From the Editor

For my patient who had tried several antidepressants, psilocybin offered hope. He’s not alone; hallucinogens are gaining attention, with many using them for purposes ranging from treating mental disorders to recreation. But how safe are these drugs, especially as their use increasingly occurs outside of clinical settings? What’s the connection with psychosis?

In the first selection, Dr. Daniel T. Myran (of the University of Ottawa) and his co-authors attempt to answer these questions in a new study published in JAMA Psychiatry. The population-based study included over nine million people who had visited an ED in Ontario, Canada over a 13-year period. The researchers compared individuals with an ED visit involving hallucinogen use to the general population and to those with ED visits involving other substances, analyzing the risk of developing a psychotic disorder. “Individuals with an ED visit involving hallucinogen use had a 21-fold greater risk of developing a schizophrenia spectrum disorder compared with the general population…” We consider the study and its implications.

Substance use rose during the early days of the pandemic. Did this trend change after lockdowns and social isolation ended? Dr. Divya Ayyala-Somayajula (of Thomas Jefferson University) and her co-authors analyzed US data related to alcohol use in a research letter for Annals of Internal Medicine. They compared the prevalence of alcohol use and heavy alcohol use before the pandemic, during the pandemic, and in 2020, finding “absolute increases of 2.7% (relative increase, 4.0%) and 1.0% (relative increase, 20.2%) and that the increases were sustained in 2022.”

And in the third selection, writer Saddal Diab discusses her decision to publicly acknowledge her mental disorder. Though people were initially supportive, things changed when she has a manic episode. She considers stigma and acceptance in this Globe and Mail essay. “Whatever gushy feelings had surfaced when I came out did not withstand the reality of mania. This left me feeling ashamed, deserted and questioning the nature of my relationships (which I concluded were flimsier than I had anticipated).”

DG

Selection 1: “Emergency Department Visits Involving Hallucinogen Use and Risk of Schizophrenia Spectrum Disorder”

Daniel T. Myran, Michael Pugliese, Jennifer Xiao, et al.

JAMA Psychiatry, 13 November 2024  Online First

Over the past 2 decades, there has been a substantial increase in interest in the potential therapeutic use of hallucinogens, including psychedelics (serotonergic hallucinogens), for the treatment of mental and substance use disorders. Public interest in hallucinogens, which include lysergic acid diethylamide (LSD), dimethyltryptamine (or ayahuasca), psilocybin, methylenedioxymethamphetamine (MDMA; also known as ecstasy), and others, has similarly increased, with estimates suggesting that adult hallucinogen use began rapidly increasing starting in the mid-2010s in North America. As of 2023, an estimated 8.9% of individuals aged 19 to 30 years in the US reported past-year hallucinogen use, more than double the 4.1% in 2015. Results from randomized clinical trials suggest that psychedelic-assisted psychotherapy may be beneficial for treatment-resistant depression, posttraumatic stress disorder, and alcohol use disorder…

Studies to date on the association between psychedelic use and psychosis have been limited by small sample sizes, self-report for both exposure and outcomes, and less clinically relevant measures of psychedelic use (eg, ever used in lifetime). Two studies using health administrative data in Denmark and Norway examined the association between an episode of substance-induced psychosis and the risk of schizophrenia but included only 114 and 69 individuals with hallucinogen-induced psychosis, respectively. A survey of US and UK individuals found no association between psychedelic use and changes in psychotic symptoms 2 months later. However, the study included only 100 individuals who used psychedelics, and both psychedelic use and psychotic symptoms were self-reported. While psychedelic use was associated with increased risk of psychosis for individuals with a family history of psychosis, the small sample size and short follow-up period limited the power and generalizability of the study.

So begins a paper by Myran et al.

Here’s what they did:

  • They conducted a “population-based, retrospective cohort study (January 2008 to December 2021) included all individuals aged 14 to 65 years in Ontario, Canada, with no history of psychosis…”
  • They considered those who had incident ED visit involving hallucinogen use compared with “members of the general population (primary analysis) or individuals with ED visits involving alcohol or cannabis (secondary analysis).”
  • Main outcome: Diagnosis of a schizophrenia spectrum disorder “using a medical record–validated algorithm.”
  • Statistical analyses included cause-specific adjusted hazard models.

