Reply to Manthey et al .: Estimating the association between THC and health outcomes requires rigorous research methods and continued monitoring of cannabis markets

Manthey and colleagues [1] discuss the challenges in establishing a link between delta-9-tetrahydrocannabinol (THC) and cannabis use disorder (CUD). In our study [2], we assessed cannabis use comprehensively with the Enhanced Cannabis Timeline Follow-Back (EC-TLFB) tool [3], administered every 3 months over a period of 1 year. Using data on frequency, type and quantity, we estimated THC consumption in standard THC units (1 unit = 5 mg THC). To estimate THC content across product types, we used UK police seizure data from 2015 to 2016, representing the most recent and highest quality available data [4], corresponding to our 2017–2019 study. Samples were collected from five constabularies, including London, where most participants were recruited, and the study carefully identified product types and their %THC. Standard THC units generated using these %THC estimates had the strongest association with urinary 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH) concentrations of all EC-TLFB cannabis use measures [3]. Manthey et al. highlight other European sources that indicate the THC concentration in hash/resin products has dramatically increased, which may not be reflected in the estimates we used [5]. Although we agree that there is some uncertainty about the estimates we used, hash/resin was rarely consumed in our sample (e.g. 91% of adults most commonly used herbal/sinsemilla cannabis) [6]. European data are useful for estimating trends across a wide geographical region; however, they come from various sources, without detailed information on sampling methodology, sample size or distinct product types (e.g. different types of herbal cannabis). More regular monitoring and reporting of THC concentrations in the UK and internationally is needed to characterise changes in cannabis markets and estimate health effects. We agree with Manthey et al. that the frequency of cannabis use is strongly associated with risk of CUD. Our pre-registered study was intended to provide proof-of-concept evidence for a new approach (weekly THC unit thresholds) rather than to compare it with existing methods. If weekly THC unit thresholds are incorporated into lower risk guidelines, they could be complementary to existing recommendations, such as refraining from daily or near-daily use [7]. However, as an exploratory step we calculated an area under the receiver operating characteristic curve (AUC) of 0.75 for frequency on CUD in our sample. We also conducted a power calculation for a future study comparing this with the AUC for standard THC units (0.79). A future study with approximately n = 900 would be needed to detect this difference, though this will depend on the rate of CUD in the population studied. Importantly, the extent to which these methods compare may be strongly dependent on the population studied (e.g. general population vs those who use cannabis regularly). Recent findings provide some of the strongest evidence to date that among those who consume cannabis daily, the amount of THC consumed is associated with the risk and severity of CUD [8]. Thus, for people who use cannabis daily, reducing THC consumption could be a particularly relevant harm reduction strategy. In conclusion, our study provides proof-of-concept evidence for a new approach to cannabis harm reduction. To address challenges in estimating THC consumption, rigorous methods are needed to assess cannabis use, alongside the regular monitoring of cannabis products. Rachel Lees Thorne: Conceptualization; data curation; formal analysis; project administration; writing—original draft; writing—review and editing. Will Lawn: Conceptualization; supervision; writing—review and editing. Tom P. Freeman: Conceptualization; supervision; writing—review and editing. None. None to declare. Data sharing not applicable to this article as no datasets were generated or analysed.