Repeated exposure to the synthetic cannabinoid AKB48 worsens the visual sensorimotor, sensory gating, and motor reactivity response to the hallucinogens 2C-I and 25I-NBOMe in mice. This effect is more prolonged in males than in females. The underlying mechanism involves neuroplastic changes in the cerebellum and cortex, specifically at serotonin 2A receptors and the serotonin transporter. These changes occur more markedly and rapidly in female mice. The findings highlight a significant interaction between synthetic cannabinoids and psychedelic drugs, which may be relevant to long-term effects and psychiatric consequences of their consumption.
Methoxetamine (MXE), a dissociative drug similar to ketamine and phencyclidine, alters neurological and sensorimotor functions in mice in a dose-dependent manner. Acute systemic administration of MXE, ketamine, and phencyclidine (0.01–30 mg/kg i.p.) differentially affected visual, acoustic, and tactile responses, thermal and mechanical pain, motor activity, and acoustic startle reactivity. MXE and ketamine (1 and 30 mg/kg i.p.) and phencyclidine (1 and 10 mg/kg i.p.) also significantly affected cardiorespiratory parameters and systolic and diastolic blood pressure. The findings suggest MXE produces effects comparable to its parent compounds, with specificity depending on dose and parameter examined.