Researchers in the United Kingdom have found, perhaps ironically, that cannabidiol (CBD) from cannabis, used in medical marijuana, can help tackle cannabis dependence among users. The study led by researchers from the University of Bath and University College London, just been published in The Lancet Psychiatry.
Cannabis affects everyone differently and can create deleterious effects for some individuals. There is no established treatment for cannabis use disorder, but the UK study provides some answers and some treatment hope in the forms of the non-intoxicating cannabidiol.
One recent study indicates that 30% of marijuana consumers have some degree of cannabis use disorder, writes Brendan Bures for The French Toast content agency in a 31 July article published in the Chicago Tribune.
These disorders are characterised by dependence. When a user experiences withdrawal symptoms when not using cannabis, these can include irritability, sleeping problems and appetite fluctuations.
Some research suggests that 9% of marijuana users will become dependent on the plant, while other studies have found 22 million people worldwide struggle to function in their daily lives because of cannabis.
Previous research has shown the possibility that CBD may help to alleviate cannabis use disorder, but this is the first double-blind, placebo-controlled study to explore the concept in a rigorous scientific setting.
The study
The research team is from the University of Bath, University College London, Kings College London and the University of Exeter and the Substance Misuse Services at Camden and Islington National Health Service Foundation Trust in London.
Researchers recruited 82 participants motivated to quit marijuana but who had struggled on their own in the past. Subjects, all diagnosed with cannabis use disorder, were then given three varying amounts of medical-grade CBD or a placebo in the first stage of the trial. Researchers discovered 200mg of CBD was ineffective and so only administered 400mg and 800mg doses in the second trial.
By the end of the study, researchers reported conclusive evidence that 400mg or 800mg CBD doses outperformed lesser doses of CBD in helping decrease marijuana use. It’s worth noting that prescription-grade CBD, as used in the study, can be up to 16 times stronger than commercially available CBD.
"The results from our trial open up a novel therapeutic strategy for managing problematic cannabis use in clinical settings,” said lead author Dr Tom Freeman, in the article published by Chicago Tribune.
He added later: "Whilst it may seem counterintuitive to treat problematic cannabis use with CBD – a constituent part of the cannabis plant – THC and CBD have contrasting effects on our own endogenous cannabinoid system,” Freeman said.
“Unlike THC, CBD does not produce intoxicating or rewarding effects and it shows potential for a treating several other medical disorders.”
Canabidiol for the treatment of cannabis use disorder: a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial
The Lancet Psychiatry. Published on 28 July 2020.
Authors
Tom P Freeman, Chandni Hindocha, Professor Gianloca Baio, Natacha DC Shaban, Emily M Thomas, Danica Astbury, Abigail M Freeman, Rachel Lees, Sam Craft, Paul D Morrison, Michael AP Bloomfield, Dominic O’Ryan, Jane Kinghorn, Professor Celia JA Morgan, Ali Mofeez and Professor H Valerie Curran.
Abstract
A substantial and unmet clinical need exists for pharmacological treatment of cannabis use disorders. Cannabidiol could offer a novel treatment, but it is unclear which doses might be efficacious or safe. Therefore, we aimed to identify efficacious doses and eliminate inefficacious doses in a phase 2a trial using an adaptive Bayesian design.
Methods
We did a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial at the Clinical Psychopharmacology Unit (University College London, London, UK). We used an adaptive Bayesian dose-finding design to identify efficacious or inefficacious doses at a-priori interim and final analysis stages. Participants meeting cannabis use disorder criteria from DSM-5 were randomly assigned (1:1:1:1) in the first stage of the trial to 4-week treatment with three different doses of oral cannabidiol (200 mg, 400 mg, or 800 mg) or with matched placebo during a cessation attempt by use of a double-blinded block randomisation sequence. All participants received a brief psychological intervention of motivational interviewing. For the second stage of the trial, new participants were randomly assigned to placebo or doses deemed efficacious in the interim analysis. The primary objective was to identify the most efficacious dose of cannabidiol for reducing cannabis use. The primary endpoints were lower urinary 11-nor-9-carboxy-δ-9-tetrahydrocannabinol (THC-COOH):creatinine ratio, increased days per week with abstinence from cannabis during treatment, or both, evidenced by posterior probabilities that cannabidiol is better than placebo exceeding 0·9. All analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT02044809) and the EU Clinical Trials Register (2013-000361-36).
Findings
Between May 28, 2014, and Aug 12, 2015 (first stage), 48 participants were randomly assigned to placebo (n=12) and to cannabidiol 200 mg (n=12), 400 mg (n=12), and 800 mg (n=12). At interim analysis, cannabidiol 200 mg was eliminated from the trial as an inefficacious dose.
Between May 24, 2016, and Jan 12, 2017 (second stage), randomisation continued and an additional 34 participants were allocated (1:1:1) to cannabidiol 400 mg (n=12), cannabidiol 800 mg (n=11), and placebo (n=11).
At final analysis, cannabidiol 400 mg and 800 mg exceeded primary endpoint criteria (0·9) for both primary outcomes. For urinary THC-COOH:creatinine ratio, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9995 for cannabidiol 400 mg and 0·9965 for cannabidiol 800 mg.
For days with abstinence from cannabis, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9966 for cannabidiol 400 mg and 0·9247 for cannabidiol 800 mg. Compared with placebo, cannabidiol 400 mg decreased THC-COOH:creatinine ratio by −94·21 ng/mL (95% interval estimate −161·83 to −35·56) and increased abstinence from cannabis by 0·48 days per week (0·15 to 0·82).
Compared with placebo, cannabidiol 800 mg decreased THC-COOH:creatinine ratio by −72·02 ng/mL (−135·47 to −19·52) and increased abstinence from cannabis by 0·27 days per week (−0·09 to 0·64). Cannabidiol was well tolerated, with no severe adverse events recorded, and 77 (94%) of 82 participants completed treatment.
Interpretation
In the first randomised clinical trial of cannabidiol for cannabis use disorder, cannabidiol 400 mg and 800 mg were safe and more efficacious than placebo at reducing cannabis use.
Funding
Medical Research Council.
[link url="https://www.chicagotribune.com/marijuana/sns-tft-cbd-effectively-treats-cannabis-use-20200731-5luqzb236vbwva7oiyfl4ev2bq-story.html"]Research finds CBD effective at treating cannabis use disorder[/link]
[link url="https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(20)30290-X/fulltext"]Canabidiol for the treatment of cannabis use disorder: a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial[/link]