Today I woke up feeling blue, feeling stressed. I consider myself privileged, I have a job I enjoy, a healthy family and social circle I love and a comfortable house to live in. So why from one day to another,  can I feel happy, ready to get things done, then anxious and stressed about my day to come? This is all part of mental health; mental health is “a state of well-being in which the individual realizes his or her own abilities, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to his or her community” (WHO). Mental health affects the emotional, social and psychological domains of our life. It has an impact on how we think, how we feel, how we act, how we communicate. 

Mental health used to be only considered in terms of disorders, such as those described in the Diagnostic and Statistical Manual of mental disorders (DSM-V, 2013). However, mental illnesses and mental health are different. You can be free of a mental illness and still have poor mental health. 

The COVID-19 pandemic emphasized the importance of mental health in every individual as billions of people fell into confinement, greatly affecting their mental health status. Health workers and essential workers on the front-line during the pandemic were even more affected. A survey conducted in Canada showed that “one in four (25%) Canadians aged 18 and older screened positive for symptoms of depression, anxiety or posttraumatic stress disorder (PTSD) in spring 2021, up from one in five (21%) in fall 2020”(Statistic Canada, 2021).

The pandemic also highlighted the critical need for the government to provide better, more affordable, and faster access to mental health services. In Quebec, the current wait time for a public sector psychological consultation can be up to two years, which is problematic, as people seeking help may be in crises, and mental health conditions are likely to deteriorate during that time. 

This is why the theme for the 2021 world mental health day was “Mental health care for all: let’s make it a reality”.

At Santé Cannabis we recognize the need for multi prong approaches to mental health and wellbeing; that there is a need for therapy, medication, community, education, mindfulness, support and more in an individualized approach for each specific person. At Santé Cannabis we try to provide our patients and their community with as many of these supports as possible, but our primary ability is in providing access to trained professionals who can help people navigate medical cannabis to improve their mental health.  

How can Cannabinoid-Based Medicines (CBMs) Help? 

After years of tabous and marginalisation, mental health issues are now being discussed at the forefront and finally considered. CBM research is riding the wave with an increasing number of studies on the topic. Whereas we acknowledge many mental health symptoms and mental illnesses exist, the following sections will detail research on cannabinoid-based medicines (CBMs) and anxiety, depression, and post-traumatic stress disorder (PTSD). For those interested in reading more about current evidence on other mental health and psychiatric disorders, such as schizophrenia, attention-deficit hyperactivity deficit or bipolar disorder, several recent reviews have been published (Black et al., 2019; Sarris et al., 2020; Scherma et al., 2018). 

Anxiety and Depression in the Literature

As seen in the recent Statistic Canada survey, anxiety and depression are the most frequent mental health conditions experienced by Canadians. Despite limited clinical evidence from randomized clinical trials many observational studies show that mental health symptoms are the second reason for CBM use after chronic pain (Bonn-Miller et al., 2014; Lintzeris et al., 2020; Lucas et al., 2017).

Santé Cannabis recently published a blog post on anxiety and CBMs, discussing what anxiety is and how CBMs may be a treatment to consider.  CBMs generally contain diverse concentrations of the primary cannabinoids, Δ9-tetrahydrocannabinol (THC), and cannabidiol (CBD). Even though the exact mechanism of action is still not fully understood, CBD has shown to have anxiolytic (anti-anxiety) effects (Campos et al., 2012). Multiple clinical trials indicate a reduction in subjective anxiety ratings with CBD intake compared to placebo in response to an anxiety-provoking stimulus (Zuardi et al., 2017; Bergamaschi et al., 2011; Skelley et al., 2020 for a review on CBD and anxiety disorders). 

There is scarce scientific literature to address the relevance of CBMs for the treatment of depressive disorders (Turna et al., 2017). On the other hand, patients frequently use cannabis for medical purposes for the relief of depressive symptoms, and 7 out of 9 cross-sectional studies on medical cannabis reported mood improvement (Walsh et al., 2017). 

Besides, improvements in mood were generally reported in studies assessing medical cannabis for chronic pain, multiple sclerosis, HIV, and other conditions (Ellis et al., 2009; Lahat et al., 2012; Page & Verhoef, 2006; Ware et al., 2015)

Anxiety and Depression in our Clinical Experience

Observational evidence from Santé Cannabis patients are in line with the literature. Across the dataset of 1,342 Santé Cannabis patients assessed between 2017 and 2019, 5.4 % of patients have a primary diagnosis related to mental health. However, 59% of patients have identified anxiety or mood-related secondary symptoms. Furthermore, anxious and depressive symptoms frequently co-occur in patients with a primary diagnosis related to chronic pain: 73% of Santé Cannabis patients with a primary diagnosis of chronic pain also have anxiety or mood-related secondary symptoms. 

