Alcohol & Other Drugs
Everywhere you turn today, it seems somebody is talking about cannabis.
Some of the information we hear about cannabis is conflicting, making it hard to understand the ways it may affect our children. Is it addictive? Does it cause psychosis? Is it really a medicine? What will happen if my child uses it? What should I tell—or not tell—my child about it?
As cannabis has now been legalized for adults in Canada, the Canadian Institute for Substance Use Research has revised and updated a previous resource developed in partnership with the F.O.R.C.E. Society for Kids’ Mental Health and the Canadian Mental Health Association (BC Division). This new edition retains the aim of the earlier work.
Our goal is to offer you an honest and thoughtful discussion on cannabis so you can make better decisions about cannabis use—or non-use—in the context of your family.
Hemp. Cannabis. Marijuana. Hash.
Chances are you’ve heard these words before, though you many not know the difference between them. Are they the same or different? The answer is “both.”
HEMP is a plant that, like other plants, has roots, a stalk, leaves, flowers and seeds. Hemp stalks are often used to make fibre-based items such as paper and fabric.
CANNABIS is the scientific name for the hemp plant. There are many different kinds of cannabis. The leaves and flowers of each kind produce varying mind-altering and medicinal effects when smoked or consumed. The most talked-about strains of the hemp plant are cannabis sativa and cannabis indica.
MARIJUANA is a Mexican slang word for cannabis leaves and flowers (aka buds).
HASH, short for hashish, is made of pressed resin from cannabis buds, and is therefore stronger in effect.
You may have heard.
You may have heard a variety of claims about cannabis in the media or in everyday conversation. For instance, you may have heard that cannabis use causes cancer or leads to quitting school. You may have also heard that the risk of developing cancer is low for cannabis smokers and that the drug can help relieve anxiety about school.
As a parent, making sense of these conflicting claims can be confusing. While there is at least some truth in almost all of them, accurate and balanced information about cannabis is more complex than simple statements.
There are no simple answers to explain the ways cannabis use may affect people’s minds, bodies, relationships and future opportunities. Why? Because people are complex beings, and our choices and behaviours are complex too.
Even if you have only limited experience with drugs, you likely know more than you think about the key issues. Most people, for example, understand intuitively that all drugs can be both good and bad. Even medication recommended by a doctor can cause harm, especially if not taken properly. When it comes to cannabis, almost everyone knows people who have had fun or benefitted in some other way from using cannabis or other drugs. Likewise, most people know of someone who has had bad experiences.
While most drugs are useful in some way, all drug use carries some risk. Generally, it is safest not to use any drug unless one can be sure the potential benefits clearly outweigh the potential harms. This includes assessing the context and reasons for use.
It can help to think of drug use as occurring within a matrix with two separate axes representing potential benefit and potential harm (see the illustration). Different types of use have different benefit/harm profiles, but even these change depending on many factors.
The potential that drug use might lead to certain harms and/or benefits is influenced by several things:
More drug equals more risk. Increased risk is linked with a greater amount and more frequent drug use, and higher strength of a drug.
Younger age equals more risk. The younger a person is when they start using a drug regularly, the more likely they are to experience harms or develop problematic substance use later in life.
Places, times and activities influence risk. Trying cannabis with friends at a weekend party and walking home later is less likely to result in harm than smoking cannabis on school property or driving under the influence.
The reasons young people use cannabis are important. Curiosity or experimentation often lead only to occasional use. Youth may use cannabis as a way to feel better, reducing anxiety in social situations and helping them connect with friends. While using cannabis can help reduce the symptoms of anxiety and depression, if young people use cannabis regularly to ease troubling feelings, use can become problematic. If a youth uses cannabis to perform better at school or fit in with a particular group, they may be listening to others, rather than valuing their own needs and wants, which can result in poor choices.
The reasons a young person uses cannabis, family history, the context, amount and way in which they use the drug all contribute to whether that use is beneficial, harmful, or both. Risks related to cannabis use vary from person to person, and sometimes, from day to day for a particular person. This can make deciding if, when and how to use cannabis difficult. Parents often have to weigh potential benefits and harms, and guide decisions in their particular family situation.
So, with this in mind, and in light of what the research tells us, let’s take a closer look at some of the common claims about cannabis.
PSYCHOACTIVE SUBSTANCES are drugs that affect our central nervous system (especially the brain) and make us see, think, feel, and behave differently than we usually do.
Common claims about cannabis
The human brain begins to develop in the womb but is not fully formed until well into adulthood. Drugs influence the way our brains develop. Regular cannabis use at an early age may have negative effects on brain development.
All psychoactive substances, from caffeine to heroin, have an immediate effect on the brain. The negative effects of cannabis, however, are much less than the effects of some substances such as alcohol.
While the negative effects of cannabis on the brain are often minimal and reversible, exposure to psychoactive substances during development should be minimized.
Available evidence cannot answer whether or not cannabis causes psychosis. But it does reveal an association between the two, with greater risk of psychosis for people who use cannabis frequently.
Cannabis may be one factor that interacts with other factors, such as a vulnerability to psychosis. For instance, someone with a family history of psychosis may be more sensitive to the potential psychosis-producing properties of cannabis than people without this vulnerability in their family.
That said, for some people, cannabis use can result in short-term psychotic symptoms such as unusual perceptions and feelings (e.g., they may hear voices or think someone is trying to harm them). Cannabis use can also negatively affect a person living with a psychotic disorder such as schizophrenia.
Studies on the effects of cannabis use on depression are also inconclusive. Some evidence suggests a link between frequent cannabis use and depression. But it is not clear how much of the relationship is based on cannabis use and how much is due to other factors such as family and social problems, living in poverty and other situations that may be beyond the person’s control.
Even though cannabis smoke contains carcinogens (cancer-causing toxins), the risk of developing some cancers (e.g., mouth, tongue and lung) is less for cannabis smokers than tobacco smokers. This is because cannabis smokers tend to smoke less. Cannabis smokers typically smoke one to three cannabis cigarettes a day compared to 10 to 30 tobacco cigarettes by tobacco smokers.
Another factor is related to the properties of the cannabis plant. For example, cannabis contains chemicals called cannabinoids, which some scientists think play a protective role against cancer in the lungs.
While there is an association between cannabis and quitting school, the linkages may be the result of common factors— personality traits or family issues, for example—that increase the risks of both cannabis use and dropping out of school. Or school policy related to cannabis use may be the cause. For instance, a zero-tolerance school policy for drug use, which isolates suspended students from their peers and teachers, may be more likely to lead to a student dropping out than drug use itself.
While there is an association between cannabis use and the use of other illicit drugs, the apparent linkages are related to personal, social and environmental factors rather than the effects of the drug.
Personal factors include particular personality traits (e.g., sensation seeking) which might drive a young person to use cannabis and go on to try other illicit drugs. Or a young person might try cannabis to relieve symptoms of a mental health problem (e.g., anxiety) and experiment with other substances to see if they have the same effect.
Social and environmental factors related to the use of other illicit drugs include how acceptable particular drugs are in the young person’s social group, and how available they are in their community.
As parents, thinking about cannabis and making decisions with your family can be a complex and challenging task. Personal history and attitudes to drug use, family values, medical history, legal status, community mores, and individual desires are factors that can affect what you choose to do. Thoughtful consideration of the issues can take some time. It is important to remember that you will make the best decision you can at that moment. You can re-evaluate your position and make different decisions as the situation and information available changes.
Is cannabis legal?
