CBD Oil Dosing Pediatrics

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Purpose: There is uncertainty regarding the appropriate dose of Cannabidiol (CBD) for childhood epilepsy. We present the preliminary data of seven participants from the Cannabidiol in Children with Refractory Epileptic Encephalopathy (CARE-E) study. Methods: The study is an open-label, prospective, dose-escalation trial. Participants received escalating doses of a Cannabis Herbal Extract (CHE) preparation of 1:20 9-tetrahydrocannabinol (THC):CBD up to 10-12 mg CBD/kg/day. Seizure frequency was monitored in daily logs, participants underwent regular electroencephalograms and parents filled out modified Quality of Life in Childhood Epilepsy (QOLCE) and Side Effect rating scale questionnaires. Steady-state trough levels (Css Min) of selected cannabinoids were quantified. Results: All seven participants tolerated the CHE up to 10-12 mg CBD/kg/day and had improvements in seizure frequency and QOLCE scores. CSS,Min plasma levels for CBD, THC, and cannabichromene (CBC) showed dose-independent pharmacokinetics in all but one participant. CSS,Min CBD levels associated with a greater than 50% reduction in seizures and seizure freedom were lower than those reported previously with purified CBD. In most patients, CSS,Min levels of THC remained lower than what would be expected to cause intoxication. Conclusion: The preliminary data suggest an initial CBD target dose of 5-6 mg/kg/day when a 1:20 THC:CBD CHE is used. Possible nonlinear pharmacokinetics of CBD and CBC needs investigation. The reduction in seizure frequency seen suggests improved seizure control when a whole plant CHE is used. Plasma THC levels suggest a low risk of THC intoxication when a 1:20 THC:CBD CHE is used in doses up to 12 mg/kg CBD/kg/day. We outline whether or not it's safe to use CBD oil with your youngsters, as well as outline our favorite CBD oil for kids brands in this comprehensive guide. Benefits of CBD use for children include the treatment of epilepsy, anxiety, and high blood pressure. But what about the dosage? Let's discuss it here.

Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study

Richard J. Huntsman 1,2 * , Richard Tang-Wai 1,3 , Jane Alcorn 1,4 , Stephanie Vuong 4 , Bryan Acton 1,5 , Scott Corley 1,6 , Robert Laprairie 1,4 , Andrew W. Lyon 1,7 , Simona Meier 6 , Darrell D. Mousseau 1,8 , Doris Newmeyer 2 , Erin Prosser-Loose 2 , Blair Seifert 1,9 , Jose Tellez-Zenteno 1,10 , Linda Huh 11 , Edward Leung 12 and Philippe Major 13

  • 1 Cannabinoid Research Initiative of Saskatchewan, University of Saskatchewan, Saskatoon, SK, Canada
  • 2 Department of Pediatrics, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada
  • 3 Division of Child Neurology, Department of Pediatrics, Loma Linda University, San Bernardino, CA, United States
  • 4 College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada
  • 5 Saskatchewan Health Authority and Department of Psychology, University of Saskatchewan, Royal University Hospital, Saskatoon, SK, Canada
  • 6 Clinical Trial Support Unit, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada
  • 7 Department of Pathology and Laboratory Medicine, Royal University Hospital, Saskatchewan Health Authority, Saskatoon, SK, Canada
  • 8 Cell Signalling Laboratory, Departments of Psychiatry and Physiology, University of Saskatchewan, Saskatoon, SK, Canada
  • 9 Department of Pharmaceutical Services, Royal University Hospital, Saskatchewan Health Authority, Saskatoon, SK, Canada
  • 10 Division of Neurology, Department of Medicine, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada
  • 11 Division of Pediatric Neurology, Department of Pediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, BC, Canada
  • 12 Division of Pediatric Neurology, Department of Pediatrics, Children’s Hospital, University of Manitoba, Winnipeg, MB, Canada
  • 13 Service de Neurologie Pédiatrique, Département de Neurosciences, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, QC, Canada

Purpose: There is uncertainty regarding the appropriate dose of Cannabidiol (CBD) for childhood epilepsy. We present the preliminary data of seven participants from the Cannabidiol in Children with Refractory Epileptic Encephalopathy (CARE-E) study.

Methods: The study is an open-label, prospective, dose-escalation trial. Participants received escalating doses of a Cannabis Herbal Extract (CHE) preparation of 1:20 Δ 9 -tetrahydrocannabinol (THC): CBD up to 10–12 mg CBD/kg/day. Seizure frequency was monitored in daily logs, participants underwent regular electroencephalograms, and parents filled out modified Quality of Life in Childhood Epilepsy (QOLCE) and Side Effect rating scale questionnaires. Steady-state trough levels (Css, Min) of selected cannabinoids were quantified.

Results: All seven participants tolerated the CHE up to 10–12 mg CBD/kg/day and had improvements in seizure frequency and QOLCE scores. CSS, Min plasma levels for CBD, THC, and cannabichromene (CBC) showed dose-independent pharmacokinetics in all but one participant. CSS, Min CBD levels associated with a >50% reduction in seizures and seizure freedom were lower than those reported previously with purified CBD. In most patients, CSS, Min levels of THC remained lower than what would be expected to cause intoxication.

Conclusion: The preliminary data suggest an initial CBD target dose of 5–6 mg/kg/day when a 1:20 THC:CBD CHE is used. Possible non-linear pharmacokinetics of CBD and CBC needs investigation. The reduction in seizure frequency seen suggests improved seizure control when a whole plant CHE is used. Plasma THC levels suggest a low risk of THC intoxication when a 1:20 THC:CBD CHE is used in doses up to 12 mg/kg CBD/kg/day.

Introduction

Recent trials with pharmaceutical grade cannabidiol (CBD) or CBD-enriched Cannabis Herbal Extract (CHE) support CBD’s ability to reduce seizure frequency in children with intractable epilepsy, including those with epileptic encephalopathy (1–5). Yet, there are significant knowledge gaps regarding the use of CBD and other cannabinoids in children, including the pharmacokinetics (PK), pharmacogenetics, and dose-concentration-effect relationships for these compounds (6). The resultant inability to provide evidence-based dosing and therapeutic monitoring of Cannabis-based products in children, combined with concerns regarding potential intoxicant effects of Δ 9 -tetrahydrocannabinol (THC), leads to a reluctance by many physicians to authorize CHE to these patients.

The age-related developmental changes that influence drug PK and pharmacodynamics (PD) complicate the development of appropriate dosing regimens for pediatric age groups (6). Without an understanding of dose concentration-effect relationship, a dosing regimen is largely empirical and/or anecdotal, and fraught with potential safety concerns.

CARE-E is a multi-center, phase 1, open-label, dosage escalation study using a Health Canada approved and Good Manufacturing Practices certified 1:20 THC:CBD CHE as adjunct therapy to treat children with epileptic encephalopathy. The primary objectives were to assess the safety and efficacy of CBD-enriched CHE, whereas secondary objectives included an analysis of trough steady state (CSS, Min) levels of CBD, THC, and cannabichromene (CBC); as well as an assessment of the correlation between cannabinoid levels and therapeutic effect. CBC levels were measured as the CHE used in this study contained 4% CBC by volume. We present results for seven CARE-E participants recruited at the University of Saskatchewan site.

Methods

Trial Design

The study is a phase 1, open-label, dosage-escalation clinical trial in which participants receive a 1:20 THC:CBD CHE in twice daily dosing. Upon enrollment (Visit 1) participants continue their current anticonvulsant regimen and baseline seizure frequency is determined for 1 month. At Visit 2 CHE dosing is initiated with a CBD dose of 2–3 mg/kg/day. At Visits 3–5 the CHE is increased at 1-month intervals with CBD doses of 5–6 mg/kg/day at Visit 3, 8–9 mg/kg/day at Visit 4, and 10–12 mg/kg/day at Visit 5. At Visit 6 the CHE is weaned over a 1-month period after which the participants have their end of study visit (Visit 7). Care-givers monitor and record seizure frequencies in daily seizure logs. The complete study design and methodology have been described previously (7).

Ethics

Prior to enrollment, written and informed consent was obtained from the child’s parents or legal guardian. This study received a No Objection Letter (NOL) from Health Canada, was approved by the University of Saskatchewan Biomedical Research Ethics Board and registered with ClinicalTrials.gov (NCT03024827).

