Does psilocybin help PTSD, burnout or depression? In a research article published in JAMA Network Open, this week, researchers presented the results of a randomized clinical trial that tested whether magic mushrooms could help medics recover from high-stress work conditions.1
Two years into the pandemic, burnout, PTSD and depression were slamming frontline medics across the world. And so, Washington State University psychiatrists set to work looking for ways to help their colleagues survive the mental health epidemic that came along with COVID-19. Their drug of choice? Psilocybin the active compound that puts the magic in magic mushrooms.
The researchers claim that compared to a non-psychoactive placebo control, the small group of clinicians treated with magic mushrooms showed a significant improvement in measures of mental health.
Mental Health Emergency
As the pandemic raged on, even after the introduction of vaccines, medics were struggling to cope. With frontline clinicians fearing for their lives and the lives of their families while making life and death decisions for their patients, working conditions had been extreme for two years.
A 2022 systematic review of the global literature found that during the pandemic up to 21% of healthcare workers reported suicidal thoughts, with younger, less hardened, workers most likely to find conditions intolerable.2
The WSU team, comprising psychiatrists, biostatisticians and psychedelic practitioners may have chosen a surprisingly groovy approach to medicating the medics, but their intent was deadly serious.
Seriously psychedelic
The era of Timothy Leary and hippy doctors cavorting in the Canadian wilds is over. These days, investigation of drugs like LSD, psilocybin and MDMA relies on trials conducted using real controls and defined clinical measures. Psychiatry is getting serious about finding clinically effective uses for these controversial mind-melding meds.
The psychonautic Seattle-based psychiatrists carried a heavy responsibility: they needed to conduct the trial in a safe and scientifically sound manner. Their aim was not only to find a path back from PTSD and burnout for their co-workers but to find hard evidence on the utility of psychedelics.
So just how well did psilocybin help burnout, PTSD or depression, if at all?
Numbers matter
Before we go further, it’s important to say that this trial only involved 30 people. That’s 15 who were given a placebo and 15 took psilocybin. Given that psilocybin has been banned in many regions for decades, definitive data about its safety and long-term effects on the brain is hard to collect.
This means when the researchers designed this trial they may not have been allowed by the ethics board to recruit a large number of participants. It’s also possible that they did not have enough funding to provide safety measures and follow-up for more than 30 people. Remember, the maxim ‘Do no harm’ applies to clinical trials too.
In this trial one person who used psilocybin open label at the end reported suicidal thoughts during their trip. This illustrates the importance of supervision and safety considerations in these studies. No other serious adverse events were reported.
Setting the Scene
The researchers placed online ads targetting doctors, nurses and APPs across the United States who had been frontline workers during the pandemic. Over 2000 medics volunteered to take part in the trial. In order to qualify, the volunteers had to have experienced two or more of the following:
- they cared for critically ill COVID-19 patient
- they worked longer than normal hours to care for patients with COVID-19
- they witnessed or were the first to respond to a COVID-19 death
- they provided care to a patient who died without their family present because of COVID-19 restrictions.
They must not have suffered from depression or other mental health issues before the pandemic, and no family history of mental illnesses with a hereditary component. Only those with a moderate to severe rating on the Montgomery-Asberg Depression Rating Scale for at least six months at the time of the trial in 2022, qualified.This ensured that the study was targetting mental health problems that had been triggered by their experiences during the pandemic rather than long-term problems.
Thirty applicants who met the inclusion criterion were selected, mostly from the West Coast. Twenty-five participants identified as white non-hispanic, two as Asian, two as Black or African American and one as Latine.
Double Blind? Kind of…
Once the 30 volunteers had gone through a battery of health checks to make sure that they were safe to proceed, their subject files were anonymized by the recruiters and randomized by a colleague from the research institute who was not involved in the study.
This was to ensure that when the subjects were split into two groups, nobody involved in the experiment would know who was assigned the treatment and who was assigned a placebo. This is the absolute gold standard for conducting a trial because it means that neither the patient nor the experimenter can unintentionally bias the results.
The subjects were then randomly assigned 15 to the control group and 15 to the test group. Neither group knew which group they were in. Well… they tried. As you will see, this didn’t quite work out.
Testing Psilocybin Against Depression, Burnout and PTSD
Over the next year, each subject attended a set of therapy sessions spread over two weeks. They’d have two sessions to prepare them for a trip, a medication session where they’d be given their dose of niacin placebo or psilocybin and then three debriefing sessions. The preparatory and debriefing sessions involved talking therapy with a psychedelic facilitator and centred around their difficulties and what they hoped to achieve. The medication sessions were up to eight hours long and were led by the subject. Subjects completed questionnaires about their symptoms and experiences before and after the sessions and then received a follow-up assessment 28 days later.
It became obvious to both the subjects and the facilitators which group they were in once the medication sessions started. This has been a major point of contention in FDA assessments based on RCTS of certain psychoactive drugs i.e. psilocybin, LSD, MDMA, etc.
