Clinical Description of Findings From Pediatric Studies of Medical Cannabinoids

Study by Indication Authors, yDuration of Treatment and Follow-upMedication Dosing, Frequency, and FormulationPrimary and Secondary OutcomesSide EffectsAdditional Clinical Findings
 Elder and Knoderer,7 2015Duration of inpatient hospitalization for chemotherapyMost common dronabinol dose was 2.5 mg/m2 Q6H, scheduled in 55% and PRN in 45% of patientsSixty percent of children had a positive response (0–1 bouts of emesis), 13% had a fair response (2–3 bouts), and 27% had a poor response (>4 bouts)Not availableSixty-five percent received repeated courses, and 62% received outpatient prescriptions, suggesting good tolerability
Ninety-five percent received lower doses than guideline referred (5 mg/m2)
Median 3.5 doses received during hospitalization (range 1–129)
 Abrahamov et al,8 1995Four hundred eighty 24-h chemotherapy cyclesΔ-8-THC dose of 18 mg/m2 2 h before chemotherapy, repeated Q6H hours for 4 total dosesPrevented vomiting in all treatment cyclesIrritability (n = 2) and euphoria (n = 1)Preliminary trials with only the first 1–2 doses of δ-8-THC led to vomiting in most cases
Δ-8-THC prepared from CBD by cyclization, has 25%–50% less psychotropic potency than δ-9-THCIn 2 treatment cycles in which δ-8-THC was declined, repeated vomiting occurred. Subsequent cycles with δ-8-THC prevented vomiting
Oil drops-based solution
 Chan et al,9 1987Two consecutive, identical cycles of chemotherapy in a crossover designNabilone oral capsule 0.5–2 mg BID (by weight)Nabilone decreased retching and emesis in 70% of patients compared with prochloperazine (30%; P = .003)Drowsiness (67%), dizziness (50%), euphoria (11%), ocular swelling and/or irritation (11%), and orthostatic hypotension (8%)Sixty-six percent preferred nabilone compared with 17% who preferred prochloperazine (P = .015)
Prochloperazine 2.5–5 mg BIDNabilone decreased total episodes of retching or emesis compared with prochloperazine (13 vs 27 episodes; P <.05)Sixty-six percent continued nabilone in the open-label study, with no evidence of tolerance
 Dalzell et al,10 1986Five-d course of chemotherapy in each arm of the crossover designNabilone oral capsule 0.5 mg BID to 1 mg TID (by weight)Nabilone reduced vomiting episodes per chemotherapy cycle (5.9 vs 16.7; P <.01), and nausea severity rating (1.5 vs 2.5; scaled 0–3; P = .01) in comparison with domperidoneDrowsiness (55%), dizziness (35%), elevated mood (14%), and hallucinations (n = 1)Sixty-six percent preferred nabilone, and 6% preferred domperidone (P <.01)
Domperidone 5–15 mg TID (by weight)
 Ekert et al,11 1979Consecutive chemotherapy courses randomly assigned to THC or control antiemeticΔ-9-THC 10 mg/m2, up to maximum dose of 15 mgΔ-9-THC reduced nausea (6 vs 21 episodes) and completely prevented vomiting (12 vs 5 cycles) compared with metoclopramide (P <.01).Increased drowsiness (P >.02) and less anorexia (P >.05) compared with metoclopramide
Metoclopramide 5 or 10 mg (BSA >0.7 m2)Δ-9-THC reduced nausea (6 vs 18 episodes) and completely prevented vomiting (9 vs 0 cycles) compared with prochlorperazine (P <.001)Increased appetite (n = 7)
Prochlorperazine 5 or 10 mg (BSA dependent)One patient had agitation, anxiety, and bad dreams and refused further THC treatment
Schedule for antiemetic dosing 2 h before and 4, 8, 16, and 24 h after chemotherapy except placebo is given instead of control antiemetic at 4 h to prevent neurologic toxicityOne patient had euphoria and lightness
 Devinsky et al,12 2017Fourteen-wk treatment; 15% discontinued treatment before 14 wksCBD titrated up to 20 mg/kg per d in twice-daily dosing over 2 wksMedian monthly convulsive seizures decreased from 12.4 to 5.9, as compared with 14.9 to 14.1 with a placebo (P = .01), for an adjusted median seizure reduction of 22.9% with CBD compared with a placeboSomnolence (36%), diarrhea (31%), decreased appetite (28%), and vomiting (15%)Median frequency of total seizures (all seizure types) decreased 28.6% with CBD compared with 9.0% with a placebo (P = .03)