Participants

Inclusion criteria included pediatric patients between the ages of 1 to 10 years with epileptic encephalopathy resistant to standard medical treatment (as per International League Against Epilepsy definition of drug resistant epilepsy) and at minimum one major seizure per week or four major seizures per month (8). Seven participants from Saskatoon who met the inclusion criteria completed the study. All study data were collected and managed using the REDCap electronic data capture tool hosted at the University of Saskatchewan (9).

Efficacy Outcome Measures

Seizures occurring in a cluster were counted as a single seizure due to challenges arising from caregivers individually recording each seizure within a cluster. The data from the seizure logs was entered into REDCap (9) at each visit and underwent an independent audit performed by the University of Saskatchewan Clinical Trial Support Unit. To allow for variations in the length between study visits, the average daily number of seizures between visits was calculated by dividing the number of seizures recorded between each visit by the number of days between visits.

At Visits 2–6, participants underwent a 2-h EEG for assessment of degree of background slowing and spike index. The first EEG was performed prior to starting the CHE and each subsequent EEG was performed prior to a scheduled CHE dosage increase. To ensure consistency in EEG interpretation, an EEG rating scale for background slowing (encephalopathy) proposed by Lüders was used (10). A spike index ranked on a five-point scale ranging from 0 (= No Spikes) to 4 (= Continuous Spiking, defined as spikes occupying more than 70% of the EEG) was also calculated for each EEG.

At Visits 2–7, parents completed a modified Quality of Life in Childhood Epilepsy (QOLCE-55) survey which, in addition to questions assessing the domains including cognition, physical independence, social engagement, well-being, behavior (11), contained 13 additional items about sleep, verbal and non-verbal communication, interpersonal interactions, and irritability. Each item was rated from 1 (= Very Often) to 5 (= Never) or marked “Not Applicable.” The scores for reverse items were inverted and then all scores were transformed using (Score-1) × 25. The mean score for each subscale was calculated ignoring those marked “Not Applicable.”

Safety Outcome Measures

During the study caregivers recorded a description all adverse events associated with CHE in a participant diary. From Visit 3 to Visit 7, caregivers rated adverse effects previously described with CBD. Sleepiness/Lethargy and Irritability were rated from 0 (= Not Present) to 4 (= Present All The Time). Nausea/Vomiting and Diarrhea were rated from 0 (= Not Present) to 5 (= More Than Once Per Day). At each visit, the information for the preceding month was self-reported and provided to the study nurse.

At Visits 2–6, blood samples were collected for complete cell count and differential cell count, sodium, potassium, chloride, calcium, magnesium, phosphate, creatinine, urea, aspartate transaminase, alanine transaminase, alkaline phosphatase, and gamma glutamyltransferase, total and direct bilirubin, lipase, albumin, cholesterol, and triglycerides. Elevations in liver enzymes or lipase were considered significant if they were more than three times the upper limit of the normal reference range.

Quantification of Cannabinoids in Plasma and Steady State Trough Levels (CSS, Min)

To measure plasma trough steady-state (CSS, Min) cannabinoid levels, blood was collected on Visits 2–5 into lithium heparin Barricor vacutainers and centrifuged for 10 min in a clinical centrifuge (1,500 rpm) (12). These plasma samples (200 μL) were prepared and analyzed for CBD, CBC, and THC levels according to a validated liquid chromatography-mass spectrometry (LC-MS/MS) method that while developed independently in our lab is similar to a previously reported validated plasma cannabinoid assay (7, 13). All samples were stored at −70°C prior to analysis. Analytical method validation indicated the assay was specific and linear from 0.49 to 125 ng ml −1 , for THC and CBD, and 0.98–125 ng ml −1 CBC with r 2 > 0.998. Matrix effects ranged from 40 to 50% depending upon analyte resulting in extraction efficiencies in a similar range but recoveries were >88%. Intra- and inter-day precision and accuracy of the method was within ± 15%. The samples were analyzed in three batches (October 2017, May 2018, and March 2019). While most samples were analyzed within 3 months of collection, some were analyzed up to 8 months after collection. Stability analysis indicates stability of cannabinoids stored frozen for 3 months but stability beyond this is unknown. Full details of the quantification method of cannabinoids in plasma samples are available as Supplementary Protocol provided with this manuscript.

Steady-State Trough Anticonvulsant Levels

During the study, the participants’ anticonvulsant medications were not adjusted. The exception was clobazam, which was decreased if it was felt that clobazam side effects were being exacerbated by the known interaction between CBD and clobazam (14). Prior to decreasing the dose of clobazam, trough clobazam, and norclobazam levels were measured.

Trough anticonvulsant levels were measured at Visits 2–6 to identify a possible drug interaction with CBD, a known competitive inhibitor of CYP2C and CYP3A isozymes (15). CSS, Min levels were obtained for valproic acid, lamotrigine, levetiracetam, topiramate, and clonazepam. CSS, Min levels for stiripentol were not obtained as this assay was not available to us through the Saskatchewan Provincial Health Laboratory or its partnering laboratories.

Statistical Analysis

Due to the small sample size reported a formal statistical analysis was not performed. Data are presented from individual participants and as the mean ± standard error of the mean (s.e.m.) (Figures 1, 3) and in a descriptive manner to illustrate trends emerging from the data (Figure 2). A formal analysis will be done when all patients are included in the trial.

Figure 1. (A) Percentage reduction in daily average seizure frequency as compared to baseline. The value shown at each visit represents the decrease in seizure frequency from baseline during the preceding month. (B) Average percentage reduction in daily average seizure frequency from baseline for all seven participants at each study visit. (C) Average percentage reduction in daily seizure frequency from baseline for all seven participants broken down into seizure type. Data are shown as mean ± s.e.m.

Figure 2. Pooled QOLCE-55 scores and subscores for all seven participants. The values shown at each visit represent the QOLCE-55 total and subscores for the preceding month. Data are mean from seven participants.

Figure 3. Participant minimum steady state (CSS,Min) plasma concentrations and average plasma CSS,Min levels for each cannabinoid of cannabidiol (CBD) (A,B), cannabichromene (CBC) (C,D), and Δ 9 -tetrahydrocannabinol (THC) (E,F) analyzed with LC-MS/MS. Values shown represent steady state levels after 1 month on the corresponding dosage of CBD measured just prior to a dose administration. Data are mean ± s.e.m.

Results

Demographic Characteristics and Compliance

At time of enrolment, all participants failed at least 2 appropriate anticonvulsants, and none were using the ketogenic diet or had a vagal nerve stimulator. All participants were fully compliant with all study protocols. Table 1 summarizes study participant characteristics. As per the publishing guidelines of this journal the participants’ gender is not included and age at recruitment is provided in ranges (1–3, 4–6, 7–10 years).

Table 1. Participant characteristics at time of recruitment into CARE-E including age, epilepsy diagnosis, and concomitant anticonvulsant medications.

Safety and Tolerability Outcome Measures

While all participants reported Sleepiness/Lethargy and Irritability during the study, no scores increased by more than two points. Irritability improved in two participants following a decrease in clobazam dosage. Occasional incidences of nausea and vomiting, diarrhea, increased appetite, difficulty sleeping and spasticity were reported. Changes in the side-effect rating scales were not consistent and, apart from nausea and vomiting, did not correlate with increased doses of the CHE. None of the side effects were severe enough to prompt withdrawal from the study. The side effects rating scale scores are provided in Supplementary Tables 1A–D.

No significant changes in complete blood count and differential, electrolytes, renal panels, triglyceride, cholesterol, albumin, or bilirubin levels were observed. All participants had elevated ALP at Visit 1; however, these levels did not increase with the introduction and titration of CHE, with the exception of participant A-07, whose ALP increased to 300 U/L (reference: 30–110 U/L) at Visit 4, but decreased back to 144 U/L at Visit 5.

Participant A-01 had a slight elevation of GGT at 44 U/L (reference 10–35 U/L) seen at Visit 3 only. Participant A-03 had a marked elevation of GGT to 738 U/L (10–50 U/L) during an admission to Pediatric Intensive Care for sepsis. GGT decreased to 73 U/L the following month and returned to normal on post-study follow up despite continuing CHE.

