The Cannabis plant contains more than 100 currently known phytocannabinoids. Regarding the rising consumption of the non-psychotropic phytocannabinoid cannabidiol (CBD) in people’s everyday life (e.g., beauty products, food and beverages), the importance of studies on the influence of CBD on healthy humans and rodents is evident. Therefore, the behavioral profile of CBD was investigated with a battery of behavioral tests, including motor, anxiety, and memory tests after prolonged CBD treatment. Adult C57Bl/6J wildtype (WT) mice were daily intraperitoneally injected with 20 mg/kg CBD for 6 weeks starting at two different points of ages (3 months and 5 months) to compare the influence of prolonged CBD treatment with a washout period (former group) to the effects of long term CBD treatment (current group). Our results show that CBD treatment does not influence motor performance on an accelerating Rotarod test, while it also results in a lower locomotor activity in the open field (OF). No influence of CBD on spatial learning and long term memory in the Morris Water Maze (MWM) was observed. Memory in the Novel Object Recognition test (NORT) was unaffected by CBD treatment. Two different anxiety tests revealed that CBD does not affect anxiety behavior in the Dark-Light Box (DLB) and OF test. Although, anxiety is altered by current CBD treatment in the Elevated Plus Maze (EPM). Moreover, CBD-treated C57Bl/6J mice showed an unaltered acoustic startle response (ASR) compared to vehicle-treated mice. However, current CBD treatment impairs prepulse inhibition (PPI), a test to analyze sensorimotor gating. Furthermore, prolonged CBD treatment did not affect the hippocampal neuron number. Our results demonstrate that prolonged CBD treatment has no negative effect on the behavior of adult C57Bl/6J mice.

The presynaptic protein Mover/TPRGL/SVAP30 is absent in Drosophila and C. elegans and differentially expressed in synapses in the rodent brain, suggesting that it confers specific functions to subtypes of presynaptic terminals. In order to investigate how the absence of this protein affects behavior and learning, Mover knockout mice (KO) were subjected to a series of established learning tests. To determine possible behavioral and cognitive alterations, male and female 8-week-old KO and C57Bl/6J wildtype (WT) control mice were tested in a battery of memory and anxiety tests. Testing included the cross maze, novel object recognition test (NOR), the Morris water maze (MWM), the elevated plus maze (EPM), and the open field test (OF). Mover KO mice showed impaired recognition memory in the NOR test, and decreased anxiety behavior in the OF and the EPM. Mover KO did not lead to changes in working memory in the cross maze or spatial reference memory in the MWM. However, a detailed analysis of the swimming strategies demonstrated allocentric-specific memory deficits in male KO mice. Our data indicate that Mover appears to control synaptic properties associated with specific forms of memory formation and behavior, suggesting that it has a modulatory role in synaptic transmission.

In recent years, there has been growing evidence that cannabinoids have promising medicinal and pharmacological effects. However, the growing interest in medical cannabis highlights the need to better understand brain alterations linking phytocannabinoids or synthetic cannabinoids to clinical and behavioral phenotypes. Therefore, the aim of this study was to investigate the effects of long-term WIN 55,212-2 treatment—with and without prolonged abstinence—on cerebral metabolism and memory function in healthy wildtype mice. Adult C57BI/6J mice were divided into two treatment groups to study the acute effects of WIN 55,212-2 treatment as well the effects of WIN 55,212-2 treatment after an extended washout phase. We could demonstrate that 3 mg/kg WIN 55,212-2 treatment in early adulthood leads to a hypometabolism in several brain regions including the hippocampus, cerebellum, amygdala and midbrain, even after prolonged abstinence. Furthermore, prolonged acute WIN 55,212-2 treatment in 6-months-old mice reduced the glucose metabolism in the hippocampus and midbrain. In addition, Win 55,212-2 treatment during adulthood lead to spatial memory and recognition memory deficits without affecting anxiety behavior. Overall we could demonstrate that treatment with the synthetic CB1/CB2 receptor aganist Win 55,212-2 during adulthood causes persistent memory deficits, especially when mice were treated in early adulthood. Our findings highlight the risks of prolonged WIN 55,212-2 use and provide new insights into the mechanisms underlying the effects of chronic cannabinoid exposure on the brain and behavior.

Background Limited therapeutic effects of current Alzheimer treatments highlight the need for new research approaches. Targeting the endocannabinoid system could be such an approach. The endocannabinoid system plays a role in brain development, memory formation, and presynaptic activity as well as in neuro‐inflammatory processes and neuroprotection (Mechoulam et al., 2014; Salzet et al., 2000). Several in vitro studies showed that cannabinoids could stimulate phagocytosis and degradation of Aβ as well as stimulate the removal of intraneuronal Aβ in vitro (Currais et al., 2016). The current study aims to investigate the therapeutic potential of a WIN‐based Alzheimer’s disease therapy using mouse models of sporadic (Tg4‐42; Bouter et al., 2013) and familial (5xFAD; Oakley et al., 2006) Alzheimer’s disease. WIN 55,212‐2 (WIN) is a synthetic cannabinoid binding more efficiently to CB1 and CB2 receptors than Tetrahydrocannabinol. Method Tg4‐42 and 5XFAD mice were treated by intraperitoneal injections with the synthetic cannabinoid WIN 55,212‐2 (0,2mg/kg) over a period of 42 days. Sex‐ and age‐matched control groups are treated with vehicle solution (5% ethanol, 5% Tween80 in 0,9% sodium chloride solution). Spatial reference memory was assessed using the Morris water maze, motor performance with the Rotarod and anxiety behavior was evaluated using the elevated plus‐maze and the dark‐light box. 5xFAD mice carry five mutations strongly linked to amyloid processing. The effects of WIN on the Aβ pathology in 5XFAD mice will be investigated using immunohistochemistry and presented. Result WIN 55,212‐22 treatment of Tg4‐42 mice showed increased spatial reference memory and increased motor performance in comparison to the control group. Preliminary data analysis of 5xFAD mice shows significant results pointing in the same direction. Analysis of 5xFAD mice will be completed and presented. Conclusion Our findings reinforce a cannabinoid‐based therapy as a promising strategy for treating Alzheimer’s disease with WIN 55,212‐22 as a possible candidate.

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