Comment on: Patient-reported outcomes in those consuming medical cannabis: a prospective longitudinal observational study in patients with chronic pain

Abstract

To the Editor, The recent article by Meng et al. presents an interesting and courageous longitudinal investigation on the administration of cannabis extracts for the management of chronic pain. The authors discuss study limitations, and we agree with the points made. Yet, the lack of welldefined good manufacturing practice certifications for the cannabis extracts used throughout the investigation could in part explain the administration of cannabis reported high participant attrition/low completion rate, of 25% at 12 months. Moreover, many participants in the longitudinal study used the cannabis extracts orally as an oil, and gut dysbiosis could have been a limiting factor for cannabinoid absorption. Concerning the management of pain, an increasing body of clinical research supports the combined administration of D9-tetrahydrocannabinol (D9THC) and cannabidiol (CBD) for the relief of certain types of chronic pain, including neuropathic pain and spasticity. Therefore, batches of cannabis extracts with inconsistent D9THC and CBD content can have widely variable levels of therapeutic efficacy for the management of chronic pain. Therefore, it is plausible that the high level of patient attrition could be a consequence of cannabis plant extracts with unknown or variable cannabinoid content of D9THC and CBD, resulting in ineffective therapeutic pain relief and dropout. This notion is further supported by the large percentage of naı̈ve cannabis users (60.9% at baseline) that was included in the study. Further, a lack of reliable and reproducible cannabinoid content of the extracts or oil administered and the various modes of delivery (e.g., oral ingestion) raise uncertainty. It is known that habitual users of cannabis do respond differently to naı̈ve users, as was notably shown in an early placebo-controlled study in patients with HIV polyneuropathy; habitual users will know more readily than new users whether the cannabis used will produce an effect. Other than the fact that different amounts of cannabis extract were self-reported, it is not known what cannabis molecules patients were consuming in the study by Meng et al. Quantities ranging from \\ 1 g to [ 20 g, predominantly from dried cannabis extracts or extracts in oil, were the most common forms used. Formulations of cannabis-based medicines that improve chronic pain must include consistent well-defined and specific levels of D9THC and CBD—a notion supported by the published literature and systematic reviews. The longitudinal study teaches that real-world observational data require stable standardized cannabinoid-based medicines that explore additional delivery methods (e.g., orobuccal delivery) to achieve efficacy and tolerability for the treatment of pain.