Stress is a major determinant of psychopathology, with coping and cognitive impairment arising from abnormal glucocorticoid activity and brain-derived neurotrophic factor (BDNF)-dependent neuroplasticity in the hippocampus. The endocannabinoid system modulates stress and hippocampal functioning since early development, thus its early-life disruption may program vulnerability to stress-related...
Minor cannabinoids and semisynthetic cannabis constituents, such as derivatives of tetrahydrocannabinol (THC) and hexahydrocannabinol (HHC), are increasingly encountered in consumer products, yet their signaling profiles at cannabinoid receptors remain incompletely characterized. Here, we describe how structural modifications of THC and HHC, including variations in alkyl side-chain length...
Long-chain polyunsaturated fatty acids (LC-PUFAs) are crucial for brain development, with ω-3 species supporting neuronal membrane architecture, synaptogenesis and cognitive maturation, and ω-6 species linking lipid metabolism to neuronal signalling via the endocannabinoid system (ECS), the network of receptors, lipid mediators, and enzymatic pathways that orchestrate neurodevelopmental...
Background: Endocannabinoid (eCB) signalling is pivotal for brain programming, including the reward system neurodevelopment. Prenatal exposure to Δ9-tetrahydrocannabinol (THC), cannabis psychoactive component, can perturb eCB tone via CB1 receptor and alter the response to salient stimuli. Aim: We hypothesise that prenatal THC exposure disrupts the eCB-dopamine nexus in the nucleus accumbens...
Hexahydrocannabinol (HHC) is a new psychoactive substance known for its mind-altering effects and temporary legal status. It is widely used in parts of the Europe and United Kingdom as a legal alternative to ∆9-tetrahydrocannabinol, yet little research has explored its effects and safety. This study examined how HHC is processed in the body, its toxicity, and its impact on behavior in male...
Mitochondria are central to cellular energy metabolism, contributing to synaptic transmission and plasticity. The mitochondrial membranes present the cannabinoid type-1 receptor (mito-CB1R), which has been functionally linked to neuronal energy supply and cognitive processing. Prenatal exposure to Δ9-tetrahydrocannabinol (pTHC) has been associated with cognitive impairments associated with...
Background and purpose: Hexahydrocannabinol (HHC) is a novel psychoactive substance that has gained attention due to its psychotropic effects and temporary legal status. It is widely abused in several EU and US countries, where it serves as a legal and easily accessible alternative to ∆ 9 -tetrahydrocannabinol (∆ 9 -THC). Despite its widespread use, few studies have examined its in vivo effects...
Abstract The Cannabis sativa plant has been used for centuries as a recreational drug and more recently in the treatment of patients with neurological or psychiatric disorders. In many instances, treatment goals include relief from posttraumatic disorders, anxiety, or to support treatment of chronic pain. Ligands acting on cannabinoid receptor 1 (CB1R) are also potential targets for the...
Adolescent exposure to cannabinoids as a postnatal environmental insult may increase the risk of psychosis in subjects exposed to perinatal insult, as suggested by the two-hit hypothesis of schizophrenia. Here, we hypothesized that peripubertal Δ9-tetrahydrocannabinol (aTHC) may affect the impact of prenatal methylazoxymethanol acetate (MAM) or perinatal THC (pTHC) exposure in adult rats. We...
agonists containing substances emerging on the illicit drug market as a replacement for N,N-diethyllysergamide (LSD). Despite the increasing use of NBOMes for diagnostic, research and recreational purposes, only a limited number of studies have focussed on their in vivo effect. Here, we investigated pharmacokinetics, systemic toxicity, thermoregulation in individually and group-housed animals,...