Cannabis is regulated in the province of BC. You must be 19 or over to purchase, possess or use cannabis or cannabis products for non-medical purposes in BC. It is illegal to sell or give cannabis to people under 19. People under 19 may not legally possess cannabis unless authorized to use it for medical purposes by their health care practitioner. Access to medical cannabis is regulated under the Access to Cannabis for Medical Purposes Regulations (ACMPR). Under the ACMPR, Canadians (including those under 19) who have been authorized by their health care practitioner to access cannabis for medical purposes are able to purchase safe, quality-controlled cannabis from one of the producers licensed by Health Canada, produce a limited amount of cannabis for their own medical purposes, or designate someone to produce it for them.
For more information on cannabis regulations in BC visit: http://cannabis.gov.bc.ca/
Data on the potency or strength of cannabis is limited, but the available evidence suggests there is a wide range in levels of THC (the main psychoactive ingredient). While there has been an increase in the average THC level over the past two decades, the rise has not been dramatic. Increases in THC levels are primarily related to selective breeding and more advanced cultivation techniques.
While the long-term negative effects of higher-potency cannabis on respiratory health or mental health are unknown, some researchers point out that using smaller amounts of higher potency cannabis reduces a person’s exposure to smoke and toxins and therefore might reduce risks. Clinical studies have shown that smokers regulate their dosage according to the strength of the cannabis by taking smaller or fewer puffs and/or inhaling more air with their puffs.
Cannabis purchased through government outlets in BC is tested for quality. If purchased from a dealer or friend the THC content may not be known, and people may use more than desired, and, in doing so, may experience negative consequences.
What is THC?
THC is short for the chemical compound delta-9-tetrahydrocannabidinol. THC is the most talked-about active ingredient in cannabis because it delivers the “high” feeling associated with using the drug.
Cannabis affects driving ability, including reaction time, lane maintenance, information processing, speed and distance estimation, eye movement control and attention. It also causes fatigue, which is itself a driving hazard. For these reasons, it is safest to avoid driving for three to four hours after using cannabis.
Cannabis in combination with even small doses of alcohol is a greater threat to safety than either drug used alone.
In the three to four hours after using cannabis, a person may have problems remembering or learning things. If a young person uses cannabis before or during school or work, these effects could impair their ability to do well in school or perform at work. However, most of the evidence suggests that any long-lasting effects on learning and memory are minimal.
Any kind of smoke can irritate the respiratory tract. People who smoke cannabis on a regular basis can develop inflammation in their respiratory tract (the part of the body involved in breathing). This can put them at risk of chronic coughing, shortness of breath and wheezing.
Using a device called a vaporizer can reduce the risk of respiratory problems. But “safest” does not mean “no risk.” Using a vaporizer only reduces smoking-related risks, not those related to the drug itself.
Comparing common ways to use cannabis
Some ways of smoking cannabis are safer than others. For example, using unfiltered joints is less risky than using water pipes (aka bongs) and joints with cigarette filters.
With unfiltered joints, cannabis smokers inhale less tar and more THC, the active ingredient in cannabis. Cigarette filters and water pipes reduce the THC, leading smokers to inhale more vigorously and increase the amount of tar in their lungs.
Vaporizers are the safest way to use cannabis. They release THC as a fine mist while reducing the toxic by-products of smoked cannabis. Ingesting cannabis also avoids the risks related to smoke and toxins but introduces other concerns. For instance, it is harder to find the right dose because it takes longer for the body to absorb the THC. This can result in a person using more than they intended and maybe having a negative or even scary experience.
While most people who use cannabis do not progress to problematic use, those who use cannabis frequently (daily or near daily) over a period of time may be putting themselves at risk of dependence.
A person may be dependent if they feel like they need to use cannabis just to feel normal and function during the day. People who stop using cannabis after regular use can experience mild feelings of withdrawal. Common symptoms of cannabis withdrawal are restlessness, nervousness, irritability, loss of appetite and difficulty sleeping.
The risk of developing dependence is higher for those who start to use cannabis regularly at an early age.
While some people worry that cannabis sold on the streets may be laced with crystal meth or other unpredictable substances, there is little evidence of this happening.
It is important to know the source of your cannabis. Buying from government distribution centres is safest.
Exploring medical cannabis use
Cannabis has been used as a medicine in many parts of the world for thousands of years. These days, many people in Canada want more evidence about what cannabis is (and is not) effective in treating, and the best way to deliver that treatment.
As it stands today, there is scientific evidence of the therapeutic benefits of cannabis for the following conditions: anti-spasm for multiple sclerosis, anti-convulsive for epilepsy, anti-nausea for chemotherapy, and appetite stimulant for people experiencing extreme weight loss. Recent research has shown cannabis is effective in managing pain.
Although cannabis can impact mental health in certain circumstances, some people with a mental health problem use it to relieve the symptoms of their condition or the unpleasant side effects of their medication.
When it comes to youth, research suggests that young people may be using cannabis for reasons that are similar to those of adults. Some studies suggest that youth experiencing mental health problems might be seeking relief through cannabis use. Mental health issues such as depression, insomnia and anxiety were reported as significant problems that interfered with their ability to function at school and with family and friends.
More research is needed to understand whether cannabis may have a place among treatment options for mental health problems such as anxiety and ADHD. For instance, evidence shows that cannabis has the potential to both increase and reduce anxiety. Some researchers believe these conflicting effects may be a reflection of the various cannabinoids in cannabis.
THC and other compounds in cannabis—notably CBD or cannabidiol—are being studied for their healing potential. Researchers believe that the ratio of THC to CBD is a crucial factor in how cannabis affects a person’s mind and body.
You and your child
When you’re thinking about talking with your child about drugs, knowing about some of the risks (and benefits) of cannabis use may help you feel more prepared. But it is not the most important way you can help your child navigate their world, a world where drug use is common.
More than information about cannabis, what your child needs is YOU. Research suggests that one of the most important factors in healthy child development is a strong, open relationship with a parent.
Intuitively, most of us already know this. But sometimes it helps to remind ourselves that it is our attention, love and patience that really count. It may also be helpful to remember that, ultimately, our goal as parents is to find ways to inspire our children to want to communicate with us—about cannabis or anything else.
Opening up a discussion about cannabis may be one way to strengthen your relationship with your child. It may encourage open lines of communication about other topics too. Inviting and allowing open, honest conversation about cannabis (or any other subject) makes your child know that what they are thinking, feeling and experiencing matters to you.
The exact words you use are less important than the underlying message you are sending—engaging in conversation with them says that you want to establish a connection with them, one that you hope lasts for a long time.
Connecting through conversation
Talking about cannabis or other drugs may not always be easy, fun or comfortable. But it may help to keep in mind that most people with kids struggle with parenting at least some of the time. No matter what you are going through as a parent, chances are there are others going through the exact same thing. In other words, you are not alone in your fears and frustrations—or in the joys and triumphs—of being a parent.
Starting a conversation
Some parents wonder when, where and how to start a conversation about cannabis. They ask themselves or others, “What age is the right age to start talking about drugs?” or “Should I ask the questions or should I wait until my child asks me something?”
Every child is different, so there is no “right age” to start talking about cannabis. But it makes sense to have your first conversation before your child is likely to try using cannabis. That way, you can establish a connection and share your expectations before they are exposed to any risks associated with cannabis.
There is no rule about how or where a conversation about cannabis should start either. But considering how often drugs are talked about on TV, in the newspaper, on social media, and at school, the subject might easily be brought up naturally while watching a movie together or while swapping stories about what happened at work and school that day.
