CoChat
Sign Up
Cited by 564Cannabis and Cannabinoid ResearchMedicinal Plant Extracts EffectsPsychedelics and Drug Studies

Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis

Open access
Black, Nicola, Stockings, Emily, Campbell, Gabrielle, Tran, Lucy T, Zagic, Dino, Hall, Wayne D, Farrell, Michael, Degenhardt, Louisa·2019·The Lancet Psychiatry
DOI 10.1016/s2215-0366(19)30401-8PMC PMC6949116
Open this paper in CoChat — free account

Abstract

Background Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested to have a therapeutic role in certain mental disorders. We analysed the available evidence to ascertain the effectiveness and safety of all types of medicinal cannabinoids in treating symptoms of various mental disorders.Methods For this systematic review and meta-analysis we searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for studies published between Jan 1, 1980, and April 30, 2018. We also searched for unpublished or ongoing studies on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australian and New Zealand Clinical Trials Registry. We considered all studies examining any type and formulation of a medicinal cannabinoid in adults (≥18 years) for treating depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder, or psychosis, either as the primary condition or secondary to other medical conditions. We placed no restrictions on language, publication status, or study type (ie, both experimental and observational study designs were included). Primary outcomes were remission from and changes in symptoms of these mental disorders. The safety of medicinal cannabinoids for these mental disorders was also examined. Evidence from randomised controlled trials was synthesised as odds ratios (ORs) for disorder remission, adverse events, and withdrawals and as standardised mean differences (SMDs) for change in symptoms, via random-effects meta-analyses. The quality of the evidence was assessed with the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO (CRD42017059372, CRD42017059373, CRD42017059376, CRD42017064996, and CRD42018102977).Findings 83 eligible studies (40 randomised controlled trials, n=3067) were included: 42 for depression (23 randomised controlled trials; n=2551), 31 for anxiety (17 randomised controlled trials; n=605), eight for Tourette syndrome (two randomised controlled trials; n=36), three for ADHD (one randomised controlled trial; n=30), 12 for post-traumatic stress disorder (one randomised controlled trial; n=10), and 11 for psychosis (six randomised controlled trials; n=281). Pharmaceutical THC (with or without CBD) improved anxiety symptoms among individuals with other medical conditions (primarily chronic non-cancer pain and multiple sclerosis; SMD -0·25 [95% CI -0·49 to -0·01]; seven studies; n=252), although the evidence GRADE was very low. Pharmaceutical THC (with or without CBD) worsened negative symptoms of psychosis in a single study (SMD 0·36 [95% CI 0·10 to 0·62]; n=24). Pharmaceutical THC (with or without CBD) did not significantly affect any other primary outcomes for the mental disorders examined but did increase the number of people who had adverse events (OR 1·99 [95% CI 1·20 to 3·29]; ten studies; n=1495) and withdrawals due to adverse events (2·78 [1·59 to 4·86]; 11 studies; n=1621) compared with placebo across all mental disorders examined. Few randomised controlled trials examined the role of pharmaceutical CBD or medicinal cannabis.Interpretation There is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, post-traumatic stress disorder, or psychosis. There is very low quality evidence that pharmaceutical THC (with or without CBD) leads to a small improvement in symptoms of anxiety among individuals with other medical conditions. There remains insufficient evidence to provide guidance on the use of cannabinoids for treating mental disorders within a regulatory framework. Further high-quality studies directly examining the effect of cannabinoids on treating mental disorders are needed.Funding Therapeutic Goods Administration, Australia; Commonwealth Department of Health, Australia; Australian National Health and Medical Research Council; and US National Institutes of Health.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/s2215-0366(19)30401-8

Cites

99 of 99 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Previous systematic reviews have been limited in their coverage of all relevant diseases and primarily ignored that medical cannabinoid products differ in their pharmacology.

    “Previous systematic reviews have been limited in their coverage of all relevant diseases, but most importantly primarily ignored the fact that medical cannabinoid products—a term that encompasses all plant-derived and synthetic derivatives—differ in their pharmacology [1–5].”

