Use of Cannabis-Based Medical Products for Pediatric Health Conditions: A Systematic Review of the Recent Literature
Cannabis-Based Medical Products and Pediatric Health Conditions
Health Economics and Outcomes Research Division, Leafwell, Miami, FL, USA
Department of Medicine, Duke University, Durham, NC, USA
Correspondence to: Mitchell L. Doucette, mdoucette@leafwell.comAbstract
Introduction
Cannabis policy is rapidly changing in the USA and across the globe, with 24 states legalizing cannabis for adult use and 38 states making medical cannabis available for those with qualified conditions. Building on prior evidence, we reviewed the recently published literature (from the past 5 years) focused on the treatment effects of naturally derived medical cannabis products within the pediatric population.
Methods
We conducted a systematic literature review of three electronic databases using MeSH terms and free-text. A study was eligible for inclusion if it investigated the efficacy of medical cannabis for any condition, it was published in 2019 or later, and the mean age of participants was under 21. We excluded studies that tested the effect of pharmaceutical cannabis-derived drug products.
Results
We identified a total of 10 studies that met our inclusion/exclusion criteria. Of the 10, 2 utilized a double-arm randomized control trial (RCT) design, 3 used a single-arm trial design, and the remaining were observational studies, a case series, or a qualitative design. Aside from autism spectrum disorder (ASD) (n = 4), studies focused on cancer, treatment-resistant epilepsy, and Sturge-Weber syndrome (SWS). Four of the five single- or double-arm trials used a CBD:THC compound in a specific ratio as treatment. Both RCTs found significant improvement in ASD-related validated measures. Other studies found general improvements in validated measures of efficacy for SWS and epilepsy. Minimal adverse events were reported.
Conclusion
In the pediatric population, emerging evidence, combined with existing literature, suggests medical cannabis may be beneficial for quality-of-life symptoms related to specific conditions, like cancer, ASD, treatment-resistant epilepsy, and SWS. More clinical trial data are necessary to establish medical cannabis as an addition to established medical guidelines.
Introduction
Cannabis policy in the USA and the world is rapidly changing [1]. Access to medical cannabis has increased and so have patients’ and families’ willingness to use cannabis as a medical treatment [2–8]. In recent years, research has increasingly focused on evaluating the relationship between medical cannabis and various conditions in the pediatric population, such as epilepsy [2, 9–12], palliative care [13, 14], autism spectrum disorder (ASD) [15–20], pain management [21], the gastrointestinal tract [22], and other conditions.
Cannabis, also known as marijuana, is a complex plant with over 100 compounds [23, 24]. Cannabis is a naturally occurring plant processed into various products for consumption. The plant contains many substances including terpenes that affect smell, flavonoids that affect flavor, and over 100 different phytocannabinoids [24]. There is no standardized form of cannabis, and each plant contains variable amounts of these substances. Medical cannabis can be administered through various methods, including smoking, vaporizing, oral tinctures or solutions, edibles, or topical applications such as patches or lotions. We refer to these as cannabis-based medical products.
Phytocannabinoids, or plant-derived cannabinoids, include delta-9 tetrahydrocannabinol (THC), known as the psychoactive component, and cannabidiol (CBD). These are the most widely used and studied components of cannabis. These elements interact with endocannabinoids and cannabinoid receptors distributed across the brain and spinal cord [25]. The receptors, part of the endocannabinoid system, play a regulatory role in various physiological processes. These include immune and cardiovascular functions, development of the nervous system, pain, inflammation, appetite regulation, among other functions [23–25].
Cannabis-derived drug products are also used for medical purposes. These products are either synthetic or plant-derived and are manufactured to treat various medical conditions. Major drug products include synthetic delta-9 THC products like dronabinol (brand names Marinol and Syndros) and nabilone (brand name Cesamet). Plant-derived products include nabiximols (brand name Sativex) and CBD (brand name Epidiolex), a CBD-based product.
