Impact Factor 4.157 | CiteScore 3.5
More on impact ›

OPINION article

Front. Psychiatry, 06 September 2021 | https://doi.org/10.3389/fpsyt.2021.716593

Psychedelic-Assisted Psychotherapy After COVID-19: The Therapeutic Uses of Psilocybin and MDMA for Pandemic-Related Mental Health Problems

Elena Argento1,2*, Devon Christie1, Lindsay Mackay1, Cody Callon2 and Zach Walsh2,3
  • 1Department of Medicine, University of British Columbia, Vancouver, BC, Canada
  • 2British Columbia Centre on Substance Use, Vancouver, BC, Canada
  • 3Department of Psychology, University of British Columbia, Kelowna, BC, Canada

COVID-19-Related Impacts on Mental Health

The COVID-19 pandemic stands to have impacts on mental health and well-being that will extend beyond its formal resolution. Before COVID-19, mental health disorders were already challenging global healthcare systems, directly accounting for 7.4% of the total burden of disease (1, 2). An estimated 1 billion people worldwide suffer from a mental health disorder, with the two most common disorders—depression and anxiety—costing the global economy US$1 trillion per year (3). Stigma and limited treatment options have amounted to substantial unmet need and violations in human rights for people with mental health disorders (1, 4, 5). Looking ahead, heightened post-pandemic demand for mental healthcare signifies an urgent need to bolster clinical capacity by integrating novel, cost-effective approaches into existing systems (6).

Emergent literature globally describes the diverse impacts of COVID-19 on mental health (7, 8). For instance, available data among hospitalized COVID-19 patients in China revealed that approximately 96% suffered post-traumatic stress symptoms (9). Studies among intensive care unit (ICU) patients with previous coronaviruses infer high rates of posttraumatic stress disorder (PTSD), depression and anxiety (30-40%) persisting months after discharge (10), with similar rates observed in patients infected with COVID-19 (11). Highly exposed individuals such as frontline healthcare workers are susceptible to similarly negative outcomes due to prolonged occupational stress, elevating risk of PTSD and suicidality (1214). Importantly, post-pandemic mental disorders are not limited to individuals directly exposed to COVID-19. Rather, research documents PTSD symptoms among individuals who have been indirectly exposed by witnessing (e.g., via the media) or being confronted with the threat of death or serious illness (e.g., worry/anticipation about the future) (7).

COVID-19 has significantly altered lives in ways that exacerbate drivers of mental health problems, with widespread uncertainty, increased experiences of grief and loss, social isolation, economic and housing instability, and decreased access to critical services related to lockdowns (6, 15). Further, available data on the impacts of COVID-19 on substance use patterns indicate increased use of alcohol and other substances in response to stress and negative emotions (8, 16, 17). Social connections are crucial for people struggling with addiction and comorbidities such as depression, and increased social disconnection represents a key risk factor for adverse outcomes (e.g., relapse and overdose) (1, 6, 18). The societal and economic consequences are tremendous, with structurally vulnerable groups at greatest risk of harms. For example, North America has seen dramatic spikes in fatal overdoses attributable to socio-structural conditions worsened by COVID-19 (18, 19), disproportionately impacting racialized groups (20).

The legacy of mental health problems that will be left behind by COVID-19 incites innovative solutions to address rising rates of PTSD, depression, anxiety, addictions, and social disconnection. As such, we would be remiss not to consider a novel approach with anti-depressive, anxiolytic, and antiaddictive potential that may also foster a sense of social and environmental connectedness, known as psychedelic-assisted psychotherapy (2124).

Opening Regulatory Doors to Psychedelics

A considerable and growing body of evidence speaks to the potential of psychedelic-assisted psychotherapies to enhance treatments for PTSD, depression, end-of-life anxiety, and substance use disorders (23, 24). The ensuing government, industry and social support includes the US Food and Drug Administration (FDA) granting breakthrough therapy designation for psilocybin and 3,4-methylenedioxymethamphetamine (MDMA) for treatment-resistant depression and PTSD, respectively (24).

