cbd oil for fetal alcohol syndrome

THC and CBD during early pregnancy might cause alcohol-like fetal defects

The research suggests that there is no safe period to consume marijuana during pregnancy.

Scientists have shown in a new study that one-time exposure during early pregnancy to cannabinoids (CBs) like THC or CBD can trigger growth abnormalities in the developing embryo. This was the first time that such a connection has been highlighted in the mammalian womb.

Scott Parnell, an assistant professor of cell biology and physiology at the University of North Carolina, administered either cannabinoids or cannabinoids with alcohol in varying amounts to female mice in their eight-day of pregnancy, which corresponds to 3-4 weeks of pregnancy in humans. This early pregnancy period is the most vulnerable for a developing embryo and is especially dangerous due to the fact that many women are not aware they are pregnant during this stage.

The study went on to show that the one-time use of CBD and THC, which are the primary ingredients in marijuana, caused brain and facial development effects similar to those experienced during fetal alcohol syndrome. When alcohol was administered together with either CBD or THC, the birth defects doubled.

“The development of the embryo in this time period is very similar across all vertebrates,” said Parnell in a statement. “In this study we also test a synthetic cannabinoid in zebrafish that yielded similar growth deformations as the natural CBs. Having the same results across animal models reinforces our findings.”

Parnell says that CBD and THC may be causing defects as a result of interactions at the cellular level that disrupt signaling between molecules and cells that control growth and development.

Left: brain of control mouse. Right: brain of a mouse exposed to alcohol and cannabinoids on the 8th day of pregnancy.

The CBD concentration was equivalent to what is considered a therapeutic range for humans, while the THC concentration was similar to that reached by a person smoking cannabis.

“The interaction between alcohol and CBs we witnessed is very concerning,” said the study’s first author, Eric Fish, PhD, research associate in the UNC School of Medicine Bowles Center for Alcohol Studies. “Previous studies have shown that CBs and alcohol are frequently used together, and for pregnant women we’re learning that could be very dangerous to a developing child.”

In the future, the researchers would like to run more tests but for now, the findings are worrisome.

According to previous research, marijuana use has not been associated with birth defects, stillbirth or preterm birth. This, in itself, is good news for pregnant women who have decided to take CBD oil, but this is by no means an endorsement. The absence of evidence is not evidence of absence. For instance, because cannabinoid receptors are involved in brain development, some fear that CBD oil might trigger growth abnormalities in the developing brain — which is exactly what he new study showed. However, others believe the opposite effect could be true — that is promoting healthy fetal brain development — since CBD can promote neurogenesis.

“We know that there is no safe period to drink alcohol during a pregnancy, and I think this research shows the same is likely true of marijuana use,” Parnell said.

Use of Cannabis in Fetal Alcohol Spectrum Disorder

1 Motherisk Israel Program, Shamir Hospital, Zerifin, Israel.

2 Adelson Faculty of Medicine, Ariel University, Ariel, Israel.

Rana Cohen

1 Motherisk Israel Program, Shamir Hospital, Zerifin, Israel.

Ornie Sachs

2 Adelson Faculty of Medicine, Ariel University, Ariel, Israel.

Abstract

Background: Fetal alcohol spectrum disorder (FASD) has been recently estimated to afflict up to 5% of American children. Most of these children exhibit different degrees of symptomatology of disruptive behaviors. Yet, there has been very little research on the efficacy and safety of pharmacological modalities, limited mostly to stimulants for attention deficit hyperactive disorder or second generation atypical antipsychotics for aggression. Recently, the use of cannabinoids has been described for symptoms related to autistic spectrum disorder with apparent favorable effects, as well as for other disruptive behaviors. The objective of our study was to follow up in a retrospective case series the effect of cannabis in children and young adults diagnosed with FASD.

Methods: In two children and three FASD young adults with severe disruptive behavior, changes in behavior after cannabis use were measured by the parent version of the Nisonger Child Behavior Rating Form.

Results: In all five cases, there was a highly statistical decrease in the disruptive behavior score from 18±1.0 before cannabis use to 6±2.1 after introduction of cannabis (p=0.0002).