In the USA, 38 states and the District of Columbia have legalized cannabis for both adult and/or medical use [26]. All states where cannabis is medically available have developed a medical cannabis program administered at the state level. In most states with operational medical cannabis programs, patients are required to obtain a medical card allowing them to purchase cannabis-based medical products. Medical cannabis use by a minor is permitted but necessitates consent from a legal guardian and certification from a physician.1 Notably, registering with a medical cannabis program does not entitle patients to a prescription of FDA-approved drug products; only cannabis-based medical products are sold at dispensaries. The number of registered medical cannabis patients in the USA, including those under the age of 18, has grown in the past decade [27–31].
While the past decade has seen increases in state-level medical cannabis program registrations within the USA [29, 30], other countries with analogous medical programs have not experienced the same growth. In the UK, although medical cannabis is legal, patients encounter significant challenges in accessing products [32, 33], and thus, enrollment and usage have remained low. Canada, which has one of the oldest medical cannabis programs (beginning in 2001), is believed to have experienced increases in self-medication associated with the 2018 legalization of cannabis [34]. Challenges related to access and program complexity likely hinder registration in the Canadian medical cannabis program [34], and limited data reporting restricts research on pediatric medical cannabis use [7].
There have been two literature reviews published since 2017 regarding the overall efficacy and safety of medical cannabis in the pediatric population. Both of these reviews include cannabis-based medical products and cannabis-derived drug products as treatment arms. Wong and Wilens [35] published a systematic review of medical cannabis in children and adolescents. The authors did not focus on a specific disease state and identified 22 studies, of which five were randomized controlled trials. They found that the beneficial evidence was greatest for chemotherapy-induced nausea and vomiting, with some evidence also suggesting a benefit for pediatric patients with epilepsy. The authors noted insufficient evidence for muscle spasticity, neuropathic pain, post-traumatic stress disorder, and Tourette’s syndrome [35]. Unsurprisingly, the majority of studies lacked control groups and were limited by small sample sizes.
Pawliuk and colleagues [3] published a scoping review examining the effect of medical cannabis in the pediatric population, citing the fast-evolving literature and building on Wong and Wilens’ [35] work. The authors used multiple databases and the gray literature to identify articles that met their inclusion criteria, finding 36 studies. Of the 36 studies, 32 (88%) focused on accessing the efficacy or safety of medical cannabis in treatment-resistant (TR) epilepsy. The remaining 12% (n = 4) focused on various conditions, including studies related to pediatric cancer. Although the study’s primary finding indicated a lack of evidence supporting the efficacy and safety of medical cannabis in the pediatric population, they did find a strong signal that medicinal cannabis provided benefits for children with drug-resistant epilepsy and those with Dravet and Lennox-Gastaut syndromes [3]. However, they noted potential safety concerns, with treatment discontinuation due to adverse events ranging from less than 1–20%.
While Wong and Wilens [35] and Pawliuk and colleagues [3] provided timely reviews of medical cannabis treatment effects within the pediatric population, the former’s literature review considered published articles until May 2017, while the latter’s review considered articles published prior to 2019. In the intervening years, many more states have authorized or legalized cannabis, and additional literature has been published regarding the efficacy of medical cannabis in the pediatric population.
Thus, we aimed to contribute to this body of literature by reviewing recent studies on the efficacy and safety of cannabis-based medical products in the pediatric population. In this review, we focused on cannabis-based medical products, excluding cannabis-derived drug products like Epidiolex and Sativex. We made this decision because an increasing number of medical cannabis patients are using non-FDA-approved flower-based products for their conditions [29, 36]. It is more probable, especially in the USA and Canada, that a pediatric patient uses cannabis-based medical products purchased at a dispensary due to the product’s ubiquity rather than a government-approved drug product. Therefore, reviewing the current literature on the effects of cannabis-based medical products on pediatric patients is essential.
