Anxiety disorders are the most common mental health conditions found in the western world. In the US alone, reports indicate that 19% of adults are currently affected by anxiety disorders, and it is estimated that 33% of the population will experience anxiety at one point in their lifetime.  While a large number of different anxiety disorders exist, they often result in similar behavioral disturbances (e.g. increased heart rate, restlessness, trembling) and excessive stress (NIMH., n.d). Additionally, anxiety disorders are often linked with other health conditions such as depression, eating disorders and obsessive-compulsive disorders (OCD). Particularly, chronic anxiety disorders can negatively impact work performance as well as social and intimate relationships.

Currently, selective serotonin reuptake inhibitors (SSRIs) antidepressants, for example Prozac (fluoxetine) and Paxil (paroxetine), are the most commonly used medical treatment for anxiety. However SSRI often come with a wide range of negative side-effects such as lack of hunger, agitation, or difficulties sleeping, leading many individuals to seek alternative therapeutics (NIMH., n.d.; Turna et al., 2017).

As of 2017, anxiety stands as the fifth most common medical condition for which individuals consume Cannabis in both the USA and Canada (Welsh, et al., 2013; Turna et al., 2017). 

In the 80s and 90s, synthetic cannabinoids were often used in the past to investigate the effect of cannabinoids on individual anxiety disorders. Many of these studies were performed with small groups, and using old (DSM)-classifications (Diagnostic and Statistical Manual of Mental Disorders) , limiting the ability to fairly compare old data to results obtained in newer studies (Turna et al., 2017). Therefore, in this newsletter, we will refrain from discussing compounds which are no longer used, or studies deemed no longer clinically relevant.

Neuroimaging studies have shown that, by varying consumption doses, THC is able to both increase or decrease emotional arousing (processing of negative stimuli) (Fusar-Poli et al., 2010; Bossong et al., 2013; respectively).  High CBD content has repeatedly shown anxiolytic effects, with 300mg of CBD resulting in a similar effect as 5mg of isapirone (a selective 5-HT1a receptor partial agonist) (Zuardi et al., 1993).  On the other hand, acute cannabis use (strains with high THC/low CBD content) is also thought be a cause in the development of other neurological disorders in addition to anxiety (for example depression, Alzheimer’s disease [AD], or bipolar disorder [BP]), especially in individuals with a genetic predisposition.  The following section discusses the therapeutic potential of cannabis to aid in treating various anxiety disorders.   

Low-levels of 5-HT1A are often found in individuals with mood and/or anxiety disorders. Furthermore, excessive stress can exacerbate disorders and further reduce 5-HT1A levels, in turn leading to a worsening of the condition. CBD has been observed as an agonist of 5-HT1A activity, resulting in decreased 5-HT firing in the short-term, but increasing over-time by repeated exposure. Recent studies have shown that 5-HT1A mice and rat models serve as accurate animal models to study anxiety in humans. A recent study on rats with decreased 5-HT firing and anxiety-like symptoms showed that over a period of 7-days, daily exposure to low-levels of CBD increases overall 5-HT firing via desensitization of 5-HT1A (De Gregorio et al., 2019). A study based on perceived anxiety from individuals with Social Anxiety Disorder (SAD) repeatedly showed that CBD is able to reduce perceived anxiety. CBD ingestion resulted in participants showing less anxiety and decreased self-deprecation during and following a simulated public speaking task (Bergamaschi et al., 2011). 

THC on the other hand was observed to aid in the treatment of Post Traumatic Stress Disorder (PTSD) symptoms. Following a 3-week treatment with 2.5mg dose of THC (once in the morning and once before bed), participants reported decreased PTSD hyperarousal symptoms, as well as decrease in nightmare frequency and mental overstimulation from the nightmares (Roitman et al., 2014).            

A study on 104 participants with PTSD-nabilone treatment (a synthetic cannabinoid that behaves similarly to THC) reported positive effects on quality of life over the course of 11.2 weeks. Nabilone was shown to significantly reduce PCL-C scores (lower numbers are equal to a lower PTSD severity and chance of onset/PTSD presence). Furthermore, participants reported a significant increase in the number of hours slept, with a decrease in nightmare frequency (Cameron et al., 2014). Two more studies, in 2009 and 2015, reported decreases in nightmare frequency and intensity following nabilone treatment (Fraser, 2009; Jetly et al., 2015). This also resulted in increased scores in the general well-being questionnaires, However no direct effect was reported on quantity or quality of sleep overall (Jetly et al., 2015). Participants also reported a re-increase in nightmare frequency when stopping nabilone treatment but responded positively when nabilone treatment resumed (Fraser, 2009).  

Another study also investigated the effect of the synthetic cannabinoid dronabinol in two cases of OCD with either comorbid depression or schizophrenia. Following 14-days, significant symptom improvement was observed in both cases, with a significant decrease in Yale Brown Obsessive Compulsive Scale (Y-BOCS) ratings (Schindler et al., 2008). A decrease in Y-BOCS score means increased quality of life, whilst decreased impairment caused via the disorder.              

There are also risks associated with cannabis use and the development of anxiety disorders. Interestingly, frequent cannabis users have a high prevalence of anxiety disorders, and individuals with anxiety disorders have relatively high rates of cannabis use (Crippa et al., 2009). This would suggest that high-concentrations of THC are associated in the development of acute anxiety (Manzanares et al., 2004; Roitman et al., 2014). There are also other studies that associate cannabis use with the on-set and development of bipolar disorder and PTSD. However, findings on depression or other anxiety disorders aren’t as clear cut on the effect of cannabis. There have only-been very few high-quality studies on cannabinoids pharmaceutical effects in clinical settings, and many older studies have small cohorts of participants and outdated experimental designs for longitudinal studies (Botsford et al., 2020). Since results on Cannabis consumption for treating anxiety are contrasting, more research is needed in order to fully understand the associated risks but more importantly the potential benefits of cannabis to soothe our daily lives.