Here’s what they found:

  • The study included 9 244 292 individuals.
  • Demographics. The mean age was 40.4 years and the majority were female (50.2%).
  • Hallucinogen use. 0.1% had an incident ED visit involving hallucinogen use. The most common types of ED visits were categorized as harmful use (36.6%) and intoxication (22.2%).
  • Demographics & hallucinogen use. These individuals were younger (mean age of 26.69 years), more likely to be male (70.8%), and live in low-income neighborhoods (27.9%).
  • Use over time. “Annual rates of incident ED visits involving hallucinogens were stable between 2008 and 2012 and then increased by 86.4% between 2013 and 2021 (3.4 vs 6.4 per 100 000 individuals).” 
  • Psychosis & hallucinogen use. They had “a greater risk of being diagnosed with an SSD within 3 years compared with the general population (age- and sex-adjusted hazard ratio [HR], 21.3…).” Adjusting for comorbid substance use and mental health conditions: “individuals with hallucinogen ED visits had a greater risk of SSD compared with the general population (HR, 3.53)…”
  • Psychosis & other substances. “Emergency department visits involving hallucinogens were associated with an increased risk of SSD within 3 years compared with ED visits involving alcohol (HR, 4.66…) and cannabis (HR, 1.47…) in the fully adjusted model.”

A few thoughts:

1. This is a good study – looking at a relevant question with a strong data set and published in a major journal. Bonus: the comparison with those who used other substances.

2. The main finding in a sentence: “Individuals with an ED visit for hallucinogen-induced psychosis had the greatest risk (14.7-fold adjusted increase) of developing an SSD compared with the general population (3-year risk, 20.11% vs 0.15%). Emergency department visits for hallucinogens were associated with 4.7-fold and 1.5-fold higher risk of SSD compared with ED visits for alcohol and cannabis, respectively.”

3. Let’s be clear about what they didn’t show: that hallucinogen use caused psychotic illness. “Our study could not establish a causal link between hallucinogen use requiring care in the ED and SSD, and the associations presented in this study should not be interpreted as causal in nature.”

4. Still, they see a clear clinical implication: “Our findings revealed a group that may have high risk of development of SSD who may benefit from close follow-up and intervention or preventative efforts.”

5. Our society grows more permissive about substance. Is that a mistake?

6. To the point about permissiveness: in 2022, Siegel et al. looked at psychedelic drug legislation in the United States, finding a huge increase in legalization bills at the state level.

That paper was considered in a past Reading, which can be found here:

https://davidgratzer.com/reading-of-the-week/reading-of-the-week-motor-vehicle-crashes-and-mental-disorders-the-new-cjp-paper-also-psychedelics-the-states-and-hogan-on-nyc-coercion/

The full JAMA Psych paper can be found here:

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2825649



Selection 2: “Trends in Alcohol Use After the COVID-19 Pandemic: A National Cross-Sectional Study”

Divya Ayyala-Somayajula, Jennifer L. Dodge, Adam M. Leventhal, et al.

Annals of Internal Medicine, 12 November 2024

Alcohol is a leading cause of morbidity and mortality in the United States. The COVID-19 pandemic was associated with increases in stress-related drinking and alcohol-related deaths. Analyses of whether increased alcohol use has persisted since the pandemic and trends among subpopulations could inform public policy and health care initiatives to mitigate alcohol-related morbidity and mortality.

So begins a letter by Ayyala-Somayajula et al.

Here’s what they did:

  • They conducted “a population-based study using cross-sectional data from serial nationally representative surveys of adults aged 18 years or older who participated in the National Health Interview Survey (NHIS) from 2018 to 2022.” 
  • NHIS data included demographic, health, and socioeconomic factors at the family and person levels and was done by trained interviewers in face-to-face or telephone interviews.
  • The primary outcomes: prevalence of any alcohol use and heavy alcohol use. 
  • Different statistical analyses were done, including logical regression for the difference in prevalence by year (vs 2018).

Here’s what they found:

  • The study included 24 965 respondents from 2018, 30 829 from 2020, and 26 806 from 2022.
  • Compared with 2018, there were absolute increases in any alcohol use in 2020 (2.69%) and 2022 (2.96%). “Increases in any alcohol use occurred in 2020 and 2022 versus 2018 among all subgroups.”
  • Compared with 2018, there were absolute increases in heavy alcohol use in 2020 (1.03%) and 2022 (1.18%). “Numerical increases in heavy alcohol use occurred in 2020 and 2022 versus 2018 among all subgroups except among American Indians and Asians in 2022.” See figure below.