Methods
Search Sources and Strategies
We conducted a systematic literature review following methods recommended by the Cochrane Collaboration. We documented our process and results in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (see Fig. 1). Table 1 details the databases, search terms, and results related to our literature searches. We used free-text terms and explored MeSH headings for the topics of medical cannabis, medical marijuana, synthetic cannabinoids, and pediatrics. We first developed our search strategy in PubMed and adapted our search terms for the following databases: EBSCO – Academic Search Ultimate and Web of Science. We restricted our searches to include only articles written in English and excluded studies published before 2019. We included studies published through September 30, 2023, the date on which all final searchers were completed. We retrieved additional studies based on hand searches of reference sections from relevant articles.
| Database | Search term | Articles found, n |
|---|---|---|
| PubMed | (“Pediatrics” [Mesh]) AND (“Medical Marijuana” [Mesh]) | 4 |
| PubMed | (“Pediatrics” [Mesh]) AND Medical Marijuana | 23 |
| PubMed | (“Pediatrics” [Mesh]) AND Medical Cannabis | 27 |
| PubMed | (“Pediatrics” [Mesh]) AND (“Cannabinoids” [Mesh]) | 20 |
| Academic Search Complete | (DE “MEDICAL marijuana”) AND “pediatrics” AND therapeutics | 39 |
| Web of Science | “Medical Cannabis” (All Fields) and “Pediatrics” (All Fields) | 16 |
| Web of Science | “Medical Marijuana” (All Fields) and “Pediatrics” (All Fields) | 29 |
| Web of Science | “Cannabinoids” (All Fields) and “Pediatrics” (All Fields) | 47 |
| Additional Citation Review | 6 | |
| Total | 211 |
Study Selection and Extraction
We established the following inclusion criteria for this literature review. Included articles needed to involve the use of cannabis or a synthetic cannabinoid as a treatment option within a pediatric population. Articles were not limited by the type of medical condition being treated, nor were they limited by the methodology used. Additionally, we included review articles and commentaries. We excluded articles that focused on cannabis-derived drug products, such as Epidiolex and Sativex, and synthetic cannabis-related drug products, such as Marinol, Syndros, and Cesamet. We included studies that used phytocannabinoids, either THC or CBD. We excluded any articles in which the mean age of participants was 21 years or older. We included studies published within the past 5 years (2019 and later).
We reviewed all titles and abstracts, extracting the full texts of potentially relevant articles. M.L.D. and D.H. independently reviewed each paper to determine if it met the predefined inclusion criteria. We excluded duplicate publications. M.L.D. and D.H. met to resolve disagreements and finalized the list of publications included in the review (Fig. 1). From this final list, M.L.D. and D.H. independently extracted intervention details, outcome measures, and other study characteristics, documenting them in a data extraction spreadsheet.
We provided several tables in the results section. First, we reported characteristics for all included studies, including study authors, year, sample characteristics (such as population and mean age), presence of a control group, cannabis dosage, and administration routes. Second, we presented the primary and secondary outcomes, notable findings, and adverse events reported for the placebo-controlled and single-arm trials. We chose to provide this information only for placebo-controlled and single-arm trials as these designs incorporate temporality, making their reported outcomes and adverse events more robust from an inference perspective.
Results
From the 211 potential articles identified, 56 were excluded as duplicates, 111 were excluded based on title and/or abstract, and 3 were exlcuded as they were conference material (presentation/poster etc.) (Fig. 1). Among the remaining articles, 1 was excluded for not focusing on the pediatric population, 11 for not evaluating effects, and 19 for being commentaries, reviews, or a case studies (where n = 1). We included 10 full-text articles that met inclusion criteria for this analysis. Among the 10 studies, 1 was qualitative in nature. The study by Ananth and colleagues [37] was included as it uniquely captured qualitative effects of medical cannabis among pediatric cancer patients and their parents.
