cbd oil for healthcare professionals

Can Cannabidiol Help Frontline Healthcare Workers?

— Fewer emotional exhaustion symptoms for doctors, nurses during pandemic, trial suggests

by Judy George, Senior Staff Writer, MedPage Today August 13, 2021

Frontline physicians, nurses, and therapists working with COVID-19 patients had fewer emotional exhaustion symptoms when they were treated with cannabidiol (CBD), the BONSAI randomized clinical trial showed.

Scores on the emotional exhaustion subscale of the Maslach Burnout Inventory substantially decreased at days 14, 21, and 28 among 120 healthcare workers randomized to either CBD 300 mg plus standard care or standard care alone, reported José Alexandre Crippa, PhD, of University of São Paulo in Brazil, and co-authors in JAMA Network Open.

Five participants, all in the CBD group, experienced serious adverse events, including four cases of elevated liver enzymes and one case of severe pharmacodermia, with recovery after treatment was discontinued.

“Cannabidiol may act as an effective agent for the reduction of burnout symptoms among a population with important mental health needs worldwide,” Crippa and colleagues wrote. “However, it is necessary to balance the benefits with potential adverse and undesired effects when making decisions regarding the use of this compound.”

The findings were “consistent with a growing number of placebo-controlled studies in both rodents and humans suggesting that CBD lowers stress-provoked negative emotional states including fear, anxiety, depression, and anger,” observed Michael Telch, PhD, of the University of Texas at Austin, who wasn’t involved with the study.

“What accounts for this multi-emotion dampening? One potential explanation is that CBD appears to directly affect multiple brain targets implicated in stress reactivity, which plays a central role in the activation of emotional dysfunction,” Telch told MedPage Today.

Other studies, however, suggest that CBD may not significantly curb emotional distress. “The jury’s still out on how robust the anxiolytic effects of CBD actually are,” noted Mallory Loflin, PhD, of the University of California, San Diego, who also wasn’t involved with the trial. “We have a lot of folks self-reporting benefits, but that data is hard to interpret because it’s conflated by expectation or placebo, and uncontrolled amounts of trace THC [tetrahydrocannabinol].”

The latter is important because THC also might be anxiolytic, at least in small doses, Loflin pointed out. “We do have a couple of studies showing acute improvement in social anxiety, but in highly contrived, experimental settings. Those data look pretty compelling, but the doses are exponentially higher than most folks are taking on a daily basis,” she told MedPage Today.

“The big benefit here, though, is that if CBD actually does end up being effective, its safety profile looks really good, particularly in comparison to benzodiazepines or SSRIs [selective serotonin reuptake inhibitors],” Loflin added.

The open-label BONSAI trial randomized 120 physicians, nurses, and physical therapists working with patients with COVID-19 at the Ribeirão Preto Medical School University Hospital in São Paulo between June and November 2020 to either oral cannabidiol 300 mg (150 mg twice per day) plus standard care, or standard care alone, for 28 days. CBD had 99.6% purity and was dissolved in medium-chain triglyceride oil.

Standard care included motivational and instructional videos about low-impact physical exercise and weekly consultations with psychiatrists who offered psychological support. Hospital executives offered personal protective equipment, work schedule adjustments, and ongoing testing, and also hired new personnel and provided a specific outpatient treatment unit during the pandemic.

The primary outcome was assessed with the emotional exhaustion subscale of the Brazilian version of the Maslach Burnout Inventory, Human Services Survey for Medical Personnel (subscale score range is 0-54 points, with higher scores indicating greater emotional exhaustion). Secondary outcomes including anxiety and depression, were assessed with other measures. Blood samples were collected at baseline and days 7, 14, 21, and 28.

The average age of healthcare workers involved in the study was about 34, and 67% were women. About 55% were nurses, and 42% were physicians; all worked in ICUs, emergency departments, or hospital wards.

Three participants in the CBD arm withdrew from the study: one experienced severe pharmacodermia, one had critical elevation of liver enzymes, and one left to participate in a COVID-19 vaccine clinical trial. During follow-up, both participants who discontinued CBD therapy because of serious adverse events experienced full recovery.

