Methylphenidate for long COVID
METHYLPHENIDATE
What is methylphenidate, and how does it work?
Methylphenidate is a stimulant medication that belongs to the drug class amphetamines. This medication acts on the central nervous system (CNS) by increasing levels of two chemicals, dopamine and norepinephrine, in the brain. Norepinephrine is thought to play a role in the body’s stress response and helps to regulate sleep, alertness, and blood pressure. Dopamine plays a crucial role in movement and affects motivation, perception of reality, and the ability to experience pleasure [1]. By increasing these levels of chemicals, it leads to an increase in focus and attention. Methylphenidate is a controlled substance and does have the potential for abuse if used in a manner inconsistent with how it is prescribed.
How can methylphenidate be used in long-COVID?
Sufferers of long-COVID often deal with “brain fog,” a persistent cognitive defect resulting in memory problems, poor focus, and decreased ability to concentrate. Although the reasoning is still unclear, researchers think COVID-19 may linger in the brain for months afterward. Even though it does not cause an active infection, it is a foreign substance in the body. This leads to constant attack by the immune system, causing inflammation. Over time, the continuous inflammation manifests as “brain fog” symptoms [2].
Stimulants, such as methylphenidate, can improve focus, attention span, and even fatigue. A case study completed in 2022 showed benefits when methylphenidate and other agents were used to help reduce “brain fog” [3]. Although no formal studies have been conducted on using methylphenidate for “brain fog,” one provider stated he has been using it, in conjunction with behavioral exercises, as a treatment option. He saw improved memory, attention, and concentration difficulties [4].
The chronic fatigue many patients face may be mitigated using methylphenidate as well. A study found that treatment with methylphenidate was significantly better than placebo in 17% of patients regarding their fatigue symptoms [5]. Although current recommendations do not advocate for the use of stimulants to treat long-COVID or symptoms of long-COVID, for those suffering from “brain fog” or fatigue, it may be an attractive option to those looking for symptom management.
References:
1https://americanaddictioncenters.org/antidepressants-guide/ndris#
3https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10102822/
4https://www.ohsu.edu/sites/default/files/2023-02/PCR23-Mon-18-AndersonWM.pdf
5https://pubmed.ncbi.nlm.nih.gov/16443425/
Remdesivir for long COVID
REMDESIVIR
What is remdesivir (Veklury)?
Remdesivir is an intravenous (IV) medication used to treat COVID-19. It was approved in 2020 and can be used in adults and children (over 28 days old and weighing at least 3 kilograms) [1]. Remdesivir is a nucleotide analog that works by inhibiting the process COVID-19 uses to replicate. This helps keep viral levels low so the body’s immune system has a chance to fight it off. It is best used within seven days of the start of symptoms [2].
Can remdesivir help with long-COVID?
Currently, remdesivir is only indicated for the treatment of COVID-19. However, research has been dedicated to exploring whether the use of remdesivir decreases the risk of contracting long-COVID. The results of these studies have been mixed. One study looked at patients two years after using remdesivir and found no effect on long-term recovery, quality of life, or long-COVID symptoms. Roughly one in four patients reported fatigue, and one in six felt their recovery from COVID-19 was incomplete. There were downfalls to this study; specifically, their sample population was small, leading to a large amount of uncertainty regarding the results [3]. A second study of remdesivir found treatment reduced long-COVID symptoms for at least six months [4]. Further, additional research showed patients receiving antiviral drugs (such as remdesivir) were less likely to develop long COVID than untreated participants [5].
There are mixed reviews concerning the use of remdesivir in preventing long-COVID, so it is difficult to determine whether it has a true benefit. For those already diagnosed with long-COVID, there has been no evidence to date that it could be a viable treatment option for eradication or symptom management of COVID-19.
References:
1https://www.gilead.com/-/media/files/pdfs/medicines/covid-19/veklury/veklury_pi.pdf
2https://www.nhs.uk/medicines/remdesivir-veklury/common-questions-about-remdesivir/
3https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9579198/
4https://pubmed.ncbi.nlm.nih.gov/34850210/
5https://www.contagionlive.com/view/can-early-outpatient-treatment-reduce-the-risk-of-long-covid-
Active Clinical Trials: Long COVID, remdesivir | Card Results | ClinicalTrials.gov
Cannabidiol (CBD) for long COVID
CANNABIDIOL (CBD)
What is cannabidiol?
