Clearing up the smoke: Physical and mental health considerations regarding cannabis use in adolescents with cystic fibrosis

Abstract

The cannabis plant is the most used federally illegal drug in the United States and is widely used by adolescents. Cannabis has complex effects on the body and mind. All health professionals who take care of adolescents with cystic fibrosis (CF) should be aware of the factors impacting cannabis use in CF. Given limited evidence regarding the benefits of cannabis and the significant risks, clinicians have the responsibility to identify risk of cannabis use early, counsel patients about the risks, provide a safe space for ongoing conversations about cannabis use in the context of CF care, and deliver evidence‐based interventions.

1. INTRODUCTION

The cannabis plant is the most commonly used federally illegal drug in the United States and is widely used by adolescents. ¹ Cannabis has more than 120 different chemical compounds, including delta‐9‐tetrahydrocannabinol (THC) and cannabidiol (CBD). These chemical compounds exert effects on multiple targets with diverse downstream effects on cognition, emotion, respiration, digestion, circulation, pain regulation, and immunity. ² The psychoactive component of the plant, THC, is a partial agonist at both G‐protein‐coupled endocannabinoid receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), ³ and can cause euphoria and psychosis in addition to its analgesic and anti‐inflammatory effects. ⁴ The nonpsychoactive component of the plant, CBD, has poor affinity for CB1 and CB2, ⁵ and instead acts as an agonist on transient receptor potential vanilloid‐1, decreasing neuronal excitability, ⁶ and as an antagonist on the orphan G protein‐coupled receptor‐55, inhibiting intracellular calcium release. ⁶ These receptor interactions, in addition to interactions with voltage‐gated potassium channels and 5‐HT1A receptors, are implicated in the antiepileptic properties of CBD. ⁶

Contextually, adolescents are living in an era of increasing support for the legalization of medical and recreational uses of cannabis. In 2021, the Monitoring the Future study reported that 10.2% of 8th graders, 22% of 10th graders, and 38.6% of 12th graders reported lifetime use of cannabis. ⁷ In 1969, only 12% of Americans supported cannabis legalization for recreational use, whereas in 2015, 53% supported legalization. ⁸ Recreational use is now legal in 18 states, two territories, and the District of Columbia. ⁹ Furthermore, in the United States, there is a trend toward higher THC potency, especially with the extract products, such as tinctures, capsules, vaporizer cartridges, dabbing, and wax. ¹⁰ From 1979 to 2009, the mean THC value increased globally on average by 4.7%. ¹¹ In addition, adolescents now use vaping and edibles more commonly than smoking. ¹²

Cystic Fibrosis (CF) is the most common autosomal recessive disease among Caucasian youth with an incidence of 1 in 3500 births in the United States and Europe. ¹³ It is a result of a mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene which codes epithelial ion channel protein (CFTR protein) that transports chloride and bicarbonate across epithelial surfaces. ¹⁴ As a result, thick and viscous mucus secretions cause obstruction in internal organs. Youth become symptomatic shortly after birth with significant effects on respiratory function and proclivity for recurrent respiratory infection and inflammation. CF may also result in pancreatic exocrine dysfunction, CF‐related diabetes, male infertility, and CF liver disease. ¹⁴ These conditions have several downstream sequelae that can dramatically impact quality of life, and effect family functioning, academic performance, social interactions, identity formation, and mental health.

Given the significant impact of CF on the life experiences and development of the adolescent, as well as its complex effects on the body and mind, it is important to understand the prevalence of cannabis use in adolescents with CF. In 1990s, Britto et al. ¹⁵ conducted a study among 115 adolescents with CF aged 12–19 years (mean age, 15.5 years; 51.3% female) and showed that 9.7% of these youth reported lifetime cannabis use, compared with 29.4% among the comparison group, drawn from a sample of in‐school North Carolina adolescents. In 2015, Weitzman et al. ¹⁶ conducted a study on 403 children and adolescents with various chronic medical conditions, including asthma, type I diabetes mellitus, inflammatory bowel disease (IBD), and juvenile arthritis. In the analysis, they grouped those diagnosed with asthma and CF and found that nearly one in every five patients in this group reported lifetime cannabis use. ¹⁵ Even though cannabis use was less prevalent among those youth compared with other chronic medical conditions, its prevalence in light of the implications on lung function and clinical outcomes was still concerning. ¹⁵ In a recent survey of 16‐year‐olds with CF being treated at CF care centers in New Jersey and Pennsylvania, 15.4% reported cannabis use (31/193) and 46% (72/156) reported interest in trying medical cannabis if it were available. ¹⁷