Another “natural” way to start a conversation about cannabis is to bring it up in the context of other drug use. For instance, if you are planning to visit a relative who uses tobacco, you could inform your child about it and ask them what they know about smoking or how they feel about smoking. Or if you are having a beer or taking medication, you could ask, “Why do you think some people accept the use of alcohol and medication but not cannabis?”
It may be more comfortable to talk when you are not sitting across the table looking directly at each other. Try starting a conversation in the car or on the basketball court. You could say, “I’ve heard things on the news about kids smoking pot at school. How about your school? How does your principal deal with students who use drugs?”
Monitoring your motives
The goal of open communication is to get your child talking and sharing their thoughts and feelings with you. Ideally, they will one day ask you what you think and feel about things too. Establishing a connection through conversation is more important than assessing the details of what they tell you. After all, it is not really an open conversation if you are only inviting your child to talk so you can jump on them for ideas you do not like.
Practising good conversation skills
Your child, like anyone else you talk to, will be a better conversation partner if you stick to some basic rules about communication.
Be a good listener. Avoid the temptation to shower them with wisdom, and let them do at least half of the
Acknowledge their point of view. This does not mean you have to agree with what they say, but instead, to try not to react in a way that will shut down their desire to tell you how they think and feel about things.
Use open-ended questions that encourage reflection and the expression of feelings and views rather than simple yes/no answers.
Be clear about your expectation. Being honest about how you think or feel about cannabis use, and why you think or feel that way, can offer a broader perspective to your discussion.
??Keep them from tuning out. Avoid “lecture mode” and judgmental comments, and keep in mind that exaggerating the negative aspects of cannabis or any drug will not work for a child who has witnessed or experienced its positive effects.
“We know when we’ve screwed up. We don’t need to hear about it for hours. It’s embarrassing enough knowing we’ve done something we shouldn’t have and that our parents are mad about it.”
Responding to your child’s cannabis use
Discovering (or suspecting) your child has been using cannabis or any other drug can be scary, especially if you sense that it is not just part of “normal” experimentation.
While it can be tough to resist the urge to go wild with worry or anger, the best thing you can do for your child is to respond responsibly. It is important not to let your concerns harm the relationship and the trust you have with your child.
Yelling and making threats will not help the situation. If anything, “freaking out” will give your child another reason to hide things from you. Searching their room or personal belongings may harm the trust between you and your child.
Talk to your child
Sit down with them and tell them how you feel. If they are high, wait until the effects have worn off so you can have a more meaningful discussion. Say, “I’m worried because. ” or “I’m afraid because. ” Then give your child an opportunity to express their own feelings. Make sure they know you are really listening. And allow them time to think things through before speaking.
Learn why your child is using
Find out what led them to try cannabis in the first place. Was it because their friends were using it and they wanted to fit in? Was it for the “buzz” that comes from having an altered state of consciousness? Was it because they wanted a way to escape? Was it to manage symptoms of anxiety or other mental health problems? If so, you might want to consider seeking help from a mental health professional. It may also be helpful to find out how often your child uses cannabis.
Understand the difference between a youth who uses drugs and a youth with a drug problem
Young people use cannabis because they feel it benefits them. The most common reasons youth use cannabis are:
To feel good—Youth may use cannabis to feel more social, celebrate or relax. Using cannabis to feel good is associated with moderate use. There is still some risk, as there is in life in general.
To feel better—Cannabis can help reduce anxiety in social situations or when trying to connect with others or reduce symptoms of chronic anxiety or depression. If young people use cannabis regularly to deal with troubling feelings, then use may become problematic.
To do better—Some young people feel pressure to improve their performance, “get going” or “keep going.”
To explore—Young people particularly may use cannabis out of curiosity or to “walk on the edge,” trying something new and different.
It is important to keep in mind that sustained drug use problems are most common among people who feel isolated or marginalized. Youth without connections or meaningful relationships in their lives may seek solace in “feel-good” drugs. On the other hand, even well-connected young people can get into serious trouble from using too much or in the wrong place.
If your child is using drugs because they like the buzz, you may want to suggest activities that will naturally boost their adrenaline levels, such as rock climbing or mountain biking. If your child is using cannabis to calm themselves or to relieve feelings of anxiety, you could help them explore calming or meditative activities, such as yoga, running and swimming.
Lower the risks
A child who is using cannabis may need help learning to manage the risks and use the drug in the safest way possible. One way to help your child lower the risks related to using cannabis is to have a conversation about safer ways to smoke (see Quick tips for safer cannabis use). Another way is to discuss safer contexts and settings for use. Allowing your child to smoke cannabis at home may help to provide a safer environment but it is important to weigh the risks involved.
If your child is engaging in risky activities such as using cannabis at school or selling cannabis, it is important to talk with them about why they are engaging in these activities so that you can assess the level of risk, help them think through the consequences and identify alternatives. For example, if your child is selling cannabis to make money, talk with them about safer ways to earn an income.
“It didn’t make me want to use drugs. I liked that they were honest with me.”
Quick tips for safer cannabis use
Avoid smoking cannabis with tobacco
Avoid deep inhalation or breath-holding
Use a vaporizer
If smoking cannabis, use joints rather than water bongs
Use a small piece of rolled unbleached cardboard as a filter to prevent burns
Only use cannabis purchased from a trusted source
“I wouldn’t want my parents to tell me if they used drugs. I’d be embarrassed.”
Consider what to share (or not share) about your past
Many parents want to know if it is good or bad to tell their children about their own experiences with cannabis or other drugs. The answer is “it depends on your child and situation.”
One thing to think about is your motive for talking about your past. Are you telling them because you want to warn or frighten them in some way? Are you telling them because they asked and you do not want to lie to them? Are you telling them because you feel it might enhance your relationship in some way?
Another thing to consider is that some young people have a hard time seeing how any of their parents’ experiences are relevant to those of young people today. They may simply tune out when they hear stories about your past because they see no relationship between then and now.
Keep the art of motivation in mind
While no parent is 100% responsible for their child’s choices and behaviours, part of our job is to try to influence our kids in positive ways. One way involves checking in with them about their goals—over the next semester or year or even longer—and getting them to articulate how their use of cannabis or other drugs might impact those goals.
Taking a motivational approach is less about pressuring your child to change their cannabis use and more about supporting their internal reflection on their possible need and ability to change. It means steering a conversation toward possibility and action. And it is light in spirit and tone because it involves imagining success in the future.
In short, rather than make your child say and do what you want, help them identify what they want—to earn money, get a driver’s licence or graduate from high school—and support their efforts. You might need to help them understand what is involved in reaching a goal, and help them identify both internal and external resources they can draw on to ensure their success.
Give it time
It will likely take more than one conversation for you to understand your child’s drug use. But the good news is that, over time, you might discover your child has less of a problem than you thought. That is, your teen could very well be experimenting with cannabis the way many young people do without ever developing a risky or harmful pattern of use.
If a harmful pattern is emerging, you will need to be even more patient. But it may help to consider this: the path to your child’s drug use took time to build, so it makes sense not to expect a quick fix. A harmful pattern of drug use may be related to life challenges—feelings of failure or a lack of connection at school or with loved ones—that sometimes take a great deal of work to resolve. It might even be related to physical and mental health issues.
Signs of risky or harmful cannabis use
using regularly at an early age
daily or near daily use
using during school or work
using as a major form of recreation
using to cope with negative moods
experiencing chronic coughing, shortness of breath, wheezing or psychotic symptoms
NOTE: A young person may have one or more of these signs without having a short-term or long-term problem with cannabis. However, the more signs, the higher the risk.