CBD is an active ingredient found in the cannabis plant that does not contain THC (the component of marijuana that produces a high). According to the 2018 Farm Bill, hemp-derived products that are less than 0.3% THC are federally legal; therefore, CBD is considered legal at the federal level, but individual states may have different regulations. The FDA has currently approved one CBD product (Epidiolex), which is an oral solution that can be prescribed for certain types of epilepsy, such as Lennox-Gastaut syndrome and Dravet syndrome. CBD products can come in many forms and strengths, such as capsules, oil solutions, sublingual formulations, and sprays.
How can cannabidiol help alleviate certain long COVID symptoms?
In vitro, cannabidiol is a potent inhibitor of the SARS-CoV-2 virus. It has been suggested that CBD activates the interferon pathway, an antiviral component of the immune response that prevents viral replication, which leads to the degradation of viral RNA and subsequently prevents the release of cytokines (small proteins released by the body that can promote an inflammatory response).1
An analysis done by the University of Chicago on 1,212 patients showed that patients taking a prescribed oral solution of CBD for the treatment of epilepsy tested positive for COVID at significantly lower rates than matched patients who did not take CBD.2 This is believed to be due to the antiviral and anti-inflammatory effects of CBD.
Long COVID is believed to result from a prolonged hyperinflammatory state caused by dysregulation in the immune system. CBD can also cross the blood-brain barrier, downregulating the immune system and lowering neuroinflammation. By reducing the production of pro-inflammatory cytokines and increasing the levels of anti-inflammatory cytokines, CBD is hypothesized to improve long COVID symptoms.3 In addition, CBD improves symptoms common in many long COVID patients, such as anxiety, insomnia, cognitive impairment, and neuropathic pain.
What evidence supports the use of cannabidiol for long COVID?
Cannabidiol has been previously studied as a potential treatment for COVID symptoms in mild to moderate-severity infections. In a randomized placebo-controlled study of 105 patients, participants were randomized to receive 300 mg of CBD or placebo added to standard care for 14 days.4 The study found no differences between CBD and placebo in reducing or preventing worsening of clinical status for a COVID infection. Thus, CBD should not be used in the treatment or prevention of an active COVID infection.
There is currently a lack of studies investigating the use of cannabidiol for long COVID. A randomized controlled trial of 24 participants studied the use of a cannabidiol formulation in post-acute COVID-19 syndrome and found subjectively reported improvement in overall symptoms.5 A study conducted in the UK is currently under peer review in which 30 participants were prescribed CBD-dominant medical cannabis daily for five months. Breathlessness, fatigue, mood, cognition, and pain were assessed to determine the safety and efficacy of CBD for long COVID.6
What are some things to watch out for with cannabidiol?
No serious adverse events have been reported from trials. CBD is often well-tolerated but can cause side effects such as dry mouth, nausea, diarrhea, fever, drowsiness, fatigue, and changes in appetite.4,7 It is important to remember that the FDA does not approve nonprescription CBD products, and the quality and purity of these products may vary. CBD can also have drug interactions with many medications, including blood thinners (such as warfarin), anti-epileptic drugs, antidepressants, opioids, statins, and more. It is important to tell your doctor or pharmacist if you are taking CBD regularly to see if there are any potential drug interactions with your other medications.
References:
2) Reyer M. Researchers recommend clinical trials for CBD to prevent COVID-19 based on promising animal data. UChicagoMedicine. January 20, 2022. Accessed November 10, 2023. https://www.uchicagomedicine.org/forefront/research-and-discoveries-articles/researchers-recommend-clinical-trials-for-cbd
6) Thurgur H, Lynskey M, Schlag A, et al. Feasibility of a cannabidiol (CBD)-dominant cannabis based medicinal product (CBMP) for the treatment of Long COVID symptoms: A single arm open label feasibility trial. Authorea. July 4, 2023. Accessed November 10, 2023. https://www.authorea.com/users/635694/articles/652949-feasibility-of-a-cannabidiol-cbd-dominant-cannabis-based-medicinal-product-cbmp-for-the-treatment-of-long-covid-symptoms-a-single-arm-open-label-feasibility-trial
7) Bauer BA. What are the benefits of CBD – and is it safe to use? Health Lifestyle Consumer Health. Mayo Clinic. December 6, 2022. Accessed November 10, 2023. https://www.mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/is-cbd-safe-and-effective/faq-20446700#:~:text=Though%20it%27s%20often%20well%2Dtolerated,dosage%20of%20CBD%20in%20products
Active Clinical Trials: Long COVID, cannabidiol | Card Results | ClinicalTrials.gov
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Methylprednisolone for long COVID
METHYLPREDNISOLONE
What is methylprednisolone (Medrol)?