There are multiple factors associated with cannabis use among adolescents with CF. Youth may often experience comorbid pain, depression, anxiety, a sense of isolation, insomnia, nausea/vomiting, decreased appetite, and weight loss, all of which could make cannabis use appealing. While the literature is still growing for therapeutic potential of cannabis as a treatment of various physical and mental health conditions for children and adolescents, for adults, a meta‐analysis conducted by Whiting et al. ¹⁸ revealed that cannabis products have moderate‐quality evidence for the treatment of chronic neuropathic or cancer pain; low‐quality evidence for improvement of nausea and vomiting due to chemotherapy, or for aiding with sleep disturbances; and very low‐quality evidence for improvement in anxiety.

To date, the Federal Drug Administration (FDA) has approved one cannabis‐derived drug product, Epidiolex (CBD), and three synthetic cannabis‐related drug products: marinol (dronabinol), syndros (dronabinol), and cesamet (nabilone). ¹⁹ CBD (Epidolex) is approved for seizures associated with Dravet syndrome and Lennox‐Gestaut syndrome, and tuberous sclerosis complex, dronabinol is approved for chemotherapy‐induced nausea and vomiting (CINV), as well as appetite stimulation in wasting conditions, and nabilone is approved for chemotherapy‐induced nausea and vomiting. ²⁰ In Pediatrics, there is limited evidence for its use outside of pediatric epilepsy. ²¹ In 2015, the American Academy of Pediatrics (AAP) opposed recreational or medical cannabis use in children and adolescents outside the regulatory process of the FDA, while recognizing that cannabis may be an option for children with life‐limiting or severely debilitating conditions and when current therapies are inadequate. ²²

Among clinicians, there is still debate over what constitutes “severely debilitating conditions” to qualify for cannabis use and whether adolescents who have long‐term physical health issues should use cannabis. Thus, clinicians should be well prepared to discuss cannabis and its potential risks and benefits with their patients, which can be a challenging task. Frequently, clinicians express a lack of confidence in their ability to counsel patients about cannabis use and identify the need for more training. ²³ Multiple factors may contribute to providers' reticence to engage in these discussions, including time constraints within a busy practice, the political undertones and variable social perceptions around the issue, and the potential psychological and psychiatric comorbidities that can arise with cannabis use. This review article has several aims: (1) discuss the potential systemic effects of cannabis, including pulmonary, gastrointestinal (GI), and endocrine function in adolescent CF; (2) discuss its unique potential effects on emotional and behavioral health in adolescent CF; (3) summarize possible therapeutic applications to aid clinicians in balancing risks and benefits; and (4) provide practical strategies on how to counsel and help manage cannabis use among adolescent CF.

2. POTENTIAL SYSTEMIC EFFECTS OF CANNABIS

The activation of cannabinoid receptors produces effects within organ systems throughout the body, including the pulmonary, GI, and endocrine systems. These effects are often dose‐dependent, unique to each person, and can involve various synergistic responses to heighten the effects on end‐organ targets.

2.1. Pulmonary function

Much of the current data regarding cannabis and its potential effects on pulmonary function is related to inhaled use. In a convenience sample of adults divided into three groups based on inhalation habits—cannabis only smokers, cannabis and tobacco smokers, and nonsmokers—a dose–response relationship was found between smoking cannabis and large airway function, including a decrease in the forced expiratory volume in 1 s (FEV1) to forced vital capacity ratio. ²⁴ High‐resolution computed tomography showed decreased lung density with cannabis smoking. ²⁴ Airflow obstruction from one cannabis joint was comparable with as many as five tobacco cigarettes. ²⁴ Cannabis, independent of CF status, is associated with developing pneumothorax ²⁵ and hemoptysis. ²⁶ Cannabis‐based e‐cigarette products are formulated with additives which can adversely affect the pulmonary system, as seen in e‐cigarette or vaping use‐associated lung injury. ²⁷ Potential effects of oral consumption of cannabis on pulmonary function is not currently well described, yet may have possible indirect implications on lung function through drug‐drug interactions with medications used in the treatment of CF, such as the CFTR modulators. ²⁸