Discussion: In children and young adults with FASD, cannabis, mostly cannabidiol (CBD), has been associated with a marked and statistically significant improvement in serious disruptive behavior. These cases suggest that the efficacy and safety of CBD should be tested in well-controlled studies.

Introduction

Fetal alcohol spectrum disorder (FASD) has been recently estimated to afflict up to 5% of American children, 1 a higher incidence than the previously quoted 1% 2 and is considered the most prevalent congenital neurobehavioral disability. With numerous theories attempting to identify the mechanisms underlying the neurobehavioral damage, most of these children exhibit different degrees of symptomatology of disruptive behaviors, attention deficit hyperactivity disorder (ADHD), oppositional behavior, depression and other neurobehavioral problems. 2 Yet, there has been very little research published on the efficacy and safety of pharmacological modalities, limited mostly to stimulants for ADHD, or second generation atypical antipsychotics for aggression. 3

During the past few years, in parallel to their legalization in increasing number of countries, the use of cannabinoids has been described for symptoms related to autistic spectrum disorder (ASD) with apparent favorable effects, 4 as well as for other disruptive behaviors. 5

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In our FASD diagnostic clinic, we have begun to encounter cases of children and young adults with FASD treated with cannabinoids, which have been initiated by their parents for symptoms related to FASDs. A focused literature review has failed to identify any such published cases.

The aim of this report is to describe five cases of children and young adults treated for disruptive symptoms related to FASD with different cannabinoids.

Methods

All five cases described here were diagnosed by us in recent years as suffering from FASD. At the time of diagnosis, none of them received cannabinoids. In all cases, the initiation of cannabinoid use was by the parents. The study protocol was approved by Shamir hospital research ethics committee and informed consent was given by the parents for use of anonymous data. The diagnosis of FASD was based on the internationally accepted criteria. 6 Disruptive symptomatology was ranked by the parent version of the Nisonger Child Behavior Rating Form, a visual analog scale for disruptive symptoms. 7

Changes in disruptive symptoms before versus after cannabis use were quantified by Student’s t-test for paired data.

Cases

Case 1

The case is a 5-year 4-month-old boy with FASD whose behavior has been characterized by aggressiveness toward kindergarten peers and, numerous daily tantrum attacks resulting in damage to toys and furniture. His FASD was characterized by global cognitive delay, ADHD, and conduct disorder. He has been reported to have taken parcels and toys belonging to other children and used to disappear regularly.

Over the 2 years since the initiation of two oil drops containing cannabidiol (CBD) (20%) with traces of tetrahydrocannabinol (THC, 0.2%), there has been a dramatic change in his behavior: his tantrum attacks have been reduced to once a day or less and his aggressiveness toward other children has disappeared. He asks permission before taking things belonging to other people, communicates his feelings more clearly. And his disappearances have decreased substantially. During the CBD exposure, he did not receive any antipsychotic drug.

Case 2

The case is a 12-year-old boy diagnosed with FASD characterized by learning disability and conduct disorder; he displayed severe restlessness, aggressive behavior, and impulsivity despite treatment with methylphenidate and risperidone. The initiation of three morning drops of CBD oil (15% CBD and 1% of THC) has led to a marked reduction in aggressiveness, restlessness, and impulsivity, and has allowed to cancel the plan to increase the dose of risperidone.

Case 3

The case is a 19-year-old young man diagnosed with FASD characterized by global cognitive delay, ADHD, and conduct disorder. He exhibited severe bouts of aggressive behavior, impulsivity, and inability to control his behavior. Two years of smoking cannabis (THC) twice daily (0.5 g per cigarette) has been associated with a marked decrease in his anger levels, calming his anger attacks and allowing him to think in a balanced way.

Case 4

The case is a 20-year-old young woman with FASD, characterized by learning disability, cognitive delay, and conduct disorder. She exhibited high levels of aggression and impulsivity, inability to concentrate and listen, and numerous episodes of disappearance. Previous use of risperidone was associated with severe dysphoria and vegetative behavior. Over the 5-month use of 1 g daily preparation of flowers containing CBD, there has been a dramatic decrease in aggressiveness and impulsivity, and she has not disappeared over the whole of 5 months. After several weeks the dose could be reduced to 0.5 g/day with similar favorable effects. According to her mother, her ability to listen and retain information increased substantially.

