The promise of cannabidiol in anti-anxiety treatment.

The endless epidemic has caused anxiety, and a legal, non-toxic medication that can be targeted to treat this condition can be purchased online, at a nearby pharmacy, or at a roadside mall, respectively. With anxiety ranking in the top three common reasons for using CBD in many surveys, it is not surprising that many people are experimenting with CBD to address anxiety.

But how does science explain it? Does cannabidiol really help reduce anxiety? Many scientific papers have addressed this question over the past two decades, and reviews in 2015 and 2020 concluded that the evidence is promising, if incomplete, and that various molecular mechanisms may be at work, including CBD activation of the 5-HT1A serotonin receptor, antagonism of the TRPV1 receptor, amplification of GABA-A signalling, and indirectly via endocannabinoids (also known as 'happiness molecules') that promote CB1 receptor activation. also known as 'bliss molecules') indirectly contribute to the activation of CB1 receptors.

Preclinical and clinical research into the anxiolytic properties of CBD is accelerating, with nearly a dozen papers published in the last few months alone.

Before we discuss a few recent studies, a brief explanation of the professional definition of anxiety is in order. Unlike stress, which is usually defined as a short-term or acute response to a specific recognised threat, anxiety is considered a more persistent mental health disorder with no single identifiable cause. Characteristics of anxiety may include nagging, and excessive worry that does not go away even in the absence of the stressor.

This means that treating anxiety is not as simple as just eliminating the source (which is difficult to do in the context of a global epidemic) and that treatment may require a mix of psychiatric, physical and pharmacological therapies. So can CBD be one of these tools?

Not only does a high daily dose of CBD appear to have benefits for mental health, including anxiety, these effects may also last up to a month after stopping the drug. These are the core messages of a new paper published in the journal Frontiers in Pharmacology by an international team of researchers from Brazil, Canada, the United States and Israel (including respected cannabis scientist Rafael Enzyme Cholam), which includes some caveats.

Treating anxiety is not just about eliminating the source.

The paper builds on an earlier article by the same team published in 2021, who found that among 118 frontline healthcare workers in Brazil in the first year of the epidemic, those who used 300 milligrams per day of pure hemp-derived CBD from grams of medium-chain triglyceride oil for four weeks, accompanied by 'standard care' (motivational and instructional videos on low-intensity physical exercise and weekly consultations with psychiatrists providing psychological support) had significantly lower levels of anxiety, depression and emotional exhaustion than those who received only standard care.

However, the clinical trial described above has one obvious flaw. Although it included a control group, there was no blank control group. This means that there is no way to rule out the possibility that the benefits in the experimental group were due to the positive expectations of the individuals using CBD rather than strictly pharmacological effects.

The latest study, published in October 2022, extended the experiment by administering a questionnaire to 71 study participants for two months after the end of CBD administration. And this experiment included a different, arguably even less effective, control group: the third study in mental health, in which 79 Brazilian frontline healthcare workers completed the same questionnaire at the same time during the three months of the epidemic, but they were not subjected to any intervention. (No urine tests were carried out to exclude the use of CBD or other substances)

These limitations aside, the new follow-up study showed that participants who used CBD for one month in the clinical trial generally maintained lower levels of anxiety, depression and emotional exhaustion in the month following discontinuation of CBD - after which they began to return to baseline. The study also found that in all these areas, even after two months of discontinuation, CBD subjects continued to perform better than non-CBD subjects relative to their own baseline.

Admittedly, these results are intriguing. But in conclusion, the authors state the obvious: "A double-blind blank-controlled clinical trial is still needed to confirm the present findings".

The case of the stressed Mexican practitioner.

From a non-blank controlled clinical trial and online questionnaire to a number of case studies: not entirely impeccable evidence, but consistent positive results nonetheless.In a paper published in September 2022 in the journal Drugs in Context, a private clinician and employees of the Mexican Institute of Cannabis Research (ICAN), and a company that isolates CBD products from hemp and Botican brand medical hemp preparations, reported four cases of individuals who used very low doses of CBD to help treat anxiety and improve sleep and quality of life during the epidemic in late 2020 and early 2021.

Recent research supports the popular notion of CBD as a safe anxiety treatment, especially when doses are individualised and paired with other targeted therapies.

Case 1, a 54-year-old male business manager who sought treatment for periodic high levels of tension, fidgeting, difficulty concentrating, irritability and fatigue that began around November 2020. He found that adding 80 mg of CBD to olive oil daily led to "an improvement in his sleep quality, relief of anxiety symptoms and improvement in activities of daily living", which at the time of writing had lasted for three months.

Case 2, a 45-year-old female employee reported that her anxiety symptoms had worsened since January 2021: falling asleep became more difficult, her mood began to become unstable, she had difficulty concentrating, and she felt angry, sad and guilty from time to time. According to the authors, by taking 33.3 mg of CBD, 10 mg of the antidepressant citalopram daily, plus cognitive behavioural therapy, her sleep, concentration and overall health improved significantly.

Case 3, a 49-year-old male lawyer, reported poor sleep quality and further worsening of ongoing stress and anxiety by 2020. After suspending the antidepressant vortioxetine and transitioning to 33.3 mg of CBD per day, his sleep improved dramatically, with no significant manifestations of anxiety, a "stable emotional state" and no side effects.

Case 4, a 35-year-old female photographer with chronic anxiety, poor sleep and recurrent migraine attacks, worsened in May 2020. After three months of taking 20 mg of CBD daily plus supplements such as chamomile, lemon balm, vitamin B6 and tryptophan, she reported feeling well, sleeping well, no further migraine attacks and a significant reduction in her anxiety levels.

Due to the absence of anecdotal evidence from blank controls and a possible conflict of interest between the two authors, these case studies cannot be taken as proof of the effectiveness of CBD for anxiety disorders. However, they at least add some credibility to the popular notion of cannabidiol as a safe anxiety treatment, especially when doses are individualised and paired with other targeted therapies.

The authors conclude: "The results found in this study add to the existing clinical evidence that provides support for the safety of CBD use (as long as the CBD is medical grade and of legal origin), which also suggests that CBD may be useful for patients suffering from intractable anxiety disorders or with low response rates to conventional treatments. Nevertheless, it is recommended that randomized, controlled studies continue to be conducted on patients with more diverse anxiety disorders to determine whether this cannabinoid is beneficial for these disorders, as well as the safety and efficacy of long-term CBD treatment".