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.
Aim: To determine the prevalence, aetiology, and treatment profile of abnormal sexual behaviour in subjects with dementia in psychogeriatric practices. Methods: A retrospective cross sectional study was conducted in a long term care psychiatry consultation service, community based geriatric psychiatry service, and an inpatient dementia behavioural unit in Edmonton, Canada. Results: Forty one subjects (1.8%) had sexually inappropriate behaviour. Of those cognitively impaired subjects with sexually inappropriate behaviour, 20 (48.8%) were living in nursing homes and the rest, 21 (51.2%) in the community. Of these subjects, 53.7% had vascular dementia, 22% had Alzheimer's, and 9.8% had mild cognitive impairment. History of alcohol misuse and psychosis were reported in 14.6% and 9.8% of subjects respectively. Twenty seven (65.7%) had verbally inappropriate behaviour and 36 (87.8%) had physically inappropriate behaviour. In this study, verbally inappropriate behaviour was more commonly seen in the community sample (81%) than in the nursing home sample (50%) (p = 0.04). Behavioural treatment was also more commonly seen in the community sample (81%) than in the nursing home sample (45%) (p = 0.01). Conclusion: In this study sexually inappropriate behaviour was seen in all stages of dementia, more commonly associated with subjects of vascular aetiology, and is as commonly seen in community dwelling subjects with dementia as in nursing home subjects.
The cannabis constituent cannabidiol (CBD) possesses anxiolytic and antipsychotic properties. We have previously shown that transmembrane domain neuregulin 1 mutant (Nrg1 TM HET) mice display altered neurobehavioural responses to the main psychoactive constituent of cannabis, Δ9-tetrahydrocannabinol. Here we investigated whether Nrg1 TM HET mice respond differently to CBD and whether CBD reverses schizophrenia-related phenotypes expressed by these mice. Adult male Nrg1 TM HET and wild type-like littermates (WT) received vehicle or CBD (1, 50 or 100 mg/kg i.p.) for 21 days. During treatment and 48 h after withdrawal we measured behaviour, whole blood CBD concentrations and autoradiographic receptor binding. Nrg1 HET mice displayed locomotor hyperactivity, PPI deficits and reduced 5-HT2A receptor binding density in the substantia nigra, but these phenotypes were not reversed by CBD. However, long-term CBD (50 and 100 mg/kg) selectively enhanced social interaction in Nrg1 TM HET mice. Furthermore, acute CBD (100 mg/kg) selectively increased PPI in Nrg1 TM HET mice, although tolerance to this effect was manifest upon repeated CBD administration. Long-term CBD (50 mg/kg) also selectively increased GABAA receptor binding in the granular retrosplenial cortex in Nrg1 TM HET mice and reduced 5-HT2A binding in the substantia nigra in WT mice. Nrg1 appears necessary for CBD-induced anxiolysis since only WT mice developed decreased anxiety-related behaviour with repeated CBD treatment. Altered pharmacokinetics in mutant mice could not explain our findings since no genotype differences existed in CBD blood concentrations. Here we demonstrate that Nrg1 modulates acute and long-term neurobehavioural effects of CBD, which does not reverse the schizophrenia-relevant phenotypes.
The ABC transporters P-glycoprotein (P-gp, Abcb1) and breast cancer resistance protein (Bcrp, Abcg2) regulate the CNS disposition of many drugs. The main psychoactive constituent of cannabis Δ9-tetrahydrocannabinol (THC) has affinity for P-gp and Bcrp, however it is unknown whether these transporters modulate the brain accumulation of THC and its functional effects on the CNS. Here we aim to show that mice devoid of Abcb1 and Abcg2 retain higher brain THC levels and are more sensitive to cannabinoid-induced hypothermia than wild-type (WT) mice. Abcb1a/b (−/−), Abcg2 (−/−) and wild-type (WT) mice were injected with THC before brain and blood were collected and THC concentrations determined. Another cohort of mice was examined for THC-induced hypothermia by measuring rectal body temperature. Brain THC concentrations were higher in both Abcb1a/b (−/−) and Abcg2 (−/−) mice than WT mice. ABC transporter knockout mice exhibited delayed elimination of THC from the brain with the effect being more prominent in Abcg2 (−/−) mice. ABC transporter knockout mice were more sensitive to THC-induced hypothermia compared to WT mice. These results show P-gp and Bcrp prolong the brain disposition and hypothermic effects of THC and offer a novel mechanism for both genetic vulnerability to the psychoactive effects of cannabis and drug interactions between CNS therapies and cannabis.
Although CFAB is reliable, it is only moderately valid in evaluating executive dysfunction among Chinese stroke patients with small subcortical infarct. The clinical use of CFAB in the evaluation of executive dysfunction among this group of patients cannot be recommended at this stage.
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