1-Compose a one-page critical analysis of the following article. 2- Provide your opinion about the article.

2 The Brown UniversiTy Child & AdolesCenT PsyChoPhArmACology UPdATe APril 2017

What’s NeW iN ReseaRch

The earlier the exposure, the more serious the adult sequelae of adolescent cannabis use

précis • Clinical and preclinical studies

show that cannabis exposure during adolescence is associated with harmful cognitive and affective adult outcomes.

• The evidence is not clear that the link is causal in humans, as it is impossible to control for confounders such as predisposition to use, related to nonuse factors that may also predispose these adolescents to other problems.

• Regardless of whether the link is causal, youth who use cannabis are at higher risk for psychiatric morbidity and learning problems, as well as suicidality and addiction in adulthood.

• The earlier the use, the more serious the problems are in adulthood.

E xposure to cannabis in adolescence is associated with possible harm- ful cognitive and affective outcomes in adulthood, researchers have found. A literature search examining the poten- tial effects of exposure to cannabis and related synthetic cannabinoids during adolescence has found that regardless of whether cannabis causes these con- sequences, youth who are exposed are also at higher risk for potential psychi- atric morbidity and learning problems, as well as suicidality and addiction as adults. The earlier the onset of cannabis use, the higher the risk for problems in adulthood, according to the study.

Most of the clinical and preclinical (animal) data found a strong correlation between adolescent cannabinoid expo- sure and adverse, persistent psychiatric problems in adulthood. However, the literature does not prove that cannabis alone is causing these deficits in hu- mans. In animals, however, there is a clear indication that cannabis exposure that starts in adolescence leads to mo- lecular processes that cause persistent functional deficits in adulthood.

Trend of increasing use Not since 1933, when prohibition

was repealed, has there been so much support for legalization of a criminalized substance, the researchers write. “The trajectory is clear: legalized cannabis is the fastest growing market in the United States,” they write. Even though access to cannabis is denied to people under 21, younger people will still be able to acquire it, just as they can alcohol and tobacco. More high school seniors now use marijuana than cigarettes, with 6 to 7 percent reporting daily or almost-daily use, and more than 38 percent reporting use in the past year.

Most of the studies of adolescent can- nabis use in humans identify at least one poor outcome related to mental health in adulthood, specifically linking early- onset use with deficits in cognition and memory, as well as an increase in af- fective and psychotic disorders, and a transition to substance use disorders in adulthood. While these outcomes are dis- proportionately represented among those who started cannabis use in early adoles- cence and were frequent users, the studies were not conclusive.

One big problem is ethical and logi- cal limitations in conducting cannabis research on adolescents. The studies are observational, as it would not be ethical to give human adolescents marijuana as part of a controlled trial because of the “unknown safety of pediatric can- nabis exposure,” the researchers note. Therefore, it’s very difficult to control for pre-existing confounders — traits in the cannabis users or other factors that might themselves have led to the adverse outcomes. Twin studies and genomewide association studies have shown that the decision to use cannabis, as well as the development of problematic use, may have a genetic component. In addition, the same variants involved in cannabis consumption are also involved in schizo- phrenia and depression. Recently, some studies have looked at the possibility that early cannabis use is associated with spe-

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cific alleles (a gene alternative found on the same chromosome).

The “gateway” theory that has been popular in some arenas and criticized in others does have grounding in fact, at least in the past. For decades, the pattern of consumption among teens was first alcohol and cigarettes, then cannabis, and then other drugs, such as opioids and stimulants. Recently, however, teens have been more likely to try cannabis first. Even infrequent teen use of cannabis is linked to an eightfold increase in the use of nicotine, compared to teens who don’t use cannabis. Among adults reporting illicit drug use, such as cocaine, meth- amphetamine, or heroin use, adolescent cannabis use overwhelmingly came first.

Animal models Animal models can control for pre-

morbid traits, dosing schedules, age of first drug exposure, and the washout du- ration preceding behavioral and molecu- lar testing. Persistent deficits in adult memory and learning were among the first reported outcomes of adolescent cannabinoid exposure in rodents. But two studies using lower doses of THC, most closely resembling the mild pat- terns of cannabis use most common among adolescents, found no long-term deficits. A prolonged washout period into adulthood also resulted in no ob- served impairment.