In a recent study, we also showed that patients reported decreased anxiety scores after three months of CBD treatment (Rapin et al., 2021). 

Post-Traumatic Stress Disorder in the literature

Post-Traumatic Stress Disorder (PTSD) is characterized by the exposure to trauma and symptoms such as intrusive memories, avoidance of distressing factors, increased arousal and alteration of mood/cognition. Nightmares and sleep disturbances are very frequent. PTSD can affect an estimated 9.2% of Canadians in their lifetime, with the disorder twice as prevalent in women compared to men  (Katzman et al. 2014).

CBMs are becoming more recognized as a potential treatment for PTSD symptoms; trials conducted on nabilone and THC have demonstrated some benefits in improving sleep disturbances, but larger and longer trials (and more randomized controlled trials) are needed to provide good-quality evidence for cannabinoids’ use in PTSD. 

That being said, there are increasing reports of patients self-treating with cannabis as well as anecdotal evidence and case reports that cannabis could reduce PTSD symptoms (Hindocha et al., 2020; Fernández-Ruiz et al., 2020). Anecdotal evidence may not be as scientifically or clinically lauded; but when little evidence from randomized controlled trials is available, anecdotal data should not be disregarded. Even-though, research is still in its infancy and has not yet found the exact cannabinoid formulation to alleviate patients’ PTSD-related symptoms, current trial results indicate promising therapeutic avenues that should be considered.

Post-Traumatic Stress Disorder in our Clinical Experience

“I feel a tremendous amount of compassion for people living with post-traumatic stress disorder. 

Since working at Santé Cannabis, I’ve been fortunate to be able to learn so much more about this condition during my interviews with patients with this diagnosis. What has stuck with me the most is all the areas of life that are affected by this disorder. I think of the nightmares, the anger, the pain, the vivid images that keep coming back, and the severe anxiety that prevents one from functioning but also makes interpersonal relationships very difficult. 

I think of one veteran in particular that I interviewed several years ago. He told me about having to make a few rounds around his house every night before he could go to bed. He also told me about all his former colleagues and friends that had PTSD and took their own lives because they couldn’t find a way to regain a reasonable quality of life. He had heard about medical cannabis from a veteran friend who said he had found a lot of relief from taking CBD oil. The patient I was evaluating was very shocked by this as he had been against cannabis all his life and after 20 years of researching and trying to find what would help him with his PTSD symptoms, he could not believe that the answer could be cannabis! 

What I can say is that, In my practice and that of many of my colleagues, we indeed see significant improvement in many of these patients with medical cannabis.” – Andrée Charbonneau, RN

During Dr. Howard Mitnick’s workshop at the Conference on Cannabinoid-based medicine on May 5th, 2021, Dr. Mitnick also shared his clinical experience with medical cannabis and post-traumatic stress disorder. In his clinical practice, particularly in 2016 when many soldiers deployed to Afghanistan returned, Dr. Mitnick said he was impressed by the very significant impact medical cannabis had on patients that were struggling with PTSD-related anxiety, grasping at anything to just stop their brain.

Despite this, statistics show that the Quebec population is under-represented in Canada’s pool of patients with access to medical cannabis and veterans are no exception, regardless of the extensive Veterans Affairs Canada coverage.

We also know that many veterans who have had a prescription do not have support from medical professionals to navigate their medical cannabis. We want to help improve this situation. That’s why we offer educational presentations open to the public to inform people living with post-traumatic stress disorder about this treatment option, and to let them know about our services and our mission. 

Next for CBMs and Mental Health Disorders

This brief overview on a few mental health disorders and symptoms demonstrates the pressing need of more research to evaluate and assert the impact of CBMs on such disorders. Increasing evidence points towards a beneficial effect of CBD on anxiety symptoms, however there is still little evidence for depression. THC may reduce PTSD symptoms but again, current evidence is too low to definitively conclude. 

We know that regardless of the formal, scientific evidence, people are using medical cannabis to treat their mental illness and try and improve mental health. We believe in empowering people to make the best decisions with the best evidence, and therefore we need continued study in this critical area.

