Anxiety

There is limited evidence that cannabis compound cannabidiol (CBD) is effective in the treatment of anxiety symptoms.¹ Researcher Bergamaschi and colleagues showed that patients with social anxiety disorder treated with oral capsules of 600mg of CBD had lower anxiety, measured by a reduction of 16.5 on a 100 point scale in a simulated public speaking test.² Other studies that looked at the effect of oral CBD (400 mg or 600 mg) on anxiety using brain imaging studies and subjective measures of anxiety symptoms found that, compared to placebo, CBD isolated from cannabis decreased subjective anxiety that was caused by THC.³^, ⁴^, ⁵ Research with doses that were lower and higher than the dosages in the previously mentioned studies, e.g. 100 or 900mg, have not shown to be efficacious against certain types of anxiety.⁶ Also, studies so far have only investigated single doses instead of taking multiple doses over a longer period of time, and therefore long-term effects of CBD on anxiety are unknown. Zuardi and colleagues showed that when testing three different doses of CBD, 100 mg, 300 mg and 900 mg, only the 300 mg dose attenuated the anxiety in the post-speech phase. Note that this was seen in healthy subjects in a simulated public speaking test, and that the results will need to be replicated in clinical patients.⁶ Although it seems strange that a high dose of an effective compound can counteract the beneficial effect, there are pharmacological explanations for this phenomenon. Also, this phenomenon is not exclusive to anxiety-related effects: similar effects have been observed in animals and humans in, for example, pain.⁷ The mechanisms of how CBD works on anxiety are not fully understood, but there are some interesting players in this area:

CB₁ receptor – CBD may decrease the breakdown, and therefore the presence of the endocannabinoid anandamide in a brain area that is involved in anxiety and fear. This way, anandamide could influence emotional states via the CB₁ receptor.⁵^, ⁸
Serotonin receptor – “…another possibility is that CBD directly acts on the receptors that are involved with anxiety. These receptors are referred to as serotonin receptors, and are also called 5-HT_1A.”⁹^, ¹⁰
Capsaicin receptor – The question arises: Why does CBD show anxiety relief at 300 and 400mg, but not at 900mg? This is thought to happen in the following manner: Higher doses of CBD start activating an additional type of receptor, called capsaicin receptor, or TRPV1. Upon activation, these receptors release a compound (called glutamate) that counteracts anxiety relieving effects caused by CB₁ and serotonin receptor activation.¹¹ This theory has been affirmed by the observation that blocking the capsaicin receptor in mice, induces anxiety-relieving effects for a CBD dose that would otherwise have been too high to be effective.¹²

Furthermore, neuroimaging studies in humans indicate that CBD acts on the brain areas involved with anxiety.⁵^, ¹³ Δ⁹-Tetrahydrocannabinol (THC) has been shown to induce anxiety in both naïve users and in experienced users that consume relatively high doses of THC.¹⁴^, ¹⁵^, ¹⁶^, ¹⁷^, ¹⁸ Recently, one study has shown that low doses of cannabis, and THC in particular, had “subjective stress-relieving effect,” but more studies need to be done.¹⁹ It is important to note that if you are seeking treatment for anxiety, using products containing THC might give the opposite effects than the ones you were looking for due to THC’s anxiety-inducing properties. Figure 1 gives a schematic idea of how a potentially effective THC dose could imply precision work, but the exact doses are different for every individual. Precision work illustration of CBD effects on anxiety

Precision work illustration of CBD effects on anxiety

Figure 1: Schematic visualization as a warning that THC dosing is precision work. THC could help, but at the same time be cautious: a ‘low dose’ of THC might be helpful with decreasing symptoms of anxiety, whereas a higher dose can induce anxiety. Very high levels of THC can result in serious panic attacks. The dose ranges for all effects are different per individual and can be related to genetic predisposition and cannabis experience, among other factors. In summary, there are more scientific publications on CBD than on THC that observed anxiety-lowering effects. For both CBD and THC, certain ranges within the beneficial effects have been found, with CBD’s range being wider than THC’s range. THC can induce anxiety, with risk increasing as dose increases. All in all, more studies need to be done to unravel more about the effects of CBD and THC on anxiety.References:

Education

Anxiety

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