Does cannabidiol make cannabis safer? A randomised, double-blind, cross-over trial of cannabis with four different CBD:THC ratios
Amir Englund, D. Oliver, Edward Chesney, Lucy Chester, Jack Wilson, Simina Sovi, A. de Micheli, John Hodsoll, Paolo Fusar‐poli, John Strang, Robin Murray, Tom P. Freeman, P. McGuire
Neuropsychopharmacology November 16, 2022 DOI: 10.1038/s41386-022-01478-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, within-subject, randomised trial Randomized Peer reviewed |
|---|---|
| Sample size | 46 |
| Population | Healthy, infrequent cannabis users |
| Interventions | 10 mg 20 mg |
| Dose | 10 mg THC with either 0 mg (0:1 CBD:THC), 10 mg (1:1), 20 mg (2:1), or 30 mg (3:1) CBD |
| Duration | Initial baseline visit followed by four drug administration visits |
| Measures | Hopkins Verbal Learning Task, Positive and Negative Syndrome Scale (PANSS) positive subscale |
| Topics | Cannabis CBD |
| Key findings | THC (10 mg) impaired delayed verbal recall and induced positive psychotic symptoms, and these effects were not significantly modulated by any dose of CBD (10, 20, or 30 mg). The authors report no evidence that CBD protects against the acute adverse effects of cannabis at CBD:THC ratios common in medicinal and recreational products, and argue this should be considered in health policy and safety decisions. |
Abstract
As countries adopt more permissive cannabis policies, it is increasingly important to identify strategies that can reduce the harmful effects of cannabis use. This study aimed to determine if increasing the CBD content of cannabis can reduce its harmful effects. Forty-six healthy, infrequent cannabis users participated in a double-blind, within-subject, randomised trial of cannabis preparations varying in CBD content. There was an initial baseline visit followed by four drug administration visits, in which participants inhaled vaporised cannabis containing 10 mg THC and either 0 mg (0:1 CBD:THC), 10 mg (1:1), 20 mg (2:1), or 30 mg (3:1) CBD, in a randomised, counter-balanced order. The primary outcome was change in delayed verbal recall on the Hopkins Verbal Learning Task. Secondary outcomes included change in severity of psychotic symptoms (e.g., Positive and Negative Syndrome Scale [PANSS] positive subscale), plus further cognitive, subjective, pleasurable, pharmacological and physiological effects. Serial plasma concentrations of THC and CBD were measured. THC (0:1) was associated with impaired delayed verbal recall (t(45) = 3.399, d = 0.50, p = 0.001) and induced positive psychotic symptoms on the PANSS (t(45) = −4.709, d = 0.69, p = 2.41 × 10–5). These effects were not significantly modulated by any dose of CBD. Furthermore, there was no evidence of CBD modulating the effects of THC on other cognitive, psychotic, subjective, pleasurable, and physiological measures. There was a dose-response relationship between CBD dose and plasma CBD concentration, with no effect on plasma THC concentrations. At CBD:THC ratios most common in medicinal and recreational cannabis products, we found no evidence that CBD protects against the acute adverse effects of cannabis. This should be considered in health policy and safety decisions about medicinal and recreational cannabis.
Comparable studies
Other randomized controlled trials on CBD, most cited first.
Citations in the library
Cited by 27
- Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on Plasma Endocannabinoid Levels in Healthy Volunteers: A Randomized Double-Blind Four-Arm Crossover Study Cannabis and Cannabinoid Research December 9, 2022
- Acute effects of different types of cannabis on young adult and adolescent resting-state brain networks Neuropsychopharmacology May 28, 2024
- Cannabidiol Increases Psychotropic Effects and Plasma Concentrations of Δ9-Tetrahydrocannabinol Without Improving Its Analgesic Properties. Clinical Pharmacology & Therapeutics November 1, 2024
- High-Concentration Delta-9-Tetrahydrocannabinol Cannabis Products and Mental Health Outcomes : A Systematic Review. Annals of Internal Medicine October 1, 2025
- Pharmacological characterization of cannabidiol as a negative allosteric modulator of the 5-HT2A receptor. Cellular signalling March 1, 2025
and 22 more in the library
Cites 13
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- Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Psychopharmacology May 1, 2019
- Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis ‘amotivational’ hypotheses Psychopharmacology September 2, 2016
- The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study The Lancet Psychiatry May 1, 2019
- Individual and combined effects of acute delta-9-tetrahydrocannabinol and cannabidiol on psychotomimetic symptoms and memory function. Translational Psychiatry September 5, 2018
and 8 more in the library