autism

Medical marijuana: effects on pediatric patients with autism and the developing brain

Virginia Thornley, M.D., Neurologist, Epileptologist

@VThornleyMD

May 6, 2018

Introduction

Medical cannabis is being more and more commonly used in medical conditions specifically neurological. The CB1 receptor is found predominantly within the nervous system and in a few other organs on a lesser basis. The CB2 receptor is mainly in the immune system and found in other organs to a lesser extent.

Recent arguments have arisen promoting medical cannabis in children particularly in those with autism and attention deficit hyperactivity disorder.  It has already been well-established in patients with epilepsy. However, the effects on the developing brains of children have not yet been well-documented as it is not yet widely used or studied in the pediatric population. There are many animal models but this does not always correspond to translate into similar human findings.

Effect in autism in animal models and clinical studies

A current topic of debate is not only using THC in pediatric patients but those with autism. Autism is part of the pervasive developmental disorder consisting of social inhibition and isolation including poor eye contact, delayed language skills, aggressive behavior and may be characterized as having stereotypies such as flapping of the arms. Self-injury, eating and sleep disorders may occur. The etiology may be related to genetic, neurobiochemical or environmental and the exact cause is unclear.

In one animal model study, mice with induced Dravet syndrome-like symptoms was noted to improve in autistic-like social interactions with the addition of low dose cannabidiol (2) of 10mg/kg. At low doses, the DS mice interacted more with stranger mice. At higher doses, this was not noted. Dravet syndrome is a type of epileptic syndrome affecting the SCN1A gene causing medically refractory seizures combined with autism.  However, this was an animal model. Scientific studies do not necessarily translate into positive human clinical results.

There was one case report of a six-year-old boy with early autism. Dronabinol  (delta-9-THC) was administered at 3.62mg a day and followed for 6 months. Using the ABC scale (aberrant behavior checklist), the patient improved in terms of stereotypies which were less, lethargy was reduced, hyperactivity improved, and inappropriate speech improved (4).

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Endocannabinoid system and mechanisms in relation to autism

There are several lines of thinking regarding the role of the endocannabinoid and autism. It is thought that the endocannabinoid system plays a role in neurological development, but can also be modulated by outside cannabinoids. Another line of thinking is that autism spectrum disorders may be related to disrupted pathways that have been affected by the endocannabinoid pathway (5). In one animal study, it was found that the oxytocin peptide may be responsible for disrupting normal signaling pathways giving rise to autism spectrum disorders. Oxytocin appears to be crucial in mediating social reward which is impaired in autistic patients. Anandamide seems to play a role in the signaling pathways for oxytocin which is responsible for the social reward.   Social reward is aberrant in those with autism and this pathway thought to play a key role in causing its pathogenesis. By increasing anandamide at the CB1 receptor, ASD and social impairment is improved (5).

Effect on a fetus

Tetrahydrocannabinol is lipophilic and crosses the blood-brain barrier. It can get stored in the fatty stores which are likely the reason it may have a long-lasting effect.  Cannabinoids have been found to cross the placenta and affect the fetus. It may result in hyperactivity and impulsivity in babies with cannabinoid exposure in utero.

 

Effect on early cerebral development

It was found that in adolescents who used cannabis, there is a reduction in the IQ by the age of 38. It was found that cannabinoid receptors influence axonal migrations as well as subcortical projections within the cerebrum. This affects synaptic connections during childhood and adolescence(3).

The adolescent brain is still not fully matured and likely still subject to neuronal plasticity and changes. It may be affected by substances. One study showed that the frontal lobe is vulnerable to cannabis in adolescents who used it heavily and that cannabis use may impact working memory. (1)

 

 

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During adolescence, when cannabis is initiated it may affect the neuronal circuitry developing in the immature brain. The richest regions in the brain with cannabinoid receptors are the prefrontal cortex, medial temporal lobes, striatum, white matter connections, and cerebellum. When cannabis is introduced during this neurocritically important time of development, these regions can become dysfunctional although some functional studies have shown altered, weakened, strengthened or combination of changes (6).

