As millions of patients know firsthand, anxiety disorders present as conditions of unfulfilled opportunities and painful psychological experiences. Responsible for a wide range of social and occupational difficulties, these disorders have a handful of different clinical presentations, including generalized anxiety disorder (GAD), social anxiety, and post-traumatic stress disorder (PTSD). While there are cognitive and pharmaceutical interventions that provide symptom relief for many, efficacy is not universal and tolerability can be a hindrance to adherence even when symptoms are alleviated. As such, many patients continue to seek alternatives to standard treatment. In light of a growing body of evidence, patients and doctors are now increasingly finding success with promising new approach: cannabidiol therapy.
Cannabidiol (CBD) is derived from cannabis, and, like other cannabinoid class chemicals such as tetrahydrocannabinol (THC), behaves as a potent neurotransmitter in the brain with both excitatory and inhibitory capabilities. In the case of THC, the consequent neurotransmission can cause intoxication and, as a result, THC is most commonly used recreationally. Unfortunately, some patients are hesitant to consider CBD as a legitimate anti-anxiety therapy due to its association with illicit cannabis use and the mistaken assumption that they will experience psychoactive effects such as those produced by THC. But while CBD is a major constituent of cannabis, it is widely recognized to be non-intoxicating and of little recreational value. Furthermore, CBD causes no side effects which people traditionally associate with cannabis use like exaggerated appetite, hypersomnia, or spiraling paranoia. On the contrary, CBD’s side effect profile, while mild, includes symptoms like decreased appetite and insomnia. More serious side effects of recreational cannabis use—such as its potential role in the onset of schizophrenia—are also notably absent from CBD when used therapeutically.
Due largely to its anecdotally-supported efficacy and high tolerability, patients are already turning to CBD—via their doctors or otherwise—to cope with anxiety disorders. Indeed, a survey of over 2400 CBD users conducted in late 2017 found that approximately 30% of respondents were using CBD specifically for their anxiety disorders. Significantly, the survey also found that patients were using CBD to treat multiple pathologies at once; on average, patients treated 2.67 different symptoms with CBD. This means that patients are using CBD to address multiple symptoms of closely linked pathologies such as anxiety and depression or anxiety and chronic pain. The results also suggest that CBD is highly effective; 36% of the respondents reported that CBD treats their medical condition “very well by itself” whereas a mere 4.3% of the patients reported that CBD was not sufficient to treat their symptoms on its own and that additional medications were required.
For patients looking to supplement or potentially replace their current anti-anxiety therapies, all evidence suggests that CBD therapy is a promising new field, potentially opening up new avenues for symptom relief for patients with a broad variety of anxiety disorders.
Research Suggests CBD Attenuates Anxiety
The basis for using CBD to treat anxiety disorders is well-established within the scientific literature despite lagging public perceptions regarding cannabinoid therapeutics. Of particular interest is a research review published in the August 2018 issue of Epidemiology and Psychiatric Sciences, which finds that currently available evidence supports CBD as an effective therapy for anxiety. Authored by Drs Mandolini and Lazzaretti of the University of Milan’s Department of Neurosciences and Mental Health, the review goes beyond confirming the evidence of efficacy and argues that doctors should begin implementing CBD therapy into their clinical practices sooner rather than later. To make this point, the authors draw on a plethora of research findings in clinical trials, animal studies, an in vitro experiments published over the course of the decades of scientific exploration of CBD. In the estimation of Dr. Mandolini, the synthesis of the scientific literature strongly supports using CBD to treat certain forms of anxiety disorders. CBD may also be useful to treat psychosis, schizophrenia, and over-eating, but more research is needed.
While CBD is effective at treating many anxiety disorders, the Mandolini review cites several studies indicating that CBD may be exceptionally effective at treating social anxiety disorder via its vasodilatory effect in certain brain regions. By selectively increasing the blood flow to structures of the brain responsible for processing fear and anxiety emotions, like the amygdala, CBD is hypothesized to increase their function and consequently reduce anxiety. CBD may also slightly reduce blood flow in areas responsible for recalling traumatic memories. Mandolini believes that this is made possible by CBD’s ability to bind to the 5HT1A serotonin receptor in the brain. The reduction in anxiety caused by CBD therapy carries over to improvement in cognitive processes which anxiety typically hampers; individuals with these disorders to have racing thoughts, subjective blankness of thought, and difficulty maintaining attention on external stimuli. These cognitive impairments can significantly interfere with functionality, diminishing quality of life and potentially increasing symptoms of comorbid mood disorders. As such, addressing the cognitive effects of anxiety disorders is necessary for many patients to achieve recovery. Unfortunately, anxiety therapies like benzodiazepines may actively weaken or slow cognitive processes owing to their inhibitory effects.
Stunningly, in one of the studies cited by Mandolini, doses of 600 mg of CBD were found to reduce or nearly eliminate the cognitive impairment associated with public speaking anxiety, resulting in cognitive function that was equivalent to healthy controls. In the study, a group of patients who experienced social anxiety when performing public speaking was split into two groups. One group would be administered CBD therapy, whereas the other would only receive a placebo. Following the administration of the therapy, the patients were subjected to a public speaking simulation while their anxiety levels and cognitive functioning were measured before, during, and after the simulation. In terms of the overall reduction of anxiety levels in comparison to healthy controls, patients treated with CBD scored nearly 50% lower on the Changes In Visual Analogue Mood Scale (VAMS) anxiety assessment instrument than the group with anxiety that received placebo. The VAMS measures both the intensity of the subjective experience of anxiety and also the cognitive impairment which accompanies high levels of anxiety. Likewise, the general discomfort score of patients treated with CBD was 10% lower than in the placebo group.
