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Psychedelics hold promise for primary care research

Psychedelics hold promise for primary care research Dear Editor, We are in the midst of a so-called “psychedelic renaissance,” a time of renewed interest in the therapeutic potential of psychoactive drugs such as psilocybin, mescaline, and lysergic acid diethylamide. When they first emerged as topics of academic interest in the mid-20th century, these substances were greeted with exuberance for their apparent panacea-like effects in treating a range of conditions from depression and anxiety to post-traumatic stress disorder to existential grief in terminal cancer patients. Despite their promise, these compounds became associated with the counterculture movement in the public imagination and research was suppressed by political forces aligned with the so-called “War on Drugs.” It seems, however, that we have reached a watershed moment as psychedelic research has reemerged and even become mainstream, reaching the front page of the New York Times in May of this year.1 Already, psilocybin has been granted “Breakthrough Therapy” status by the US Food and Drug Association (FDA) and is permitted in limited therapeutic contexts in Canada.2,3 As of this writing, over 300 trials are currently registered on clinicaltrials.gov examining the therapeutic effects of psychedelic substances. Until now, the mantle of psychedelic research has been taken up by our colleagues in psychiatry and palliative medicine. It would be a mistake, however, for family physicians and primary care researchers to not take seriously the opportunity before us. Psychedelics, mental health, and primary care There is substantial evidence to suggest that they have dramatic therapeutic effects in treating anxiety disorders and depression.4 Take, for example, a 2016 trial which found that 80% of cancer patients treated with psilocybin saw clinically significant decreases in depressed mood or anxiety.5 Another study published in Lancet Psychiatry found marked and sustained improvements in depression and anxiety in patients with moderate-to-severe depression who had failed standard therapy.6 These and other studies like them provide beacons of hope for those in despair. Depression and anxiety disorders confront primary care doctors daily. An estimated 60% of mental health care services are provided by primary care physicians (PCPs), and an overwhelming 79% of antidepressant prescriptions are written by PCPs.7 Importantly, psychedelics appear to have an improved safety and tolerability profile compared with earlier generation antidepressant medications, even the relatively innocuous selective serotonin reuptake inhibitors. A 2018 systematic review of 10 systematic reviews found that in a controlled setting, psychedelics have a very good safety and tolerability profile. One of the major contributing factors to this safety profile is that they appear to produce a sustained therapeutic effect after just 1 administration.4 Despite fears promulgated by proponents of the War on Drugs, prolonged psychotic-like reactions were not described in any of the randomized control trials performed in the last 25 years.8 A safe, effective, single-dose medication to treat depression or anxiety disorders would be revolutionary. Promise for substance abuse treatment Perhaps the greatest challenge facing family physicians is inspiring behaviour change in our patients. Many of the most trenchant issues facing family doctors, from depression and substance abuse to obesity and metabolic syndrome, have significant behavioural components. Psychedelics offer a way forward. The power of these substances to inspire behaviour change has long been known among traditional communities. Mescaline has been used in Native American communities to treat substance use disorder for decades. A recent study found that among daily tobacco smokers who were given 2–3 moderate doses of psilocybin in conjunction with cognitive behaviour therapy, 67% were smoking abstinent at 12 months and 60% remained abstinent at long-term follow-up (16–57 months, with a mean interval of 30 months).9 This is a rate of success far greater than cognitive behavior therapy alone, and unrivalled by the “Stages of Change” and motivational interviewing interventions taught in medical schools today. “Destabilization” and meaningful change The neurophysiology of how these drugs inspire behaviour change is poorly understood. Morten Kringlebach, a researcher at Oxford University, has proposed a “Destabilization” hypothesis. According to the hypothesis, poor health habits, anxious, and depressive thoughts are the end result of neurological pruning, the diminishment of neural pathways until few paths exist and neurotransmitters pass along the remaining neurological superhighways. These neural pathways become rut-like in response to habitual overuse. Psychedelics, according to the hypothesis, “destabilize” this status quo, freeing the mind from these well-worn paths and forming new, healthier neural networks, in a sense simulating childlike neuroplasticity.10 Need for further research There are reasons to believe that the benefits of psychedelic therapy extend beyond the brain and affect a range of physical health markers. Retrospective data from the National Survey on Drug Use and Health