Efficacy and Safety of Cannabidiol Plus Standard Care vs Standard Care Alone for the Treatment of Emotional Exhaustion and Burnout Among Frontline Health Care Workers During the COVID-19 Pandemic: A Randomized Clinical Trial

Free Download JAMA Network Logo Vector from Tukuz.Com“Importance: Frontline health care professionals who work with patients with COVID-19 have an increased incidence of burnout symptoms. Cannabidiol (CBD) has anxiolytic and antidepressant properties and may be capable of reducing emotional exhaustion and burnout symptoms.

Objective: To investigate the safety and efficacy of CBD therapy for the reduction of emotional exhaustion and burnout symptoms among frontline health care professionals working with patients with COVID-19.

Interventions: Cannabidiol, 300 mg (150 mg twice per day), plus standard care or standard care alone for 28 days.

Main outcomes and measures: The primary outcome was emotional exhaustion and burnout symptoms, which were assessed for 28 days using the emotional exhaustion subscale of the Brazilian version of the Maslach Burnout Inventory-Human Services Survey for Medical Personnel.

Results: A total of 120 participants were randomized to receive either CBD, 300 mg, plus standard care (treatment arm; n = 61) or standard care alone (control arm; n = 59) for 28 days. Of those, 118 participants (59 participants in each arm; 79 women [66.9%]; mean age, 33.6 years [95% CI, 32.3-34.9 years]) received the intervention and were included in the efficacy analysis. In the treatment arm, scores on the emotional exhaustion subscale of the Maslach Burnout Inventory significantly decreased at day 14 (mean difference, 4.14 points; 95% CI, 1.47-6.80 points; partial eta squared [ηp2] = 0.08), day 21 (mean difference, 4.34 points; 95% CI, 0.94-7.73 points; ηp2 = 0.05), and day 28 (mean difference, 4.01 points; 95% CI, 0.43-7.59 points; ηp2 = 0.04). However, 5 participants, all of whom were in the treatment group, experienced serious adverse events: 4 cases of elevated liver enzymes (1 critical and 3 mild, with the mild elevations reported at the final 28-day assessment) and 1 case of severe pharmacodermia. In 2 of those cases (1 with critical elevation of liver enzymes and 1 with severe pharmacodermia), CBD therapy was discontinued, and the participants had a full recovery.

Conclusions and relevance: In this study, CBD therapy reduced symptoms of burnout and emotional exhaustion among health care professionals working with patients during the COVID-19 pandemic. However, it is necessary to balance the benefits of CBD therapy with potential undesired or adverse effects. Future double-blind placebo-controlled clinical trials are needed to confirm the present findings.”

https://pubmed.ncbi.nlm.nih.gov/34387679/

“Daily administration of CBD, 300 mg, combined with standard care reduced the symptoms and diagnoses of anxiety, depression, and emotional exhaustion among frontline health care professionals working with patients with COVID-19. Cannabidiol may act as an effective agent for the reduction of burnout symptoms among a population with important mental health needs worldwide.”

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2782994

Lifestyle Interventions Improving Cannabinoid Tone During COVID-19 Lockdowns May Enhance Compliance With Preventive Regulations and Decrease Psychophysical Health Complications

CrossFit | 190629“Studies investigating the psychosomatic effects of social isolation in animals have shown that one of the physiologic system that gets disrupted by this environment-affective change is the Endocannabinoid System. As the levels of endocannabinoids change in limbic areas and prefrontal cortex during stressful times, so is the subject more prone to fearful and negative thoughts and aggressive behavior. The interplay of social isolation on the hypothalamic-pituitary-adrenal axis and cannabinoid tone triggers a vicious cycle which further impairs the natural body’s homeostatic neuroendocrine levels and provokes a series of risk factors for developing health complications. In this paper, we explore the psychosomatic impact of prolonged quarantine in healthy individuals, and propose management and coping strategies that may improve endocannabinoid tone, such as integration of probiotics, cannabidiol, meditation, and physical exercise interventions with the aim of supporting interpersonal, individual, and professional adherence with COVID-19 emergency public measures whilst minimizing their psycho-physical impact.”

https://pubmed.ncbi.nlm.nih.gov/34335317/

https://www.frontiersin.org/articles/10.3389/fpsyt.2021.565633/full

 

Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment

ijms-logo“Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes.

