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Biomedical subjects

Michael Farrell

Publications and source records attributed to Michael Farrell.

At least 19 recordsLinked to original sources
PubMed2026

Cannabis and cannabinoids for the treatment of mental and substance use disorders and symptoms: A systematic review and meta-analysis of experimental and observational studies.

BACKGROUND: Interest in cannabinoids for mental and substance use disorders is increasing. We examined experimental and observational evidence for treating these disorders and their symptoms. METHODS: Systematic review and meta-analysis (PROSPERO CRD42023467536). We searched CENTRAL, MEDLINE, Embase and PsycINFO to May 2025 for studies of cannabinoids in adults (≥18 years) with ADHD, anxiety, depression, PTSD, psychosis or Tourette syndrome, or alcohol, cannabis, opioid or tobacco use disorders. Two reviewers screened, extracted and assessed quality using a risk-of-bias tool and GRADE. RESULTS: We included 82 experimental and 118 observational studies. In RCTs, cannabinoids reduced anxiety symptoms (SMD=-0.40; 95% CI: -0.57, -0.23; I²=90%) and, in one small trial, PTSD symptoms (SMD=-2.60; 95% CI: -4.58, -0.62; n=20), with trivial-to-no effect on depression (SMD=-0.20; 95% CI: -0.43, 0.04; I²=91.6%), ADHD, psychosis and Tourette syndrome. Much anxiety and depression evidence came from symptoms measured as secondary outcomes in other primary conditions. Cannabinoids worsened cannabis use disorder severity in one RCT (SMD=2.35; 95% CI: 1.49, 3.21), with no effect on craving or withdrawal; evidence for alcohol, opioid and tobacco use disorders was very limited. Observational studies suggested improvements but had high risk of bias. The only significant safety finding was increased withdrawals due to adverse events with THC (OR=2.78; 95% CI: 1.66, 4.65). Certainty was predominantly very low. DISCUSSION: The evidence base shows very low certainty, high heterogeneity and methodological limitations, and is insufficient to support cannabinoids as first-line treatment. Signals for anxiety and PTSD are limited by indirectness and low certainty; no benefit was evident for depression; THC-related safety signals warrant careful consideration.

Humans↗
PubMed2006

Violence and psychiatric morbidity in a national household population--a report from the British Household Survey.

This study measured the prevalence of self-reported violence and associations with psychiatric morbidity in a national household population, based on a cross-sectional survey in 2000 of 8,397 respondents in Great Britain. Diagnoses were derived from computer-assisted interviews, with self-reported violent behavior over the previous 5 years. The 5-year prevalence of nonlethal violence in Britain was 12% (95% confidence interval: 11, 13). The risk of violence was substantially increased by alcohol dependence (odds ratio=2.72, 95% confidence interval: 1.85, 3.98), drug dependence (odds ratio=2.63, 95% confidence interval: 1.45, 4.74), and antisocial personality disorder (odds ratio=6.12, 95% confidence interval: 3.87, 9.66). Low prevalences of these conditions (7%, 4%, and 4%, respectively) contrasted with their relatively high proportions of attributed risk of violence (23%, 15%, and 15%). Hazardous drinking was associated with 56% of all reported violent incidents. Screening positive for psychosis did not independently increase risk (odds ratio=3.20, 95% confidence interval: 0.35, 29.6). The study concluded that psychiatric morbidity makes a significant public health impact on violence exerted primarily by persons with any personality disorder, substance dependence, and hazardous drinking. Population interventions for violent behavior are appropriate for hazardous drinking as are targeted interventions for substance dependence and antisocial personality disorder. Despite public concern, the risks of violence from persons with severe mental illness were very low.

Adolescent↗
PubMed2006

Obsessive-compulsive disorder and personality disorder: evidence from the British National Survey of Psychiatric Morbidity 2000.

BACKGROUND: Previous studies indicate that most individuals with obsessive-compulsive disorder (OCD) have comorbid personality disorders (PDs), particularly from the anxious cluster. However, the nature and strength of this association remains unclear, as the majority of previous studies have relied heavily on clinical populations. We analysed the prevalence of screen positive personality disorder in a representative sample of adults with OCD living in private households in the UK. METHODS: A secondary analysis of data from the 2000 British National Survey of Psychiatric Morbidity. The prevalence of PD, as determined by the SCID-II questionnaire, was compared in participants with OCD, with other neuroses and non-neurotic controls. Within the OCD group we also analysed possible differences relating to sex and subtypes of the disorder. RESULTS: The prevalence of any screen positive PD in the OCD group (N=108) was 74%, significantly greater than in both control groups. The most common screen positive categories were paranoid, obsessive-compulsive, avoidant, schizoid and schizotypal. Compared to participants with other neuroses, OCD cases were more likely to screen positively for paranoid, avoidant, schizotypal, dependent and narcissistic PDs. Men with OCD were more likely to screen positively for PDs in general, cluster A PDs, antisocial, obsessive-compulsive and narcissistic categories. The presence of comorbid neuroses in people with OCD had no significant effect on the prevalence of PD. CONCLUSIONS: Personality pathology is highly prevalent among people with OCD who are living in the community and should be routinely assessed, as it may affect help-seeking behaviour and response to treatment.