Participant A-04 had slight elevations of AST at Visits 3 and 6 (48 U/L and 44 U/L, respectively -reference: 10–40 U/L). GGT was elevated prior to, and remained elevated throughout, the study, reaching a peak of 88 U/L at Visit 4. Participant A-04’s serum lipase at 173 U/L (normal: 22–51 U/L) was significantly elevated at Visit 5. As he was asymptomatic and an abdominal ultrasound was normal, he continued to receive CHE. By Visit 6, lipase levels decreased to 83 U/L and returned to normal following the study after valproic acid dosing was decreased and CHE was continued at 10–12 mg/kg/day.

No clinically significant adverse events directly attributed to the CHE were encountered. Two participants had serious adverse events requiring hospitalization, but these were not related to the study drug. During their hospitalizations, both remained on their routine anticonvulsants and CHE.

Efficacy Outcome Measures

The average reduction in daily seizure frequency between visits for each participant is displayed in Figure 1A. Over the study period, all seven participants had an improvement in seizure frequency with CHE. One participant (A-04) had a transient worsening of seizures at a CBD equivalent dose of 2–3 mg/kg/day. All participants had a reduction in average daily seizure frequency at a CBD equivalent dose of 5–6 mg/kg/day with six participants having a decrease >25% and four participants having a decrease >50%. After increasing to 10–12 mg/kg/day, the average reduction across all participants was 74% (Figure 1B) with all participants having a >25% reduction in daily seizure frequency, five participants having a decrease >50%, and three participants being seizure free. One participant was seizure free on an 8–9 mg/kg/day CBD equivalent dose.

During the final month of the study, when CHE was weaned off completely in the first three weeks, the reduction in seizure frequency was maintained in all participants and continued to improve in three participants (A-02, A-04, A-05) despite no changes to their anticonvulsant regimens.

While there was a reduction in daily seizure frequency between visits for all seizure types recorded, the greatest reduction was seen in atonic and versive seizures while epileptic spasms increased in frequency (Figure 1C). The percentage reduction in frequency of reported seizure types compared to baseline for all seven participants at each visit are also provided as Supplementary Figures 1A–G.

By the time the CBD dose was increased to 10–12 mg/kg/day, all participants -except for participant A-07, who had a normal background activity on the initial EEG– had an improvement in their EEG encephalopathy rating scale with most improving by one point on the rating scale. Participant A-03 had an improvement by two points. During the course of the study, three participants had an improvement in their EEG Spike Index scores. Participants A-03 and A-04 had resolution of their continuous spike activity in sleep. Full details of EEG results are provided in Supplementary Figures 2A,B.

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An improvement in the total QOLCE-55 scores was observed in all participants with the greatest improvements were found on the Cognitive, Social and Emotional Functioning subscales (Figure 2). While the improvements in the QOLCE scores decreased during the weaning period following Visit 6 the scores remained improved over the baseline scores.

Plasma Cannabinoid Plasma Levels in Relation to Dosage Escalation and Decrease in Seizure Frequency

Cannabinoid CSS, Min plasma concentrations were measured at the end of each subsequent month’s dosage escalation (Figures 3A–F). With each dosage escalation, CBD and CBC CSS, Min values generally increased proportionally with dose in all participants, except for participant A-04, whose last dose escalation resulted in non-proportional increases in both CBD and CBC CSS, Min values (Figures 3A–C).

Following a month of CBD at 5–6 mg/kg/day, the four participants with a >50% reduction in average daily seizure frequency, had CSS, Min CBD levels ranging from 14.8 to 24.4 ng/mL. After a month of CBD at 10–12 mg/kg/day, the five participants with a >50% reduction in average daily seizure frequency, had CSS, Min CBD level ranging from 42.5 to 124.7 ng/mL. The CSS, Min CBD levels corresponding with the CBD dosage at which the three participants became seizure free, ranged from 54.8 to 78.9 ng/mL (Figure 3A).

In all but two participants (A-04 and A-07), CSS, Min THC levels were detectable at 2–3 mg/kg/day. Even at the highest dose of CHE, the CSS, Min THC levels were low—below 4 ng/mL in all but two participants with the highest level being 4.34 ng/mL (Figure 3E).

Effect of CHE on Steady State Levels of Anticonvulsants

Apart from clobazam, CSS, Min anticonvulsant levels did not change significantly and remained within therapeutic limits with the following exceptions. Valproic acid levels for participant A-07 doubled between visits 2 and 6 but remained within therapeutic range (350–700 umol/L). For participant A-06, Valproic acid levels decreased to below therapeutic range at 16 umol/L between visits 4 and 5 suggesting medication non-compliance. CSS, Min clobazam and norclobazam levels of the four participants taking clobazam during the study are provided in Supplementary Table 2. For participants A-02 and A-03 these levels are not available for visit 6 due to the samples being misplaced in our hospital central laboratory. Three participants (A-01, A-02, and A-03) experienced side effects felt to be secondary to clobazam prompting a decrease in their clobazam dosage. In all three participants, these apparent side-effects of clobazam resolved with a decrease in clobazam dosing. Co-administration of clobazam did not appear to correlate with higher levels of CBD or CBC at each dosage escalation.

Discussion

CARE-E is an open label dosage finding study designed to assess the safety and efficacy of a CBD-Enriched Cannabis Herbal Extract (CHE) in children with intractable epileptic encephalopathy. The study involved measurement of CSS, Min levels of CBD, THC, and CBC and their relationship with safety, tolerability, and efficacy outcome measures in hopes to identify appropriate doses of similar Cannabis products in children. This study is the first to report pediatric CSS, Min levels of CBD, THC, and CBC in any pediatric dosage escalation study and provide guidance on initial dosing of CBD-enriched CHEs.

Escalating doses of CBD-enriched CHE from 2–3 mg/kg/day to 10–12 mg/kg/day resulted in no serious adverse events related to the CHE. Parents reported sleepiness/lethargy and irritability in most participants, but these side effects were assessed after starting the study drug and were likely pre-existing. Transient increases in sleepiness and irritability in three participants taking clobazam resolved after clobazam dose was decreased, suggesting these side-effects could be secondary to an interaction between the CHE and clobazam (14). Laboratory monitoring noted significant elevations in GGT, AST, and lipase levels in two participants, both of whom were also taking valproic acid. Participant A-03’s marked elevation of GGT was likely secondary to sepsis, which occurred during the study. Participant A-04’s transient and non-significant elevation of AST and significant elevation of lipase levels were likely secondary to a predisposition to hepatic and pancreatic dysfunction from high-dose valproic acid and corroborates observations reported elsewhere (3, 16). The fact that this participant had a preexisting elevated GGT suggests that liver enzymes should be screened prior to starting CHE, especially if the child is already prescribed valproic acid.

The concentrations of CBD, THC, and CBC appeared to increase linearly with dosage in six of the seven participants, suggesting dose-independent pharmacokinetics for these participants within this dosage escalation trial. The greater than proportional increase in CSS, Min CBD with the final dosage increase in participant A-04 may suggest dose-dependent pharmacokinetics with saturation of first-pass metabolism and an increase in the oral bioavailability. Participant A-04 did not exhibit any change in clinical status or in anticonvulsant therapy to explain this disproportional increase in CSS, Min. To confirm the possible non-linear pharmacokinetics in children, a dosage escalation study involving a larger sample size and a higher dose beyond the doses used in the current trial will be necessary. The possibility of dose-dependent PK, though, raises a safety concern, which also warrants further investigation in pediatric patients and suggests a need to limit dose sizes and not to simply continue increasing doses until an appropriate effect is observed.

CBD and THC both inhibit enzymes involved in the metabolism of many anticonvulsants including CYP2C and CYP3A isoenzymes (17). While increases in Clobazam and norClobazam levels were seen in some participants taking clobazam, overall co-administration of CHE did not significantly affect Css, min levels of the other concomitant anticonvulsants. It would have been of interest to measure Css, min levels of stiripentol given that many children with Dravet syndrome would also be taking this medication and stiripentol is metabolized by CYP2C19 and CYP3A4 isoenzymes. At present it is unknown if there is a pharmacokinetic interaction between CBD and Stiripentol. Although an assay to measure stiripentol levels is described, it is not indicated for therapeutic purposes by the manufacturer or regulatory bodies such as Health Canada, FDA or the EU. As such, it was not available for us for the purposes of this study (18).

