Cannabis use is extremely common among adolescents and young adults, with an estimated 14% of students in the 10th grade, 23% of students in the 12th grade, and 22% of college students and young adults engaging in at least monthly use in 2016.1 In 2015, 1.8 million adolescents (aged 12-17 years) and 6.9 million young adults (aged 18-25 years) were current users of cannabis.2 Moreover, the problem is increasing: 30-day prevalence of use among students in the 12th grade rose from 19% in 2007 to 23% in 2017.3 There is even higher use in Canada: In 2013, an estimated 28% of youths aged 11 to 15 years admitted to using cannabis at least once a year, and a high number reported weekly or daily use.4

The National Institute on Drug Abuse reports that cannabis use is more prevalent among males than females, indicating a sex gap that is continuing to widen.5 The effects of the drug also differ between the sexes, in that males show a greater cannabis-induced high compared with their female counterparts.6 By 9th grade, approximately 1 in 3 boys and 1 in 4 girls will have used cannabis.7 A survey of more than 2000 cannabis users found that men reported using cannabis more frequently and in higher quantities than women, and were also more likely to use joints/blunts, vaporizers, and concentrates, whereas women were more likely to use pipes and oral administration.8

“We are in the midst of a huge epidemic of young people using marijuana,” observed Meldon Kahan, MD, Associate Professor, Department of Family Medicine, University of Toronto, and Medical Director of the Substance Use Service at Women’s College Hospital, Toronto, Ontario, Canada.

“The epidemic is driven partially by changed attitudes toward its use and by legalization, but is driven largely, at least in Canada, by cannabis companies that are pushing it to this age group and claiming it’s safe, while in reality, it’s anything but safe,” he told Psychiatry Advisor.

Misperceived Safety

Cannabis consists of numerous compounds, but the central 2 are cannabidiol (CBD) and Δ-tetrahydrocannabinol (THC), which is responsible for the psychoactive effects that occur via its interaction with the endocannabinoid system.9 Adolescents typically do not think that cannabis use is as risky as other substances, a belief that has been “steadily growing.”1 When asked, “How much do you think people risk harming themselves if they smoke marijuana regularly?” less than one-third of high school seniors responded that there was a “great risk” in 2016 compared with 58% in 2006.1 The pervasiveness of cannabis, together with its “relatively low lethality,” has led to the misperception among adolescents and adults alike that it is innocuous9; for example, many baby boomers who used cannabis when they were in college have resumed use.10 However, the amount of THC is considerably higher than it was in the 1960s and 1970s, with rates that continue to climb. THC levels in cannabis have risen from 8.9% in 2008 to 17.1% in 2017, and the mean THC:CBT ratio also rose substantially, going from 23 in 2008 to 104 in 2017.11

Cannabis use in adolescence is associated with harmful outcomes during adulthood (eg, adverse social behaviors,12 decreased neuropsychological and cognitive function,13 and increased risk for depression, anxiety, and suicidality14).

Moreover, during adolescence, cannabis is associated with increased psychiatric emergency department (ED) visits15,16 and increased risk for psychosis,17with some research suggesting that it might as much as double the risk for psychosis and schizophrenia.18

Misperceived Benefits: Adolescent ADHD and Anxiety

In addition to sometimes inaccurate safety perceptions, there is an “increasingly popular perception” that cannabis is beneficial for attention-deficit/hyperactivity disorder (ADHD), and many individuals with the condition are turning to cannabis for relief of symptoms such as poor concentration or hyperactivity.19

“In the past month, I have treated 6 young men — adolescents or young adults — who presented to the ED with psychosis induced by vaping high-potency cannabis,” Wilfrid Noel Raby, PhD, MD, Adjunct Assistant Clinical Professor, Albert Einstein College of Medicine, Bronx, New York, told Psychiatry Advisor.

“It could be that the cannabis temporarily overrides some of the deficits that are associated with ADHD; for example, more aberrant frontal lobe functioning or hyperactivity,” he suggested.

However, “many of these youngsters are also taking stimulants, and stimulants can work synergistically with THC when consumed in low quantities, since THC can also have excitatory effects. In fact, many people get agitated when using it,” Dr Raby pointed out.

In contrast, “I’ve had people tell me that marijuana balances out the stimulant effects and adds relaxation when smoked in higher quantities, but the excessive glutamate release from the combination of THC and stimulants can lead to psychosis.”

The dose and potency of cannabis are very important, Dr Raby noted.

“We know that cannabidiol can have inhibitory effects that protect against the psychoactive and stimulating effects of THC alone, and there may be other cannabinoids contained in cannabis that have a similar effect,” he said.

