Measurement of rates of propulsion in the small intestine in control and experimental groups of male Sprague-Dawley rats (200-250 g) were carried out as a means of assessing antidiarrhoeal activity of aqueous extracts of the leaf of Psidium guajava (L.), using morphine as the standard drug of reference. Hyperpropulsion (diarrhoea) was induced by gavaging rats in a control group with Microlax, using phenol red mixed into it as a marker in the intestine, and the mean rate of the hyperpropulsion was determined. The normal rate of propulsion, defined as the percentage of the length of the ileum traversed by the front of the dye in 1 h after gavaging animals with a liquid paraffin-phenol red meal, was also determined in another control group. In experimental groups pretreated with enteral administration of either morphine or aqueous extracts, 1 h before the challenge with Microlax, the percentage inhibition to the hyperpropulsive rate (antidiarrhoeal activity) was calculated. Both morphine and the extracts produced a dose-response relationship in their antidiarrhoeal effects. A dose of 0.2 ml/kg fresh leaf extract produced 65% inhibition of propulsion. This dose is equiactive with 0.2 mg/kg of morphine sulphate. The antidiarrhoeal action of the extract may be due, in part, to the inhibition of the increased watery secretions that occur commonly in all acute diarrhoeal diseases and cholera.
Studies were carried out on the suppression of both exploratory and spontaneous locomotor activities in the mouse by a non-polar fraction from a methanol extract of the dried leaves of Psidium guajava. Shortly after intraperitoneal administration of this fraction, typical narcotic-like effects were observed, including catalepsy, analgesia, Straub tail, shallow respiratory movements and exophthalmos. The dose for 90% suppression of exploratory activity was between 3.3 and 6.6 mg/kg intraperitoneally and the onset of action was 6-8 min. The duration of activity was dose-dependent and, for a dose of 13.2 mg/kg given intraperitoneally, it was found to be more than 6 h. Qualitatively similar results on exploratory activity were obtained when the extract was administered orally. Doses of 3.3-6.6 mg/kg i.p. depressed spontaneous locomotor activity and tunnel running was curtailed. Higher doses abolished the spontaneous locomotor reflex action. A flavonoid compound or compounds appear to account for the activity seen.
Incarcerated people living with HIV and opioid dependence face enormous challenges to accessing evidence-based treatment during incarceration and after release into the community, placing them at risk of poor HIV treatment outcomes, relapse to opioid use and accompanying HIV transmission risk behaviors. Here we describe in detail the design and implementation of Project Harapan, a prospective clinical trial conducted among people living with HIV and opioid dependence who transitioned from prison to the community in Malaysia from 2010 to 2014. This trial involved 2 interventions: within-prison initiation of methadone maintenance therapy and an evidence-based behavioral intervention adapted to the Malaysian context (the Holistic Health Recovery Program for Malaysia, HHRP-M). Individuals were recruited and received the interventions while incarcerated and were followed for 12months after release to assess post-release HIV transmission risk behaviors and a range of other health-related outcomes. Project Harapan was designed as a fully randomized 2×2 factorial trial where individuals would be allocated in equal proportions to methadone maintenance therapy and HHRP-M, methadone maintenance therapy alone, HHRP-M alone, or control. Partway through study implementation, allocation to methadone maintenance therapy was changed from randomization to participant choice; randomization to HHRP-M continued throughout. We describe the justification for this study; the development and implementation of these interventions; changes to the protocol; and screening, enrollment, treatment receipt, and retention of study participants. Logistical, ethical, and analytic issues associated with the implementation of this study are discussed.
Kratom is a medicinal plant that exhibits promising results as an opiate substitute. However, there is little information regarding the abuse profile of its main psychoactive constituent, mitragynine (MG), particularly in relapse to drug abuse. Using the place conditioning procedure as a model of relapse, this study aims to evaluate the ability of MG to induce conditioned place preference (CPP) reinstatement in rats. To evaluate the cross-reinstatement effects, MG and morphine were injected to rats that previously extinguished a morphine- or MG-induced CPP. Following a CPP acquisition induced by either MG (10 and 30 mg/kg, i.p.) or morphine (10 mg/kg, i.p.), rats were subjected to repeated CPP extinction sessions. A low dose priming injection of MG or morphine produced a reinstatement of the previously extinguished CPP. In the second experiment of this study, a priming injection of morphine (1, 3 and 10 mg/kg, i.p.) dose-dependently reinstated an MG-induced CPP. Likewise, a priming injection of MG (3, 10 and 30 mg/kg, i.p.) was able to dose-dependently reinstate a morphine-induced CPP. The present study demonstrates a cross-reinstatement effect between MG and morphine, thereby suggesting a similar interaction in their rewarding motivational properties. The findings from this study also suggesting that a priming exposure to kratom and an opioid may cause relapse for a previously abused drug.