Cannabidivarin (CBDV) and cannabidiol (CBD) have recently emerged among cannabinoids for their potential antiepileptic properties, as shown in several animal models. We report the case of a patient affected by symptomatic partial epilepsy who used cannabis as self-medication after the failure of countless pharmacological/surgical treatments. Clinical and video electroencephalogram (EEG) evaluations were periodically performed, and the serum levels of CBDV, CBD, and Δ9-tetrahydrocannabinol were repeatedly measured.
View Article and Find Full Text PDFRationale: Compulsive symptoms develop in patients exposed to pramipexole (PPX), a dopaminergic agonist with high selectivity for the D3 receptor. Consistently, we demonstrated that PPX produces an exaggerated increase in contrafreeloading (CFL) for water, a repetitive and highly inflexible behavior that models core aspects of compulsive disorders.
Objectives: Given the role of the hippocampus in behavioral flexibility, motivational control, and visuospatial working memory, we investigated the role of hippocampus in the expression of PPX-induced CFL.
Pharmacol Res
September 2014
Aims: Gender-related differences in the pharmacological effects of addictive drug are an emerging issue. This review examines gender differences in both pharmacokinetic and pharmacodynamic aspects of alcohol and cocaine intake since they cause complex pharmacological interactions, not least the formation of the active metabolite cocaethylene.
Methods: The MEDLINE database was searched from 1990 to 2014 in order to find articles related to gender differences in alcohol, cocaine and cocaethylene pharmacokinetics and pharmacodynamics.
The literature documents that personality characteristics are associated with healthy lifestyles, including smoking. Among positive traits, Positivity (POS), defined as a general disposition conducive to facing experience under a positive outlook has shown robust associations with psychological health. Thus, the present study investigated the extent to which POS is able to predict (i) relapse after quitting smoking and (ii) the desire to smoke again.
View Article and Find Full Text PDFBiomed Res Int
February 2015
Aims of the study were to compare medical students (MS) to non-MS with respect to their knowledge of smoking and to investigate the effect of a short educational intervention on MS knowledge. MS (n = 962) and students of architecture and law (n = 229) were asked to complete a 60-item questionnaire addressing knowledge of smoking epidemiology and health effects ("Score 1"), and effectiveness of cessation treatments ("Score 2"). Upon completion of questionnaire, fourth year MS received a lecture on tobacco dependence.
View Article and Find Full Text PDFThe objective was to test the psychometric properties of an Italian version of the Severity of Dependence Scale, a five-item measure designed to assess the compulsive dimension of drug dependence. 635 smokers enrolled in a tobacco dependence treatment program served as the participants. The Fagerström Test for Nicotine Dependence was used as a comparative measure.
View Article and Find Full Text PDFRationale: Dopaminergic D2/D3 agonist quinpirole (QNP) elicits nonregulatory drinking in rats, a model of psychotic polydipsia. Why only a fraction of QNP-treated rats responds to the treatment becoming polydipsic is still unclear.
Objectives: To unveil possible factors contributing to such variability, we analyzed drinking microstructure in saline and QNP-treated rats, the hypothalamic expression of the cocaine and amphetamine regulated transcript (CART), and the monoaminergic turnover in selected brain areas.
We have previously found that phenanthrenic opioids, including codeine, modulate morphine glucuronidation in the rat. Here codeine and five of its derivatives were compared in their effects on the synthesis of morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) from morphine by rat liver microsomal preparations, and by primary cultures of rat hepatocytes previously incubated for 72 h with either codeine or its derivatives. Acetylcodeine and pivaloylcodeine shared the capability of the parent compound of inhibiting the synthesis of M3G by liver microsomes through a noncompetitive mechanism of action.
View Article and Find Full Text PDFMorphine is mainly transformed to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in the liver. Glucuronidation is also performed by rat brain homogenates and UDP-glucuronosyltransferases (UGTs) are present in the brain. Here we investigated the possibility that microglia transforms morphine into its metabolites M3G and M6G.
View Article and Find Full Text PDFClin Neuropharmacol
August 2014
Background: Drug abuse is rarely limited to a single substance; polydrug use is the norm rather than the exception. In many cases, the misuse of potentially psychoactive substances can lead to serious intoxications and results in addictive behavior.
Case Description: A 22-year-old heroin-addicted woman presented in our clinic reporting a 2-year history of intravenous injection of an eyedrop solution containing 1% tropicamide, an antimuscarinic agent.
Rationale: In rats, quinpirole, a dopaminergic D2/D3 receptor agonist, elicits both hyperdipsia and water "contrafreeloading" (CFL), a putative model of compulsivity. The role of D3 receptors in this effect remains unclear. Clomipramine (CIM) was found to contrast both hyperdipsia and CFL, but the role of serotonin in this effect requires further investigation.
View Article and Find Full Text PDFWe have previously found that phenantrenic opioids, such as heroin or naltrexone, modulate morphine glucuronidation in the rat. Here we further investigated the effects of phenantrenic opioids on morphine glucuronidation comparing the effects of codeine and heroin. In particular, we measured the synthesis of morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) from morphine: in the liver microsomal preparations obtained from rats repeatedly treated with two different doses of codeine (ex vivo study); in primary cultures of rat hepatocytes previously incubated for 72h with codeine, or heroin (in vitro study); in the latter conditions, the levels of expression of genes coding for uridine-5'-diphosphate-glucuronosyltransferases (UGTs) A1, A6, A7 and 2B1 were also determined; finally, the levels of glucuronic acid in rat hepatocytes previously incubated for 72h with codeine or heroin were assessed.
