https://jamanetwork.com/journals/jamasurgery/article-abstract/2723261

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THC Inhibits Hedgehog-dependent Patterning During Pregnancy

(Maternal cannabis use is associated with suppression of immune gene networks in placenta and increased anxiety phenotypes in offspring)

PNAS November 23,2021; https://doi.org/10.1073/pnas.2106115118

Significance: Cannabis use is becoming more prevalent, including during developmentally sensitive periods such as pregnancy. Here we find that maternal cannabis use is associated with increased cortisol, anxiety, aggression, and hyperactivity in young children. This corresponded with widespread reductions in immune-related gene expression in the placenta which correlated with anxiety and hyperactivity. Future studies are needed to examine the effects of cannabis on immune function during pregnancy as a potential regulatory mechanism shaping neurobehavioral development.

Abstract: While cannabis is among the most used recreational drugs during pregnancy, the impact of maternal cannabis use (mCB) on fetal and child development remains unclear. Here, we assessed the effects of mCB on psychosocial and physiological measures in young children along with the potential relevance of the in utero environment reflected in the placental transcriptome. Children (∼3 to 6 y) were assessed for hair hormone levels, neurobehavioral traits on the Behavioral Assessment System for Children (BASC-2) survey, and heart rate variability (HRV) at rest and during auditory startle. For a subset of children with behavioral assessments, placental specimens collected at birth were processed for RNA sequencing. Hair hormone analysis revealed increased cortisol levels in mCB children. In addition, mCB was associated with greater anxiety, aggression, and hyperactivity. Children with mCB also showed a reduction in the high-frequency component of HRV at baseline, reflecting reduced vagal tone. In the placenta, there was reduced expression of many genes involved in immune system function including type I interferon, neutrophil, and cytokine-signaling pathways. Finally, several of these mCB-linked immune genes organized into coexpression networks that correlated with child anxiety and hyperactivity. Overall, our findings reveal a relationship between mCB and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood.

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By Karen Schmidt, American Heart Association News

At a time of increasing legalization of marijuana, a growing number of people under 50 diagnosed with cannabis use disorder were later hospitalized for a heart attack, new research has found.

The rising trend from 2007 to 2018 was most pronounced in three groups: ages 18 to 34, men and African Americans, according to findings being presented this Sunday at the American Heart Association's virtual Scientific Sessions conference. The results are considered preliminary until published in a peer-reviewed journal.

Although AHA statistics show heart attacks are much less common in people under 50 compared to older adults, the study suggests people who use cannabis should be followed more closely for possible heart problems.

Now that cannabis is becoming legal in many states, "we need to specifically pay attention to this," said lead researcher Darshi Desai, a clinical observer at the University of California Riverside who is applying for her medical residency.

"If we have more (heart attack) patients coming in because of cannabis use disorder, if there is a temporal relationship, it is definitely going to put a huge stress on health care resources in general," Desai said.

She and her colleagues analyzed medical records of 819,354 people from a large public database of hospital stays. They identified people 18 to 49 who had been hospitalized for a heart attack and whose records showed a previous diagnosis of cannabis use disorder. That is defined as excessive, chronic use of marijuana with symptoms of dependence, inability to control use and impairment in social functioning.

The new analysis found that overall, 4.1% of patients hospitalized for heart attacks also had cannabis use disorder, and the proportion nearly tripled from 2.4% in 2007 to 6.7% in 2018.

When researchers broke the data into subgroups, they found the biggest increases during the decade among:

• people 18 to 34, 7.3% in 2007 to 20.2% in 2018
• African Americans, 15.8% in 2007 to 35.2% in 2018
• men, 71.6% in 2007 to 78.1% in 2018

Although previous studies suggested a link between cannabis use and heart attack, this adds to the evidence, said Robert Page, a professor of pharmacy at the University of Colorado in Aurora. He holds a doctorate in pharmacy and chaired the group that prepared an AHA scientific statement published last year on cannabis and cardiovascular health.

"These data add to the body of literature that there is a red flag with cannabis use in young adults," said Page, who was not involved in the new study. Cannabis users need to realize that just because it's "natural" does not mean it is safe. "It is not safe. It's like any other psychotropic medication – it has side effects, and this could be one of them."

"We need to determine whether or not cannabis is a risk factor for heart disease, particularly in younger adults," Page said. "Because as we know, young adults think that they're invincible, and they're not."

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For more research…

• Cannabis may be linked to strokes and heart rhythm disturbances in young people
• Cannabis dependence and abuse nearly doubled risk of heart attack post-surgery
• Study ties heart disease, diabetes to cannabis exposure in utero
• Cannabis and Cardio Don’t Mix!
• Medical Marijuana, Recreational Cannabis, and Cardiovascular Health
• Cannabis use predicts risks of heart failure and cerebrovascular accidents: results from the National Inpatient Sample
• Frequent marijuana use could literally change a person's heart

JAMA Psychiatry. 2021;78(9):1013-1019. doi:10.1001/jamapsychiatry.2021.1471

Question:  Has the population-attributable risk fraction for cannabis use disorder in schizophrenia increased over time, as would be expected with increasing use and potency of cannabis?

Findings: In this Danish nationwide, register-based cohort study, the population-attributable risk fraction for cannabis use disorder in schizophrenia increased from approximately 2% in the period to 1995 to approximately 6% to 8% since 2010.

Meaning: These findings may indicate that cannabis use disorders are associated with an increase in the proportion of cases of schizophrenia.

Abstract

Importance:  Cannabis use and potency of cannabis have increased during the past 2 decades. If the association between cannabis use and schizophrenia is causal, this should be reflected in an increase in the proportion of cases of schizophrenia being attributable to cannabis, the population-attributable risk fraction (PARF).

Objective: To determine whether the PARF for cannabis use disorder in schizophrenia has increased over time.

Exposure:  Diagnosis of cannabis use disorder.

Main Outcomes and Measures:  Diagnosis of schizophrenia, with estimated PARF of cannabis use disorder in schizophrenia from 1972 to 2016.

Results:  A total of 7 186 834 individuals were included in the analysis, including 3 595 910 women (50.0%) and 3 590 924 men (50.0%). The adjusted hazard ratio for schizophrenia fluctuated at approximately 4 (with 95% CIs ranging from approximately 3 to 6) throughout most of the study period when people diagnosed with cannabis use disorder were compared with those without cannabis use disorder. The PARF of cannabis use disorder in schizophrenia also fluctuated, but with clear evidence of an increase from 1995 (when the PARF was relatively stable around 2.0%, with a 95% CI of approximately 0.3% to either side) until reaching some stability around 6.0% to 8.0% (with a 95% CI of approximately 0.5% to either side) since 2010.

Conclusions and Relevance:  The results from these longitudinal analyses show the proportion of cases of schizophrenia associated with cannabis use disorder has increased 3- to 4-fold during the past 2 decades, which is expected given previously described increases in the use and potency of cannabis. This finding has important ramifications regarding legalization and control of use of cannabis.

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