2.2. GI function

The potential effects of cannabis and its derivatives, in the GI tract include those on the liver, pancreas, esophagus, stomach, and colon. These effects include decreased lower esophageal sphincter pressure, decreased gastric emptying, and slowed GI motility. ²⁹ Symptomatic improvement in pain related to chronic pancreatitis and IBD, and improvement in nausea associated with gastroparesis and CINV have also been reported. ²⁸ There is ongoing research into how cannabis and its derivatives may modify the intestinal microbiome. Interestingly, there is conflicting data regarding the role of cannabis in mitigating or contributing to liver fibrosis. Further research is needed to understand the effects of cannabis use on hepatic function and pathology. Studies regarding possible uses of cannabis in the treatment of conditions such as IBD, irritable bowel syndrome, and nonalcoholic fatty acid liver disease are needed to further investigate its safety and efficacy. ³⁰

2.3. Endocrine function

Cannabis can significantly influence hypothalamic–pituitary–adrenal (HPA) axis, thyroid, and gonadal function. ³¹ Furthermore, cannabis use can affect glycemic control, lipid regulation, and bone metabolism. ³² Some potential endocrine effects of cannabinoids include reduced female fertility, reduced sperm count and function, decreased thyroid hormone levels, increased risk of development of diabetes, increase in fracture risk, and variable changes in high‐density lipoprotein and triglycerides. ³² With chronic use, cannabis can blunt HPA axis and the associated stress response in adolescents. ³³ These potential consequences are based on limited animal and population data, with need for future studies investigating short‐ and long‐term effects from exogenous cannabinoid exposure, as well as differential effects of THC versus CBD. ³²

3. POTENTIAL EFFECTS ON EMOTIONAL AND BEHAVIORAL HEALTH

Developmentally, adolescence is characterized by a strong emphasis on creating and maintaining social connections and developing one's own sense of self. During adolescence, children try to become more independent, express a stronger demand for autonomy, develop their emotional control and conflict resolution skills, and start seeking internal validation for self‐worth. Contending with CF during this already challenging time can cause disruptions to routine, impact identity formation and autonomy, and influence interpersonal interactions, with significant implications for one's emotional and behavioral health. The relationship between physical illness and emotional and behavioral health is often bidirectional, with substantial contributions from psychological, developmental, illness‐related, familial, and treatment factors. ³⁴

3.1. Cognition and decision‐making

Adolescents may engage in risk‐taking behavior without considering future consequences. This can promote learning and independence, but can significantly increase the risk of injury, psychopathology, and substance use. ³⁵ This risk can be amplified in the presence of peers, where social pressures to assimilate can increase risky or reckless behavior. ³⁶ Adolescents with CF desire normalcy and social acceptance, ³⁷ which may increase the risk of engaging in cannabis use.

Cannabis is harmful to the developing brain, causing abnormalities in gray and white matter that are often correlated with cognitive deficits including executive functioning and intelligence quotient (IQ). ³⁸ In a prospective cohort study of 10 individuals from birth to age 38, cannabis was linked to drop in IQ even after accounting for years of education. ³⁹ Adolescents with CF have additional unique risks to cognitive development secondary to direct CF‐related pathophysiology and malnutrition. Youth with CF performed worse than healthy controls on attention and memory tests. This finding was attributed to chronic vitamin E deficiency secondary to pancreatic insufficiency, neuronal damage mediated through respiratory hypoxia, and a mutated CFTR gene. ⁴⁰ CFTR gene is expressed in the central nervous system and could have potential role in neurological function. ⁴¹ Due to these global effects on cognition, adolescents with CF are at increased risk for emotional dysregulation, difficulties completing complex tasks, challenges with organization and adaptive problem‐solving, as well as impairments in remembering treatments. The overlapping effects of CF and cannabis on attention, memory, executive function, processing emotional information, and sequencing complex tasks has downstream effects not only on cognition but also on decision‐making, adherence, and global functioning.

3.2. Anxiety

According to data from the 2013–2019 National Survey of Children's Health (NSCH), 9.4% of children and adolescents aged 3–17 years had ever received a diagnosis of an anxiety‐related problem. ⁴¹ According to a meta‐analysis of youth and young adults with life‐limiting conditions, the pooled anxiety prevalence was reported as 22.8% (95% confidence interval [CI]: 17.1%–29.1%) in patients with CF. ⁴² This is more than double the prevalence of anxiety among the same‐aged general population.

