Feasibility of Cannabidiol for the Treatment of Long COVID This is an open label, phase 2 clinical trial to assess the feasibility of a cannabidiol (CBD) dominant medicinal cannabis for the The pandemic caused by Sars-CoV-2 (COVID-19) has been a great concern for public and mental health systems worldwide. The identification of risk groups is essential for the establishment of preventive and therapeutic strategies, as for substance users. During COVID-19 pandemic, there was an increase in the use of psychoactive substances during the lockdown, including cannabis. This commentary reviews relevant findings and discusses scientific evidence on the risks of worse clinical and psychiatric complications due to coronavirus disease COVID-19 in subjects who use cannabis. Although they are not included as a risk group in the health recommendations for that disease, they may have a more vulnerable respiratory system to viral diseases. There are certain similarities between the harmful cardiovascular and respiratory effects of cannabis use and those of smoking. Due to the different modes of smoking, cannabis chemicals are retained in the body for longe and may also contain other toxic substances such as tar, a substance found in tobacco and which has been associated with the development of lung cancer, bronchitis and pulmonary emphysema. Therefore, we discuss if individuals who use cannabis regularly might be more vulnerable to COVID-19 infection. This population deserves more clinical attention worldwide and this manuscript can help clinicians become more aware of cannabis risks during pandemics and develop specific intervention strategies. COVID-19 pandemic has resulted in devastating mortality and morbidity consisting of socioeconomic and health effects that have included respiratory/pulmonary, cardiovascular, mental health and neurological consequences such as anxiety, depression, and substance use. Extensive efforts are underway to …
Feasibility of Cannabidiol for the Treatment of Long COVID
This is an open label, phase 2 clinical trial to assess the feasibility of a cannabidiol (CBD) dominant medicinal cannabis for the treatment of Long COVID. The primary aim is to assess the feasibility of recruiting and retaining individuals diagnosed with Long COVID into a treatment trial of medicinal cannabis, as well as assessing the safety and tolerability of a dominant medicinal cannabis in this population. The secondary aim is to determine the effect of a CBD dominant medicinal cannabis on symptoms associated with Long COVID.
|Condition or disease||Intervention/treatment||Phase|
|Long COVID||Drug: MediCabilis Cannabis sativa 50||Phase 2|
Long COVID, also defined as post-COVID-19 syndrome, is a common outcome after infection with the SARS-COV-2 virus. The need for treatment and ongoing support for people experiencing Long COVID has been increasingly recognised, including through the establishment of dedicated treatment units within the NHS. While symptoms and their severity may vary greatly between individuals, some of the common symptoms associated with Long COVID include fatigue, breathlessness, pain, sleep disturbances and dysautonomia. In this study, we will test the feasibility of a broad spectrum cannabidiol (CBD) dominant formulation, MediCabilis Cannabis sativa 50, for treating these symptoms in people with a diagnosis of Long COVID. CBD is the primary non-psychoactive ingredient in cannabis, and it is being increasingly used in the treatment of symptoms which are similar to those associated with Long COVID. Additionally, there is some evidence that CBD may be effective in reducing inflammation associated with COVID infection. Together, this evidence suggests that it is possible that CBD may be an effective treatment for people diagnosed with Long COVID. We will therefore conduct a feasibility trial in which 30 people are prescribed CBD dominant medical cannabis. Patients will take this medication daily for a total of 21 weeks (2-week titration period, 18-weeks steady dose, 1-week dose reduction), followed by 3-weeks with no medication. We will collect monthly self-report assessments of common symptoms including breathlessness, fatigue, mood, cognition and pain via a smartphone app, as well as real-time data on heart rate, physical activity and sleep using wearable technology. We will also collect daily self-report assessments of key symptoms (mood, pain, fatigue and breathlessness) via a smartphone app for 7 days per 28 days. Our study will establish whether it is feasible to recruit and retain patients with a diagnosis of Long COVID into a trial of a CBD dominant medical cannabis. We will also monitor whether there are any side effects to assess the safety and tolerability of a CBD dominant medical cannabis. Our results will determine the feasibility of medicinal cannabis in the treatment of Long COVID and whether it is safe to use.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Safety and Tolerability of Full Spectrum Cannabidiol Dominant Medicinal Cannabis in Treating Symptoms Associated With Long COVID: A Feasibility Study|
|Actual Study Start Date :||April 14, 2022|
|Estimated Primary Completion Date :||April 2023|
|Estimated Study Completion Date :||April 2023|
The medicinal cannabis used for this study is MediCabilis Cannabis sativa 50, a full spectrum CBD dominant plant based medicinal cannabis containing 50 mg/ml CBD and 2 mg/ml THC.
