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Exploring the relationship of COVID-19 vaccines and fertility
Introduction
Amidst an aggressive vaccination campaign for COVID-19, misinformation has spread over the Internet, affecting public perception and making some people hesitant to participate in ongoing immunization campaigns. Of chief concern are issues pertaining to fertility or viability of sperm – information circulating on social networks posits that the coronavirus vaccine may influence infertility in men, which, according to physicians, is not grounded in reality. From the perspective of evidence-based medicine, there is a dearth of information suggesting an untoward effect of the vaccine on male fertility. The risk of adverse reactions arising from approved vaccines is negligible, with mild, albeit controllable, side effects demonstrated by patients in clinical trials. Therefore, there is no plausible reason for the general public to avoid vaccinations.1
Infertility following vaccination
The source of confusion can be traced back to a study conducted by researchers at the University of Miami Miller School of Medicine; the general public has conflated a side effect of the virus, namely, infertility and erectile dysfunction, with that of the vaccine.2 According to Ranjith Ramasamy, MD, director of the urology program at Miller, “We were the first to demonstrate that the COVID virus, itself, can affect male fertility and be a potential cause for erectile dysfunction. We are now the first to examine if there is any impact of the COVID vaccine on male fertility potential, which we did not find.”3
Coronavirus can indeed cause significant damage to the testicular tissue of infected men by means of mediating ACE2 expression on Leydig and Sertoli cells of the testis. It should be noted that COVID-19 may potentially attack any type of cell in the body that expresses the enzyme ACE2. However, it is particularly harmful to cells with high levels of expression of this enzyme, such as testicular cells. The spermatogenesis process can be affected, thereby posing a risk to male fertility.4
Expanding on the theme of fertility during the pandemic, a number of false claims5-7 about the vaccine and its overall effect on the placenta and fertility have also emerged as a contentious topic for debate on social media; doctors continue to explain why the theories are not reasonable or a cause for concern. The World Health Organization (WHO) provides recommendations on COVID-19 vaccinations for pregnant and/or lactating women and encourages a shared decision process involving risk/benefit assessment with the prescribing physician.5 Pregnant women, especially those with underlying comorbid conditions, are susceptible to developing severe symptom manifestations of COVID-19 with the disease also being associated with an increased likelihood of premature birth. As far as lactating women are concerned, the evidence thus far has indicated that the risk of side effects of the vaccine is very low, suggesting that these women could be vaccinated.5
The vaccine is the best option
While more studies are needed to ascertain the relationship between COVID-19 and male infertility, the vaccine is currently the best option for those who are concerned about their fertility from exposure to the coronavirus. Because of delayed wholesale acceptance of vaccines by the general population, clinicians should continue to emphasize the importance of preventive care with respect to disease exposure.6
In addition, those who are concerned with fertility can opt for ways to preserve their reproductive capacity, such as the removal of semen for freezing sperm, albeit with adherence to sperm-washing procedures to preclude cross-contamination from viruses.8,9 For the preservation of sperm, the noninvasive method is often performed, preferably collected in several samples. Then, the semen is cryopreserved.8 In some instances, the sperm can also be removed directly from the testicles with a simple needle or by means of a minor surgical procedure.
A wait and try approach is advocated by clinicians for individuals who have already experienced COVID-19 symptoms and are therefore concerned about the prospect of childbearing.10 If the couple is unable to conceive after a year of trying, it is recommended that they consult a reproductive specialist; the clinician can carry out a comprehensive evaluation and order a series of tests to identify the source of the problem, indicating whether there are alternative methods for helping the couple to start a family (addressing the underlying factors involved in infertility, or treating via assisted reproduction procedures, such as in vitro fertilization).11
Dr. Aman is faculty member at the biology department of City Colleges of Chicago, and a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF). She disclosed no relevant financial relationships. Dr. Islam is a medical writer for the IMCHF, Montreal, is based in New York, and disclosed no relevant financial relationships. Mr. Choudhry is a research assistant at the IMCHF and he has no disclosures. Dr. Zia Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF. He has no disclosures.
References
1. Berry SD et al. J Am Geriatr Soc. 2021 May;69(5):1140-6.
2. Achua JK et al. World J Men’s Health. 2021 Jan;39(1):65-74.
3. Broderick JM. Urology Times. 2021 June.
4. Huang C et al. Andrology. 2021 Jan;9(1):80-7.
5. Sajjadi NB et al. J Osteopath Med. 2021 Apr 12;121(6):583-7.
6. Sallam M et al. Vaccines. 2021 Jan;9(1):42.
7. Islam MS et al. PloS One. 2021 May 12;16(5):e0251605.
8. Tesarik J. J Fertil Preserv. 2021;2:art246111.
9. Adiga SK et al. Reprod BioMed Online. 2020 Dec;41(6):991-7.
10. FAQs related to COVID-19. Q: If I get sick or test positive for COVID-19, when is it safe to become pregnant? American Society for Reproductive Medicine.
11. Cross C. Wellness and Prevention: Why can’t I get pregnant? John Hopkins Medicine.
Introduction
Amidst an aggressive vaccination campaign for COVID-19, misinformation has spread over the Internet, affecting public perception and making some people hesitant to participate in ongoing immunization campaigns. Of chief concern are issues pertaining to fertility or viability of sperm – information circulating on social networks posits that the coronavirus vaccine may influence infertility in men, which, according to physicians, is not grounded in reality. From the perspective of evidence-based medicine, there is a dearth of information suggesting an untoward effect of the vaccine on male fertility. The risk of adverse reactions arising from approved vaccines is negligible, with mild, albeit controllable, side effects demonstrated by patients in clinical trials. Therefore, there is no plausible reason for the general public to avoid vaccinations.1
Infertility following vaccination
The source of confusion can be traced back to a study conducted by researchers at the University of Miami Miller School of Medicine; the general public has conflated a side effect of the virus, namely, infertility and erectile dysfunction, with that of the vaccine.2 According to Ranjith Ramasamy, MD, director of the urology program at Miller, “We were the first to demonstrate that the COVID virus, itself, can affect male fertility and be a potential cause for erectile dysfunction. We are now the first to examine if there is any impact of the COVID vaccine on male fertility potential, which we did not find.”3
Coronavirus can indeed cause significant damage to the testicular tissue of infected men by means of mediating ACE2 expression on Leydig and Sertoli cells of the testis. It should be noted that COVID-19 may potentially attack any type of cell in the body that expresses the enzyme ACE2. However, it is particularly harmful to cells with high levels of expression of this enzyme, such as testicular cells. The spermatogenesis process can be affected, thereby posing a risk to male fertility.4
Expanding on the theme of fertility during the pandemic, a number of false claims5-7 about the vaccine and its overall effect on the placenta and fertility have also emerged as a contentious topic for debate on social media; doctors continue to explain why the theories are not reasonable or a cause for concern. The World Health Organization (WHO) provides recommendations on COVID-19 vaccinations for pregnant and/or lactating women and encourages a shared decision process involving risk/benefit assessment with the prescribing physician.5 Pregnant women, especially those with underlying comorbid conditions, are susceptible to developing severe symptom manifestations of COVID-19 with the disease also being associated with an increased likelihood of premature birth. As far as lactating women are concerned, the evidence thus far has indicated that the risk of side effects of the vaccine is very low, suggesting that these women could be vaccinated.5
The vaccine is the best option
While more studies are needed to ascertain the relationship between COVID-19 and male infertility, the vaccine is currently the best option for those who are concerned about their fertility from exposure to the coronavirus. Because of delayed wholesale acceptance of vaccines by the general population, clinicians should continue to emphasize the importance of preventive care with respect to disease exposure.6
In addition, those who are concerned with fertility can opt for ways to preserve their reproductive capacity, such as the removal of semen for freezing sperm, albeit with adherence to sperm-washing procedures to preclude cross-contamination from viruses.8,9 For the preservation of sperm, the noninvasive method is often performed, preferably collected in several samples. Then, the semen is cryopreserved.8 In some instances, the sperm can also be removed directly from the testicles with a simple needle or by means of a minor surgical procedure.
A wait and try approach is advocated by clinicians for individuals who have already experienced COVID-19 symptoms and are therefore concerned about the prospect of childbearing.10 If the couple is unable to conceive after a year of trying, it is recommended that they consult a reproductive specialist; the clinician can carry out a comprehensive evaluation and order a series of tests to identify the source of the problem, indicating whether there are alternative methods for helping the couple to start a family (addressing the underlying factors involved in infertility, or treating via assisted reproduction procedures, such as in vitro fertilization).11
Dr. Aman is faculty member at the biology department of City Colleges of Chicago, and a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF). She disclosed no relevant financial relationships. Dr. Islam is a medical writer for the IMCHF, Montreal, is based in New York, and disclosed no relevant financial relationships. Mr. Choudhry is a research assistant at the IMCHF and he has no disclosures. Dr. Zia Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF. He has no disclosures.
References
1. Berry SD et al. J Am Geriatr Soc. 2021 May;69(5):1140-6.
2. Achua JK et al. World J Men’s Health. 2021 Jan;39(1):65-74.
3. Broderick JM. Urology Times. 2021 June.
4. Huang C et al. Andrology. 2021 Jan;9(1):80-7.
5. Sajjadi NB et al. J Osteopath Med. 2021 Apr 12;121(6):583-7.
6. Sallam M et al. Vaccines. 2021 Jan;9(1):42.
7. Islam MS et al. PloS One. 2021 May 12;16(5):e0251605.
8. Tesarik J. J Fertil Preserv. 2021;2:art246111.
9. Adiga SK et al. Reprod BioMed Online. 2020 Dec;41(6):991-7.
10. FAQs related to COVID-19. Q: If I get sick or test positive for COVID-19, when is it safe to become pregnant? American Society for Reproductive Medicine.
11. Cross C. Wellness and Prevention: Why can’t I get pregnant? John Hopkins Medicine.
Introduction
Amidst an aggressive vaccination campaign for COVID-19, misinformation has spread over the Internet, affecting public perception and making some people hesitant to participate in ongoing immunization campaigns. Of chief concern are issues pertaining to fertility or viability of sperm – information circulating on social networks posits that the coronavirus vaccine may influence infertility in men, which, according to physicians, is not grounded in reality. From the perspective of evidence-based medicine, there is a dearth of information suggesting an untoward effect of the vaccine on male fertility. The risk of adverse reactions arising from approved vaccines is negligible, with mild, albeit controllable, side effects demonstrated by patients in clinical trials. Therefore, there is no plausible reason for the general public to avoid vaccinations.1
Infertility following vaccination
The source of confusion can be traced back to a study conducted by researchers at the University of Miami Miller School of Medicine; the general public has conflated a side effect of the virus, namely, infertility and erectile dysfunction, with that of the vaccine.2 According to Ranjith Ramasamy, MD, director of the urology program at Miller, “We were the first to demonstrate that the COVID virus, itself, can affect male fertility and be a potential cause for erectile dysfunction. We are now the first to examine if there is any impact of the COVID vaccine on male fertility potential, which we did not find.”3
Coronavirus can indeed cause significant damage to the testicular tissue of infected men by means of mediating ACE2 expression on Leydig and Sertoli cells of the testis. It should be noted that COVID-19 may potentially attack any type of cell in the body that expresses the enzyme ACE2. However, it is particularly harmful to cells with high levels of expression of this enzyme, such as testicular cells. The spermatogenesis process can be affected, thereby posing a risk to male fertility.4
Expanding on the theme of fertility during the pandemic, a number of false claims5-7 about the vaccine and its overall effect on the placenta and fertility have also emerged as a contentious topic for debate on social media; doctors continue to explain why the theories are not reasonable or a cause for concern. The World Health Organization (WHO) provides recommendations on COVID-19 vaccinations for pregnant and/or lactating women and encourages a shared decision process involving risk/benefit assessment with the prescribing physician.5 Pregnant women, especially those with underlying comorbid conditions, are susceptible to developing severe symptom manifestations of COVID-19 with the disease also being associated with an increased likelihood of premature birth. As far as lactating women are concerned, the evidence thus far has indicated that the risk of side effects of the vaccine is very low, suggesting that these women could be vaccinated.5
The vaccine is the best option
While more studies are needed to ascertain the relationship between COVID-19 and male infertility, the vaccine is currently the best option for those who are concerned about their fertility from exposure to the coronavirus. Because of delayed wholesale acceptance of vaccines by the general population, clinicians should continue to emphasize the importance of preventive care with respect to disease exposure.6
In addition, those who are concerned with fertility can opt for ways to preserve their reproductive capacity, such as the removal of semen for freezing sperm, albeit with adherence to sperm-washing procedures to preclude cross-contamination from viruses.8,9 For the preservation of sperm, the noninvasive method is often performed, preferably collected in several samples. Then, the semen is cryopreserved.8 In some instances, the sperm can also be removed directly from the testicles with a simple needle or by means of a minor surgical procedure.