A few thoughts:

1. This is a good letter with solid data.

2. The main finding in a sentence: “This nationally representative study suggests that the prevalence of any alcohol use and heavy alcohol use during the COVID-19 pandemic (2020 vs. 2018) showed absolute increases of 2.7% (relative increase, 4.0%) and 1.0% (relative increase, 20.2%) and that the increases were sustained in 2022.”

3. Is the rise of substance seen in the pandemic now the “new normal,” so to speak?

4. There are obvious implications for public policy. The authors comment: “Our results highlight an alarming public health issue that may require a combination of policy changes. Increased screening efforts for harmful drinking with systematic integration and rapid linkage to behavioral health treatments by health care professionals, in tandem with community-based interventions for at-risk populations, should be considered to mitigate the public health consequences of the pandemic-related increase in alcohol use.”

5. The authors note several limitations, including that the data is based on self-reporting of alcohol use, which may result in underreporting.

The full Ann Intern Med letter can be found here:

https://www.acpjournals.org/doi/10.7326/ANNALS-24-02157

Selection 3: “Being open about being bipolar isn’t easy”

Saddal Diab

The Globe and Mail, 2 June 2024

I don’t remember a time when it was so commonplace to be open about personal struggles. It seems like everyone can be honest about the less palatable parts of themselves. Colleagues at work casually mention that they are seeing their therapist in the evening, and among friends ‘My therapist said,’ is simply a matter of fact.

I have been in therapy since 2002 and was diagnosed as bipolar in 2008. Only a select few knew this at the time, but in the changing climate where mental health seemed less of a hush-hush issue that you sweep under the rug, I sometimes felt the urge to dive right in and come out.

As I inched closer to my confession, I had visions of amassing a following and becoming an advocate.

So begins an essay by Diab.

“With the gentlest voice I could summon, I laid myself bear with a crescendo of confessions which culminated in what I sensed was the jewel of my delivery: ‘Ten years ago, my psychiatrist told me I should wear a mask, otherwise people would stigmatize me. This mask is sweat-leaden, stuffy and I can’t do this anymore.’”

“The response on Instagram was overwhelmingly positive.”

The author provides details. “I was showered with endearing comments and emoticons, many from people I barely communicated with beforehand. They messaged me saying, ‘Big up to you for owning your truth!’ or ‘Proud of you sis.’ Love, love, love. It felt like I had traversed a rite of passage and arrived at an oasis of renewal. For an instant I wasn’t bipolar anymore but ‘brave,’ ‘inspiring’ and ‘cool.’”

She notes things changed when she had “a full-blown manic episode only weeks later.”

“Everyone has their unique poison during a manic episode. For some, it’s excessive spending, alcohol or sex. I binge on social media. I still can’t stomach that I posted over 100 reels on Instagram in one day. I’m whipped by shame when my mood is stable, but in the sweep of an episode, I’m convinced my commentary is insightful and flippant and I am well on my way to being discovered… I lunge between one impulse and another, ricocheting like a bullet. But eventually, the spinning stops. This time around three weeks later it was as if a loose cog snapped into place. I was horrified that my mind had betrayed me yet again and could feel an iron pressure on my chest.”

She writes about the rawness of her emotions. “One of the cruelties of mania is how it exposes you. Your madness is on display and you can’t take any of it back. There is no clean slate once the mania subsides. As an insecure person who has always been preoccupied by what people think of me, the shame was excruciating.”

She is left with questions. “I also wondered whether this wave of self-acceptance excludes serious mental-health conditions. Would I have been better off if I came out as queer? Am I expecting too much of others? All are mounting questions to an unresolved dilemma that defines the contours of my life.”

A few thoughts:

1. This is a well-written essay.

2. While we can all agree that progress has been made and stigma has faded, are there limits?

3. Is Diab fundamentally right in her argument that acceptance is for some disorders but not for serious mental illness? Is social media caustic by its very nature? Are both comments true?

The full Globe essay can be found here:

https://www.theglobeandmail.com/life/first-person/article-being-open-about-being-bipolar-isnt-easy/

Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.