Medicinal Cannabis and Anxiety

In times of global crisis and uncertainty, it is perfectly normal to feel anxious, nervous, or stressed. Prolonged feelings of excessive fear and anxiety, however, can be harmful if they impact our normal daily life. When these symptoms are persistent, they may be indicative of an anxiety disorder. These disorders are common in normal times, with 26.3% of Australians aged 16-85 having experienced an anxiety disorder, including social phobia, panic disorder and generalised anxiety disorder[1]. During extraordinary times, such as the current global pandemic, these numbers increase with an estimated 33% of the community impacted[2]. Those most at risk include healthcare workers, the unemployed workforce, those who are quarantined and people with pre-existing mental health conditions[3].

Anxiety disorders can be effectively managed, and the first step is diagnosis in partnership with your trusted medical practitioner. This can be a challenging step as symptoms can be both physical and psychological, can coexist with other conditions such as depression, and be exacerbated by lifestyle factors and stressful situations. Anxiety disorders are often chronic and relapsing, and management strategies are most beneficial when they are practiced long term.

The first strategy to manage anxiety often involves partnering with a practitioner trained in support therapies, such as eTherapy or cognitive behavioural therapy (CBT). Cognitive approaches can be as effective as medication, and have fewer adverse effects, especially for those with mild-to-moderate disorders[4]. Strategies such as physical exercise, a balanced diet, reduction of alcohol, caffeine and sugar intake, mindfulness, adequate sleep, and self-care have all been shown to reduce anxiety, which in turn allows optimal immune system function.

People with more severe or persistent anxiety disorders, however, may require medication in addition to lifestyle strategies and cognitive approaches.

Typical medications which may be prescribed for anxiety disorders have historically included selective serotonin reuptake inhibitors (SSRIs), and benzodiazepines. An estimated 40% of patients prescribed an SSRI will experience side effects, the most reported of which are fatigue, weight gain and sexual dysfunction[5]. Benzodiazepines have been prescribed widely for anxiety disorders, however, there has been a slow recognition that large numbers of patients develop issues of tolerance and dependence4. Both SSRIs and benzodiazepines can be toxic in overdose and precipitate withdrawal symptoms making it increasingly difficult to discontinue medication.

Where benzodiazepines work by potentiating GABA in the brain, which induces a sedating effect, there is another increasingly well understood system modulating mood, called the endocannabinoid system. Cannabinoid receptors are widely distributed throughout the body and the brain and have been identified as playing a key role in anxiety disorders[6]. As cannabis directly interacts with this system, it is a logical suggestion for the treatment of anxiety.

‘Cannabis’, however, is not a single compound, but a combination of hundreds of active components including phytocannabinoids, like THC and CBD, terpenoids, flavonoids, carotenoids and a vast array of other substances, which create its unique fragrance, taste, pigment and range of therapeutic effects.

Numerous recent studies have validated cannabis to be an effective anxiolytic[7], and one component appears to be a major player in anxiety: cannabidiol or CBD. This cannabinoid has been found to impact activity in the limbic and paralimbic areas[8], which are the emotional processing brain structures. Dysregulation in these regions is implicated in stress sensitivity, mood and anxiety disorders, fear response and fear-related memories.

Clinical research finds that both subjective anxiety and physical measures of anxiety are reduced in patients taking CBD when compared to placebo8, making it a viable treatment option for subtypes of anxiety. There is also promising research that CBD enhances extinction of conditioned fear[9], which is a hallmark of generalised anxiety disorder and PTSD.

Whilst CBD appears to be a uniquely effective anxiolytic, the leading minds in medicinal cannabis research postulate that the synergistic activity of multiple components of cannabis are more therapeutically active than any single cannabinoid in isolation. This idea that the whole is greater than the sum of its parts has been coined the entourage effect[10]. This hypothesis has been clinically validated in showing that a positive contribution is derived from the inclusion of terpenes and minor cannabinoids in CBD-dominant cannabis extracts, and cannabinoid activity on psychiatric symptoms is therefore enhanced[11].

Importantly, CBD-dominant medicinal cannabis is widely tolerated, has a minimal side effect profile and, unlike traditional anxiolytic drugs, does not induce sedation or alter the natural sleep-wake cycle[1]. CBD does not create tolerance, dependence and is not toxic in overdose. CBD can interact with some medications, and a thorough medication history should always be taken when considering any cannabis treatment.

Medicinal cannabis is available as a treatment option to eligible patients in Australia and can be prescribed where appropriate under the guidance of a medical practitioner.

If you are experiencing symptoms of anxiety, speak with your doctor and seek support. More tips and advice are available free online from BeyondBlue, Headspace and Head to Health.

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[1] Australian Bureau of Statistics. National Health Survey: First Results 2017-18. 2018 Canberra: ABS
[2] Bults M, et al. Perceptions and behavioral responses of the general public during the 2009 influenza A (H1N1) pandemic: a systematic review. Disaster Med Public Health Prep 2015 9(2):207-19
[3] Black Dog Institute. Mental Health Ramifications of COVID-19: The Australian context. Sourced at: blackdoginstitute.org.au, May 2020
[4] Therapeutic Guidelines. eTG complete [digital]. Melbourne: Therapeutic Guidelines Limited; 2019 Jun. Sourced at: tg.org.au, May 2020

[5] Cascade E, et al. Real-world data on SSRI antidepressant side effects. Psychiatry (Edgmont) 2009 6(2):16–18
[6] Viveros M, et al. Endocannabinoid system and stress and anxiety responses. Pharmacol. Biochem. Behav 2005 81:331-342
[7] Blessing E, et al. Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics 2015 12:825-836
[8] Crippa J, et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J Psychopharmacol 2011 25(1):121-130
[9] Das R, et al. Cannabidiol enhances consolidated of explicit fear extinction in humans. Psychopharmacology 2013 226:781-792
[10] Russo E. The case for the entourage effect and conventional breeding of clinical cannabis: no ‘strain’, no gain. Front. Plant Sci 2019(9): 1969
[11] Ferber S, et al. The “entourage effect”: terpenes coupled with cannabinoids for the treatment of mood disorders and anxiety disorders. Current Neuropharmacology 2020 18(2):87-96

[12] Linares I, et al. No acute effects of cannabidiol on the sleep-wake cycle of healthy subjects: a randomized, double-blind, placebo-controlled crossover study. Frontiers in pharmacology 2018 9:315

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