There are no published randomized, placebo‐controlled trials exploring the relationship of cannabinoids on pediatric anxiety disorders. Animal studies reveal that long‐term exposure to cannabinoids during adolescence induces anxiety‐like behaviors in adulthood with concurrent serotonergic hypoactivity and noradrenergic hyperactivity. ⁴³ Furthermore, cannabis may alter stress response both acutely and chronically, which can foster maladaptive coping and poor psychological distress tolerance. ⁴⁴

A meta‐analysis of 23,317 young adults examining anxiety development in cannabis users, compared with nonusers, demonstrated a pooled odds ratio for anxiety of 1.18 (0.84–1.67), which was not statistically significant. ⁴⁵ A cohort study conducted among 1601 students aged 14–15 showed that daily cannabis use is associated with higher odds of anxiety and depression. ⁴⁶ Data from a birth cohort study demonstrated that the age at onset and frequency of cannabis use is significantly associated with symptoms of anxiety and depression by age 21. ⁴⁷ Youth with CF are already susceptible to anxiety symptoms, and cannabis use may exacerbate these symptoms.

3.3. Depression

According to NSCH, the prevalence of depression is 4.4% for children and adolescents aged 3–17 years. ⁴¹ A multisite study across nine countries demonstrated depression prevalence as 19% in adolescents with CF, over four times greater when compared with the general population. ⁴⁸ Being female, history of hemoptysis or pneumothorax in the previous 6 months, taking psychiatric medication for depression or anxiety, and receiving psychotherapy for depression or anxiety were associated with elevated symptoms of depression. ⁴⁸ Depressed adolescents with comorbid CF are at higher risk of decreased lung function, lower body mass index, worse treatment adherence, poorer quality of life, increased hospitalizations, longer length of hospital stay, increased post‐lung transplant mortality, and increased healthcare costs. ³⁴ , ⁴⁹

Cannabis can also increase the risk of both depressive symptoms and clinical depression in youth. The estimated population‐attributable risk of cannabis is 7.2%. ⁴⁵ In addition, cannabis can lead to decreased motivation. ⁵⁰ Management of CF requires empowering patients to be active participants in their treatment and to maintain health‐enhancing behaviors. Depression and chronic cannabis use could dampen this drive and thus may lead to worse outcomes.

Furthermore, parental depression and anxiety are associated with higher risk of these disorders in their teens. ⁴⁸ A history of parental depression marginally increases the likelihood that a young adult will use cannabis (adjusted OR: 1.42; 95% CI: 1.00–2.01). ⁵¹ In addition, young adults with a history of parental divorce and depression are more than twice as likely to concurrently use cannabis (adjusted OR: 2.38; 95% CI: 1.26–4.48). ⁵¹ Therefore, parents of adolescents with CF should also be evaluated for depressive symptoms, given their effects on teen's mental health and risk of cannabis use. ⁵²

3.4. Suicide

Suicide is the second leading cause of death in youth ages 10–19. ⁵³ Compared with healthy controls, youth with chronic physical health conditions have a 28% increase in suicidal thoughts, 134% increased risk of suicidal planning, and 363% increased risk of attempting suicide. ⁵⁴ Logan et. al. ⁵⁵ screened 18 youth with CF, ages 8–17, with the Children's Depression Inventory, and four patients (22%) reported a history of suicidal ideation. According to the CF Foundation, among the 252 deaths in 2020, 11 individuals (4.4%) died by suicide or drug overdose. ⁵⁶ There is minimal data examining suicide ideation or attempts among adolescents with CF and comorbid cannabis use. However, it is known that cannabis is independently associated with increased suicidal ideation. ⁵⁷ Among 281,650 participants in the 2008–2019 National Surveys of Drug Use and Health, cannabis use was associated with a higher prevalence of past‐year suicidal ideation, suicide planning, and suicide attempts, even after controlling for major depressive disorder. ⁵⁷ Another meta‐analysis conducted among adolescents and young adults with cannabis use showed the pooled OR for suicide attempt as 3.46 (95% CI: 153–7.84). ⁴⁵

3.5. Psychosis

There appears to be no evidence to indicate a relationship between CF and psychosis. However, corticosteroids and glucocorticoids, commonly used in CF exacerbations, can induce psychosis. ⁵⁸ In addition, cannabis use is strongly associated with development of psychosis in a dose–response fashion. ⁵⁹ The OR for development of schizophrenia, or other psychotic disorders, in heavy users of cannabis, as compared with nonusers is 3.90 (95% CI: 2.84–5.34). ⁵⁹ Clinicians should assess if there are possible drug interactions with current medications (e.g., CFTR modulators) and CBD.