Collectively, the animal studies pro- vide molecular and behavioral evidence of an adolescent vulnerability to can- nabinoid-induced memory impairments

that are structurally related to hippo- campal abnormalities after exposure to higher levels of cannabinoids.

The findings point to the potential risk that the rising potency of can- nabis products and the accessibility of synthetic cannabinoids may result in an increase in long-term learning and memory impairments among adolescent- onset users. So far, in humans, the effect of cannabis on hippocampal develop- ment in adolescence has not been exam- ined extensively, and the animal findings suggest this is an area warranting further study.

For schizophrenia, animal research has used a positive symptom, called prepulse inhibition, which assesses the ability to obtain and process information and is often impaired in humans with psychotic disorders. Animal models of psychotic disorders have close overlap with animal models of cannabis-induced cognitive and emotional alterations. In humans, a decrease in prepulse inhibi- tion is strongly correlated with the pres- ence of psychotic disorders, and is also impaired in people who abuse cannabis.

Clinical research “The increasing acceptance of me-

dicinal and recreational cannabis use in our society, and the policy and legis- lative changes that have followed and occasioned this, are largely based on research and experience derived from, and pertinent to, adults,” the researchers conclude. “From the clinical research, we find a connection repeatedly drawn be-

tween adolescent cannabis use and poorer life outcomes, and when examining the preclinical research, we find evidence to suggest that predisposing genetic or sociocultural aspects do not fully ac- count for the poor functional outcomes observed in adults who initiate cannabis use in adolescence,” they write.

“There is a need for additional, rigor- ous research to determine whether earlier age of onset and a heavier pattern of use play causal roles in increasing one’s risk for persistent, if not permanent, impair- ments in mental health and cognition later in life,” they write. “We cannot yet say whether there is or is not a specific amount of cannabis that youth can ‘safe- ly’ consume, but it remains important for clinicians to keep in mind that youth who use cannabis on the whole represent an at-risk group for potential cognitive difficulties and psychiatric morbidity, in- cluding suicidality. The earlier the onset of use, and the more frequent the use, the higher the risk.”

Future research will require carefully designed animal models and longitudinal studies to discover whether cannabis use alone has a deleterious impact on the human adolescent brain, the researchers concluded. ▪

• • • • • • • • • • • • • • • • • • • • • • • • • • • •

Levine A, Clemenza K, Rynn M, Lieberman J. Evi- dence for the risks and consequences of adolescent cannabis exposure. J Am Acad Child Adolesc Psy- chiatry 2017 Mar; 56(3):214–225. doi: 10.1016/j. jaac.2016.12.014. Epub 2016 Dec 29. Email: [email protected].

The researchers concluded that mothers of preschool children should be screened for depression as well.

Child behavior problems are typically divided into internalizing (negative mood states and behavioral inhibition) and exter- nalizing (behavioral disinhibition) in gen- eral. Maternal depression is on the inter- nalizing spectrum but has been associated with both externalizing and internalizing symptoms in offspring.

Because biological parents and chil- dren share a family environment as well as

mateRNal depRessioN continued from page 1

genes, some of the reported associations could be due to genetic or environmen- tal confounding. There have been some genetic studies investigating the link be- tween maternal depression and child be- havior problems, but most were based on unique samples, with no sibling compari- son. In addition, most of the research has focused on either perinatal depression or exposure to maternal depression when the child was older.

The aim of the study was to investi- gate associations between prenatal, post- natal, or concurrent maternal depression and internalizing or externalizing prob-

lems in children, to clarify whether links were due to familial confounding, and to investigate the effect to the child’s age on associations.

Study details The researchers looked at a prospective

longitudinal sample of 11,599 families, including 17,830 siblings, from the Nor- wegian Mother and Child Cohort Study, conducted by the Norwegian Institute of Public Health. Participants in the study were recruited from 1999 to 2009 during a routine ultrasound offered to all pregnant

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