Cannabis and Drug Tolerance - Savikalpa Academy

Regulation of CB1 cannabinoid receptor internalization by a promiscuous phosphorylation-dependent mechanism

Agonists stimulate CB1 receptor internalization. Previous work suggests that the extreme carboxy-terminus of the receptor regulates this internalization – likely through the phosphorylation of serines and threonines clustered within this region. While truncation of the carboxy-terminus (V460Z CB1) and consequent removal of these putative phosphorylation sites prevents endocytosis in AtT20 cells, the residues necessary for CB1 receptor internalization remain elusive.

Rapid CB1 cannabinoid receptor desensitization defines the time course of ERK1/2 MAP kinase signaling

Key results: The administration of CBD significantly blocked the increase in motor activity and the increased number of rearings, rubbings and jumpings associated with cannabinoid withdrawal, and it normalized the decrease in the number of groomings. However, CBD did not change somatic signs in vehicle-treated animals.

Time course for the induction and maintenance of tolerance to Delta(9)-tetrahydrocannabinol in mice

The time course for the development of tolerance to delta-9-tetrahydrocannabinol (Delta(9)-THC) was studied in an effort to determine the role that length of dosing may have in the onset and maintenance of tolerance. Mice were chronically treated with either vehicle or 10 mg/kg of Delta(9)-THC subcutaneously twice a day.

Clinical relevance of cannabis tolerance and dependence

Experimental approach: Spontaneous cannabinoid withdrawal was evaluated 12 h after cessation of CP-55,940 treatment (0.5 mg·kg-1 every 12 h, i.p.; 7 days) in C57BL/6J mice. The effects of CBD (5, 10 and 20 mg·kg-1 , i.p.) on withdrawal-related behavioural signs were evaluated by measuring motor activity, somatic signs and anxiety-like behaviour.

Aspects of tolerance to and dependence on cannabis

Tolerance at all levels of complexity in the brain involves “learning” in the sense of the acquisition of compensatory adaptations to the consequences of the presence of a drug-produced disturbance in function. Depending on the function, species, and dose of cannabis, “tissue tolerance,” behaviorally augmented (to provide the presence of the disturbed function) or not, develops at different rates or not all (e.g., to impairment of the logical sequence of thoughts, to which no tolerance has yet been demonstrated).

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