Co-exposure of cannabinoids with amphetamines and biological, behavioural and health outcomes a scoping review of animal and human studies.
The growing prevalence of psychostimulant (including amphetamine) use and associated health harms, with limited treatment options, present a global challenge. There is an increasing availability and medical applications of cannabinoids, and growing interest in their therapeutic potential for addictive disorders. The objective of this study is to review available data regarding cannabiscannabinoid co-use or exposure on amphetamine-related outcomes. Towards the present scoping review, we systematically searched four databases (Medline, Web-of-Science, CINAHL Plus and PsycInfo) using cannabiscannabinoid and amphetamine text-terms identifying peer-reviewed, English-language studies published in 2000-2020 involving multiple methods approaches among both human and animal study samples, assessing the association of co-useadministration of cannabiscannabinoids products with non-medical amphetamines on biological, behavioural or health outcomes. Twenty-five articles were included. Pre-clinical studies (n 15) found mostly protective effects of single or repeated cannabinoids administration on rodents in amphetamine addiction models, amphetamine-induced models of human mental disorders (e.g. schizophrenia) and amphetamine-induced neurotoxicity. Human studies (n 10) were more heterogeneously designed (e.g. cross-sectional, case-control, longitudinal) and assessed natural ongoing cannabis and methamphetamine use or dependence, showing mostly enhanced harms in a diversity of outcomes (e.g. mental health, methamphetamine use, cognition). While human studies suggest cannabis use as an adverse risk factor among non-medical amphetamine users, pre-clinical studies suggest therapeutic potential of cannabinoids, especially cannabidiol, to alleviate amphetamine addiction and harms, including treatment outcomes. Given increasing psychostimulant harms but lack of care options, rigorous, high-quality design studies should aim to translate and investigate pre-clinical study results for potential therapeutic benefits of cannabinoids for amphetamine useabuse in human subjects.