A range of jurisdictions worldwide are expanding access to psychedelic-assisted psychotherapies, including through compassionate use or “right-to-try” pathways. In 2019, the Israeli government approved its first Compassionate Use Program for MDMA-assisted psychotherapy, shortly followed by FDA approval for an Expanded Access program in the US (25). Switzerland has permitted compassionate use of MDMA and lysergic acid diethylamide (LSD) since 2014 (26). The state of Oregon has now legalized psilocybin-assisted psychotherapy and decriminalized all drugs, alongside dozens of similar legislative reforms to legalize or decriminalize psychedelic plants and fungi across the US, including bills to expand “right-to-try” laws for people with serious or life-threatening illnesses (27). In Canada, a growing number of permissions have been granted by the federal government to use psilocybin for existential distress, and for therapist training purposes (28). Health Canada recently announced a notice of intent to restore access to psilocybin and MDMA through the Special Access Programme, which followed a national petition signed by nearly 15,000 Canadians in support of decriminalizing psychedelic plants and fungi (29).

Mounting public interest in psychedelic-assisted psychotherapy is reflected in the 2020 Global Drug Survey. Nearly 6% of 110,000 respondents used psychedelics in the past year for self-treatment of mental health conditions, and 90% who had a supervised psychedelic experience in an uncontrolled setting indicated interest in taking psychedelics under a legally regulated and approved treatment system (30). These findings underscore the need for increased public education, training of qualified care providers, and harm reduction approaches as regulatory frameworks evolve.

While, the pandemic has illuminated deficiencies and inequalities in our healthcare systems, it also provides a rare opportunity for change. The collective experience of COVID-19 has rearranged priorities by bringing mortality, loss, and mental health to the forefront, and is generating innovation. Rapidly evolving regulations around psychedelics come at an opportune time and may open doors to new treatment modalities. In this context, below we provide an overview of the clinical evidence for psilocybin- and MDMA-assisted psychotherapy, which, if larger studies continue to validate findings, are poised to make a substantial impact on mental healthcare and bolstering treatments for post-pandemic stress and trauma disorders.

Psilocybin-Assisted Psychotherapy for Depression and Existential Distress

Clinical evidence for psilocybin-assisted psychotherapy in promoting long-lasting relief from existential distress is highly relevant in a post-pandemic world. Randomized clinical trials (RCTs) have observed large effect sizes sustained 4.5 years after a single dose of psilocybin delivered in the context of psychotherapy: 60–80% of participants with cancer-related existential distress had clinically significant reductions in depression and anxiety (31). Between 1960 and 2017, 11 psychedelic clinical trials involving 445 participants with life-threatening diseases demonstrated significant reductions in symptoms of depression and anxiety, highlighting overall safety and efficacy (22, 32).

Likewise, open-label trials of psilocybin-assisted psychotherapy for treatment-resistant depression have observed rapid and sustained improvements up to 6 months follow-up (33, 34). A recent RCT found psilocybin-assisted psychotherapy produced marked antidepressant effects in patients with major depressive disorder: 71% had clinically significant reductions and 54% achieved remission 4 weeks later, demonstrating effect sizes greater than are typical for psychotherapy alone and for other pharmacological treatments (35). Most recently, a double-blind RCT published during the pandemic that compared psilocybin with a selective serotonin reuptake inhibitor (SSRI), found similar efficacy between the two groups with some secondary outcomes favoring psilocybin (36).

As the pandemic continues to intensify experiences of disconnection and existential distress, it is noteworthy that spiritual or mystical experiences occasioned by psychedelics are thought to mediate several therapeutic outcomes (3741) by eliciting powerful emotional responses including awe, ego-dissolution, sense of unity, sacredness, and insight (42, 43). Approximately, 70–90% of participants across clinical trials rated their psilocybin experience among the top five most personally meaningful and spiritually significant experiences of their entire lives (38, 39, 44).

Psilocybin-Assisted Psychotherapy for Substance Use Disorders

Increases in problematic substance use represent an imminent health concern that is likely to linger well beyond the formal conclusion of the pandemic. Given the ongoing overdose crisis and mounting concerns around post-pandemic stress and increasing use of alcohol and tobacco (17, 45, 46), relevant preliminary studies of psilocybin-assisted psychotherapy signal an important area for further investigation. For example, a small, open-label pilot study for tobacco smoking cessation demonstrated high abstinence rates at 6 months and 1 year following two or three doses of psilocybin in combination with Cognitive Behavioral Therapy among long-term cigarette smokers (47, 48). Promising results were also observed in a pilot study for alcohol use disorder, with significant increases in abstinence rates and reduced craving following one or two psilocybin sessions in addition to weekly Motivational Enhancement Therapy (49). These findings have encouraged further development of clinical trials to assess psilocybin-assisted psychotherapy for other substance use disorders.