Corticosteroids, often called steroids, are a class of medication used to decrease inflammation. Steroids, like methylprednisolone, reduce the production of chemicals that cause inflammation [1]. They are used in a variety of disease states when inflammation is abundant. Steroids should be used for the shortest duration and lowest dose possible and should not be stopped abruptly. Doing so could lead to withdrawal symptoms or a flare-up if used for an autoimmune condition such as rheumatoid arthritis.
Can methylprednisolone treat long-COVID?
Patients dealing with symptoms of long-COVID may see some beneficial results with the use of methylprednisolone. In long-COVID, it is theorized that the body is under constant inflammation via a cytokine storm, an overresponse of the immune system. Although a person is not actively infected with COVID-19, the body still sheds the virus. Since COVID-19 is a foreign material, the immune response is invoked, resulting in inflammation [2]. Since methylprednisolone decreases inflammation, it could alleviate some of the symptoms of long-COVID, such as “brain fog, chronic fatigue, and exercise intolerance.
Although few studies have tested methylprednisolone’s effectiveness in treating long-COVID, the limited results show promise. In one study on 14 patients, researchers looked at the immune response before and after four-day treatment with steroids. Results showed the immune response decreased and was maintained for at least four months following therapy [2]. A second study found that treatment with tapering steroids improved breathing, increased oxygen levels, and decreased inflammation on chest X-rays [3].
Methylprednisolone may offer symptom improvement for patients suffering from side effects of long-COVID. However, there has been no evidence it treats the disease state itself. It may be an attractive option to patients as it is relatively affordable and, for a short duration, may help with lung capacity and oxygen levels. A conversation with a healthcare provider can offer additional insight as to whether methylprednisolone would be a potential therapy option for long-COVID.
References:
1https://my.clevelandclinic.org/health/drugs/4812-corticosteroids
3https://pubmed.ncbi.nlm.nih.gov/34730322/
Active Clinical Trials: Long COVID, Methylprednisolone | Card Results | ClinicalTrials.gov
Rosuvastatin for long COVID
ROSUVASTATIN
What is rosuvastatin (Crestor)?
Rosuvastatin is part of a class of drugs commonly referred to as “statins,” whose role is to reduce the amount of cholesterol the liver makes. Cholesterol comprises HDL, the “good” cholesterol, and LDL, the “bad” cholesterol. It is used by the body to produce various hormones and other substances. However, if a person has too much LDL, it can cause a buildup in the arteries, leading to stroke, heart attack, or other health problems.
How does rosuvastatin relate to long-COVID?
Rosuvastatin possesses anti-inflammatory and modifying effects on the immune system (1). A recent study conducted in vitro (in test tubes) showed that simvastatin reduced levels of pro-inflammatory proteins and inhibited human cells from being infected with COVID-19 (2). However, statins can also upregulate or increase an enzyme called ACE2. ACE2 is how COVID-19 makes its way into the cells, leading to an influx of disease ( 3).
For those who suffer from long-COVID, the effects of statins may prolong illness even further. Highlights of long-COVID include chronic fatigue, exercise intolerance, and muscle weakness. Muscle weakness or muscle pain (myalgia) is also a primary side effect associated with the use of statins. Therefore, many believe that statins are exaggerating long-COVID in patients. Additionally, statins can decrease the amount of CoQ10 available for use by the body. CoQ10 is an antioxidant that has a role in cell energy production (4). For those suffering from long-COVID and already with a decreased energy reserve, statin use could only exacerbate this problem further.