Adolescent↗
PubMed2006

Human medullary responses to cooling and rewarming the skin: a functional MRI study.

A fall in skin temperature precipitates a repertoire of thermoregulatory responses that reduce the likelihood of a decrease in core temperature. Studies in animals suggest that medullary raphé neurons are essential for cold-defense, mediating both the cutaneous vasoconstrictor and thermogenic responses to ambient cooling; however, the involvement of raphé neurons in human thermoregulation has not been investigated. This study used functional MRI with an anatomically guided region of interest (ROI) approach to characterize changes in the blood oxygen level-dependent (BOLD) signal within the human medulla of nine normal subjects during non-noxious cooling and rewarming of the skin by a water-perfused body suit. An ROI covering 4.9 +/- 0.3 mm(2) in the ventral midline of the medulla immediately caudal to the pons (the rostral medullary raphé) showed an increase in BOLD signal of 3.9% (P < 0.01) during periods of skin cooling, compared with other times. Overall, that signal showed a strong inverse correlation (R = 0.48, P < 0.001) with skin temperature. A larger ROI covering the internal medullary cross section at the same level (area, 126 +/- 15 mm(2)) showed no significant change in mean BOLD signal with cooling (+0.2%, P > 0.05). These findings demonstrate that human rostral medullary raphé neurons are selectively activated in response to a thermoregulatory challenge and point to the location of thermoregulatory neurons homologous to those of the raphé pallidus nucleus in rodents.

Adult↗
PubMed2006

An evaluation of a brief motivational intervention among young ecstasy and cocaine users: no effect on substance and alcohol use outcomes.

AIMS: To investigate whether a stimulant- and alcohol-focused brief motivational intervention induces positive behaviour change among young, regular users of MDMA ('ecstasy'), cocaine powder and crack cocaine. DESIGN AND MEASUREMENTS: A randomized trial of the intervention versus a control group who received written health risk information materials only. All participants completed a baseline self-assessment questionnaire before randomization. Outcome measures were self-reported period prevalence abstinence from ecstasy, cocaine powder and crack cocaine and the frequency and amount of stimulant and alcohol use in the previous 90 days, recorded at 6-month follow-up via self-completion questionnaire and personal interview. PARTICIPANTS AND SETTING: A total of 342 adolescent and young adult stimulant users (aged 16-22 years) were recruited and 87% were followed-up. The intervention was delivered by a team of 12 agency youth drug workers and two researchers at five locations in Greater London and south-east England. FINDINGS: There were no significant differences in abstinence for ecstasy, cocaine powder or crack cocaine use between the experimental and control groups. Contrasting follow-up with baseline self-reports, there were no between-group effects for changes in the frequency or amount of stimulant or alcohol use. Participant follow-up data suggested that the baseline assessment was a contributing factor in within-group behaviour change among experimental and control condition participants. CONCLUSIONS: Our brief motivational intervention was no more effective at inducing behaviour change than the provision of information alone. We hypothesize that research recruitment, baseline self-assessment and contact with study personnel are influences that induce positive reactive effects on stimulant use.

Adolescent↗
PubMed2006

Obsessive-compulsive disorder: prevalence, comorbidity, impact, and help-seeking in the British National Psychiatric Morbidity Survey of 2000.