MDMA-Assisted Psychotherapy for Trauma-Related Disorders

Several decades of clinical trials have demonstrated the safety and efficacy of MDMA-assisted psychotherapy, culminating in recent findings from a double-blind RCT published in Nature Medicine. The phase 3 study found that 67% of participants no longer met clinical criteria for PTSD 2 months following MDMA-assisted psychotherapy, demonstrating rapid treatment efficacy for participants with severe PTSD and comorbidities such as depression, historical childhood trauma and substance use disorders (50). Six prior phase 2 RCTs signaled the promise of MDMA to bolster outcomes of traditional psychotherapy (51), and long-term follow-up demonstrated lasting therapeutic benefits (52). Research remains ongoing in over 16 international jurisdictions with active phase 3 RCTs in Canada, the US and Israel (53). While two SSRIs have been approved for PTSD, pooled data indicate that MDMA-assisted psychotherapy may constitute “a substantial improvement over available pharmacotherapies in terms of safety and efficacy” (54). Other research suggests MDMA-assisted psychotherapy may be efficacious for treating social anxiety among adults with autism, end-of-life anxiety/psychological distress, alcohol use disorder and eating disorders (5558). Based on these findings, researchers recommend that MDMA-assisted psychotherapy be expeditiously evaluated for clinical use (50). MDMA represents a potentially cost-effective (59) and promising novel enhancement to psychotherapy for trauma-related disorders further challenged in post-pandemic times.

Overall, psychedelic-assisted psychotherapies may have potential to specifically and uniquely address post-pandemic issues, such as PTSD, bereavement, and depression due to their distinct mechanisms of action that are proposed to engage processes related to meaning in life, acceptance of change, and the reiteration of core personal and spiritual values (60, 61).

Context and Safety

Clinical trials suggest psychedelics are physiologically and psychologically safe (24, 32, 51, 53, 62) when delivered in supportive settings that adhere to guidelines covering a range of factors (63). Psilocybin mushrooms, as with other psychedelic plants, have been used for centuries, if not millennia, as traditional medicines for a wide range of healing purposes without reports of safety concerns (64). In the early era (1977–1985) of clinical study when MDMA was still legal, approximately 4,000 psychiatrists and psychologists administered MDMA-assisted psychotherapy to an estimated 500,000 patients without evidence of serious harm (65, 66). Nevertheless, psychedelic-assisted psychotherapy is not without risk. As regulations trend toward expanding access to psychedelics, thoughtful consideration of “set and setting” (mindset of the patient and the broader physical environment) is needed to ensure safe and adequately supported use of these medicines (63), in addition to expanding therapist training programs (67).

A Novel Enhancement to Post-Pandemic Mental Healthcare

Amid escalating need for enhanced mental health services in the wake of COVID-19, psychedelic-assisted psychotherapy represents a promising breakthrough treatment, including for refractory conditions (68). Novel alternatives are urgently needed to address the limitations of existing treatment options. Widely prescribed psychiatric medications are ineffective for many who have access, and myriad unwanted side effects are associated with low compliance (69, 70). Further, an estimated 90,000 visits are made annually to US emergency departments due to adverse events (71). Importantly, the novel therapeutic value of psychedelics stems from their role as enhancements to a psychotherapeutic change process grounded in a relationship-centered approach that views mental health through a biopsychosocial lens (68). Psychedelic-assisted psychotherapy holds potential to empower patients by enhancing self-reflection and self-directed change, which may help to facilitate meaningful and lasting benefits to well-being. Given the tremendous economic burden of mental health disorders globally (3, 72), should the benefits described in pilot studies hold consistent in larger RCTs, there are considerable potential cost savings to healthcare systems.

Conclusion

Rising rates of pandemic-related stress and trauma disorders call for concerted efforts to find innovative strategies to bolster treatments. Psychedelic-assisted psychotherapy is certainly no quick fix. However, the therapeutic use of psychedelics such as psilocybin and MDMA, carefully and thoughtfully integrated into existing evidence-based interventions denotes one of the most promising paths forward (73). The COVID-19 pandemic underscores longstanding challenges to mental health, but also presents an opportunity to develop promising new therapeutic approaches founded on evidence, compassion, and meaningful connection to bring about lasting benefits to health and well-being.

Author Contributions

EA conceptualized the topic of the paper with inputs from DC and ZW and wrote the first draft. EA, DC, LM, CC, and ZW all made significant contributions to the manuscript. All authors critically revised and approved the final draft.