On commencing the oral medication, it will be titrated over a 2 week period to a dose of 1 ml twice a day (total dose 2 ml = 100 mg CBD and 4 mg THC). Participants will be given a written titration schedule at the initial clinic visit. There will be the potential for a further dose increase to a total dose of 3 ml per day (150 mg CBD and 6 mg THC) at the 1-month follow-up visit.
Recruitment rate [ Time Frame: 12 months (48 weeks) ]
Retaining participants in a six month trial of medicinal cannabis using the proposed battery of assessments. Retention rate (%) of participants enrolled into the trial who complete the six-month protocol.
Long COVID symptoms [ Time Frame: 5 months (20 weeks) ]
Assessed by the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS, Sivan et al., 2021). This scale includes: breathlessness, cough/ voice, swallowing/ nutrition, fatigue, continence, cognition, pain/discomfort, anxiety, depression, post-traumatic stress disorder, communication, mobility, personal care, activities of daily living, social role, perceived health status and family/carers views. The C19-YRS provides an overview of 3 outcomes: symptoms severity score, functional disability score and global health score.
Fatigue will be assessed using the nine item Fatigue Severity Scale (Krupp et al., 1989). This scale, which was initially designed for use in multiple sclerosis and systemic lupus erythematosus has been used extensively across multiple disorders and has bene demonstrated to have good reliability and validity. Each of the nine items in this scale is assessed on a seven-point scale from 1 (strongly disagree) to 7 (strongly agree). Thus, the composite scale ranges from 9 to 63 with higher ratings representing more severe fatigue.
The health-related quality of life instrument that will be used in this study is the EuroQol 5 Dimensions (EQ-5D; Devlin et al., 2017). It is a widely used, validated, and reliable tool that assesses the quality of life of patients in many disease areas through assessment of the severity of each of 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). Each dimension has 5 levels (1-5): no problems, slight problems, moderate problems, severe problems and extreme problems. The digits for the five dimensions can be numerically summed into a single number, varying from 5 to 25 with higher numbers representing a lower quality of life. In addition, this measure contains a 100-point visual analogue which asks respondents to rate their current health with higher numbers representing better health.
The Brief Pain Inventory Short Form (BPI-SF; Cleeland, 1989; Cleeland & Ryan, 1994), a 9 item self-administered questionnaire, will be used to evaluate the severity of a patient’s pain and the interference of this pain on the patient’s daily feeling and functioning. The patient rates their worst, least, average, and current pain intensity, list current treatments and their perceived effectiveness, and rate the degree that pain interferes with general activity, mood, walking ability, normal work, relations with other persons, sleep, and enjoyment of life on a 10-point scale. The BPI scale defines pain as follows: 1-4=Mild Pain, 5-6=Moderate Pain, 7-10=Severe Pain. Thus, a mean of the items can be presented with higher ratings representing more severe pain. In addition, the mean of the 7 items assessing interference, each rated on a scale from 0 to 10, will be used as a measure of mean pain interference with higher numbers representing more interference.
The Generalised Anxiety Disorder Assessment (GAD-7; Spitzer et al., 2006) will be used to measure depression. The GAD-7 is a seven-item instrument that is used to measure or assess the severity of generalised anxiety disorder (GAD). Each item asks the individual to rate the severity of their symptoms over the past two weeks. Response options include “not at all”, “several days”, “more than half the days” and “nearly every day”. The GAD-7 score is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of “not at all,” “several days,” “more than half the days,” and “nearly every day,” respectively, and then adding together the scores for the seven questions. GAD-7 total score for the seven items ranges from 0 to 21.