The potential intoxicating effects of any THC present in CHE remain a concern for pediatric patients. Oral consumption of Cannabis products results in lower peak levels of THC as compared to smoking due to a high first-pass effect and slow erratic absorption from the gastrointestinal tract. However, intoxication can still occur because of greater distribution into the central nervous system and conversion to 11-hydroxy-THC, which is also intoxicating and has a half-life as long as, or longer, than THC (17, 19, 20). The CSS, Min levels of THC increased in a seemingly linear relationship to dosage, and with the exception of two participants at the highest dosage level, these remained lower than levels that have been reported to cause intoxication (19). Tachycardia and conjunctival injection—felt to be reliable markers of intoxication from THC—were not seen during the study. The lack of intoxication seen in our participants whose plasma THC levels exceeded 4 ng/mL may have been due to the reported CBD-mediated attenuation of the intoxicant effects of THC (21).

An overall trend for improvement in seizure control and QOLCE scores was observed with increasing CHE dosage and CSS, Min CBD levels. A >50% reduction in average daily seizure frequency occurred in four of seven participants at a CBD dose of 5–6 mg/kg/day, and all participants had a >25% reduction in seizures at a CBD dose of 10–12 mg/kg/day. In the QOLCE scores, there was a trend toward improvements in cognitive, social, and emotional function in relation to CBD dosage. These data suggest that the initial target dose of CBD should be 5–6 mg/kg/day when a 1:20 THC:CBD whole plant extract is used and can be increased as needed up to 10–12 mg/kg/day with careful consideration of potential non-linear pharmacokinetics at higher doses.

Trembly and Sherman reported that adult patients taking purified CBD had no improvement in seizure control when their plasma CBD levels ranged from 20 to 30 ng/mL, while a significant decrease in seizure control occurred when plasma CBD levels increased above 150 ng/mL (22). While it is challenging to correlate CSS, Min levels of CBD and CBC with efficacy in reducing seizure frequency based on our data, we do note that the CSS, Min CBD levels associated with a >50% reduction in average daily seizure frequency and seizure freedom in this study were lower. Further analysis with larger sample sizes are needed to delineate which CSS, Min level of CBD is associated with optimal seizure control and improved QOLCE scores.

Two recent systematic reviews of clinical trials assessing pharmaceutical grade CBD in children with treatment epilepsy provide insight into the expected outcomes at the CBD doses used in these trials. In pooled data of 17 observational studies, Stockings et al. found that CBD at 20 mg/kg/day resulted in 48.5% of patients having a 50% reduction in seizures and QoLCE scores improved in 55.8% (23). Lattanzi et al. also performed a systematic review of the four clinical trials assessing pharmaceutical grade CBD in children with treatment resistant Lennox Gastaut and Dravet Syndromes. They reported that the pooled average difference in seizure frequency between CBD and placebo with CBD at 10 mg/kg/day was 19.5% while that with CBD at 20 mg/kg/day was 19.9% both in favor of CBD. A seizure frequency reduction of 50% (for all seizure types) was 37.2% with CBD at 20 mg/kg/day and 21.2% with placebo (24).

An “entourage” effect in which the clinical efficacy of cannabinoids when used in combination are greater than when used individually has been demonstrated in several animal models of epilepsy but has yet to be reported for human trials (25–27). While we saw clinical efficacy with regards to reduction in seizure frequency and improvements in QoL scores with CBD doses lower than those reported in studies using pharmaceutical grade CBD, the small number of participants reported require caution when interpreting the results and preclude drawing definite conclusions in particular with regards to possible entourage effect. Additionally, CARE-E was not designed to compare efficacy of CHE to pharmaceutical grade CBD. This can only be addressed in a head to head comparative study.

The preliminary findings presented in this manuscript are however, in keeping with the results of a metanalysis of clinical studies comparing whole plant Cannabis CHE to pharmaceutical grade CBD in children with refractory epilepsy. This metanalysis found that while there was no significant difference between the CHE and pharmaceutical grade CBD in attaining 50% reduction in seizures, 71% of children taking CHE had improvement in seizure frequency compared to 46% taking purified CBD (p < 0.0001). The average CBD dose for children taking CHE was 6 mg/kg/day (28).

The three participants who became seizure free were taking long acting benzodiazepines (clobazam or clonazepam) but clobazam and clonazepam levels did not increase for two of these participants. This suggests that, while CBD and long acting benzodiazepines likely have a synergistic effect, this is not necessarily due to an increase in plasma benzodiazepine levels.

The reported half-life of CBD ranges from 9 to 32 h; however, the influence of age and concomitant anticonvulsants on the half-life remain largely unknown (29). These influences on half-life, however, would not explain the month-long continued improvements in seizure control and QOLCE scores observed in our three participants during the wean-off CHE. Such sustained effects often involve epigenetic changes and therefore it is possible that any long-term beneficial effect of CBD may reflect, in part, an as-of-yet unrecognized epigenetic effect (30). In order to assess if any long-lasting effect might be mediated through an active metabolite of CBD, we will measure participants’ plasma levels of CBD, CBC, THC, and their metabolites upon completion of the 1-month weaning period in subsequent participants who are enrolled in CARE-E.

While an improvement in background EEG activity was seen in four participants, there was no correlation between CBD dosing and improvements on the background score. A more complete examination of a potential relationship between the improvement in cognitive functioning seen in the QOLCE scores and improved background activity seen on EEG is warranted. The reduction in spike count following CBD treatment in three participants is reminiscent of the effect observed with broad-spectrum anticonvulsants such as benzodiazepines and valproic acid (31).

Although the reported improvement in seizure control and quality of life are promising, these findings must be interpreted with caution as there are several limitations in this preliminary report, in particular the small sample size and potential reporting bias inherent with open label studies. The lack of a placebo group and self-reporting of outcomes may limit the ability to discern any placebo effect which is seen in many drug trials. Reporting fatigue experienced by caregivers also may be a confounder, in particular for seizure frequency data.

Conclusion

The preliminary results of seven participants from the CARE-E study suggest CBD-enriched CHE up to 10–12 mg/kg/day is generally well tolerated. All participants had improvements in seizure frequency, modified Quality of Life in Childhood Epilepsy (QOLCE), and electroencephalogram (EEG) rating scores. Steady state CSS, Min data for CBD, THC, and CBC suggest linear PK, although one participant gave possible evidence of non-linear PK at higher doses. The preliminary data suggest an initial CBD target dose of 5–6 mg/kg/day when using a 1:20 THC:CBD CHE in children with treatment resistant epileptic encephalopathy. CSS, Min CBD levels suggest that dosing with a CHE containing THC and other cannabinoids may be more effective than purified CBD alone. Based on clinical observations and measurement of plasma THC levels, intoxication from THC is unlikely to occur when a 1:20 THC:CBD CHE is used within therapeutic doses. The anticonvulsant effect of CHE persisted after it was weaned off, suggesting an enduring anticonvulsant effect.

Data Availability

The datasets generated for this study are available on request to the corresponding author.

Ethics Statement

This study was carried out in accordance with the University of Saskatchewan Biomedical Research Ethics Review Board with written informed consent from the parents/legal guardians of all subjects. The parents/legal guardians of all subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the University of Saskatchewan Biomedical Research Ethics Review Board.

Author Contributions

RH, RT-W, JA, BA, SC, RL, AL, SM, DM, DN, EP-L, BS, and JT-Z contributed to the design of the study protocol. RH, LH, EL, and PM are site investigators for CARE-E. SC analyzed the data. RH, RT-W, JA, RL, and AL interpreted the data. SV assisted with the development and validation of the plasma cannabinoid assay used in this study. RH drafted the manuscript. All authors contributed to the revision of the manuscript and approved it for submission.

Funding

This study was funded through research grants from the Saskatchewan Health Research Foundation, the Jim Pattison Children’s Hospital Foundation, the Durwood Seafoot Estate, and the Savoy Foundation. As grant numbers were not provided with these awards, copies of the award letters from these granting agencies to our research team are available upon request. The granting agencies and CanniMed, from whom we purchased the study drug at cost, had no influence on study design, or the collection, interpretation, and/or reporting of data.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

The authors would like to acknowledge the financial support to perform this study received from the Jim Pattison Children’s Hospital Foundation, the Durwood Seafoot Estate, the Saskatchewan Health Research Foundation and the Savoy Foundation. We also acknowledge the operational support provided by the Department of Pediatrics, University of Saskatchewan and the Saskatchewan Health Authority.