Funding

EA was supported by Canadian Institutes of Health Research (CIHR) and Michael Smith Foundation for Health Research postdoctoral awards.

Conflict of Interest

EA, DC, LM, and CC work part-time with Numinus Wellness, a Canadian mental health company interested in the use of psychedelics for medical purposes. Numinus Wellness was not involved in the writing of this manuscript or the decision to submit for publication. ZW is in paid advisory relationships Numinus Wellness, EntheoTech & Synthesis Health, and is an unpaid advisor to the Multidisciplinary Association for Psychedelic Science - Canada and Mycomedica Life Sciences regarding the medical development of psychedelics or related compounds. None of these organizations were involved in the writing of this manuscript or the decision to submit for publication.

Publisher's Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

1. Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, Erskine HE, et al. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study (2010). Lancet. (2013) 382:1575–86. doi: 10.1016/S0140-6736(13)61611-6

PubMed Abstract | CrossRef Full Text | Google Scholar

2. Rehm J, Shield KD. Global burden of disease and the impact of mental and addictive disorders. Curr Psychiatry Rep. (2019) 21:1–7. doi: 10.1007/s11920-019-0997-0

PubMed Abstract | CrossRef Full Text | Google Scholar

3. The Lancet Global H. Mental health matters. Lancet Glob Health. (2020) 8:e1352. doi: 10.1016/S2214-109X(20)30432-0

PubMed Abstract | CrossRef Full Text | Google Scholar

4. Becker AE, Kleinman A. Mental health and the global agenda. N Engl J Med. (2013) 369:66–73. doi: 10.1056/NEJMra1110827

PubMed Abstract | CrossRef Full Text | Google Scholar

5. Campbell M, Williams MT. The ethic of access: an AIDS activist won public access to experimental therapies, and this must now extend to psychedelics for mental illness. Front Psychiatry. (2021) 12:680626. doi: 10.3389/fpsyt.2021.680626

PubMed Abstract | CrossRef Full Text | Google Scholar

6. Moreno C, Wykes T, Galderisi S, Nordentoft M, Crossley N, Jones N, et al. How mental health care should change as a consequence of the COVID-19 pandemic. Lancet Psychiatry. (2020) 7:813–24. doi: 10.1016/S2215-0366(20)30307-2

PubMed Abstract | CrossRef Full Text | Google Scholar

7. Bridgland VME, Moeck EK, Green DM, Swain TL, Nayda DM, Matson LA, et al. Why the COVID-19 pandemic is a traumatic stressor. PLoS ONE. (2021) 16:e0240146. doi: 10.1371/journal.pone.0240146

PubMed Abstract | CrossRef Full Text | Google Scholar

8. Czeisler M, Lane R, Petrosky E. Mental Health, Substance Use, and Suicidal Ideation During the COVID-19 Pandemic - United States. Centers for Disease Control and Prevention (2020).

PubMed Abstract | Google Scholar

9. Bo HX, Li W, Yang Y, Wang Y, Zhang Q, Cheung T, et al. Posttraumatic stress symptoms and attitude toward crisis mental health services among clinically stable patients with COVID-19 in China. Psychol Med. (2020) 51(6):1052–3. doi: 10.1017/S0033291720000999

PubMed Abstract | CrossRef Full Text | Google Scholar

10. Ahmed H, Patel K, Greenwood DC, Halpin S, Lewthwaite P, Salawu A, et al. Long-term clinical outcomes in survivors of severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus outbreaks after hospitalisation or ICU admission: a systematic review and meta-analysis. J Rehabil Med. (2020) 52:jrm00063. doi: 10.2340/16501977-2694

PubMed Abstract | CrossRef Full Text | Google Scholar

11. Janiri D, Carfì A, Kotzalidis GD, Bernabei R, Landi F, Sani G. Posttraumatic stress disorder in patients after severe COVID-19 infection. JAMA Psychiatry. (2021) 78:567–9. doi: 10.1001/jamapsychiatry.2021.0109

PubMed Abstract | CrossRef Full Text | Google Scholar

12. Sheraton M, Deo N, Dutt T, Surani S, Hall-Flavin D, Kashyap R. Psychological effects of the COVID 19 pandemic on healthcare workers globally: a systematic review. Psychiatry Res. (2020) 292 :113360. doi: 10.1016/j.psychres.2020.113360