published earlier this year demonstrated that respondents who reported having used classical psychedelics had lower body mass indexes (BMIs), lower odds of developing heart disease and diabetes, and significantly greater self-reported overall health.11,12 These results are far from conclusive and may, of course, be attributed simply to younger age, but the implications are such that it would be negligent to not investigate these findings further. These hypotheses and retrospective correlations are just that, and critics are right to point out these shortcomings. The results remain compelling. The nascent nature of this research ought not be seen as a limitation but rather as an opportunity. This research is often criticized due to small sample sizes and open-label designs. The small sample sizes are the result of a historic reluctance of government agencies and pharmaceutical companies to fund psychedelic research. This is changing: The “War on Drugs” having failed so spectacularly and public opinion towards these psychedelic compounds so rapidly shifting, there is every reason to believe that waves of research funding will soon be hitting the shores of psychedelic research. It would be a disservice to our patients for family physicians and primary care researchers to not be ready when it does. Conclusion As with any area of rapidly evolving social change, there will be concerns on the part of patients, families, regulatory agencies, and physicians themselves. For those who have been taught to fear these substances, beginning to see psychedelics as novel clinical tools is nothing short of revolutionary. There is a danger that optimal patient care will be held back by stigma, as has happened with medication-assisted treatment for opioid addiction.13 Who better to answer questions, alleviate fears, and guide patients into a more hopeful and healthful future than family physicians? There is a space opening for high-quality randomized control trials examining the effects of these compounds on substance use disorder, depression, anxiety, BMI, rates of heart disease and diabetes, and manifold other outcomes relevant to family medicine. Why not be pioneers of this new frontier? Funding There are no funders to report for this article. Conflict of interest None declared. Data availability There are no new data associated with this article. References 1. Jacobs A. Psychedelics are poised to reshape psychiatry. New York Times . 2021 May 10. Google Scholar OpenURL Placeholder Text WorldCat 2. Business Wire. FDA grants breakthrough therapy designation to Usona Institute’s psilocybin program for major depressive disorder. Business Wire . 2019 . https://www.businesswire.com/news/home/20191122005452/en/. Accessed December 19, 2021 . OpenURL Placeholder Text WorldCat 3. Hager M. Psilocybin, or magic mushrooms, therapy approved to help some facing end-of-life care. The Globe and Mail . 2020 Aug 13. https://www.theglobeandmail.com/canada/british-columbia/article-psilocybin-or-magic-mushroom-therapy-approved-to-help-some-facing/. Accessed December 19, 2021 . Google Scholar OpenURL Placeholder Text WorldCat 4. Vargas MV , Meyer R, Avanes AA, Rus M, Olson DE. Psychedelics and other psychoplastogens for treating mental illness. Front Psychiatry . 2021 ; 12 : 1 – 19 . Google Scholar Crossref Search ADS WorldCat 5. Griffiths RR , Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol . 2016 ; 30 ( 12 ): 1181 – 1197 . Google Scholar Crossref Search ADS PubMed WorldCat 6. Carhart-Harris RL , Bolstridge M, Rucker J, Day CMJ, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry . 2016 ; 3 ( 7 ): 619 – 627 . Google Scholar Crossref Search ADS PubMed WorldCat 7. Park LT , Zarat CA Jr. Depression in the primary care setting. N Engl J Med . 2019 ; 380 (6): 559 – 568 . Google Scholar Crossref Search ADS PubMed WorldCat 8. dos Santos RG , Bouso JC, Alcázar-Córcoles MA, Hallak JEC. Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews. Expert Rev Clin Pharmacol . 2018 ; 11 ( 9 ): 889 – 902 . Google Scholar Crossref Search ADS PubMed WorldCat 9. Johnson MW , Garcia-Romeu A, Griffiths RR. Long-term follow-up of psilocybin facilitated smoking cessation. Am J Drug Alcohol Abuse . 2017 ; 43 ( 1 ): 55 – 60 . Google Scholar Crossref Search ADS PubMed WorldCat 10. Kringelbach ML , Cruzat J, Cabral J, Knudsen GM, Carhart-Harris R, Whybrow PC, Logothetis NK, Deco G. Dynamic coupling of whole-brain neuronal and neurotransmitter systems. Proc Natl Acad Sci U S A . 2020 ; 117 ( 17 ): 9566 – 9576 . Google Scholar Crossref Search ADS PubMed WorldCat 11. Simonsson O , Sexton JD, Hendricks PS. Associations between lifetime classic psychedelic use and markers of physical health. J Psychopharmacol . 2021 ; 35 ( 4 ): 447 – 452 . Google Scholar Crossref Search ADS PubMed WorldCat 12. Simonsson O , Osika W, Carhart-Harris R, Hendricks PS. Associations between lifetime classic psychedelic use and cardiometabolic diseases. Sci Rep . 2021 ; 11 ( 1 ): 14427 . doi:10.1038/s41598-021-93787-4 Google Scholar Crossref Search ADS PubMed WorldCat 13. Madden EF. Intervention stigma: how medication-assisted treatment marginalizes patients and providers. Soc Sci Med . 2019 ; 232 : 324 – 331 . Google Scholar Crossref Search ADS PubMed WorldCat © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Family Practice Oxford University Press