Although currently, there is no definitive answer regarding the role of rosuvastatin use in patients with long-COVID, the consensus is to aid on the side of caution. A benefit versus risk scenario for every patient should be warranted for providers to assess whether the cardio-protective use of statins outweighs the prolonged effects of long-COVID in patients.
References:
1https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520195/
2https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1011050
3https://jamanetwork.com/journals/jama/fullarticle/2780872
4 https://www.mdpi.com/2077-0383/12/14/4659
Cannabidivarin (CBDV) for long COVID
CANNABIDIVARIN
What is cannabidivarin?
Cannabidivarin, or CBDV, is a cannabinoid product derived from the cannabis plant that is closely related to CBD but has a slight difference in its chemical structure. This change in chemical structure allows CBDV to have unique effects on the body that are not found with CBD. CBDV can be used for similar indications as CBD, such as epilepsy and nausea; however, it should not be expected to have the same effects as CBD.
How can cannabidivarin help alleviate certain long COVID symptoms?
Interestingly, out of the cannabinoids, only cannabidiol is a potent inhibitor of the SARS-CoV-2 virus. Despite its structural similarity, CBDV has not been found to inhibit COVID infection as potently as CBD.1 In addition, while researchers at the University of Chicago conducted an analysis demonstrating that patients taking CBD tested positive for COVID at significantly lower rates, this finding did not extend to CBDV or other closely related cannabinoids of CBD.2 Thus, the use of CBDV for long COVID symptoms is uncertain.
CBDV also does not activate cannabinoid receptors, making it less effective in pain relief compared to CBD. On the other hand, CBDV blocks a receptor called toll-like receptor 4 (TLR4), which regulates the activation of immune cells and is a target for treating inflammation.3 The SARS-CoV-2 virus can directly infect the brain and cause inflammation in the central nervous system. Thus, CBDV may have beneficial effects on reducing neuroinflammation caused by long COVID with potential downstream impacts on cognitive symptoms of long COVID.
What evidence supports the use of cannabidivarin for long COVID?
CBDV is currently being studied to determine its potential use for various conditions. A study in children with autism spectrum disorder is looking to assess the effects of CBDV on mood, social, and cognitive functions.4 CBDV has also been studied for neuropathic pain in HIV patients and was not found to have beneficial effects on pain relief when given at 400 mg per day for four weeks.5 Other studies have also not found significant reductions in pain with CBDV.6
However, an in vitro and in vivo study found that CBDV can block pro-inflammatory factors activated by downstream effects of TLR4 signaling and specifically improves pain relief in the setting of morphine use.3 This suggests that CBDV may reduce neuroinflammation in long COVID, but further human studies are needed to assess its efficacy.
What are some things to watch out for with cannabidivarin?
No serious adverse events have been reported from trials. CBDV is often well-tolerated but can cause side effects such as diarrhea, dizziness, drowsiness, headache, and nausea.7 It is important to remember that the FDA does not approve CBDV products, and the quality and purity of these products may vary. CBDV can also have drug interactions with many medications, including blood thinners, anti-epileptic drugs, antidepressants, opioids, statins, certain blood pressure medications, and more. It is important to tell your doctor or pharmacist if you are taking CBD regularly to see if there are any potential drug interactions with your other medications.
References:
2) Reyer M. Researchers recommend clinical trials for CBD to prevent COVID-19 based on promising animal data. UChicagoMedicine. January 20, 2022. Accessed November 10, 2023. https://www.uchicagomedicine.org/forefront/research-and-discoveries-articles/researchers-recommend-clinical-trials-for-cbd
4) Hollander E. Cannabidivarin (CBDV) versus placebo in children with autism spectrum disorder. Defense Technical Information Center. August 1, 2020. Accessed November 10, 2023. https://apps.dtic.mil/sti/citations/AD1113593
7) Bauer BA. What are the benefits of CBD – and is it safe to use? Health Lifestyle Consumer Health. Mayo Clinic. December 6, 2022. Accessed November 10, 2023. https://www.mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/is-cbd-safe-and-effective/faq-20446700#:~:text=Though%20it%27s%20often%20well%2Dtolerated,dosage%20of%20CBD%20in%20products
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