Behavioral Mechanism of Action

The behavioral mechanism most associated with opioids is their effects on pain processing and the relief of pain and suffering. Pain relief takes on many forms in several parts of the central nervous system and outside it. Within this book, a behavioral mechanism of action refers to a unifying principle of order and predictability at the behavioral level. Each drug class has behavioral effects that define its phenotype. This behavioral mechanism may derive from medical use, behavioral pathology, or some combination of both.

Opioids can also relieve emotional pain, and this is one of the behavioral mechanisms strongly implicated in the addiction cycle. A unique aspect of heroin addiction has been described as:

β€œThe special role the drug comes to play in the personality organization of these patients. They have not successfully established familiar defensive, neurotic, characterological or other common adaptive mechanisms as a way of dealing with their distress. Instead, they have resorted to the use of opioids as a way of coping with a range of problems including ordinary human pain, disappointment, anxiety, loss, anguish, sexual frustration, and other suffering.”

(Khantzian EJ, Mack JE, Schatzberg AF. Heroin use as an attempt to cope: clinical observations. American Journal of Psychiatry, 1974, (131), 160–164 [p. 162].)

This aspect of drug addiction has been extended to an overall hypothesis of self-medication, in which patients are purported to experiment with various classes of drugs to discover the one that is particularly well-suited for that individual because it changes the emotional states that the patient finds particularly problematic, painful, or desirable. Opioids have been hypothesized to be preferred by many individuals because of their powerful actions in diminishing the disorganizing and threatening effects of rage and aggression. Subjects who experienced or expressed physical abuse and violent behavior have described the way that opioids helped them feel normal, calm, mellow, soothed, and relaxed.

FIGURE 5.4 Biotransformation pathway for heroin in humans. [Taken with permission from Pichini S, Altieri I, Pellegrini M, Zuccaro P, Pacifici R. The role of liquid chromatography-mass spectrometry in the determination of heroin and related opioids in biological fluids. Mass Spectrometry Reviews, 1999, (18), 119–130.]

Paradoxically, opioids can also induce pain as a result of counteradaptive processes. Patients who receive long-term opioid therapy that lasts from weeks to years can develop unexpectedly abnormal pain and hyperalgesia upon withdrawal from the opioid treatment. In a review of the clinical experiences of over 750 patients who received epidural or spinal morphine over an average of 124 days, it was reported that many of these developed increased sensitivity to sensory stimuli (hyperesthesia) and that normally innocuous sensory stimulations elicited pain (allodynia).

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