Case 5

The case is a 20-year-old young man with FASD characterized by global cognitive delay, ADHD, and conduct disorder. He exhibited extreme restlessness and aggression, affecting his ability to think rationally, to focus or maintain a steady line of rational activities. Two years of twice daily use of smoked CBD (0.5+0.5 g) has allowed him to be much more restful and focused, to execute tasks, to think and solve issues, and “to count to 10 before I respond to things.” According to his mother, with the CBD he is capable of maintaining rational thinking.

In none of these five cases did the parents report on adverse effects, nor did they detect tolerance over time.

Statistical analysis

There was a highly statistical decrease in the disruptive behavior score from (mean±SD) 18±1.0 before cannabis use to 6±2.1 after introduction of cannabis (p=0.0002).

Discussion

Many children and adults diagnosed with FASD suffer from symptoms stemming from disruptive behavior, characterized by agitation, aggression, restlessness, impulsivity, and related symptoms. 2 These typically interrupt substantially with their ability to interact with peers and adults, maintain tasks, sitting in class or hold a job, with numerous other difficulties.

Because a high percentage of children with FASD exhibit symptoms of ADHD, they often receive stimulants that may favorably improve their hyperactivity, inattention, and impulsivity. However, not rarely, the stimulants increase agitation, impulsivity, and related symptoms. 3 The symptomatic aggressive child with FASD often receives a second generation antipsychotic drug, with risperidone being the most widely used. 3 However, the common adverse effects in achieving calm in these cases are sedation, apathy, and loss of cognitive ability among other adverse behavioral reactions, in addition to excessive weight gain and the metabolic syndrome.

Over the past few years, a slowly growing body of research has aimed at examining the potential role of cannabinoids in treating different pediatric conditions. In general, the attempt has been to avoid the habit forming THC in favor of the generally nonaddictive CBD. 8 Although the best evidence to date related to CBD use for specific forms of epilepsy, several studies have shown its apparent efficacy for symptoms of ASD. 4,5 We have recently shown that based on parents’ reports, CBD improved symptoms of aggression and restlessness in the majority of children with ASD. In parallel, it also improved their sleep and ability to communicate. 4

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The five cases presented here are, to the best of our knowledge, the first reports of the use of cannabinoids for symptoms of FASD. The initiation of their use was by highly concerned parents who felt that existing therapeutic options have not addressed the severity and seriousness of the children’s symptoms of disruptive behavior. As such, this is not a controlled study from any aspect: the different cannabinoids used, the differing routes of administration, and the wide range of ages should be acknowledged. However, these cases may inform clinical researchers how to design a proper study with cannabis for children with FASD. A common denominator of all five cases has been the nature of symptoms, including restlessness, aggression, agitation, and impulsivity, and the very high score on the Nisonger disruptive behavior scale. This allows to begin evaluating the cannabinoid efficacy for these symptoms, which is quite similar to what we and others have encountered in children with ASD. 4,5 It is apparent that these five children and young adult did not experience serious adverse drug reactions.

Before a properly powered prospective study is initiated, one must consider potential adverse effects of cannabis on children’s brain development. Several recent studies have suggested that the recreational use of cannabis is associated with adverse effects on different brain functions among adolescents. 9,10

These cases suggest that the efficacy and safety of CBD should be tested in well-controlled studies. Adding them to the very restricted armamentarium of pharmacological solutions for disruptive behavior may be very meaningful, especially because second generation antipsychotic drugs carry high risk of adverse central nervous system effects, in addition to serious weight gain and complex metabolic changes. Future studies should select a single source of cannabis with accurate evidence of content, a randomized controlled design, either against placebo or a standard psychoactive drug, and objective measures of improvement and short- and long-term adverse effects.

CBD and Fetal Alcohol Syndrome – March 2022

A 2019 study , published in Scientific Reports, tested whether cannabinoids intensify alcohol-induced congenital disabilities ( 2 ) . The study was the first research to show such a connection in mammals.

