Different responses of repetitive behaviours in juvenile and young adult mice to Δ 9 -tetrahydrocannabinol and cannabidiol may affect decision making for Tourette syndrome
Background and purpose: Medicinal cannabis is in increasing use by patients with Tourette syndrome, a neuropsychiatric disorder that affects about 1% of the general population and has a childhood onset. However, the pharmacological effects of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD) have not been systematically screened or compared between juvenile and young adult rodents in a model of Tourette syndrome.
Experimental approach: The administration of 2,5-dimethoxy-4-iodoamphetamine (DOI) increases head twitch response (HTR) and ear scratch response (ESR) and has been proposed as an animal model useful to respectively study motor tics and premonitory urges associated with tic disorders.
Key results: Comparing the potency of Δ 9 -THC to inhibit DOI-induced repetitive behaviours, the rank order was ESR > grooming > HTR versus ESR = grooming > HTR in young adult versus juvenile mice. Δ 9 -THC (5 mg·kg -1 ) induced severe adverse effects in the form of cataleptic behaviour in control mice and significantly increased ESR in juveniles. The pharmacological effects of CBD have not been studied in models of Tourette syndrome. In juveniles, CBD had no effect on DOI-induced ESR and grooming behaviours. CBD alone induced side effects, significantly increasing the frequency of HTR in juveniles and young adults.
Conclusion and implications: Δ 9 -THC efficaciously reverses peripheral but not central motor tics. Δ 9 -THC may reduce ambulatory movements and evoke premonitory urges in some paediatric patients. The small “therapeutic window” in juveniles suggests that CBD may not effectively treat motor tics in children and may even exacerbate tics in a population of patients with Tourette syndrome.
Keywords: 2,5-dimethoxy-4-iodoamphetamine (DOI); Tourette syndrome; motor tic; premonitory urge; side effect; tic disorder; Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD).
© 2020 The British Pharmacological Society.
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CBD: What Parents Need to Know
Parents are giving it to kids to combat anxiety and other problems. But there are risks, and little research to support it.
What You’ll Learn
- Is CBD safe for kids?
- What are the risks of giving kids CBD?
- Can CBD help kids who have mental health disorders?
- Quick Read
- Full Article
- What do we know about CBD?
- Concerns about CBD
- Is CBD safe?
- CBD oil for anxiety
- CBD and autism
- Research boom
These days, you can find CBD everywhere. Some people believe that it can treat everything from chronic pain and cancer to anxiety and ADHD. But is it safe for kids?
CBD is still pretty new, so there’s very little research about its safety or how well it works, especially for children. So far, there’s only one marijuana-derived medication that has been approved by the Food and Drug Administration. It’s called Epidiolex, and it’s used to treat a rare form of epilepsy in patients who are at least two years old.
Because CBD is so new, there also aren’t a lot of rules about what can and cannot be included in CBD products. So, there’s a huge variety in the quality of products. You may even find different amounts of CBD in different packages of the same product.
Since there isn’t a lot of research about CBD, doctors say there are some risks with using CBD for kids. For example, CBD products may contain things other than CBD, and those things could be harmful. Plus, we don’t yet know if CBD works well with other medications or how much you should give your child.
Although a few studies have found that CBD oil might work for anxiety, they only looked at healthy people who were put in situations that made them anxious. There are no studies yet on people with chronic anxiety. Researchers are also exploring CBD for kids with autism spectrum disorder. The results are good so far, but more research needs to be done before we can know if it’s safe and effective.
CBD is everywhere. From corner stores and bars to medical marijuana dispensaries, it’s being offered for its reputed ability to relieve pain and make people feel better.
Though CBD — full name cannabidiol — is extracted from marijuana or hemp, it doesn’t contain THC, the chemical in marijuana that has psychoactive effects, so it doesn’t make you feel high.
Available in the form of vaping, oils, lotions, cocktails, coffee, gummies — you name it — CBD has been touted as a treatment for complaints as far-reaching as chronic pain, cancer, migraines, anxiety and ADHD. You know it’s gone mainstream when even Consumer Reports has issued guides on how to shop for CBD and tips for safe CBD use.
Not only are adults experimenting with CBD for whatever is bothering them, increasingly parents are turning to CBD to help their kids focus, sleep, calm down and more.
But popular use of CBD is blowing up with very little research into its safety or its efficacy, especially in children. The first and only marijuana-derived drug approved by the Food and Drug Administration, Epidiolex, is used to treat a rare, severe form of epilepsy in patients two years of age and older. And since cannabis is in the early stages of legalization and regulation, there is a huge variety in the quality and dosage of products — risks associated with using products that have not been vetted by the FDA.
What do we know about CBD?
For millennia, hemp plants have been used for medicinal purposes around the world. In 1851 marijuana was classified by the United States Pharmocopeia as a viable medical compound used to treat conditions like epilepsy, migraines and pain. But since marijuana and cannabis-related products were made illegal in the US in 1970, there has been a dearth of research about either marijuana or CBD. Its classification as a Schedule 1 drug made it nearly impossible to get federal funding to study cannabis.
“The biggest problem is there’s a lot that we still need to know, especially in kids,” says Paul Mitrani, MD, a clinical psychiatrist at the Child Mind Institute. “In regards to treating mental health disorders in children and adolescents, there’s a lack of evidence to support its use.”
