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 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cannabis has a potential for clinical use often obscured by unreliable and purely anecdotal reports. The most important natural cannabinoid is the psychoactive tetrahydrocannabinol (delta9-THC); others include cannabidiol (CBD) and cannabigerol (CBG). Not all the observed effects can be ascribed to THC, and the other constituents may also modulate its action; for example CBD reduces anxiety induced by THC. A standardised extract of the herb may be therefore be more beneficial in practice and clinical trial protocols have been drawn up to assess this. The mechanism of action is still not fully understood, although cannabinoid receptors have been cloned and natural ligands identified. Cannabis is frequently used by patients with multiple sclerosis (MS) for muscle spasm and pain, and in an experimental model of MS low doses of cannabinoids alleviated tremor. Most of the controlled studies have been carried out with THC rather than cannabis herb and so do not mimic the usual clincal situation. Small clinical studies have confirmed the usefulness of THC as an analgesic; CBD and CBG also have analgesic and antiinflammatory effects, indicating that there is scope for developing drugs which do not have the psychoactive properties of THC. Patients taking the synthetic derivative nabilone for neurogenic pain actually preferred cannabis herb and reported that it relieved not only pain but the associated depression and anxiety. Cannabinoids are effective in chemotherapy-induced emesis and nabilone has been licensed for this use for several years. Currently, the synthetic cannabinoid HU211 is undergoing trials as a protective agent after brain trauma. Anecdotal reports of cannabis use include case studies in migraine and Tourette's syndrome, and as a treatment for asthma and glaucoma. Apart from the smoking aspect, the safety profile of cannabis is fairly good. However, adverse reactions include panic or anxiety attacks, which are worse in the elderly and in women, and less likely in children. Although psychosis has been cited as a consequence of cannabis use, an examination of psychiatric hospital admissions found no evidence of this, however, it may exacerbate existing symptoms. The relatively slow elimination from the body of the cannabinoids has safety implications for cognitive tasks, especially driving and operating machinery; although driving impairment with cannabis is only moderate, there is a significant interaction with alcohol. Natural materials are highly variable and multiple components need to be standardised to ensure reproducible effects. Pure natural and synthetic compounds do not have these disadvantages but may not have the overall therapeutic effect of the herb.
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PMID:Cannabinoids in clinical practice. 1115 13

During the last decade, brain nicotinic acetylcholine receptors were extensively characterized from electrophysiological and pharmacological points of view. These receptors play important roles in memory and cognition and participate in the pathogenesis of several brain disorders (Parkinson's and Alzheimer's diseases, Tourette's syndrome, schizophrenia, depression, attention deficit disorder). In the same diseases, clinical studies showed that nicotine had beneficial effects, both as therapeutic and prophylactic agent. This review presents recent data concerning the structure and properties of neuronal nicotinic receptors, their involvement in the pathogenesis of various brain disorders and the beneficial effects of nicotine as therapeutic agent.
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PMID:Nicotine and brain disorders. 1126 71

Gilles de la Tourette Syndrome (GTS) and obsessive-compulsive disorder (OCD) share obsessive-compulsive phenomena. The aims of this study were to compare the OC symptom distribution between GTS and OCD and to investigate whether a subdivision of these phenomena into obsessions, compulsions and 'impulsions' is useful in distinguishing GTS and OCD patients. Thirty-two GTS, 31 OCD (10 with tics, 21 without tics) and 29 control subjects were studied using the Leiden repetitive behaviors semi-structured interview to assess GTS as well as OCD-related behaviors. Each reported repetitive thought or action was evaluated on the presence of anxiety and on goal-directedness. This information was used to define whether the behavior was an obsession, compulsion, or 'impulsion'. Both the GTS and OCD study groups showed higher scores than control subjects on rating scales measuring depression, OC behavior and anxiety. In GTS, Y-BOCS severity scores and trait anxiety were lower than in the OCD groups. Furthermore, GTS patients differed from OCD patients in the distribution of symptoms. Aggressive repetitive thoughts, contamination worries and washing behaviors were reported more frequently by tic-free OCD, while mental play, echophenomena, touching and (self)-injurious behaviors were reported more frequently by GTS. OCD individuals with tics were intermediate, but closer to tic-free OCD. GTS individuals reported significantly more 'impulsions' and fewer obsessions and compulsions than OCD individuals with and without tics. Factor analysis revealed three factors accounting for 44% of the variance, resulting in an 'impulsive' factor related to GTS, a 'compulsive' factor related to OCD and an 'obsessive' factor related to tic-free OCD. In conclusion, OCD individuals reported more anxiety and goal-directedness associated with their behaviors than did GTS subjects. The distinction between obsessions, compulsions and impulsions is of importance in identifying Tourette-related vs. non-Tourette-related repetitions.
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PMID:Repetitive behaviors in Tourette's syndrome and OCD with and without tics: what are the differences? 1128 20