After the final assessment of the control treatment, if they wished they could take a second set of sessions, this time with the psilocybin. This gave researchers a chance to investigate differences between an individual’s response to therapy with no psilocybin and therapy with psilocybin. This was a separate study to the RCT because the subjects knew the testing conditions.
Did it work?
At the 28-day follow-up, a licensed professional administered the Montgomery-Asberg Depression Rating Scale (MADRS) on the subject. The assessor was not involved in the psychedelic sessions and did not know whether a participant had been given a placebo or psilocybin.
Using this defined clinical measure of depression, the researchers discovered that the subjects who were given 25Â mg psilocybin at their session reported lower depression scores.
MADRS is a well-characterized test that allows comparisons to be made between the mental state that a subject has at one time or another. The rating allows the clinician to assign a score to the subject that seems to consistently correspond to the severity of their depression. Experiences of depression, trauma and stress are subjective and qualitative. This tool allows mental health professionals to convert these experiences into a quantitative measure so that they can make comparisons and measure changes.
Based on the changes in scores between MADRS tests before and after therapy, the psychedelic therapy worked well to reduce depressive symptoms. The average MADRS score went down by 6.4 points versus 2.3 points with the placebo. A six point reduction is considered clinically meaningful.
Six months later the average change in MADRS score for subjects who were given psilocybin (either as part of the placebo trial or afterwards) was 21 points lower. It’s not clear whether this was because of the therapy, or because 20 out of 30 participants changed jobs.
The Future for Mushrooms
While the results of this trial included clinically significant reductions in measures of depression, don’t hold your breath for your local GP to get her teapot brewing. As explained earlier, the problems with RCTs where the intervention is obvious to everyone involved, complicate the path to drug approval.
In 2024 a highly anticipated application for use of MDMA for PTSD was rejected by the FDA because it was impossible to design a study to test the effects of euphoria where the subject wouldn’t experience euphoria. 3
Still with mounting evidence of its utility, maybe at some point we will see psilocybin prescribed for depression, burnout or PTSD.
References
- Back AL, Freeman-Young TK, Morgan L, et al. Psilocybin Therapy for Clinicians With Symptoms of Depression From Frontline Care During the COVID-19 Pandemic: A Randomized Clinical Trial. JAMA Network Open. 2024;7(12):e2449026. doi:10.1001/jamanetworkopen.2024.49026
- GarcÃa-Iglesias JJ, Gómez-Salgado J, Fernández-Carrasco FJ, et al. Suicidal ideation and suicide attempts in healthcare professionals during the COVID-19 pandemic: A systematic review. Front Public Health. 2022;10:1043216. doi:10.3389/fpubh.2022.1043216
- FDA rejected MDMA-assisted PTSD therapy. Other psychedelics firms intend to avoid that fate. Accessed January 6, 2025. https://www.science.org/content/article/fda-rejected-mdma-assisted-ptsd-therapy-other-psychedelics-firms-intend-avoid-fate
Does psilocybin help PTSD, burnout or depression? In a research article published in JAMA Network Open, this week, researchers presented the results of a randomized clinical trial that tested whether magic mushrooms could help medics recover from high-stress work conditions.1 Two years into the pandemic, burnout, PTSD and depression were slamming frontline medics across the world. And so, Washington State University psychiatrists set to work looking for ways to help their colleagues survive the mental health epidemic that came along with COVID-19. Their drug of choice? Psilocybin the active compound that puts the magic in magic mushrooms. The researchers claim that compared to a non-psychoactive placebo control, the small group of clinicians treated with magic mushrooms showed a significant improvement in measures of mental health. As the pandemic raged on, even after the introduction of vaccines, medics were struggling to cope. With frontline clinicians fearing for their lives and the lives of their families while making life and death decisions for their patients, working conditions had been extreme for two years. A 2022 systematic review of the global literature found that during the pandemic up to 21% of healthcare workers reported suicidal thoughts, with younger, less hardened, workers most likely to find conditions intolerable.2 The WSU team, comprising psychiatrists, biostatisticians and psychedelic practitioners may have chosen a surprisingly groovy approach to medicating the medics, but their intent was deadly serious. The era of Timothy Leary and hippy doctors cavorting in the Canadian wilds is over. These days, investigation of drugs like LSD, psilocybin and MDMA relies on trials conducted using real controls and defined clinical measures. Psychiatry is getting serious about finding clinically effective uses for these controversial mind-melding meds. The psychonautic Seattle-based psychiatrists carried a heavy responsibility: they needed to conduct the trial in a safe and scientifically sound manner. Their aim was not only to find a path back from PTSD and burnout for their co-workers but to find hard evidence on the utility of psychedelics. So just how well did psilocybin help burnout, PTSD or depression, if at all? Before we go further, it’s important to say that this trial only involved 30 people. That’s 15 who were given a placebo and 15 took psilocybin. Given that psilocybin has been banned in many regions for decades, definitive data about its safety and long-term effects on the brain is hard to collect. This means when the researchers designed this trial they may not have