Psychedelics hold promise for primary care research

Family Practice , Volume 39 (5): 2 – Feb 7, 2022

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References (23)

Publisher
Oxford University Press
Copyright
© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
ISSN
0263-2136
eISSN
1460-2229
DOI
10.1093/fampra/cmac009
Publisher site
See Article on Publisher Site

Abstract

Dear Editor, We are in the midst of a so-called “psychedelic renaissance,” a time of renewed interest in the therapeutic potential of psychoactive drugs such as psilocybin, mescaline, and lysergic acid diethylamide. When they first emerged as topics of academic interest in the mid-20th century, these substances were greeted with exuberance for their apparent panacea-like effects in treating a range of conditions from depression and anxiety to post-traumatic stress disorder to existential grief in terminal cancer patients. Despite their promise, these compounds became associated with the counterculture movement in the public imagination and research was suppressed by political forces aligned with the so-called “War on Drugs.” It seems, however, that we have reached a watershed moment as psychedelic research has reemerged and even become mainstream, reaching the front page of the New York Times in May of this year.1 Already, psilocybin has been granted “Breakthrough Therapy” status by the US Food and Drug Association (FDA) and is permitted in limited therapeutic contexts in Canada.2,3 As of this writing, over 300 trials are currently registered on clinicaltrials.gov examining the therapeutic effects of psychedelic substances. Until now, the mantle of psychedelic research has been taken up by our colleagues in psychiatry and palliative medicine. It would be a mistake, however, for family physicians and primary care researchers to not take seriously the opportunity before us. Psychedelics, mental health, and primary care There is substantial evidence to suggest that they have dramatic therapeutic effects in treating anxiety disorders and depression.4 Take, for example, a 2016 trial which found that 80% of cancer patients treated with psilocybin saw clinically significant decreases in depressed mood or anxiety.5 Another study published in Lancet Psychiatry found marked and sustained improvements in depression and anxiety in patients with moderate-to-severe depression who had failed standard therapy.6 These and other studies like them provide beacons of hope for those in despair. Depression and anxiety disorders confront primary care doctors daily. An estimated 60% of mental health care services are provided by primary care physicians (PCPs), and an overwhelming 79% of antidepressant prescriptions are written by PCPs.7 Importantly, psychedelics appear to have an improved safety and tolerability profile compared with earlier generation antidepressant medications, even the relatively innocuous selective serotonin reuptake inhibitors. A 2018 systematic review of 10 systematic reviews found that in a controlled setting, psychedelics have a very good safety and tolerability profile. One of the major contributing factors to this safety profile is that they appear to produce a sustained therapeutic effect after just 1 administration.4 Despite fears promulgated by proponents of the War on Drugs, prolonged psychotic-like reactions were not described in any of the randomized control trials performed in the last 25 years.8 A safe, effective, single-dose medication to treat depression or anxiety disorders would be revolutionary. Promise for substance abuse treatment Perhaps the greatest challenge facing family physicians is inspiring behaviour change in our patients. Many of the most trenchant issues facing family doctors, from depression and substance abuse to obesity and metabolic syndrome, have significant behavioural components. Psychedelics offer a way forward. The power of these substances to inspire behaviour change has long been known among traditional communities. Mescaline has been used in Native American communities to treat substance use disorder for decades. A recent study found that among daily tobacco smokers who were given 2–3 moderate doses of psilocybin in conjunction with cognitive behaviour therapy, 67% were smoking abstinent at 12 months and 60% remained abstinent at long-term follow-up (16–57 months, with a mean interval of 30 months).9 This is a rate of success far greater than cognitive behavior therapy alone, and unrivalled by the “Stages of Change” and motivational interviewing interventions taught in medical schools today. “Destabilization” and meaningful change The neurophysiology of how these drugs inspire behaviour change is poorly understood. Morten Kringlebach, a researcher at Oxford University, has proposed a “Destabilization” hypothesis. According to the hypothesis, poor health habits, anxious, and depressive thoughts are the end result of neurological pruning, the diminishment of neural pathways until few paths exist and neurotransmitters pass along the remaining neurological superhighways. These neural pathways become rut-like in response to habitual overuse. Psychedelics, according to the hypothesis, “destabilize” this status quo, freeing the mind from these well-worn paths and forming new, healthier neural networks, in a sense simulating childlike neuroplasticity.10 Need for further research There are reasons to believe that the benefits of psychedelic therapy extend beyond the brain and affect a range of physical health