Psychosocially-Assisted Pharmacological Treatment of Opioid Dependent Adults: A Systematic Review

Background: Opioid dependence is a conundrum that significantly contributes to global mortality, crimes, and transmission of diseases such as hepatitis (B and C), human immunodeficiency virus and perhaps, coronavirus disease 2019 (COVID-19). There are contradictory findings on the efficacy of psychosocially-assisted pharmacological treatment of opioid dependence in adults. Objective: The overall objective of this research is to investigate if psychosocially-assisted pharmacological therapy has significantly better effect than pharmacological therapy with regards treatment outcomes of opioid dependent adults. Methods: All methods employed in this study are in conformity with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) framework for systematic review which involve identification, screening, eligibility and inclusion. This systematic review involved PubMed literature search on randomized controlled trials published between 1st January 2015 to 1st October 2021. Results: PubMed search yielded 5,216 articles which were screened using inclusion and exclusion criteria resulting in 19 articled being retained for data extraction. Of the 19 articles used in this study, 13 (68.4%) articles having a combined sample size of 1,928 (60.6%) showed that addition of psychosocial intervention to pharmacotherapy significantly improved abstinence from opioid abuse. Conclusion: The outcome of evaluation of the overall evidences presented in the 19 articles used in this study is that psychosocially-assisted pharmacological therapy is significantly better than pharmacological treatment with respect to enhancement of abstinence from opioid abuse among opioid-dependent adults. Additionally, this study has provided specific combinations of psychosocial and pharmacological treatment that can produce significant beneficial effect on opioid abstinence. The huge downturn in randomized controlled trials on treatment of opioid dependence among adults has been highlighted in this study.

Anticonvulsant activity of aqueous fraction of Carissa edulis root bark.

CONTEXT: Carissa edulis Vahl (Apocynaceae) is used in Nigerian folk medicine to manage a plethora of diseases including epilepsy, cancer, and inflammation; its efficacy is widely acclaimed among communities of northern Nigeria. OBJECTIVE: This study establishes anticonvulsant activities of aqueous fraction of ethanol root bark extract of Carissa edulis (RAF) and sub-fractions (S1 and S2) in animal models. MATERIALS AND METHODS: We evaluated the acute toxicity of the RAF, S1 and S2, and the anticonvulsant activity using pentylenetetrazole (PTZ), picrotoxin, strychnine, N-methyl-d-aspartate (NMDA), isoniazid (INH), and aminophylline-induced seizures in mice. Their effects on maximal electroshock (MES) and kindling-induced seizures were studied in chicks and in rats, respectively, and in the electrophysiological study. The doses used for RAF were 150, 300, and 600 mg/kg while S1 and S2 were 250, 500, and 1000 mg/kg. Both RAF and sub-fractions were administered once during the experiment. RESULTS: The intraperitoneal LD50 of the RAF was estimated to be 2222.61 mg/kg and that of the S1 and S2 were above 5000 mg/kg. RAF protected the mice by 50% while sub-fractions by 16.67% against PTZ-induced seizures. RAF offered 33.33 and 16.67% protection against strychnine and NMDA models, respectively. However, RAF offered 66.67-33.33% protections against aminophylline-induced seizures at doses of 150 and 600 mg/kg, but RAF, S1, and S2 had no effect on MES-induced seizures. DISCUSSION AND CONCLUSION: Our results validate the use of the plant traditionally in the management of epilepsy, thus supporting the appraisal of biologically active components of this plant as antiepileptic agents.

Psychopharmacological properties of saponins from Randia nilotica stem bark.