Results showed how a single exposure to cannabinoids during early pregnancy could cause growth problems in a developing embryo.
The investigation was performed in mice, which are very accurate models for the development that occurs during early pregnancy, according to Scott Parnell, Ph.D., the study’s senior author and assistant professor of cell biology and physiology in the UNC School of Medicine.

In the study, cannabinoids and cannabinoids with alcohol were given in varying amounts on day eight of the animals’ pregnancy, which is equivalent to the third and fourth weeks of human pregnancy.

This period is when alcohol and cannabinoid exposure is most damaging to a growing embryo, and the time when some women do not realize they are pregnant.

The CBD amounts administered to the mice were equivalent to the accepted therapeutic range for humans. Meanwhile, the THC concentration given was comparable to levels reached by a person smoking marijuana.

In the study, researchers found that the brain and facial developmental effects caused by exposure to cannabinoids CBD and THC were very similar to what is seen in fetal alcohol syndrome.

Parnell and his team of researchers also found that when cannabinoids and alcohol interact, the probability of these congenital disabilities more than doubled.

Parnell says that CBD and THC may be causing defects due to the interactions at the cellular level that disrupt the signaling between cells and molecules that regulate growth and development.

“The interaction between alcohol and cannabinoids we witnessed is very concerning. Previous studies have shown that cannabinoids and alcohol are frequently used together, and for pregnant women, we’re learning that could be very dangerous to a developing child.”

—Eric Fish, Ph.D., author of the study and research associate in the UNC School of Medicine Bowles Center for Alcohol Studies

The Dangers of Using Cannabis During Pregnancy

CBD oil is extracted mainly from hemp plants and is neither psychoactive nor addictive. It has been gaining popularity among people who are searching for a natural remedy for ailments such as stress and pain.

Pregnant women who experience discomforts brought about by their pregnancy, such as pain, nausea, and vomiting, might be inclined to use CBD.

A 2012 study published in the Journal of Experimental Medicine suggests that using CBD can reduce pain and inflammation ( 3 ) .

The researchers also found that subjects were not likely to develop a tolerance to the effects of CBD, eliminating the need to increase their dose continually.

In the British Journal of Pharmacology , a 2011 study shows how CBD may alleviate nausea and vomiting produced by chemotherapy ( 4 ) .

However, given the lack of l ongitudinal research on human subjects on the use of CBD oil during pregnancy, women are advised against using it under any circumstances.

Doctors are also wary about recommending it because of its close association with marijuana and the lack of research on it alone.

The American College of Obstetricians and Gynecologists (ACOG), in its 2017 Committee Opinion , states that “Pregnant women or women contemplating pregnancy should be encouraged to discontinue use of marijuana for medicinal purposes in favor of alternative therapy for which there are better pregnancy-specific safety data ( 5 ) .”

“I am emphasizing the importance of protecting our Nation from the health risks of marijuana use in adolescence and during pregnancy. Recent increases in access to marijuana and in its potency, along with misperceptions of safety of marijuana endanger our most precious resource, our nation’s youth.”

— Surgeon General VADM Jerome Adams

The U.S. Food and Drug Administration (FDA), in its Consumer Updates , also strongly advises against the use of CBD, THC, and marijuana in any form when pregnant or while breastfeeding ( 7 ) .

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According to the Centers for Disease Control and Prevention (CDC), smoking or vaping marijuana when pregnant may also be damaging to the fetus ( 8 ) . When expectant mothers smoke or consume marijuana, chemicals go through the placenta and reach the fetus.

Meanwhile, a 2011 study published by the National Institutes of Health demonstrated the long-term behavioral consequences of maternal exposure to cannabinoids during pregnancy and lactation ( 9 ) .

Although the aforementioned study was conducted on animal subjects, and it did not specifically examine the impact of CBD when used alone, the researchers say that their findings are in line with clinical studies reporting hyperactivity and cognitive impairments in humans exposed in utero to cannabis.

What is FAS?

FAS or fetal alcohol syndrome is a congenital medical condition in a child that is a consequence of alcohol exposure during the mother’s pregnancy.

While symptoms of FAS differ from child to child, the condition may also lead to brain damage and growth problems. Unfortunately, the defects caused by fetal alcohol syndrome are not reversible.