Supplementary Material

References

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4. Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome(GWPCARE4); a randomized, double blind, placebo controlled phase 3 trial. Lancet. (2018) 391:1085–96. doi: 10.1016/S0140-6736(18)30136-3

5. McCoy B, Wang L, Zak M, Al-Mehmadi S, Kabir N, Alhadid K, et al. A prospective open label trial of a CBD/THC cannabis oil in Dravet syndrome. Ann Clin and Transl Neur. (2018) 5:1077–88 doi: 10.1002/acn3.621

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8. Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. (2010) 51:1069–77. doi: 10.1111/j.1528-1167.2009.02397.x

9. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap) – A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. (2009) 42:377–81. doi: 10.1016/j.jbi.2008.08.010

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11. Connolly AM, Sabaz M, Lawson JA, Bye AME, Cairns DR. Quality of life in childhood epilepsy; validating the QOLCE. J Paediatr Child Health. (2005) 41:156–8. doi: 10.1111/j.1440–1754.2005.570_2.x

See also  Best CBD Oil Affiliate Program

12. Vuong S, Michel D, Alcorn J, Huntsman R, Tang-Wai R, Lyon AW. BD. Vacutainer ® Barricor ® Blood Collection Tube is the Tube of Choice for LC-MS/MS Analysis of Bioactive Cannabinoids in Plasma. (2018). Available online at: https://research-groups.usask.ca/cris/documents/Bioactive_Cannabinoids_Barricor_Tube_Study_Report.pdf (accessed March 13, 2019).

13. Barco S, Fucile C, Manfredini L, De Grandis E, Gherzi M, Martelli A, et al. A UHPLC-MS method for the quantification of Δ9-tetrahydrocannabinol and cannabidiol in decoctions and in plasma samples for therapeutic monitoring of medical cannabis. Bioanalysis. (2018) 10:2003–14. doi: 10.4155/bio-2018-0184

14. Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. (2015) 56:1246–51. doi: 10.1111/epi.13060

15. Bornheim LM, Everhart ET, Li J, Correia MA. Characterization of cannabidiol-mediated cytochrome p450 inactivation. Biochem Pharmcol. (1993) 45:1323–3. doi: 10.1016/0006-2952(93)90286-6

16. Sonmez FM, Demir E, Orem A, Yildirmis S, Orhan F, Aslan A, et al. Effect of antiepileptic drugs on plasma lipids, lipoprotein (a), and liver enzymes. J Child Neurol. (2006) 21:70–4. doi: 10.1177/08830738060210011301

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19. Ohlsson A, Lindgren J-E, Wahlen A, Agurell S, Hollister LE, Gillespie HK. Plasma delta-9-tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clin Pharmacol Ther. (1980) 28:409–16. doi: 10.1038/clpt.1980.181

20. Zuardi AW, Hallak JE, Crippa JA. Interaction between cannabidiol (CBD) and (9)-tetrahydrocannabinol (THC) influence of administration interval and dose ratio between the cannabinoids. Psychopharmacology. (2012) 219:247–9. doi: 10.1007/s00213-011-2495-x

21. Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. (2007) 4:1770–804. doi: 10.1002/cbdv.200790152

22. Trembly B, Sherman M. Double-blind clinical study of cannabidiol as a secondary anticonvulsant. Presented at: Marijuana’90. In: International Conference on Cannabis and Cannabinoids, Crete (1990).

23. Stockings E, Zagic D, Campbell G, Weier M, Hall WD, Nielsen S, et al. Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence. J Neurol Neurosurg Psychiatry. (2018) 89:741–53. doi: 10.1136/jnnp-2017-317168

24. Lattanzi S, Brigo F, Trinka E, Zaccara G, Cagnetti C, Del Giovane C, et al. Efficacy and safety of cannabidiol in epilepsy: a systematic review and meta-analysis. Drugs. (2018) 78:1791–804. doi: 10.1007/s40265-018-0992-5

25. Russo EB. Taming THC: potential cannabis synergy and phytocannbinoid-terpenoid entourage effects. Brit J Pharmacol. (2011) 163:1344–64. doi: 10.1111/j.1476-5381.2011.01238.x

26. Wilkinson JD, Whalley BJ, Baker D, Pryce G, Constanti A, Gibbons S, et al. Medicinal Cannabis; is delta9-tetrahydrocannabinol necessary for its effects? J Pharm Pharmacol. (2003) 55:1687–94. doi: 10.1211/0022357022304

27. Ryan D, Drysdale AJ, Pertwee RG, Platt B. Differential effects of cannabis extracts and pure cannabinoids on hippocampal neurons and glia. Neurosci Lett. (2006) 408:236–41. doi: 10.1016/j.neulet.2006.09.008

28. Pamplona FA, da Silva LR, Coan AC. Potential clinical benefits of CBD-rich Cannabis extracts over purified CBD in treatment-resistant epilepsy: observational data meta-analysis. Front Neurol. (2018) 9:759. doi: 10.3389/fneur.2018.00759

29. Campbell CT, Shaw Phillips M, Manasco K. Cannabinoids in pediatrics. J Pediatr Pharmacol Ther. (2017) 22:176–85. doi: 10.5863/1551-6776-22.3.176

30. Szutorisz H, Hurd YL. Epigenetic effects of Cannabis exposure. Biol Psychiatry. (2016) 79:586–94. doi: 10.1016/j.biopsych.2015.09.014

31. Van Cott AC, Brenner RP. Drug effects and toxic encephalopathies. In: Ebersole JS, Pedley TA, editors: Current Practice in Clinical Electroencephalography, 3rd edition. Philadelphia, PA: Lippincott Williams and Wilkins. (2003).

Keywords: cannabidiol, Δ 9 -tetrahydrocannabinol, cannabis, epileptic encephalopathy, cannabinoid plasma levels

Citation: Huntsman RJ, Tang-Wai R, Alcorn J, Vuong S, Acton B, Corley S, Laprairie R, Lyon AW, Meier S, Mousseau DD, Newmeyer D, Prosser-Loose E, Seifert B, Tellez-Zenteno J, Huh L, Leung E and Major P (2019) Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study. Front. Neurol. 10:716. doi: 10.3389/fneur.2019.00716

Received: 01 May 2019; Accepted: 17 June 2019;
Published: 03 July 2019.

Pasquale Striano, University of Genoa, Italy

Ugo De Grazia, Istituto Neurologico Carlo Besta (IRCCS), Italy
Simona Lattanzi, Marche Polytechnic University, Italy

Copyright © 2019 Huntsman, Tang-Wai, Alcorn, Vuong, Acton, Corley, Laprairie, Lyon, Meier, Mousseau, Newmeyer, Prosser-Loose, Seifert, Tellez-Zenteno, Huh, Leung and Major. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

CBD Oil for Kids: Is It Safe for Children with ADHD & Anxiety?

If you’re a parent, you’ll go above and beyond to keep your child healthy.

You may have heard your friends saying they’re using CBD oil with their kids. If you don’t know what CBD is, don’t worry — I’ll explain everything in this article, including why you may want to consider using the supplement with your children too.

Long story short, CBD stands for cannabidiol, a natural compound in cannabis plants with an array of positive effects on the body and brain but is non-psychoactive, unlike THC.

CBD is becoming increasingly popular for various negative symptoms, from anxiety to pain and inflammation (read more here).

It comes in many different forms, including CBD oil, capsules, edibles, beverages, vaping liquids, and topical products.

But which CBD oil will be the best for your little one?

In this guide, you’ll learn about 3 brands that, I believe, deserve your attention as a parent.

I’ve also mapped out several areas where CBD oil appears to be particularly effective, as well as what to look for when searching for the best CBD oil products for kids.

How to Find the CBD Oil for Your Kids

Several steps are involved in the production of CBD oil; each of them is a make-or-break factor.

Quality is paramount when buying CBD oil for kids, so if you want to rest assured your money goes in the right hands, I suggest researching the following information:

1. Hemp Source

It all starts in the soil.

Hemp is an effective bioaccumulator. What does this mean?

It means it absorbs everything from the environment it’s cultivated in.

In essence, when grown in clean and fertile soil, hemp will pull all the good nutrients to grow strong, healthy, and produce plenty of CBD.

But when the growing conditions are inferior and the soil polluted, the plant will draw every contaminant, resulting in very poor sourcing material.

With that said, I strongly recommend buying CBD from domestic farmers who grow organic hemp plants, even if they aren’t certified organic.

This ensures you’ll only get pure CBD oil that is safe for your kid.

2. Extraction Method

The method by which CBD oil is processed can tell much about its quality.