While evidence is still weak, results are encouraging for future research to take place. The favorable safety profile of CBMs, compared to anxiolytics and antipsychotics for example, as well as the observational reports of patients mentioning decreased symptoms and improved quality of life following CBMs are to be considered to those resistant to further pursuing research on the topic. 

While we wait for strong clinical evidence to support the potential of CBMs in mental health disorders, mental health symptoms are still occurring in many people, negatively affecting their everyday life. 

The testimony of one of our patients illustrates accurately the impact of mental health symptoms on everyday life: 

“It took me a while to admit it to myself, but I have lived with a lot of anxiety since a very young age. This anxiety has had an impact on my ability to work and on my interpersonal relationships, not to mention the immense impact on my body: from daily painful tensions to gastrointestinal difficulties. However, I can say that recognizing anxiety has allowed me to better manage it, to regain my quality of life and my self-esteem.

I had to learn to say no to others, but also to myself. I learned to reduce my financial needs so that I could work less and have more time to invest in my general health.

I felt guilty about this and felt like an “imposter” who could have done better. However, my family doctor was very helpful in validating my feelings and praising me for taking care of myself. Just the fact that she took this approach with me was very helpful in accepting myself and my limitations. 

I think the support of my friends and my doctor made all the difference.”

– Nancy Raymond, Santé Cannabis patient

We know that mental health is extremely complex and even with treatments demonstrated for use through rigorous research people regularly need to trial and error a combination of treatments to find what works for them and this may change over their lifetime. Adding another treatment to this cause could be the treatment that works for the next person. 

In our clinical practice we have enough data to make informed decisions with our patients, understand drug interactions, and watch for contraindications. We spend time learning about each person before providing an individualized treatment plan and providing regular follow-up – with the objective to ensure that their CBM plan is working towards their mental health goals without side effects. We also know that many people continue to self-treat and may not understand the complexity of using CBMs to treat mental health issues. Mental health is health and needs to be treated with the same level of care and follow up as any other health condition and new medication treatment. We encourage the training of healthcare professionals to understand medical cannabis in the treatment of mental health issues, and support research to improve our evidence-base as we all work together to ensure that patients’ mental health is treated properly. 

Conclusion

Mental health plays a significant role in our life, it is crucial that it is taken seriously by both the individuals and governments. Health is not simply the absence of disease, it is a complete state of physical, mental and social wellbeing (WHO) and for many of us, the past 2 years have highlighted the important role our mental and social wellbeing play in our daily experience.

For me, when I start feeling anxious, I step away from screens, take a walk in my neighbourhood and try to put things into perspective – these are strategies I developed that work for me. Some days even that is hard to prioritize, yet I have learned that it  is essential to listen to my wellbeing and adjust my day to ensure favorable mental health. 

I’m fortunate that these strategies work for me, but in my life, work and research, I know that these strategies don’t work for everyone. For some, it can be helpful to have positive and good-hearted social interactions, satisfying sleep and eating habits, exercise, outdoors, work-family balance, and mindfulness. For others it may be the support of professionals with group or individualized therapy, and/or medication. At Santé Cannabis we hope that among the medications considered for mental health are CBMs, and we encourage further research, and for those interested in trying CBMs to reach out to their doctor.  

If you feel deterioration in your mental health it is important to seek help:

• https://wellnesstogether.ca/en-CA
• https://www.canada.ca/en/public-health/services/mental-health-services/mental-health-get-help.html
• https://www.quebec.ca/en/health/advice-and-prevention/mental-health
• https://www.crisisservicescanada.ca/en/

At Santé Cannabis, our clinicians and nurses are here to help our patients find the right treatment for their symptoms. We also offer our patients support groups, presentations and tools including stress management and mindfulness.

Santé Cannabis is committed to advancing knowledge about mental health and cannabinoid-based treatments, and as such, we offer research services to companies and institutions interested in developing clinical studies. 

For clinicians currently treating people with mental health symptoms who wish to include medical cannabis in their practice, our preceptorships are available to all local and international physicians. For prescribers in Quebec, we also offer a free training program on cannabinoid-based treatments and how to prescribe them.

Author: Lucile Rapin avec le soutien de Charlotte Bastin et Eva McMillan

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

It would be difficult to deny the impact of the COVID-19 pandemic on anxiety and anxiety disorders in the population. Whether there are new anxiety symptoms or an exacerbation of existing ones, most of us know people who have been affected, if not ourselves. 

Reasons for increased anxiety in 2020/2021? 