    From Medical cannabinoids: a pharmacology-based systematic review and meta-analysis for all relevant medical indications. (2022) · cites this paper as [2]

    The Introduction says previous reviews had limited coverage of mental disorders and that no single review had considered the potential differential effects of different medicinal cannabinoids. It does not extend that assessment to all relevant diseases or specifically say that previous reviews ignored differences in pharmacology. Page numbers are not available in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Effects are larger in small studies using cannabinoids.

    “Small study sizes are of particular concern as it has been previously demonstrated that effects are larger in small studies using cannabinoids [2, 168].”

    From Medical cannabinoids: a pharmacology-based systematic review and meta-analysis for all relevant medical indications. (2022) · cites this paper as [2]

    The Discussion (Limitations and future directions; page not supplied) says larger effects had previously been identified in small studies of medicinal cannabinoids for chronic non-cancer pain (CNCP). The citing sentence omits that condition and presents the finding as applying to studies using cannabinoids generally. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 9

  1. [15]Veritas Health Innovation. Covidence systematic review software. Melbourne, Australia: Available at www.covidence.org.
  2. [16]Cochrane T Review Manager (RevMan) 5.3. Copenhagen: The Nordic Cochrane Centre 2008.
  3. [20]Deeks J, Higgins J, Altman D. Chapter 9: Analysing data and undertaking metaanalyses In: Higgins J, Churchill R, Chandler J, Cumpston M, eds. Cochrane Handbook for Systematic Reviews of Interventions: Cochrane; 2017.
  4. [26]Bellnier T, Brown G, Ortega T, Insull R. A preliminary evaluation of the effcacy, safety, and costs associated with the treatment of chronic pain with medical marijuana in the elderly. Consultant Pharmacist 2017; 32(10): 597.
  5. [33]Gerardi MC, Batticciotto A, Talotta R, Ditto MC, Atzeni F, Sarzi-Puttini P. Efficacy of cannabis flos in patients with fibromyalgia: A monocentric observational study. Arthritis and Rheumatology 2016; 68: 72– 4.
  6. [63]Bergamaschi MM, Queiroz RHC, Chagas MHN, Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-nave social phobia patients. Neuropsychopharmacology 2011; 36(6): 1219– 26. 21307846 PMC3079847
  7. [74]Arad S, Bar-Lev Schleider L, Knanni J, Medical cannabis for the treatment of Tourette syndrome: A descriptive analysis of 24 patients. Movement Disorders 2017; 31: S309– S10.
  8. [84]Quinn D, Hunter MA, Hager BW. Medicinal cannabis reduces agitation in acquired brain injury: Case study. Journal of Neurotrauma 2014; 33(13): A– 80.
  9. [104]Henquet C, Rosa A, Krabbendam L, An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology 2006; 31(12): 2748– 57. 16936704

Cited by

Sorted by citations

Related

Authors
Black, N., Stockings, E., Campbell, G., Tran, L. T., Zagic, D., Hall, W. D., Farrell, M., & Degenhardt, L.
Affiliations
  • UNSW Sydney (AU)
  • The University of Queensland (AU)
Corresponding author
Degenhardt, Louisa
ORCID
Venue
The Lancet Psychiatry
Publisher
Elsevier BV
Published
2019-12
Volume
6
Issue
12
Pages
995-1010
ISSN
2215-0366 (ISSN-L)
DOI
10.1016/s2215-0366(19)30401-8
PMC
PMC6949116
OpenAlex
W2981824949
Cited by
564
References
99
Citations by year
2026: 49 · 2025: 56 · 2024: 88 · 2023: 126 · 2022: 72 · 2021: 87 · 2020: 79 · 2019: 7
FWCI
7.85
Type
journal article
Language
en
Update notices
erratum (2020-01-01)
Open access
Licence
Locations
  • The Lancet Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
Funders
  • National Institutes of Health (NIDA R01DA1104470)
  • National Drug and Alcohol Research Centre
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
Keywords
tetrahydrocannabinol, cannabidiol, depression, anxiety, attention deficit hyperactivity disorder, Tourette syndrome, post-traumatic stress disorder, psychosis, symptom remission, adverse events, treatment safety, cannabinoids, mental illness, treatment withdrawal, medication adherence
MeSH terms
Anxiety, Attention Deficit Disorder with Hyperactivity, Australia, Cannabinoids, Depression, Tourette Syndrome, Humans, Stress Disorders, Post-Traumatic, Chronic Pain

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review