Some of the most common adverse effects

At high doses in chronic users, it was found to induce anxiety, panic attacks. It can increase blood pressure. However, clinically, it may control seizures

 

In summary

There is a small body of evidence from a scientific standpoint that cannabis may work to help alleviate autism-like symptoms based on the animal models. There is a not enough evidence from a clinical evidence standpoint in human studies to support its use in pediatric patients, with one case report that it helped with impulsivity, reduced lethargy, and inattention. Randomized placebo-controlled clinical trials are needed.

Research has found that cannabinoids may help oxytocin and disrupted signaling pathways that play a role in social reward which is impaired in autism. At present, there is evidence that cannabis may affect neurocognitive development but these are studies in pregnant mothers who used it heavily recreationally and adolescents who used it heavily. It is unclear if there may be a similar impact when used in the pediatric population at a medical dosage and administration as there are not enough studies to expound on this.

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Introduction/Disclaimer

https://neurologybuzz.com/

Reference

  1. Jager, et al, “Cannabis use and memory brain function in adolescent boys: a cross-sectional multicenter fMRI study,” J. Am. Acad. Child Adolesc. Psychiatry, 2010, Jun., 49(6):561-572.
  2. Kaplan, et al, “Cannabidiol attenuates seizures and social deficits in a mouse model in Dravet syndrome,” Proceedings of the National Academy of Science, 2017, Oct.. 114 (42):11229-11234.
  3. Scott, et al, “Medical marijuana: a review of the science and implications for developmental-behavioral pediatric practice,” J. Dev. Behav. Ped., 2016, Feb., 36 (2):115-123.
  4. Kurz, et al, “Use of dronabinol  (delta-9-THC) in autism: a prospective single-case study with early infantile autistic child,” Cannabinoids, 2010, 5 (4):4-6.
  5. Wei, et al, “Enhancement of anandamide-mediated endocannabinoid signaling corrects autism-related social impairment,” Cannabis Cannabinoid Research, 2016, 1(1):81-89
  6. Kelly, et al, “Distinct effects of childhood ADHD and cannabis use on brain functional architecture in young adults, Neuroimage Clin., 2017, 13:188-200.

 

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ADHD

Medical marijuana: effect in pediatric patients with ADHD, long-term cognitive effects in children and review of literature

Virginia Thornley, M.D.,  Neurologist, Epileptologist
May 2, 2018

Introduction
With the advent of a wider use of cannabinoids in neurological disease compared to previously, attention hyperactivity deficit disorder has arisen as one of the possible disorders where patients may benefit. Because it starts in childhood, questions arise whether it may be applied to the pediatric patients with ADHD. If so, what are the long-term consequences on the developing brain?

Effect of cannabis in ADHD and on the brain
There is a paucity of literature on cannabis use in children with ADHD, most have been on adults.  There are some recent clinical trials and its use in adult patients with ADHD.  In a recent study on ADHD in adults, 30 patients were studied, 15 were in the placebo-controlled group and 15 were given Sativex oromucosal spray (combination CBD:THC). There was no statistical difference in cognitive performance although the score patterns on those on Sativex were higher. There was some improvement in attention. There was a significant improvement in emotional lability and hyperactivity (p=0.3). This implies that cannabinoids may play a role in adult ADHD (1).

In a study of 579 young adult patients with an early history of ADHD of which 129 had to be excluded, it was found that the dorsal attention network found in the parietal region was stronger in those with ADHD. The right fronto-parietal and right inferior frontal region connections were weaker in the ADHD group. The left prefrontal dorsal connections and the right prefrontal cortex connections in ADHD were reduced (2).

One of the key components of ADHD in children is motor dysregulation and weakened connections in the somatosensory region. The stronger connections in ADHD in the frontal-opercular regions suggests compensatory adaptations to maintain normal cognition.  There are stronger right parietal region connections in patients with ADHD possibly suggesting maladaptive mechanisms. When patients with ADHD and cannabis use were studied it appeared that there were neuroadaptive processes. In those who used cannabis, there were stronger intrinsic connections with a superior delayed recall.  There were stronger connections in the left fusiform gyrus that correlated with a) less cognitive interference, these are emotional thoughts or personality traits that can intrude and affect tasks at hand and b) better response inhibition performance, this is the ability to ignore distractions. This is consistent with other studies showing an increased task activation response (2).