A wait and try approach is advocated by clinicians for individuals who have already experienced COVID-19 symptoms and are therefore concerned about the prospect of childbearing.10 If the couple is unable to conceive after a year of trying, it is recommended that they consult a reproductive specialist; the clinician can carry out a comprehensive evaluation and order a series of tests to identify the source of the problem, indicating whether there are alternative methods for helping the couple to start a family (addressing the underlying factors involved in infertility, or treating via assisted reproduction procedures, such as in vitro fertilization).11
Dr. Aman is faculty member at the biology department of City Colleges of Chicago, and a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF). She disclosed no relevant financial relationships. Dr. Islam is a medical writer for the IMCHF, Montreal, is based in New York, and disclosed no relevant financial relationships. Mr. Choudhry is a research assistant at the IMCHF and he has no disclosures. Dr. Zia Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF. He has no disclosures.
References
1. Berry SD et al. J Am Geriatr Soc. 2021 May;69(5):1140-6.
2. Achua JK et al. World J Men’s Health. 2021 Jan;39(1):65-74.
3. Broderick JM. Urology Times. 2021 June.
4. Huang C et al. Andrology. 2021 Jan;9(1):80-7.
5. Sajjadi NB et al. J Osteopath Med. 2021 Apr 12;121(6):583-7.
6. Sallam M et al. Vaccines. 2021 Jan;9(1):42.
7. Islam MS et al. PloS One. 2021 May 12;16(5):e0251605.
8. Tesarik J. J Fertil Preserv. 2021;2:art246111.
9. Adiga SK et al. Reprod BioMed Online. 2020 Dec;41(6):991-7.
10. FAQs related to COVID-19. Q: If I get sick or test positive for COVID-19, when is it safe to become pregnant? American Society for Reproductive Medicine.
11. Cross C. Wellness and Prevention: Why can’t I get pregnant? John Hopkins Medicine.
Should clinicians recommend vitamin D for psychiatric patients during COVID-19?
Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility.
Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
What is the role of vitamin D in human physiology?
Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.1 As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.2
It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.3
Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.4
Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
The rationale for vitamin D supplementation therapy in COVID-19
When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.5
What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries6 and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,7 further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,8 four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.9 Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.10
Revisiting vitamin D supplementation therapy for mental health patients with COVID-19
It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.
Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.11
In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.12
It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.13
However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.
Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.
References
1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.
2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.
3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.
4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.
5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.
6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.
7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.
8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.
9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.
10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.
11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.
12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.
13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.
Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility.
Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
What is the role of vitamin D in human physiology?
Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.1 As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.2
It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.3
Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.4
Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
The rationale for vitamin D supplementation therapy in COVID-19
When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.5
What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries6 and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,7 further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,8 four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.9 Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.10
Revisiting vitamin D supplementation therapy for mental health patients with COVID-19
It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.
Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.11
In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.12
It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.13
However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.
Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.
References
1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.
2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.
3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.
4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.
5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.
6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.
7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.
8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.
9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.
10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.
11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.
12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.
13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.
Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility.
Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
What is the role of vitamin D in human physiology?
Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.1 As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.2
It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.3
Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.4
Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
The rationale for vitamin D supplementation therapy in COVID-19
When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.5
What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries6 and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,7 further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,8 four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.9 Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.10
Revisiting vitamin D supplementation therapy for mental health patients with COVID-19
It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.
Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.11
In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.12
It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.13
However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.
Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.
References
1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.
2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.
3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.
4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.
5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.
6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.
7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.
8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.
9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.
10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.
11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.
12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.
13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.
Separating myth from reality: The role of cannabinoids in COVID-19
An intriguing pattern has emerged for cannabis enthusiasts as a result of lockdowns and statewide safety restrictions for COVID-19.
Consumers, as of late, have been shopping for larger marijuana baskets per trip to the dispensaries in various states, including California, Colorado, Nevada, and Washington, . However, they are also cutting down on the number of trips, perhaps, as a preventive measure to reduce the risk of exposure to coronavirus during this pandemic. Sales dipped considerably by the end of March only to experience a resurgence after the issuing of stimulus checks and unemployment benefits.
For the past few years, cannabis consumption remained steady while the industry continued to thrive with robust sales of the drug. It is a recession-proof phenomenon, therefore presenting a unique opportunity for clinicians with respect to patient education and individualized care.1
An unfortunate carryover of the governmental restrictions, self-isolation, and social estrangement is that consumers are now turning to the dark web as a source for continuous supply of cannabis. Prepandemic, according to the U.N. 2020 World Drug Report, there was already a 30% increase in sales of cannabis between 2009 and 2018. COVID-19 has fractured the drug’s supply chain and created an inescapable void that is being filled by drug traffickers.2 A clinical dilemma is posed when a user procures counterfeit cannabis or a drug batch with impurities.
Riding the cytokine storm
Cytokines are a host of proteins with designated regulatory and immune responses that play an instrumental role in cell signaling. The aptly named “cytokine storm” conjures up the image of an imperiled immune system spiraling out of control; it is, in fact, an extreme immune response that culminates into a massive influx of cytokines released into the bloodstream. Without the presence of an immunologic threat, cytokines are responsible for maintaining homeostasis and the functionality of immune cells. However, acute cytokine release (i.e., cytokine storm), as is the case with severe COVID-19, jeopardizes organ function (for example, interstitial lung disease) with clinical symptoms, such as fever, cough, dyspnea, and myalgia.
Benefits and drawbacks of immunosuppressive agents
To inhibit cytokine release (e.g., interleukin-6 cytokine levels), immunosuppressive agents such as tocilizumab have been leveraged to damper the body’s overactive inflammatory response to perceived immunologic stressors, in particular, COVID-19. While the aforementioned agent was remarkably effective with respect to lung consolidation clearance in most of the patients tested, a host of untoward effects prevent its general applicability and use. However, a team of researchers from the University of Nebraska, Omaha, with the Texas Biomedical Research Institute, San Antonio, might have stumbled upon a strategic workaround for mitigating the immune response.
They have proposed that cannabidiol (CBD) be used in lieu of other agents with potentially toxic effects. Animal and human trials have established that CBD confers a relatively high margin of safety coupled with favorable tolerance, providing a viable option for effectively targeting the inflammatory processes of SARS-CoV-2–based pulmonary disease. Furthermore, efficacy increased when CBD was combined with a terpene formulation, especially with respect to the more traditional steroid therapy.3
SARS-CoV-2 exhibits binding affinity for the ACE2 receptor, which is expressed in the lungs as well as other known predilection sites of infection. Ongoing studies attempt to modulate ACE2 expression, thereby eliminating its conspicuous role as “viral gateways,” perhaps even more so in patients with lung pathologies (e.g., people with chronic obstructive pulmonary disease [COPD] and smokers) as they already are prone to increased respiratory morbidity. CBD lacks tetrahydrocannabinol (THC), or the psychoactive component of cannabis sativa, rendering the agent to be particularly attractive from a therapeutic perspective. In addition to being devoid of abuse potential, CBD exhibits remarkable anti-inflammatory properties. It should be noted that considerable overlap exists between tobacco and cannabis users, and it is too early to determine the impact on COVID-19. As opposed to cannabis’s effect on ACE2 levels, smoking exhibits a proinflammatory role by up-regulating ACE2 expression.3 However, there are currently numerous conflicting reports in circulation about the positive effect of nicotine on COVID-19 outcome; confounding variables will need to be explored further in patients with a history of using nicotine and cannabis together.
From an immunologic perspective, the endocannabinoid system (ECS) plays an integral role in cell signaling by interacting with natural chemicals of the body, namely, cannabinoids with designated targets at the cannabinoid receptor 1 (CB1) and the CB2, respectively. The CB2 receptor is of particular interest as it is intimately involved in immune homeostasis; the primary goal of these COVID-19 studies is to modulate the endocannabinoid system via targeted CB2 therapies to produce an immunosuppressant effect.4 CB2 activation, be it by means of THC or CBD agonism, may prove to be beneficial by inhibiting the cytokine influx.
Unfortunately, there is a general dearth of data on COVID-19–exposed cannabis users, whether the drug is consumed for medication or recreational purposes. It has been suggested that cannabis intake might contribute toward the development of a cough, complicating the overall clinical outcome for those infected with the virus. The presence of a cough, even in an otherwise asymptomatic individual, facilitates viral spread. As for those cannabis users experiencing COVID-19 symptomatology, they can expect rapid clinical deterioration, including pronounced fatigue and a change in mental status.
According to pulmonary specialists and representatives of the American Lung Association, recreational cannabis use may be associated with a bronchitis-like inflammation (comparable with chronic bronchitis/COPD for chronic users) of the airways, along the lines of cigarette smoking.5 As far as cannabis smokers are concerned, the rationale for lung irritation is believed to stem from the relatively large portion of unburnt plant content that is inhaled in a given joint. If there is a superimposed infection, as is the case with COVID-19, the patient may experience further risk of adverse respiratory effects. This serves as a diagnostic dilemma for physicians, especially when they encounter patients who recently started dabbling with cannabis as a means of placating themselves or because they’ve heard rumors that it will somehow protect them from COVID-19. The entire assessment plan is slowed down as a result of the confounding variable (onset of a cough), which may arise independently of COVID-19 in cannabis users. Vulnerable populations include smokers and those with COPD or asthma, as they are more likely to require ventilator assistance during the course of COVID-19 therapy.5 Asthmatics and COPD patients are prone to bronchospasms because of sensitive airways.
COVID-19 safety protocols for cannabis users
Because of increased risk of respiratory morbidity, clinicians advise that consumption of recreational cannabinoids be scaled back during the course of the pandemic. In light of conflicting news from several media outlets regarding the efficacy of cannabis intake with respect to COVID-19, preexisting users might unwittingly increase their consumption as a preemptive measure against being exposed to the infection. To prevent transmission among users, clinicians should discourage patients from sharing joints. This recommendation is thematically consistent with general precautionary measures about the dangers of sharing utensils, drinking cups/glasses, and so on, amid the pandemic.
Despite promising preliminary research results, CBD cannot be wholeheartedly recommended at this time; patients already on medically administered cannabinoids are urged to discuss the risk-benefit ratio with their respective health care clinicians. Cannabinoid therapies present a massive opportunity from the perspective of immunomodulation, especially when considering the prevalence of drug use. However, to improve clinical guidelines with respect to COVID-19 outcomes, it would be prudent to increase the overall volume of preclinical knowledge by gathering retrospective data (from case-control designs) and randomized prospective trials.
A more comprehensive list of advice from physicians concerning casual or chronic cannabis users may also include: adopting a dedicated delivery or dispensing system for cannabis products, making considerations for decontamination (i.e., disinfecting mouthpieces), ensuring cleansing precautions are maintained (washing thoroughly before and after use or procurement), switching to inhalation alternates (e.g., tinctures, edibles, and/or oils) to decrease further irritation to the lungs. For bong users, it is recommended that they apply rubbing alcohol to clean their device followed with a minute of air-drying.6
Conclusion
The literature from preclinical studies appears to largely favor the use of CBD, but there remains an element of uncertainty with respect to implementing cannabinoids for the treatment of coronavirus.
COVID-19 cannabinoid intervention is a hot topic with renewed interest from the industry and the public at large, but viral-focused therapies remain a relatively underused area worth exploring with case-control designs and randomized prospective trials. As cannabis legalization is picking up momentum across five additional states, the time is ripe to systematically investigate the therapeutic applications of the drug beyond merely preclinical data. Aside from educational reform initiatives, clinicians might proactively launch a platform that integrates telemedicine as well as digital apps, directly linking the patient to the clinician and monitoring the efficacy of program initiatives in real time.
