System‐specific activity in response to Δ⁹‐tetrahydrocannabinol: a functional magnetic resonance imaging study in awake male rats

Abstract

The aim of this study was to assess the effects of two doses of Δ -tetrahydrocannabinol (THC, cannabis' main psychoactive agent) and vehicle on blood-oxygen-level dependent (BOLD) activity in drug-naïve, awake rats, in an effort to obtain a THC-specific map of activation in clinically-relevant regions and systems. Intraperitoneal injections of low dose of THC resulted in increased positive and negative BOLD signals compared to vehicle and high dose in areas rich in cannabinoid receptor 1, as well as throughout the pain and hippocampal neural systems. These results offer unique maps of activity, or 'fingerprints', associated with systemic THC administration, allowing for further comparisons with either additional doses or compounds, or between THC administration modalities (i.e. systemic vs. ingested vs. inhaled), which ultimately adds to the translatability assessment of THC-induced BOLD between animal and human studies.

Chronic exposure to inhaled vaporized cannabis high in Δ9-THC alters brain structure in adult female mice

“…Both VBM and DWI in this study on adult female mice revealed changes in the accumbens, ventral pallidum and caudate putamen, key brain areas high in afferent connections from the midbrain DA system. The sensitivity of these areas to Δ9-THC is consistent with the preclinical literature ( Kolb et al, 2006 ; Madularu et al, 2017 ). Interestingly, the Coleman study on periadolescent mice exposed to vaporized cannabis found no change in the DA system with VBM and a modest change in ADC values, and only then to the accumbens core ( Coleman et al, 2022 ).…”

Cannabidiol Has a Unique Effect on Global Brain Activity: A Pharmacological, Functional MRI Study in Awake Mice 

“…The absence of BOLD signal change in brain areas between the rostral/caudal axis of the brain (e.g., hippocampus, sensorimotor cortices, thalamus, hypothalamus, amygdala, and basal ganglia) made this pattern of activation and deactivation especially intriguing. This is unlike anything reported in awake animal imaging following tests on numerous CNS active drugs (33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45). Here we show the positive and negative changes in BOLD signal occur within 10 min of injection, and while CBD is known to rapidly penetrate the brain within seconds following systemic administration (46), its effects could be orchestrated easily by both peripheral and central targets.…”

Cannabidiol has a unique effect on global brain activity: a pharmacological, functional MRI study in awake mice

“…The absence of BOLD signal change in brain areas between the rostral/caudal axis of the brain (e.g., hippocampus, sensorimotor cortices, thalamus, hypothalamus, amygdala, and basal ganglia) made this pattern of activation and deactivation especially intriguing. This is unlike anything reported in awake animal imaging following tests on numerous CNS active drugs [8][9][10][11][39][40][41][42][43][44][45][46][47]. Here we show the positive and negative changes in BOLD signal occur within 10 min of injection, and while CBD is known to rapidly penetrate the brain within seconds following systemic administration [48], its effects could be orchestrated easily by both peripheral and central targets.…”