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Background:Kratom orMitragyna speciosaKorth has been widely used to relieve the severity of opioid withdrawal in natural settings. However, several studies have reported that kratom may by itself cause dependence following chronic consumption. Yet, there is currently no formal treatment for kratom dependence. Mitragynine, is the major psychoactive alkaloid in kratom. Chronic mitragynine treatment can cause addiction-like symptoms in rodent models including withdrawal behaviour. In this study we assessed whether the prescription drugs, methadone, buprenorphine and clonidine, could mitigate mitragynine withdrawal effects. In order to assess treatment safety, we also evaluated hematological, biochemical and histopathological treatment effects.Methods:We induced mitragynine withdrawal behaviour in a chronic treatment paradigm in rats. Methadone (1.0 mg/kg), buprenorphine (0.8 mg/kg) and clonidine (0.1 mg/kg) were i.p. administered over four days during mitragynine withdrawal. These treatments were stopped and withdrawal sign assessment continued. Thereafter, toxicological profiles of the treatments were evaluated in the blood and in organs.Results:Chronic mitragynine treatment caused significant withdrawal behaviour lasting at least 5 days. Methadone, buprenorphine, as well as clonidine treatments significantly attenuated these withdrawal signs. No major effects on blood or organ toxicity were observed.Conclusion:These data suggest that the already available prescription medications methadone, buprenorphine, and clonidine are capable to alleviate mitragynine withdrawal signs rats. This may suggest them as treatment options also for problematic mitragynine/kratom use in humans.

Objectives : The aim of this study is to review the acupoints used in cocaine studies and interpret the effectiveness in an aspect of meridian theory of Korean medicine. Methods : Authors searched 50 articles in PubMed, 16 in KISS, 9 in OASIS, 40 in NDSL, and 19 in DBPIA, with the keyword of ‘cocaine’ or ‘acupuncture’. The articles written in English only were included. The articles related with cocaine(abuse, dependence, sensitization, intake, withdrawal sign, withdrawal syndrome, reinstatement, seeking) only were subjected. The articles which used manual- or electro-acupuncture were included, and auricular was excluded. Results : The most frequently used acupoint was HT7, while LI4, LU9, ST36, and SP6 were used once respectively. HT7 could be understood to be used from the meaning of the name as well as the theory that Heart Meridian is deeply related with the brain function. LU9 seems to be used to enhance the effect of HT7. LI4 is thought to control reverting yin that flows toward the top of head following the theory of Jang Bu Sang Tong. ST36 appears to be used because it could regulate stress reaction that reverting yin is associated with. SP6 seems to have effect on brain function due to its ability to control spiritual disorder. Conclusions : The acupoints used in the cocaine studies are thought to influence the brain function through diverse mechanism, and Jang Bu Sang Tong theory seems to be involved in the mechanism, at least in part.

Substance abuse and dependence pose several risks in the perioperative setting. For example, excessive alcohol use increases the risk of morbidity during surgery—including cardiopulmonary, infections, wound, bleeding, and neurologic complications. Surgical patients who drink over four alcoholic drinks daily have a two- to threefold increased risk for postoperative complications when compared to patients who drink less than two drinks a day. However, other than for alcohol, there are limited data for interventions to improve perioperative outcomes.

Using various administration schedules, the physical dependence produced by dihydroetorphine (DHE) was compared with that of morphine in mice. Physical dependence, evaluated by naloxone-precipitated withdrawal signs, did not develop following daily treatment with DHE (10, 20, 100 and 1000μg/kg, i. p. or 30, 100 and 1000 ng/mouse, i. c. v.) for 6d. However, 5 repeated injections of DHE (10μg/kg, i. p.) at 1 or 2 h intervals did produce physical dependence and the dependent state disappeared after 2h. Accordingly, it was demonstrated that a sufficient degree of antinociceptive activity needed to be maintained, longer than several hours, for the development of physical dependence on DHE and that the duration of the dependent state was very short. In the single dose suppression test, a single dose of DHE completely suppressed the natural withdrawal signs that appeared following abstinence in morphine-dependent animals without reappearance of significant withdrawal signs, indicating the suitability of DHE as a substitute for morphine. The characteristic properties of DHE, the extremely potent antinociceptive effect and minimal dependence, indicate the separation of the antinociceptive effect from dependence, and suggest that it may be possible to develop a novel drug which may be safely used in clinical situations., Biological & Pharmaceutical Bulletin, 17(8), pp.1056-1059; 1994

Prostaglandines and other eicosanoids are involved in a multitude of normal and pathological processes at CNS level.

Prolonged exposure of neuronal cells to an addictive drug causes adaptations which may manifest themselves in tolerance to and dependence on the drug concerned. With respect to opioids, several theories have been advanced to explain these compensatory mechanisms; these theories have centered on changes at the opioid receptor level or related to other components of the neurotransmitter systems (Shuster 1961; Collier 1968; Goldstein and Goldstein 1968; Jaffe and Sharpless 1968; Smith et al. 1988). Further interest has focused on the issue of whether adaptations are confined to opioid-responsive nerves (“cellular dependence”; Collier 1980) or involve cells adjacent to the opioid receptor-carrying neurons (Wuster et al. 1985).

Evidence has been accumulating to indicate that the spinal cord plays an important role in the expression of several narcotic abstinence signs in the intact animal. One characteristic and reproducible withdrawal sign which can be elicited in both intact and spinal-transected dependent rats is the naloxone-induced increase in arterial blood pressure. Employing this model, this autonomic component of narcotic withdrawal was quantitated in dependent spinal (C1)-transected rats with intact dorsal roots and in those with surgical lesions of the dorsal roots from T3 to L4. The withdrawal-associated hypertension observed in animals with intact dorsal roots was abolished in the rats having the lesioned roots. The central spinal location of the opiate receptors mediating the naloxone response was confirmed by experiments demonstrating the failure of a selective peripherally acting narcotic antagonist to elicit a comparable withdrawal response. It was concluded that continuous afferent input and spinal opiate receptors are requirements for the expression of spinal narcotic withdrawal.

The identification of the neurobiological concomitants of ethanol dependence and withdrawal would not only provide a better understanding of the basic nature of such phenomena, but would also facilitate the development of techniques of detection, prevention, and treatment of alcoholic disease and its psychobiological consequences.

The clinical manifestations of a benzodiazepine abstinence syndrome, implying physical dependence, resemble those that occur with sedatives, including barbiturates, and with alcohol, but show some differences of time and degree rather than nature.

The question as to whether and in which manner opiates interact with central nervous transmission has gained fresh impetus from the recent discovery of endogenous opiate receptor ligands. Since these ligands mimic to a greater or lesser degree the whole spectrum of opiate actions, it seems opportune to reconsider present knowledge on the interaction of opiates with neurotransmitters in the central nervous system (CNS) in the hope that this may throw some light on the possible physiologic significance of endorphins. The following is an attempt to evaluate the extensive literature dealing with the involvement of catecholamines (CAs) in opioid action. Particular emphasis will be placed upon current studies and unanswered questions.