Characteristics of Included Studies
We examined various characteristics of the 10 included articles. All studies were published in 2019 or later. The types of studies included were three single-arm clinical trials [16, 17, 36], three observational studies [38–40], 1 case series [13], one qualitative interview study [37], and two randomized controlled trials (RCTs) [15, 41]. The studies represented a diverse range of populations, with 2 studies from the USA, 3 from Israel, and 1 each from Italy, Brazil, Canada, and Switzerland (Table 2). Mean age was reported in 7 of the 10 articles, ranging from 7.7 to 13.4 years. The median age was provided in two studies: 11 and 12 years old. The largest study had 188 participants [17], and the smallest had 6 participants [13]. Overall, the average study population size was 64.4.
| First author, published year | Article type | Sample, n | Country of origin | Primary type of cannabis | Control group (y/n) | Products used | Administration route | Mean age (median), years | Conditions |
|---|---|---|---|---|---|---|---|---|---|
| Ananth [37] (2021) | 1:1 interview | 15 | USA | n/a | n/a | n/a | n/a | n/a | Cancer |
| Aran [41] (2021) | RCTb | 150 | Israel | CBD:THC | Yes | 20:1 CBD:THC | Oral solution | 11.8 | ASD |
| Barchel [16] (2019) | Single-arm trial | 53 | Israel | CBD:THC | No | 16 mg/kg CBD, 0.8 mg/kg (recommended) | Oral drops of oil | (11) | ASD |
| Bar-Lev Schleider [17] (2019) | Single-arm trial | 188 | Israel | CBD:THC | No | 30% CBD, 1.5% THC, three times a day | Oil applied sublingually and dried flower | 12.9 | ASD |
| Divisic [13] (2021) | Case series | 6 | Italy | THC | No | Average 0.37 (mg/kg/day) effective dose | Oral solution | 12 | Palliative care |
| Erridge [38] (2023) | Observational | 35 | UK | CBD isolate, CBD broad spectrum, CBD:THC | No | Varied dosage | Varied usage | 9.71 | TR epilepsy |
| Silva [15] (2022) | RCT | 60 | Brazil | CBD:THC | Yes | 9:1 CBD:THC with 0.5% mg/mL THC | Oral solution | 7.7 | ASD |
| Smegal [36] (2023) | Single-arm trial | 10 | USA | CBD | No | 5–20 mg/kg/day | Oral solution | 13.4a | SWS |
| Vaillancourt [39] (2020) | Observational | 37 | Canada | CBD:THC | No | Varied dosage | Varied usage | 11.9 | All |
| Zürcher [40] (2022) | Observational | 90 | Switzerland | CBD, CBD:THC, THC | No | Varied dosage | Varied usage | 11.5 | All |
The most frequently studied condition was ASD, with 4 studies examining the therapeutic effects of medical cannabis on ASD. Two observational studies did not focus on any specific type of illness and documented the effects of medical cannabis across a range of outcomes; one observational study examined the therapeutic effects on TR epilepsy. The case series examined the use of medical cannabis in the palliative care. Other conditions included pediatric cancer, TR epilepsy, and Sturge-Weber syndrome.
Treatment Dosage and Administration Routes
The primary treatment type used in the studies was some ratio compound of CBD:THC. Among the five single- or two-arm trials identified, four [15–17, 41] used a CBD:THC product and one used CBD only [36]. Aran and colleagues [41] used a 20:1 CBD:THC oral treatment, given sublingually whenever possible. Notably, the study was a 28-week cross-over design with a 4-week washout period and tested both a whole-plant extract and a purified extract, both with the same 20:1 ratio. Barchel and colleagues [16] used a 16 mg/kg: 0.8 mg/kg ratio of CBD:THC oral solution as treatment. Bar-Lev Schleider and colleagues [17] used a 30% CBD to 1.5% THC oil, applied under the tongue and dried flower. Silva and colleagues [15] used a 9:1 CBD:THC oral solution where THC was restricted to 0.5 mg/mL as treatment. Smegal and colleagues [36] used an oral solution that escalated over the study period, beginning at 5 mg/kg/day CBD and increasing up to 20 mg/kg/day as tolerated. Fifty percent of the study participants reached 20 mg/kg/day. Divisic and colleagues’ study [13], which was a 6-person case series, was the only study to test THC only. In this study, the average dosage was 0.37 mg/kg/day, administered in oil.