Not every parent is equipped to handle drug use issues on their own. If you need help understanding or communicating with your child, look for local resources and organizations that can assist you. You could try talking to
a school counsellor
your family doctor
your regional Health Authority
the Alcohol and Drug Information and Referral Service at 1-800-663- 1441 (BC) or 604-660-9382 (Greater Vancouver)
“The counsellor helped my child see he had other interests besides cannabis. And we learned to look at things in a more balanced way. We realized our child had more than just his pot-smoking friends in his life. He also had his sports friends and many other associations with people who didn’t use cannabis.”
In summary, try to remember.
As a parent, you are a powerful influence in your child’s life. Your approach to life, and how you deal with good things as well as difficulties, provides multiple opportunities for your children to learn how to be human, make mistakes (whether you want them to or not) and the process of making good decisions. Life presents us with many challenges each day. How to deal with drugs, including cannabis, may be one of those issues.
There are many things to consider, and you may struggle to make good decisions about complex issues like cannabis. Responsibilities to protect, support, and guide your children must be balanced with your values and the changing social and cultural realities of the twenty-first century. Reviewing your thoughts and feelings about cannabis, your personal history with it (did you use cannabis, do you still use it and why?) and the reasons your child is using cannabis are important considerations in thinking about what to do.
As noted earlier in this guide, young people use cannabis because they see benefit in doing so. They use cannabis to feel good, feel better, do better or explore. Entering into dialogue with your child about the benefits they receive from using cannabis will assist you to gather information and develop a mutual understanding that will help you make a good decision together about cannabis. In this process you may also discover your child has mental or physical health issues which may need to be addressed. Discussing your and your child’s concerns in the context of an open, caring and respectful relationship makes space for further dialogue on cannabis, and other issues that arise in the future.
For further information and supports please check out the resources listed on the following page.
HERE TO HELP
The following resources are available on the Here to Help website:
Other websites to visit
Canadian Institute for Substance Use Research
Dedicated to research and knowledge related to substance use, mental health and well-being. The CISUR website provides fact sheets and self-help tools to help British Columbians make decisions about their well-being. The site also includes resources to support schools, campuses and communities to take effective action in addressing the impact of substance use.
Canadian Mental Health Association (BC Division)
Promotes the mental health of all British Columbians. The website provides self-help resources, personal stories and discussion of public issues related to mental illness, such as housing, employment and discrimination.
Provides a variety of supports for families and those who work with families. The website includes resources to promote greater understanding and increased collaboration among all involved in family well-being.
Foundry offers young people ages 12-24 health and wellness resources, services and supports – online and through integrated service centres in seven communities across BC.
Kelty Mental Health Resource Centre
Offers information and resources on mental health and substance use issues affecting children and youth including resources for parents and caregivers, healthcare professionals, school professionals, youth and young adults.
The therapeutic role of Cannabidiol in mental health: a systematic review
The therapeutic application of cannabidiol (CBD) is gaining interest due to expanding evidence for its use.
To summarize the clinical outcomes, study designs and limitations for the use of CBD and nabiximols (whole plant extract from Cannabis sativa L. that has been purified into 1:1 ratio of CBD and delta-9-tetrahydrocannabinol) in the treatment of psychiatric disorders.
Materials and method
A systematic review was conducted including case reports, case series, open-label trials, non-randomized and randomized controlled trials (RCTs). The search resulted in 23 relevant studies on CBD and nabiximols in the treatment of a wide range of psychiatric disorders. The quality of evidence was judged by using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence that ranges from Level 1 to Level 5 based on the quality and study design. These levels of evidence help in grading the recommendations, including Grade A (strong), Grade B (moderate), Grade C (weak), and Grade D (weakest).
CBD and CBD-containing compounds such as nabiximols were helpful in alleviating psychotic symptoms and cognitive impairment in patients with a variety of conditions, and several studies provided evidence of effectiveness in the treatment of cannabis withdrawal and moderate to severe cannabis use disorder with Grade B recommendation. There is Grade B recommendation supporting the use of CBD for the treatment of schizophrenia, social anxiety disorder and autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD). Grade C recommendation exists for insomnia, anxiety, bipolar disorder, posttraumatic stress disorder, and Tourette syndrome. These recommendations should be considered in the context of limited number of available studies.
CBD and CBD-containing compounds such as nabiximols were helpful in alleviating symptoms of cannabis-related disorders, schizophrenia, social anxiety disorder, and comorbidities of ASD, and ADHD with moderate recommendation. However, there is weaker evidence for insomnia, anxiety, bipolar disorder, posttraumatic stress disorder, and Tourette syndrome. The evidence for the use of CBD and CBD-containing compounds for psychiatric disorders needs to be explored in future studies, especially large-scale and well-designed RCTs.
Cannabis sativa, a species of cannabis plant, is well known to humankind, with its earliest use in ancient Chinese culture dating as far back as 2700 B.C. (Zuardi, 2006). The use of medical cannabis in China was reported in the world’s oldest pharmacopoeia (Martin et al., 1999). However, interest in the role of cannabis flourished in the late twentieth century after the recognition of an endogenous cannabinoid system in the brain (Zuardi, 2006; Martin et al., 1999). More recently, research has centered on the description and cloning of specific receptors and the therapeutic effects of medical cannabis, and different cannabinoids in the cannabis plant have gained interest (Martin et al., 1999). Recent studies have focused on the therapeutic role of medical cannabis in different disorders. As a result, there is a growing need to summarize and review the evidence for its therapeutic and adverse effects as an aid to public health policy development, and to provide direction and impetus to pharmaceutical research in this field.
The cannabis plant has more than 140 cannabinoid compounds, with Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) attracting significant interest (Citti et al., 2018). Δ9-THC is the primary psychoactive ingredient, and CBD is a non-intoxicating ingredient (Zuardi, 2006; Citti et al., 2018). Evidence from preclinical studies suggested that CBD had potential therapeutic benefits ranging from antiinflammatory to neuroprotective, antipsychotic, analgesic, anticonvulsant, antiemetic, antioxidant, antiarthritic, and antineoplastic properties; for a review, see (Pertwee, 2006). CBD has several receptors and molecular targets. This compound antagonizes the action of CB1 and CB2 receptor agonist (Blessing et al., 2015; Peres et al., 2018). The CB1 and CB2 receptors are coupled negatively through G-proteins to adenylate cyclase and positively to mitogen-activated protein kinase (Pertwee, 2006). In addition to CB1 and CB2 receptor activity, CBD is an agonist of vanilloid receptor TRPV1. It also acts as an agonist of serotonin receptor 5-hydroxytryptamine (5-HT1A), an antagonist of G-protein-coupled receptor GPR55, and an inverse agonist of GPR3, GPR6, and GPR12 (Peres et al., 2018). Data from single-photon emission computed tomography showed CBD to exert anxiolytic effects by acting on paralimbic and limbic pathways (Crippa et al., 2011). The agonist effect of CBD on 5-HT1A also supports its anxiolytic and antidepressant properties (Russo et al., 2005). CBD inhibits enzymatic hydrolysis and anandamide uptake through its agonist action on CB1, CB2, and TRPV1 receptors (Peres et al., 2018). In addition, CBD indirectly enhances endogenous anandamide signaling by inhibiting the intercellular degradation of anandamide (Leweke et al., 2012). This endogenous neurotransmitter exerts antipsychotic effects in patients with schizophrenia (Leweke et al., 2012).