References
1. Long A. Consumers’ cannabis buying patterns change markedly in wake of COVID-19 pandemic. Marijuana Business Daily. 2020 Sep 22. https://mjbizdaily.com/consumers-cannabis-buying-patterns-change-markedly-in-wake-of-covid-pandemic/.
2. Bures B. How the coronavirus pandemic is increasing global demand for marijuana. Chicago Tribune. 2020 Jul 1. https://www.chicagotribune.com/marijuana/sns-tft-coronavirus-increases-global-marijuana-demand-20200701-oygaxryb7vhcjfeu44cgacicaa-story.html.
3. Walters J. Marijuana and COVID-19: Top studies. CannaMD. 2020 Aug 19. https://www.cannamd.com/marijuana-covid-19-top-studies/.
4. El Biali M et al. Med Cannabis Cannabinoids. 2020 Aug 19. doi: 10.1159/000510799.
5. LaMotte S. “Smoking weed and coronavirus: Even occasional use raises risk of COVID-19 complications.” CNN Health. 2020 Apr 10. https://www.cnn.com/2020/04/10/health/smoking-weed-coronavirus-wellness/index.html
6. Yafai S and Etengoff S. The case for cannabis: Advising cannabis users about COVID-19. Emergency Medicine News. 2020 May 20;42(5B).
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Mr. Choudhry is a research assistant at the IMCHF. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. Dr. Islam, Mr. Choudhry, and Dr. Choudhry reported no relevant disclosures.
An intriguing pattern has emerged for cannabis enthusiasts as a result of lockdowns and statewide safety restrictions for COVID-19.
Consumers, as of late, have been shopping for larger marijuana baskets per trip to the dispensaries in various states, including California, Colorado, Nevada, and Washington, . However, they are also cutting down on the number of trips, perhaps, as a preventive measure to reduce the risk of exposure to coronavirus during this pandemic. Sales dipped considerably by the end of March only to experience a resurgence after the issuing of stimulus checks and unemployment benefits.
For the past few years, cannabis consumption remained steady while the industry continued to thrive with robust sales of the drug. It is a recession-proof phenomenon, therefore presenting a unique opportunity for clinicians with respect to patient education and individualized care.1
An unfortunate carryover of the governmental restrictions, self-isolation, and social estrangement is that consumers are now turning to the dark web as a source for continuous supply of cannabis. Prepandemic, according to the U.N. 2020 World Drug Report, there was already a 30% increase in sales of cannabis between 2009 and 2018. COVID-19 has fractured the drug’s supply chain and created an inescapable void that is being filled by drug traffickers.2 A clinical dilemma is posed when a user procures counterfeit cannabis or a drug batch with impurities.
Riding the cytokine storm
Cytokines are a host of proteins with designated regulatory and immune responses that play an instrumental role in cell signaling. The aptly named “cytokine storm” conjures up the image of an imperiled immune system spiraling out of control; it is, in fact, an extreme immune response that culminates into a massive influx of cytokines released into the bloodstream. Without the presence of an immunologic threat, cytokines are responsible for maintaining homeostasis and the functionality of immune cells. However, acute cytokine release (i.e., cytokine storm), as is the case with severe COVID-19, jeopardizes organ function (for example, interstitial lung disease) with clinical symptoms, such as fever, cough, dyspnea, and myalgia.
Benefits and drawbacks of immunosuppressive agents
To inhibit cytokine release (e.g., interleukin-6 cytokine levels), immunosuppressive agents such as tocilizumab have been leveraged to damper the body’s overactive inflammatory response to perceived immunologic stressors, in particular, COVID-19. While the aforementioned agent was remarkably effective with respect to lung consolidation clearance in most of the patients tested, a host of untoward effects prevent its general applicability and use. However, a team of researchers from the University of Nebraska, Omaha, with the Texas Biomedical Research Institute, San Antonio, might have stumbled upon a strategic workaround for mitigating the immune response.
They have proposed that cannabidiol (CBD) be used in lieu of other agents with potentially toxic effects. Animal and human trials have established that CBD confers a relatively high margin of safety coupled with favorable tolerance, providing a viable option for effectively targeting the inflammatory processes of SARS-CoV-2–based pulmonary disease. Furthermore, efficacy increased when CBD was combined with a terpene formulation, especially with respect to the more traditional steroid therapy.3
SARS-CoV-2 exhibits binding affinity for the ACE2 receptor, which is expressed in the lungs as well as other known predilection sites of infection. Ongoing studies attempt to modulate ACE2 expression, thereby eliminating its conspicuous role as “viral gateways,” perhaps even more so in patients with lung pathologies (e.g., people with chronic obstructive pulmonary disease [COPD] and smokers) as they already are prone to increased respiratory morbidity. CBD lacks tetrahydrocannabinol (THC), or the psychoactive component of cannabis sativa, rendering the agent to be particularly attractive from a therapeutic perspective. In addition to being devoid of abuse potential, CBD exhibits remarkable anti-inflammatory properties. It should be noted that considerable overlap exists between tobacco and cannabis users, and it is too early to determine the impact on COVID-19. As opposed to cannabis’s effect on ACE2 levels, smoking exhibits a proinflammatory role by up-regulating ACE2 expression.3 However, there are currently numerous conflicting reports in circulation about the positive effect of nicotine on COVID-19 outcome; confounding variables will need to be explored further in patients with a history of using nicotine and cannabis together.
From an immunologic perspective, the endocannabinoid system (ECS) plays an integral role in cell signaling by interacting with natural chemicals of the body, namely, cannabinoids with designated targets at the cannabinoid receptor 1 (CB1) and the CB2, respectively. The CB2 receptor is of particular interest as it is intimately involved in immune homeostasis; the primary goal of these COVID-19 studies is to modulate the endocannabinoid system via targeted CB2 therapies to produce an immunosuppressant effect.4 CB2 activation, be it by means of THC or CBD agonism, may prove to be beneficial by inhibiting the cytokine influx.
Unfortunately, there is a general dearth of data on COVID-19–exposed cannabis users, whether the drug is consumed for medication or recreational purposes. It has been suggested that cannabis intake might contribute toward the development of a cough, complicating the overall clinical outcome for those infected with the virus. The presence of a cough, even in an otherwise asymptomatic individual, facilitates viral spread. As for those cannabis users experiencing COVID-19 symptomatology, they can expect rapid clinical deterioration, including pronounced fatigue and a change in mental status.
According to pulmonary specialists and representatives of the American Lung Association, recreational cannabis use may be associated with a bronchitis-like inflammation (comparable with chronic bronchitis/COPD for chronic users) of the airways, along the lines of cigarette smoking.5 As far as cannabis smokers are concerned, the rationale for lung irritation is believed to stem from the relatively large portion of unburnt plant content that is inhaled in a given joint. If there is a superimposed infection, as is the case with COVID-19, the patient may experience further risk of adverse respiratory effects. This serves as a diagnostic dilemma for physicians, especially when they encounter patients who recently started dabbling with cannabis as a means of placating themselves or because they’ve heard rumors that it will somehow protect them from COVID-19. The entire assessment plan is slowed down as a result of the confounding variable (onset of a cough), which may arise independently of COVID-19 in cannabis users. Vulnerable populations include smokers and those with COPD or asthma, as they are more likely to require ventilator assistance during the course of COVID-19 therapy.5 Asthmatics and COPD patients are prone to bronchospasms because of sensitive airways.
COVID-19 safety protocols for cannabis users
Because of increased risk of respiratory morbidity, clinicians advise that consumption of recreational cannabinoids be scaled back during the course of the pandemic. In light of conflicting news from several media outlets regarding the efficacy of cannabis intake with respect to COVID-19, preexisting users might unwittingly increase their consumption as a preemptive measure against being exposed to the infection. To prevent transmission among users, clinicians should discourage patients from sharing joints. This recommendation is thematically consistent with general precautionary measures about the dangers of sharing utensils, drinking cups/glasses, and so on, amid the pandemic.
Despite promising preliminary research results, CBD cannot be wholeheartedly recommended at this time; patients already on medically administered cannabinoids are urged to discuss the risk-benefit ratio with their respective health care clinicians. Cannabinoid therapies present a massive opportunity from the perspective of immunomodulation, especially when considering the prevalence of drug use. However, to improve clinical guidelines with respect to COVID-19 outcomes, it would be prudent to increase the overall volume of preclinical knowledge by gathering retrospective data (from case-control designs) and randomized prospective trials.
A more comprehensive list of advice from physicians concerning casual or chronic cannabis users may also include: adopting a dedicated delivery or dispensing system for cannabis products, making considerations for decontamination (i.e., disinfecting mouthpieces), ensuring cleansing precautions are maintained (washing thoroughly before and after use or procurement), switching to inhalation alternates (e.g., tinctures, edibles, and/or oils) to decrease further irritation to the lungs. For bong users, it is recommended that they apply rubbing alcohol to clean their device followed with a minute of air-drying.6
Conclusion
The literature from preclinical studies appears to largely favor the use of CBD, but there remains an element of uncertainty with respect to implementing cannabinoids for the treatment of coronavirus.
COVID-19 cannabinoid intervention is a hot topic with renewed interest from the industry and the public at large, but viral-focused therapies remain a relatively underused area worth exploring with case-control designs and randomized prospective trials. As cannabis legalization is picking up momentum across five additional states, the time is ripe to systematically investigate the therapeutic applications of the drug beyond merely preclinical data. Aside from educational reform initiatives, clinicians might proactively launch a platform that integrates telemedicine as well as digital apps, directly linking the patient to the clinician and monitoring the efficacy of program initiatives in real time.
References
1. Long A. Consumers’ cannabis buying patterns change markedly in wake of COVID-19 pandemic. Marijuana Business Daily. 2020 Sep 22. https://mjbizdaily.com/consumers-cannabis-buying-patterns-change-markedly-in-wake-of-covid-pandemic/.
2. Bures B. How the coronavirus pandemic is increasing global demand for marijuana. Chicago Tribune. 2020 Jul 1. https://www.chicagotribune.com/marijuana/sns-tft-coronavirus-increases-global-marijuana-demand-20200701-oygaxryb7vhcjfeu44cgacicaa-story.html.
3. Walters J. Marijuana and COVID-19: Top studies. CannaMD. 2020 Aug 19. https://www.cannamd.com/marijuana-covid-19-top-studies/.
4. El Biali M et al. Med Cannabis Cannabinoids. 2020 Aug 19. doi: 10.1159/000510799.
5. LaMotte S. “Smoking weed and coronavirus: Even occasional use raises risk of COVID-19 complications.” CNN Health. 2020 Apr 10. https://www.cnn.com/2020/04/10/health/smoking-weed-coronavirus-wellness/index.html
6. Yafai S and Etengoff S. The case for cannabis: Advising cannabis users about COVID-19. Emergency Medicine News. 2020 May 20;42(5B).
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Mr. Choudhry is a research assistant at the IMCHF. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. Dr. Islam, Mr. Choudhry, and Dr. Choudhry reported no relevant disclosures.
An intriguing pattern has emerged for cannabis enthusiasts as a result of lockdowns and statewide safety restrictions for COVID-19.
Consumers, as of late, have been shopping for larger marijuana baskets per trip to the dispensaries in various states, including California, Colorado, Nevada, and Washington, . However, they are also cutting down on the number of trips, perhaps, as a preventive measure to reduce the risk of exposure to coronavirus during this pandemic. Sales dipped considerably by the end of March only to experience a resurgence after the issuing of stimulus checks and unemployment benefits.
For the past few years, cannabis consumption remained steady while the industry continued to thrive with robust sales of the drug. It is a recession-proof phenomenon, therefore presenting a unique opportunity for clinicians with respect to patient education and individualized care.1
An unfortunate carryover of the governmental restrictions, self-isolation, and social estrangement is that consumers are now turning to the dark web as a source for continuous supply of cannabis. Prepandemic, according to the U.N. 2020 World Drug Report, there was already a 30% increase in sales of cannabis between 2009 and 2018. COVID-19 has fractured the drug’s supply chain and created an inescapable void that is being filled by drug traffickers.2 A clinical dilemma is posed when a user procures counterfeit cannabis or a drug batch with impurities.
