An observational study of the effects of edible cannabis and its constituent cannabinoids on pain, inflammation, and cognition

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Chronic pain effects 76 million Americans and is the most commonly cited reason for use of medical marijuana. Marijuana and its constituent cannabinoids, including 9-delta-tetrahydrocannabinol (THC), are thought to be involved in reducing pain and associated inflammation. However, THC also is associated with harmful cognitive side effects. Synergistic interactions of cannabinoids are believed to produce different effects on pain and inflammation, as well as on cognitive function as compared to THC alone. For example, cannabidiol (CBD) is another primary cannabinoid that may work synergistically with THC in a multi-target analgesic and antiinflammatory approach. In addition, CBD does not have psychoactive properties and is thought to attenuate the negative cognitive side effects of THC. Despite limited data on their effects, there is a vast array of widely used marijuana products available for pain treatment across dispensaries throughout the US. These marijuana products contain a range cannabinoid potencies and ratios, which may have a large impact on their effects in chronic pain patients, including cognitive side effects. We propose an observational study to examine the effects of cannabinoid levels in blood on pain relief, inflammation, and cognitive dysfunction in chronic low back pain patients who choose to use edible cannabis in the context of a short-term (2 weeks) mechanistic study using a patient-oriented approach and a mobile pharmacology lab that solves many of the logistical problems with marijuana research. Our global hypothesis is that our observations of self-report and objective measures of the effects of marijuana edible products by pain patients who choose to use these products will vary as a function of the ratio of THC to CBD in their blood. Further, we hypothesize that cognitive impacts observed will differ by the THC/CBD ratio in blood. To that end, we will measure the association of pain, inflammation, and cognitive impairment with the levels of THC and CBD in the blood of pain patients who wish to use edible cannabis to treat their pain. This approach is ecologically valid and timely given that marijuana edibles of various cannabinoid potencies and ratios are widely used medically by patients in our state and across the US, yet absolutely no research has been done on these products to date. Blood levels of THC and CBD will be measured before, during, and after the exposure period (when participants in the observational study ingest a product they have purchased and choose to ingest) to determine whether there are associations with pain, inflammation, and cognitive dysfunction. Results from this study will provide critical and timely data to the public and health professionals regarding the effects of self-directed marijuana use, including the associations of various cannabinoids, on pain and related processes.