Social isolation, monetary stress, sudden major changes, uncertainty about the future, sensation of losing control, fear of illness, etc. Some people have been in extremely close contact with COVID-19: people who have been infected, people who have lost loved ones or who have feared losing them, essential workers and, of course, healthcare professionals in many areas.

According to a  survey by Statistics Canada and the Public Health Agency of Canada conducted between September and December 2020 and published in March 2021, 7 out of 10 Canadians have been negatively affected by the pandemic and 2 out of 5 have experienced distress related to it. 

A survey was also conducted by the University of Sherbrooke on the psychosocial impacts of the pandemic: 

“What we see today is that levels of depression and anxiety in Quebec are currently considerably higher than what was observed pre-pandemic. These numbers are similar to the levels observed in the community of Fort McMurray, 6 months after the 2016 forest fires” (Dr Mélissa Généreux, septembre 2020 – Link available in french)

WHAT IS ANXIETY?

Anxiety is an emotion characterized by feelings of tension, worry and physical changes such as increased blood pressure.

Although this emotion can be useful to us, it sometimes takes on magnitudes that have a negative impact on our ability to function, our quality of life and on our interpersonal relationships. It can even have a significant impact on our long-term health. The effects that anxiety and anxiety disorders can have on a person are real, undeniable and deserve our attention.

According to Anxiety Canada, there are 11 categories of anxiety disorders in adults: Agoraphobia, Separation Anxiety, Health Anxiety, Body-Centred Repetitive Behaviours, Specific Phobia, Generalized Anxiety Disorder, Compulsive Hoarding Disorder, Social Anxiety Disorder, Post-Traumatic Stress Disorder, Obsessive Compulsive Disorder and Panic Disorder.

In addition to considering the impact of anxiety on a person, specialists also evaluate 4 broad categories of symptoms and their frequency: 

• Physical responses
• Thoughts
• Emotions
• Behaviors

If you think you may be suffering from anxiety, an anxiety disorder or any other psychological condition, it is important to talk to your doctor. You can also refer to several resources such as those offered by the Government of Canada on their website.

TREATMENTS AVAILABLE AT THIS TIME

• Pharmaceutical Treatments: The main pharmaceutical treatments for anxiety are usually antidepressants. Benzodiazepines may also be prescribed for acute symptoms and/or until the therapeutic effects of the antidepressant are achieved, as antidepressants can take several weeks to have an impact on mood-related symptoms.
• Psychotherapy: Several approaches in psychology are recommended for the management of anxiety, such as cognitive-behavioral therapy and psychodynamic therapy, and can be of great help. 
• Exercise: Experts agree that exercise has great benefits on anxiety. This is because physical activity activates the production of neurotransmitters in the brain. These neurotransmitters include those targeted by many antidepressants such as serotonin, which helps combat anxiety.
• Mindfulness techniques: Often associated with meditation, mindfulness is an approach, an attitude as well as a set of techniques including meditation. Many of these techniques can also be practiced in everyday life, for example, while eating, walking or exercising. These techniques allow you to better understand and identify what triggers anxiety. They allow you to take a step back from these stressors and make it easier to manage them. Moreover, as this approach can be very beneficial both mentally and physically, we have recently partnered with MindSpace to offer opportunities for our patients to practice mindfulness techniques. If you are interested, you can join the mindfulness-based stress reduction program this coming fall. Our patients are eligible to 20% off. You can ask our clinic staff for the promo code!
• Cannabinoids: The endocannabinoid system present in our body also plays a role in the mechanisms related to anxiety. This is why they are also used as an adjunctive therapy for anxiety symptoms.

A treatment that combines several options (e.g., pharmaceutical treatment and psychological therapy) is far more effective than each treatment option alone.

CANNABINOID-BASED TREATMENTS FOR ANXIETY

The human body has an endocannabinoid system that manages many functions, including emotional behavior. This system includes cannabinoids and enzymes produced by this system that bind to various receptors. Cannabis is a plant that includes more than 100 cannabinoids, the main ones being cannabidiol (CBD) and delta-9 tetrahydrocannabinol (THC). We also know that CBD interacts with many receptors/anxiety targets. Indeed, strong preclinical evidence supports the use of CBD as a short-term treatment for generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, and post-traumatic disorder (Blessing et al., 2015). The promising effects demonstrated by CBD in the preclinical phase – certainly influencing the “CBD craze” – highlight the critical need for more clinical studies. We recently published an article on this craze, and you can read it here. 