The observational studies documented various types of medical cannabis treatments used during their study periods. As these studies were not controlled trials, the dosage and treatment types varied. Erridge and colleagues [38] used data from the UK Medical Cannabis Registry to identify those with drug-resistant epilepsy. Of the 35 pediatric cases, 19 received a CBD isolate, and 17 received a broad-spectrum CBD or a CBD combination therapy (not mutually exclusive). In Vaillancourt and colleagues [39] conducted a retrospective chart review study using data from the Children’s Hospital of Eastern Ontario from 2014 to 2017. The authors found that treatment type information was not always available, but for cases with data, a CBD:THC ratio product was used in various forms. Zürcher and colleagues [40] analyzed medical data from one pharmacy in Switzerland (one of only two pharmacies eligible to provide medical cannabis in the country at the time). The study found CBD, CBD:THC, and THC treatments with varying dosages and administration routes.
Findings and Adverse Events
Table 3 provides primary and secondary reported outcomes (if noted), along with notable findings and information on adverse events from the five included trials. Two trials (Aran, 2021, and Silva, 2022) used a placebo-controlled, double-blinded RCT study design. Both studies evaluated the impact of a CBD:THC medical cannabis treatment on ASD, with one in Israel and one in Brazil.
| First author, published year | Primary reported outcomes | Secondary outcomes | Notable primary findings | Adverse events reported |
|---|---|---|---|---|
| Aran [41] (2021) | Home Situation Questions-ASD & Clinical Global Impression-Improvement Scale (CGI-I) | ADOS-2, VABS, CARS-2, APSI | CGI-I improved 49% (p value = 0.005), no change in HSQ-ASD | Somnolence (28%), decreased appetite (25%); placebo group reported 8% and 15%, respectively |
| Barchel [16] (2019) | Number of self-injury and rage attacks, sleep problems, anxietya | Overall, 74.5% of patients reported improvement in symptoms, 11% reported no change, and 3.9% reported worsening | Adverse events were mild and included somnolence and change in appetite | |
| Bar-Lev Schleider [17] (2019) | Quality-of-lifec | Rage attacks, agitation, sleep problems, speech impairment, cognitive impairment, anxiety, incontinence, seizures, limited mobility, constipation, tics, digestion problems, increased appetite, lack of appetite, depression | There was a statistically significant increase in the percent of patients who reported good life quality at baseline compared to 6 months (31.3% compared to 66.8%, p value <0.001) | Of the sample, 25.2% reported at least on side effect included restlessness (6.6%), sleepiness (3.2%), psychoactive effects (3.2%) increase appetite (3.2%), digestion problems (3.2%), dry mouth (2.2%), and lack of appetite (2.2%) |
| Silva [15] (2022) | Aggressiveness, psychomotor agitation, concentration, meals, sleep, social interaction, verbal language, anxiety, repetitive and stereotyped movements, ATEC & CARS-2b | Study found improvements in all primary outcomes. Secondary outcomes did not show statistically significant changes | Of the treatment group, 9.7% of the patients reported adverse events including dizziness, insomnia, colic, and weight gain | |
| Smegal [36] (2023) | SWS NeuroScore, quality-of-life, anxiety, emotional regulation, migraines, bimanual ability | All subjects showed improvements from SWS NeuroScores from baseline (p = 0.002). Seven of nine participants reported improvements to quality-of-life scores | Seven out of ten subjects reported adverse events including dizziness, headache, and decreased appetite |
Aran and colleagues [41] found that 49% of respondents in the whole-plant extract arm reported being either “much improved” or “very much improved” on the Clinical Global Impression-Improvement Scale (CGI-I), a primary outcome measure (p value = 0.005). The CGI-I is a validated measure assessing a patient’s global function before and after the initiation of medication [42, 43]. They did not find any significant change in their other primary outcome, scores from the Home Situation Questionnaire-Autism Spectrum Disorder (HSQ-ASD) [44]. As this study was a 28-week cross-over trial with a 4-week washout period, the authors only evaluated the first 12-week period due to potential treatment order effects. The adverse events in this study were relatively mild, with 28% and 25% reporting somnolence and decreased appetite, respectively, while 8% and 15% of the placebo group also reported somnolence and decreased appetite.
