A total of 388 responses were made, of whom 277/388 (71%) were logged as not experiencing any side-effects. Dry mouth was experienced by 44/388 (11%), and 13/288 (3%) experienced fatigue. All other side-effects were reported less than 2% (e.g. dizziness, nausea, upset stomach, rapid heartbeat, diarrhoea, headache, anxiety, psychotic symptoms, sexual problems, trouble concentrating). No respondents reported vomiting, fainting, liver problems (raised liver enzymes in blood test), or seizures. Adjusted logistic models show no associations of age, of sex with “no side effects” or fatigue. Location of the participants was associated with dry mouth, those who lived outside of the UK had greater odds of experiencing dry mouth (aOR 2.44, [95% CI 1.25–4.75], p = 0.009). No other side-effects were analysed due to the small number of respondents citing other side-effects.
In adjusted logistic models, more males (47.4%) were using CBD for general health and wellbeing than females (30.7%; aOR 0.464, [95% CI 0.30–0.72], p = 0.001). More females were using CBD for self-perceived anxiety (47.9%) than males (34.2%; aOR 1.595, [95% CI 1.021, 2.49], p = 0.04), and for self-perceived insomnia (females 28.6%, males 17.8%; aOR 1.871, [95% CI 1.125–3.112], p = 0.015). More males (14.1%) than females (7.1%) were using CBD for post-workout sore muscles (aOR 0.462, [95% CI 0.236–0.905], p = 0.024).
When used in high doses, somnolence is a primary adverse effect (Machado Bergamaschi et al. 2011). Patients in CBD clinical trials were more likely to experience sedation (OR 4.21, 95% CI 1.18–15.01) and somnolence (OR 2.23, 95% CI 1.07–4.64) in comparison to placebo (Chesney et al. 2020). Despite this preclinical and experimental research, there is a lack of human clinical trials to establish the efficacy and appropriate CBD indications fully. The effective dose for most of the above indications is still to be determined. In much of the research, high doses of CBD are used (between 300 and 1200 mg), whilst at the same time, globally, millions of CBD users are using low dose CBD. Thus, a disconnect exists between clinical research and the current state of the market.
Given the low quality of CBD available on the market, it may be that these individuals were not taking CBD, or that CBD is not efficacious in sleep, so many individuals report better sleep by virtue of the placebo effect, fuelled by marketing (Haney 2020). Another reason may be that CBD is acting on other aspects of stress and anxiety that indirectly reduce sleep problems. Still, in this survey, participants directly attributed improved sleep to CBD. This points to the need for RCTs, as the effect of expectations (i.e. the result of the placebo effect), particularly with compounds advertised as cure-alls (Haney 2020). Suggesting that the placebo effect may contribute to the purported impact of CBD does not reject the potential medical value of CBD, but it does mean we must be wary of the results of observational studies (Haney 2020).
CBD has not demonstrated any potential for abuse or dependency and is considered well tolerated with a good safety profile, according to a report released by the World Health Organization (WHO) (Geneva CANNABIDIOL (CBD) n.d.). Since January 2019, the European Union (EU) has classified CBD as a novel food, implying that before 1997, consumption was insignificant. Each country has implemented the regulation of CBD differently. In the UK, The Food Standards Agency (FSA) recommends limiting the daily dose of CBD to 70 mg (Cannabidiol (CBD) n.d.). However, researchers have used doses up to 1200 mg without serious side-effects (Davies and Bhattacharyya 2019). Conversely, few clinical trials involving children with treatment-resistant epilepsy who received either 10 or 20 mg/kg of CBD (Epidiolex) for 12 weeks recorded side-effects, such as a reversible rise in liver enzymes (Devinsky et al. 2018a; Thiele et al. 2018).
The sample consisted of 387 current or past-CBD users who answered a 20-question online survey. The survey was sent out to CBD users through email databases and social media. Participants reported basic demographics, CBD use patterns, reasons for use, and effects on anxiety, sleep, and stress.