PubMed Abstract | CrossRef Full Text | Google Scholar

13. Brooks SK, Webster RK, Smith LE, Woodland L, Wessely S, Greenberg N, et al. The psychological impact of quarantine and how to reduce it: rapid review of the evidence. Lancet. (2020) 395:912–20. doi: 10.1016/S0140-6736(20)30460-8

PubMed Abstract | CrossRef Full Text | Google Scholar

14. Rose C. Am I part of the cure or Am I part of the disease? keeping coronavirus out when a doctor comes home. N Engl J Med. (2020) 382:1684–5. doi: 10.1056/NEJMp2004768

PubMed Abstract | CrossRef Full Text | Google Scholar

15. Crockford D. The COVID-19 pandemic and its impact on addiction treatment. Can J Addict. (2020) 11:7–8. doi: 10.1097/CXA.0000000000000084

PubMed Abstract | CrossRef Full Text | Google Scholar

16. Addiction CCoSUa. COVID-19 and Increased Alcohol Consumption: NANOS Poll Summary Report (2020).

17. Ramalho R, Adiukwu F, Gashi Bytyçi D, El Hayek S, Gonzalez-Diaz JM, Larnaout A, et al. Alcohol and tobacco use during the COVID-19 pandemic. A call for local actions for global impact. Front Psychiatry. (2021) 12:634254. doi: 10.3389/fpsyt.2021.634254

PubMed Abstract | CrossRef Full Text | Google Scholar

18. Volkow ND. Collision of the COVID-19 and addiction epidemics. Ann Internal Med. (2020) 173:61–2. doi: 10.7326/M20-1212

PubMed Abstract | CrossRef Full Text | Google Scholar

19. CBC. More People Died of An Illicit Drug Overdose in First 8 Months of 2020 Than all of 2019: BC Coroner. Canadian Broadcasting Corporation (2020).

20. Khatri UG, Pizzicato LN, Viner K, Bobyock E, Sun M, Meisel ZF, et al. Racial/ethnic disparities in unintentional fatal and nonfatal emergency medical services-attended opioid overdoses during the COVID-19 pandemic in Philadelphia. JAMA Netw Open. (2021) 4:e2034878. doi: 10.1001/jamanetworkopen.2020.34878

PubMed Abstract | CrossRef Full Text | Google Scholar

21. Gandy S, Forstmann M, Carhart-Harris RL, Timmermann C, Luke D, Watts R. The potential synergistic effects between psychedelic administration and nature contact for the improvement of mental health. Health Psychol Open. (2020) 7:2055102920978123. doi: 10.1177/2055102920978123

PubMed Abstract | CrossRef Full Text | Google Scholar

22. dos Santos RG, Hallak JEC. Therapeutic use of serotoninergic hallucinogens: a review of the evidence and of the biological and psychological mechanisms. Neurosci Biobehav Rev. (2020) 108:423–34. doi: 10.1016/j.neubiorev.2019.12.001

PubMed Abstract | CrossRef Full Text | Google Scholar

23. Bahji A, Forsyth A, Groll D, Hawken ER. Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for posttraumatic stress disorder: a systematic review and meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. (2020) 96:109735. doi: 10.1016/j.pnpbp.2019.109735

PubMed Abstract | CrossRef Full Text | Google Scholar

24. Reiff CM, Richman EE, Nemeroff CB, Carpenter LL, Widge AS, Rodriguez CI, et al. Psychedelics and psychedelic-assisted psychotherapy. Am J Psychiatry. (2020) 177:391–410. doi: 10.1176/appi.ajp.2019.19010035

PubMed Abstract | CrossRef Full Text | Google Scholar

25. MAPS. PRESS RELEASE: FDA Agrees to Expanded Access Program for MDMA-Assisted Psychotherapy for PTSD. Multidisciplinary Association for Psychedelic Studies (2020).

26. Schmid Y, Gasser P, Oehen P, Liechti ME. Acute subjective effects in LSD- and MDMA-assisted psychotherapy. J Psychopharmacol. (2021) 35:362–74. doi: 10.1177/0269881120959604

PubMed Abstract | CrossRef Full Text | Google Scholar

27. Adlin B. Missouri Bill Would Add MDMA, Psilocybin Mushrooms And LSD To Right-To-Try Law. Brooklyn, NY: Marijuana Moment (2021).