OBJECTIVE: There is little information about obsessive-compulsive disorder in large representative community samples. The authors aimed to establish obsessive-compulsive disorder prevalence and its clinical typology among adults in private households in Great Britain and to obtain generalizable estimates of impairment and help-seeking. METHOD: Data from the British National Psychiatric Morbidity Survey of 2000, comprising 8,580 individuals, were analyzed using appropriate measurements. The study compared individuals with obsessive-compulsive disorder, individuals with other neurotic disorders, and a non-neurotic comparison group. ICD-10 diagnoses were derived from the Clinical Interview Schedule-Revised. RESULTS: The authors identified 114 individuals (74 women, 40 men) with obsessive-compulsive disorder, with a weighted 1-month prevalence of 1.1%. Most individuals (55%) in the obsessive-compulsive group had obsessions only. Comorbidity occurred in 62% of these individuals, which was significantly greater than the group with other neuroses (10%). Co-occurring neuroses were depressive episode (37%), generalized anxiety disorder (31%), agoraphobia or panic disorder (22%), social phobia (17%), and specific phobia (15%). Alcohol dependence was present in 20% of participants, mainly men, and drug dependence was present in 13%. Obsessive-compulsive disorder, compared with other neurotic disorders, was associated with more marked social and occupational impairment. One-quarter of obsessive-compulsive disorder participants had previously attempted suicide. Individuals with pure and comorbid obsessive-compulsive disorder did not differ according to most indices of impairment, including suicidal behavior, but pure individuals were significantly less likely to have sought help (14% versus 56%). CONCLUSIONS: A rare yet severe mental disorder, obsessive-compulsive disorder is an atypical neurosis, of which the public health significance has been underestimated. Unmet need among individuals with pure obsessive-compulsive disorder is a cause for concern, requiring further investigation of barriers to care and interventions to encourage help-seeking.

Comorbidity↗
PubMed2006

Violence and psychiatric morbidity in the national household population of Britain: public health implications.

BACKGROUND: It is unclear whether psychiatric morbidity contributes to the small proportion of the population responsible for a large percentage of antisocial behaviour, including violence. AIMS: To measure associations between psychiatric morbidity and severity, chronicity and types of victims of violence in the national household population of Britain. METHOD: Cross-sectional survey of persons in households (n = 8397).Data included self-reported location, victims and outcome of violence over the previous 5 years. Diagnoses were determined by computer-assisted interviews. RESULTS: Hazardous drinking was associated with over half of all incidents involving injury. Antisocial personality disorder conveyed an attributable risk of 24% of respondents reporting victim injuries, but screening positive for psychosis conveyed an attributable risk of only 1.2%. CONCLUSIONS: The burden of care resulting from violence associated with hazardous drinking supports population interventions. Despite exceptional risks, half of respondents with antisocial personality disorder were not violent, indicating limitations in targeted interventions to detain high-risk individuals.

Adolescent↗
PubMed2005

Brief report: Methadone treatment of injecting opioid users for prevention of HIV infection.

OBJECTIVE: To assess the effects of oral substitution treatment for opioid-dependent injecting drug users on HIV risk behaviors and infections. DATA SOURCES: Multiple electronic databases were searched. Reference lists of retrieved articles were checked. METHODS: Because of varying methodologies of available studies, this systematic review was limited to a descriptive summary, looking at consistency of outcomes across studies. RESULTS: Twenty-eight studies involving methadone treatment were included in the review. Methadone maintenance treatment is associated with statistically significant reductions in injecting use and sharing of injecting equipment. It is also associated with reductions in numbers of injecting drug users reporting multiple sex partners or exchanges of sex for drugs or money, but has little effect on condom use. It appears that the reductions in risk behaviors do translate into fewer cases of HIV infection. CONCLUSIONS: Methadone maintenance treatment for injecting drug users significantly reduces the risk of transmission of HIV and should be provided as a component of a strategic approach to the prevention and control of HIV infection. There is insufficient evidence to determine whether other forms of oral substitution treatment also reduce the risk of HIV transmission.

HIV Infections↗
PubMed2005

Concurrent and construct validity of the audit in an urban brazilian sample.

AIMS: To assess the concurrent and the construct validity of the Alcohol Use Disorders Identification Test (AUDIT) in an urban Brazilian sample. METHODS: A random sample of 166 clients of a health management organization, participated in this study. They were visited in their households and completed a self-report questionnaire, which included the AUDIT. Later, they answered the alcohol-related disorders (ARDs) Section of the Composite International Diagnostic Interview. The receiver operating curve (ROC) was used to find the best cut-off point for ICD-10 diagnosis of ARDs. Confirmatory factor analysis was run to assess the construct validity. RESULTS: The ROC analysis showed the same cut-off point (7/8) for ICD-10 diagnosis of ARDs found in previous studies carried out in primary care settings, including in Brazil, with a sensitivity of 100% and a specificity of 76%. The confirmatory factor analysis suggested a two-factor structure. The first factor measured consumption and the second factor alcohol-related problems. CONCLUSIONS: The results supported the use of the self-reported version of the AUDIT in epidemiologic studies, and showed a similar cut-off point for detection of ARDs and hazardous drinking.

Adolescent↗
PubMed2005

Cortical, thalamic, and hypothalamic responses to cooling and warming the skin in awake humans: a positron-emission tomography study.

