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Adolescence represents one of the most crucial periods of human brain development. This unique neurodevelopmental window involves a complex interplay of synaptic re-modelling, the establishing of cortical and sub-cortical emotional processing and cognitive neural circuits along with a greater propensity for engaging in risky behaviours and experimentation with illicit drugs. A growing body of both clinical and pre-clinical evidence has demonstrated that exposure to cannabis, and more specifically, Δ-9-tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, can strongly increase the likelihood of developing serious neuropsychiatric disorders in later life. Adolescent THC exposure is linked to long-term cognitive impairments, emotional dysregulation, mood disorders and increased vulnerability to schizophrenia. The interplay between adolescent THC exposure and mental health risks have been linked to a wide array of underlying neurobiological pathologies, including structural and morphological alterations in brain circuits linked to cognitive function and emotional regulation. Despite this growing body of data, there remains considerable confusion and misinformation regarding how and why adolescent cannabis use can ultimately increase these psychopathological risk factors. Nevertheless, the confluence of clinical and pre-clinical neuroscience research related to these questions is finally providing much needed insight into the relative risks and identifying useful biomarkers that may ultimately allow us to establish more reliable criteria and guidelines for safer cannabis access and help mitigate these risks to mental health.