The pharmacokinetic profile of CBD has been extensively explored in the existing literature. A recently published systematic review of the pharmacokinetics of CBD found that the area under curve (AUC0 − t) and maximum serum concentration (Cmax) occurs between 1 and 4 h (Millar et al., 2018). The AUC0 − t and Cmax reach maximum values faster after smoking or inhalation compared to oral or oromucosal routes. Bioavailability was 31% after smoking, but no other studies reported the absolute bioavailability of CBD after other routes in humans. The half-life of CBD ranges between 1.4 and 10.9 h after oromucosal spray and 2–5 days after chronic oral administration (Millar et al., 2018). Fed states and lipid formulations increase Cmax (Millar et al., 2018). The bioavailability of oral CBD ranges between 11 and 13%, compared to 11 to 45% (mean 31%) via inhalation (Scuderi et al., 2009). CBD is well-tolerated, yet despite a relatively lower risk of drug–drug interactions, it should be used cautiously in combination with drugs metabolized by the CYP3A4 and CYP2C19 pathways, and the substrates of UDP-glucuronosyltransferases UGT1A9 and UGT2B7 (Millar et al., 2018). The clinical relevance of these interactions needs to be explored in future studies (Brown & Winterstein, 2019).
Dronabinol and nabilone are synthetic in origin, whereas nabiximols is plant-based (Papaseit et al., 2018). The percentage of THC and its ratio to CBD (THC/CBD ratio) defines the potency and psychoactive effects of a given formulation (Papaseit et al., 2018). Those with higher CBD/Δ9-THC ratios have euphoric, anxiolytic, and relaxing effects, whereas lower CBD/Δ9-THC ratios have sedative properties (Papaseit et al., 2018). Nabiximols, a CBD-containing compound, contains Δ9-THC and CBD at a 1:1 ratio (Papaseit et al., 2018). The Food and Drug Administration has approved Epidiolex® (an oral formulation of CBD) for two forms of childhood seizures (Lennox–Gastaut syndrome and Dravet syndrome) in children 2 years of age and older (Papaseit et al., 2018).
Previous efforts to synthesize the evidence for medical cannabis use in patients with psychiatric disorders have been published (Hoch et al., 2019; Lowe et al., 2019). For example, Hoch et al. conducted an excellent systematic review that summarized four systematic reviews and 14 randomized controlled trials (RCTs), but did not consider non-clinical trial evidence (case reports and case series) (Hoch et al., 2019). A review by Mandolini et al. recently summarized the clinical findings from 14 studies of psychiatric disorders, but these authors did not provide information about nabiximols (Mandolini et al., 2018). In contrast to the review articles noted above, the present article aims to provide a more comprehensive review of the use of CBD and CBD-containing compounds such as nabiximols to treat psychiatric disorders. The present review included studies focused on schizophrenia, cannabis-related disorders, attention deficit hyperactivity disorder (ADHD), comorbidities in autism spectrum disorder (ASD), social anxiety disorder (SAD), other anxiety disorders, insomnia, bipolar disorder, post-traumatic stress disorder (PTSD), psychosis in Parkinson’s disease, and Tourette syndrome. This article broadly reviews the efficacy, safety, and psychiatric benefits of CBD and CBD-containing compounds (nabiximols). We distinguish clearly here between the clinical findings for CBD and nabiximols, as the latter also contains THC.
The main inclusion criterion was studies of the psychiatric use of CBD and CBD-containing compounds such as nabiximols. Only case reports, case series, retrospective chart reviews, open-label trials, and RCTs were considered. All books, conference papers, theses, editorials, review articles, metaanalyses, in-vitro studies, laboratory studies, animal studies, studies of participants without psychiatric disorders, and abstract-only articles were excluded. No restrictions on language, country, publication year, or patients’ age, gender, or ethnicity were applied.
Eight electronic databases were searched on October 28th, 2018: PubMed, Scopus, Web of Science, POPLINE, New York Academy of Medicine Grey Literature Report, PsycINFO, Psycarticles, and CINAHL. The following search strategy was used in all cases: (CBD OR Cannabi* OR nabiximols) AND (psychiat* OR Depress* OR Anxiety OR Psycho* OR schizo* OR Bipolar OR Substance OR ADHD OR Attention OR Autism) AND (treatment). The manual search of references of included studies was performed by four independent reviewers.
The search results from the eight databases were imported to Endnote v. 7 (Thompson Reuters, CA, USA) to remove any duplicates. Four independent reviewers (RK, NM, AF, MAF) screened the titles and abstracts (when available), followed by full-text screening of each included article with the predetermined eligibility criteria. All articles included after full-text screening were then searched manually. Discrepancies were resolved by consensus through discussion among reviewers, or with guidance from a third reviewer (SN).
Data extraction and grading
The data were extracted independently by the authors, and were cross-checked by discussion among the four reviewers (RK, NM, AF, MAF), with guidance from the senior author (SN) in case of discrepancy. The data were categorized as pertaining to target diagnosis, study design, sample size, duration of the trial, age range, dose ranges, measurement scales, clinical outcomes, study limitations, and common side effects.
The Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence was used to grade the quality of evidence (OCEBM, 2019). Level 1 evidence is for systematic review of RCTs or individual RCT of narrow confidence interval, Level 2 for cohort studies or systematic review of cohort studies, Level 3 for case-control studies or systematic review of case-control studies, and Level 4 for case-series for studies focused on therapy, prevention, etiology and harm (OCEBM, 2019). These levels of evidence are used to generate Grades of Recommendation. Grade A is for consistent level 1 studies, Grade B for consistent level 2 or 3 studies or extrapolations from level 1 studies, and Grade C for level 4 studies or extrapolations from level 2 or 3 studies. Grade D is ranked for level 5 evidence or inconsistent or inclusive studies of any level (OCEBM, 2019).
Results & discussion
The search of eight electronic databases and our manual screening method generated 511 results. After the removal of duplicates, titles and abstracts were screened, resulting in the exclusion of 459 articles. Full-text screening of 52 articles was performed, and 23 articles meeting the inclusion criteria were analyzed. Figure 1 summarizes the screening process.
PRISMA Flow Diagram
Of the 23 articles, there were eight RCTs, one clinical trial, four open-label trials, one retrospective chart review, seven case reports, and two case series, comprising a total patient population of 526. The studies focused on CBD and nabiximols use in the treatment of schizophrenia, cannabis-related disorders, ADHD, ASD and comorbidities, anxiety, insomnia, SAD, bipolar disorder, PTSD, psychosis in Parkinson’s disease, and Tourette syndrome. No studies of substance use disorders other than cannabis use were identified. In this review article, the authors have used DSM-5 terminologies for most of the disorders except for DSM-IV-Text Revised terminology of substance dependence. A comparable DSM-5 terminology of moderate-severe substance use disorder was used in this case.
