Cannabis Tied to Self-Harm, Death in Youth With Mood Disorders

Batya Swift Yasgur, MA, LSW

February 01, 2021

Adolescents and young adults with mood disorders and cannabis use disorder (CUD) are at significantly increased risk for self-harm, all-cause mortality, homicide, and death by unintentional overdose, new research suggests.

Investigators found the risk for self-harm was three times higher, all-cause mortality was 59% higher, unintentional overdose was 2.5 times higher, and homicide was more than three times higher in those with versus without CUD.

"The take-home message of these findings is that we need to be aware of the perception that cannabis use is harmless, when it's actually not," lead author Cynthia Fontanella, PhD, associate professor of psychiatry, Ohio State University Wexner Medical Center, Columbus, told Medscape Medical News.

"We need to educate parents and clinicians that there are risks associated with cannabis, including increased risk for self-harm and death, and we need to effectively treat both cannabis use disorder and mood disorders," she said.

The study was published online January 19 in JAMA Pediatrics

Little Research in Youth

"There has been very little research conducted on CUD in the adolescent population, and most studies have been conducted with adults," Fontanella said.

Research on adults has shown that even in people without mood disorders, cannabis use is associated with the early onset of mood disorders, psychosis, and anxiety disorders and has also been linked with suicidal behavior and increased risk for motor vehicle accidents, Fontanella said.

"We were motivated to conduct this study because we treat kids with depression and bipolar disorder and we noticed a high prevalence of CUD in this population, so we were curious about what its negative effects might be," Fontanella recounted.

The researchers analyzed 7-year data drawn from Ohio Medicaid claims and linked to data from death certificates in 204,780 youths between the ages of 10 and 24 years (mean [SD] age was 17.2 [4.10] years at the time of mood disorder diagnosis). Most were female, non-Hispanic White, enrolled in Medicaid due to poverty, and living in a metropolitan area (65.0%, 66.9%, 87.6%, and 77.1%, respectively).

Participants were followed up to 1 year from diagnosis until the end of enrollment, a self-harm event, or death.

Researchers included demographic, clinical, and treatment factors as covariates.

Close to three quarters (72.7%) of the cohort had a depressive disorder, followed by unspecified/persistent mood disorder and bipolar disorder (14.9% and 12.4%, respectively). Comorbidities included attention-deficit/hyperactivity disorder (12.4%), anxiety disorder (12.3%), and other mental disorders (13.1%).

One tenth of the cohort (10.3%) were diagnosed with CUD.

CUD Treatment Referrals

Associations between characteristics of youth and CUD are listed in Table 1.

Table 1. Association Between Participant Characteristics and CUD

Characteristic Adjusted risk ratio (95% CI)
Older age
14-18 vs 10-13 years
9-24 vs 10-13 years

9.35 (8.57 - 10.19)
11.22 (10.27 - 12.26)
Male sex 1.79 (1.74 - 1.84)
Black race 1.39 (1.35 - 1.44)
Bipolar disorder 1.24 (1.21 - 1.29)
Other mood disorders 1.20 (1.15 - 1.25)
Prior history of self-harm 1.66 (1.52 - 1.82)
Previous mental health outpatient visits 1.26 (1.22 - 1.30)
Psychiatric hospitalizations 1.66 (1.57 - 1.76)
Mental health emergency department visits 1.54 (1.47 - 1.61)

Associations between CUD and outcomes of interest (except suicide) were highly significant (Table 2).

Table 2. Association Between Outcomes of Interest and CUD

Outcome Adjusted risk ratio (95% CI)
Nonfatal self-harm 3.28 (2.55 - 4.22)
All-cause mortality 1.59 (1.13 - 2.24)
Death by unintentional overdose 2.40 (1.39 - 4.16)
Homicide 3.23 (1.22 - 8.59)
Suicide 1.22 (0.44 - 3.43)


"Although CUD was associated with suicide in the unadjusted model, it was not significantly associated in adjusted models," the authors report.

Fontanella noted that the risk for these adverse outcomes is greater among those who engage in heavy, frequent use or who use cannabis that has higher-potency tetrahydrocannabinol (THC) content.

Reasons why CUD might be associated with these adverse outcomes are that it can increase impulsivity, poor judgment, and clouded thinking, which may in turn increase the risk for self-harm behaviors, she said.

She recommended that clinicians refer youth with CUD for "effective treatments," including family-based models and individual approaches, such as cognitive behavioral therapy and motivational enhancement therapy.

Open Dialogue

Commenting on the study for Medscape Medical News, Wilfrid Noel Raby, MD, PhD, adjunct clinical professor, Albert Einstein College of Medicine, New York City, noted that psychosis can occur in patients with CUD and mood disorders — especially bipolar disorder — but was not included as a study outcome. "I would have liked to see more data about that," he said.

However, a strength of the study was that it included children as young as 10 years old. "The trend is that cannabis use is starting at younger and younger ages, which has all kinds of ramifications in terms of cerebral development."

Also commenting on the study for Medscape Medical News, Christopher Hammond, MD, PhD, assistant professor of psychiatry, Johns Hopkins School of Medicine, Baltimore, Maryland, said: "Three major strengths of the study are the size of the sample, its longitudinal analysis, and that the authors controlled for a number of potential confounding variables."

In light of the findings, Hammond recommended clinicians and other health professionals who work with young people "should screen for cannabis-related problems in youth with mood disorders."

Hammond, who is the director of the Co-occurring Disorders in Adolescents and Young Adults (CODA) Clinical and Research Program, Johns Hopkins Bayview Medical Center, and was not involved with the study, recommended counseling youth with mood disorders and their parents and families "regarding the potential adverse health effects related to cannabis use."

He also recommended "open dialogue with youth with and without mental health conditions about misleading reports in the national media and advertising about cannabis' health benefits."

The study was funded by the National Institute of Mental Health. Fontanella has reported receiving grants from the National Institute of Mental Health during the conduct of the study. Disclosures for the other authors are listed in the article. Raby has reported no relevant financial relationships. Hammond has reported receiving research grant funding from the National Institutes of Health, the American Academy of Child & Adolescent Psychiatry, Substance Abuse Mental Health Services Administration (SAMHSA), the National Network of Depression Centers, and the Armstrong Institute at Johns Hopkins Bayview and serves as a scientific advisor for the National Courts and Science Institute and as a subject matter expert for SAMHSA related to co-occurring substance use disorders and severe emotional disturbance in youth. 

JAMA Pediatr. Published online January 19, 2021. Abstract

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