However, it is important to note that, for now, only limited evidence supports the use of medical cannabis for anxiety disorders (Walsh et al., 2015). 

Nevertheless, Santé Cannabis has observed some success with medical cannabis for the treatment of anxiety. In addition, in reviewing our patient data, we have also seen positive results with medical cannabis in patients with unrelieved secondary symptoms of anxiety or depression (chronic pain being the most common primary condition) (Rapin et al., 2021).  

The place of medical cannabis in the treatment of anxiety

On May 5th 2021, Santé Cannabis held a large-scale Conference on Cannabinoid-Based medicine focused on International Research and Innovation. As part of this event, Dr. Howard Mitnick presented a workshop exploring the question regarding the place of medical cannabis in the treatment of anxiety and managed to make this interactive workshop both amusing and incredibly insightful. He delivered powerful arguments starting with stating that cannabis isn’t the only field where evidence-based medicine and it’s usual hierarchy is a challenge. Obstetric and breast-feeding medicine are examples among others and for various reasons. In his clinical practice, particularly in 2016, when many veterans were coming back from Afghanistan, Dr. Mitnick said he was impressed by the very significant impact cannabis had on patients that were struggling with PTSD-related anxiety, grasping at anything to just stop their brain. He humorously pointed out that “if this talk was about what evidence there is supporting the use of medical cannabis on anxiety, it would be a very short talk.” The question then becomes,  how can we, as clinicians and as a community, negotiate with this limited evidence, while clinicians see that medical cannabis helps many patients effectively manage their anxiety?

ANXIETY AT SANTÉ CANNABIS

As clinicians, we have seen first hand the improvement many patients are able to experience with medical cannabis treatment. However, we know that individual success stories are not enough to provide insight into how to prescribe this medicine on a large scale. Through the use of our real-world data, our clinic strives to provide better patient care by advancing science including data regarding the place of cannabis in the treatment of anxiety.

We also offer our patients support groups, presentations and tools including stress management and mindfulness.

The combination of formal training of healthcare professionals and high quality research is essential to increase the selection of anxiety treatments and provide the best care for patients. 

Join us in working to develop the highest quality treatments for people with anxiety.  

Santé Cannabis is committed to advancing knowledge about anxiety and cannabinoid-based treatments, and as such, we offer research services to companies and institutions interested in developing clinical studies. 

For clinicians currently treating people with anxiety who wish to include medical cannabis in their practice, our preceptorships are available to all local and international physicians. For prescribers in Quebec, we also offer a free training program on cannabinoid-based treatments and how to prescribe them.

Author

Andrée Charbonneau, Nurse Coordinator

With thanks to the Research Department

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

During this unprecedented crisis, Mental Health Week offers an important opportunity to discuss misconceptions and taboos surrounding medical cannabis and mental health, particularly in the context of the growing popularity, evolving access and new regulatory frameworks. 

Indeed, healthcare professionals and their patients are increasingly turning to medical cannabis as a possible option when conventional approaches to treating anxiety have proven ineffective. 

Yet the use of medical cannabis as a mental health treatment is particularly complex, and high-quality clinical evidence is still limited and sometimes conflicting. Treatments  are also often poorly understood by patients, some of whom have unrealistic expectations about possible therapeutic benefits. 

THE IMPORTANCE OF SUPPORT AND SUPERVISION

In Santé Cannabis’ own experience, the effects of cannabinoids are highly individualized. Clinical approaches to different mental health conditions also each rely on very specific cannabis compounds, dosages and administration methods. 

The integration of individualized education and supervised access to cannabinoid treatments is crucial to ensure that patients struggling to find effective treatments receive the support they need to make safe and informed decisions. 

In regulatory environments like Canada and some U.S. states, where cannabis is legal and readily available, integration into healthcare models can help mitigate the risks of unsupervised use. 

Any decision to use medical cannabis to treat a mental health condition should be taken in conjunction with the close support of a healthcare professional and a mental health expert. 

SUFFERING ANXIETY? YOU’RE NOT ALONE

According to a 2016 Canadian Public Health Agency study, more than three and a half million Canadians are believed to live with anxiety or a mood disorder. Anxiety disorders encompass a range of conditions, including generalized anxiety disorder, social anxiety disorder, specific phobias and other conditions characterized by significant feelings of anxiety and fear. 