 Gofshteyn et al,13 2017Acute treatment after status epilepticus (n = 2)CBD titrated up to 25 mg/kg per dMarked reduction in seizure frequency and duration in 86% of patientsDrowsiness (29%) and decreased appetite with weight loss (n = 1)With addition of CBD, mean adjunct AEDs reduced from 7.1 to 2.8
Median 91 d for chronic treatment (range 3–87 mo)Final dose ranged from 15 to 25 mg/kg per dDuring chronic treatment, seizure frequency reduced by 91% at 4 wks and 65% at 48 wks
 Kaplan et al,14 2017Mean 48.6 wk of treatment (range 6–82)CBD titrated from 2 mg/kg per d in twice-daily dosing to a maximum of 25 mg/kg per d. Final dose ranged from 5 to 25 mg/kg per dSeizure frequency decreased in 4 of 5 subjects by 14 wks and most recent visitTemporary increased seizures (n = 3) and behavioral issues (n = 2)Improved quality of life, with subjective fine motor and cognitive improvements (n = 3)
 Treat et al,15 2017Mean 11.7 mo of treatment (range 0.3–57)OCESeizures improved in 49% of patients, with 24% considered responders (>50% reduction in seizure burden)Worsening seizures (10%), somnolence (6%), and GI symptoms (5%)Seventy-one percent discontinued OCE use during the study period
Cannabinoid ratios and dose information infrequently documented and not analyzedHigher response with LGS (58%) compared others (P <.05)Nineteen percent reported an adverse event
 Devinsky et al,16 2016Twelve-wk treatment; 7% discontinued treatment before 12 wksCBD titrated from 2–5 mg/kg per d up to 50 mg/kg per dTotal seizures decreased by median of 35% (P <.05)Somnolence (25%), diarrhea (19%), decreased appetite (19%), and fatigue (13%)Concurrent clobazam use associated with a 50% reduction in motor seizures (P = .01)
Mean CBD dose was 22.7 mg/kg per d in efficacy analysis group and 22.9 mg/kg per d in safety analysis groupMonthly motor seizures decreased by median of 37%, from a baseline of 30 to 16 monthly motor seizuresSix percent had treatment-emergent status epilepticusGreatest seizure reduction in patients with focal seizures (median 55% decrease) and atonic seizures (54%), followed by tonic seizures (37%) and tonic-clonic seizures (16%)
Median 3 daily doses (range 1–7)Thirty-seven percent of patients had at least a 50% reduction in seizures, 22% had at least a 70% reduction, and 8% had a 9% reductionThree percent discontinued treatment because of adverse events
Ninety-nine percent pure oil-based CBD extract dissolved in sesame oil-based solution
 Tzadok et al,17 2016Median 5.5 mo of treatment (range 3–12), with median 10 mo follow-upCBD-enriched OCE, with CBD dose of 1–20 mg/kg per d, titrated by seizure response and side effectsReduced seizures in 89% of patientsSeven percent of patients reported worsening seizures leading to discontinuation
CBD to THC ratio of 20:1Eighteen percent of patients had a 75%–100% reduction, 34% had a 50%–75% reduction, 12% had a 25%–50% reduction, and 26% had a <25% reduction
Canola oil-based solution
 Hussain et al,18 2015Median 6.8 mo of CBD treatmentCBD-enriched OCE, with at least 15:1 CBD-to-THC ratioReduced seizures in 85% of patientsIncreased appetite (30% vs 13%; P = .002) and weight gain (29% vs 18%, P = .08) compared with pretreatmentMedian 2 AEDs adjunct to CBD
Median reported CBD dose of 4.3 mg/kg per d, administered 2–3 times dailyFourteen percent reported seizure freedom
 Press et al,19 2015Mean follow-up of 5.6 mo (range 1–24)OCE with 70% reporting CBD only and 11% reporting CBD only with other OCEReduced seizures in 57% of patientsIncreased seizures (13%), somnolence and/or fatigue (12%), and GI symptoms (11%)Fifteen percent of patients discontinued use, of which 91% had treatment response