3.6. Social functioning

Adolescents with CF may experience stigma, especially given the outward evidence of disease in some individuals related to taking enzymes with meals, frequent coughing, having short stature, and weight loss. ⁶⁰ Despite this, adolescents with CF tend to shy away from making their illness public. ³⁷ Adults with CF recount experiencing perceived extreme reactions from the school in response to their physical health, such as being sent home for coughing. ⁶¹ The stigmatizing nature of CF is associated with increased psychological distress, lower quality of life (QoL), poor body image, low self‐esteem, lower sense of personal control, lower levels of optimism, and lower pulmonary function. ⁶² Furthermore, to decrease the risk of cross‐infection, adolescents with CF are sometimes advised to not have direct physical contact with their peers with CF. Beyond the stigma and impact on identity, this can cause a further sense of isolation. ⁶³ Adolescents with CF, like their healthy peers, are at risk for engaging in cannabis use to fit in socially and alleviate the sense of isolation. It can be valuable, during routine psychosocial assessment, to ask adolescents about their social networks and perceptions of their social functioning, which can provide further insight into their risk of cannabis use or other psychosocial sequelae of CF.

Family instability and dysfunction impact adolescent social functioning. These familial factors have a substantial impact on both the initial decision to use cannabis and the progression to problematic use. ⁶⁴ CF affects the whole family, and family cohesion, expressiveness, and conflict have been shown to have an impact on the psychological health of adolescents with CF. ⁶⁵ When parents utilize coping skills and exhibit behaviors emphasizing family integration and support for self, the patient's FEV1 trend improves. ⁶⁶ Family cohesion is also positively correlated with higher individual QoL measures of physical functioning, energy, emotional functioning, body image, and nutrition. ⁶⁵ Family dynamics not only negatively affect CF outcomes but also may increase the risk of cannabis use, compounding the adverse effects on physiologic and psychological functioning. In addition, among medically vulnerable youth, cannabis use is associated with lower socioeconomic status. ¹⁶ The correlation of low socioeconomic status with poorer CF outcomes is already established. ⁶⁷ Therefore, the astute clinician should be aware of the potential elevated risk that complex family dynamics and lower socioeconomic status can have both on increased risk for cannabis use and on CF clinical outcomes.

4. POTENTIAL DRUG–DRUG INTERACTIONS BETWEEN CANNABIS AND DRUGS USED FOR CF

Clinicians should assess for potential drug interactions when adolescents with CF share current or anticipated use of cannabis, in any form (topical, oral, and so forth). The pharmacokinetics of inhaled cannabinoids may be similar to intravenous administration. Thus, possible drug interactions and other systemic effects from inhalation route should not be minimized, as this route also bypasses first‐pass metabolism. Oral formulations have variable absorption since THC and CBD are highly lipophilic and have lower oral bioavailability. ⁶⁸ As such, some adolescents may report a need to use more oral cannabis to achieve the same intended effects as compared with inhaled use. Although the inhaled route has clear deleterious effects on pulmonary diseases like CF, oral use is not without its risks. THC and CBD are primarily hepatically metabolized via cytochrome P450 isoenzymes. Although greater clinical context is needed to make informed decisions, clinicians should consider CYP P450 isoenzymes associated with a given medication and those which are affected by THC and CBD. ²⁸ , ⁶⁸ THC is primarily metabolized by CYP2C9, as well as CYP2C19 and CYP3A4, common with medications such as proton pump inhibitors and CFTR modulators. THC also inhibits CYP2D6, which metabolizes various antidepressants, and induces CYP1A2, which is responsible for metabolism of medications such as fluvoxamine, olanzapine, haloperidol, and theophylline. ²⁸ , ⁶⁸ CBD is primarily metabolized by CYP2C19, CYP3A4, CYP1A1, CYP1A2, CYP2C9, and CYP2. ⁶⁸ CBD is a potent inhibitor of CYP2C8, CYP2C9, and CYP3A4, where CYP3A4 inhibition may results in considerable interaction with CFTR modulators such as elexacaftor/tezacaftor/ivacaftor. ²⁸ Again, this highlights the need to routinely screen for cannabis use in a nonjudgmental manner to get as accurate a report as possible, and then to thoughtfully review together the potential risks, including drug‐drug interactions. ²⁸