markers. Retrospective data from the National Survey on Drug Use and Health published earlier this year demonstrated that respondents who reported having used classical psychedelics had lower body mass indexes (BMIs), lower odds of developing heart disease and diabetes, and significantly greater self-reported overall health.11,12 These results are far from conclusive and may, of course, be attributed simply to younger age, but the implications are such that it would be negligent to not investigate these findings further. These hypotheses and retrospective correlations are just that, and critics are right to point out these shortcomings. The results remain compelling. The nascent nature of this research ought not be seen as a limitation but rather as an opportunity. This research is often criticized due to small sample sizes and open-label designs. The small sample sizes are the result of a historic reluctance of government agencies and pharmaceutical companies to fund psychedelic research. This is changing: The “War on Drugs” having failed so spectacularly and public opinion towards these psychedelic compounds so rapidly shifting, there is every reason to believe that waves of research funding will soon be hitting the shores of psychedelic research. It would be a disservice to our patients for family physicians and primary care researchers to not be ready when it does. Conclusion As with any area of rapidly evolving social change, there will be concerns on the part of patients, families, regulatory agencies, and physicians themselves. For those who have been taught to fear these substances, beginning to see psychedelics as novel clinical tools is nothing short of revolutionary. There is a danger that optimal patient care will be held back by stigma, as has happened with medication-assisted treatment for opioid addiction.13 Who better to answer questions, alleviate fears, and guide patients into a more hopeful and healthful future than family physicians? There is a space opening for high-quality randomized control trials examining the effects of these compounds on substance use disorder, depression, anxiety, BMI, rates of heart disease and diabetes, and manifold other outcomes relevant to family medicine. Why not be pioneers of this new frontier? Funding There are no funders to report for this article. Conflict of interest None declared. Data availability There are no new data associated with this article. References 1. Jacobs A. Psychedelics are poised to reshape psychiatry. New York Times . 2021 May 10. Google Scholar OpenURL Placeholder Text WorldCat 2. Business Wire. FDA grants breakthrough therapy designation to Usona Institute’s psilocybin program for major depressive disorder. Business Wire . 2019 . https://www.businesswire.com/news/home/20191122005452/en/. Accessed December 19, 2021 . OpenURL Placeholder Text WorldCat 3. Hager M. Psilocybin, or magic mushrooms, therapy approved to help some facing end-of-life care. The Globe and Mail . 2020 Aug 13. https://www.theglobeandmail.com/canada/british-columbia/article-psilocybin-or-magic-mushroom-therapy-approved-to-help-some-facing/. Accessed December 19, 2021 . Google Scholar OpenURL Placeholder Text WorldCat 4. Vargas MV , Meyer R, Avanes AA, Rus M, Olson DE. Psychedelics and other psychoplastogens for treating mental illness. Front Psychiatry . 2021 ; 12 : 1 – 19 . Google Scholar Crossref Search ADS WorldCat 5. Griffiths RR , Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol . 2016 ; 30 ( 12 ): 1181 – 1197 . Google Scholar Crossref Search ADS PubMed WorldCat 6. Carhart-Harris RL , Bolstridge M, Rucker J, Day CMJ, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry . 2016 ; 3 ( 7 ): 619 – 627 . Google Scholar Crossref Search ADS PubMed WorldCat 7. Park LT , Zarat CA Jr. Depression in the primary care setting. N Engl J Med . 2019 ; 380 (6): 559 – 568 . Google Scholar Crossref Search ADS PubMed WorldCat 8. dos Santos RG , Bouso JC, Alcázar-Córcoles MA, Hallak JEC. Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews. Expert Rev Clin Pharmacol . 2018 ; 11 ( 9 ): 889 – 902 . Google Scholar Crossref Search ADS PubMed WorldCat 9. Johnson MW , Garcia-Romeu A, Griffiths RR. Long-term follow-up of psilocybin facilitated smoking cessation. Am J Drug Alcohol Abuse . 2017 ; 43 ( 1 ): 55 – 60 . Google Scholar Crossref Search ADS PubMed WorldCat 10. Kringelbach ML , Cruzat J, Cabral J, Knudsen GM, Carhart-Harris R, Whybrow PC, Logothetis NK, Deco G. Dynamic coupling of whole-brain neuronal and neurotransmitter systems. Proc Natl Acad Sci U S A . 2020 ; 117 ( 17 ): 9566 – 9576 . Google Scholar Crossref Search ADS PubMed WorldCat 11. Simonsson O , Sexton JD, Hendricks PS. Associations between lifetime classic psychedelic use and markers of physical health. J Psychopharmacol . 2021 ; 35 ( 4 ): 447 – 452 . Google Scholar Crossref Search ADS PubMed WorldCat 12. Simonsson O , Osika W, Carhart-Harris R, Hendricks PS. Associations between lifetime classic psychedelic use and cardiometabolic diseases. Sci Rep . 2021 ; 11 ( 1 ): 14427 . doi:10.1038/s41598-021-93787-4 Google Scholar Crossref Search ADS PubMed WorldCat 13. Madden EF. Intervention stigma: how medication-assisted treatment marginalizes patients and providers. Soc Sci Med . 2019 ; 232 : 324 – 331 . Google Scholar Crossref Search ADS PubMed WorldCat © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Journal

Family PracticeOxford University Press

Published: Feb 7, 2022

There are no references for this article.