Structural and functional images of the brain play an important role as powerful adjuncts in the management of an increasing number of neurologic and psychiatric diseases. Brain SPECT, in particular, with perfusion agents or with neuroreceptor imaging radiopharmaceuticals, is rapidly becoming a clinical tool in many places. For many neurologic and psychiatric conditions, this imaging modality has been used in diagnosis, prognosis assessment, evaluation of response to therapy, risk stratification, detection of benign or malignant viable tissue, and choice of medical or surgical therapy. The importance of this technique in nuclear medicine today should not be overlooked, particularly in cerebrovascular diseases, dementias, epilepsy, head injury, malignant brain tumors, movement disorders, obsessive-compulsive disorder, Gilles de la Tourette's syndrome, schizophrenia, depression, panic disorder, and drug abuse.
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PMID:Brain SPECT in neurology and psychiatry. 1133 51

Family studies suggest an interrelationship between Gilles de la Tourette Syndrome (GTS) and some forms of obsessive-compulsive disorder (OCD). Some authors consider GTS to be part of a serotonergically mediated cluster of OCD spectrum disorders. The present study was undertaken to compare measures of psychopathology, personality and blood serotonin between GTS and OCD (without tics), and to investigate whether an OCD spectrum hypothesis is supported for GTS. Fifteen GTS without OCD subjects, 21 tic with (+) OCD subjects, 15 OCD without tic subjects and 26 controls (all without serotonergic medication) were evaluated with self-rated and clinician-rated measures of psychopathology and personality. Whole blood serotonin (5-HT) and platelet monoamine oxidase activity (MAO) was measured, and Spearman's correlations were calculated between whole blood 5-HT, MAO and rating scale scores within the entire sample and within subgroups. There were main effects of OCD on anxiety, obsessive-compulsive, neuroticism and extraversion scores. There were main effects of tics on depression, obsessive-compulsive, trait anxiety and neuroticism scores, and on platelet MAO. There were interaction effects on platelet MAO, 5-HT, Yale-Brown Obsessive-Compulsive Rating Scale severity, trait anxiety and Eysenck Personality Questionnaire neuroticism scores. Platelet MAO activity was elevated in tic-free OCD subjects when compared to tic + OCD, GTS without OCD and controls. Whole blood 5-HT was lowered in tic + OCD patients in comparison to GTS without OCD and tic-free OCD subjects. Whole blood 5-HT and obsessive-compulsive severity were negatively correlated within OCD without tic patients and MAO and Leyton Obsessive Inventory scores were negatively related within GTS without OCD patients. The biochemical data of this study suggest that in tic + OCD and in tic-free OCD patients, 5-HT dysregulations play a role, but not necessarily in pure GTS. Serotonergic dysregulations within tic + OCD and tic-free OCD patients are distinct, suggesting differences in underlying pathophysiology. The finding that obsessions and compulsions can be associated with either 5-HT hypofunctionality or hyperfunctionality reveals a major weakness in the OCD spectrum theory, i.e. that the associations between obsessive-compulsive behaviours and 5-HT abnormalities are less specific than suggested by the original obsessive-compulsive spectrum model.
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PMID:Psychopathology and personality characteristics in relation to blood serotonin in Tourette's syndrome and obsessive-compulsive disorder. 1144 84

