A review of potential side effects in humans found that . Mechanisms underlying the anxiolytic. The biphasic effects of cannabinoids on . The anxiolytic action of CBD may be linked to 5-HT1A mechanism may be essential for the anxiolytic. The mechanism underlying this pattern of dose-response effect of CBD cannot yet be fully explained. In humans, limbic and paralimbic brain.
Anxiolytic Effect Behind CBD Mechanisms
Most of what we know about the effects of CBD in chronic anxiety is anecdotal, but as I will show below, the scientific studies we do have so far are encouraging. There is also strong evidence that CBD helps with acute anxiety in humans.
If you are not stressed or anxious to begin with, single CBD doses will not necessarily make you feel more relaxed. Several studies of single dose CBD have been performed in healthy, non-anxious people and CBD did not do very much to their mental state a few examples: However, when acute anxiety was induced, CBD did show a significant anxiety-reducing effect.
What all of the above studies have in common is that they are single dose studies in experimentally-induced anxiety. What is missing is a study of chronic CBD dosing in chronically stressed people or patients with a clinical anxiety disorder such as GAD or SAD but wait until the last section, the answer may be on its way!
In chronically-stressed mice, repeated CBD administration had an anxiolytic effect. This is where things get tricky.
There is not yet a commonly accepted dose of CBD to treat anxiety. However, the data that we do have so far shows that it could be easy to get the dose wrong. Moderate doses are anxiolytic, but this effect is actually lost at higher doses. Until recently, most human studies of CBD and anxiety have only tested a single dose level. This always left me wondering whether the optimal dose of CBD was used in many of these studies.
However, a recent study of public speaking-related anxiety confirmed the bell-shaped dose-response in humans. The studies that showed an effect of CBD in experimentally-induced anxiety listed in previous section used doses of mg, mg, or mg. So it appears that they were in the right range. CBD may counteract THC-induced anxiety at lower doses than those needed to reduce anxiety from acute stress.
Perhaps an even lower dose may be effective, but 15 mg of CBD was the lowest dose that I found tested. As I mentioned previously, all of the above studies were single-dose studies of acute anxiety. So far, no clinical studies have been performed to establish a regular dosing regimen for chronic anxiety. I do realize there is a wealth of anecdotal data around this, but you can google that for yourself. Overall though, repeated doses of CBD for chronic anxiety are probably much lower.
I will say that it is a well validated anti-anxiety target with decades of study. So why does CBD show the bell-shaped dose-response curve, with higher doses not having any anti-anxiety effect? This appears to be related to another receptor, called TRPV1. TRPV1 is expressed in a part of the brain called the periaqueductal gray area PAG , where its activation produces anxiety. This brings up the question: It is safe and generally well-tolerated, with decades of study behind it it was approved by the FDA in It has generic versions available i.
The appropriate dosing regimen for anxiety is well-established. Something that differentiates it from buspirone and makes it worthy of further study?
The next section on repeated CBD dosing shows that the answer may be yes. Although 5-HT 1A agonism by CBD may contribute to its still unproven efficacy in chronic anxiety, there are other mechanisms of action. Chronic anxiety can be driven by stress, which dysregulates the endocannabinoid system here is a open-access review with more detail. This neurogenesis was critical to reducing anxiety behavior of the mice.
Yet another mechanism of anti-anxiety effects is through reduction of inflammation. Neuroinflammation has been linked to anxiety , and this may be reduced by CBD. This may be a particularly important anti-anxiety mechanism in specific brain diseases such as multiple sclerosis. Surprisingly, there was only one upcoming study where the main focus was on anxiety.
This study has two phases. The first is an open-label assessment of 4 weeks of CBD treatment in adults with anxiety dosing 9. The second phase is similar, but will be double-blind and placebo-controlled. This study will start in March There were several other studies where anxiety is not the main focus, but assessing anxiety is a secondary objective of the study.