5. POTENTIAL RISKS AND BENEFITS OF CANNABIS AND CANNABINOIDS IN PATIENTS WITH CF

Under the Controlled Substances Act of 1970, cannabis and cannabis products continue to be listed as Schedule I substances indicating no currently accepted medical use and a high potential for abuse. Thus far, we reviewed several potential risks associated with cannabis use in youth, especially in the context of CF. To successfully counsel adolescents with CF, clinicians should also be aware of the potential health benefits of cannabis.

Current evidence demonstrates that medical cannabis in children and adolescents has limited clinical indications outside of CINV and epilepsy. ⁶⁹ There is minimal data on cannabis products and their therapeutic application in CF beyond the general benefits associated with appetite stimulation and antiemetic properties. Weight loss is also a significant concern for youth with CF. In a study conducted in over 11 adolescents with CF with severe malnutrition who had failed conventional nutritional interventions, nutritional counseling, and high‐calorie supplements, administration of dronabinol 5 mg twice daily (starting dose was 2.5 mg once daily) resulted in an average weight gain of 7 lbs. over 3 months. ⁷⁰

Although there is growing evidence that cannabinoids may reduce chronic, noncancer pain in adults, ⁷¹ there is scant evidence in children and adolescents. There are currently no data for CF. A 2020 retrospective chart review reported potential benefits for children with life‐limiting conditions in palliative care, but none of the participants had CF. ⁷² The study was conducted over an 8‐year period on 21 children, with an average age of 8.3 years, who received medically prescribed oral cannabis extracts (high CBD [1:20 or 1:10], mixed [1:1], high THC [18:0 or 9:1]). ⁷² Four participants (19%) used cannabis extracts to treat chronic pain and three participants (14%) used it for nausea and vomiting with evidence of improved pain, nausea, or emesis and no observed adverse events. ⁷² However, in this study cannabis extracts were taken along with opioids or analgesics. ⁷²

6. CANNABIS USE IN YOUTH WITH CF: RISKS, BENEFITS, AND YOUTH'S PERSPECTIVE

Tables 1 and 2

Table 1.

Cannabis use in youth with CF: Risks

1. Decline in intelligence quotient 39

2. Impairment in judgment and engagement in risky behaviors 73

3. Thinning in prefrontal cortex 74

4. Addiction 75

5. Impairment in executive functioning (organization, planning, regulating emotions, self‐monitoring, and so forth) 76

6. Depressive disorder 77

7. Suicidal ideation, intent, or plan 45 , 57

8. Psychosis 59

9. Poor school performance 78

10. Dropping out of high school 79

11. Unemployment in adulthood 80

12. Impairment in driving and motor vehicle accidents 81

13. Dizziness 82

14. Hyperemesis syndrome 83

15. Potential drug interactions 28

16. Decrease in FEV1 24

17. Decrease in lung density 24

18. Pneumothorax 25

19. Hemoptysis 26

20. Decrease in LES pressure, gastric emptying, and slowed GI mobility 29

21. Reduced female fertility and male sperm count and function 32

22. Various effects on thyroid and adrenal function 32

Abbreviations: FEV1, forced expiratory volume in 1 s, GI, gastrointestinal; LES, lower esophageal sphincter.

Table 2.