28. Hawkswell S. TheraPsil: Open Letter to Heatlh Canada. TheraPsil (2021).

29. Boudreau M. Notice of Intent to Amend the Food and Drug Regulations and the Narcotic Control Regulations to Restore Potential Access to Restricted Drugs Through Health Canada's Special Access Program. Government of Canada (2020).

30. Winstock AR, Timmermann C, Davies E, Maier LJ, Zhuparris A, Ferris JA, et al. Global Drug Survey (GDS) 2020. Psychedelics Key Findings Report (2021).

31. Agin-Liebes GI, Malone T, Yalch MM, Mennenga SE, Ponté KL, Guss J, et al. Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. J Psychopharmacol. (2020) 34:155–66. doi: 10.1177/0269881119897615

PubMed Abstract | CrossRef Full Text | Google Scholar

32. Reiche S, Hermle L, Gutwinski S, Jungaberle H, Gasser P, Majić T. Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: a systematic review. Prog Neuropsychopharmacol Biol Psychiatry. (2018) 81:1–10. doi: 10.1016/j.pnpbp.2017.09.012

PubMed Abstract | CrossRef Full Text | Google Scholar

33. Carhart-Harris R, Bolstridge M, Day CMJ, Rucker J, Watts R, Erritzoe DE, et al. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology. (2018) 235:399–408. doi: 10.1007/s00213-017-4771-x

PubMed Abstract | CrossRef Full Text | Google Scholar

34. Carhart-Harris RL, Bolstridge M, Rucker J, Day CMJ, Erritzoe D, Kaelen M, et al. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. (2016) 3:619–27. doi: 10.1016/S2215-0366(16)30065-7

PubMed Abstract | CrossRef Full Text | Google Scholar

35. Davis AK, Barrett FS, May DG, Cosimano MP, Sepeda ND, Johnson MW, et al. Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA Psychiatry. (2020) 78:481–9. doi: 10.1001/jamapsychiatry.2020.3285

PubMed Abstract | CrossRef Full Text | Google Scholar

36. Carhart-Harris R, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Murphy R, et al. Trial of psilocybin versus escitalopram for depression. N Engl J Med. (2021) 384:1402–11. doi: 10.1056/NEJMoa2032994

PubMed Abstract | CrossRef Full Text | Google Scholar

37. Garcia-Romeu A, Griffiths RR, Johnson MW. Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Curr Drug Abuse Rev. (2014) 7:157–64. doi: 10.2174/1874473708666150107121331

PubMed Abstract | CrossRef Full Text | Google Scholar

38. Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol. (2016) 30:1181–97. doi: 10.1177/0269881116675513

PubMed Abstract | CrossRef Full Text | Google Scholar

39. Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. (2016) 30:1165–80. doi: 10.1177/0269881116675512

PubMed Abstract | CrossRef Full Text | Google Scholar

40. Hartogsohn I. The meaning-enhancing properties of psychedelics and their mediator role in psychedelic therapy, spirituality, and creativity. Front Neurosci. (2018) 12:129. doi: 10.3389/fnins.2018.00129

PubMed Abstract | CrossRef Full Text | Google Scholar

41. Nour MM, Evans L, Nutt D, Carhart-Harris RL. Ego-dissolution and psychedelics: validation of the ego-dissolution inventory (EDI). Front Hum Neurosci. (2016) 10:269. doi: 10.3389/fnhum.2016.00269

PubMed Abstract | CrossRef Full Text | Google Scholar

42. Griffiths RR, Richards WA, McCann U, Jesse R. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology. (2006) 187:268–83. doi: 10.1007/s00213-006-0457-5

PubMed Abstract | CrossRef Full Text | Google Scholar

43. Hendricks PS. Awe: a putative mechanism underlying the effects of classic psychedelic-assisted psychotherapy. Int Rev Psychiatry. (2018) 30:1–12. doi: 10.1080/09540261.2018.1474185

PubMed Abstract | CrossRef Full Text | Google Scholar

44. Johnson MW, Griffiths RR. Potential therapeutic effects of psilocybin. Neurotherapeutics. (2017) 14:734–40. doi: 10.1007/s13311-017-0542-y

PubMed Abstract | CrossRef Full Text | Google Scholar

45. Finlay I, Gilmore I. Covid-19 and alcohol-a dangerous cocktail. BMJ. (2020) 369:m1987. doi: 10.1136/bmj.m1987

PubMed Abstract | CrossRef Full Text | Google Scholar

46. Jacob L, Smith L, Armstrong NC, Yakkundi A, Barnett Y, Butler L, et al. Alcohol use and mental health during COVID-19 lockdown: a cross-sectional study in a sample of UK adults. Drug Alcohol Depend. (2021) 219:108488. doi: 10.1016/j.drugalcdep.2020.108488