Changes in Visual Analogue Mood Scale VAMS factors induced by simulated public speaking test SPST , measured in 12 social anxiety patients who received cannabidiol , 12 social anxiety patients who received placebo and 12 healthy controls. The phases of the experimental session are: Points in the curves indicate mean and vertical bars SEM. On the sedation factor, there are significant effects of phases F 3.
Other specifications are in the legend of Figure 1. Changes in relation to the pretest phase of BSS in the three groups showed a significant effect of phases F 3. In this phase the changes in relation to the pretest phase were 8. Changes in relation to the pretest showed significant repeated-measures ANOVA effect only in phases for the following physiological measures: In these measures, the values were significantly elevated during SPS without differences among the groups.
This was expected as the fear of speaking in public is a cardinal manifestation of SAD Brunello et al , Pretreatment of SAD patients with CBD significantly reduced anxiety, cognitive impairment, and discomfort in their speech performance S and significantly decreased alert in their anticipatory speech A.
These preliminary results indicate that a single dose of CBD can reduce the anxiety-enhancing effect provoked by SPST in SAD patients, indicating that this cannabinoid inhibits the fear of speaking in public, one of the main symptoms of the disorder.
The anxiolytic effects of CBD had been extensively demonstrated in animal studies and in healthy volunteers submitted to anxiety induced by several procedures, including the simulation of public speaking Crippa et al , , However, there is only one published report of the anxiolytic effect of CBD in an anxiety disorder Crippa et al , , The SPECT analysis of this study and of a previous one with healthy volunteers Crippa et al , showed that the CBD effects were associated with the activity of the parahippocampal gyrus and hippocampus.
Moreover, CBD has shown to disrupt forward intrinsic connectivity between the amygdala and the anterior cingulate during the neural response to fearful faces Fusar-Poli et al , b. Taken together, these studies demonstrate the action of CBD in limbic and paralimbic brain areas, which are known to be associated with anxiety.
Additionally, CBD injected into the dorsolateral periaqueductal gray of rats produced anxiolytic-like effects in the elevated plus-maze and elevated T-maze, and these effects were prevented by a 5HT1A receptor antagonist Soares et al , ; Campos and Guimaraes, Another important observation of this study was that the increase of negative self-evaluation during public speaking was almost abolished by CBD.
In a previous study, we suggested that the negative self-evaluation during the phobic situation of public speaking would be important for the avoidance and impairment in social functioning that support the diagnosis of SAD Freitas-Ferrari et al , submitted. In that way, the observed effect of CBD for improving the self-evaluation during public speaking, which is one of the pivotal aspects of SAD, will influence the therapy of SAD patients.
Although physiological measures have not shown significant differences among the groups, the self-report of somatic symptoms BSS increased significantly only for the SAD patients who received placebo during the test.
Following the same rationale as above, it is well-known that more pronounced bodily symptoms may contribute to the clinical diagnosis of SAD, and this result suggests that CBD also protects the patients from their subjective physiological abnormalities induced by the SPST. The findings reported herein need to be interpreted with caution, given the limitations of the study.
First, it would have been desirable to measure plasma levels of CBD and to relate such measurements to changes in the VAMS scores; however, it should be pointed out that previous investigations have not been able to confirm whether there is a direct relationship between plasma levels of cannabinoids, in particular CBD, and their clinical effects Agurell et al , Another limitation refers to the size of the sample included; however, the statistical power of the data from the VAMS and SSPS was shown to be relatively robust even with small subject numbers.