Riding the cytokine storm
Cytokines are a host of proteins with designated regulatory and immune responses that play an instrumental role in cell signaling. The aptly named “cytokine storm” conjures up the image of an imperiled immune system spiraling out of control; it is, in fact, an extreme immune response that culminates into a massive influx of cytokines released into the bloodstream. Without the presence of an immunologic threat, cytokines are responsible for maintaining homeostasis and the functionality of immune cells. However, acute cytokine release (i.e., cytokine storm), as is the case with severe COVID-19, jeopardizes organ function (for example, interstitial lung disease) with clinical symptoms, such as fever, cough, dyspnea, and myalgia.
Benefits and drawbacks of immunosuppressive agents
To inhibit cytokine release (e.g., interleukin-6 cytokine levels), immunosuppressive agents such as tocilizumab have been leveraged to damper the body’s overactive inflammatory response to perceived immunologic stressors, in particular, COVID-19. While the aforementioned agent was remarkably effective with respect to lung consolidation clearance in most of the patients tested, a host of untoward effects prevent its general applicability and use. However, a team of researchers from the University of Nebraska, Omaha, with the Texas Biomedical Research Institute, San Antonio, might have stumbled upon a strategic workaround for mitigating the immune response.
They have proposed that cannabidiol (CBD) be used in lieu of other agents with potentially toxic effects. Animal and human trials have established that CBD confers a relatively high margin of safety coupled with favorable tolerance, providing a viable option for effectively targeting the inflammatory processes of SARS-CoV-2–based pulmonary disease. Furthermore, efficacy increased when CBD was combined with a terpene formulation, especially with respect to the more traditional steroid therapy.3
SARS-CoV-2 exhibits binding affinity for the ACE2 receptor, which is expressed in the lungs as well as other known predilection sites of infection. Ongoing studies attempt to modulate ACE2 expression, thereby eliminating its conspicuous role as “viral gateways,” perhaps even more so in patients with lung pathologies (e.g., people with chronic obstructive pulmonary disease [COPD] and smokers) as they already are prone to increased respiratory morbidity. CBD lacks tetrahydrocannabinol (THC), or the psychoactive component of cannabis sativa, rendering the agent to be particularly attractive from a therapeutic perspective. In addition to being devoid of abuse potential, CBD exhibits remarkable anti-inflammatory properties. It should be noted that considerable overlap exists between tobacco and cannabis users, and it is too early to determine the impact on COVID-19. As opposed to cannabis’s effect on ACE2 levels, smoking exhibits a proinflammatory role by up-regulating ACE2 expression.3 However, there are currently numerous conflicting reports in circulation about the positive effect of nicotine on COVID-19 outcome; confounding variables will need to be explored further in patients with a history of using nicotine and cannabis together.
From an immunologic perspective, the endocannabinoid system (ECS) plays an integral role in cell signaling by interacting with natural chemicals of the body, namely, cannabinoids with designated targets at the cannabinoid receptor 1 (CB1) and the CB2, respectively. The CB2 receptor is of particular interest as it is intimately involved in immune homeostasis; the primary goal of these COVID-19 studies is to modulate the endocannabinoid system via targeted CB2 therapies to produce an immunosuppressant effect.4 CB2 activation, be it by means of THC or CBD agonism, may prove to be beneficial by inhibiting the cytokine influx.
Unfortunately, there is a general dearth of data on COVID-19–exposed cannabis users, whether the drug is consumed for medication or recreational purposes. It has been suggested that cannabis intake might contribute toward the development of a cough, complicating the overall clinical outcome for those infected with the virus. The presence of a cough, even in an otherwise asymptomatic individual, facilitates viral spread. As for those cannabis users experiencing COVID-19 symptomatology, they can expect rapid clinical deterioration, including pronounced fatigue and a change in mental status.
According to pulmonary specialists and representatives of the American Lung Association, recreational cannabis use may be associated with a bronchitis-like inflammation (comparable with chronic bronchitis/COPD for chronic users) of the airways, along the lines of cigarette smoking.5 As far as cannabis smokers are concerned, the rationale for lung irritation is believed to stem from the relatively large portion of unburnt plant content that is inhaled in a given joint. If there is a superimposed infection, as is the case with COVID-19, the patient may experience further risk of adverse respiratory effects. This serves as a diagnostic dilemma for physicians, especially when they encounter patients who recently started dabbling with cannabis as a means of placating themselves or because they’ve heard rumors that it will somehow protect them from COVID-19. The entire assessment plan is slowed down as a result of the confounding variable (onset of a cough), which may arise independently of COVID-19 in cannabis users. Vulnerable populations include smokers and those with COPD or asthma, as they are more likely to require ventilator assistance during the course of COVID-19 therapy.5 Asthmatics and COPD patients are prone to bronchospasms because of sensitive airways.
COVID-19 safety protocols for cannabis users
Because of increased risk of respiratory morbidity, clinicians advise that consumption of recreational cannabinoids be scaled back during the course of the pandemic. In light of conflicting news from several media outlets regarding the efficacy of cannabis intake with respect to COVID-19, preexisting users might unwittingly increase their consumption as a preemptive measure against being exposed to the infection. To prevent transmission among users, clinicians should discourage patients from sharing joints. This recommendation is thematically consistent with general precautionary measures about the dangers of sharing utensils, drinking cups/glasses, and so on, amid the pandemic.
Despite promising preliminary research results, CBD cannot be wholeheartedly recommended at this time; patients already on medically administered cannabinoids are urged to discuss the risk-benefit ratio with their respective health care clinicians. Cannabinoid therapies present a massive opportunity from the perspective of immunomodulation, especially when considering the prevalence of drug use. However, to improve clinical guidelines with respect to COVID-19 outcomes, it would be prudent to increase the overall volume of preclinical knowledge by gathering retrospective data (from case-control designs) and randomized prospective trials.
A more comprehensive list of advice from physicians concerning casual or chronic cannabis users may also include: adopting a dedicated delivery or dispensing system for cannabis products, making considerations for decontamination (i.e., disinfecting mouthpieces), ensuring cleansing precautions are maintained (washing thoroughly before and after use or procurement), switching to inhalation alternates (e.g., tinctures, edibles, and/or oils) to decrease further irritation to the lungs. For bong users, it is recommended that they apply rubbing alcohol to clean their device followed with a minute of air-drying.6
Conclusion
The literature from preclinical studies appears to largely favor the use of CBD, but there remains an element of uncertainty with respect to implementing cannabinoids for the treatment of coronavirus.
COVID-19 cannabinoid intervention is a hot topic with renewed interest from the industry and the public at large, but viral-focused therapies remain a relatively underused area worth exploring with case-control designs and randomized prospective trials. As cannabis legalization is picking up momentum across five additional states, the time is ripe to systematically investigate the therapeutic applications of the drug beyond merely preclinical data. Aside from educational reform initiatives, clinicians might proactively launch a platform that integrates telemedicine as well as digital apps, directly linking the patient to the clinician and monitoring the efficacy of program initiatives in real time.
References
1. Long A. Consumers’ cannabis buying patterns change markedly in wake of COVID-19 pandemic. Marijuana Business Daily. 2020 Sep 22. https://mjbizdaily.com/consumers-cannabis-buying-patterns-change-markedly-in-wake-of-covid-pandemic/.
2. Bures B. How the coronavirus pandemic is increasing global demand for marijuana. Chicago Tribune. 2020 Jul 1. https://www.chicagotribune.com/marijuana/sns-tft-coronavirus-increases-global-marijuana-demand-20200701-oygaxryb7vhcjfeu44cgacicaa-story.html.
3. Walters J. Marijuana and COVID-19: Top studies. CannaMD. 2020 Aug 19. https://www.cannamd.com/marijuana-covid-19-top-studies/.
4. El Biali M et al. Med Cannabis Cannabinoids. 2020 Aug 19. doi: 10.1159/000510799.
5. LaMotte S. “Smoking weed and coronavirus: Even occasional use raises risk of COVID-19 complications.” CNN Health. 2020 Apr 10. https://www.cnn.com/2020/04/10/health/smoking-weed-coronavirus-wellness/index.html
6. Yafai S and Etengoff S. The case for cannabis: Advising cannabis users about COVID-19. Emergency Medicine News. 2020 May 20;42(5B).
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Mr. Choudhry is a research assistant at the IMCHF. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. Dr. Islam, Mr. Choudhry, and Dr. Choudhry reported no relevant disclosures.
COVID-19: Optimizing therapeutic strategies for children, adolescents with ADHD
Recently, the Yakima Health District (YHD), in collaboration with the Washington State Department of Health, issued dramatic revisions to its educational curriculum, opting for exclusively remote learning as an important next step in COVID-19 containment measures.
The newly implemented “enhanced” distance-learning paradigm has garnered considerable national attention. Even more noteworthy is how YHD addressed those with language barriers and learning differences such as ADHD as a “priority group”; these individuals are exempt from the newly implemented measures, and small instructional groups of no more than five “at-risk” students will be directly supervised by specialized educators.1,2 To overcome these new unprecedented challenges from the coronavirus pandemic, especially from the perspective of distance education and mental health for susceptible groups such as those with ADHD, it is of utmost importance to explore various programs of interest, as well as the targeted therapies being considered during this crisis.
From a therapeutic standpoint, individuals with learning differences are more likely to play catch-up with their age-matched peers. This puts them at significant risk for developmental delays with symptoms manifesting as disruptive behavioral issues. This is why ongoing parental guidance, coupled with a paradoxically stimulating environment, is critical for children and adolescents with ADHD.3 Accumulating evidence, based on a myriad of studies, demonstrates that childhood treatment with ADHD stimulants reduces the incidence of future substance use, as well as that of other negative outcomes.4,5
Therapeutic strategies that work
“The new normal” has forced unique challenges on clinicians for mitigating distress by novel means of health care delivery. Given the paucity of research exploring the interactions of individuals with ADHD within the context of COVID-19, Take for example, the suggested guidelines from the European ADHD Guidelines Group (EAGG) – such as the following:
- Telecommunications in general, and telepsychiatry in particular, should function as the primary mode of health care delivery to fulfill societal standards of physical distancing.
- Children and adolescents with ADHD should be designated as a “priority group” with respect to monitoring initiatives by educators in a school setting, be it virtual or otherwise.
- Implementation of behavioral strategies by parent or guardian to address psychological well-being and reduce the presence of comorbid behavioral conditions (such as oppositional defiant disorder).
In addition to the aforementioned guidance, EAGG maintains that individuals with ADHD may be initiated on medications after the completion of a baseline examination; if the patients in question are already on a treatment regimen, they should proceed with it as indicated. Interruptions to therapy are not ideal because patients are then subjected to health-related stressors of COVID-19. Reasonable regulations concerning access to medications, without unnecessary delays, undoubtedly will facilitate patient needs, allowing for a smooth transition in day-to-day activities. The family, as a cohesive unit, may benefit from reeducation because it contributes toward the therapeutic process. Neurofeedback, coping skills, and cognitive restructuring training are potential modalities that can augment medications.
Although it may seem counterintuitive, parents or caregivers should resist the urge to increase the medication dose during an outbreak with the intended goal of diminishing the psychosocial burden of ADHD symptomatology. Likewise, unless indicated by a specialist, antipsychotics and/or hypnotics should not be introduced for addressing behavioral dysregulation (such as agitation) during the confinement period.
Historically, numerous clinicians have suggested that patients undergo a routine cardiovascular examination and EKG before being prescribed psychostimulants (the rationale for this recommendation is that sympathomimetics unduly affect blood pressure and heart rate).6,7 However, the American Academy of Pediatrics (AAP) and the American Heart Association (AHA) eventually amended their previous stance by releasing a joint statement in which they deemed a baseline EKG necessary only in ADHD patients with preexisting cardiac risk. For all other patients, the use of EKGs was entirely contingent on physician discretion. However, given the nature of safety precautions for COVID-19, it is prudent to discourage or delay in-person cardiovascular examination/monitoring protocols altogether, especially in those patients without known heart conditions.
