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cannabis and anxiety research

The research team behind the review, led by Madison Wright, notes that anxiety disorders are the most common mental health disorders worldwide. Despite the pervasiveness of anxiety disorder diagnoses, existing behavioral treatments offer limited effectiveness and the current pharmacological treatments carry unwanted negative consequences.

“Following the recent push to legalize cannabis in many jurisdictions, CBD has gained a lot of attention from the public and scientific community for its potential therapeutic properties. Given the data demonstrating that CBD is well tolerated and demonstrates little potential for abuse or dependence in humans, we were interested in reviewing the animal and human literature on its use as a treatment option for anxiety disorders.”

“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.”

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.

Next, clinical studies among patients with social anxiety disorder have found anxiety-reducing effects with single doses of either 400 or 600 mg of CBD. During a public speaking simulation task, these doses were found to lower anxiety symptoms, reduce cognitive impairment, and reduce discomfort associated with one’s speech performance. A collection of brain imaging studies additionally revealed that CBD intake alters blood flow in the amygdala, hippocampus, hypothalamus, and cingulate cortex — four brain structures implicated in anxiety.

Although the aim of the Valjent et al. (2002) [21] study was to determine the effect of THC and nicotine administered together, we were able to utilise their results in this review, as THC was first administered alone. This involved the acute administration of either 0.03, 0.1, 0.3, 1, 2.5 or 5 mg/kg to determine at what dosage THC would produce a clear anxiolytic-like response. It was found that anxiolysis occurred at a dosage of 0.3 mg/kg. This markedly changed to an anxiogenic effect when 5.0 mg/kg was administered and there was no change in the response relative to vehicle for all other dosages given. These findings were further confirmed when in the same year the low dosage of 0.3 mg/kg THC was again given to male CD1 mice and once again an anxiolytic-like response was observed [20]. This was done based on the conclusions of the previous study, and with the intention to induce this anxiolytic-like response. Alternative dosages of 0.3, 1, 3 or 10 mg/kg were also employed [69]. The timeframe also differed, with these given in 21 daily injections. This study implies that there is a clear correlation between increasing dosages of THC and time spent in the dark area of the LD box.

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.

Cannabis has been documented for use in alleviating anxiety. However, certain research has also shown that it can produce feelings of anxiety, panic, paranoia and psychosis. In humans, Δ 9 -tetrahydrocannabinol (THC) has been associated with an anxiogenic response, while anxiolytic activity has been attributed mainly to cannabidiol (CBD). In animal studies, the effects of THC are highly dose-dependent, and biphasic effects of cannabinoids on anxiety-related responses have been extensively documented. A more precise assessment is required of both the anxiolytic and anxiogenic potentials of phytocannabinoids, with an aim towards the development of the ‘holy grail’ in cannabis research, a medicinally-active formulation which may assist in the treatment of anxiety or mood disorders without eliciting any anxiogenic effects.

Elevated plus-maze (EPM)

The three cross-sectional studies found that respondents reported that they used cannabis medicinally for anxiety, second only to pain [50, 52, 55], with close to half of all survey participants stating they use cannabis for anxiety [50,51,52, 56]. In a study of 1429 participants, Sexton et al. (2016) [50] found that over half (59.8%) of medical users reported using cannabis as an alternative to pharmaceutical prescriptions [50]. Similarly, a US study of 2774 participants found this to be 46% of users [53]. Additionally, one study of 2032 people found that nearly half of the respondents had substituted an anxiety medication prescribed to them by their physician, with medical cannabis [56], and 61% indicated that cannabis had completely replaced their prescribed medication. Likewise, another study consisting of 1513 participants found similar results, with 71.8% indicating that they had reduced their intake of anti-anxiety medications [54] (Table 2).

Process of identification and screening of articles for inclusion

McLendon et al. (1976) [65] used pairing one of two tones with the delivery of a peripheral electric shock in male Rhesus monkeys to establish the cardiac conditioned response (CCR). The conditioned response is considered to be part of the complex of physiological and behavioural changes characteristic of anxiety and has been used to study anxiety in human [65, 76]. The effect of various dosages of 0.2, 0.5 or 1.0 mg/kg intravenous THC was given. The results revealed that THC blocked the CCR in a dosage dependent manner and this was consistent across trials and across animals. At the lowest dosage tested of 0.2 mg/kg a slight attenuation was consistently noticed with a reduction in the conditioned response of 5 to 6 beats per minute observed. At the next highest dosage of 0.5 mg/kg a reduction of 10 to 15 beats per minute was noted for each animal and at the highest dosage of 1 mg/kg, there was a resultant complete block of the CCR in every case.

Acute doses of CBD were found to reduce anxiety both in animals and humans, without having an anxiogenic effect at higher doses. Epidemiological studies tend to support an anxiolytic effect from the consumption of either CBD or THC, as well as whole plant cannabis. Conversely, the available human clinical studies demonstrate a common anxiogenic response to THC (especially at higher doses).