Silva and colleagues [15] measured the impact of medical cannabis over a 12-week period. The study team used semi-structured interviews to assess a variety of ASD-related symptoms. They also utilized the Autism Treatment Evaluation Checklist (ATEC), a diagnostic tool for evaluating treatment effectiveness in autistic patients [45], and the Childhood Autism Rating Scale (CARS), a rating scale used in autism detection and diagnosis in children [46]. The authors found that psychomotor agitation, meals, social interaction, and anxiety showed significantly lower scores in the treatment group compared to the placebo group (all p values <0.05). However, they did not find any significant changes to the ATEC subscales or the CARS scale. The number of adverse events was similar in the treatment group (n = 4) compared to the control group (n = 5), with only 3 subjects reporting 4 symptoms in the treatment group.
Other single-arm trials found general symptom improvements related to medical cannabis treatment with relatively mild adverse events. Barchel and colleagues [16] found general improvement in patient symptoms in their sample of 53 pediatric patients, with mild adverse events including somnolence and changes in appetite. Bar-Lev Schleider and colleagues [17] found statistically significant increases in quality-of-life scores compared with baseline to the 6-month follow-up. However, in this study of 188 participants, 25% reported at least one adverse event, with the most common being restlessness (6.6%). Smegal and colleagues [36], in their study of 10 participants, found significant improvements in multiple outcomes, including patient-reported quality of life. The authors reported that the treatment was well tolerated, with mild to moderate side effects in 6 out of 10 patients. The three observational studies identified in this review also found results similar to the placebo-controlled or single-arm trials, indicating that medical cannabis produced measurable effects with relatively modest adverse events.
Results from the one qualitative study included, while not generalizable to the broader population, provide notable contextual information related to the use of medical cannabis in the pediatric population. Ananth and colleagues [37] conducted semi-structured interviews with 15 pediatric cancer patients and their parent(s) at a comprehensive cancer center in the USA. Findings of the study noted that parents were generally receptive toward using medical cannabis, often mentioning relief from nausea, anorexia, and pain related to chemotherapy or supportive care. Parents also expressed concerns about potential negative effects and the lack of comprehensive scientific literature, basing their decision to allow medical cannabis use on weighing both the benefits and risks A lack of trust in the medical system was evident as only a few participants consulted their oncologist about medical cannabis use, instead turning to other sources of information (e.g., internet, friends, peers).
Discussion
This systematic literature review identified 10 studies that evaluated the therapeutic efficacy and safety of medical cannabis in the pediatric population from 2019 onward. Specifically, we examined studies that focused on the effects of cannabis-based products and found generally positive effects across various disease states and populations. In total, the combined studies evaluated the effects of medical cannabis treatment in 644 children and adolescents. The studies included participants with mean ages ranging from 7.7 to 13.4 years across seven countries, utilizing various treatment products, dosages, and administration routes. The study methods were heterogeneous, with two placebo-controlled, double-blinded RCTs, three single-arm trials, three observational studies, one qualitative study, and one case series. Both RCTs reported notable improvements in ASD-related measures with mild to moderate adverse events.
Results from our review suggest that medical cannabis may be an emerging treatment complement when addressing ASD among the pediatric population. The studies with the strongest design (e.g., randomized controlled trials) both focused on ASD and found improvement in some primary outcomes related to medical cannabis treatment [15, 41]. Additionally, these two studies found no significant differences in other outcomes, suggesting that medical cannabis treatment did not worsen ASD-related health outcomes. In one single-arm trial by Barchel and colleagues [16], a small proportion of the ASD sample (3.9%) experienced worsening primary outcomes, while 74.5% reported improvement. In studies focused on ASD, the percentage of participants reporting adverse events ranged from 9.7% to 28%. Taken together, the strength of study designs, consistent findings, and relatively low adverse effect rates suggest that medical cannabis may contribute positively to patient treatment. However, there is large phenotypic variation across pediatric-aged ASD patients. Newer research ought to investigate whether there are specific ASD subtypes for whom medical cannabis may be more effective or less safe and which routes of administration are most effective.