Another area of concern is sleep dysfunction, which might exist as an untoward effect of ADHD medication intake or because of the presence of COVID-19 psychosocial stressors. However, clinicians advise that unnecessary psychopharmacology (such as hypnotics or melatonin) be avoided. Instead, conservative lifestyle measures should be enacted, emphasizing the role of proper sleep hygiene in maintaining optimal behavioral health. Despite setbacks to in-person appointments, patients are expected to continue their pharmacotherapy with “parent-focused” ADHD interventions taking a primary role in facilitating compliance through remote monitoring.
ADMiRE, a tertiary-level, dedicated ADHD intervention program from South Dublin, Ireland, has identified several roadblocks with respect to streamlining health care for individuals with ADHD during the confinement period. The proposed resolution to these issues, some of which are derived from EAGG guidelines, might have universal applications elsewhere, thereby facilitating the development of therapeutic services of interest. ADMiRE has noted a correspondence between the guidelines established by EAGG and that of the Canadian ADHD Resource Alliance (CADDRA), including minimal in-person interactions (in favor of virtual teleconferencing) and a cardiovascular screen can be performed in lieu of baseline cardiac auscultation. Moreover, in the event that the patient is a low cardiac risk candidate for ADHD treatment, monitoring protocols may be continued from a home setting. However, if a physical examination is indicated, CADDRA recommends the use of precautionary PPE before commencing ADHD pharmacotherapy.
One of the most significant hurdles is that of school closures because teacher feedback for baseline behavior was traditionally instrumental in dictating patient medical management (for example, for titration schedule). It is expected that, for the time being, this role will be supplanted by parental reports. As well as disclosing information on behavioral dysregulation, family members should be trained to relay critical information about the development of stimulant-induced cardiovascular symptoms – namely, dyspnea, chest pain, and/or palpitations. Furthermore, as primary caregivers, parents should harbor a certain degree of emotional sensitivity because their mood state may influence the child’s overall behavioral course in terms of symptom exacerbation.8
Toward adopting an integrated model for care
Developing an effective assessment plan for patients with ADHD often proves to be a challenging task for clinicians, perhaps even more so in environments that enforce social distancing and limited physical contact by default. As a neurodevelopmental disorder from childhood, the symptoms (including inattention, hyperactivity, and/or impulsivity) of ADHD do not arise in a vacuum – comorbid conditions include mood and anxiety disorders, which are complicated further by a background risk for substance use and self-medicating tendencies.9 Unfortunately, the pandemic has limited the breadth of non-COVID doctors visits, which hinders the overall diagnostic and monitoring process for identifiable comorbid conditions, such as autism spectrum disorder, intellectual disability, oppositional defiant and conduct disorders, and so on.10 Since ADHD symptoms cannot be treated by pharmacotherapy or behavioral interventions alone, our team advocates that families provide additional emotional support and continuous encouragement during these uncertain times.
ADHD and the self-medication hypothesis
The Khantzian self-medication hypothesis posits that a drug seeker may subconsciously gravitate toward a particular agent only to discover a sense of relief concerning inner turmoil or restlessness after use. Observations support the notion that individuals with undiagnosed ADHD have sought cocaine or even recreational designer drugs (such as methylenedioxypyrovalerone, or “bath salts”).11 Given the similar mechanism of action between cocaine, methylenedioxypyrovalerone, and prescribed psychostimulants such as methylphenidate, the results are hardly surprising because these agents all work on the brain’s “reward center” (for example, the nucleus accumbens) by invoking dopamine release. Aside from the aforementioned self-medication hypothesis, “downers” such as Xanax recently have experienced a prescription spike during the outbreak. While there isn’t an immediate cause for concern of Xanax abuse in ADHD individuals, the potential for addiction is certainly real, especially when taking into account comorbid anxiety disorder or sleep dysfunction.
Because of limited resources and precautionary guidelines, clinicians are at a considerable disadvantage in terms of formulating a comprehensive diagnostic and treatment plan for children and adolescents with ADHD. This situation is further compounded by the recent closure of schools and the lack of feedback with respect to baseline behavior from teachers and specialized educators. This is why it is imperative for primary caregivers to closely monitor children with ADHD for developing changes in behavioral patterns (for example, mood or anxiety issues and drug-seeking or disruptive behavior) and work with health care professionals.
References
1. “Distance learning strongly recommended for all Yakima county schools.” NBC Right Now. 2020 Aug 5.
2. Retka J. “Enhanced” remote learning in Yakima county schools? What that means for students this fall. Yakima Herald-Republic. 2020 Aug 8.
3. Armstrong T. “To empower! Not Control! A holistic approach to ADHD.” American Institute for Learning and Development. 1998.
4. J Child Psychol Psychiatry. 2014 Aug;55(8):878-85.
5. Ir J Psychol Med. 2020 May 21:1-22.
6. Lancet Child Adolesc Health. 2020 Jun;4(6):412-4.
7. O’Keefe L. AAP News. 2008 Jun;29(6):1.
8. Asian J Psychiatr. 2020 Jun;51:102077.
9. Current Psychiatry. 2015 Dec;14(12):e3-4.
10. Encephale. 2020 Jun 7;46(3S):S85-92.
11. Current Psychiatry. 2014 Dec; 3(12): e3-4.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry is the chief scientific officer and head of the department of mental health and clini-cal research at the IMCHF and is Mr. Choudhry’s father. He has no disclosures.
Recently, the Yakima Health District (YHD), in collaboration with the Washington State Department of Health, issued dramatic revisions to its educational curriculum, opting for exclusively remote learning as an important next step in COVID-19 containment measures.
The newly implemented “enhanced” distance-learning paradigm has garnered considerable national attention. Even more noteworthy is how YHD addressed those with language barriers and learning differences such as ADHD as a “priority group”; these individuals are exempt from the newly implemented measures, and small instructional groups of no more than five “at-risk” students will be directly supervised by specialized educators.1,2 To overcome these new unprecedented challenges from the coronavirus pandemic, especially from the perspective of distance education and mental health for susceptible groups such as those with ADHD, it is of utmost importance to explore various programs of interest, as well as the targeted therapies being considered during this crisis.
From a therapeutic standpoint, individuals with learning differences are more likely to play catch-up with their age-matched peers. This puts them at significant risk for developmental delays with symptoms manifesting as disruptive behavioral issues. This is why ongoing parental guidance, coupled with a paradoxically stimulating environment, is critical for children and adolescents with ADHD.3 Accumulating evidence, based on a myriad of studies, demonstrates that childhood treatment with ADHD stimulants reduces the incidence of future substance use, as well as that of other negative outcomes.4,5
Therapeutic strategies that work
“The new normal” has forced unique challenges on clinicians for mitigating distress by novel means of health care delivery. Given the paucity of research exploring the interactions of individuals with ADHD within the context of COVID-19, Take for example, the suggested guidelines from the European ADHD Guidelines Group (EAGG) – such as the following:
- Telecommunications in general, and telepsychiatry in particular, should function as the primary mode of health care delivery to fulfill societal standards of physical distancing.
- Children and adolescents with ADHD should be designated as a “priority group” with respect to monitoring initiatives by educators in a school setting, be it virtual or otherwise.
- Implementation of behavioral strategies by parent or guardian to address psychological well-being and reduce the presence of comorbid behavioral conditions (such as oppositional defiant disorder).
In addition to the aforementioned guidance, EAGG maintains that individuals with ADHD may be initiated on medications after the completion of a baseline examination; if the patients in question are already on a treatment regimen, they should proceed with it as indicated. Interruptions to therapy are not ideal because patients are then subjected to health-related stressors of COVID-19. Reasonable regulations concerning access to medications, without unnecessary delays, undoubtedly will facilitate patient needs, allowing for a smooth transition in day-to-day activities. The family, as a cohesive unit, may benefit from reeducation because it contributes toward the therapeutic process. Neurofeedback, coping skills, and cognitive restructuring training are potential modalities that can augment medications.
Although it may seem counterintuitive, parents or caregivers should resist the urge to increase the medication dose during an outbreak with the intended goal of diminishing the psychosocial burden of ADHD symptomatology. Likewise, unless indicated by a specialist, antipsychotics and/or hypnotics should not be introduced for addressing behavioral dysregulation (such as agitation) during the confinement period.
Historically, numerous clinicians have suggested that patients undergo a routine cardiovascular examination and EKG before being prescribed psychostimulants (the rationale for this recommendation is that sympathomimetics unduly affect blood pressure and heart rate).6,7 However, the American Academy of Pediatrics (AAP) and the American Heart Association (AHA) eventually amended their previous stance by releasing a joint statement in which they deemed a baseline EKG necessary only in ADHD patients with preexisting cardiac risk. For all other patients, the use of EKGs was entirely contingent on physician discretion. However, given the nature of safety precautions for COVID-19, it is prudent to discourage or delay in-person cardiovascular examination/monitoring protocols altogether, especially in those patients without known heart conditions.
Another area of concern is sleep dysfunction, which might exist as an untoward effect of ADHD medication intake or because of the presence of COVID-19 psychosocial stressors. However, clinicians advise that unnecessary psychopharmacology (such as hypnotics or melatonin) be avoided. Instead, conservative lifestyle measures should be enacted, emphasizing the role of proper sleep hygiene in maintaining optimal behavioral health. Despite setbacks to in-person appointments, patients are expected to continue their pharmacotherapy with “parent-focused” ADHD interventions taking a primary role in facilitating compliance through remote monitoring.
ADMiRE, a tertiary-level, dedicated ADHD intervention program from South Dublin, Ireland, has identified several roadblocks with respect to streamlining health care for individuals with ADHD during the confinement period. The proposed resolution to these issues, some of which are derived from EAGG guidelines, might have universal applications elsewhere, thereby facilitating the development of therapeutic services of interest. ADMiRE has noted a correspondence between the guidelines established by EAGG and that of the Canadian ADHD Resource Alliance (CADDRA), including minimal in-person interactions (in favor of virtual teleconferencing) and a cardiovascular screen can be performed in lieu of baseline cardiac auscultation. Moreover, in the event that the patient is a low cardiac risk candidate for ADHD treatment, monitoring protocols may be continued from a home setting. However, if a physical examination is indicated, CADDRA recommends the use of precautionary PPE before commencing ADHD pharmacotherapy.
One of the most significant hurdles is that of school closures because teacher feedback for baseline behavior was traditionally instrumental in dictating patient medical management (for example, for titration schedule). It is expected that, for the time being, this role will be supplanted by parental reports. As well as disclosing information on behavioral dysregulation, family members should be trained to relay critical information about the development of stimulant-induced cardiovascular symptoms – namely, dyspnea, chest pain, and/or palpitations. Furthermore, as primary caregivers, parents should harbor a certain degree of emotional sensitivity because their mood state may influence the child’s overall behavioral course in terms of symptom exacerbation.8
Toward adopting an integrated model for care
Developing an effective assessment plan for patients with ADHD often proves to be a challenging task for clinicians, perhaps even more so in environments that enforce social distancing and limited physical contact by default. As a neurodevelopmental disorder from childhood, the symptoms (including inattention, hyperactivity, and/or impulsivity) of ADHD do not arise in a vacuum – comorbid conditions include mood and anxiety disorders, which are complicated further by a background risk for substance use and self-medicating tendencies.9 Unfortunately, the pandemic has limited the breadth of non-COVID doctors visits, which hinders the overall diagnostic and monitoring process for identifiable comorbid conditions, such as autism spectrum disorder, intellectual disability, oppositional defiant and conduct disorders, and so on.10 Since ADHD symptoms cannot be treated by pharmacotherapy or behavioral interventions alone, our team advocates that families provide additional emotional support and continuous encouragement during these uncertain times.
ADHD and the self-medication hypothesis
The Khantzian self-medication hypothesis posits that a drug seeker may subconsciously gravitate toward a particular agent only to discover a sense of relief concerning inner turmoil or restlessness after use. Observations support the notion that individuals with undiagnosed ADHD have sought cocaine or even recreational designer drugs (such as methylenedioxypyrovalerone, or “bath salts”).11 Given the similar mechanism of action between cocaine, methylenedioxypyrovalerone, and prescribed psychostimulants such as methylphenidate, the results are hardly surprising because these agents all work on the brain’s “reward center” (for example, the nucleus accumbens) by invoking dopamine release. Aside from the aforementioned self-medication hypothesis, “downers” such as Xanax recently have experienced a prescription spike during the outbreak. While there isn’t an immediate cause for concern of Xanax abuse in ADHD individuals, the potential for addiction is certainly real, especially when taking into account comorbid anxiety disorder or sleep dysfunction.