CONTEXT: Decoctions of Randia nilotica Stapf. (Rubiaceae) have been used in the Nigerian traditional medicine for the management of epilepsy, anxiety, depression and psychosis for many years and their efficacies are widely acclaimed among the rural communities of Northern Nigeria. OBJECTIVE: The aim of this study is to establish whether the saponins present in R. nilotica are responsible for its acclaimed beneficial effects in Nigerian traditional medicine. MATERIALS AND METHODS: The behavioural properties of the saponin-rich fraction (SFRN) of R. nilotica stem bark were studied on hole-board, diazepam-induced sleep, rota-rod and beam-walking in mice. The anticonvulsant properties of SFRN were also examined on maximal electroshock, pentylenetetrazole- and strychnine-induced seizures in mice. RESULTS: The intraperitoneal LD50 of SFRN in mice and rats were estimated to be 11.1 and 70.7 mg/kg, respectively. SFRN significantly prolonged the duration of diazepam-induced sleep; diminished head dip counts in the hole-board test and protected mice against maximal electroshock seizures. SFRN failed to protect mice against pentylenetetrazole- and strychnine-induced seizures; and had no effect on motor coordination on the rota-rod treadmill at the doses tested. SFRN significantly decreased the number of foot slips in the beam-walking assay in mice with no effect on time to reach the goal box. DISCUSSION AND CONCLUSION: This study provides evidence of the psychopharmacological effects of SFRN, thus supporting further development of the psychoactive components as remedies for epilepsy.

Wound healing potential of formulated extract from hibiscus sabdariffa calyx.

Wound healing agents support the natural healing process, reduce trauma and likelihood of secondary infections and hasten wound closure. The wound healing activities of water in oil cream of the methanol extract of Hibiscus sabdariffa L. (Malvaceae) was evaluated in rats with superficial skin excision wounds. Antibacterial activities against Pseudomonas aeroginosa, Staphylococcus aureus and Echerichia coli were determined. The total flavonoid content, antioxidant properties and thin layer chromatographic fingerprints of the extract were also evaluated. The extract demonstrated antioxidant properties with a total flavonoid content of 12.30±0.09 mg/g. Six reproducible spots were obtained using methanol:water (95:5) as the mobile phase. The extract showed no antimicrobial activity on the selected microorganisms, which are known to infect and retard wound healing. Creams containing H. sabdariffa extract showed significant (P<0.05) and concentration dependent wound healing activities. There was also evidence of synergism with creams containing a combination of gentamicin and H. sabdariffa extract. This study, thus, provides evidence of the wound healing potentials of the formulated extract of the calyces of H. sabdariffa and synergism when co-formulated with gentamicin.

Safety assessment of the standardized extract of Carissa edulis root bark in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Preparations of Carissa edulis (Vahl) have been used in the Nigerian traditional medicine for the management of fever, sickle cell disease, epilepsy, pain and inflammation for many years and their efficacy is widely acclaimed among the Hausa communities of northern Nigeria. AIM OF THE STUDY: The present studies aimed at evaluating the toxicological properties of the standardized ethanol extract of C. edulis root bark in rats, in order to determine its safety and to complement earlier efficacy studies on this widely used medicinal plant. MATERIALS AND METHODS: High performance liquid chromatography (HPLC) and preliminary phytochemical analysis of the extract were conducted and its oral median lethal dose (LD50) determined. Signs of toxicity, body weight changes, relative organs weight, feed and water consumption were monitored following 28 days of daily oral administration of graded doses of the extract in rats. Effects of the extract on sex hormones, low- and high-density lipids, hematological and biochemical parameters were examined and pathological changes of the vital organs after treatment with the extract were also investigated. RESULTS: The oral LD50 of the extract was estimated to be >5000 mg/kg. The body weights of treated rats increased progressively, but the changes were not significantly different from the control groups. The extract neither produces significant changes in feed and water consumption nor affected the relative organs weight. Although some variations were observed in hormonal and lipid profiles hematological and biochemical indices, these important parameters were normal and within acceptable limits. No lesions or pathological changes of the organs attributable to treatment with the extract were observed from the pathological examinations. The HPLC fingerprint of the extract shows a spectrum profile characteristic of C. edulis, while the preliminary phytochemical screening revealed the presence of saponins, flavonoids, tannins, anthraquinones and cardiac glycosides. CONCLUSION: Our results provided evidence that short-term administration of the standardized ethanol extract of C. edulis root bark at doses lower than 1000 mg/kg is safe in rats and may not exert severe toxic effects.

Potential roles of stem cells in the management of sensorineural hearing loss.

