacy.”

In respect to the animal model research, there is strong evidence suggesting that an anxiolytic effect occurs after the administration of a small acute dose of CBD [60, 61, 63]. Results however differed depending on whether CBD was acutely or chronically administered, as well as the animal model used. This was demonstrated by Rubino et al. (2007) [67] and Schleicher et al. (2019) [70], who both observed no change in anxiety behaviour in the open field test, but significant changes in behavior in the elevated plus maze.

In humans, research has also shown that the anxiogenic effects of THC are greater among infrequent or non-users relative to frequent users [16], and high potency THC in cannabis products in particular, are thought to induce the development of psychotic-like symptoms or overt psychosis in vulnerable individuals. Similarly, intoxication by low-dose CBD has been found to be particularly prominent in infrequent cannabis users [38]. Further, it has been observed in early 1970s research that individuals who were anxious before receiving it became less anxious under the influence of cannabis (note that potentially far lower THC preparations would have been used). Conversely, non-anxious persons became more anxious [87]. In an animal model, Long et al. (2010) [69] found that differences were observed amongst mice depending on the day in which they were tested, which suggests that the length of time over which the treatment is given also effects the anxiolytic and anxiogenic properties. Kasten et al. (2019) [72] also observed inconsistencies across the groups investigated, with adolescent male mice performing differently to adult male mice, which in turn performed differently to adolescent female and adult female mice. This clearly shows that age, sex and background of exposure may have an impact on how an animal or human reacts to THC or CBD inoculation, something which was found by Cuttler et al’s. (2016) [59] epidemiological survey, where different results were reported depending on the sex of the person responding.

The plant’s anxiety-modulating action has largely been attributed to a biphasic interaction with the CB1 receptor. Rey et al. (2012) [40] found that the anxiolytic effects of low doses occur when they interact with the CB1 receptor on cortical glutamatergic terminals. Conversely, interaction with the CB1 receptor on the GABAergic terminals is responsible for anxiogenesis, something which takes place when higher doses are administered. Further, the use of a CB1 receptor antagonist has been found to fully reverse the effects of THC [41]. However, other non-CB1 receptors are also believed to be involved including serotonin 5-HT1A receptors [42] and the opioid system [20, 43, 44]. There has also been research in recent years to determine the neural site at which these interactions take place. These studies have largely involved injecting THC into various parts of the brain in animal models and observing any anxiolytic or anxiogenic effect [41]; or by observing the effects of oral doses on the brains of individuals under the influence of THC using functional magnetic resonance imaging (fMRI) [45]. Not surprisingly, it has also been found that an individual’s history of cannabis use plays a role in the response of an individual to cannabis intake [46], something which has been observed in both animal [20, 42, 43, 47] and human models [48].

Acute human clinical trials

These discrepancies could be due to the fact that while a substantial number of patients cross-sectionally report using cannabis and related products to treat anxiety symptoms or disorders, it has not been firmly established whether this anxiety occurred before or as a result of the cannabis usage [16, 85]. As epidemiological research largely relies on anonymous surveys, the composition of the cannabis being used is unable to be confirmed. It is known however, that between 1995 and 2015 there has been a 212% increase in THC content in the marijuana flower [86]. It is also known that plants producing high levels of THC are incapable of producing much CBD [86]. Thus, recent studies looking at whole cannabis consumption in theory should provide a relatively reliable source of information regarding the anxiogenic and/or anxiolytic properties of THC. Our review also highlights the lack of data from jurisdictions where cannabis is not legal, as most of the included studies are based on surveys by those living in certain states in the US or Canada where medicinal use is legal. An important consideration to note when assessing the epidemiological data is that many studies are based on self-reported effects from participants who are purposively using cannabis for their anxiety, and thus due to the sample bias, conclusions must be tempered.

Another method saw male Sprague–Dawley exposed to either 10 days of chronic unpredictable stress or no stressor [64]. After this period, they were injected with either a low (0.5 mg/kg) or a high (1.0 mg/kg) dosage of THC, then being placed in an EPM. It was observed that in unstressed animals, the rats that were administered either 0.5 mg/kg or 1 mg/kg THC showed anxiolytic-like effects. In stressed animals, however, only the high dosage of THC induced an anxiolytic-like response, whereas the low dosage induced anxiogenic effects. These results directly contradict both the idea that THC is anxiolytic at low dosages, and anxiogenic at high dosages at least when stress is applied.

Process of identification and screening of articles for inclusion

To provide a comprehensive review of the area, both animal and human studies were sought for inclusion. In order to include as many relevant sources as possible, there were no exclusions based on types of animals or models (testing anxiety or mood paradigms) used in the studies. Human studies included in the review involved either epidemiological studies exploring the cross-sectional or longitudinal association between cannabis use and anxiety, or interventional studies using whole cannabis extracts or isolates (botanically-derived only) for any anxiety disorder, or to test an acute anxiogenic or anxiolytic effect. Synthetic cannabinoid analogues were excluded from this review.