“But vaping a product that is almost exclusively THC means that there is nothing to counterbalance it,” he explained.

Many youngsters and adults associated cannabis with relaxation or relief of insomnia, Dr Kahan added. “Patients who would like to reduce anxiety, increase sleep, or address pain should look specifically for products made exclusively or primarily with CBD,” he recommended.

Cannabis and the Adolescent Brain: Vulnerability to Psychosis

Whether adolescents are using cannabis recreationally or medicinally, Thorsten Rudroff, PhD, Assistant Professor, Department of Health and Human Physiology and Department of Neurology, University of Iowa, Iowa City, cautions, “Adolescence and young adulthood are critical periods in which the use of a high-THC product can have a big effect on the structure and function of the developing brain.”

“Blood flow and glucose metabolism may be impaired in regions associated with maturation, especially when cannabis is being used together with alcohol, as many young people do,” he told Psychiatry Advisor.

Cannabis has been found to be involved in as much as 50% of cases of psychosis, schizophrenia, and schizophreniform episodes.20 Although the exact neurobiological processes are not fully understood,20there are several hypothesis explaining the association.

“The endocannabinoid system is critical for neurodevelopment and as such is present in early development, and maintains expression throughout life.”9 Numerous important changes take place in the brain during adolescence; in particular, neuronal maturation and rearrangement processes (eg, myelination, synaptic pruning, and dendritic plasticity).21

“Exogenously ingested cannabis produces supraphysiologic effects at [endocannabinoid]-targeted receptors and thus usurp[s] the normal endocannabinoid system,”9 resulting in a “cascade of neurochemical and neurostructural aberrations.”21Synaptic plasticity may be impaired in schizophrenia, and it is likely that the effect of cannabis on neuroplasticity of the developing brain may play a role in the vulnerability to psychosis.20

Moreover, the disruptions in brain development caused by neurotoxic effects of regular cannabis use might significantly alter neurodevelopmental trajectories, not only by changing neurochemical communication and genetic expression of neural development but also by having a toxic effect on brain tissue itself.21

In addition, individuals at familial risk for psychosis have an increased sensitivity to the effects of cannabis, suggesting a biological interaction between cannabis use and underlying genetic vulnerability.22

“THC affects regions of the brain that are responsible for psychosis and hallucinations,” Dr Rudroff wrote. He noted that in his research, which focused on the use of cannabis in people with multiple sclerosis, his team looked at the effect of both THC and CBD on glucose uptake in the brain.23

“THC caused increased glucose metabolism in the left temporal area, a region associated with executive dysfunction and psychosis, which is especially problematic in patients with [multiple sclerosis] because they already have brain impairments that can lead to psychosis,” he explained. Although CBD may have some medical benefits, “the medical benefits of THC are unclear and debatable,” Dr Rudroff added.

Screening for Cannabis Use

Physicians should ask all patients about cannabis use, especially adolescents, young adults, or those with concurrent psychiatric or substance use disorders, Dr Kahan urged.

“At baseline or annually, at least ask all patients if they have used any form of marijuana and ask youth or others at higher risk more frequently,” he said.

Be specific in asking these questions, he advised. “Especially with teenagers, you have to ask detailed questions such as, ‘Do you smoke, vape, or eat it? How often do you use: Is it regular or occasional? Do you use it once a week, or every few days, or more frequently? Do you use it primarily on weekends?'”

Moreover, patients should be questioned and screened if they present with symptoms or conditions associated with cannabis use.

Red flags or problematic use include daily or near daily use, social dysfunction, poor function at work or school, repeated unsuccessful attempts to stop or reduce use, and expressions of concern from family or friends, according to Dr Kahan.

Two helpful assessment tools are the CRAFFT Questionnaire,24 which screens for patients who require additional assessment, and the Severity of Dependence Scale,25 which assesses how serious the patient’s problem might be. (Tables 1 and 2)

It is essential to take a careful history because it can be difficult to differentiate between cannabis-induced psychosis and schizophrenia.26 (Table 3)

Treatment Approaches: Pharmacotherapy

Dr Kahan noted that daily or very frequent users often experience withdrawal symptoms on discontinuation of cannabis, including hypersomnia or insomnia, fatigue, anxiety, depression, irritability, and cravings. These symptoms typically come on between 24 and 48 hours of last use and resolve quickly with resumed use. Because withdrawal is so unpleasant, it can have a “negative reinforcing effect” that makes relapse common during that period.

Selective serotonin antidepressants, mixed-action antidepressants, bupropion, buspirone, and atomoxetine are “probably of little value” in treating cannabis dependence.27 Gabapentin, oxytocin, N-acetylcysteine, and nabilone can be helpful for cannabis withdrawal, although the evidence for their use is weak. 27 Dr Raby added that other sympatholytic medications (naltrexone, quetiapine, clonidine, or Prazosin) can also be helpful.