Possible reasons for cannabis use from the perspective of youth

1. To fit in with friends 84

2. To promote weight gain 70

3. Appetite stimulant 17

4. Improvement in nausea and vomiting 17

5. Improvement with chronic pain in palliative care 72

6. To alleviate migraines 17

7. To alleviate arthritis 17

8. Dyspnea relief 17

9. Relaxation 17

10. Stress relief 84

11. Treating insomnia 17

12. Helping with depression 17

7. COMMUNICATION, SCREENING, AND INTERVENTION REGARDING CANNABIS USE IN CF

Substance use disorder screening should be included in CF care. According to a study conducted by Muirhead et al., ⁸⁵ 36.2% of CF providers (i.e., physicians, nurses, pharmacists, dietitians, social workers, and psychologists) “rarely” or “never” ask about cannabis use with their patients, and 34.8% of them do not feel prepared to answer patients′ questions about cannabis and CF. In speaking with adolescents, it is important to engage them directly, often without the caregiver present, to honor their autonomy and desire for individuation from their caregivers. It is important to understand their perceptions of their CF and cannabis use, how CF impacts functioning, and their beliefs about the potential benefits and harms of cannabis use. This dialogue should be conducted in a neutral, empathic, and nonjudgmental way to seek greater understanding and to partner with the adolescent to support them in achieving goals for their health and well‐being that align with that of their care team. This requires that the provider listen to the patient without a set agenda, reflect their understanding of the patient's experience, and facilitate open dialogue so that the adolescent feels safe and heard in their communications about cannabis use in the context of their CF care.

An example of a highly effective communication style to help providers partner with adolescents and families in communicating about cannabis, as well as health behavior change in general, is motivational interviewing. ⁸⁶ Motivational interviewing focuses on the patient being the agent for health behavior change and the provider facilitating that change through exploration of the patient's reasons for change. ⁸⁷ Clinicians evoke “change‐talk” in an engaging, empathic, and compassionate way by exploring discrepancies between the adolescents’ values and behaviors and responding with reflective listening to build up the patient's own case for change. As a result, the patient hears their reasons for change facilitated by the clinician through reflective listening and builds their own internal resolve to make behavior change in a way that feels feasible and meaningful to them ⁸⁸ (Table 3).

Table 3.

Open questions, affirmation, reflective listening, and summary reflections technique (adapted from Miller & Rollnick Motivational Interviewing, 3rd Edition, 2013) ⁸⁸

Open Question

“What brings you here today?”

“How has this problem affected your day‐to‐day life?”

“How do you hope your life might be different 5 years from now?”

“What would you say are the five things that you most value in life?”

“How do you hope I might be able to help you?”

Affirmation

“You really tried hard this week”

“Your intention was good even though it didn't turn out as you would like.”

“Look at this! You did a really good job of keeping records this week.”

“Thanks for coming in today, and even arriving early!”

Reflective Listening

“So, you feel …”

“You said you are also someone who …”

“You also said you might like to”

“You felt really …”

“You are really pleased that …”

Summary Reflections

“…Have I missed anything?”

“Let me pause and summarize what we have just talked about…”

Clinicians should never assume whether a patient is using or not using cannabis. Screening can be an effective, nonjudgmental way to routinely elicit information about cannabis use that can also be explored further in the clinical interview. The AAP encourages primary care clinicians to follow the screening, brief intervention, and referral to treatment model and recommends universal screening for substance use with adolescents. ⁸⁹ The National Institute on Drug Abuse (NIDA) has launched two brief online screening tools, Screening to Brief Intervention (S2BI) tool and Brief Screener for Tobacco, Alcohol and other Drugs (BSTAD) to assess to for substance use disorder risk among adolescents 12–17 years old. ⁹⁰ Clinicians can access S2BI via https://nida.nih.gov/ast/s2bi/#/ and to BSTAD via https://nida.nih.gov/ast/bstad/#/. Routine urine drug screening is not advised, as the relative utility and yield is low. Urine testing can be further stigmatizing for youth who are not prepared to discuss or disclose their cannabis use and can result in avoidance or disengagement from treatment.

Education directed toward the child should be developmentally appropriate and collaborative. Discussion should be provided at a time and in a setting where the child feels safe and can pay full attention to the conversation. Careful use of language is important to support dialogue, foster understanding, and enhance patient engagement. Using language that is simple, succinct, familiar, and nonthreatening can significantly contribute to improved interactions with the adolescent patient. Educational interventions should be geared to the literacy level, preferred language, level of education attainment, and baseline understanding of the caregiver. Equally important is empowering families with the necessary information and tools to have thoughtful, nonconfrontational conversations with their adolescent. It can be helpful to ask, in advance, the caregiver's understanding of the adolescent's CF status and its cares, as well as their understanding of their child's use of cannabis and its impacts on CF. This will then guide what content should be delivered and focused on. It can be helpful to then ask the adolescent and/or the family for permission to share information with them so they may serve as active, rather than passive, participants in receiving information. Checking for understanding after sharing communications can ensure that the adolescent and/or the family and the clinician have a shared understanding of the factors influencing the adolescent's presentation and care. Further resources for clinicians, families, and teachers are freely available and can be reviewed through NIDA (https://nida.nih.gov/research-topics/parents-educators).