ADHD is a polygenic disorder due to the additive effect of genes affecting dopamine, norepinephrine, serotonin, GABA, and other neurotransmitters. Some of the specific loci involved are dopamine genes--DRD2, DRD4, DRD5, and the dopamine transporter; norepinephrine (NE) and epinephrine (EPI) genes--dopamine beta-hydroxylase, ADRA2A, ADRA2C, PNMT, norepinephrine transporter, MAOA, COMT; serotonin genes--TDO2, HTR1A, HTR1DA, serotonin transporter; GABA genes--GABRB3; androgen receptor and other genes. This model is consistent with all of the present knowledge about ADHD including (a) the increased frequency of ADHD in the relatives of ADHD probands, (b) the presence of a wide spectrum of comorbid behaviors (depression, anxiety, learning, conduct, oppositional-defiant, conduct and substance abuse disorders) in ADHD probands and their relatives on both parental sides, (c) the close relationship to Tourette syndrome (TS), (d) the failure to find the genes for TS using linkage analysis, (e) the brain imaging studies showing hypometabolism of the frontal lobes, (f) the relationship between dopamine D2 receptor density and regional blood flow, (g) the correlation between tics and dopamine D2 receptor density in TS, (h) the motor hyperactivity of dopamine transporter and dopamine D3 receptor gene knockout mice, (i) the LeMoal and Shaywitz dopamine deficiency animal models of ADHD, (j) the NE models of ADHD, (k) the failure to explain ADHD on the basis of any single neurotransmitter defect, (l) the response of ADHD to dopamine and alpha 2-adrenergic agonists, (m) the small percentage of the variance of specific behaviors accounted for by each gene, and numerous other aspects of ADHD. The implications of the polygenic model for the understanding, diagnosis and treatment of ADHD and TS, as well as other psychiatric disorders, are reviewed.
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PMID:Clinical and molecular genetics of ADHD and Tourette syndrome. Two related polygenic disorders. 1146 57

Prior studies have suggested a common etiology involved in Tourette's syndrome and several comorbid conditions and symptomatology. Reportedly, current medications used in Tourette's syndrome have intolerable side-effects or are ineffective for many patients. After thoroughly researching the literature, I hypothesize that magnesium deficiency may be the central precipitating event and common pathway for the subsequent biochemical effects on substance P, kynurenine, NMDA receptors, and vitamin B6 that may result in the symptomatology of Tourette's syndrome and several reported comorbid conditions. These comorbid conditions and symptomatology include allergy, asthma, autism, attention deficit hyperactivity disorder, obsessive compulsive disorder, coprolalia, copropraxia, anxiety, depression, restless leg syndrome, migraine, self-injurious behavior, autoimmunity, rage, bruxism, seizure, heart arrhythmia, heightened sensitivity to sensory stimuli, and an exaggerated startle response. Common possible environmental and genetic factors are discussed, as well as biochemical mechanisms. Clinical studies to determine the medical efficacy for a comprehensive magnesium treatment option for Tourette's syndrome need to be conducted to make this relatively safe, low side-effect treatment option available to doctors and their patients.
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PMID:The central role of magnesium deficiency in Tourette's syndrome: causal relationships between magnesium deficiency, altered biochemical pathways and symptoms relating to Tourette's syndrome and several reported comorbid conditions. 1186 98

Nurses in a variety of settings encounter children with the unfamiliar diagnosis of Asperger syndrome (AS). This disorder, which falls clinically along the autism spectrum, is receiving increasing attention because of its inclusion in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as one of the pervasive developmental disorders. The characteristic features of AS include deficits in social skills, atypical understanding of and use of pragmatic language, behavior problems, and a restricted set of interests. Cognitive abilities vary, and some children with AS have high intelligence. In addition, many children with AS have other conditions, such as attention deficit hyperactivity disorder, Tourette's syndrome, obsessive-compulsive disorder, and depression. The disorder can result in significant functional difficulties in the home, school, and community contexts. A case study highlights the features of AS, and a related individualized school health care plan demonstrates the school nurse's role in family and staff education, monitoring for comorbidities, behavioral management, medication management, support to family members, and referral.
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PMID:Understanding and caring for the child with Asperger syndrome. 1188 20