Because of limited resources and precautionary guidelines, clinicians are at a considerable disadvantage in terms of formulating a comprehensive diagnostic and treatment plan for children and adolescents with ADHD. This situation is further compounded by the recent closure of schools and the lack of feedback with respect to baseline behavior from teachers and specialized educators. This is why it is imperative for primary caregivers to closely monitor children with ADHD for developing changes in behavioral patterns (for example, mood or anxiety issues and drug-seeking or disruptive behavior) and work with health care professionals.
References
1. “Distance learning strongly recommended for all Yakima county schools.” NBC Right Now. 2020 Aug 5.
2. Retka J. “Enhanced” remote learning in Yakima county schools? What that means for students this fall. Yakima Herald-Republic. 2020 Aug 8.
3. Armstrong T. “To empower! Not Control! A holistic approach to ADHD.” American Institute for Learning and Development. 1998.
4. J Child Psychol Psychiatry. 2014 Aug;55(8):878-85.
5. Ir J Psychol Med. 2020 May 21:1-22.
6. Lancet Child Adolesc Health. 2020 Jun;4(6):412-4.
7. O’Keefe L. AAP News. 2008 Jun;29(6):1.
8. Asian J Psychiatr. 2020 Jun;51:102077.
9. Current Psychiatry. 2015 Dec;14(12):e3-4.
10. Encephale. 2020 Jun 7;46(3S):S85-92.
11. Current Psychiatry. 2014 Dec; 3(12): e3-4.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry is the chief scientific officer and head of the department of mental health and clini-cal research at the IMCHF and is Mr. Choudhry’s father. He has no disclosures.
Recently, the Yakima Health District (YHD), in collaboration with the Washington State Department of Health, issued dramatic revisions to its educational curriculum, opting for exclusively remote learning as an important next step in COVID-19 containment measures.
The newly implemented “enhanced” distance-learning paradigm has garnered considerable national attention. Even more noteworthy is how YHD addressed those with language barriers and learning differences such as ADHD as a “priority group”; these individuals are exempt from the newly implemented measures, and small instructional groups of no more than five “at-risk” students will be directly supervised by specialized educators.1,2 To overcome these new unprecedented challenges from the coronavirus pandemic, especially from the perspective of distance education and mental health for susceptible groups such as those with ADHD, it is of utmost importance to explore various programs of interest, as well as the targeted therapies being considered during this crisis.
From a therapeutic standpoint, individuals with learning differences are more likely to play catch-up with their age-matched peers. This puts them at significant risk for developmental delays with symptoms manifesting as disruptive behavioral issues. This is why ongoing parental guidance, coupled with a paradoxically stimulating environment, is critical for children and adolescents with ADHD.3 Accumulating evidence, based on a myriad of studies, demonstrates that childhood treatment with ADHD stimulants reduces the incidence of future substance use, as well as that of other negative outcomes.4,5
Therapeutic strategies that work
“The new normal” has forced unique challenges on clinicians for mitigating distress by novel means of health care delivery. Given the paucity of research exploring the interactions of individuals with ADHD within the context of COVID-19, Take for example, the suggested guidelines from the European ADHD Guidelines Group (EAGG) – such as the following:
- Telecommunications in general, and telepsychiatry in particular, should function as the primary mode of health care delivery to fulfill societal standards of physical distancing.
- Children and adolescents with ADHD should be designated as a “priority group” with respect to monitoring initiatives by educators in a school setting, be it virtual or otherwise.
- Implementation of behavioral strategies by parent or guardian to address psychological well-being and reduce the presence of comorbid behavioral conditions (such as oppositional defiant disorder).
In addition to the aforementioned guidance, EAGG maintains that individuals with ADHD may be initiated on medications after the completion of a baseline examination; if the patients in question are already on a treatment regimen, they should proceed with it as indicated. Interruptions to therapy are not ideal because patients are then subjected to health-related stressors of COVID-19. Reasonable regulations concerning access to medications, without unnecessary delays, undoubtedly will facilitate patient needs, allowing for a smooth transition in day-to-day activities. The family, as a cohesive unit, may benefit from reeducation because it contributes toward the therapeutic process. Neurofeedback, coping skills, and cognitive restructuring training are potential modalities that can augment medications.
Although it may seem counterintuitive, parents or caregivers should resist the urge to increase the medication dose during an outbreak with the intended goal of diminishing the psychosocial burden of ADHD symptomatology. Likewise, unless indicated by a specialist, antipsychotics and/or hypnotics should not be introduced for addressing behavioral dysregulation (such as agitation) during the confinement period.
Historically, numerous clinicians have suggested that patients undergo a routine cardiovascular examination and EKG before being prescribed psychostimulants (the rationale for this recommendation is that sympathomimetics unduly affect blood pressure and heart rate).6,7 However, the American Academy of Pediatrics (AAP) and the American Heart Association (AHA) eventually amended their previous stance by releasing a joint statement in which they deemed a baseline EKG necessary only in ADHD patients with preexisting cardiac risk. For all other patients, the use of EKGs was entirely contingent on physician discretion. However, given the nature of safety precautions for COVID-19, it is prudent to discourage or delay in-person cardiovascular examination/monitoring protocols altogether, especially in those patients without known heart conditions.
Another area of concern is sleep dysfunction, which might exist as an untoward effect of ADHD medication intake or because of the presence of COVID-19 psychosocial stressors. However, clinicians advise that unnecessary psychopharmacology (such as hypnotics or melatonin) be avoided. Instead, conservative lifestyle measures should be enacted, emphasizing the role of proper sleep hygiene in maintaining optimal behavioral health. Despite setbacks to in-person appointments, patients are expected to continue their pharmacotherapy with “parent-focused” ADHD interventions taking a primary role in facilitating compliance through remote monitoring.
ADMiRE, a tertiary-level, dedicated ADHD intervention program from South Dublin, Ireland, has identified several roadblocks with respect to streamlining health care for individuals with ADHD during the confinement period. The proposed resolution to these issues, some of which are derived from EAGG guidelines, might have universal applications elsewhere, thereby facilitating the development of therapeutic services of interest. ADMiRE has noted a correspondence between the guidelines established by EAGG and that of the Canadian ADHD Resource Alliance (CADDRA), including minimal in-person interactions (in favor of virtual teleconferencing) and a cardiovascular screen can be performed in lieu of baseline cardiac auscultation. Moreover, in the event that the patient is a low cardiac risk candidate for ADHD treatment, monitoring protocols may be continued from a home setting. However, if a physical examination is indicated, CADDRA recommends the use of precautionary PPE before commencing ADHD pharmacotherapy.
One of the most significant hurdles is that of school closures because teacher feedback for baseline behavior was traditionally instrumental in dictating patient medical management (for example, for titration schedule). It is expected that, for the time being, this role will be supplanted by parental reports. As well as disclosing information on behavioral dysregulation, family members should be trained to relay critical information about the development of stimulant-induced cardiovascular symptoms – namely, dyspnea, chest pain, and/or palpitations. Furthermore, as primary caregivers, parents should harbor a certain degree of emotional sensitivity because their mood state may influence the child’s overall behavioral course in terms of symptom exacerbation.8
Toward adopting an integrated model for care
Developing an effective assessment plan for patients with ADHD often proves to be a challenging task for clinicians, perhaps even more so in environments that enforce social distancing and limited physical contact by default. As a neurodevelopmental disorder from childhood, the symptoms (including inattention, hyperactivity, and/or impulsivity) of ADHD do not arise in a vacuum – comorbid conditions include mood and anxiety disorders, which are complicated further by a background risk for substance use and self-medicating tendencies.9 Unfortunately, the pandemic has limited the breadth of non-COVID doctors visits, which hinders the overall diagnostic and monitoring process for identifiable comorbid conditions, such as autism spectrum disorder, intellectual disability, oppositional defiant and conduct disorders, and so on.10 Since ADHD symptoms cannot be treated by pharmacotherapy or behavioral interventions alone, our team advocates that families provide additional emotional support and continuous encouragement during these uncertain times.
ADHD and the self-medication hypothesis
The Khantzian self-medication hypothesis posits that a drug seeker may subconsciously gravitate toward a particular agent only to discover a sense of relief concerning inner turmoil or restlessness after use. Observations support the notion that individuals with undiagnosed ADHD have sought cocaine or even recreational designer drugs (such as methylenedioxypyrovalerone, or “bath salts”).11 Given the similar mechanism of action between cocaine, methylenedioxypyrovalerone, and prescribed psychostimulants such as methylphenidate, the results are hardly surprising because these agents all work on the brain’s “reward center” (for example, the nucleus accumbens) by invoking dopamine release. Aside from the aforementioned self-medication hypothesis, “downers” such as Xanax recently have experienced a prescription spike during the outbreak. While there isn’t an immediate cause for concern of Xanax abuse in ADHD individuals, the potential for addiction is certainly real, especially when taking into account comorbid anxiety disorder or sleep dysfunction.
Because of limited resources and precautionary guidelines, clinicians are at a considerable disadvantage in terms of formulating a comprehensive diagnostic and treatment plan for children and adolescents with ADHD. This situation is further compounded by the recent closure of schools and the lack of feedback with respect to baseline behavior from teachers and specialized educators. This is why it is imperative for primary caregivers to closely monitor children with ADHD for developing changes in behavioral patterns (for example, mood or anxiety issues and drug-seeking or disruptive behavior) and work with health care professionals.
References
1. “Distance learning strongly recommended for all Yakima county schools.” NBC Right Now. 2020 Aug 5.
2. Retka J. “Enhanced” remote learning in Yakima county schools? What that means for students this fall. Yakima Herald-Republic. 2020 Aug 8.
3. Armstrong T. “To empower! Not Control! A holistic approach to ADHD.” American Institute for Learning and Development. 1998.
4. J Child Psychol Psychiatry. 2014 Aug;55(8):878-85.
5. Ir J Psychol Med. 2020 May 21:1-22.
6. Lancet Child Adolesc Health. 2020 Jun;4(6):412-4.
7. O’Keefe L. AAP News. 2008 Jun;29(6):1.
8. Asian J Psychiatr. 2020 Jun;51:102077.
9. Current Psychiatry. 2015 Dec;14(12):e3-4.
10. Encephale. 2020 Jun 7;46(3S):S85-92.
11. Current Psychiatry. 2014 Dec; 3(12): e3-4.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry is the chief scientific officer and head of the department of mental health and clini-cal research at the IMCHF and is Mr. Choudhry’s father. He has no disclosures.
Revisiting Xanax amid the coronavirus crisis
One of the more alarming trends that has emerged during the coronavirus crisis is the concomitant rise in the use of benzodiazepines, such as Xanax. It has been reported that at-risk individuals began seeking prescription anxiolytics as early as mid-February with a consequent peak of 34% the following month, coinciding with the World Health Organization’s declaration of a global pandemic.1
Consistent with the available literature indicating that women are twice as likely to be affected by anxiety disorders, the prescription spikes were almost double when compared with those of their male counterparts.2 The pandemic has instilled a sense of fear in people, leading to social repercussions, such as estrangement, insomnia, and paranoia for at-risk populations.3,4
“Benzos” are commonly prescribed to help people sleep or to assist them in overcoming a host of anxiety disorders. The rapid onset of effects make Xanax a desirable and efficacious benzodiazepine.5 The use of these medications might not be an immediate cause for concern because patients might be taking it as intended. Nevertheless, clinicians are shying away from medical management in favor of counseling or therapy.
Dangerous trends
Numerous factors might contribute to this grim scenario, including patient dependence on benzodiazepines, paranoia about engaging with health care professionals because of fear tied to potential COVID-19 exposure, and/or increased access to illicit counterfeit pills from drug dealers or the dark web markets.