The risk of developing substance use disorders is higher in children with attention deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder. ⁹¹ Therefore, comorbid psychiatric conditions that are associated with cannabis use could also be explored and addressed while discussing cannabis use and screening. The International Committee on Mental Health recommends annual screening of adolescents for anxiety and depression in all CF care centers globally using the 9‐question patient health questionnaire and 7‐item generalized anxiety disorder scale. ⁴⁹

For comorbid psychiatric disorders, such as anxiety and depression, or even subsyndromal symptoms such as poor self‐worth or maladaptive coping, cognitive behavior therapy (CBT) or interpersonal therapy should be recommended. ⁴⁹ Psychopharmacological interventions can also be considered. Selective serotonin reuptake inhibitors such as fluoxetine, escitalopram, or sertraline are usually used first line for anxiety and depression in youth. ⁹² When deciding whether to start a psychotropic medication in patients with CF, providers should take into account the patient's clinical status, severity of symptom presentation, past experience with psychotropic medications, family history, proposed medication delivery method, and patient/family preference.

There are currently no FDA‐approved drugs specifically for cannabis use disorder. N‐acetylcysteine (NAC), which affects glutamate modulation, has a presumed role in restoring the imbalanced cysteine‐glutamate exchange, thus reducing compulsive drug‐seeking behaviors. ⁹³ In an 8‐week double‐blind randomized placebo‐controlled trial, treatment‐seeking cannabis‐dependent adolescents (ages 15–21 years; N = 116) received NAC (1200 mg by mouth) or placebo twice daily, as well as a contingency management intervention and brief (8–10 min) weekly cessation counseling. Participants receiving NAC had more than twice the odds, compared with those receiving placebo, of having negative urine cannabinoid test results during treatment (OR = 2.4, 95% CI = 1.1–5.2), although secondary abstinence outcomes (confirmed 2‐ and 4‐week abstinence at end of treatment, time to first negative urine test, and change in percentage of days using cannabis during treatment) were not statistically significant. ⁹⁴ Oral administration of NAC is usually well tolerated with minimal adverse events. ⁹⁵ NAC is less commonly used in current CF management as a mucolytic, but further exploration of the use of NAC for dual therapy in youth with CF and concurrent cannabis use is needed. Additionally, FDA‐regulated and approved oral formulations (e.g., tablets) are needed to optimize accuracy and safety of use, currently, they consider supplements and thus are not required to meet the same standard for data supporting efficacy and safety as approved prescribed or over‐the‐counter medications.

8. CONCLUSION

Biological, psychological, and social factors and their interplay affect the evaluation and management of cannabis use in adolescents with CF. All health professionals who take care of adolescents with CF, including primary care and mental health providers and staff, should be aware of the factors impacting cannabis use in CF and ways to ameliorate the potential risks cannabis can have on CF. Given limited evidence regarding the benefits of cannabis and the significant risks associated with cannabis use, clinicians have the responsibility to identify risk of cannabis use early, counsel patients about the risks of cannabis, provide a safe space for ongoing conversations about cannabis use in the context of CF care, and deliver evidence‐based interventions to manage cannabis use among adolescents with comorbid CF.

AUTHOR CONTRIBUTIONS

H. Yavuz Ince: Conceptualization; writing – original draft; methodology; writing – review & editing; project administration. Hanna Phan: Writing – original draft; methodology; writing – review & editing; conceptualization. Samya Z Nasr: Supervision; writing – review & editing. Jessica M. Pierce: Supervision; writing – review & editing. Nasuh Malas: Writing – review & editing; supervision; conceptualization; writing – original draft.

Ince HY, Phan H, Nasr SZ, Pierce JM, Malas N. Clearing up the smoke: physical and mental health considerations regarding cannabis use in adolescents with cystic fibrosis. Pediatric Pulmonology. 2023;58:398‐407. 10.1002/ppul.26241

DATA AVAILABILITY STATEMENT

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.