Some manufacturers use toxic solvents like propane and butane for extraction to avoid higher production costs and sell cheap CBD oil. The toxic residue in such products is what you want to steer clear of. I, for example, couldn’t imagine myself purposefully exposing my children to hazardous substances.

Two extraction methods yield clean and potent extracts without leaving any harmful chemicals behind — Ethanol and CO2 extraction.

Ethanol is used in making CBD tinctures. The high-CBD bud is soaked in high-proof alcohol like Ethanol, so the cannabinoids and other hemp compounds can be extracted.

CO2 extraction calls for using pressurized CO2 at varying temperatures to obtain an oily extract suspended in a carrier oil (most often MCT oil). This method is the golden standard in the industry.

3. Is It Full-Spectrum CBD Oil or Isolate?

Full-spectrum CBD oil contains all phytonutrients from hemp, including cannabinoids (with trace amounts of THC), terpenes, flavonoids, and essential oils, whereas CBD isolate carries only pure, isolated cannabidiol.

While isolates offer the highest dose of CBD per serving and are more versatile than full-spectrum CBD (it has no odor and no flavor), it lacks the synergy achieved by other hemp compounds in the full-spectrum extract.

CBD oil obtained from the whole plant is believed to have a greater therapeutic value than isolate-based products, and the user needs less CBD to achieve the desired effect. More scientific evidence supports the theory about the synergy between cannabinoids, especially when it comes to pain and inflammation.

I, too, believe that full-spectrum CBD oil is a better choice, but if your child is allergic to certain constituents of the hemp plant — or you don’t want even a negligible amount of THC in their system — isolates might be your only option.

4. Third-party Testing & Lab Results

Once a CBD oil is manufactured, companies can submit their products for third-party testing conducted by non-company staff to ensure the product is safe for consumption and consistent with the bottle’s label.

CBD oils should always feature information about third-party tests; if they don’t, it should raise some red flags.

It’s all the better if the actual lab results accompany that information. As a rule of thumb, companies that include lab results are generally better than those that aren’t open about them.

When buying CBD oil for your kid, it’s essential to choose the one that will suit their dosage needs. I would always go for the lower potency with children unless there’s a specific reason you want to give them CBD.

CBD Oil Effects on Kids

CBD has coined its fame thanks to its anticonvulsant properties in children with rare forms of epilepsy. Still, this cannabinoid can also alleviate less severe conditions, too — not to mention it’s a great supplement to keep your little pumpkin in good health in a natural way.

Below I go over the most common uses of CBD oil in kids and how it may improve selected health problems. Keep in mind that both the amount of CBD intake and the time of the day can affect how your kid responds to CBD oil.

CBD Oil for Kids With ADHD

If your child has an attention disorder — they quickly get overstimulated and have problems maintaining focus — CBD can help with symptom management.

Research on CBD as a potential treatment for ADHD is sparse. We know most of what we know about the link between these two stems from studies on cannabis as a whole, not the specific CBD compound.

However, there’s a lot of anecdotal evidence from parents giving CBD to their kids that CBD oil helps manage their hyperactivity symptoms.

Moreover, a 2014 study published in Current Neuropharmacology suggests that CBD can be a wake-promoting agent at low doses, making users more alert throughout the day (1).

Interestingly, our sleep-wake cycle largely depends on our level of alertness during the day, so CBD oil may also help when your kiddo has problems falling asleep at night.

CBD Oil for Kids With Anxiety

CBD exerts several actions in the brain that regulate our brain’s response to feelings of fear and anxiety. The research in this subject is mostly preclinical or based on animal studies, but there are thousands of testimonies from parents whose children found relief from anxiety in CBD oil.

But how exactly does CBD work for anxiety disorders?

Research suggests that cannabidiol inhibits serotonin reuptake in the brain. In other words, it makes serotonin more available for the body (2). With better control of your serotonin resources, CBD could help stabilize mood and reduce anxiety.

The second benefit is associated with CBD’s ability to prompt the endocannabinoid system to produce more natural cannabinoids (3). This includes anandamide — the endocannabinoid regulating emotions such as fear, bliss, and euphoria.

Insufficient anandamide production has been linked to low mood or overreaction to anxiety triggers.

As with serotonin, CBD stimulates the release of anandamide and helps it stay in the body for a longer duration — assisting the user in maintaining sanity.

Last but not least, CBD may stimulate the hippocampus (a critical brain area playing a vital role in an array of brain functions) to regenerate neurons (4). These findings are particularly interesting because brain scans of patients suffering from anxiety and depression often show a smaller hippocampus.

CBD Oil for Kids With Autism

A study led by the director of pediatric neurology at Jerusalem’s Shareek Zedek Hospital, Dr. Adi Aran, treated 60 autistic children with CBD oil for at least seven months.

After the treatment period, parents were asked to fill out assessment questionnaires about changes in their child’s condition. The researchers asked questions about behavioral changes, anxiety levels, and communication skills.

According to the collected data, 80% of parents noted a decline in problematic behaviors, with 62% reporting great improvements. Half of the examined children showed improved communication, and 40% of parents reported significant decreases in their children’s anxiety (5).

While these are some really promising results, we need more longitudinal studies on larger groups of patients for the research to be conclusive.

Top 4 CBD Oil Brands

I’ve tested plenty of CBD brands in my life, and I have a list of my personal favorites. It turns out that three of them are a perfect match for my children’s needs.

I always base my product recommendations on extensive testing and thousands of verified customer reviews to give you a full picture of any given product I tackle. I would never suggest any product that fails to meet my quality and safety criteria.

Below you’ll find the top 4 brands selling CBD oil.

1. Royal CBD (Best Overall)

Get 15% off all Royal CBD products. Use code “CFAH” at checkout.

Pros:

  • Full-spectrum of phytocannabinoids
  • Made from 100% natural ingredients
  • Extracted with supercritical CO2
  • Contained in premium-quality MCT oil
  • Lab-tested for potency and purity
  • The 500mg bottle is easy to dose
  • They also sell CBD infused gummies

Cons:

What I Like About Royal CBD:

I remember receiving a press release from Royal CBD shortly before their launch, so I couldn’t help but try their products — as I do with any new brand that grabs my attention.

I’m a visualizer, so I was instantly bought with the minimalistic design of their products. Of course, I did some solid research to not rely solely on my gut, and it turned out this company has an unparalleled level of transparency.

They explain everything about how they source their hemp and what extraction they use for their CBD oil. Not only that, but they were also able to prove it with the lab results. I ordered two bottles — the 1000mg (for me) and 500mg (for my two boys).

What I love about Royal CBD is that their full-spectrum oil does what it’s advertised to do — it brings relief. My children sleep better, they don’t get irritated so easily, and I can finally get them focused on their homework for longer than 3 minutes, which is a blessing for me.

Oh, and it doesn’t leave that botanical aftertaste on the tongue. I’m a fan of everything related to hemp, but my boys don’t share my enthusiasm to that extent. Thankfully, the MCT oil does a stellar job at masking the natural hemp flavor.

2. Gold Bee (Best Organic CBD Oil)

Pros:
  • Made from US-grown, organic hemp
  • Contains full-spectrum CBD
  • 1200 mg of CBD per bottle (40 mg/mL)
  • Extracted with supercritical CO2
  • Delicious Kiwi flavor
  • Sweetened with organic honey
  • Third-party tested for cannabinoid content and purity
Cons:
  • Only one concentration available
  • Limited flavor options
What I Like About Gold Bee CBD Oil for Kids

Gold Bee offers craft-quality CBD oils that are well suited for kids, both in their potency and ingredients. The company sources its CBD from organic hemp grown in Colorado, which is then gently extracted using pressurized CO2. Gold Bee’s farming and processing practices yield pure CBD extracts that maintain consistent potency throughout all batches.

The CBD oil contains full-spectrum CBD, meaning there are other cannabinoids and terpenes to support the health benefits of CBD. These compounds contribute to the much-desired entourage effect. As a result, your kid needs less oil than they would if you gave them isolated CBD, making this product very affordable compared to competitor brands.

Even though Gold Bee only carries 2 potencies, 1200mg, and 2400mg, but their oils have proven to be much more effective than other brands. So if you are giving your child GB’s 1200mg CBD Oil, you should start with a quarter dropper, around 10mg of CBD.

I especially like Gold Bee because its product contains only organic ingredients, including the honey in the CBD oil and the cane sugar in the gummies. The brand is a safe pick for health-conscious parents.

