CBD can potentiate the psychoactive and physiological effects of THC in rats, most likely by delaying the metabolism and elimination of THC through an action on the CYP450 enzymes that metabolise both drugs.

Impairments in cognitive ability and widespread pathophysiological changes caused by neurotoxicity, neuroinflammation, oxidative damage, and altered cholesterol homeostasis are associated with Alzheimer's disease (AD). Cannabidiol (CBD) has been shown to reverse cognitive deficits of AD transgenic mice and to exert neuroprotective, anti-oxidative, and anti-inflammatory properties in vitro and in vivo. Here we evaluate the preventative properties of long-term CBD treatment in male AβPPSwe/PS1ΔE9 (AβPP × PS1) mice, a transgenic model of AD. Control and AD transgenic mice were treated orally from 2.5 months of age with CBD (20 mg/kg) daily for 8 months. Mice were then assessed in the social preference test, elevated plus maze, and fear conditioning paradigms, before cortical and hippocampal tissues were analyzed for amyloid load, oxidative damage, cholesterol, phytosterols, and inflammation. We found that AβPP × PS1 mice developed a social recognition deficit, which was prevented by CBD treatment. CBD had no impact on anxiety or associative learning. The prevention of the social recognition deficit was not associated with any changes in amyloid load or oxidative damage. However, the study revealed a subtle impact of CBD on neuroinflammation, cholesterol, and dietary phytosterol retention, which deserves further investigation. This study is the first to demonstrate CBD's ability to prevent the development of a social recognition deficit in AD transgenic mice. Our findings provide the first evidence that CBD may have potential as a preventative treatment for AD with a particular relevance for symptoms of social withdrawal and facial recognition.

Previous studies have suggested that administration of oxytocin (OT) can have modulatory effects on social and anxiety-like behavior in mammals that may endure beyond the time of acute OT administration. The current study examined whether repeated administration of OT to male Wistar rats (n = 48) during a key developmental epoch (early adolescence) altered their physiology and behavior in later-life. Group housed rats were given intraperitoneal injections of either 1 mg/kg OT or vehicle during early adolescence (post natal-days [PND] 33–42). OT treatment caused a transient inhibition of body weight gain that recovered quickly after the cessation of treatment. At PND 50, the rats pre-treated with OT displayed less anxiety-like behavior on the emergence test, while at PND 55 they showed greater levels of social interaction. A subgroup of OT pre-treated rats examined at PND 63 showed a strong trend towards increased plasma OT levels, and also displayed significantly increased OT receptor mRNA in the hypothalamus. Rats pre-treated with OT and their controls showed similar induction of beer intake in daily 70 min test sessions (PND 63 onwards) in which the alcohol concentration of beer was gradually increased across days from 0.44% to 4.44%. However, when given ad libitum access to beer in their home cages from PND 72 onwards (early adulthood), consumption of beer but not water was significantly less in the OT pre-treated rats. A “booster” shot of OT (1 mg/kg) given after 25 days of ad libitum access to beer had a strong acute inhibitory effect on beer intake without affecting water intake. Overall these results suggest that exogenous OT administered during adolescence can have subtle yet enduring effects on anxiety, sociability and the motivation to consume alcohol. Such effects may reflect the inherent neuroplasticity of brain OT systems and a feed-forward effect whereby exogenous OT upregulates endogenous OT systems.

Lysosomes are the primary catabolic compartment for the degradation of intracellular proteins through autophagy. The presence of abnormal intracellular α-synuclein-positive aggregates in Parkinson's disease (PD) indicates that the degradative capacity of lysosomes is impaired in PD. Specific dysfunction of chaperone-mediated autophagy (CMA) in PD is suggested by reductions in the CMA membrane receptor, lysosomal-associated membrane protein (LAMP) 2A, although whether LAMP2A is the only LAMP2 isoform affected by PD is unknown. Messenger RNA (mRNA) and protein expression of all three LAMP2 isoforms was assessed in brain extracts from regions with and without PD-related increases in α-synuclein in autopsy samples from subjects in the early pathological stage of PD (n = 9), compared to age- and postmortem delay-matched controls (n = 10). In the early stages of PD, mRNA expression of all LAMP2 isoforms was not different from controls, with LAMP2B and LAMP2C protein levels also unchanged in PD. The selective loss of LAMP2A protein directly correlated with the increased levels of α-synuclein and decreased levels of the CMA chaperone heat shock cognate protein 70 in the same PD samples, as well as with the accumulation of cytosolic CMA substrate proteins. Our data show that LAMP2 protein isoforms are differentially affected in the early stages of PD, with LAMP2A selectively reduced in association with increased α-synuclein, and suggests that dysregulation of CMA-mediated protein degradation occurs before substantial α-synuclein aggregation in PD.