PubMed Abstract | CrossRef Full Text | Google Scholar

47. Johnson MW, Garcia-Romeu A, Cosimano MP, Griffiths RR. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol. (2014) 28:983–92. doi: 10.1177/0269881114548296

PubMed Abstract | CrossRef Full Text | Google Scholar

48. Johnson MW, Garcia-Romeu A, Griffiths RR. Long-term follow-up of psilocybin-facilitated smoking cessation. Am J Drug Alcohol Abuse. (2017) 43:55–60. doi: 10.3109/00952990.2016.1170135

PubMed Abstract | CrossRef Full Text | Google Scholar

49. Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa PCR, Strassman RJ. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol. (2015) 29:289–99. doi: 10.1177/0269881114565144

PubMed Abstract | CrossRef Full Text | Google Scholar

50. Mitchell JM, Bogenschutz M, Lilienstein A, Harrison C, Kleiman S, Parker-Guilbert K, et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. (2021) 27:1025–33. doi: 10.1038/s41591-021-01336-3

PubMed Abstract | CrossRef Full Text | Google Scholar

51. Mithoefer MC, Feduccia AA, Jerome L, Mithoefer A, Wagner M, Walsh Z, et al. MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology. (2019) 236:2735–45. doi: 10.1007/s00213-019-05249-5

PubMed Abstract | CrossRef Full Text | Google Scholar

52. Jerome L, Feduccia AA, Wang JB, Hamilton S, Yazar-Klosinski B, Emerson A, et al. Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology. (2020) 237:2485–97. doi: 10.1007/s00213-020-05548-2

PubMed Abstract | CrossRef Full Text | Google Scholar

53. Feduccia AA, Holland J, Mithoefer MC. Progress and promise for the MDMA drug development program. Psychopharmacology. (2018) 235:561–71. doi: 10.1007/s00213-017-4779-2

PubMed Abstract | CrossRef Full Text | Google Scholar

54. Feduccia AA, Jerome L, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. Breakthrough for trauma treatment: safety and efficacy of MDMA-assisted psychotherapy compared to paroxetine and sertraline. Front Psychiatry. (2019) 10:650. doi: 10.3389/fpsyt.2019.00650

PubMed Abstract | CrossRef Full Text | Google Scholar

55. Brewerton TD, Lafrance A, Mithoefer MC. The potential use of N-methyl-3,4-methylenedioxyamphetamine (MDMA) assisted psychotherapy in the treatment of eating disorders comorbid with PTSD. Med Hypotheses. (2020) 146:110367. doi: 10.1016/j.mehy.2020.110367

PubMed Abstract | CrossRef Full Text | Google Scholar

56. Danforth AL, Grob CS, Struble C, Feduccia AA, Walker N, Jerome L, et al. Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study. Psychopharmacology. (2018) 235:3137–48. doi: 10.1007/s00213-018-5010-9

PubMed Abstract | CrossRef Full Text | Google Scholar

57. Sessa B, Sakal C, O'Brien S, Nutt D. First study of safety and tolerability of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in patients with alcohol use disorder: preliminary data on the first four participants. BMJ Case Rep. (2019) 12:1–4. doi: 10.1136/bcr-2019-230109

PubMed Abstract | CrossRef Full Text | Google Scholar

58. Wolfson PE, Andries J, Feduccia AA, Jerome L, Wang JB, Williams E, et al. MDMA-assisted psychotherapy for treatment of anxiety and other psychological distress related to life-threatening illnesses: a randomized pilot study. Sci Rep. (2020) 10:1–15. doi: 10.1038/s41598-020-75706-1

PubMed Abstract | CrossRef Full Text | Google Scholar

59. Marseille E, Kahn JG, Yazar-klosinski B, Doblin R. The cost-effectiveness of MDMA-assisted psychotherapy for the treatment of chronic treatment-resistant PTSD. PLoS ONE. (2020) 15: e0239997. doi: 10.1371/journal.pone.0239997

PubMed Abstract | CrossRef Full Text | Google Scholar

60. Garcia-Romeu A, Richards WA. Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions. Int Rev Psychiatry. (2018) 30:291–316. doi: 10.1080/09540261.2018.1486289