Lessons can be gleaned from the most extensive dark web drug busts in Britain’s history, in which a deluge of “pharmaceutical grade” Xanax pills made it to the hands of drug dealers and consumers between 2015 and 2017.6 A similar phenomenon emerged stateside.7 Virtually indistinguishable from recognized 2-mg Xanax pills, these fake pills posed a serious challenge to forensic scientists.8 The threat of overdose is very real for users targeted by the counterfeit Xanax trade, especially since those at risk often bypass professional health care guidelines.
In broad daylight, the drug dealers ran their operations revolving around two fake Xanax products: a primary knockoff and a limited edition – and vastly more potent “Red Devil” variant that was intentionally dyed for branding purposes. Because the “Red Devil” formulations contained 2.5 times the dose of the 2-mg pill, it had even more pronounced tolerance, dependence, and withdrawal effects (for example, panic attacks, anxiety, and/or hallucinations) – fatal consequences for users involved in consuming other drugs, such as alcohol or opioids. Preexisting drug users tend to gravitate toward benzodiazepines, such as alprazolam (Xanax), perhaps in part, because of its relatively rapid onset of action. Xanax also is known for inducing proeuphoric states at higher doses, hence the appeal of the “Red Devil” pills.
Benzodiazepines, as a class of drugs, facilitate the neurotransmitter gamma-aminobutryric acid’s (GABA) effect on the brain, producing anxiolytic, hypnotic, and/or anticonvulsant states within the user.9 Unbeknownst to numerous users is the fact that drugs such as alcohol and opioids, like Xanax, also serve as respiratory depressants, overriding the brain’s governance of the breathing mechanism. This, in turn, leads to unintended overdose deaths, even among seasoned drug seekers.
Overdose deaths have been steadily climbing over the years because it is common for some users to consume alcohol while being on Xanax therapy – without realizing that both substances are depressants and that taking them together can lead to side effects such as respiratory depression.
Forensic cases also have revealed that preexisting opioid consumers were drawn to Xanax; the drug’s potent mechanism of action would likely appeal to habituated users. A typical behavioral pattern has emerged among users and must be addressed. According to Australian Professor Shane Darke: “So they take their Xanax, they take their painkiller, then they get drunk, that could be enough to kill them.”
Fatalities are more likely when benzodiazepines are combined with other drug classes or if the existing supply is contaminated or laced (for example, with fentanyl).8
As far as deaths by accidental benzodiazepine overdose are concerned, a similar epidemic has been recorded in the United States. In 2013, almost one-third of all prescription overdose deaths can be attributed to the use of benzodiazepines (for example, Xanax, Valium, and Ativan). However, media attention has been considerably muted, especially when compared with that of narcotic abuse. This is even more puzzling when taking into account that three-quarters of benzodiazepine mortalities co-occur within the context of narcotic consumption. Substance Abuse and Mental Health Services Administration data confirm the ubiquitous nature of benzodiazepine (such as alprazolam) coprescriptions, accounting for roughly half of the 176,000 emergency department cases for 2011. The Centers for Disease Control and Prevention noted that there was a 67% increase in benzodiazepine prescriptions between 1996 and 2013, which warranted more stringent regulations for this particular class of drugs.
In 2016, the CDC issued new guidelines for opioid use acknowledging the danger of benzodiazepine coprescriptions. Food and Drug Administration “black box” warnings now grace the prescriptions of both of these drug classes.10 This trend remains on an upward trajectory, even more so during the pandemic, as there are 9.7 million prescriptions of anxiolytics/hypnotics such as Xanax, Ativan, and Klonopin in the United States as of March 2020, which represents a 10% increase over the previous year. , as well as the implementation of urine drug screening monitoring for drug adherence/compliance and diversion in those with suspected benzodiazepine addiction or a history of polysubstance abuse.11,12
Clinical correlates
For patients who present acutely with Xanax toxicity in the emergency room setting, we will need to initially stabilize the vital signs and address the ongoing symptoms. It is advisable to arrange health care accommodations for patients with physical dependence to monitor and treat their withdrawal symptoms. The patient should be enrolled in a comprehensive addiction facility after undergoing formal detoxification; a tapered treatment protocol will need to be implemented because quitting “cold turkey” can lead to convulsions and, in some cases, death. Patient education, talk therapy, and alternatives to benzodiazepines should be discussed with the clinician.13,145
However, to truly address the elephant in the room, we will need to consider institutional reforms to prevent a similar situation from arising in the future. Primary care physician shortages are compounded by changes in insurance policies. Nurses and physician assistants will need to be trained to manage benzodiazepine prescriptions. If there are community shortages in physicians, patients might turn to illegal means to secure their benzodiazepine supply, and it is imperative that we have the necessary fellowship and education programs to educate nonphysician health care clinicians with benzodiazepine management. Because physicians were prescribing benzodiazepines liberally, the Prescription Drug Monitoring Programs (PDMP) was enacted to monitor physician practices. Unfortunately, this ultimately intimidated physicians and effectively curbed reasonable physician prescribing patterns. It might be necessary to revisit existing prescription monitoring programs, encourage drug evaluations and guidelines based on evidence-based medicine and embrace telemedicine in order to facilitate patient-physician communication.
As of now, it is too early to prescribe Xanax routinely for ongoing anxiety experienced during the coronavirus crisis, and several physicians are cautious about prescribing antianxiety medications for more than a few months.17 Surprisingly, researchers in Barcelona have even explored the role of Xanax as potentially inhibiting Mpro, the primary protease of coronavirus, thereby forestalling the virus’s ability to replicate.16 However, it is worth noting that, given the preliminary nature of the results, any attempts at conclusively integrating Xanax within the context of coronavirus therapy would be premature.
References
1. Luhby T. Anti-anxiety medication prescriptions up 34% since coronavirus. CNN. 2020 Apr 16.
2. Women and Anxiety. Anxiety and Depression Association of America.
3. Shigemura J et al. Psychiatry Clin Neurosci. 2012 Apr 7;74(4):281-2.
4. Petersen A. More people are taking drugs for anxiety and insomnia, and doctors are worried. The Wall Street Journal. 2020 May 25.
5. Downey M. Xanax overdose and related deaths. National Drug & Alcohol Research Centre. UNSW Sydney.
6. Bryant B. Fake Xanax: The UK’s biggest ever dark net drugs bust. BBC. 2018 Mar 10.
7. Reinberg S. Fatal overdoses rising from sedatives like Valium, Xanax. HealthDay. 2016 Feb.
8. Is counterfeit Xanax dangerous? American Addiction Centers. Updated 2018 Nov 14.
9. McLaren E. Xanax history and statistics. Drugabuse.com.
10. Benzodiazepines and opioids. National Institute on Drug Abuse. 2018 Mar 15.
11. Choudhry Z et al. J Psychiatry. 2015;18(5). doi: 10.4172/2378-5756.1000319.
12. Islam FA et al. Current Psychiatry. 2018 Dec 17(12):43-4.
13. Adams M. Xanax death rate on the rise. White Sands Treatment. 2017 Sept.NEED LINK
14. Storrs C. Benzodiazepine overdose deaths soared in recent years, study finds. CNN. 2016 Feb. 18.
15. Hanscom DA. Plan A – Thrive and survive COVID-19. Back in Control. 2020.
16. Smith C. Xanax, a common anxiety medication, might actually block coronavirus. BGR. 2020 May 29.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships.
Mr. Choudhry is a research assistant at the IMCHF. He has no disclosures.
Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. He has no disclosures.
One of the more alarming trends that has emerged during the coronavirus crisis is the concomitant rise in the use of benzodiazepines, such as Xanax. It has been reported that at-risk individuals began seeking prescription anxiolytics as early as mid-February with a consequent peak of 34% the following month, coinciding with the World Health Organization’s declaration of a global pandemic.1
Consistent with the available literature indicating that women are twice as likely to be affected by anxiety disorders, the prescription spikes were almost double when compared with those of their male counterparts.2 The pandemic has instilled a sense of fear in people, leading to social repercussions, such as estrangement, insomnia, and paranoia for at-risk populations.3,4
“Benzos” are commonly prescribed to help people sleep or to assist them in overcoming a host of anxiety disorders. The rapid onset of effects make Xanax a desirable and efficacious benzodiazepine.5 The use of these medications might not be an immediate cause for concern because patients might be taking it as intended. Nevertheless, clinicians are shying away from medical management in favor of counseling or therapy.
Dangerous trends
Numerous factors might contribute to this grim scenario, including patient dependence on benzodiazepines, paranoia about engaging with health care professionals because of fear tied to potential COVID-19 exposure, and/or increased access to illicit counterfeit pills from drug dealers or the dark web markets.
Lessons can be gleaned from the most extensive dark web drug busts in Britain’s history, in which a deluge of “pharmaceutical grade” Xanax pills made it to the hands of drug dealers and consumers between 2015 and 2017.6 A similar phenomenon emerged stateside.7 Virtually indistinguishable from recognized 2-mg Xanax pills, these fake pills posed a serious challenge to forensic scientists.8 The threat of overdose is very real for users targeted by the counterfeit Xanax trade, especially since those at risk often bypass professional health care guidelines.
In broad daylight, the drug dealers ran their operations revolving around two fake Xanax products: a primary knockoff and a limited edition – and vastly more potent “Red Devil” variant that was intentionally dyed for branding purposes. Because the “Red Devil” formulations contained 2.5 times the dose of the 2-mg pill, it had even more pronounced tolerance, dependence, and withdrawal effects (for example, panic attacks, anxiety, and/or hallucinations) – fatal consequences for users involved in consuming other drugs, such as alcohol or opioids. Preexisting drug users tend to gravitate toward benzodiazepines, such as alprazolam (Xanax), perhaps in part, because of its relatively rapid onset of action. Xanax also is known for inducing proeuphoric states at higher doses, hence the appeal of the “Red Devil” pills.
Benzodiazepines, as a class of drugs, facilitate the neurotransmitter gamma-aminobutryric acid’s (GABA) effect on the brain, producing anxiolytic, hypnotic, and/or anticonvulsant states within the user.9 Unbeknownst to numerous users is the fact that drugs such as alcohol and opioids, like Xanax, also serve as respiratory depressants, overriding the brain’s governance of the breathing mechanism. This, in turn, leads to unintended overdose deaths, even among seasoned drug seekers.
Overdose deaths have been steadily climbing over the years because it is common for some users to consume alcohol while being on Xanax therapy – without realizing that both substances are depressants and that taking them together can lead to side effects such as respiratory depression.
Forensic cases also have revealed that preexisting opioid consumers were drawn to Xanax; the drug’s potent mechanism of action would likely appeal to habituated users. A typical behavioral pattern has emerged among users and must be addressed. According to Australian Professor Shane Darke: “So they take their Xanax, they take their painkiller, then they get drunk, that could be enough to kill them.”
Fatalities are more likely when benzodiazepines are combined with other drug classes or if the existing supply is contaminated or laced (for example, with fentanyl).8
As far as deaths by accidental benzodiazepine overdose are concerned, a similar epidemic has been recorded in the United States. In 2013, almost one-third of all prescription overdose deaths can be attributed to the use of benzodiazepines (for example, Xanax, Valium, and Ativan). However, media attention has been considerably muted, especially when compared with that of narcotic abuse. This is even more puzzling when taking into account that three-quarters of benzodiazepine mortalities co-occur within the context of narcotic consumption. Substance Abuse and Mental Health Services Administration data confirm the ubiquitous nature of benzodiazepine (such as alprazolam) coprescriptions, accounting for roughly half of the 176,000 emergency department cases for 2011. The Centers for Disease Control and Prevention noted that there was a 67% increase in benzodiazepine prescriptions between 1996 and 2013, which warranted more stringent regulations for this particular class of drugs.