Qualitative synthesis of eligible studies
Schizophrenia and psychosis in Parkinson’s disease
There were three RCTs (164 patients), one clinical trial (27 patients), one case series (three patients), one case report for schizophrenia, and one open-label trial (six patients) for psychosis in Parkinson’s disease (Table 1) (Leweke et al., 2012; Hallak et al., 2010; Boggs et al., 2018; McGuire et al., 2018; Zuardi et al., 2006; Zuardi et al., 1995; Zuardi et al., 2009). Of the seven studies, level 2 evidence was found in three RCTs, level 3 evidence in two clinical trial, and level 4 evidence in one case report and one case series (OCEBM, 2019). Since most of the studies were from level 2 and level 3 evidence, there is Grade B recommendation for schizophrenia. The dose of CBD in these studies ranged from 200 to 1500 mg daily. The highest dose was titrated to 1500 mg daily as reported by Zuardi and colleagues (Zuardi et al., 1995). Irrespective of the study design, three studies reported that CBD alleviated psychotic symptoms and cognitive impairment in patients with chronic cannabis use and Parkinson’s disease (Leweke et al., 2012; Zuardi et al., 1995; Zuardi et al., 2009), while only two RCTs and one clinical trial provided evidence for the effectiveness of CBD among patients with schizophrenia, albeit with mixed results (Leweke et al., 2012; McGuire et al., 2018; Zuardi et al., 2009).
In a clinical trial, Hallak and colleagues suggested an improvement in schizophrenia-associated cognitive impairment with a CBD dose of 300 mg/day, while no significant improvement was seen at a CBD dose of 600 mg/day (Hallak et al., 2010). In another RCT, McGuire and colleagues found that CBD (1000 mg/day) improved positive psychotic symptoms, but failed to improve negative symptoms and general psychopathology associated with this illness (McGuire et al., 2018). In another RCT, Boggs and colleagues found that CBD (600 mg/day) failed to improve outcomes pertaining to reasoning and problem-solving domains (Boggs et al., 2018).
In a comparison of CBD with amisulpride, Leweke and colleagues reported similar improvements in patients taking CBD 800 mg/day and those taking amisulpride (Leweke et al., 2012). This study also indicated an increase in intrinsic anandamide signaling, an effect that explained the antipsychotic properties of CBD (Leweke et al., 2012). Moreover, CBD treatment was associated with a lower risk of extrapyramidal symptoms, less weight gain, and a lower increase in prolactin, which is a predictor of galactorrhea and sexual dysfunction (Leweke et al., 2012). An open-label study of CBD to treat psychosis in Parkinson’s disease also suggested promising results at a dose of 400 mg daily; however, there was a strong risk of bias because of inadequate blinding of participants, personnel and outcome assessors (Zuardi et al., 2009).
The remaining evidence comprised two minimal quality case reports and case series. Zuardi and colleagues were the first to report favorable findings for CBD in patients with schizophrenia (Zuardi et al., 1995). The dose of CBD ranged from 600 to 1500 mg daily in schizophrenia studies. A case series of three patients with treatment-resistant schizophrenia found improvement in only one patient (Zuardi et al., 2006). In the first case, there was an improvement in psychotic symptoms with CBD at 1280 mg/day; however, the symptoms worsened after CBD was discontinued. In second case, CBD was ineffective for the symptoms. Patient had an improvement in symptoms with clozapine. In the third case, no improvement with CBD and partial improvement with olanzapine were observed, although clozapine was subsequently required. In case 3, mild improvement was reported with CBD in a patient who had previously failed to respond to olanzapine, clozapine, or haloperidol decanoate. These results suggest a limited role of CBD in treatment-resistant schizophrenia (Zuardi et al., 2006). The dose were not individually mentioned for case 1 and 2.
Four of the included studies did not report any adverse effects of CBD among patients with psychosis. CBD was well-tolerated in these patients except for mild transient sedation, hyperlipidemia, and gastrointestinal distress. Patients with schizophrenia had fewer instances of extrapyramidal symptoms, less weight gain, and a lower increase in prolactin levels.
CBD is postulated to improve cognitive performance in psychosis through the mediation of CB1 and CB2 receptor agonism at lower concentrations (Hallak et al., 2010; Solowij et al., 2018; Manseau & Goff, 2015). This cognitive improvement has been hypothesized due to the higher concentration of cannabinoid receptors in the hypothalamus, suggesting a role in superior cognitive functioning (Hallak et al., 2010). Naturalistic studies of CBD report better cognitive performance including memory, increased grey matter in the hippocampus, and fewer psychotic symptoms in patients given higher doses of CBD (Solowij et al., 2018).
The therapeutic benefits for psychosis is hypothesized due to the inhibition of anandamide re-uptake and degradation, resulting in increased anandamide levels in the brain (Manseau & Goff, 2015). Increased anandamide levels and improvements in the symptoms of psychosis were reported in another 4-week-long RCT comparing the efficacy of CBD to amisulpride for the treatment of schizophrenia (Leweke et al., 2012). Interestingly, anandamide levels were elevated in patients with acute schizophrenia compared to chronic schizophrenia, indicating a compensatory increase in an acute state (Giuffrida et al., 2004).
The present review included three RCTs (107 patients), two open-label trials (28 patients), one case series of four patients, and two case reports for cannabis-related disorders as summarized in Table 2 (Solowij et al., 2018; Crippa et al., 2013; Trigo et al., 2016a; Trigo et al., 2018; Trigo et al., 2016b; Allsop et al., 2014; Pokorski et al., 2017; Shannon & Opila-Lehman, 2015). Of the eight studies, level 2 evidence was found in three RCTs, level 3 evidence in two clinical trial, and level 4 evidence in two case reports and one case series (OCEBM, 2019). For cannabis-related disorders, there is Grade B recommendation based on majority of studies ranked at the level 2 and level 3 of evidence.
Four of these studies evaluated the efficacy of nabiximols, and four others reported the use of CBD. The doses tested ranged from 20 mg CBD to a maximum of 1200 mg/day. Nabiximols was used in spray form at doses ranging from an average of 28.9 sprays/day (equivalent to 77.5 mg THC or 71.7 mg CBD) to 40 sprays/day (equivalent to 108 mg THC or 100 mg CBD). In CBD-only studies the dose of CBD ranged from 200 to 600 mg/day in divided doses. All three RCTs in this section provided evidence for the use of nabiximols for moderate to severe cannabis use disorder. These trials tested different doses of nabiximols ranging from 21.6 mg THC and 20 mg CBD (twice a day) to 113.4 mg THC or 105 mg CBD per day. All trials reported lower withdrawal rates, better tolerance, and retention rates in the experimental group. Moreover, no serious adverse effects were reported in any of these studies. In one RCT, nabiximols (total dose of 21.6 mg THC and 20 mg CBD at 4 and 10 in evening and night, respectively) was associated with marked improvement in cannabis withdrawal symptoms, leading to shorter withdrawal times and higher retention rates (Allsop et al., 2014). In a second RCT, a fixed dose of nabiximols produced more positive results compared to self-titrated administration (Trigo et al., 2016a). Patients in the fixed-dose group had four sprays of medications every hour compared to four sprays as needed every hour in self-titrated dose group. The maximum dose was 40 sprays/day in the self-titrated dose group. Medication intake was higher with fixed doses, which were associated with fewer withdrawal symptoms compared to the self-titrated regimen (Trigo et al., 2016a). In another RCT, the efficacy and safety of nabiximols were compared to a placebo while all participants also received weekly motivational enhancement therapy (MET) and cognitive–behavioral therapy (CBT) (Trigo et al., 2018). The dose range of 4.1 to 12.8 sprays/day was reported among nabiximols group. The withdrawal scores in this study were similar in both groups (Trigo et al., 2018). Only one of the studies reported decreased appetite, while the number and severity of adverse effects were not reported or observed in the other two RCTs.