Dosing information infrequently documented and not analyzedThirty-three percent considered treatment responders, with >50% reduction in seizures
Response greater in LGS compared with Dravet and Doose syndromes (P <.05)
 Saade and Joshi,20 20156 mo of treatmentCBD titrated from 10 to 25 mg/kg per d over 15 d, divided twice dailySeizure frequency decreased from 10–20 per d to 5 per wk, with up to 9 d of clinical seizure freedomNone observed
 Porter and Jacobson,21 2013Treatment ranged from 2 wks to >1 yCBD-enriched OCEReduced seizures in 84% of patients.Drowsiness (37%), fatigue (16%), and decreased appetite (5%)
CBD content ranged from <0.5 to 28.6 mg/kg per d. THC dose ranged from 0 to 0.8 mg/kg per dForty-two percent reported a >80% seizure frequency reduction, 32% reported a 25%–60% reduction, and 11% reported seizure freedom
 Lorenz,22 2004Dronabinol mean dose of 0.07 mg/kg per dReduced seizures in 2 of 6 patientsBoth patients who responded had a temporary increase in seizure severityOne patient had no observed changed, 1 could not be evaluated because of NCL progression, and
1 could not be evaluated because of AED changes
One had stable seizure burden despite NCL progression
One had increased sensitivity to aversive smells
Neuropathic pain
 Rudich et al,23 200312 mo treatment with weekly follow-upDronabinol oral capsule started at 5 mg QHS, titrated in 5 mg increments, to maximum of 20 and 25 mg dailyAt 4 mo, 40% and 60% reduction in the affective component of pain, and functional improvements in sleep (50% and 100%), ADL (60% and 75%), mood (75% and 100%), and academics (10% and 100%)Increased appetite, morning sleepiness, lightheadedness, and dysphoria, all of which subsided with slower titration or lower doseEfficacy declined after 6–12 mo, resulting in discontinuation
One patient reported a 45% reduction in voiding pain
 Shannon and Opila-Lehman,24 20165 mo of treatmentCBD 25 mg Q6PM, with 6–12 mg QD PRN anxietyDecreased anxiety with SCARED score reduced from 34 to 18None observed
Improved sleep with SDSC score reduced from 59 to 38
 Kuhlen et al,25 2016Median 181 d of treatment (range 23–1429)Dronabinol 2.5% solution BID, titrated from 0.83 mg BID to 0.08–1.0 mg/kg per d (median 0.33 mg/kg per d)Clinician-documented spasticity reduced in 75% of patientsRestlessness (n = 1), mood deterioration (n = 1), and vomiting (n = 1)No habituation effect noted in responders
One patient discontinued treatment because of restlessness and a lack of efficacyResponse in 13% of patients could not be objectively determined
 Lorenz,26 2002Dronabinol 0.07 mg/kg per d, dispensed in 2.5% oil drops, divided twice dailyReduced spasticity within a few daysNone reported
Tourette syndrome
 Hasan et al,27 20109 wksΔ-9-THC titrated from 5 mg QAM to 15 mg dailyYGTSS score decreased from 97 to 54 and GTS-QoL score decreased from 54 to 21 at 7 wkTransient mild euphoria (n = 1)Minimal decrease of ADHD symptoms before the addition of methylphenidate
TMS measures of intracortical inhibition increased
  • ADHD, attention-deficit/hyperactivity disorder; ADL, activities of daily living; AED, antiepileptic drug; BID, twice daily; BSA, body surface area; GI, gastrointestinal; GTS-QoL, Gilles de la Tourette Syndrome–Quality of Life Scale; LGS, Lennox-Gastaut syndrome; NCL, neuronal ceroid lipofuscinosis; OCE, oral cannabis extract; PRN, as needed; Q6H, every 6 hours; Q6PM, every night at 6 PM; QD, once daily; QHS, every night; SCARED, Screen for Child Anxiety Related Disorders; SDSC, Sleep Disturbance Scale for Children; TID, 3 times daily; TMS, transcranial magnetic stimulation; YGTSS, Yale Global Tic Severity Scale; —, not applicable.