Skip to content

Does cannabidiol make cannabis safer? A randomised, double-blind, cross-over trial of cannabis with four different CBD:THC ratios

Amir Englund, D. Oliver, E. Chesney, Lucy A. Chester, Jack Wilson, Simina Sovi, A. de Micheli, J. Hodsoll, P. Fusar-Poli, J. Strang, Robin M. Murray, T. 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.

Study Year Design Participants
Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants 2012 Randomized controlled trial n = 48
Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... 2009 Double-blind, randomized, placebo-controlled crossover trial n = 15
Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life Healthy subjects aged 18 to 35 years 2017 Randomized controlled trial n = 60
Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects 2012 Randomized controlled trial n = 16
Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... 2009 Randomized controlled trial n = 15

Explore topics