The Patient Health Questionnaire (PHQ-9; Kroneke et al., 2001) will be used to measure mood/ depression. It is a reliable and valid measure of depression severity and is comprised of a 9-item self-rated instrument that has been validated in general populations, medical populations and psychiatric samples.
It is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of not at all, several days, more than half the days, and nearly every day, respectively. PHQ-9 total score for the nine items ranges from 0 to 27.
Assessed using Pittsburgh self-report questionnaires and wearable technology. The Pittsburgh Sleep Quality Index (PSQI) includes a scoring key for calculating a patient’s seven subscores, each of which can range from 0 to 3. The subscores are tallied, yielding a “global” score that can range from 0 to 21. A global score of 5 or more indicates poor sleep quality; the higher the score, the worse the quality. Mean ratings on this global score will be used in our analyses. Furthermore, the wearable technology (i.e. Fitbit) will provide the patients’ total time in sleep and time in sleep stages (light, deep and REM sleep), as well as a daily Sleep Score accessed via the Fitbit app. Seven day averages (means) of the Fitbit measures will be calculated for each participant across the duration of the study.
The wearable technology will provide 24/7 heart rate tracking and heart rate variability. We will have access to the daily resting heart rate and averages across discrete periods. We will analyse mean resting heart rate (beats per minute). Variation in the time between each heartbeat (heart rate variability) will be accessed via the Fitbit app. Seven day averages (means) of the Fitbit measures will be calculated for each participant across the duration of the study.
Activity levels assessed via wearable technology. The wearable technology (i.e. Fitbit) tracks all-day activity including number of steps walked, distance walked (expressed in kilometres), floors climbed, active minutes and calories burned. We will analyse the seven-day mean number of daily steps, distance walked, stairs climbed, active minutes and calories burned. Seven day averages (means) of the Fitbit measures will be calculated for each participant across the duration of the study.
Oxygen saturation expressed as percentage saturation, with typical numbers being in the region of 95% will also be assessed via the Fitbit. Seven day averages (means) of the Fitbit measures will be calculated for each participant across the duration of the study.
Assessed using daily reports of key symptoms (breathlessness, fatigue, mood and pain) adapted from the COVID-19 Yorkshire Rehabilitation Scale. Each symptom will be scored out of 10 for a period of 7 days per 28 days, to produce an average score for each symptom.
Multiple clinical risks for cannabis users during the COVID-19 pandemic
The pandemic caused by Sars-CoV-2 (COVID-19) has been a great concern for public and mental health systems worldwide. The identification of risk groups is essential for the establishment of preventive and therapeutic strategies, as for substance users. During COVID-19 pandemic, there was an increase in the use of psychoactive substances during the lockdown, including cannabis. This commentary reviews relevant findings and discusses scientific evidence on the risks of worse clinical and psychiatric complications due to coronavirus disease COVID-19 in subjects who use cannabis. Although they are not included as a risk group in the health recommendations for that disease, they may have a more vulnerable respiratory system to viral diseases. There are certain similarities between the harmful cardiovascular and respiratory effects of cannabis use and those of smoking. Due to the different modes of smoking, cannabis chemicals are retained in the body for longe and may also contain other toxic substances such as tar, a substance found in tobacco and which has been associated with the development of lung cancer, bronchitis and pulmonary emphysema. Therefore, we discuss if individuals who use cannabis regularly might be more vulnerable to COVID-19 infection. This population deserves more clinical attention worldwide and this manuscript can help clinicians become more aware of cannabis risks during pandemics and develop specific intervention strategies.
The pandemic caused by Sars-CoV-2 (COVID19) has caused the collapse of health systems worldwide. Alongside the clinical risk, the appearance or intensification of psychiatric symptoms has also been generating a mental health pandemic within another. The identification of risk groups is essential for the establishment of preventive and therapeutic strategies, for people who are infected by the COVID-19 virus, as well as for users os psychoative substances (PS). During the COVID-19 pandemic, it was identified that the consumption of PS, such as tobacco, cannabis, and cocaine increased the risk of contamination of influenza and was associated with a worse clinical prognosis . A study found that patients with a recent use of PS were at significant risk greater risk of developing COVID-19 compared to patients without a recent substance use disorder (SUD) diagnosis, after adjusting for age, sex, race and types of insurance. Although cannabis users have a lower odds ratio than other drugs (opioids, tobacco, alcohol and cocaine) the risk is five times greater than in people who do not use PS . Thus, cannabis users can be at risk of clinical complications if infected with COVID-19 due to deteriorating health status.
