The cell-permeant antioxidant D-thiol ester D-cysteine ethyl ester overcomes physical dependence to morphine in male Sprague Dawley rats

The ability of morphine to decrease cysteine transport into neurons by inhibition of excitatory amino acid transporter 3 (EAA3) may be a key molecular mechanism underlying the acquisition of physical and psychological dependence to morphine. This study examined whether co-administration of the cell- penetrant antioxidant D-thiol ester, D-cysteine ethyl ester (D-CYSee), with morphine, would diminish the development of physical dependence to morphine in male Sprague Dawley rats. Systemic administration of the opioid receptor antagonist, naloxone (NLX), elicited pronounced withdrawal signs (e.g., wet-dog shakes, jumps, rears, circling) in rats that received a subcutaneous depot of morphine (150 mg/kg, SC) for 36 h and continuous intravenous infusion of vehicle (20 μL/h, IV). The NLX-precipitated withdrawal signs were reduced in rats that received an infusion of D-CYSee, but not D-cysteine, (both at 20.8 μmol/kg/ h, IV) for the full 36 h. NLX elicited pronounced withdrawal signs in rats treated for 48 h with morphine (150 mg/kg, SC), plus continuous infusion of vehicle (20 μL/h, IV) that began at the 36 h timepoint of morphine treatment. The NLX-precipitated withdrawal signs were reduced in rats that received a 12 h infusion of D-CYSee, but not D-cysteine, (both at 20.8 μmol/kg/h, IV) that began at the 36 h timepoint of morphine treatment. These findings suggest that D-CYSee may attenuate the development of physical dependence to morphine and reverse established dependence to the opioid in male Sprague Dawley rats. Alternatively, D-CYSee may simply suppress the processes responsible for NLX-precipitated withdrawal. Nonetheless, D-CYSee and analogues may be novel therapeutics for the treatment of opioid use disorders

Revising the Treatment Plan and/or Ending Addiction Treatment (DRAFT)

Where Chapter 18 discusses revision of the treatment plan and ending of pain treatment, Chapter 23 focuses on the conclusion of addiction treatment. It closes the loop to Chapter 11, Initiating Treatment and Monitoring Patient Progress. The authors describe the conditions which will oblige a revision of the treatment plan; such as alterations in prescription medications with cross-metabolism, pregnancy or menopause, liver disease, or aging. There are also behavioral conditions that will oblige plan modification, whether dysfunctional or hostile behaviors or other psychiatric instability. Consequently, a significant portion of the chapter is dedicated to the identification of relapse, its psychodynamic and developmental meanings, and the appropriate interventions for it. Voluntary and involuntary terminations and the therapeutic steps taken with both are discussed as logical continuations of any treatment plan.</p

Understanding and Preventing Opioid Misuse and Abuse (DRAFT)

This chapter describes the dynamics of opioid misuse and abuse, and of opioid use disorder, as a basis for choosing risk mitigation strategies. Its opening words capture the dichotomy confronting the physician, describing opioids’ virtues and simultaneous risks. Factors contributing to the misuse and compulsive use of opioids preface a review of the best practices in prevention: prescription drug monitoring programs (PDMPs), consultation and collateral source interrogation, lost prescription replacement policies, and development of and mutual adherence to formal monitoring plans. The chapter is directed to all physicians in clinical practice. Included is a table describing appropriate and inappropriate opioid use, with clinical examples. A second table distinguishes medical from nonmedical uses of opioids according to intent, effect, pattern, control, and legality. A final table distinguishes between the physician’s and the patient’s responsibilities.</p