According to a 2019 review published by the National Center for Biotechnology Information, alcohol is extremely teratogenic (causes developmental malformations) to a fetus, and its effects are irreversible ( 10 ) .

  • Poor nutrition during pregnancy
  • Women above 30 years old with a long history of alcohol are more likely to give birth to an infant with FAS
  • Having a child with FAS increases the risk for subsequent children
  • Women whose genetic susceptibility allows them to metabolize alcohol slowly may be at a higher risk

If a child is suspected of having fetal alcohol syndrome, talk to a doctor immediately. Early diagnosis of the disorder may help to reduce issues, such as learning difficulties and behavioral problems.

Symptoms of FAS

Signs and symptoms of FAS may include any combination of physical defects, cognitive disabilities, and inability to function and cope with daily life.

Physical defects may include:

  • Slow physical growth before and after birth
  • Small head circumference and brain size
  • Vision difficulties or hearing problems
  • Deformities of joints , limbs, and fingers
  • Distinguishing facial features, such as small eyes, an abnormally thin upper lip, an upturned nose, and unusually smooth skin between the nose and upper lip

Issues with the brain and central nervous system may include:

  • Poor judgment skills
  • Poor attention and processing information things or situations
  • Difficulty with reasoning and problem-solving
  • Jitteriness or hyperactivity

Behavioral and social problems may include:

  • Trouble adapting to change
  • Difficulty planning or working toward a goal
  • Problems with behavior and impulse control
  • Trouble getting along with others
  • Rapid change of mood

Alcohol and Pregnancy

Like Parnell, the Centers for Disease Control and Prevention (CDC) and the U.S. Surgeon General also believe that alcohol is not safe during pregnancy.

According to these agencies, “There is no known safe amount of alcohol to drink while pregnant. There is also no known safe time during pregnancy or safe type of alcohol.”

In most babies exposed to alcohol in utero, congenital abnormalities do show up as physical abnormalities. Instead, these children exhibit subtle behavioral and learning problems that are often undiagnosed or misdiagnosed as Autism or Attention Deficit Disorder (ADD) rather than one of the Fetal Alcohol Spectrum Disorders.

In a study , which was published by Brain Sciences Journal in 2015, the author examined the potential role of endocannabinoids signaling in fetal alcohol spectrum disorder ( 11 ) .

“When talking about the prenatal effects of alcohol, we usually think exclusively about the dose, the strength, and the timing of alcohol exposure. Without knowing those genetic and nutritional factors that are critically involved with the way a woman metabolizes alcohol, it is not possible to make any generalizations about a “safe” amount of alcohol during pregnancy. What may be” safe” for one woman may be “devastating” for another woman’s unborn baby.”

—Dr. Kenneth Jones – Co-discoverer ‘Fetal Alcohol Syndrome’ in 1973

Results from a review published by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in 2003, indicated that prenatal alcohol exposure is linked to a characteristic pattern of intellectual disability, particularly in arithmetic and some aspects of attention, such as planning, mental flexibility, and response to feedback ( 12 ) .

According to the researchers, as children exposed to alcohol grow old, deficits in socio-emotional functions become more apparent, particularly in the areas of judgment and interpersonal skills.

These deficits are severe and have been documented most extensively in children with FAS. However, children prenatally exposed to reduced levels of alcohol often exhibit the same problems.

Conclusion

The National Organization on Fetal Alcohol Syndrome (NOFAS) says that over four decades of published research has shown alcohol to be toxic to a developing baby, as it can cause brain damage and congenital malformations.

Based on NOFAS Fact Sheets , an estimated 40,000 newborns each year are affected by FAS or have FASD.

The American Academy of Pediatrics (AAP) is against drinking during pregnancy, saying that, “Evidence-based research has found that drinking even small amounts of alcohol while pregnant can increase the risk of miscarriage, stillbirth, prematurity, or sudden infant death syndrome.”

Given that FAS causes unrectifiable problems, pregnant women are strongly advised against alcohol consumption.

Medical experts also give similar warnings to pregnant women who may be contemplating using CBD to relieve pregnancy discomforts.