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
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
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.
Abbreviations Used
| ADHD | attention deficit hyperactive disorder |
| ASD | autistic spectrum disorder |
| CBD | cannabidiol |
| FASD | fetal alcohol spectrum disorder |
| THC | tetrahydrocannabinol |
Cite this article as: Koren G, Cohen R, Sachs O (2021) Use of cannabis in fetal alcohol spectrum disorder, Cannabis and Cannabinoid Research 6:1, 74–76, DOI: 10.1089/can.2019.0056.
References