An extensive list of medications for the pharmacological treatment of SAD was made available in recent years, including selective serotonin reuptake inhibitors SSRIs , selective serotonin and norepinephrine reuptake inhibitor SSNRI , antidepressants and benzodiazepines Schneier, However, both SSRIs and SSNRIs have an initial activation and a long latency period of response, and benzodiazepines are limited by their potential to produce motor impairment, sedation, and to induce dependence and withdrawal symptoms following discontinuation Blanco et al , Conversely, CBD has important advantages in comparison with the currently available pharmacological agents for the treatment of SAD, such as an early onset of action and lack of important side effects both with acute and chronic administration to healthy subjects Crippa et al , , Moreover, it was shown that repeated treatment with CBD but not 9-THC does not develop tolerance or dependence Hayakawa et al , and possibly reduces drug-seeking behaviors Parker et al , ; Ren et al , ; Morgan et al , Thus, because of the absence of psychoactive or cognitive effects, to its safety and tolerability profiles, and to its broad pharmacological spectrum, CBD is possibly the cannabinoid that is most likely to have initial findings in anxiety translated into clinical practice.
Therefore, the effects of a single dose of CBD, observed in this study in the face of one of the main SAD's phobic stimuli, is a promising indication of a rapid onset of therapeutic effect in patients with SAD. However, randomized, double-blind, placebo-controlled, clinical trials with larger samples and chronic use are still needed to confirm these statements.
Likewise, because CBD effects are biphasic, the determination of adequate treatment ranges for each disorder remains a challenge. Further research to determine the precise mechanisms of action of CBD in the different anxiety disorders is desirable and opportune. National Center for Biotechnology Information , U. Journal List Neuropsychopharmacology v. Published online Feb 9. Author information Article notes Copyright and License information Disclaimer.
This article has been cited by other articles in PMC. Physiological Measurements Skin conductance A computer-controlled, voltage-constant 0. Heart rate Heart rate HR was estimated by manually counting the pulse rate. Table 1 Timetable of the Experimental Session. Open in a separate window. Statistical Analysis Clinical and demographical characteristics were analyzed with the non-parametric tests gender and socioeconomic level and by the analysis of variance for one factor ANOVA , followed by post-hoc Bonferroni's test for multiple comparisons age, age of SAD onset and SPIN.
Table 2 Clinical and Demographical Characteristics of the Groups. Interactions of delta 1-tetrahydrocannabinol with cannabinol and cannabidiol following oral administration in man. Assay of cannabinol and cannabidiol by mass fragmentography.
Pharmacokinetics and metabolism of delta 1-tetrahydrocannabinol and other cannabinoids with emphasis on man. Pharmacotherapy of social anxiety disorder. Neural basis of Deltatetrahydrocannabinol and cannabidiol: Specificity of social anxiety disorder as a risk factor for alcohol and cannabis dependence.
Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats. Management of anxiety disorders. Guidelines of the Brazilian medical Association for the diagnosis and differential diagnosis of social anxiety disorder. Comparability between telephone and face-to-face structured clinical interview for DSM-IV in assessing social anxiety disorder.
Neural basis of anxiolytic effects of cannabidiol CBD in generalized social anxiety disorder—a preliminary report. Are there differences between early- and late-onset social anxiety disorder. Grey matter correlates of cognitive measures of the simulated public speaking test in social anxiety spectrum: Effects of cannabidiol CBD on regional cerebral blood flow. Therapeutical use of the cannabinoids in psychiatry. Self statements during public speaking scale SSPS: Modulation of effective connectivity during emotional processing by Delta 9-tetrahydrocannabinol and cannabidiol.
Pharmacology of human experimental anxiety. Braz J Med Biol Res. Repeated treatment with cannabidiol but not Delta9-tetrahydrocannabinol has a neuroprotective effect without the development of tolerance. An instrument to assess self-statements during public speaking: The global burden of anxiety and mood disorders: Simulated public speaking as a model of clinical anxiety.
Psychopharmacology Berl ;
Cannabidiol as a Potential Treatment for Anxiety Disorders
CBD is getting a lot of press for its anti-anxiety effects. Here is the scientific evidence, mechanisms behind how it works, and upcoming clinical. Numerous studies have highlighted the anxiolytic effects of CBD, with only a The exact mechanisms behind why CBD is effective in treating. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the. .