Prior reviews of medical cannabis treatment in the pediatric population also found similar positive effects. Similar to the findings here, prior reviews noted that most published studies lacked a control group, were limited by small sample sizes, and varied in treatment dosages [3, 35]. Adverse events, such as somnolence and changes in appetite, were similarly frequent across previous reviews. Both prior reviews found the strongest evidence supporting medical cannabis use for conditions such as chemotherapy-induced nausea and vomiting. The current manuscript found the strongest evidence to be for ASD outcomes. The discrepancy in health condition findings may stem from this manuscript’s exclusive focus on cannabis-based products. In contrast, previous reviews included cannabis-derived products, such as Epidiolex, which is specifically indicated for treating epilepsy. This is likely the primary reason for the discrepancy in the number of included studies between the 10 articles reviewed here and the 21 articles in Wong and Wilens [35] and 36 in Pawliuk and colleagues [3].
The products used in these studies typically contained a high concentration of CBD and a low concentration of THC. This is notable because individuals using medical cannabis through state-run programs in the USA or Canada may not have consistent access to similar high-CBD, low-THC products. Although the types of products available to medical cannabis patients vary by state, there is a need for physicians to educate patients on the current literature.
The evidence presented here indicates a need for further research to fully comprehend the impact of medical cannabis treatment initiation on the pediatric population. Currently, conducting double-blind, placebo-controlled RCT studies with cannabis-based products (i.e., non-FDA-approved cannabis-derived products) faces multiple challenges. First, organizations encounter limitations due to the current FDA classification of cannabis as a Schedule I drug. Conducting studies with whole-plant cannabis or related products requires obtaining materials from the National Institute on Drug Abuse, with oversight from the Drug Enforcement Administration [47, 48]. Second, the market for medical cannabis producers is characterized by fragmentation and a lack of federal regulation. Unlike pharmaceutical companies, which are legally required to track adverse event data for their products, medical cannabis producers have no such obligation. Furthermore, there are little financial incentives for growers and retailers to conduct evidence-based research on the medical value of the products they cultivate and sell.
Other aspects of medical cannabis treatment, such as long-term use and drug-drug interactions, should also be considered. Little is known about the long-term safety profile of medical cannabis formulations in the general population and specifically in the pediatric population [49]. There is a potential for adverse neurodevelopmental effects with long-term use; therefore, the prescribing physician must consider each child’s condition, prognosis, and risk profile [49]. Moreover, as THC and CBD are metabolized by CYP enzymes, there is a need for physicians to understand potential drug-drug interactions when prescribing medical cannabis [50]. In the USA, anxiety is one of the leading pediatric medical conditions treated with medical cannabis [51]. THC or CBD use may slow down the metabolism of antidepressants, resulting in adverse events.
One potential path forward for evaluating the therapeutic effects of flower-based medical cannabis is the use of real-world evidence [52, 53]. In lieu of regulated medical product markets, real-world evidence could help answer questions about effectiveness and safety [54]. Future research ought to use large-scale sources of real-world data to address these questions.
Limitations
This literature review on medical cannabis use in children and adolescents has limitations. The sample sizes in these studies were small to moderately sized, with most containing less than 100 participants. Notably, most studies lacked a control group or were observational studies. Some studies lacked long-term follow-up for potential adverse events. Furthermore, the products used in the included studies may not reflect the cannabis that is currently available on the retail medical cannabis market.
Conclusion
Statement of Ethics
This research reviews publicly available manuscripts and does not involve human subjects.
Conflict of Interest Statement
M.L.D., D.H., E.F., and D.L.M. are employees of Leafwell and hold stock or stock options in Leafwell. Leafwell is a Telehealth company that connects potential medical cannabis patients to physicians in a friendly PC model and does not produce or sell cannabis products. No grant funding was used to sponsor this research. D.J.C. was a paid research consultant for Leafwell until November 2023.
Funding Sources
This research was not supported by funding.
Data Availability Statement
All data/manuscripts analyzed for this literature review are publicly available.