Co-exposure of Cannabinoids with Amphetamines and Biological, Behavioural and Health Outcomes: a Scoping Review of Animal and Human Studies

Rationale: 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.

Objectives: The objective of this study is to review available data regarding cannabis/cannabinoid co-use or exposure on amphetamine-related outcomes.

Methods: Towards the present scoping review, we systematically searched four databases (Medline, Web-of-Science, CINAHL Plus and PsycInfo) using cannabis/cannabinoid 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-use/administration of cannabis/cannabinoids products with non-medical amphetamines on biological, behavioural or health outcomes.

Results: 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).

Conclusions: 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 use/abuse in human subjects.