The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson’s disease, Tourette’s syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been proven so far, results from the affinity of these compounds predominantly for the receptors of the endocannabinoid system (the cannabinoid receptor type 1 (CB1), type two (CB2), and the G protein-coupled receptor 55 (GPR55)) but, also, for peroxisome proliferator-activated receptor (PPAR), glycine receptors, serotonin receptors (5-HT), transient receptor potential channels (TRP), and GPR, opioid receptors.

The synergism of action of phytochemicals present in Cannabis sp. raw material is also expressed in their increased bioavailability and penetration through the blood-brain barrier. This review provides an overview of phytochemistry and pharmacology of compounds present in Cannabis extracts in the context of the current knowledge about their synergistic actions and the implications of clinical use in the treatment of selected diseases.”

https://pubmed.ncbi.nlm.nih.gov/33466734/

https://www.mdpi.com/1422-0067/22/2/778

Constituents of Cannabis Sativa

“The Cannabis sativa plant has been used medicinally and recreationally for thousands of years, but recently only relatively some of its constituents have been identified.

There are more than 550 chemical compounds in cannabis, with more than 100 phytocannabinoids being identified, including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).

These phytocannabinoids work by binding to the cannabinoid receptors, as well as other receptor systems. Also within cannabis are the aromatic terpenes, more than 100 of which have been identified.

Cannabis and its constituents have been indicated as therapeutic compounds in numerous medical conditions, such as pain, anxiety, epilepsy, nausea and vomiting, and post-traumatic stress disorder.

This chapter provides an overview of some of the biological effects of a number of the cannabinoids and terpenes, as well as discussing their known mechanisms of action and evidence of potential therapeutic effects.”

https://pubmed.ncbi.nlm.nih.gov/33332000/

https://link.springer.com/chapter/10.1007%2F978-3-030-57369-0_1

In quest of a new therapeutic approach in COVID-19: the endocannabinoid system

Publication Cover“The SARS-Cov-2 virus caused a high morbidity and mortality rate disease, that is the COVID-19 pandemic. Despite the unprecedented research interest in this field, the lack of specific treatments leads to severe complications in a high number of cases.

Current treatment includes antivirals, corticosteroids, immunoglobulins, antimalarials, interleukin-6 inhibitors, anti-GM-CSF, convalescent plasma, immunotherapy, antibiotics, circulation support, oxygen therapy, and circulation support. Due to the limited results, until specific treatments are available, other therapeutic approaches need to be considered.

The endocannabinoid system is found in multiple systems within the human body, including the immune system. Its activation can lead to beneficial results such as decreased viral entry, decreased viral replication, and a decrease in pro-inflammatory cytokines such as IL-2, IL-4, IL-6, IL-12, TNF-α, or IFN-γ. Moreover, endocannabinoid system activation can lead to an increase in anti-inflammatory cytokines, mainly represented by IL-10.

Overall, the cannabinoid system can potentially reduce pulmonary inflammation, increase the immunomodulatory effect, decrease PMN infiltration, reduce fibrosis, and decrease viral replication, as well as decrease the ‘cytokine storm’. Although the cannabinoid system has many mechanisms to provide certain benefits in the treatment of SARS-CoV-2 infected patients, research in this field is needed for a better understanding of the cannabinoid impact in this situation.”

https://pubmed.ncbi.nlm.nih.gov/33683968/

“Concerning the SARS-CoV-2 infection, the cannabinoid effects on the immune system have the potential to limit the abnormal function of the immune system and therefore decrease the overall mortality.”

https://www.tandfonline.com/doi/full/10.1080/03602532.2021.1895204

Antiseizure effects of the cannabinoids in the amygdala-kindling model

“Objective: Focal impaired awareness seizures (FIASs) are the most common seizure type in adults and are often refractory to medication. Management of FIASs is clinically challenging, and new interventions are needed for better seizure control. The amygdala-kindling model is a preclinical model of FIASs with secondary generalization.