Compared with participants who received standard care alone, participants who received CBD plus standard care had substantial reductions on the Maslach Burnout Inventory emotional exhaustion at:

  • Day 14: mean difference 4.14 points, 95% CI 1.47-6.80 points, partial eta squared [ηp 2 ]=0.08
  • Day 21: mean difference 4.34 points, 95% CI 0.94-7.73 points, ηp 2 =0.05
  • Day 28: mean difference 4.01 points, 95% CI 0.43-7.59 points, ηp 2 =0.04

At day 28, CBD plus standard care significantly reduced the number of participants with scores indicating anxiety on the seven-item Generalized Anxiety Disorder questionnaire and depression on the nine-item Patient Health Questionnaire. CBD also decreased the number of diagnoses of burnout syndrome based on ICD-11 criteria, but the difference was not statistically significant (P=0.08).

The trial had several limitations, Crippa and co-authors acknowledged. It was a single-center study with a short follow-up period and a single-intervention dose. It also did not have a double-blind placebo-controlled design.

There still are many unanswered questions about CBD, including optimal dosing regimens and formulations, Telch noted. Ongoing studies, including one comparing the effects of broad-spectrum, full-spectrum, and CBD-isolate oil on the emotional impact of COVID-19, may address some of these issues.

Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

The study was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo, the Instituto Nacional de Ciência e Tecnologia Translational em Medicina; the Global Priorities in Cannabinoid Research Excellence Program, University Global Partnership Network, the Conselho Nacional de Desenvolvimento Científico e Tecnológico, and donations from PurMed Global and Laboratório Chromatox.

Researchers reported relationships with the Fundação de Amparo à Pesquisa do Estado de São Paulo, the Instituto Nacional de Ciência e Tecnologia Translational em Medicina, the Conselho Nacional de Desenvolvimento Científico e Tecnológico, Australian Centre for Cannabinoid Clinical and Research Excellence, National Health and Medical Research Council, Phytecs, Prati-Donaduzzi, Canada Foundation for Innovation, Mitacs, Stanley Medical Research Institute, Aché Laboratorios Farmaceuticos, Daiichi Sankyo, Janssen-Cilag, Salomao Zoppi Serviços, BioSynthesis Pharma Group, and a patent pending for a cannabinoid-containing oral pharmaceutical composition.

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Cannabidiol primer for healthcare professionals

Emerging research and clinical data are demonstrating potential benefits of cannabidiol for multiple medical conditions. This article gives healthcare providers information on cannabidiol and the endocannabinoid system as a foundation on which to build their medical knowledge as the risks and benefits of CBD in various diseases are further evaluated over time.

As of April 2020, 629 clinical trials have been registered on clinicaltrials.gov investigating cannabidiol (CBD). Because CBD has been marketed as a supplement or alternative medicine rather than through pharmaceutical research and development, it has come into the medical arena with little oversight from the Food and Drug Administration. This article provides an overview of cannabinoids and the endocannabinoid system, including their methods of use and metabolism, as a foundation for understanding CBD use in patients.

CANNABINOIDS

Cannabinoids are the chemical messengers for the endocannabinoid system.1 , 2 While many different cannabinoids exist, they all fall under two categories: exogenous or endogenous. Exogenous cannabinoids are either plant based or synthetic, while endogenous cannabinoids are produced naturally by the human body. While this article focuses on cannabidiol (CBD), an exogenous cannabinoid, it is important to understand the spectrum of known cannabinoids ( Table 1 ).

Table 1.

Type Name Effects
Exogenous cannabinoids Cannabis indica (marijuana) plant  
Tetrahydrocannabinol (THC) Antioxidant, anti-inflammatory, euphoric high, analgesic
Cannabidiol (CBD) Anticonvulsant, antioxidant, anxiolytic, analgesic, anti-inflammatory; treats psychotic disorders and relieves spasms
Cannabigerol (CBG) Antibiotic, antifungal, anti-inflammatory, analgesic
Cannabinol (CBN) Sedative, antibiotic, anticonvulsant, anti-inflammatory
Cannabichromene (CBC) Antibiotic, antifungal, anti-inflammatory, analgesic
Tetrahydrocannabivarin (THCV) Euphoric high and anxiolytic
Cannabis sativa (hemp) plant  
CBD Anticonvulsant, antioxidant, anxiolytic, anti-inflammatory; reduces anxiety, treats psychotic disorders, and relieves spasms
Endocannabinoids Anandamide  
2-arachidonoyl glycerol (2-AG)  

The genus family of Cannabis produces as many as 113 different phytocannabinoids. Hemp and marijuana are harvested from different strains of the Cannabis plant—Cannabis sativa and Cannabis indica. Hemp, which is part of the Cannabis sativa strain and grown for food and fiber, contains <0.3% tetrahydrocannabinol (THC) but is rich in CBD. Of note, hemp seed oil is devoid of CBD since the phytocannabinoids are harvested from the flowers of the plant. Cannabis indica, the marijuana plant, also produces THC and CBD, the most prevalent and best understood phytocannabinoids.