Route of administration did not vary by sex. There were lower odds of those aged 55+ of vaping CBD (aOR 0.176, [95% CI 0.04–0.80], p = 0.025) as well as lower odds of those aged 35–55 (aOR 0.245, [95% CI 0.10–0.59], p = 0.002) and 55+ (aOR 0.115, [95% CI 0.025–0.520], p = 0.005) in comparison to 18–34 years old for drinking CBD. Self-reported anxiety (aOR 1.78, [95% CI 1.08–2.92], p = 0.023) and those using CBD for sleep improvement (aOR 1.945, [95% CI 1.152–3.285], p = 0.013) were associated with the sublingual route. Stress was not associated with route of administration.
CBD is readily obtainable in most parts of the United States, though its exact legal status is in flux. All 50 states have laws legalizing CBD with varying degrees of restriction, and while the federal government still considers CBD in the same class as marijuana, it doesn’t habitually enforce against it. In December 2015, the FDA eased the regulatory requirements to allow researchers to conduct CBD trials. Currently, many people obtain CBD online without a medical cannabis license. The government’s position on CBD is confusing, and depends in part on whether the CBD comes from hemp or marijuana. The legality of CBD is expected to change, as there is currently bipartisan consensus in Congress to make the hemp crop legal which would, for all intents and purposes, make CBD difficult to prohibit.
Some CBD manufacturers have come under government scrutiny for wild, indefensible claims, such that CBD is a cure-all for cancer, which it is not. We need more research but CBD may be prove to be an option for managing anxiety, insomnia, and chronic pain. Without sufficient high-quality evidence in human studies we can’t pinpoint effective doses, and because CBD is currently is mostly available as an unregulated supplement, it’s difficult to know exactly what you are getting. If you decide to try CBD, talk with your doctor — if for no other reason than to make sure it won’t affect other medications you are taking.
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CBD is commonly used to address anxiety, and for patients who suffer through the misery of insomnia, studies suggest that CBD may help with both falling asleep and staying asleep.
Side effects of CBD include nausea, fatigue and irritability. CBD can increase the level in your blood of the blood thinner coumadin, and it can raise levels of certain other medications in your blood by the exact same mechanism that grapefruit juice does. A significant safety concern with CBD is that it is primarily marketed and sold as a supplement, not a medication. Currently, the FDA does not regulate the safety and purity of dietary supplements. So, you cannot know for sure that the product you buy has active ingredients at the dose listed on the label. In addition, the product may contain other (unknown) elements. We also don’t know the most effective therapeutic dose of CBD for any particular medical condition.
“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.”
While reviewing these findings, Wright and her colleagues also pinpointed another important issue. Although males and females appear to experience anxiety differently, no clinical trials have examined sex differences in the anxiolytic effects of CBD. Most studies have examined male participants, but evidence suggests that women tend to experience worse symptoms and a higher likelihood of having an additional diagnosis. Males, on the other hand, are more likely to experience anxiety alongside alcohol and substance abuse.
The researchers noted that additional trials will be important to examine the outcomes of CBD among patients with other anxiety-related disorders, such as general anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder. They also suggest that future studies should explore the optimal dose and administration route for CBD and assess its safety in the long term.
First, findings from pre-clinical animal studies show that low to medium doses of CBD produce anxiety-reducing effects, while high doses increase anxiety. Animal research also offers evidence that the anxiety-relieving effects of CBD involve the serotonin receptor 5-HT1A. While on the whole, this research shows compelling support for CBD as an anxiety treatment, the researchers note that these studies have only been conducted among male animals.
“There are still many questions that need to be addressed and rigorously studied,” Wright said. “The only human studies examining CBD as a treatment for anxiety have been conducted in patients with social anxiety disorder, therefore, research is needed in patients with other anxiety disorders, such as generalized-anxiety disorder and panic disorder. Secondly, much remains unknown about the use of CBD as a treatment for anxiety, such as the most effective route of administration, appropriate doses to be used, and its long-term safety and efficacy.”