Beyond adolescence: cannabinoid exposure during extended human brain development

Over the past decade in the United States, cannabis use has risen dramatically, with daily or near-daily consumption now affecting an estimated 18 million individuals, up from approximately 6 million in 2012 and fewer than one million in 1992. In parallel, Δ9-tetrahydrocannabinol (THC) potency in commercial products has increased substantially, with many legal-market preparations now exceeding 20%, far above historical levels. While legalization has expanded access, regulatory frameworks have not consistently kept pace, raising concerns about public health and neurodevelopmental risk. The endocannabinoid system is a key regulator of brain maturation, governing synaptic pruning, circuit refinement, and excitatory–inhibitory balance via CB1 receptors densely expressed in corticolimbic regions. Δ9-THC exposure during sensitive developmental windows may disrupt these processes, altering prefrontal circuit maturation and producing lasting impairments in cognitive control and executive function. Neuroimaging evidence indicates atypical cortical developmental trajectories in adolescent cannabis users, consistent with disruption of sensitive-period mechanisms. Emerging data further highlight sex-dependent vulnerability, neuroimmune involvement, and dopaminergic alterations linked to reward processing and addiction risk. Importantly, brain maturation extends into the early thirties, well beyond traditional definitions of adolescence, overlapping with peak cannabis exposure and reshaping the temporal landscape of vulnerability.

This Research Topic aims to integrate mechanistic, circuit-level, clinical, and population evidence to clarify how cannabinoid exposure during adolescence and young adulthood interacts with prolonged brain maturation to shape neurodevelopmental and behavioral outcomes, with implications for mental health and public policy. By bridging molecular, neuroimaging, epidemiological, and policy perspectives, it addresses a fragmented literature and reframes cannabinoid vulnerability in light of extended brain development into the early thirties. The goal is clarity, not advocacy: to delineate what is known, what remains uncertain, and what demands urgent investigation as cannabis legalization advances faster than scientific integration.

We particularly welcome submissions of original research, systematic reviews, meta-analyses, and expert reviews spanning the following areas:

• Endocannabinoid system ontogeny and sensitive periods: developmental trajectories of CB1R/CB2R expression and endocannabinoid tone from prenatal life through young adulthood.
• Adolescent CB1R signaling and prefrontal circuit maturation: preclinical studies on how cannabinoid exposure disrupts GABAergic and glutamatergic development and downstream executive function.
• Neuroimaging correlates of adolescent cannabis use: longitudinal MRI, DTI, and PET studies linking cortical thinning, white-matter integrity, and functional connectivity alterations in CB1R-rich regions.
• Dopamine system interactions and reward processing: how developmental cannabinoid exposure alters mesolimbic and mesocortical dopamine signaling.
• Sex differences in cannabinoid sensitivity: sex-dependent modulation of CB1R expression, endocannabinoid metabolism, and cognitive outcomes.
• High-potency cannabis and dose–response relationships: effects of increasing THC concentrations on adolescent brain development and risk of psychiatric outcomes.
• Cannabis, psychosis, and schizophrenia-spectrum risk: mechanistic and epidemiological evidence, including gene–environment interactions.
• Long-term cognitive and academic outcomes: longitudinal studies of attention, executive function, verbal memory, learning, and cognitive trajectories.
• Comorbid substance use and addiction vulnerability: interactions between adolescent cannabis exposure and alcohol, nicotine, and opioid use.
• Non-psychotropic and synthetic cannabinoids: neurodevelopmental effects of CBD, CBG, and synthetic cannabinoids during adolescence.
• Glial and neuroimmune mechanisms: roles of astrocytic and microglial CB1R/CB2R signaling in neuroinflammation and developmental outcomes.
• Policy, regulation, and harm reduction: evidence-based perspectives on potency regulation, taxation, age-of-access policies, and public health interventions.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review

Keywords: Neurodevelopment, Substance use, Adolescent health, Cannabis use, mental health

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.