PubMed Abstract | CrossRef Full Text | Google Scholar

61. Walsh Z, Thiessen MS. Psychedelics and the new behaviourism: considering the integration of third-wave behaviour therapies with psychedelic-assisted therapy. Int Rev Psychiatry. (2018) 30:343–9. doi: 10.1080/09540261.2018.1474088

PubMed Abstract | CrossRef Full Text | Google Scholar

62. Studerus E, Kometer M, Hasler F, Vollenweider FX. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. J Psychopharmacol. (2011) 25:1434–52. doi: 10.1177/0269881110382466

PubMed Abstract | CrossRef Full Text | Google Scholar

63. Johnson MW, Richards WA, Griffiths RR. Human hallucinogen research: guidelines for safety. J Psychopharmacol. (2008) 22:603–20. doi: 10.1177/0269881108093587

PubMed Abstract | CrossRef Full Text | Google Scholar

64. Nichols DE. Psilocybin: from ancient magic to modern medicine. J Antibiot. (2020) 73:679–86. doi: 10.1038/s41429-020-0311-8

PubMed Abstract | CrossRef Full Text | Google Scholar

65. Mithoefer MC, Grob CS, Brewerton TD. Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA. Lancet Psychiatry. (2016) 3:481–8. doi: 10.1016/S2215-0366(15)00576-3

PubMed Abstract | CrossRef Full Text | Google Scholar

66. Rosenbaum M, Doblin R. Why MDMA Should Not Have Been Made Illegal. Thousand Oaks, CA: Sage Publications (1991).

67. Phelps J. Developing guidelines and competencies for the training of psychedelic therapist. J Human Psychol. (2017) 57:450–87. doi: 10.1177/0022167817711304

CrossRef Full Text | Google Scholar

68. Schenberg EE. Psychedelic-assisted psychotherapy: a paradigm shift in psychiatric research and development. Front Pharmacol. (2018) 9:733. doi: 10.3389/fphar.2018.00733

PubMed Abstract | CrossRef Full Text | Google Scholar

69. Lee DJ, Schnitzlein CW, Wolf JP, Vythilingam M, Rasmusson AM, Hoge CW. Psychotherapy versus pharmacotherapy for post traumaic stress disorder: a systematic review and meta-analysis to determine first line treatments. Depress Anxiety. (2016) 33:792–806. doi: 10.1002/da.22511

PubMed Abstract | CrossRef Full Text | Google Scholar

70. Arroll B, Elley CR, Fishman T, Goodyear-Smith FA, Kenealy T, Blashki G, et al. Antidepressants versus placebo for depression in primary care. Cochrane Database Syst Rev. (2009) 2009:CD007954. doi: 10.1002/14651858.CD007954

PubMed Abstract | CrossRef Full Text | Google Scholar

71. Hampton LM, Daubresse M, Chang HY, Alexander GC, Budnitz DS. Emergency department visits by adults for psychiatric medication adverse events. JAMA Psychiatry. (2014) 71:1006–14. doi: 10.1001/jamapsychiatry.2014.436

PubMed Abstract | CrossRef Full Text | Google Scholar

72. Centre for Addiction and Mental Health. The Crisis is Real. Toronto, ON (2021).

73. Yaden DB, Yaden ME, Griffiths R. Psychedelics in psychiatry - keeping the renaissance from going off the rails. JAMA Psychiatry. (2020) 78:469–70. doi: 10.1001/jamapsychiatry.2020.3672

PubMed Abstract | CrossRef Full Text | Google Scholar

Keywords: psychedelics, mental health, trauma, COVID-19 pandemic, psychedelic-assisted psychotherapy

Citation: Argento E, Christie D, Mackay L, Callon C and Walsh Z (2021) Psychedelic-Assisted Psychotherapy After COVID-19: The Therapeutic Uses of Psilocybin and MDMA for Pandemic-Related Mental Health Problems. Front. Psychiatry 12:716593. doi: 10.3389/fpsyt.2021.716593

Received: 01 June 2021; Accepted: 11 August 2021;
Published: 06 September 2021.

Edited by:

Katrin H. Preller, University of Zurich, Switzerland

Reviewed by:

Eric Vermetten, Leiden University, Netherlands
Monnica T. Williams, University of Ottawa, Canada

Copyright © 2021 Argento, Christie, Mackay, Callon and Walsh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Elena Argento, bccsu-ea@bccsu.ubc.ca