The two major endogenous cannabinoids (endocannabinoids) are anandamide and 2-arachidonoyl glycerol (2-AG). They function as retrograde messengers derived from postsynaptic nerve fibers and thereby regulate neuronal transmission. They interact with presynaptic cannabinoid receptors ( Figure 1 ) to regulate basic functions including mood, memory, appetite, pain, itch, and sleep. Anandamide was discovered in 1992. Its name comes from the Sanskrit word ananda meaning bliss, referring to its unique effects on the mind and body. In 1995, 2-AG was discovered and found at higher concentrations in the brain, while anandamide is found at higher concentrations in other areas of the body. Both endocannabinoids can  bind to CB1 and CB2 receptors, but they differ in their affinities for these receptors. Endocannabinoids are transient neurotransmitters, meaning they are synthesized on demand; after being released, they are quickly broken down by two enzymes: fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase.

THE ENDOCANNABINOID SYSTEM

The endocannabinoid system receptors, CB1 and CB2 ( Figure 1 ),3–5 have unique distributions within the body and different ligands, which explains the effects of the different cannabinoids ( Table 2 ). CB1 receptors are found throughout the body, but are mostly present in the brain and spinal cord. They are concentrated in brain regions associated with the behaviors they influence. For example, there are CB1 receptors in the hypothalamus, which is involved with appetite regulation, and the amygdala, which plays a role in memory and emotional processing. CB1 receptors are also found in nerve endings, where they act to reduce sensations of pain. CB2 receptors tend to be found in the peripheral nervous system. They are especially concentrated in immune cells. When CB2 receptors are activated, they work to reduce inflammation. Inflammation is an immune response that plays a role in many diseases and conditions.

Table 2.

Endocannabinoid system receptors

Receptor Location Effect
CB1 (brain and spinal cord) Amygdala Memory and emotional processing
Hypothalamus Appetite regulation
Nerve endings Pain
CB2 (peripheral nervous system) Immune cells Inflammation
Spleen  
Liver  

With respect to the CBD found in cannabis, researchers have found that THC binds to both CB1 and CB2 receptors, activating them just like an endocannabinoid but with higher affinity. CBD does not bind directly to cannabinoid receptors. Instead, CBD works by inhibiting  FAAH, which is responsible for the breakdown of anandamide—the most important endocannabinoid in the body. When FAAH is inhibited, it cannot break down anandamide at its normal rate. This leads to a buildup of anandamide in the synapse and results in down-regulation of nerve transmission. Additionally, CBD inhibits endocannabinoid reuptake,6 transient receptor potential vanilloid 1 activation, and G-protein-coupled receptor 55 activation and increases the activity of serotonin 5-HA1a receptors, which translates into effects on a wide array of systems in the human body, including the immune system, the nervous system (anxiety, autism, multiple sclerosis, posttraumatic stress disorder, neuropathic pain),7–13 the endocrine system, the cardiovascular system (atherosclerosis),14 the digestive system (inflammatory bowel disease and motility disorders),15 , 16 and skin (inflammatory skin disorders, disorders of hair and pigment, and itch).17–19

CANNABIDIOL EXTRACTION AND METHOD OF USE

To create a safe CBD product, Cannabis plant extraction techniques such as carbon dioxide extraction, ethanol extraction, or solvent extraction with olive oil are preferred. Extraction techniques using hexane or butane may leave harmful residues. The CBD extracts can be categorized as broad spectrum, full spectrum, or isolate. If all extracts of the Cannabis plant, including CBD, terpenes, flavonoids, essential oils, and other cannabinoids, are utilized, the extract is called full-spectrum CBD and the THC concentration should be <0.3%. Broad spectrum is similar to full spectrum with the exception that it is nearly THC free. Finally, isolate, which is typically harvested from Cannabis sativa, is pure CBD. Historically, some clinical benefits have been seen with broad- or full-spectrum CBD products due to the presumed synergistic actions of the various phytocannabinoids as well as other plant constituents, which is called the “entourage effect.”20

Table 3 lists consumer products in decreasing order of bioavailability. Consumers tend to prefer CBD in the form of topical creams and orals (gummies, candies, tinctures, and capsules). There is little regulation or oversight of the products, so consumers should seek certificates of authenticity and information on the source of CBD and other ingredients.