Today, people take CBD for anxiety, stress, depression, sleep, gastrointestinal problems, and pain. CBD’s therapeutic utility for such a broad range of conditions, though, is based on very limited scientific evidence. A major challenge in determining the true benefits of CBD depends upon the administration of a pure form of CBD. CBD is either purified synthetically or by a complex plant extraction processes that produce distillates containing many of the other phytocannabinoids and various phytochemicals. CBD products are usually provided as a ratio of CBD to THC, such as 20:1. When the ratio is this high, CBD slows the catabolism of THC and leads to elevated blood levels of THC that can have physiological consequences.

In non-purified CBD products, it can be difficult to know whether any benefits are due to CBD or other psychoactive ingredients. A recent study investigated whether there is clinical evidence for the efficacy of purified CBD without the contribution of other molecules. Much of the clinical research available has investigated whether purified CBD can effectively reduce anxiety.

Studies using a variety of animal models of anxiety have produced significant evidence of the benefits of CBD for anxiety. A series of small clinical trials that lacked control groups reported that CBD effectively reduced anxiety in young adults with substance abuse, and adults with social anxiety and depression, and cannabis withdrawal syndrome. A pair of reports on subjects obtaining CBD from clinics reported reduced anxiety. One recent study administered up to 800 mg of CBD per day for 12 weeks using an open-label study (the subjects knew that they were being given CBD). This is the most unreliable type of clinical study.

Twelve weeks of treatment with purified CBD (up to 800 mg/day) led to a significant reduction in anxiety and depression. Unfortunately, this study was also open-label and only involved 30 mostly male patients. In another study, a single oral administration of CBD (300 mg) reduced the anxiety associated with public speaking in a study that utilized placebo dosing of young male adults.

Acute doses of CBD (60 mg or 1 mg/kg) reduced the anxiety produced by a single dose of THC. This finding is consistent with our current understanding of the role of CBD in the marijuana plant. The ratio of THC to CBD in the native plant is about 2:1. When used together, the CBD tends to antagonize the stimulation and anxiety typically produced by THC.

How might CBD reduce anxiety?

Functional brain imaging studies of (mostly) male subjects discovered that CBD (600 mg dose) reduced the neuronal activity within the amygdala, a brain region responsible for producing fear and anxiety. In addition, CBD reduced activity in the cingulate cortex (a brain region responsible for controlling emotional responses to fearful sensory information) when subjects were shown pictures of intensely fearful faces. A single inhaled dose (32 mg) of CBD (32 mg, 48 subjects) helped a group of male subjects to forget fearful memories. CBD (600 mg) also reduced the blood pressure response that normally occurs in the presence of mental and physical stress.

The benefits of CBD may be sex-dependent. Three recent investigations using healthy volunteers reported no benefits of CBD (150 to 600 mg acute dose) for anxiety that was induced by an examination scenario in 32 mostly female college students. Preclinical studies suggest that the anxiolytic benefits of acute CBD are most evident in male animals and vary greatly in females across their hormonal cycle. In clinical trials, when the ratio of males to females is unity, a single oral dose of CBD (600 mg) did not affect self-reported stress levels.

CBD is not for everyone. CBD (600 mg) was not effective in patients with high paranoid traits. There was no reduction in persecutory ideation and anxiety, cortisol blood levels (an indicator of stress), or elevated blood pressure. CBD (300 mg) produced no significant reduction in anxiety, depression or sleep parameters in patients who are dependent on crack cocaine. Patients with social anxiety disorder or panic disorder with agoraphobia did not benefit from CBD (300 mg) given for eight weeks in combination with a therapy session. In contrast, in patients with generalized social anxiety disorder, or heroin use disorder, a single dose of CBD (ranging from 400 to 800 mg) effectively reduced anxiety.

In summary, in healthy (male) volunteers, there is good evidence that a single dose of CBD (300–600 mg) can reduce peripheral indicators of stress, such as blood pressure, as well as self-reported levels of anxiety.