Dr. Mitrani, who is a pediatrician and child and adolescent psychiatrist, says it’s an area worthy of investigation but recommends that parents wait until further research is done before giving a child CBD.
Concerns about CBD
While anecdotal evidence of the benefits of CBD is common, there are risks associated with using these products, especially in children. Some of the concerns:
- Products are unreliable in delivering a consistent amount of CBD. They could have less, or more, than advertised, and most do not offer independent verification of active contents. Analysis of products for sale show that many do not have the amount of CBD that they advertise. “So you can’t depend on the quality of what you’re getting,” notes Dr. Mitrani.
- How much is absorbed? Very little is known about how much CBD is actually delivered to the brain in a given product. Various delivery systems — vaping, taking it orally, eating it in baked goods, etc. — have different rates of delivery. Even the oils that the CBD is dissolved in can result in varying effects. “Effects can vary a lot based on the delivery system used and the amount people are exposed to can be inconsistent,” Dr. Mitrani says.
- Products may contain things other than CBD, and they could be harmful. Lab testing — which provides information about CBD levels, THC levels (if any), and contaminants in the product — isn’t mandatory for CBD products in every state. Without a CoA (Certificate of Analysis) it’s that much harder to verify the safety of the product. Bootleg CBD may be connected to recent lung illnesses and deaths that have been attributed to vaping. The CDC and the American Medical Association recommend avoiding vaping entirely while the cause of these illnesses is determined.
- CBD may be safe itself, but it may interact with other medications a child is taking, that are also metabolized in the liver.
- If it’s used for sleep, Dr. Mitrani worries that while it may potentially help with sleep, “your child may become tolerant to it and possibly experience worsening sleep problems if stopped.”
- Since CBD use — especially for kids — is a still so new, few people are familiar with dosing for children, so determining how much to give your child would be tricky. Clinical doses versus what you might find at a coffeehouse could vary dramatically.
- The legality of cannabis products and CBD is still murky. CBD derived from hemp is federally legal, while CBD derived from marijuana plants is subject to the legal status in each state — and remains federally illegal. Meanwhile, the FDA issued a statement making clear that products that contain CBD — even if they are derived from legal, commercial hemp — cannot claim to have therapeutic benefits or be sold as dietary supplements unless they have been approved by the FDA for that use.
Is CBD safe?
Last year the World Health Organization, acknowledging the explosion in “unsanctioned” medical uses of CBD, reviewed the evidence for its safety and effectiveness. The WHO report concluded that “CBD is generally well tolerated with a good safety profile.” Any adverse effects could be a result of interactions between CBD and a patient’s existing medications, the WHO noted.
The report found no indication of potential abuse or dependence. “To date there is no evidence of recreational use of CBD or any public health-related problems associated with the use of pure CBD.”
As for effectiveness, the WHO noted that several clinical trials had shown effectiveness for epilepsy, adding: “There is also preliminary evidence that CBD may be a useful treatment for a number of other medical conditions.”
CBD oil for anxiety
In 2015 a group of researchers led by Esther Blessing, PhD, of New York University, investigated the potential of CBD for treating anxiety. In a review of 49 studies, they found promising results and the need for more study.
The “preclinical” evidence (ie from animal studies) “conclusively demonstrates CBD’s efficacy in reducing anxiety behaviors relevant to multiple disorders,” Dr. Blessing wrote. Those include generalized anxiety disorder, PTSD, panic disorder, social anxiety disorder and OCD.
The review notes that the promising preclinical results are also supported by human experimental findings, which also suggest “minimal sedative effects, and an excellent safety profile.” But these findings are based on putting healthy subjects in anxiety-producing situations and measuring the impact of CBD on the anxiety response. Further studies are required to establish treatment with CBD would have similar effects for those who struggle with chronic anxiety, as well as what the impact of extended CBD use may be.
“Overall, current evidence indicates CBD has considerable potential as a treatment for multiple anxiety disorders,” Dr. Blessing concludes, “with need for further study of chronic and therapeutic effects in relevant clinical populations.”
CBD and autism
A group of Israeli researchers have been exploring the use of CBD to reduce problem behaviors in children on the autism spectrum. A feasibility study involving 60 children found substantial improvement in behavioral outbreaks, anxiety and communication problems, as well as stress levels reported by parents.
The researchers, led by Adi Aran, MD, director of the pediatric neurology unit at Shaare Tzedek Medical Center, went on to do a double-blind, randomized, placebo-controlled trial with 150 participants with autism. In this trial, just completed but not yet analyzed, patients were treated CBD for three months.
In the US, research has been given a boost by changing guidelines and laws. In 2015 the DEA eased some of the regulatory requirements that have made CBD, as a Schedule 1 substance, difficult to study. “Because CBD contains less than 1 percent THC and has shown some potential medicinal value, there is great interest in studying it for medical applications,” the DEA said in announcing the change.
And in approving the first CBD-based drug, Epidiolex, last year the FDA expressed enthusiasm for the research boom that is sure to come, paired with stern words for the flood of marketers of products claiming unsubstantiated health benefits.
“We’ll continue to support rigorous scientific research on the potential medical uses of marijuana-derived products and work with product developers who are interested in bringing patients safe and effective, high quality products,” the FDA pledged. “But, at the same time, we are prepared to take action when we see the illegal marketing of CBD-containing products with serious, unproven medical claims.”