Two open-label studies testing the effectiveness of two different concentrations of CBD (200 mg/day and 600–1200 mg/day) obtained positive outcomes with doses as low as 600 mg/day (Hallak et al., 2010; Pokorski et al., 2017). These studies had a small sample size of eight (Solowij et al., 2018) and 20 (Pokorski et al., 2017) participants, respectively. In the former open-label trial with eight participants, a dose of 600 mg/day was tested, and two out of five participants completed the 7-day inpatient treatment. These two participants reported abstinence at follow-up (day 28), and the remaining three participants reported decreased use of cannabis, confirmed by blood and urine analysis. In the second group, participants took 600 mg twice a day. Two out of three participants reported abstinence and in the remaining one, cannabis use had decreased, as confirmed by blood and urine analysis. All participants showed a decrease in Cannabis Withdrawal Scale scores. The second open-label trial tested the effectiveness of 200 mg CBD in divided doses in improving cognition and depressive symptomatology among patients with chronic cannabis use, and found improvement in severity of depression, verbal learning, and memory performance, and decreased frequency of positive psychotic-like symptoms and level of distress from baseline to endpoint (Solowij et al., 2018). State anxiety increased with no change in trait anxiety, functional impairment, or accuracy on cognitive tests (Solowij et al., 2018).
The remaining studies were either case series or case reports; all found positive outcomes in withdrawal and cannabis-dependence symptoms (Crippa et al., 2013; Trigo et al., 2016b; Shannon & Opila-Lehman, 2015). Mean age in the case series was 35 years, although the first participant was 19 years old and the second was 27 years old. The case series used self-titrated nabiximols at a dose of 77.5–113.4 mg THC and 71.5–105.0 mg CBD (Trigo et al., 2016b). Moreover, all participants reported a significant reduction in craving (Crippa et al., 2013; Trigo et al., 2016b; Shannon & Opila-Lehman, 2015), quicker relief (Crippa et al., 2013), lower anxiety, and an improved sleep schedule (Shannon & Opila-Lehman, 2015). However, the case series reported increased craving scores during the first 2 weeks with a subsequent reduction in craving at week 9. CBD was well-tolerated in this patient population, except for decreased appetite reported in one study (Trigo et al., 2016b). For patients receiving nabiximols or CBD, treatment should be augmented with psychotherapeutic modalities considering the positive evidence for an effect on cravings.
The effectiveness and tolerability of CBD and nabiximols for moderate to severe cannabis use disorder was reported in several studies. The efficacy may also be due to the synergetic or additive benefits of Δ9-THC and CBD rather than CBD alone. The Δ9-THC component of nabiximols decreases the severity of withdrawal symptoms, lowering the risk of relapse (Trigo et al., 2016a). However, there is mixed evidence for the role of nabiximols in cannabis-related craving (Trigo et al., 2016a; Trigo et al., 2018; Trigo et al., 2016b). Studies that included combined motivation enhancement and behavioral response prevention strategies suggested a reduction in craving (Trigo et al., 2016a; Trigo et al., 2018). CBD is thought to modulate the euphoric, anxiogenic, psychological, and physiological effects of Δ9-THC (Crippa et al., 2013). However, these benefits of CBD alone and in combination with THC need to be explored in head-to-head studies.
The present review included two RCTs (54 patients), one open-label trial (53 patients), one retrospective chart review (72 patients), and four case reports for CBD and nabiximols use in the treatment of other psychiatric disorders. Specifically, this review looked at ADHD (one RCT), comorbidities in ASD (one open-label trial), anxiety and sleep problems (one retrospective chart review), SAD (one clinical trial), bipolar disorder (one case report), PTSD (one case report), and Tourette syndrome (two case reports), as summarized in Table 3 (Cooper et al., 2017; Barchel et al., 2018; Bergamaschi et al., 2011; Shannon et al., 2019; Zuardi et al., 2010; Shannon & Opila-Lehman, 2016; Trainor et al., 2016; Pichler et al., 2019). Of the nine studies, level 2 evidence was found in two RCTs, level 3 evidence in one clinical trial, and level 4 evidence in one retrospective chart review, four case reports (OCEBM, 2019). There is Grade B recommendation for comorbidities in patients with ASD, anxiety disorders including SAD and sleep problems, and ADHD where as bipolar disorder, PTSD and Tourette Syndrome has Grade C recommendation. However, this should be considered in the context of fewer studies of each these diagnoses.
The oromucosal nabiximols spray was tested to evaluate its effects on cognitive performance, hyperactivity, inattention, and emotional lability in 15 participants in a placebo-controlled RCT (Cooper et al., 2017). The mean dose of nabiximols was 4.7 sprays per day (2.7 mg Δ9-THC and 2.5 mg CBD). Although an improvement in these symptoms was observed in the intervention group, it failed to reach statistical significance (Cooper et al., 2017). However, this result may not be valid or reliable due to the low power of the study.
One case report on the use of CBD by two patients with bipolar disorder showed limited to no improvement with doses of 600–1200 mg for bipolar mania in one of the patients (Shannon et al., 2019). The second patient was prescribed CBD 600 mg (5–9 days) and olanzapine (10–15 mg), followed by CBD 900–1200 mg (20–33 days), and showed improvement on the Brief Psychiatric Rating Scale (37% reduction) and Young Mania Rating Scale (33% reduction) with CBD and olanzapine, but no additional improvement with CBD monotherapy (Shannon et al., 2019). This effect was consistent with results from animal studies that modeled acute mania with dextroamphetamine (Shannon et al., 2019). The lack of effectiveness can be attributed to the shorter duration of treatment in both cases. This evidence from studies of bipolar mania should be considered in the context of different pharmacological agents responding differently to certain episodes of bipolar disorder. In animal studies, CBD induced a rapid, persistent antidepressant response by increasing brain-derived neurotrophic factor in the prefrontal cortex (Shannon et al., 2019). Given its possible antidepressant benefits, the role of CBD should be explored in unipolar and bipolar depression.
In an open-label trial involving children with ASD, Barchel and colleagues reported that a solution of CBD and Δ9-THC (1,20 ratio) was effective for hyperactivity, insomnia, self-injurious behaviors, and anxiety (Barchel et al., 2018). The median dose was 90 mg with an interquartile range (IQR) of 45–143 mg for CBD whereas The medical dose was 7 mg with IQR of 4–11 mg. In this cohort of 53 patients, 74.5% showed improvement in their comorbid symptoms, 68.4% in hyperactivity, 67.6% in self-injurious behaviors, 71.4% in sleep problems, and 47.1% in anxiety symptoms. This treatment regimen lasted for a median of 66 days. However, Salgado and Castellanos suggested guiding principles for the use of CBD in this population, including a better clinical understanding of CBD, open discussion with parents and patients, addressing their perceptions, promoting informed consent, and exercising caution in the use of CBD (Salgado & Castellanos, 2018). Patients with ASD make up a heterogeneous group of individuals with different comorbidities that should be considered.
The efficacy of CBD for SAD and PTSD was explored in three studies including one RCT, one case report, and one chart review. The RCT reported the results of a simulated public speaking test among 12 healthy control participants and 24 patients with SAD who received a single dose of CBD 600 mg or a placebo before the test. This study reported that pretreatment with CBD resulted in less anxiety, cognitive impairment, and discomfort during their speaking performance. It also resulted in a significant reduction in alertness in their anticipatory speech compared to the placebo group (Bergamaschi et al., 2011).