A review conducted in 2019 found that with the increasing increase in cannabis use in the population there has been an increasing number of studies associating cannabis use with serious and life-threatening cardiovascular complications, including acute coronary syndromes, potentially lethal cardiac arrhythmias and ischemic strokes. There are certain similarities between the harmful cardiovascular and respiratory effects of cannabis use and those of smoking. Despite the difference in active ingredients (tetrahydrocannabinol vs. nicotine), along with, due to the different modes of smoking, cannabis chemicals are retained in the body for longer . Furthermore, cannabis may also contain other toxic substances such as tar, a substance found in tobacco and which has been associated with the development of lung cancer, bronchitis and pulmonary emphysema . Although, it is necessary to consider that cannabis is widely used by young populations.
A recent review shows a significant association between cannabis use and symptoms of chronic bronchitis after adjustment for tobacco. Some studies have found a modest reduction in specific airway conductance in relation to marijuana, probably reflecting endoscopic evidence of bronchial mucosa edema among habitual cannabis smokers . The immunosuppressive effects of delta-9 tetrahydrocannabinol (THC) increase the possibility of an increased risk of pneumonia, but further studies are needed to assess this potential risk. Several case series have demonstrated pneumothorax / pneumomediastinum and bullous lung disease in cannabis smokers, but these associations require epidemiological studies for firmer evidence of possible causation. Another recent study reports that the use of vaping causes lung injuries similar to COVID-19 symptoms .
Moreover, most of the people who use cannabis also report tobacco use concurrently. This fact may increase the risk of exposure to toxic substances, as certain co-users (for example, blunt users) tend to have higher levels of carbon monoxide in exhaled air and cannabis smoke may have higher levels of some carcinogens than tobacco smoke . Previous studies have indicated that long-term cannabis use is associated with high mortality rates, heart disease , metabolic syndromes and changes in the immune system . In this sense, when compared to the general population, we can consider that this population may be more vulnerable to infection morbidity and mortality.
In addition to worsening the clinical outcome (especially involving respiratory risk) , cannabis use can generate or increase psychiatric disorders (mainly psychotic symptoms) , intense emotional and behavioral reactions were reported during the pandemic, such as fear, boredom, loneliness, anxiety, insomnia, anger and aggression . These symptoms might be especially intense in people who use cannabis, as it is a population that has high rates of psychiatric comorbidities, is particularly sensitive to dysphoric emotional states and has a low tolerance for frustration and stress . Futhermore, it has been described that people who use cannabis may have high rates of psychiatric disorder comorbidities such as simultaneous substance use (mainly tobacco and alcohol), anxiety disorders, mood disorders and personality disorders, potentiating higher risk symptoms in the current scenario .
A study conducted in the USA found that 36% of adults had symptoms of anxiety disorders compared to 8% of adults in January–June 2020 (N = 17,067). Anxiety can lead to increased substance use, beginning to use SPA, relapses or even increasing the amount of SPA used. . Another study, carried out with 1054 Canadian adolescents, for a previous period and after the beginning of the practices of social distancing, showed that there was an increase in the use of alcohol and cannabis by this population and although 43% of the sample reported using cannabis and alcohol alone, 23% of the sample reported using it with friends during the period of social isolation, thus placing adolescents at risk of contracting COVID-19. Besides, solitary substance use in adolescence during the pandemic, which is associated with mental health problems and coping, can also be a notable concern, worthy of further investigation .