While cognitive behavioural therapy or psychotherapy are often recommended as non-pharmaceutical treatment options, only about 20% of Canadians with anxiety or mood disorders report having undergone psychological counselling to help manage their condition. In contrast, more than 90% report using or having used prescription medication to treat their disorder. 

Serotonin inhibitors, conventional anxiolytic medication like benzodiazepine and antidepressants are the most commonly prescribed pharmaceutical treatment for anxiety. Although these treatments have proven efficient, undesired and adverse side effects are often reported from their use.

When patients do not respond well to these pharmaceutical treatments, the medical use of cannabidiol (CBD) products can be a safe alternative worth exploring. 

CBD AS A COMPLEMENTARY TREATMENT: DESIGNING TREATMENT PLANS WITH SANTÉ CANNABIS

The tolerability and generally good safety profile of CBD, as well as its demonstrated effectiveness as an anxiolytic have made it the cannabinoid of choice to treat anxiety.[i] After assessment of medical history, pharmacological and non-pharmacological interventions and screening for potential risk factors, patient treatments for anxiety at Sante Cannabis are usually initiated with ingestible CBD oils, administered with a drop counter, in capsules or a spray. 

In case of acute anxiety symptoms or panic attacks, the use of sublingual sprays or the inhalation of dried flowers or extract with a vapourizer are recommended for their rapid onset of action, which occurs in seconds or minutes. The onset of effects from ingestion, on the other hand, can take anywhere between one to two hours.

Medical cannabis treatments start with low doses but slowly increase during a titration period. Quebec physicians who want to learn more about dosages, titration recommendations and methods of administration can sign up to the Sante Cannabis Prescriber Training Program for convenient online access to clinical guidelines, education material and support.

WHAT ABOUT THC?

For some patients, small doses of THC have proven effective to counter anxiety attacks. The biphasic nature of cannabinoids is important to consider here: THC in small doses has shown anxiolytic properties, but larger doses of THC may induce or worsen anxiety. [ii]  Patients who are inexperienced with cannabis should introduce THC slowly to avoid possible adverse effects.

WHEN IS MEDICAL CANNABIS THE RIGHT TREATMENT FOR ANXIETY?

Most of our patients with anxiety are referred by their psychiatrists directly or their family doctor. When assessing a patient’s file, our staff ensures that first line medications have been tried and that the patient has consulted a mental health professional.  

It’s important to differentiate generalized anxiety from regular anxiety. Regular anxiety is a normal adaptation reaction to stress and is transitory, with a source that can often be identified. In the case of generalized anxiety, on the other hand, the source of the patient’s fear is diffuse.

In cases where medical cannabis may be an option for treating anxiety, patients should view their treatment as just one tool among many, including psychotherapy and lifestyle changes, that can help manage their mental health. Combined with this holistic approach, medical cannabis can be an empowering option for patients with difficult to treat anxiety and help them take action on the entire lifestyle spectrum, from sleep hygiene and exercise to diet and meditation. 

[i] Turna J, Simpson W, Patterson B, Lucas P, Van Ameringen M. Cannabis use behaviors and prevalence of anxiety and depressive symptoms in a cohort of Canadian medicinal cannabis users. J Psychiatr Res [Internet]. 2019 Apr 1 [cited 2019 Mar 4];111:134–9. Available from: http://www.sciencedirect.com/science/article/pii/S0022395618304783

Zuardi AW, Rodrigues NP, Silva AL, Bernardo SA, Hallak JE, Guimar.es FS, et al. Inverted Ushaped dose-response curve of the anxiolytic effect of cannabidiol during public speaking in real life. Front Pharmacol. 2017;8:259.

Crippa, JA, Derenusson, GN, Ferrari TB, Wichert-Ana L, Duran FL, Martin-Santos R, et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder- a preliminary report. J Psychopharmacol [Internet]. 2011 [cited 2019 Aug 19]; Available from: https://www.theroc.us/researchlibrary/Neural%20basis%20of%20anxiolytic%20effects%20of%20cannabidiol%20(CBD)%20in%20generalized%20social%20anxiety%20disorder-%20a%20preliminary%20report.pdf

Bergamaschi MM, Queiroz RHC, Chagas MHN, de Oliveira DCG, De Martinis BS, Kapczinski F, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-na.ve social phobia patients. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2011 May;36(6):1219–26.

[ii] Fusar-Poli P, Crippa JA, Bhattacharyya S, Borgwardt SJ, Allen P, Martin-Santos R, et al. Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch Gen Psychiatry. 2009 Jan;66(1):95–105.