In 2016, the CDC issued new guidelines for opioid use acknowledging the danger of benzodiazepine coprescriptions. Food and Drug Administration “black box” warnings now grace the prescriptions of both of these drug classes.10 This trend remains on an upward trajectory, even more so during the pandemic, as there are 9.7 million prescriptions of anxiolytics/hypnotics such as Xanax, Ativan, and Klonopin in the United States as of March 2020, which represents a 10% increase over the previous year. , as well as the implementation of urine drug screening monitoring for drug adherence/compliance and diversion in those with suspected benzodiazepine addiction or a history of polysubstance abuse.11,12
Clinical correlates
For patients who present acutely with Xanax toxicity in the emergency room setting, we will need to initially stabilize the vital signs and address the ongoing symptoms. It is advisable to arrange health care accommodations for patients with physical dependence to monitor and treat their withdrawal symptoms. The patient should be enrolled in a comprehensive addiction facility after undergoing formal detoxification; a tapered treatment protocol will need to be implemented because quitting “cold turkey” can lead to convulsions and, in some cases, death. Patient education, talk therapy, and alternatives to benzodiazepines should be discussed with the clinician.13,145
However, to truly address the elephant in the room, we will need to consider institutional reforms to prevent a similar situation from arising in the future. Primary care physician shortages are compounded by changes in insurance policies. Nurses and physician assistants will need to be trained to manage benzodiazepine prescriptions. If there are community shortages in physicians, patients might turn to illegal means to secure their benzodiazepine supply, and it is imperative that we have the necessary fellowship and education programs to educate nonphysician health care clinicians with benzodiazepine management. Because physicians were prescribing benzodiazepines liberally, the Prescription Drug Monitoring Programs (PDMP) was enacted to monitor physician practices. Unfortunately, this ultimately intimidated physicians and effectively curbed reasonable physician prescribing patterns. It might be necessary to revisit existing prescription monitoring programs, encourage drug evaluations and guidelines based on evidence-based medicine and embrace telemedicine in order to facilitate patient-physician communication.
As of now, it is too early to prescribe Xanax routinely for ongoing anxiety experienced during the coronavirus crisis, and several physicians are cautious about prescribing antianxiety medications for more than a few months.17 Surprisingly, researchers in Barcelona have even explored the role of Xanax as potentially inhibiting Mpro, the primary protease of coronavirus, thereby forestalling the virus’s ability to replicate.16 However, it is worth noting that, given the preliminary nature of the results, any attempts at conclusively integrating Xanax within the context of coronavirus therapy would be premature.
References
1. Luhby T. Anti-anxiety medication prescriptions up 34% since coronavirus. CNN. 2020 Apr 16.
2. Women and Anxiety. Anxiety and Depression Association of America.
3. Shigemura J et al. Psychiatry Clin Neurosci. 2012 Apr 7;74(4):281-2.
4. Petersen A. More people are taking drugs for anxiety and insomnia, and doctors are worried. The Wall Street Journal. 2020 May 25.
5. Downey M. Xanax overdose and related deaths. National Drug & Alcohol Research Centre. UNSW Sydney.
6. Bryant B. Fake Xanax: The UK’s biggest ever dark net drugs bust. BBC. 2018 Mar 10.
7. Reinberg S. Fatal overdoses rising from sedatives like Valium, Xanax. HealthDay. 2016 Feb.
8. Is counterfeit Xanax dangerous? American Addiction Centers. Updated 2018 Nov 14.
9. McLaren E. Xanax history and statistics. Drugabuse.com.
10. Benzodiazepines and opioids. National Institute on Drug Abuse. 2018 Mar 15.
11. Choudhry Z et al. J Psychiatry. 2015;18(5). doi: 10.4172/2378-5756.1000319.
12. Islam FA et al. Current Psychiatry. 2018 Dec 17(12):43-4.
13. Adams M. Xanax death rate on the rise. White Sands Treatment. 2017 Sept.NEED LINK
14. Storrs C. Benzodiazepine overdose deaths soared in recent years, study finds. CNN. 2016 Feb. 18.
15. Hanscom DA. Plan A – Thrive and survive COVID-19. Back in Control. 2020.
16. Smith C. Xanax, a common anxiety medication, might actually block coronavirus. BGR. 2020 May 29.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships.
Mr. Choudhry is a research assistant at the IMCHF. He has no disclosures.
Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. He has no disclosures.
One of the more alarming trends that has emerged during the coronavirus crisis is the concomitant rise in the use of benzodiazepines, such as Xanax. It has been reported that at-risk individuals began seeking prescription anxiolytics as early as mid-February with a consequent peak of 34% the following month, coinciding with the World Health Organization’s declaration of a global pandemic.1
Consistent with the available literature indicating that women are twice as likely to be affected by anxiety disorders, the prescription spikes were almost double when compared with those of their male counterparts.2 The pandemic has instilled a sense of fear in people, leading to social repercussions, such as estrangement, insomnia, and paranoia for at-risk populations.3,4
“Benzos” are commonly prescribed to help people sleep or to assist them in overcoming a host of anxiety disorders. The rapid onset of effects make Xanax a desirable and efficacious benzodiazepine.5 The use of these medications might not be an immediate cause for concern because patients might be taking it as intended. Nevertheless, clinicians are shying away from medical management in favor of counseling or therapy.
Dangerous trends
Numerous factors might contribute to this grim scenario, including patient dependence on benzodiazepines, paranoia about engaging with health care professionals because of fear tied to potential COVID-19 exposure, and/or increased access to illicit counterfeit pills from drug dealers or the dark web markets.
Lessons can be gleaned from the most extensive dark web drug busts in Britain’s history, in which a deluge of “pharmaceutical grade” Xanax pills made it to the hands of drug dealers and consumers between 2015 and 2017.6 A similar phenomenon emerged stateside.7 Virtually indistinguishable from recognized 2-mg Xanax pills, these fake pills posed a serious challenge to forensic scientists.8 The threat of overdose is very real for users targeted by the counterfeit Xanax trade, especially since those at risk often bypass professional health care guidelines.
In broad daylight, the drug dealers ran their operations revolving around two fake Xanax products: a primary knockoff and a limited edition – and vastly more potent “Red Devil” variant that was intentionally dyed for branding purposes. Because the “Red Devil” formulations contained 2.5 times the dose of the 2-mg pill, it had even more pronounced tolerance, dependence, and withdrawal effects (for example, panic attacks, anxiety, and/or hallucinations) – fatal consequences for users involved in consuming other drugs, such as alcohol or opioids. Preexisting drug users tend to gravitate toward benzodiazepines, such as alprazolam (Xanax), perhaps in part, because of its relatively rapid onset of action. Xanax also is known for inducing proeuphoric states at higher doses, hence the appeal of the “Red Devil” pills.
Benzodiazepines, as a class of drugs, facilitate the neurotransmitter gamma-aminobutryric acid’s (GABA) effect on the brain, producing anxiolytic, hypnotic, and/or anticonvulsant states within the user.9 Unbeknownst to numerous users is the fact that drugs such as alcohol and opioids, like Xanax, also serve as respiratory depressants, overriding the brain’s governance of the breathing mechanism. This, in turn, leads to unintended overdose deaths, even among seasoned drug seekers.
Overdose deaths have been steadily climbing over the years because it is common for some users to consume alcohol while being on Xanax therapy – without realizing that both substances are depressants and that taking them together can lead to side effects such as respiratory depression.
Forensic cases also have revealed that preexisting opioid consumers were drawn to Xanax; the drug’s potent mechanism of action would likely appeal to habituated users. A typical behavioral pattern has emerged among users and must be addressed. According to Australian Professor Shane Darke: “So they take their Xanax, they take their painkiller, then they get drunk, that could be enough to kill them.”
Fatalities are more likely when benzodiazepines are combined with other drug classes or if the existing supply is contaminated or laced (for example, with fentanyl).8
As far as deaths by accidental benzodiazepine overdose are concerned, a similar epidemic has been recorded in the United States. In 2013, almost one-third of all prescription overdose deaths can be attributed to the use of benzodiazepines (for example, Xanax, Valium, and Ativan). However, media attention has been considerably muted, especially when compared with that of narcotic abuse. This is even more puzzling when taking into account that three-quarters of benzodiazepine mortalities co-occur within the context of narcotic consumption. Substance Abuse and Mental Health Services Administration data confirm the ubiquitous nature of benzodiazepine (such as alprazolam) coprescriptions, accounting for roughly half of the 176,000 emergency department cases for 2011. The Centers for Disease Control and Prevention noted that there was a 67% increase in benzodiazepine prescriptions between 1996 and 2013, which warranted more stringent regulations for this particular class of drugs.
In 2016, the CDC issued new guidelines for opioid use acknowledging the danger of benzodiazepine coprescriptions. Food and Drug Administration “black box” warnings now grace the prescriptions of both of these drug classes.10 This trend remains on an upward trajectory, even more so during the pandemic, as there are 9.7 million prescriptions of anxiolytics/hypnotics such as Xanax, Ativan, and Klonopin in the United States as of March 2020, which represents a 10% increase over the previous year. , as well as the implementation of urine drug screening monitoring for drug adherence/compliance and diversion in those with suspected benzodiazepine addiction or a history of polysubstance abuse.11,12
Clinical correlates
For patients who present acutely with Xanax toxicity in the emergency room setting, we will need to initially stabilize the vital signs and address the ongoing symptoms. It is advisable to arrange health care accommodations for patients with physical dependence to monitor and treat their withdrawal symptoms. The patient should be enrolled in a comprehensive addiction facility after undergoing formal detoxification; a tapered treatment protocol will need to be implemented because quitting “cold turkey” can lead to convulsions and, in some cases, death. Patient education, talk therapy, and alternatives to benzodiazepines should be discussed with the clinician.13,145
However, to truly address the elephant in the room, we will need to consider institutional reforms to prevent a similar situation from arising in the future. Primary care physician shortages are compounded by changes in insurance policies. Nurses and physician assistants will need to be trained to manage benzodiazepine prescriptions. If there are community shortages in physicians, patients might turn to illegal means to secure their benzodiazepine supply, and it is imperative that we have the necessary fellowship and education programs to educate nonphysician health care clinicians with benzodiazepine management. Because physicians were prescribing benzodiazepines liberally, the Prescription Drug Monitoring Programs (PDMP) was enacted to monitor physician practices. Unfortunately, this ultimately intimidated physicians and effectively curbed reasonable physician prescribing patterns. It might be necessary to revisit existing prescription monitoring programs, encourage drug evaluations and guidelines based on evidence-based medicine and embrace telemedicine in order to facilitate patient-physician communication.
As of now, it is too early to prescribe Xanax routinely for ongoing anxiety experienced during the coronavirus crisis, and several physicians are cautious about prescribing antianxiety medications for more than a few months.17 Surprisingly, researchers in Barcelona have even explored the role of Xanax as potentially inhibiting Mpro, the primary protease of coronavirus, thereby forestalling the virus’s ability to replicate.16 However, it is worth noting that, given the preliminary nature of the results, any attempts at conclusively integrating Xanax within the context of coronavirus therapy would be premature.
References
1. Luhby T. Anti-anxiety medication prescriptions up 34% since coronavirus. CNN. 2020 Apr 16.
2. Women and Anxiety. Anxiety and Depression Association of America.
3. Shigemura J et al. Psychiatry Clin Neurosci. 2012 Apr 7;74(4):281-2.
4. Petersen A. More people are taking drugs for anxiety and insomnia, and doctors are worried. The Wall Street Journal. 2020 May 25.
5. Downey M. Xanax overdose and related deaths. National Drug & Alcohol Research Centre. UNSW Sydney.
6. Bryant B. Fake Xanax: The UK’s biggest ever dark net drugs bust. BBC. 2018 Mar 10.
7. Reinberg S. Fatal overdoses rising from sedatives like Valium, Xanax. HealthDay. 2016 Feb.
8. Is counterfeit Xanax dangerous? American Addiction Centers. Updated 2018 Nov 14.
9. McLaren E. Xanax history and statistics. Drugabuse.com.
10. Benzodiazepines and opioids. National Institute on Drug Abuse. 2018 Mar 15.
11. Choudhry Z et al. J Psychiatry. 2015;18(5). doi: 10.4172/2378-5756.1000319.
12. Islam FA et al. Current Psychiatry. 2018 Dec 17(12):43-4.
13. Adams M. Xanax death rate on the rise. White Sands Treatment. 2017 Sept.NEED LINK
14. Storrs C. Benzodiazepine overdose deaths soared in recent years, study finds. CNN. 2016 Feb. 18.
15. Hanscom DA. Plan A – Thrive and survive COVID-19. Back in Control. 2020.
16. Smith C. Xanax, a common anxiety medication, might actually block coronavirus. BGR. 2020 May 29.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships.
Mr. Choudhry is a research assistant at the IMCHF. He has no disclosures.
Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. He has no disclosures.