In a 10-year-old patient, 5 months of treatment with CBD oil (25 mg) and liquid CBD (6–12 mg) in a sublingual spray as needed was associated with less anxiety and better sleep quality, with no adverse effects (Shannon & Opila-Lehman, 2016). These results were replicated for anxiety in a recently published chart review of 72 adult patients with insomnia and anxiety (Shannon et al., 2019). Most patients in this group were given 25 mg CBD/day, while a few patients were given 50 or 75 mg/day, and one patient with schizoaffective disorder and trauma was given up to 175 mg/day. All patients showed less anxiety and improved sleep, with reductions of 65–80% in the Hamilton Anxiety Rating Scale and Pittsburgh Sleep Quality Index scores.
Nabiximols produced improvements in patients with Tourette syndrome at a much lower dose than what was used for cannabis-related disorders (Trainor et al., 2016; Pichler et al., 2019). These case reports tested two oromucosal nabiximols sprays used twice a day (total dose 10.8 mg Δ9-THC and 10 mg CBD per day) (Trainor et al., 2016), and the second also tested cannabis tincture (34 drops three times a day (Pichler et al., 2019). Both case reports found improvements in tic frequency (Trainor et al., 2016; Pichler et al., 2019), severity (Trainor et al., 2016; Pichler et al., 2019), quality of life, and social activity (Trainor et al., 2016). These treatments regimens were used for 4 weeks with the oromucosal spray form (Trainor et al., 2016) and 8 weeks for cannabis tincture (Pichler et al., 2019). The therapeutic benefits can be attributed to the anxiolytic and sleep-inducing properties of CBD (Trainor et al., 2016). It is difficult to ascertain whether these improvements were due to due to CBD, Δ9-THC, additive, or synergetic effects. The anxiolytic properties of CBD explain the attenuation of anxiety associated with the onset of tics, and the improvement in tics with a combination of Δ9-THC and CBD (Trainor et al., 2016; Pichler et al., 2019).
Adverse effects were reported in four of the studies, and included muscular seizures and spasms (Cooper et al., 2017), somnolence and changes in appetite (Barchel et al., 2018), fatigue, and sexually inappropriate behavior in a patient with developmental disorder (Shannon et al., 2019), mild sedation (Zuardi et al., 2010), and mild xerostomia (Pichler et al., 2019).
Summary of evidence
The present article provides a comprehensive review of the evidence supporting the use of CBD and CBD-containing compounds such as nabiximols to treat psychiatric disorders. CBD and nabiximols were effective in cannabis use-related disorders, and preliminary evidence was found in support of their use for other psychiatric disorders. Of the 23 studies reviewed here, level 2 evidence was found in eight RCTs, level 3 evidence in four open-label trials and one clinical trial, and level 4 evidence in one retrospective chart review, seven case reports, and two case series, according to the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence (OCEBM, 2019). This review covers the evidence for different routes of administration, e.g. oral, inhalation spray, and sublingual. The bioavailability of these routes (11–13% for oral vs. 11–43% for inhalation) varies significantly – a factor that can impact the efficacy of different formulations.
Their antipsychotic, neuroprotective, anxiolytic, and sedating properties suggest a potential therapeutic role of CBD and nabiximols to treat various psychiatric disorders. The use of CBD at higher doses (above 1200 mg per day) showed promising results in case studies of schizophrenia and psychosis in patients with Parkinson’s disease, except in treatment-resistant cases. Regarding the use of CBD to treat anxiety disorders, its anxiolytic effect can help patients with PTSD-related and social performance-related anxiety, and nabiximols can reduce the anxiety associated with the onset of tics. There is also favorable evidence in patients with ASD for reducing hyperactivity, self-injurious behaviors, anxiety, and insomnia. Nabiximols showed no credible effect in the treatment of ADHD, while CBD was also found to be ineffective for bipolar disorder. Of all the cases examined, the strongest evidence was found for the treatment of cannabis-related disorders. The use of nabiximols yielded positive results in multiple studies of moderate to severe cannabis use disorder; however, the use of CBD alone has not been adequately documented outside a few cases and case series. Notably, CBD compounds were helpful in alleviating psychotic symptoms and improving cognitive impairment in patients across a variety of conditions.
Recommendations for future research
This review found low-level evidence for the use of cannabis and nabiximols in a variety of disorders. Despite our comprehensive literature search, only a few RCTs related to the disorders of interest were found. These RCTs were marred by a number of limitations, most importantly failure to blind the outcome assessor, participants, and research personnel (in the open-label trials). In addition, most RCTs had a small sample size, critically reducing the power of the study to draw robust conclusions. The findings of the RCTs reviewed here need to be validated via a series of larger, well planned, randomized, double-blinded, and placebo-controlled studies. The present report can be used to design and plan further studies; however, at present the use of CBD and nabiximols in clinical practice cannot be recommended with confidence due to the drawbacks noted above.
The evidence from studies included in this review can guide future trials by providing information pertaining to the dosages, formulations and routes of administration of CBD and nabiximols. Moreover, future studies should investigate different routes of administration in light of the differences in bioavailability. In view of the (albeit limited) evidence for treatment-resistant schizophrenia, the role of CBD should be explored in the early stages of psychosis or as an adjunct medication. Although CBD was ineffective for bipolar mania, its possible efficacy as an antidepressant should be assessed in studies focused on bipolar depression. Nabiximols has been helpful in cannabis-related disorder and Tourette syndrome, owing to the synergetic benefits of CBD and THC. Future studies designed to explore the comparative benefits of these treatments can shed further light on their clinical potential. Future RCTs should also consider adding first-line treatment agents as comparison arms, to ascertain the comparative efficacy of CBD in different mental disorders. Although fewer side effects were reported overall by patients in the studies reviewed here, the vulnerability to addiction to cannabinoids should not be ignored.
Limitations of the review
This review article has several limitations that should be considered. This review article provides evidence for CBD and CBD-containing nabiximols are two different pharmacological agents. Nabiximols has two active compounds and included studies do not consider the separate effects of THC VS CBD. There is need for future analyses to carefully consider their benefits individually. Only one-third of studies (8/23) in this review article are RCTs and most of these RCTs had a small sample size decreasing the power of the study to draw robust conclusions.
The evidence reviewed here favors CBD use for patients with schizophrenia and psychosis in Parkinson’s disease in four out of seven studies, except in treatment-resistant cases. There is a Grade B recommendation this diagnosis based on the levels of evidence. Nabiximols and CBD were beneficial in cannabis-related disorders in almost all studies with Grade B recommendation, resulting in a decreased risk of withdrawal symptoms and dependence among participants. The effect on cannabis-related craving was pronounced, with an additive benefit from the use of psychotherapeutic options such as MET or CBT. One open-label trial suggested favorable evidence for the use of cannabinoids CBD and Δ9-THC for hyperactivity, self-injurious behaviors, and anxiety symptoms in patients with ASD with Grade B recommendation. CBD was helpful in patients with anxiety and insomnia related to SAD and PTSD in one chart review. Nabiximols was found to be effective in reducing the frequency and severity of tics and improving the quality of life in patients with Tourette syndrome according to case reports. There was no firm evidence to support CBD to treat bipolar mania (one case report) or nabiximols (one RCT) to treat ADHD. There is Grade B (moderate) recommendation for attention deficit hyperactivity disorder. Grade C recommendation (weaker) exists for insomnia, anxiety, bipolar disorder, posttraumatic stress disorder, and Tourette syndrome. These recommendations should be considered in the context of limited number of available studies. The authors recommend well-planned randomized controlled trials to further study the benefits of CBD and CBD-containing options such as nabiximols in patients with psychiatric disorders. It is also important to assess the individual pharmacodynamic and pharmacokinetic effects of CBD and Δ9-THC in different treatments.
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