7T Functional MRS/MRI Assessment of Pain in Cannabis Users

Abstract

Despite analgesic efficacy reported by medicinal and recreational cannabis users, mounting empirical evidence suggests that long-term cannabis use is associated with worse pain outcomes. In the US, 33 states have enacted policies that permit cannabis use to treat a range of pain conditions, including chronic lower back pain, arthritis, fibromyalgia, and clinical pain associated with various disease states. As such, the focus of considerable scientific efforts has been to understand the neurobiological mechanisms that underpin cannabinoid-related pain modulation. Unfortunately, lacking robust research practices has contributed to mixed – and at times contradictory – conclusions regarding cannabinoid pain control. To provide clarification regarding the impact of cannabis use on neurochemical and neurobiological correlates of pain processing, the current study combined functional magnetic resonance spectroscopy (fMRS) and functional magnetic resonance imaging (fMRI) to examine metabolite level changes and functional responses to acute nociceptive stimulation among cannabis users (n = 17) and non-users (n = 23). Participant eligibility was determined using accepted cutoff scores across several assessments regarding anxiety, depression, prodromal, and somatic symptom severity, as well as dependence severity scores regarding amphetamine, cocaine, heroin/opioids, and psychomotor stimulant use. To be included, cannabis users needed to be recent, frequent users (i.e., > 4 use episodes in preceding 30-day period) and non-users were not permitted to endorse more than 3 lifetime cannabis use episodes. Regarding fMRS, there was modest evidence that cannabis use impacts dorsal anterior cingulate (dACC) glutamate and glutamate + glutamine (Glx) levels but not glutamine levels. Moreover, exploratory assessments revealed associations between cannabis use and dACC aspartate. Regarding fMRI, dACC functional responses during moderate nociceptive stimulation were not associated with dACC metabolite level changes, including glutamate, glutamine, Glx, and aspartate. Importantly, understanding neurochemical and neurobiological impacts associated with cannabis among frequent, long-term cannabis users is an important step toward developing effective pain management strategies as access to medicinal and recreational cannabis continue to expand.