Evidence map›Paper›PMID 33536055›Full record

Trial reportMolecular autism2021

Cannabinoid treatment for autism: a proof-of-concept randomized trial.

Adi Aran, Moria Harel, Hanoch Cassuto, Lola Polyansky, Aviad Schnapp, Nadia Wattad, Dorit Shmueli, Daphna Golan, F Xavier Castellanos

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Molecular autism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02956226 (Cannabinoids for Behavioral Problems in Autism Spectrum Disorder), which is not on this map. Cited by 84 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 11 pooled it
23.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02956226 phase2completednot on this map

Cannabinoids for Behavioral Problems in Autism Spectrum Disorder: A Double Blind, Randomized, Placebo-controlled Trial With Crossover.

TypeinterventionalSponsorShaare Zedek Medical CenterRan2017 to 2018Enrolled150ConditionsAutistic DisorderArmsCannabinoids - 99% pure cannabinoids mix, Placebo, Cannabinoids - whole plant extract
3 · Its place in the literature

Who cites it

84 citing papers in PubMed, 11 syntheses or guidelines pooled it, 210 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. The Autism-Psychosis Continuum Conundrum: Exploring the Role of the Endocannabinoid System.International journal of environmental research and public health · 2022
    Pooled it
  9. Pooled it
  10. Pooled it
  11. Pooled it
  12. Trial
  13. Trial
  14. Trial
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. Article

24 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Adi AranNeuropediatric Unit, Shaare Zedek Medical Center, 12 Bayit Street, 91031, Jerusalem, Israel. aaran@szmc.org.il.ORCID 0000-0001-9460-4689
Moria HarelNeuropediatric Unit, Shaare Zedek Medical Center, 12 Bayit Street, 91031, Jerusalem, Israel.
Hanoch CassutoNeuropediatric Unit, Shaare Zedek Medical Center, 12 Bayit Street, 91031, Jerusalem, Israel.
Lola PolyanskyNeuropediatric Unit, Shaare Zedek Medical Center, 12 Bayit Street, 91031, Jerusalem, Israel.
Aviad SchnappNeuropediatric Unit, Shaare Zedek Medical Center, 12 Bayit Street, 91031, Jerusalem, Israel.
Nadia WattadNeuropediatric Unit, Shaare Zedek Medical Center, 12 Bayit Street, 91031, Jerusalem, Israel.
Dorit ShmueliChild Development Centers, Clalit Health Services, Tel Aviv-Yafo, Israel.
Daphna GolanChild Development Centers, Maccabi Health Services, Jerusalem, Israel.
F Xavier CastellanosDepartment of Child and Adolescent Psychiatry, NYU Grossman School of Medicine, New York, NY, USA.
Shaare Zedek Medical Center · ILClalit Health Services · ILMaccabi Healthcare Services · ILNew York University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEndocannabinoid dysfunction in animal models of autism spectrum disorder (ASD) and accumulating, albeit anecdotal, evidence for efficacy in humans motivated this placebo-controlled double-blind comparison of two oral cannabinoid solutions in 150 participants (age 5-21 years) with ASD.

methodsWe tested (1) BOL-DP-O-01-W, a whole-plant cannabis extract containing cannabidiol and Δ9-tetrahydrocannabinol at a 20:1 ratio and (2) BOL-DP-O-01, purified cannabidiol and Δ9-tetrahydrocannabinol at the same ratio. Participants (N = 150) received either placebo or cannabinoids for 12-weeks (testing efficacy) followed by a 4-week washout and predetermined cross-over for another 12 weeks to further assess tolerability. Registered primary efficacy outcome measures were improvement in behavioral problems (differences between whole-plant extract and placebo) on the Home Situation Questionnaire-ASD (HSQ-ASD) and the Clinical Global Impression-Improvement scale with disruptive behavior anchor points (CGI-I). Secondary measures were Social Responsiveness Scale (SRS-2) and Autism Parenting Stress Index (APSI).

resultsChanges in Total Scores of HSQ-ASD (primary-outcome) and APSI (secondary-outcome) did not differ among groups. Disruptive behavior on the CGI-I (co-primary outcome) was either much or very much improved in 49% on whole-plant extract (n = 45) versus 21% on placebo (n = 47; p = 0.005). Median SRS Total Score (secondary-outcome) improved by 14.9 on whole-plant extract (n = 34) versus 3.6 points after placebo (n = 36); p = 0.009). There were no treatment-related serious adverse events. Common adverse events included somnolence and decreased appetite, reported for 28% and 25% on whole-plant extract, respectively (n = 95); 23% and 21% on pure-cannabinoids (n = 93), and 8% and 15% on placebo (n = 94). Limitations Lack of pharmacokinetic data and a wide range of ages and functional levels among participants warrant caution when interpreting the results.

conclusionsThis interventional study provides evidence that BOL-DP-O-01-W and BOL-DP-O-01, administrated for 3 months, are well tolerated. Evidence for efficacy of these interventions are mixed and insufficient. Further testing of cannabinoids in ASD is recommended. Trial registration ClinicalTrials.gov: NCT02956226. Registered 06 November 2016, https://clinicaltrials.gov/ct2/show/NCT02956226.

Indexed as

AdolescentAdultAutism Spectrum DisorderAutistic DisorderCannabinoidsChildChild, PreschoolFemaleHumansMaleSocial BehaviorTreatment OutcomeYoung AdultCannabinoidsAutism spectrum disorderBehaviorCannabidiolCannabinoidsChild psychiatryClinical trials randomized controlledDevelopmental disordersEntourage effectNeuropsychologyTetrahydrocannabinol

Identifiers

PMID33536055
PMCPMC7860205
OpenAlexW3126959679

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.