Prenatal Exposure to Cannabis Tied to Aggression, Poorer Executive Function at Age 5

Children exposed to cannabis in the womb may have poorer attention skills and be more prone to aggression at age 5 than children who are not exposed prenatally to cannabis, according to a report in JAMA Pediatrics. The associations observed in the study appeared to be directly related to cannabis exposure, not to the post-natal home environment.

“These outcomes are relevant to long-term academic and adaptive functioning,” wrote Sarah A. Keim, Ph.D., of Nationwide Children’s Hospital in Columbus, Ohio, and colleagues. “These results may be considered in refining clinical recommendations regarding cannabis use during pregnancy.”

Keim and colleagues looked at 250 children of families participating in the Lifestyle and Early Achievement in Families (LEAF) study cohort. The LEAF study included in-person visits at a behavioral research facility at Nationwide Children’s Hospital when the children were between 5 and 6 years of age.

Urine samples taken during mothers’ pregnancy were assayed for tetrahydrocannabinol (THC), the primary psychoactive component of cannabis. Children were considered exposed to cannabis if they had at least one urine specimen with THC higher than 15 ng/ml, their mother self-reported cannabis use on a questionnaire, or cannabis use was noted in the clinical obstetric record. Of the 250 children, 80 (32%) were classified as having been exposed to cannabis prenatally.

The researchers assessed the children’s executive function, such as attention, planning, and memory, at age 5 using a variety of validated measurements. They also assessed children’s aggression with the inflatable Bobo Doll task; the proportion of hits to the doll’s face using a fist was the measure of observed aggression. The children’s caregivers also filled out reports rating the child’s executive function and aggression.

Overall, children exposed to cannabis prenatally had lower test scores on attention and planning than those not exposed. Those exposed to cannabis prenatally also exhibited more aggressive behavior, with 17% more fisted hits to the doll’s face observed. (There were no differences between groups in caregiver ratings of executive function and behavior.)

The researchers noted that cannabis use during pregnancy is increasing in the United States, from 3.4% of pregnant people reporting past-month use in 2002 to 7.2% in 2021. “Many perceive the drug as a safe, natural treatment for nausea, sleep problems, or mood disorders,” they wrote. “Despite guidance from the American Academy of Pediatrics and others to avoid cannabis in pregnancy, many clinicians counsel patients inconsistently and lack knowledge about long-term effects.”

For related information, see the Psychiatric News article “Exposure to Alcohol, Cannabis in Womb Can Have Long-Term Consequences.”

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Many 12th Graders Found to Use Potentially Risky Products With “Legal” THC Variant

A study published today in JAMA reports that many high school seniors are using products containing Δ8-tetrahydrocannabinol (THC), a variant of the main psychoactive compound of marijuana, Δ9-THC. The analysis also showed that Δ8-THC use was elevated in states where recreational marijuana was illegal.

“Gummies and other edibles, electronic vaping devices, and combustible flower containing Δ8-THC are marketed as providing a user experience comparable to marijuana in a product that is federally legal,” wrote Alyssa F. Harlow, Ph.D., of the University of Southern California and colleagues. “Δ8-THC exposure may pose risks to adolescents, including addiction, neurodevelopmental changes, acute psychiatric reactions from accidental overdosing, and exposure to toxic byproducts generated during Δ8-THC synthesis.”

Harlow and colleagues examined data from the 2023 Monitoring the Future study, a nationally representative classroom-based survey of 8th, 10th, and 12th grade students. The 2023 survey included a question for a subset of 12th graders on whether they used Δ8-THC in the past year, and, if yes, how many times. The students also answered a similar question on past-year marijuana use. The final sample included 2,186 responses.

Overall, 11.4% of seniors in the U.S. reported past-year Δ8-THC use and 30.4% reported past year marijuana use. Of seniors who reported using Δ8-THC, 35.4% used it at least 10 times in the past year, while 16.8% used it at least 40 times.

Other findings from the survey included the following:

• Geographically, Δ8-THC use was lowest in the Western U.S. census region (the 13 states west of Texas) at 5.0% compared with the Northeast (10.1%), South (14.3%), and Midwest (14.6%).
• Δ8-THC use was lower in states where marijuana is legal for adults (8.0%) versus states where marijuana is not legal (14.0%).
• Δ8-THC use was lower in states where Δ8-THC was banned or restricted (5.7%) versus states with no Δ8-THC regulation (14.4%).

“The unregulated proliferation of Δ8-THC represents a potential threat to the public’s health,” wrote Jennifer M. Whitehill, Ph.D., of the University of Massachusetts, Amherst, and colleagues in an accompanying editorial. “As health professionals, we need to improve our capacity for addressing the evolving cannabinoid marketplace by instituting centralized and coordinated systems for monitoring cannabis products.”

To read more on this topic, see the Psychiatric News article “Nicotine Gummies, Tablets Popular Among Adolescents.”

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Nabaximols Nasal Spray May Reduce Cannabis Use By Some Patients

A study published today in JAMA Internal Medicine reports that the cannabinoid agonist nabiximols can reduce cannabis use among people with cannabis dependence when combined with behavioral therapy. Nabiximols is a nasal spray composed of purified tetrahydrocannabinol (THC) and cannabidiol (CBD)—two of the primary active components of cannabis.

Study participants who received a combination of nabiximols and behavioral therapy reported using cannabis about 33% fewer days than those allocated to placebo and behavioral therapy, noted Nicholas Lintzeris, M.B.B.S., Ph.D., of Australia’s Drug and Alcohol Services and colleagues. “The reductions in illicit cannabis use and a safer route of administration … suggest the harm-reduction benefits of cannabinoid agonist treatment,” the authors wrote.

Lintzeris and colleagues enrolled 128 adults with cannabis dependence (as defined by the International Classification of Diseases, 10th Revision, or ICD-10) who were seeking treatment to participate in a 12-week trial. As part of the trial, the participants received either nabiximols or placebo nasal spray for daily use and were offered six individual cognitive-behavioral therapy sessions over the course of the trial. Each individual nabiximols spray contains 2.7 mg of THC and 2.5 mg of CBD, and participants could take up to 32 sprays daily.

At baseline, the participants reported using cannabis about 25 of the past 28 days. During the 12-week trial, adults in the placebo group reported significantly more days using cannabis (53 of 84 days) compared with those in the nabiximols group (35 of 84 days). Although there was no statistical difference between the groups in the number of participants who achieved cannabis abstinence (defined as at least 28 consecutive days without use), more adults in the nabiximols group were able to cut their cannabis use by 50% or more (54.1% vs. 28.9%).

The authors noted several limitations of the study, including the finding that only about half of the patients in the placebo and nabiximols groups stayed in treatment throughout the 12-week study. “Although our treatment retention of 46.9% at 12 weeks is comparable with prior randomized clinical trials of cannabinoid agonist treatment (55% at 11 weeks and 67% at 12 weeks), the limited treatment retention across these studies highlights the fact that cannabinoid agonist treatment is not effective for or acceptable to all patients,” Lintzeris and colleagues wrote. “Whereas nicotine-agonist and opioid-agonist treatments are considered frontline therapies, our findings suggest a more cautious approach for cannabinoid agonist treatment at this time.”

For related information, see the Psychiatric News article “Medications May Ease Cannabis Withdrawal But Fail to Achieve Abstinence” and the Psychiatric Services article “Thinking Carefully About Marijuana Legalization: Public Health Considerations for State Policy Makers.”

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