3. Hemp Bombs

Pros:

  • Sourced from 100% certified organic hemp from Europe
  • Extracted with CO2
  • THC-free
  • Lab-tested for purity and potency
  • Highly versatile — you can use it as is or add it to food and drinks
  • Available in 5 potencies
  • Less expensive than full-spectrum CBD oil

Cons:

  • Lacks the entourage effect from other cannabinoids
  • Your children usually won’t need anything stronger than the 300mg bottle

What I Like About HempBombs CBD:

HempBombs specializes in making 99% pure CBD products. These isolates are available as tinctures, capsules, vape oils, or gummies.

I know that some parents — especially those new to cannabis — tend to freak out about any THC in hemp products they give to their kids, so if you’re one of those parents, isolates might be a good starting point. Your child may be allergic to some plant compounds; CBD isolate might be the only option here.

Isolates are highly versatile. Given this, if your pumpkin hates the taste of natural CBD oil, the isolate should do the trick as it’s odorless and flavorless. Because of that, you can also mix CBD with foods and drinks to smuggle some CBD into your kid’s favorite muffins or a fruit salad dressing.

Remember that CBD isolate is purged from any cannabinoids other than CBD, so there’s no entourage effect. But as I said, with parents using isolate-based products, the potency of CBD is likely more important than the whole-plant synergy.

4. CBDistillery

Pros:

  • Sourced from non-GMO, pesticide-free hemp
  • Extracted with CO2
  • Available as full-spectrum CBD or pure CBD oil (broad-spectrum, zero THC)
  • Lab-tested for purity levels and consistency in potency
  • Available in 5 different potency options
  • Very affordable
See also  CBD Plus Oil

Cons:

  • Only available in the natural flavor
  • Not certified organic

What I Like About CBDistillery:

A veteran to the scene, CBDistillery never fails to deliver the highest quality and safety standards — both for adults and children.

Their oil is sold in five different potencies, from 250mg to 5000mg of full-spectrum or broad-spectrum (THC-free) extract. The 250mg CBD oil (my recommended potency for most kids) costs as little as $20, so it’s a perfect product for parents shopping for CBD on the budget.

I love the fact that you can also get a THC-free version of this oil but still enjoy the benefits of the other cannabinoids that have been preserved during extraction. I must admit it’s not as effective as Royal CBD, but it’s still a decent product. And for many young moms, this can be a golden mean between full-spectrum CBD oil and CBD isolate.

Using CBD With Children 101

I receive lots of questions from parents who would like to try CBD oil for their kids, but there’s so much confusion on the Internet that they get even more confused in the end.

So, my fellow moms, I’ve selected the 4 most frequently asked questions about CBD oil for kids, and I’m going to explain everything in the simplest way possible.

Is CBD Oil for Kids the Same as CBD Oil for Adults?

Yes, it’s precisely the same product. Companies don’t distinguish between CBD oil for kids or adults.

However, because children weigh less than adults, I suggest that you operate on lower potencies. Kids usually need lower amounts of CBD to feel the difference.

Besides, with a low-potency CBD oil (e.g., 250mg CBD per bottle), it’s easier to gauge the dosage in the dropper because you can use a few drops instead of having to measure out, say, one-tenth of the syringe for accurate dosing.

What Are the Benefits of CBD Oil for Children?

CBD is a highly versatile supplement that has a special relationship with our endocannabinoid system.

If you’re giving CBD oil to your kid for general supplementation purposes, you can expect the following benefits:

  • Improved focus
  • Higher alertness throughout the day
  • Better quality of sleep

On a practical note, CBD is easy to use, has a long shelf-life, and you can administer it to your child in many different ways.

What’s the Best Way to Use CBD With Children?

It goes without saying that your kids won’t be vaping CBD oil or dabbing CBD concentrates because first, they’re too potent, and second — the very consumption method is out of the question for children.

Most parents choose the sublingual method, which involves placing a few CBD oil drops beneath the kid’s tongue. Once there, they need to hold it for about 30–60 seconds until the oil gets absorbed into the bloodstream, then swallow.

It may happen that your tot isn’t a fan of CBD oil’s distinct taste and will turn its head away each time you try to administer it sublingually.

If that’s your story, I recommend CBD gummies. Each gummy comes with a fixed dose of CBD — you can skip that nasty dropper part — and they are sold in many delicious flavors.

I don’t need to tell you how much children love gummies, so this form of cannabidiol is a great way to give your little one the best of both worlds.

CBD Oil Dosage Guidelines for Kids

The optimal dosage for any given CBD user — including children — depends on their weight, metabolism, unique body chemistry, and desired effects.

For the pediatric population of CBD users, experts suggest starting with 0.5mg of CBD per pound and taking this dose three times a day.

Starting low and slow allows you to adjust the dosage to how your child reacts to CBD without causing any side effects (e.g., dry mouth or lightheadedness).

Quick Reference Chart for Children’s Dosages:
Weight (lbs) Low Strength Medium Strength
30 lbs (13 kg) 2.6 mg 7.8 mg
40 lbs (18 kg) 3.6 mg 10.8 mg
50 lbs (23 kg) 4.6 mg 13.8 mg
75 lbs (34 kg) 6.4 mg 19.0 mg
100 lbs (45 kg) 7.5 mg 22.5 mg

Final Thoughts on CBD Oils for Kids

CBD oil is an excellent tool for enhancing the quality of one’s life, not only for adults but also for children. Because of the non-psychoactive nature of CBD, this compound is doesn’t impact their mental development and comes with only a few mild side effects, such as dry mouth or dizziness when consumed in larger amounts.

I hope my guide has helped you understand what CBD oil is and how it can help your kid live a better life. Now you can make a well-informed decision and buy a high-quality product that will benefit the whole family.

References:

  1. Murillo-Rodríguez, E., Sarro-Ramírez, A., Sánchez, D., Mijangos-Moreno, S., Tejeda-Padrón, A., Poot-Aké, A., … Arias-Carrión, O. (2014). Potential effects of cannabidiol as a wake-promoting agent. Current Neuropharmacology, 12(3), 269–272.
  2. Russo, E.B., Burnet, A., Hall, B., Parker, K.K. (2005). Agonistic properties of cannabidiol at 5-HT1a receptors
  3. Leweke, F. M., Piomelli, D., Pahlisch, F., Muhl, D., Gerth, C. W., Hoyer, C., … Koethe, D. (2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Translational Psychiatry, 2(3), e94.
  4. Beale, C., Boyd, S. J., Chye, Y., Suo, C., Schira, M., Galettis, P., … Solowij, N. (2018). Prolonged Cannabidiol Treatment Effects on Hippocampal Subfield Volumes in Current Cannabis Users. Cannabis and cannabinoid research, 3(1), 94–107.
  5. Bar-Lev Schleider, L., Mechoulam, R., Saban, N., Meiri, G., & Novack, V. (2019). Real life Experience of Medical Cannabis Treatment in Autism: Analysis of Safety and Efficacy. Scientific reports, 9(1), 200.
Nina Julia

Nina created CFAH.org following the birth of her second child. She was a science and math teacher for 6 years prior to becoming a parent — teaching in schools in White Plains, New York and later in Paterson, New Jersey.

What Is the Correct CBD Dose for Kids?

Although proven beneficial, CBD products are something parents often hesitate to administer to their children. While the majority of states have legalized full-spectrum CBD usage, some negative connotations remain attached to these products.

We assure you that CBD oil is beneficial to kids and adults alike. Medicinal benefits of CBD use for children include the treatment of pediatric epilepsy, anxiety, and high blood pressure.

SUPA Naturals aims to enlighten people about CBD’s positive effects by providing top-notch medical cannabis products. We have years of experience in developing and distributing CBD products without adverse effects.

Contact us anytime regarding your questions about CBD oil for children.

What Is CBD?

CBD is a principal ingredient in the cannabis Sativa plant. It comes from hemp, which also contains a small amount of THC.

THC is more potent than CBD and therefore can lead to trippy effects such as hallucination. Unfortunately, cannabis haze is what many people immediately think of when learning of how CBD is derived from hemp. However, CBD is much safer than THC to use on infants and children.

CBD usage increases each year as more countries continue to legalize marijuana and hemp products. CBD will likely be legal in more countries than any other hemp product due to its safety and medical application.

CBD appeals to many people because it does not make you feel high like other hemp or marijuana products. You get most of the benefits of these products while avoiding the aloofness that comes with them.

