CBD may be potent and effective at preventing the development of chemotherapy-induced peripheral neuropathy, and its clinical use may be enhanced by co-administration of low doses of THC. These treatment strategies would increase the therapeutic window of cannabis-based pharmacotherapies.

Aims We have recently demonstrated that treatment with a cannabinoid CB2 agonist was protective in a mouse middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury. The present study aimed to determine whether these protective effects of CB2 agonism would extend to a mouse photoinjury model of permanent ischemia and determine associated alterations in cognition and infarct size. Main Methods Mice received three injections of the CB2 selective agonist O-1966 or vehicle 1 h prior to and 2 and 5 days following induction of stroke. Infarct size was assessed at 1, 3, or 7 days post injury and learning and memory effects of injury and O-1966 treatment were assessed on days 6 and 7 using a novel object recognition task and an operant acquisition and retention procedure. Key Findings O-1966 treated mice had significantly smaller infarct volumes compared with vehicle treated mice. Photoinjury was also associated with a significant memory impairment on day 7 post-injury, and this deficit was reversed with O-1966 treatment. Surprisingly, sham-operated mice receiving O-1966 treatment showed a significant learning deficit in both the recognition and operant tasks compared with vehicle treated sham mice. Significance We conclude that CB2 activation is protective against cognitive deficits and tissue damage following permanent ischemia, but may dysregulate glial or neuronal function of learning and memory circuits in the absence of injury and/or inflammation.

CBD as a monotherapy may prove to be a safer pharmacological agent, than CB receptor agonists alone or in combination with CBD, for the treatment of several disorders.

Stimulants such as amphetamine (AMPH) are popular medications for the cognitive late effects of childhood cancer treatment. While the reinforcing and stimulatory properties of AMPH are well documented, little is known about these effects in childhood cancer survivors. In this study, conditioned place preference (CPP) and locomotor activity were measured to investigate sensitivity to AMPH in adolescent (PND 35) mice following neonatal exposure to chemotherapeutic agents methotrexate (MTX) and cytarabine (Ara‐C). Mice were treated with saline, MTX (2.0 mg/kg), Ara‐C (20 mg/kg) or a combination of MTX and Ara‐C (2.0 mg/kg and+ 20 mg/kg) at PND 14, 15, and 16. At the low dose of AMPH (1 mg/kg), chemotherapy‐treated mice spent significantly more time on the AMPH‐paired side. MTX and Ara‐C treated mice showed higher activity levels compared to saline following each AMPH injection, but only the Ara‐C group displayed behavioral sensitization across repeated AMPH exposure. At the high dose of AMPH (4 mg/kg), only mice treated with Ara‐C spent significantly more time on the AMPH‐paired side. All groups showed a higher activity level following the first AMPH injection compared to baseline. Findings suggest that sensitivity to the rewarding and locomotor effects of AMPH is enhanced following early treatment with MTX and Ara‐C. Since these effects were observed at a lower AMPH dose compared to the saline‐treated group, it may be that the dose‐response curve for AMPH has shifted following early chemotherapeutic treatment. (Supported by CA129092 and T32 DA07237).

Stroke is associated with sensorimotor and cognitive deficits, and while rodent models of ischemic injury are commonly used to study infarct volume and sensorimotor deficits, relatively fewer studies have determined the cognitive impairments associated with these models. Previously we showed that selective cannabinoid CB2 agonists were able to attenuate ischemia injury using a mouse model of middle cerebral artery occlusion. The objective of this study was to extend findings on the neuroprotective properties of the CB2 agonist O‐1966 in a mouse model of photothrombotic stroke on sensorimotor and cognitive behaviors. Photothrombotic strokes or sham surgeries were induced in male C57BL/6 mice treated with the CB2 agonist O‐1966 (5.0 mg/kg IP) or vehicle at three timepoints. Post‐stroke, mice were tested in the rotarod assay to assess sensorimotor function. On day 6 mice were tested in a novel object recognition assay to assess episodic memory. Mice were then tested in an operant learning and memory assay on days 6 and 7. Photothrombotic stroke produced a deficit in novel object recognition and acquisition of an operant task, and these deficits were improved by administration of the cannabinoid‐2 agonist O‐ 1966. These findings suggest that the photothrombotic stroke procedure may model cognitive deficits seen in stroke patients and that these deficits in mice are reversed by the neuroprotective CB2 agonist O‐1966.