The present study assessed the efficacy of cannabidiol (CBD), ∆9-tetrahydrocannabinol (THC), and a combination of CBD and THC in a 15:1 ratio at suppressing focal and secondarily generalized seizures in the amygdala-kindled rat.

Results: CBD alone produced a partial suppression of both generalized seizures (median effective dose [ED50 ] = 283 mg/kg) and focal seizures (ED40 = 320 mg/kg) at doses that did not produce ataxia. THC alone also produced partial suppression of generalized (ED50 = 10 mg/kg) and focal (ED50 = 30 mg/kg) seizures, but doses of 10 mg/kg and above produced hypolocomotion, although not ataxia. The addition of a low dose of THC to CBD (15:1) left-shifted the CBD dose-response curve, producing much lower ED50 s for both generalized (ED50 = 26 + 1.73 mg/kg) and focal (ED50 = 40 + 2.66 mg/kg) seizures. No ataxia or hypolocomotion was seen at these doses of the CBD + THC combination.

Significance: CBD and THC both have antiseizure properties in the amygdala-kindling model, although THC produces suppression of the amygdala focus only at doses that produce hypolocomotion. The addition of small amounts of THC greatly improves the effectiveness of CBD. A combination of CBD and THC might be useful for the management of FIASs.”

https://pubmed.ncbi.nlm.nih.gov/34251027/

https://onlinelibrary.wiley.com/doi/10.1111/epi.16973

Δ9-Tetrahydrocannabivarin (THCV): a commentary on potential therapeutic benefit for the management of obesity and diabetes

figure1“Δ9-Tetrahydrocannabivarin (THCV) is a cannabis-derived compound with unique properties that set it apart from the more common cannabinoids, such as Δ9-tetrahydrocannabinol (THC). The main advantage of THCV over THC is the lack of psychoactive effects. In rodent studies, THCV decreases appetite, increases satiety, and up-regulates energy metabolism, making it a clinically useful remedy for weight loss and management of obesity and type 2 diabetic patients. The distinctions between THCV and THC in terms of glycemic control, glucose metabolism, and energy regulation have been demonstrated in previous studies. Also, the effect of THCV on dyslipidemia and glycemic control in type 2 diabetics showed reduced fasting plasma glucose concentration when compared to a placebo group. In contrast, THC is indicated in individuals with cachexia. However, the uniquely diverse properties of THCV provide neuroprotection, appetite suppression, glycemic control, and reduced side effects, etc.; therefore, making it a potential priority candidate for the development of clinically useful therapies in the future. Hopefully, THCV could provide an optional platform for the treatment of life-threatening diseases.”

https://pubmed.ncbi.nlm.nih.gov/33526143/

“The psychoactive effects of THC in marijuana are the main reasons for its classification as a Schedule I substance, even though it is the THC that the U.S. Food and Drug Administration (FDA) approved for appetite stimulation and weight gain. In contrast to THC, clinical and therapeutic advantages of THCV regarding its lack of psychoactive effects in human studies are of great value in pharmacotherapy. It is envisioned that the unique and diverse characteristics of THCV could be explored for further development into clinically useful medicines for the treatment of life-threatening diseases.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-020-0016-7

Cannabis sativa as a Treatment for Obesity: From Anti-Inflammatory Indirect Support to a Promising Metabolic Re-Establishment Target

View details for Cannabis and Cannabinoid Research cover image“Introduction: Obesity is defined as an excess of accumulation of fat that can be harmful to health. Storage of excess fat in the adipose tissue triggers an inflammatory process, which makes obesity a low-grade chronic inflammatory disease. Obesity is considered a complex and multifactorial disease; hence, no intervention strategy appears to be an ideal treatment for all individuals. Therefore, new therapeutic alternatives are often studied for the treatment of this disease. Currently, herbal medicines are gaining ground in the treatment of obesity and its comorbidities. In this context, much attention is being paid to Cannabis sativa derivatives, and their therapeutic functions are being widely studied, including in treating obesity. 

Objective: Highlight the pharmacological properties of Δ9-tetrahydrocannabivarin (THCV), Δ9-tetrahydrocannabidinol (THC), and cannabidiol (CBD), the predominant isolated components of Cannabis sativa, as well as its therapeutic potential in the treatment of obesity. 