CBD products offer many medical benefits for your child. Each year, we learn more about CBD and its effects on the body. However, we can assure you that it is safe for your child to consume and aids them in dealing with anxiety, pain, and many medical conditions.

How CBD Oil Benefits Your Child

While many adults use CBD products to relieve joint pain, recover from workouts, and calm their nerves, most children have different reasons for applying cannabis oil.

Pediatric Epilepsy

One of the principal reasons for the recent growth in the medical marijuana market is because CBD use can curb pediatric epilepsy. This condition was the catalyst for change in the cannabis naysayers’ perspective on CBD.

Medical studies show that CBD oil reduces the severity and frequency of seizures in epilepsy patients. If your child has pediatric epilepsy, consult with their physician about utilizing CBD oil as a potential remedy.

Your doctor must prescribe CBD for your child’s epilepsy before you use it.

Immune System Strengthening

If your child suffers from a compromised immune system, you must seek out any treatments or supplements that may help them. CBD provides necessary nourishment for your child, and many users praise its ability to improve their immune system.

Also, the properties of CBD oil contain fungi-fighting ingredients that help defend against many different types of bacteria.

Tame Anxiety

Unfortunately, anxiety affects millions of Americans each year. With stress comes a flurry of other medical conditions such as high blood pressure, migraines, and many others.

Perhaps the most common reason people use cannabis products is to lower their anxiety. CBD oil ingredients help mitigate the effects of stress and improve your child’s focus and help them remain calm throughout the day.

Many parents feel anxious when recalling stressful times from their youth. Now, you can help your child avoid those overwhelming moments with proper CBD dosage.

Autism

While medical experts are still researching the effects of CBD oil on children with autism, all signs point to a positive correlation.

A recent medical trial treated over 60 children with autism with CBD products. After the trial period, over 80% of the patients’ parents claim they saw improvements in their child’s condition. And over 60% of parents characterize the effects of CBD as ‘drastic.’

Mood Boost

In lighter terms, many parents use CBD oils on their kids to help improve their daily lives. Medical studies show that CBD ingredients are active in facilitating a mood boost.

Having a positive attitude is one of the best ways your son or daughter can live life. This mood boost will lead to better performance in school and athletics.

CBD Dose Titration for Children

Once you decide to move forward with CBD treatment for your child, you must research the correct CBD dose for kids. You want to give your children a sufficient CBD dose according to the needs of their condition.

Note that you cannot overdose on CBD, especially with an oil product. Still, it is wise to find the optimal dosage for your child.

Firstly, you should know that CBD is non-psychoactive, meaning your child will not face any hallucinogenic effects from consuming it. Because of this component, CBD oil is 100% safe for children.

Always consult a medical professional before starting your child on CBD products. While they are safe, your child may be allergic to particular ingredients in cannabis. Also, doctors may prescribe another treatment type for your child’s condition.

The best rule of thumb for pediatric CBD dosage is to begin with 0.5 milligrams per pound of bodyweight. You should apply the appropriate dosage approximately three times per day.

Therefore, if your child is thirty pounds, you should supply them with two drops of oil three times a day. If you want to be cautious with your child’s cannabis use, then you can start with a lower dose. Typically, children easily tolerate the 0.5-milligram dosage.

During the first couple of weeks of CBD therapy, you should watch for adverse effects. In most cases, however, there will be none.

If your child responds well to the cannabis product, you may increase the dosage to four drops of CBD oil three times a day. However, before you decide to increase your child’s dosage, consult a medical professional. Giving your kid a higher dosage comes with a minimal chance of side effects.

If your child has pediatric epilepsy, your doctor will recommend a unique dose that could be five to ten times more powerful than the average dosage. Your doctor will ensure that you are using the exact prescribed amount of CBD.

How To Use CBD Oil

Now that you know the proper CBD dose for kids, let’s discuss applying it correctly. There are many ways to consume CBD and THC products, including candles, vaping, sprays, and more.

However, the most common way for kids to ingest CBD is under their tongue. CBD application under your child’s tongue is recommended because the membranes there allow cannabis ingredients to absorb into the bloodstream immediately. If you are new to CBD, Try SUPA Natural’s CBD Oil.

CBD oils will taste like a marijuana strain in most cases. However, there are always new flavors coming to the market. Many users claim peppermint-flavored oils are preferable if your child does not like the taste of traditional CBD oil.

You may also consume CBD oil by mixing it with a beverage such as tea or milk. Do not mix CBD oil with water, though, as the oil will stick to the side of the glass. Also, many experts recommend that you give your child a high-fat snack in order to increase the amount of CBD they ingest.

There is another home trick CBD users recommend. You can place the CBD oil on a chocolate chip and let your child suck on the oil-drenched chip until it melts. This remedy eliminates the oil’s bitter weed taste.

Medical Facts

There are many annual medical studies on CBD oil and its effects. Here are some of the reports supporting the efficacy of CBD products.

Approved Treatment for Medical Conditions

The United States Food and Drug Administration and the European Medicines Agency approve the use of CBD products to treat Dravet syndrome, Lennox-Gastaut syndrome, and neonatal asphyxia.

Their studies show there are more benefits than disadvantages to using CBD oil on your newborn or adolescent. It takes an abundance of evidence for the FDA to approve a drug for consumption, indicating that they conclude low risk in using CBD for treatment purposes.

It Is Not Addictive

One of the most common misconceptions associated with hemp products is that they are addictive. Statements from the World Health Organization debunk this myth.

The WHO claims that there is no substantial evidence to suggest that CBD has anything in common with nicotine or other addictive drugs.

Its Legality Is Inevitable

While some states have restrictions on CBD use, CBD is legal in every state. The Farm Bill establishes that hemp is legal in the United States.

This legislation ensures that CBD oil will be legal for future products and use.

MS Remedy

Currently on the market is a CBD nasal spray that many claims to be helpful toward counteracting multiple sclerosis. Studies are ongoing as to the validity of these claims, but the forthcoming evidence is promising.

Some MS patients notice improvements in relaxing their muscle tightness and relieving pain, while others disagree.

Frequently Asked Questions

Naturally, we receive many questions regarding our cannabis products and their effects on children. Here are some of the most common questions our customers ask our management team.

Is it Legal to Use CBD on My Children?

Each state has its own policies regarding the legality of herb-based CBD products. In Washington State, CBD oil is legal to purchase.

THC use is where legality becomes tricky. However, CBD is within your right to purchase for your kids. Typically, your child’s doctor will involve themselves in the process by writing out a prescription.

Is CBD Safe for My Kids?

CBD oil is among the safest cannabis products that you can use on your child. It is impossible to overdose on CBD oils, while the chances of adverse side effects are minimal.

If you are trepidatious about giving your kids CBD oil, you can start with a low dosage to see how they react. Your child’s pediatrician can answer most of your questions about your kid’s cannabis usage. Also, we are here 24/7 to answer your questions.

How Old Do You Have to Be to Buy CBD Oil?

You must be at least eighteen years of age to purchase CBD products in Washington State. To be legal to distribute, a cannabis product cannot contain more than 0.3% THC.

Also, you should note that you cannot bring a marijuana product from another state into Washington. Any CBD oil that you purchase must originate from the Evergreen State.

How Will CBD Make My Kids Feel?

One of the first things that you will most likely notice when giving your children CBD is a sense of calmness. This effect is the most powerful of CBD oil.

With that increased calmness comes many additional benefits such as lower blood pressure, anxiety, and depression. If your child is using medical cannabis to treat an underlying condition, their doctor should supervise them to ensure that the treatment is going according to plan.

Does CBD Work for Anxiety?

The most proven benefit of CBD use is to cure stress. This effect is the most well-known effect of marijuana products. Stress and anxiety can be crippling for a child.

Luckily, today more CBD products than ever can quell your kid’s anxiety. You can start your kid on a minimum dosage to see how they react to CBD therapy.

Shop SUPA Products

As you can see, there are many benefits of using cannabis products on your children. You can help reduce your kid’s stress and treat critical medical conditions such as pediatric epilepsy.

If you want to use CBD for less severe conditions, such as minor pain relief, you should consult your doctor. The more your pediatrician gets involved, the more your chances improve of avoiding adverse side effects.

If you believe your child would benefit from using CBD oil and your child’s pediatrician agrees, we can help you by recommending the best CBD dose for kids. Our team knows the many aspects of CBD dosage and will happily address all your concerns.

Visit SUPA Naturals website or email us at [email protected] for more info!

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