Thermoregulatory mechanisms are remarkably efficient, ensuring minimal temperature variation within the core of the human body under physiological conditions. Diverse afferent and efferent neural pathways contribute to the monitoring of core and skin temperature, generation of heat, and control of thermal exchange with the external environment. We have investigated the cortical, thalamic, and hypothalamic responses to cooling and warming by using positron-emission tomography activation imaging of subjects clad in a water-perfused suit, which enabled rapid change of their skin-surface temperature. Human brain regions that respond to changes in skin temperature have been identified in the somatosensory cortex, insula, anterior cingulate, thalamus, and hypothalamus, with evidence that the hypothalamic response codes for the direction of temperature change. We conclude that signals from thermosensors in the skin providing crucial afferent information to the brain are integrated with signals from central thermosensors, resulting in thermoregulatory responses that maintain core temperature within a remarkably narrow range.

Adult↗
PubMed2005

Adenosine monophosphate-activated protein kinase disease mimicks hypertrophic cardiomyopathy and Wolff-Parkinson-White syndrome: natural history.

OBJECTIVES: The aim of this study was to investigate the clinical expression of adenosine monophosphate-activated protein kinase (AMPK) gene mutations (PRKAG2) in adenosine monophosphate (AMP) kinase disease based on 12 years follow-up of known mutation carriers and to define the prevalence of PRKAG2 mutations in hypertrophic cardiomyopathy (HCM). BACKGROUND: Adenosine monophosphate-activated protein kinase gene mutations cause HCM with Wolff-Parkinson-White syndrome and conduction disease. METHODS: Clinical evaluation of 44 patients with known AMP kinase disease was analyzed. Mutation analysis of PRKAG2 was performed by fluorescent single-strand confirmation polymorphism analysis and direct sequencing of abnormal conformers in 200 patients with HCM. RESULTS: Only one additional mutation was identified. The mean age at clinical diagnosis in the 45 gene carriers was 24 years (median 20 years, range 9 to 55 years). Symptoms of palpitation, dypspnea, chest pain, or syncope were present in 31 (69%) gene carriers; 7 (15%) complained of myalgia and had clinical evidence of proximal myopathy. Skeletal muscle biopsy showed excess mitochondria and ragged red fibers with minimal glycogen accumulation. Disease penetrance defined by typical electrocardiogram abnormalities was 100% by age 18 years. Thirty-two of 41 adults (78%) had left ventricular hypertrophy (LVH) on echocardiography, and progressive LVH was documented during follow-up. Survival was 91% at a mean follow-up of 12.2 years. Progressive conduction disease required pacemaker implantation in 17 of 45 (38%) at a mean age of 38 years. CONCLUSIONS: The AMP kinase disease is uncommon in HCM and is characterized by progressive conduction disease and cardiac hypertrophy and includes extracardiac manifestations such as a skeletal myopathy, consistent with a systemic metabolic storage disease. Defects in adenosine triphosphate utilization or in specific cellular substrates, rather than mere passive deposition of amylopectin, may account for these clinical features.

AMP-Activated Protein Kinases↗
PubMed2005

Adaptive responses to mitochondrial dysfunction in the rho degrees Namalwa cell.

Mitochondrial function depends on the synchronised expression of nuclear and mitochondrial-encoded genes. The expression of many nuclear genes is sensitive to the functional state of mitochondria. Mitochondria containing mutated mtDNA populations have been shown to withstand stress to a high level of tolerance. The prolonged survival of cells that are devoid of mitochondrial DNA is further evidence for the existence of this adaptive response. Yeast cells lacking the mitochondrial genome configure their pattern of nuclear gene expression to accommodate changes in nutrient availability and in response to different stress conditions. Little is known about the signalling pathways that mediate the adaptive response in mammalian cells with mitochondrial dysfunction. To gain a global perspective on adaptive responses in cells with mitochondrial dysfunction, we used Affymetrix microarray technology to compare the whole genome transcription profile of Namalwa cells (rho(+)) to that of a Namalwa cell depleted of mitochondrial DNA (rho degrees ). Our results demonstrate that rho degrees Namalwa induce genes encoding hypoxia target proteins, mitochondrial ribosomal proteins, transport channels, tRNA synthetases and enzymes of the glycolytic pathway and the fatty oxidation pathway suggesting that hypoxia and the ensuing cellular adaptations could play an important adaptive role in cells with mitochondrial dysfunction.

Adaptation, Physiological↗
PubMed2005

Progressive myoclonic epilepsies: a review of genetic and therapeutic aspects.