Results: Evidence shows that Cannabis sativa derivatives have therapeutic potential due to their anti-inflammatory properties. In addition, people who use cannabis have a lower body mass index than those who do not, making the plant an option to reduce and reverse inflammation and comorbidities in obesity. 

Conclusion: It is concluded that phytocannabinoids derived from Cannabis sativa have therapeutic potential due to its anti-inflammatory, antioxidant, and neuroprotective properties, making the plant a study option to reduce and reverse inflammation and comorbidities associated with obesity.”

https://pubmed.ncbi.nlm.nih.gov/34242511/

https://www.liebertpub.com/doi/10.1089/can.2021.0016

Δ 9 -Tetrahydrocannabinol promotes functional remyelination in the mouse brain

British Journal of Pharmacology“Background and purpose: Research on demyelinating disorders aims to find novel molecules that are able to induce oligodendrocyte precursor cell differentiation to promote central nervous system remyelination and functional recovery.

Δ9 -Tetrahydrocannabinol (THC), the most prominent active constituent of the hemp plant Cannabis sativa, confers neuroprotection in animal models of demyelination. However, the possible effect of THC on myelin repair has never been studied.

Experimental approach: By using oligodendroglia-specific reporter mouse lines in combination with two models of toxin-induced demyelination, we analysed the effect of THC on the processes of oligodendrocyte regeneration and functional remyelination.

Key results: We show that THC administration enhanced oligodendrocyte regeneration, white matter remyelination and motor function recovery. THC also promoted axonal remyelination in organotypic cerebellar cultures. THC remyelinating action relied on the induction of oligodendrocyte precursor differentiation upon cell cycle exit and via CB1 cannabinoid receptor activation.

Conclusions and implications: Overall, our study identifies THC administration as a promising pharmacological strategy aimed to promote functional CNS remyelination in demyelinating disorders.”

https://pubmed.ncbi.nlm.nih.gov/34216154/

“Our study provides a novel therapeutic advantage of THC-based interventions in multiple sclerosis by promoting remyelination and functional recovery. New clinical trials with improved designs on cannabinoids in people with multiple sclerosis are needed now, considering these compounds as potential remyelinating/disease-modifying drugs to try to overcome previous failures. Our work also suggests that at least part of the neuroprotective action of phytocannabinoids in multiple sclerosis animal models and potentially in patients as well may be due to an enhanced CNS remyelination. Finally, this study also identifies THC as a potent inductor of oligodendrocyte progenitor cell differentiation under demyelination in mice, opening the possibility for this molecule to become a candidate drug to promote oligodendrocyte regeneration and remyelination in the treatment of demyelinating disorders.”

https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15608

Medical cannabinoids for treatment of neuropsychiatric symptoms in dementia: systematic review

SciELO - Trends in Psychiatry and Psychotherapy“Introduction: Neuropsychiatric symptoms are an integral component of the natural history of dementia, occurring from prodromal to advanced stages of the disease process and leading to increased burden and morbidity. Clinical presentations are pleomorphic, and clinical management often requires combination of pharmacological and non-pharmacological interventions. However, limited efficacy and a non-negligible incidence of adverse events of psychotropic drugs reinforce the need for novel therapeutic options.

Aims: To review the evidence supporting the use of medical cannabinoids for the treatment of neuropsychiatric symptoms of dementia (NPS).

Results: Fifteen publications with original clinical data were retrieved, being 5 controlled clinical trials, 3 open-label/observational studies, and 7 case reports. Most studies indicated that the use of medical cannabinoids engendered favorable outcomes for the treatment of neuropsychiatric symptoms related to moderate and advanced stages of dementia, particularly agitation, aggressive behavior and sleep and sexual disinhibition.

Conclusion: Medical cannabinoids represent a promising pharmacological approach for the treatment of NPS, with preliminary evidence of benefit at least in moderate to severe dementia. Controlled trials with longitudinal design and larger samples are required to examine the long-term efficacy of these drugs in different types and stages of dementia, in addition to their adverse events and risk of interactions with other drugs. Many pharmacological details are yet to be determined, such as dosing, treatment duration and concentrations of active compounds (e.g., CBD/THC ratio) in commercial preparations of medical cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/34374269/