BACKGROUND: In the management of sensorineural hearing loss, effective therapy for degenerated hair cells, third order neurons, ganglions, dendrites and synaptic areas of the vestibulo-cochleo-cerebral pathway remains an enigma. Transplantation of stem and progenitor cells appears to be an emerging potential solution, and is the focus of this review. AIM: To review recent developments in the management of sensorineural hearing loss in the field of stem cell research. MATERIALS AND METHOD: A systematic review of the English language literature included all experimental and non-experimental studies with a Jadad score of three or more, published between 2000 and 2010 and included in the following databases: Cochrane Library Ear, Nose and Throat Disorders; Medline; Google Scholar; Hinari; and the Online Library of Toronto University. RESULTS: Of the 455 and 29 600 articles identified from Medline and Google Scholar, respectively, 48 met the inclusion criteria. These were independently reviewed and jointly analysed. CONCLUSION: Although there is not yet any evidence from successful human studies, stem cell and 'alternative stem cell' technology seems to represent the future of sensorineural hearing loss management.

Behavioral properties of Balanites aegyptiaca in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Balanites aegyptiaca is a native plant from the dry tropical areas of Africa and Arabia. It has been used in traditional medicine to treat psychoses, epilepsy, rheumatism and for the management of cough, liver and spleen conditions for many years. The plant is also used as antihelmintic and molluscicide. AIM OF THE STUDY: The present studies aimed at investigating the behavioral properties of ethanol extract of the root of this medicinal plant, which is already in common applications in the Nigerian traditional medicine. MATERIALS AND METHODS: The intraperitoneal and oral mean lethal dose (LD(50)) of the extract was determined using the Lorke's method. The preliminary phytochemical screening of the extract was carried out to identify the secondary metabolites in the extract. Furthermore, the behavioral properties of the extract were evaluated using diazepam-induced sleep, open field test, staircase test and beam walking assay all in mice. RESULTS: The extract significantly (p<0.001) prolonged the duration diazepam (20mg/kg i.p)-induced sleep in mice dose dependently. However, the extract showed no significant effect on the onset of diazepam-induced sleep. In the open field test, the extract (150 and 300 mg/kg) and diazepam (0.05 mg/kg) produced a significant (p<0.05, p<0.005 and p<0.001) decrease in the number of square crossings. There was no significant effect on the number of centre square crossing following the administration of the extract. The extract (75 and 150 mg/kg) and diazepam (0.05 mg/kg) produced a significant (p<0.05) decrease in the number of rearing suggestive of sedation. In the staircase experiment there was a decrease in the number of upward step climbing as well as number of rearing suggesting anxiolytic and sedative properties of the extract. In the beam walking assay the extract did not produce any significant increase in the time taken to complete task as compared to diazepam 1mg/kg which was significant at p<0.05. Furthermore, 30 mg/kg of the extract and diazepam 1mg/kg showed significant (p<0.05) mean number of foot slips, suggesting that the central nervous system depressant activity might not necessarily due to peripheral neuromuscular blockade. CONCLUSION: The result indicates that the extract of Balanites aegyptiaca possess biologically active compound(s) that have anxiolytic and sedative properties, which support the ethnomedicinal use of the plant as antipsychotic and antiepileptic agents.

Psychopharmacological Properties of the Saponin Fraction of Ficus Platyphylla Stem Bark

The psychopharmacological effects of a saponin-rich fraction (SFG) obtained from crude methanolic extract of Ficus platyphylla stem bark were studied on spontaneous motor activity (SMA); pentobarbitalinduced sleep; motor coordination; amphetamine-induced hyperactivity and stereotyped behaviour; catalepsy; forced swim and tail suspension tests in rodents. SFG reduced SMA dose dependently; suggesting that it may contain psychoactive principles with sedative effects. The fraction shortened the onset and prolonged the duration of pentobarbital-induced sleep; which confirmed its sedative properties. The fraction diminished immobility time in forced swim and tail suspension tests; which is indicative of antidepressant properties. It attenuated amphetamine-induced hyperactivity and stereotyped behaviour; induced catalepsy and exacerbated haloperidol-induced catalepsy in rodents; but had no effect on motor coordination in the treadmill experiment at the doses tested. These effects were similar to those of classical neuroleptics and antidepressants. Our study provides scientific evidence of psychopharmacological effects of the saponin fraction of Ficus platyphylla stem bark and therefore supports further development of its psychoactive components as antipsychotics and antidepressants

Antinociceptive profile of the methanolic extract of Neorautanenia mitis root in rats and mice.