Nevertheless, recent studies also report that the use of cannabinoids offers good results in the treatment of COVID-19, although the endocannabinoid system (ECS) is involved in the regulation of several physiological processes, including sleep and the immune response, its role during infections has not been fully studied. It is well known that the use of this substance increases the susceptibility to infections due to the impact on the modulation of the immune system. Regarding the medicinal or recreational use of cannabis, its influence on the course of an infection, whether caused by bacteria, viruses, parasites, and fungi, has been reported. In this sense, there is evidence to suggest the involvement of ECS in the control and elimination of infectious agents but few studies are available to date. The question therefore arises as to whether ECS increases the severity of viral or bacterial infections and whether consumption of cannabis or synthetic cannabis derivatives / products can influence this risk.
The ECS has a modulating effect on the immune system, but subjects who take cannabinoids or cannabis are not considered immunosuppressed . There are currently no studies available on the incidence and course COVID-19 infection in individuals taking cannabinoids. Pre-existing non-medical consumption of cannabinoids should not be increased, but decreased, during the COVID-19 pandemic, considering potential respiratory complications. One should avoid sharing cigarettes, pipes, or any equipment used for the use of cannabis, as well as any psychoactive substance, as it might be a potential form of transmission of the virus, since the greatest form of dissemination is through droplets of saliva. Likewise, cannabidiol (CBD) cannot be recommended as a possible medication, as the impact on immunity in the case of COVID-19 infection is unclear .
In this context, it is essential that this population is recognized according to their clinical and psychiatric vulnerability. It is vital to think about prevention and protection strategies, as well as the recovery of clinical and mental symptoms. In order to prevent the period of social distance from intensifying consumption and all other risks related to it, several measures must be taken. Among them, one must consider: the information must be used as a form of prevention, damage reduction policy, pharmacological approach, brief intervention, possibly online, during the most critical peak of the pandemic. Therefore, it is relevant to refer these patients to highly complex health treatment centers to evaluate and treat them according to the specificity of this population. The clinical and psychiatric aspects of addiction and its relationship with COVID-19 should be noted. There are few studies conducted to date on the increased risk of COVID-19-related morbidity and mortality in this population, although the gray literature has shown data showing the increase in cannabis use in the United States during this period. Epidemiological studies should be carried out to assess a potential increase in cannabis use by the population and investments should be intensified, as well as directed to psychoeducation, to preventive and therapeutic approaches to this substance and its consequences, enhanced by the inherent pandemic risks.
Our manuscript contains clinically relevant notes on the risks of worse clinical complications due to COVID-19 in marijuana users. Although not included as a risk group in global health recommendations, marijuana users may be more vulnerable to contagion and worsening of their clinical condition due to covid-19 infection are at high risk, this can be explained both by the action of the psychoactive substance on central nervous system and not immune system, as well as due to the method of use that this substance is usually used. In addition, the behavior of marijuana users can make them even more vulnerable to SARS-CoV-2 infection. At this stage that Pandemia is in, with increasing rates of morbidity due to contagion by COVID-19, this population deserves more clinical attention worldwide. Therefore, our letter manuscript can help doctors become more aware of this group and can develop a specific approach.
COVID-19 and Cannabidiol (CBD)
COVID-19 pandemic has resulted in devastating mortality and morbidity consisting of socioeconomic and health effects that have included respiratory/pulmonary, cardiovascular, mental health and neurological consequences such as anxiety, depression, and substance use. Extensive efforts are underway to develop preventive vaccines and therapeutics such as remdesivir, dexamethasone, convalescent plasma, and others to treat COVID-19 but many report residual mental health problems after recovery. Cannabis products such as cannabidiol (CBD) are being advertised for the treatment of COVID-19 associated mental health problems and substance use disorders. This commentary will briefly clear the myth that CBD can ameliorate a wide range of COVID-19 associated health effects including anxiety, depression, or any substance use disorder, and show that there is a clear lack of sufficient unbiased clinical evidence from well-designed double-blind, placebo-controlled clinical trials to prove the antianxiety or antidepression therapeutic properties of CBD and support its wide use as medicine to treat COVID-19- associated mental health conditions or substance use disorders. Finally, we suggest that addiction physicians must play an important role in dealing with their patients requesting CBD prescription for treating any of these conditions.
Copyright © 2020 American Society of Addiction Medicine.
Conflict of interest statement
Research grants to the institution from Merck, Inc., Gillead Sciences, and Airbutus pharmaceuticals. Other authors report no conflicts of interest.
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