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Effect of cannabis on the fetus
Tetrahydrocannabinol is lipophilic and crosses the blood-brain barrier. It can get stored in the fatty stores which are likely the reason it may have a long-lasting effect.  Cannabinoids have been found to cross the placenta and affect the fetus. It may result in hyperactivity and impulsivity in babies with cannabinoid exposure in utero (3). There was a greater incidence of inattention and delinquency in prenatal exposure to cannabis.

Effect of medical marijuana in early cerebral development
It was found that in adolescents who used cannabis, there is a reduction in the IQ by the age of 38. It was found that cannabinoid receptors influence axonal migrations as well as subcortical projections within the cerebrum. This affects synaptic connections during childhood and adolescence(4).

The adolescent brain is still not fully matured and likely still subject to neuronal plasticity and changes. It may be affected by substances. One study showed that the frontal lobe is vulnerable to cannabis in adolescents who used it heavily and that cannabis use may impact working memory (5).

During adolescence, when cannabis is initiated it may affect the neuronal circuitry developing in the immature brain. The richest regions in the brain with cannabinoid receptors are the prefrontal cortex, medial temporal lobes, striatum, white matter connections, and cerebellum. When cannabis is introduced during this neurocritically important time of development, these regions can become dysfunctional although some functional studies have shown altered, weakened, strengthened or combination of changes (2).

Some of the most common adverse effects
At high doses in chronic users, it was found to induce anxiety, panic attacks. It can increase blood pressure. However, clinically, it may control seizures

Discussion
There is a paucity of literature on the effects of medical marijuana on the pediatric population. It has been mostly studied in adult patients. It is difficult to correlate the results of beneficial effects on adults on children since the pediatric brain is still developing. In adult patients with ADHD, apparently exposure to cannabis results in a superior delayed recall, there were fewer thought intrusions when completing tasks and better able to ignore distractions.

When exposed in utero, there was a greater risk of developing inattention, hyperactivity, and impulsivity in children who were exposed before conception. There was a greater tendency towards delinquency. In addition, adolescents who had been chronically exposed to cannabis may have had their working memory impacted. The adolescent period is significant from a neurological standpoint in brain development. There were mixed reports on connections being strengthened, weakened or a combination of the two being reported.

It is difficult to correlate the data of chronic medical cannabis exposure of adolescents in a patient who will use it for its medicinal value since the route, amount and administration and frequency will be completely and distinctly different. In addition, most of the adolescent data has been derived from those who had used it recreationally usually by smoking it heavily, there may be a synthetic component which may be detrimental and it is not clear what other substances may have been added.

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In summary
In short, there is not enough scientific and clinical data to support the use of medical cannabis in pediatric patients. Most of the data is derived from animal studies or studies in adults where there are medical benefits. In the pediatric brain even while studies showed abnormal memory in chronic use it was studied in a very different population of heavy recreational users. Therefore, it is not clear if adult findings can translate into similar pediatric success and the same dysfunctional development of chronic heavy abusers would correlate with similar findings in pediatric patients using it for distinctly different reasons and dosing and administrations. If there is some adverse effect on the pediatric brain, it is unclear if the risks outweigh the benefits in a developing brain of the pediatric population. It may be used anecdotally in some practices with some benefits. Large clinical trials are needed to support this.

About

Introduction/Disclaimer

https://neurologybuzz.com/
Reference

1.  Cooper, et al, “Cannabinoid in attention-deficit/hyperactivity disorder: a randomized controlled trial,” Eur. Neuropsychopharmacol., 2017, Aug., 27 (8):795-808
2.  Kelly, et al, “Distinct effects of childhood ADHD and cannabis use on brain functional architecture in young adults, Neuroimage Clin., 2017, 13:188-200.
3.   Goldschimd, et al, “Effects of prenatal marijuana exposure on child behavior problems at age 10,” Neurotoxicol. Teratol., 2000, May-Jun., 22(3):325-326.
4.  Scott, et al, “Medical marijuana: a review of the science and implications for developmental-behavioral pediatric practice,” J. Dev. Behav. Ped., 2016, Feb., 36 (2):115-123.
5.  Jager, et al, “Cannabis use and memory brain function in adolescent boys: a cross-sectional multicenter fMRI study,” J. Am. Acad. Child Adolesc. Psychiatry, 2010, Jun., 49(6):561-572.

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