The antinociceptive activity of the methanolic extract of Neorautenania mitis was studied in mice and rats. Five experimental models of nociception employed were: acetic acid-induced abdominal constriction and hot-plate test in mice, formalin-induced pain, analgesy-meter and Randall-Selitto tests in rats. The antinociceptive action of the extract was tested against naloxone in the hot-plate test in a bid to further elucidate probable mechanisms of antinociception. Results showed that the extract at doses of 5, 10 and 20 mg/kg body weight caused significant (P<0.05) dose-dependent antinociceptive activity in all the nociceptive models. Naloxone (2 mg/kg), significantly (P<0.05) antagonised the antinociceptive activity at the highest dose of the extract (20 mg). The study showed that the methanolic extract of Neorautanenia mitis possesses both peripherally and centrally mediated antinociceptive activity. The peripherally mediated action may be linked partly to lipoxygenases and/or cyclo-oxygenases, while the central anti-nociception is likely to be mediated via opioid receptors in the CNS.

Anti-nociceptive and anti-inflammatory activities of the methanolic extract of Parinari polyandra stem bark in rats and mice.

The methanolic extract of the stem bark of Parinari polyandra (family Rosaceae) was investigated for possible anti-nociceptive and anti-inflammatory effects in mice and rats. Three models were used to study the extracts effects on nociception which were the acetic acid-induced abdominal constriction test, hot-plate method (both in mice) and the formalin test in rats. The anti-inflammatory effects were investigated employing the albumin-induced hind-paw oedema in rats. Results of the study revealed the extract to have significant (P<0.05) anti-nociceptive effect at a dose of 200 mg/kg p.o. in mice and rats in all the models for anti-nociception while 100 mg/kg p.o. showed significant (P<0.05) effect in the acetic acid-induced abdominal constriction test and in phase I of the formalin test. The extract also exhibited anti-inflammatory effects which were found to be significant (P<0.05) at 200 mg/kg p.o. in the rats tested. Preliminary phytochemical screening of the extract showed the presence of flavonoids, tannins, and saponin glycoside. The results suggest the extract contains pharmacologically active principles. The result is in agreement with the local application of the plant in painful and inflammatory conditions.

Postsynaptic dopamine (D(2))-mediated behavioural effects of high acute doses of artemisinin in rodents.

Artemisinin or qinghaosu is the active principle of quinghao (Artemisia annua L.) developed from Chinese traditional medicine, which is now widely used around the world against falciparum malaria. Behavioural effects of high acute doses of artemisinin were studied on spontaneous motor activity (SMA), exploratory behavior, apomorphine-induced stereotype behavior and pentobarbital sleeping time in mice and rats in order to provide additional evidence on its safety profile on the central nervous system (CNS). Effects of the drug on bromocriptine-induced hyperactivity in short term reserpinised mice were also evaluated. Intraperitoneal (i.p.) injection of artemisinin at doses of 50 and 100mg/kg, significantly (P<0.05) reduced the SMA in mice, prolonged the pentobarbital sleeping time in rats, and attenuated the apomorphine-induced stereotypy in mice. Mice pretreated with reserpine, showed a significant decrease in locomotor activity compared to the saline-treated group. Bromocriptine, a D(2) receptor agonist, induced locomotor activity in mice pretreated with reserpine which was attenuated by artemisinin. The results suggest that artemisinin possesses sedative property, which may be mediated via postsynaptic dopamine (D(2)) receptor in the CNS.

Central nervous system activity of the methanol extract of Ficus platyphylla stem bark.

The central nervous system (CNS) activity of the methanolic extract of Ficus platyphylla stem bark was studied on locomotor activity, pentobarbital sleeping time, exploratory behaviour, amphetamine-induced hyperactivity, apomorphine-induced stereotypy, active-avoidance and performance on tread mills (rota-rod), using mice and rats. The results revealed that the extract significantly reduced the locomotor and exploratory activities in mice, prolonged pentobarbital sleeping time in rats, attenuated amphetamine-induced hyperactivity and apomorphine-induced stereotypy in mice, dose-dependently. The extract significantly suppressed the active-avoidance response in rats, with no significant effect on motor co-ordination as determined by the performance on rota-rod. The results suggest that the extract may possess sedative principles with potential neuroleptic properties.