been allowed by the ethics board to recruit a large number of participants. It’s also possible that they did not have enough funding to provide safety measures and follow-up for more than 30 people. Remember, the maxim ‘Do no harm’ applies to clinical trials too. In this trial one person who used psilocybin open label at the end reported suicidal thoughts during their trip. This illustrates the importance of supervision and safety considerations in these studies. No other serious adverse events were reported. The researchers placed online ads targetting doctors, nurses and APPs across the United States who had been frontline workers during the pandemic. Over 2000 medics volunteered to take part in the trial. In order to qualify, the volunteers had to have experienced two or more of the following: They must not have suffered from depression or other mental health issues before the pandemic, and no family history of mental illnesses with a hereditary component. Only those with a moderate to severe rating on the Montgomery-Asberg Depression Rating Scale for at least six months at the time of the trial in 2022, qualified.This ensured that the study was targetting mental health problems that had been triggered by their experiences during the pandemic rather than long-term problems. Thirty applicants who met the inclusion criterion were selected, mostly from the West Coast. Twenty-five participants identified as white non-hispanic, two as Asian, two as Black or African American and one as Latine. Once the 30 volunteers had gone through a battery of health checks to make sure that they were safe to proceed, their subject files were anonymized by the recruiters and randomized by a colleague from the research institute who was not involved in the study. This was to ensure that when the subjects were split into two groups, nobody involved in the experiment would know who was assigned the treatment and who was assigned a placebo. This is the absolute gold standard for conducting a trial because it means that neither the patient nor the experimenter can unintentionally bias the results. The subjects were then randomly assigned 15 to the control group and 15 to the test group. Neither group knew which group they were in. Well… they tried. As you will see, this didn’t quite work out. Over the next year, each subject attended a set of therapy sessions spread over two weeks. They’d have two sessions to prepare them for a trip, a medication session where they’d be given their dose of niacin placebo or psilocybin and then three debriefing sessions. The preparatory and debriefing sessions involved talking therapy with a psychedelic facilitator and centred around their difficulties and what they hoped to achieve. The medication sessions were up to eight hours long and were led by the subject. Subjects completed questionnaires about their symptoms and experiences before and after the sessions and then received a follow-up assessment 28 days later. It became obvious to both the subjects and the facilitators which group they were in once the medication sessions started. This has been a major point of contention in FDA assessments based on RCTS of certain psychoactive drugs i.e. psilocybin, LSD, MDMA, etc. After the final assessment of the control treatment, if they wished they could take a second set of sessions, this time with the psilocybin. This gave researchers a chance to investigate differences between an individual’s response to therapy with no psilocybin and therapy with psilocybin. This was a separate study to the RCT because the subjects knew the testing conditions. At the 28-day follow-up, a licensed professional administered the Montgomery-Asberg Depression Rating Scale (MADRS) on the subject. The assessor was not involved in the psychedelic sessions and did not know whether a participant had been given a placebo or psilocybin. Using this defined clinical measure of depression, the researchers discovered that the subjects who were given 25 mg psilocybin at their session reported lower depression scores. MADRS is a well-characterized test that allows comparisons to be made between the mental state that a subject has at one time or another. The rating allows the clinician to assign a score to the subject that seems to consistently correspond to the severity of their depression. Experiences of depression, trauma and stress are subjective and qualitative. This tool allows mental health professionals to convert these experiences into a quantitative measure so that they can make comparisons and measure changes. Based on the changes in scores between MADRS tests before and after therapy, the psychedelic therapy worked well to reduce depressive symptoms. The average MADRS score went down by 6.4 points versus 2.3 points with the placebo. A six point reduction is considered clinically meaningful. Six months later the average change in MADRS score for subjects who were given psilocybin (either as part of the placebo trial or afterwards) was 21 points lower. It’s not clear whether this was because of the therapy, or because 20 out of 30 participants changed jobs. While the results of this trial included clinically significant reductions in measures of depression, don’t hold your breath for your local GP to get her teapot brewing. As explained earlier, the problems with RCTs where the intervention is obvious to everyone involved, complicate the path to drug approval. In 2024 a highly anticipated application for use of MDMA for PTSD was rejected by the FDA because it was impossible to design a study to test the effects of euphoria where the subject wouldn’t experience euphoria. 3 Still with mounting evidence of its utility, maybe at some point we will see psilocybin prescribed for depression, burnout or PTSD.
Mental Health Emergency
Seriously psychedelic
Numbers matter
Setting the Scene
Double Blind? Kind of…
Testing Psilocybin Against Depression, Burnout and PTSD
Did it work?
The Future for Mushrooms
References