Pimozide is often coprescribed with serotonin reuptake inhibitor (SSRI) antidepressants to treat depression in patients with Tourette's syndrome. In human liver microsomes (HLMs), the inhibition of the primary route of pimozide metabolism, N-dealkylation to 1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one (DHPBI), by four SSRIs (fluoxetine, sertraline, paroxetine, and fluvoxamine) and azithromycin was tested. Inhibition constants (K(i) values) were estimated from Dixon plots (three HLMs for each inhibitor) using the appropriate enzyme inhibition model by nonlinear regression. At 10 microM paroxetine, sertraline, fluoxetine, or fluvoxamine, the formation of DHPBI from pimozide (10 microM) in HLMs was inhibited by an average (three HLMs) of 7%, 7.7%, 8%, and 16%, respectively, whereas this inhibition did not exceed 55% at the maximum concentrations (100 microM) of the SSRIs tested. Azithromycin had negligible effect on pimozide (10 microM) N-dealkylation (19% at 100 microM azithromycin). These inhibition data were compared with ketoconazole, which was included as a positive control of CYP3A inhibition. At 0.1 microM and 0.5 microM ketoconazole, the formation of DHPBI from 10 microM pimozide was inhibited by 32% and 62%, respectively. The K(i) values (+/- SD) of ketoconazole, sertraline, fluvoxamine, azithromycin, fluoxetine, and paroxetine were 0.07 microM, 89 +/- 44 microM, 89 +/- 24 microM, 103 +/- 52 microM, 117 +/- 27 microM, and 129 +/- 33 microM, respectively. These values are least 100-fold higher than the expected plasma concentrations after the usual daily doses of the SSRIs and azithromycin, suggesting that coadministration of SSRIs and azithromycin are unlikely to markedly diminish the elimination of pimozide in patients. However, in vivo predictions from in vitro data are not always perfect. In vivo, the SSRIs or azithromycin may concentrate in the liver relative to plasma. In addition, the possibility that these drugs could alter pimozide disposition through effects on transport proteins or via promoter repression cannot be ruled out.
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PMID:In vitro inhibition of pimozide N-dealkylation by selective serotonin reuptake inhibitors and azithromycin. 1191 Feb 61

We undertook this study to assess the patterns of regional cerebral perfusion (RCP) with SPECT using Technetium- 99m-ethyl cysteinate dimer (Tc-99m-ECD) in children with Tourette's Syndrome (TS), and to compare these with the patterns in a group of normal controls. The study sample consisted of 38 children (7 to 14 years) who met the ICD-10 and DSM/IV criteria for Tourette's Syndrome, and a control group of 18 children (9 to 14 years). The Children's Depression Inventory and Maudsley Obsessional-Compulsive Questionnaire were used for assessment, and the severity of motor and vocal tics were assessed using the Goetz Rating Scale. The RCP values were significantly lower in the TS group in left caudate, cingulum, right cerebellum, left dorsolateral prefrontal, and the left orbital frontal region. A positive correlation was found between the severity of vocal tics and blood flow of mid-cerebellum, right dorsolateral prefrontal and left dorsolateral prefrontal regions. Although no depressive or obsessive patients were included in the study, the depression and obsession scores were found to be negatively correlated with all RCP values, especially in the temporal regions. Further studies are needed to explore the relationship between the hypoperfusion of certain brain areas and the underlying neurophysiology and neurobiology of patients with TS. Additional disturbances such as obsessive-compulsive symptoms and depressive symptoms should also be assessed
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PMID:Tc-99m-ECD SPECT brain imaging in children with Tourette's syndrome. 1224 30


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