Significantly, the CBD therapy test group returned to normal levels of arousal as rapidly as healthy controls while the placebo control group did not return to the lower level of arousal experienced by the other groups in the time points measured by the researchers. Mandolini points out that this unique therapeutic effect—causing patients to recover more quickly from episodes that cause anxiety even in healthy people—has a plethora of applications in other anxiety disorders; post-stimulus anxiety is a major detractor of patient quality of life and is a primary feature in post-traumatic stress disorder. Furthermore, pre-stimulus anxiety—like the anxiety caused by drug withdrawal—might also be effectively treated by CBD.
CBD Excels Where Other Anxiolytics Falter
Studies consistently show that the effects of CBD can be extraordinary for patients struggling with anxiety disorders. So how does CBD generate such dramatic effects in the brain? Unlike other neurotransmitters responsible for regulating arousal in the brain like GABA (gamma-aminobutyric acid), cannabidiol exhibits both excitatory and inhibitory effects on the neurons which it binds to. The downstream impact of this mixed effect profile is a subtle inhibition of anxiety without the intoxicating effects of cannabis consumption or other anxiolytics like benzodiazepines. Likewise, CBD isn’t fatal in overdoses, meaning that CBD therapy may act as a safer alternative to benzodiazepines, which can cause death via respiratory depression.
Importantly, CBD also lacks the addictive potential of benzodiazepines. While benzodiazepines present a significant risk for abuse and addiction, CBD has no recognized recreational features, nor is it physically habit-forming. This is a critical point because many doctors will hesitate to prescribe benzodiazepines to patients and insist on short-term treatment to reduce the possibility of abuse and addiction, which means they cannot be used as a long-term solution for anxiety symptoms. When patients use benzodiazepines on a long-term basis, tolerance and physical dependence may build and patients may experience uncomfortable withdrawal symptoms, including rebound anxiety, when they try to reduce their dose or discontinue the drug. In some cases, withdrawal symptoms are severe and may include seizures, dysphoria, psychosis, and mania. CBD has no such shortcoming.
The side effects of benzodiazepines are also formidable in comparison to CBD. When patients take benzodiazepines to treat their anxiety disorder, they often become transiently cognitively impaired while under the effects of the drug, potentially interfering with social and professional functioning. Patients are advised to avoid driving and may find that their ability to sustain attention is impaired, along with their reaction speed. Additionally, reduced inhibitions can cause patients taking benzodiazepines at therapeutic doses to engage in risky or undesirable behaviors. Because benzodiazepines also inhibit short-term memory consolidation, patients may also struggle to remember the events of their days. In some cases, benzodiazepines cause depression or excessive emotional numbing, which may be particularly dangerous for those struggling with a comorbid mood disorder. CBD, on the other hand, is not associated with any of these phenomena.
Benzodiazepines aren’t the only class of anxiolytic drugs that CBD outperforms. Selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed to address anxiety disorders and used on a long-term basis. These medications, while effective more many, are known for their diverse set of side effects, which include sexual dysfunction, tremors, fatigue, and weight gain. Some patients even experience additional anxiety when taking SSRIs and many patients need to try more than one SSRI before finding one to which their symptoms respond. This often results in a lengthy process of trial and error, as the effects of the medication may not be observed for weeks. In contrast, CBD has no serum concentration build-up period beyond the initial period after dosing, nor does it have the substantial side effect profile of SSRIs. Additionally, while SSRIs are not addictive, some patients build mild physical dependency as the result of their effect on neurotransmitter behavior. Upon terminating SSRI use, these patients may experience SSRI discontinuation syndrome for several days or weeks, resulting in symptoms such as malaise, anxiety, nausea, and insomnia. There is no documented discontinuation syndrome associated with CBD, nor does its short course of action give reason to suspect that there is one which is yet undiscovered.
Taking the Next Steps
Dr. Mandolini’s review ends on a strident note, stating that the present hypotheses regarding CBD’s mechanism of action should give others confidence in the chemical’s potential to treat anxiety disorders of all stripes. Large randomly controlled clinical trials will soon be conducted to shed light on the details of how CBD therapy should be implemented to address these disorders. However, clinicians already have an abundance of clues from the extant literature. Likewise, patients who need a novel anxiolytic today can try CBD therapy on their own using the information compiled by Dr. Mandolini and others. Should patients become early adopters of CBD therapy, they may finally move beyond the limits of anxiety while avoiding the shortcomings of conventional therapies.
Bergamaschi MM, Queiroz RHC, Chagas MHN, Oliveira DCGD, Martinis BSD, et al. 2011. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology. 36:1219–1226. https://www.nature.com/articles/npp20116
Corroon J, Phillips JA. 2018. A cross-sectional study of cannabidiol users. Cannabis and Cannabinoid Research. 3:152–161. https://www.liebertpub.com/doi/abs/10.1089/can.2018.0006
Mandolini GM, Lazzaretti M, Pigoni A, Oldani L, Delvecchio G, et al. 2018. Pharmacological properties of cannabidiol in the treatment of psychiatric disorders: a critical overview. Epidemiology and Psychiatric Sciences. 27:327–335. https://www.cambridge.org/core/journals/epidemiology-and-psychiatric-sciences/article/pharmacological-properties-of-cannabidiol-in-the-treatment-of-psychiatric-disorders-a-critical-overview/D7FD68F40CF30CBB48A1025C66873F26
Soares VP, Campos AC. 2017. Evidences for the anti-panic actions of cannabidiol. Current Neuropharmacology. 15:291–299. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412699/