View Article and Find Full Text PDFIntroduction: Tobacco smoking is the leading cause of premature death in the developed world. Advice and assistance by physicians help smokers quit, but little attention has been paid to the topic of tobacco dependence in the curricula of Italian medical schools. Consequently, few physicians follow the clinical practice guidelines for treating dependence.
View Article and Find Full Text PDFRationale: Heroin is rapidly metabolized to morphine that in turn is transformed into morphine-3-glucuronide (M3G), an inactive metabolite at mu-opioid receptor (MOR), and morphine-6-glucuronide (M6G), a potent MOR agonist. We have found that rats that had received repeated intraperitoneal injections of heroin exhibit measurable levels of M6G (which is usually undetectable in this species).
Objective: The goal of the present study was to investigate whether M6G synthesis can be induced by intravenous (i.
Methods based on HPLC technology are the most frequently adopted for monitoring blood levels of novel antiepileptics. Here a rapid method based on HPTLC was developed for quantitative determination of lamotrigine (LTG), zonisamide (ZNS) and levetiracetam (LVT) in human plasma and compared with HPLC and LC-MS/MS methods. Chromatographic separation was achieved on silical gel 60F(254) plates using ethylacetate:methanol:ammonia (91:10:15v/v/v) as mobile phase.
View Article and Find Full Text PDFRationale: Repeated administrations of the D2/D3 agonist quinpirole (QNP) to rats elicit an antieconomical pattern of drinking called "contrafreeloading" (CFL), a putative model of compulsive-like behavior.
Objectives: We tested the sensitivity of QNP-induced CFL to haloperidol (HAL), aripiprazole (ARI), and clomipramine (CIM), the latter proven effective in the treatment of obsessive-compulsive disorder (OCD).
Methods: Rats were trained under a schedule of reinforcement (FR3) for water.
We examined the rate of smoking cessation associated with 6 weeks of group counseling therapy (GCT) given alone or in combination with 12 weeks of varenicline (VAR) in 112 smokers. Follow-ups were conducted at 12, 26, and 52 weeks post enrollment. Since participants chose the treatment, differences between the two groups were adjusted using propensity matching.
View Article and Find Full Text PDFPsychopharmacology (Berl)
June 2011
Rationale: We have previously found that rats that were kept at all times in the self-administration (SA) chambers (resident group) self-administered more heroin than rats that were transferred to the SA chambers immediately before testing (Non-Resident group). Alcohol resembles heroin in its ability to produce, at recreational doses, mood elevation, euphoria, drowsiness, and sedation. Furthermore, alcohol presents some similarities with the mechanisms of action of heroin at the levels of the mesostriatal circuitry.
View Article and Find Full Text PDFRationale: The biological underpinnings of schizophrenic polydipsia are poorly understood.
Objectives: This study is aimed at fulfilling the requisites of an experimental model of this syndrome through the quinpirole (QNP) induction of non-regulatory drinking in rats.
Methods: In a first experiment, clozapine (10 and 40 mg/kg p.
Rationale: Repeated administration of the dopamine D2/D3 agonist quinpirole (QNP) progressively increases non-regulatory water intake. This effect may model psychotic polydipsia, a potentially fatal but poorly understood condition.
Objectives: The growing evidence for a role of orexin in mediating arousal and cognition has linked this peptide to schizophrenia, hence we examined whether manipulations of dopaminergic and orexinergic systems, as well as of setting, would further characterize the model.
The recent interest in the psychopharmacological underpinnings of religious experiences has led to both the laboratory characterizations of drug-induced mystical events and psychobiological models of religious experiences rooted in evolution and fitness. Our examination of this literature suggests that these theories may be congruent only within more modern religious and cultural settings and are not generalizable to all historical beliefs, as would be expected from an evolutionarily conserved biological mechanism. The strong influence of culture on the subjective effects of drugs as well as religious thoughts argues against the concept of a common pathway in the brain uniquely responsible for these experiences.
View Article and Find Full Text PDFIntroduction: Legal restrictions have contributed to the decline in smoking prevalence in several European countries. We investigated the impact of the Italian 2005 indoor smoking ban on the efficacy of counseling alone or in combination with bupropion for smoking cessation.
Methods: Before and after the introduction of the ban (2001-2006), 550 smokers were enrolled in the smoking cessation program in Rome and were asked to choose between a 6-week group counseling therapy (GCT) given alone or in combination with 7 weeks of daily bupropion.
Background: We have recently observed an unforeseen dissociation in the effect of environmental context on heroin versus cocaine self-administration in rats. Rats housed in the self-administration chambers (Residents) took more heroin than rats that were transferred to the self-administration chambers only for the test sessions (Nonresidents). The contrary was found for cocaine.
View Article and Find Full Text PDFRationale: We have previously reported that cocaine self-administration is facilitated in male rats not residing in the test chambers (Non Resident rats) relative to rats living in the test chambers at all times (Resident rats). Surprisingly, the opposite was found for heroin.
Materials And Methods: We predicted that, when given access to both cocaine and heroin on alternate days, Non Resident rats would take more cocaine relative to heroin than Resident rats.
We have previously found that repeated exposure to heroin reduces liver synthesis of morphine-3-glucuronide (M3G) and increases the production of morphine-6-glucuronide (M6G), which normally is not formed in the rat. By contrast repeated exposure to naltrexone does not activate M6G synthesis but increases the V(max) of M3G formation. M3G synthesis depends on the activity of two isoforms of the UDP-glucuronosyltransferase (UGT), UGT1A1 and UGT2B1.
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