The approach might be different in the case of a cannabis user who has developed psychosis, Dr Raby pointed out, as treatment must target acute psychosis, prevention of future psychosis, treating the underlying disorder (eg, ADHD), and addressing the cannabis dependence itself.

“In an attentional disorder, it is not necessarily helpful to prescribe another stimulant, because once the patient has crossed the threshold of psychosis, the risk for a future psychotic event is high,” he said.

In contrast, introducing an antipsychotic can be helpful, and although several agents in this class might have utility, Dr Raby has found one to be particularly effective.

“Although many prescribers shy away from clozapine, I have had success treating patients in this situation with this medication, especially when there is a family history of schizophrenia,” he continued. “These patients have been able to discontinue after 2 to 3 years without a return to either marijuana or psychosis, provided they do not resume cannabis use in any form.”

In the case of a pattern suggesting atypical depression, which is not uncommon in people with ADHD, he noted, a small dose of antipsychotic might be helpful, together with a monoamine oxidase inhibitor such as tranylcypromine, selegiline, or isocarboxazid.

Clues to the presence of atypical depression include mood reactivity, rejection sensitivity, and seasonal alteration of sleep and appetite.28

In particular, for prominent sleep disturbance, Dr Raby reported success with low doses of chlorpromazine together (or not together) with low-dose quetiapine. “This combination addresses not only sleep but also protects against the return of psychosis and treats the depression in a way that doesn’t exacerbate the attention disorder.”

If the psychosis is brief and transient, low-dose risperidone might “help with sleep, calmness, and provide a buffer,” he added.

Psychosocial Interventions

Pharmacotherapy is not sufficient to ensure future abstinence and return to optimal functioning, Dr Kahan emphasized.

Dr Raby agreed. “Help [adolescent patients] to understand what effects they were seeking, help them remember the effect of cannabis changes (inducing anxiety and paranoia), and when this happened, and then explain why. It is most important that they must look to this change in effect as a sign that their sanity is at stake.”

One of the most important components of counseling patients is developing a positive, nonjudgmental attitude, demonstrating empathy, and encouraging self-efficacy, Dr Kahan said.

Patients who are at risk for psychosis or other cannabis-induced problems should receive brief counseling consisting of psychoeducation and motivational interviewing, he recommended.

Psychoeducation can include information about the medical and social effects of cannabis use on areas such as academic or employment performance, mood, focus, concentration, social activities, and sleep, Dr Kahan continued.

James McKowen, PhD, Clinical Director, Addiction Recovery Management Service and Assistant Psychologist, Massachusetts General Hospital/Harvard Medical School, Boston, agreed that education is essential but challenging.

“Most young people have no clue, and it can be hard for them to link cause and effect because the onset of the longer-term effects [is] usually insidious and gradual; for example, that marijuana is contributing to poor grades or lack of interest in previously enjoyable activities, such as sports or movies, or that one’s social circle has shrunk to fellow marijuana users and other friendships have fallen to the side,” he told Psychiatry Advisor.

Dr Kahan recommended that clinicians help patients determine realistic goals (eg, reduction in use and eventual abstinence). If patients are not yet ready to change, clinicians should acknowledge the reluctance, remain supportive, keep encouraging the change, and explore the pros and cons of cannabis use.

Dr McKowen emphasized that it is critical to include family members in the therapeutic process for adolescents and young adults, as many college students still live at home or retain close ties with their families.

“Help parents understand addiction and psychosis,” he advised. “Parents are understandably terrified and at a loss what to do. They may worry that their child will be homeless and wandering the streets, especially if they have another relative with a psychotic disorder.”

Parents should also be provided with support and suggestions regarding how to talk to their teenaged children, and what to do if the teenager relapses or refuses to take medication. One helpful resource for parents is Parent CRAFT.

For young people who have moved beyond merely being at risk and are experiencing psychotic symptoms, Dr McKowen recommended cognitive behavioral therapy specifically tailored for psychosis.

Nonpharmacologic approaches to cannabis use in adolescents and young adults can be found in Table 4.

Conclusion

An increasing body of research is linking high-potency cannabis, even when used recreationally, to the risk for psychosis.29 As cannabis becomes legal in more parts of the United States and other countries, and given the paucity of research into its effects and interactions with other substances,30 it is essential for clinicians to be conversant in the types of cannabis that are available, how they are being used, how they affect the brains of adolescents and young adults, and how ongoing use and psychosis can be detected and treated.