The progressive myoclonic epilepsies (PMEs) are a group of symptomatic generalised epilepsies caused by rare disorders, most of which have a genetic component, a debilitating course, and a poor outcome. Challenges with PME arise from difficulty with diagnosis, especially in the early stages of the illness, and further problems of management and drug treatment. Recent advances in molecular genetics have helped achieve better understanding of the different disorders that cause PME. We review the PMEs with emphasis on updated genetics, diagnosis, and therapeutic options.

Adolescent↗
PubMed2005

Dying for heroin: the increasing opioid-related mortality in the Republic of Ireland, 1980-1999.

BACKGROUND: Over the past 20 years there has been a steady rise in mortality associated with opioid misuse in several Western countries. We aimed to examine trends in opioid-related mortality over a 20-year period in the Republic of Ireland. METHODS: Retrospective analysis of deaths attributed to ICD-9 codes 304.0 (morphine-type dependence) and E850.0 (accidental poisoning by opiates and related narcotics) in the Republic of Ireland between 1980 and 1999. RESULTS: The Republic of Ireland has seen a rapid increase in the number of opioid-related deaths over the 20-year period studied, from 0.01% of total deaths in 1980 to 0.15% in 1999. This is most marked in the younger age groups where, for example, it rose to 23% of 15-19 year old male deaths for 1997. The opioid-related mortality rate in the 15-44 years age range increased by nearly 14 times between 1980-1984 and 1995-1999. Over the whole period, 87% of opioid-related deaths were amongst males. Outside Dublin there has been a considerable increase in opioid-related mortality, nearly doubling the percentage of the total from 6% in the 1980s to 11% in the 1990s. CONCLUSIONS: Opioid-related mortality is an increasing problem in the Republic of Ireland, as in other Western countries. Today, young people have a very low mortality rate, and hence this rapid increase may need specific targeted interventions. The spread of opioid-related mortality outside Dublin to rural and other urban areas will have implications for service planning and provision.

Adolescent↗
PubMed2005

Psychosis in the community and in prisons: a report from the British National Survey of psychiatric morbidity.

OBJECTIVE: Reports of increased rates of psychosis in prisons could be due to sampling and ascertainment differences. The authors compared two samples of subjects 16-64 years of age: those from the general population of residents in Great Britain and prisoners in England and Wales. METHOD: A random sample of remanded and sentenced male and female prisoners (N=3,142) and a two-phase, cross-sectional random sample of household residents (N=10,108) were assessed with structured questionnaires and the semistructured Schedules for Clinical Assessment in Neuropsychiatry. RESULTS: The weighted prevalence of probable functional psychosis in the past year was 4.5 per thousand (95% CI=3.1 to 5.8) in the household survey. In the prison survey, the weighted prevalence was over 10 times greater: 52 per thousand (95% CI=45 to 60). One in four prisoners with a psychotic disorder had psychotic symptoms attributed to toxic or withdrawal effects of psychoactive substances. The proportion of subjects with specific types of hallucinations or delusions did not differ between prison and household psychosis cases. CONCLUSIONS: This large study using standardized comparisons showed that the prevalence of psychosis in prisons is substantially higher than in the community and is deserving of greater attention to treatment and prevention. Apart from a minority of prisoners with symptoms attributable to psychoactive substances, the clinical symptom profile of psychosis is the same in both settings. Longitudinal research is needed to better understand these prevalence differences.

Adolescent↗
PubMed2005

Alcohol consumption as a risk factor for anxiety and depression: results from the longitudinal follow-up of the National Psychiatric Morbidity Survey.

BACKGROUND: Longitudinal studies have been in conclusive in identifying alcohol as a risk factor for anxiety and depression. AIMS: To examine whether excessive alcohol consumption is a risk factor for anxiety and depression in the general population, and whether anxiety and depression are risk factors for excessive alcohol consumption. METHOD: Data were analysed from the 18-month follow-up of the Psychiatric Morbidity Among Adults Living in Private Households, 2000 survey. RESULTS: Hazardous and dependent drinking were not associated with onset of anxiety and depression at follow-up. Binge-drinking was non-significantly associated with incident anxiety and depression (adjusted OR=1.36, 95% CI 0.74-2.50). Abstainers were less likely to have new-onset anxiety and depression at follow-up. Anxiety and depression or sub-threshold symptoms at baseline were not associated with incident hazardous or binge-drinking at follow-up, but there was weak evidence linking sub-threshold symptoms with onset of alcohol dependence (adjusted OR=2.04, 95% CI 0.84-4.97). CONCLUSIONS: Excessive alcohol consumption was not associated with the onset of anxiety and depression but abstinence was associated with a lower risk. Sub-threshold symptoms were weakly associated with new-onset alcohol dependence.

Adolescent↗