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CORK Bibliography: Drugs, Beneficial Effects

59 citations. January 2010 to present

Prepared: March 2012

Aranda JV; Beharry K; Valencia GB; Natarajan G; Davis J. Caffeine impact on neonatal morbidities. Journal of Maternal-Fetal & Neonatal Medicine 23(Supplement 3): 20-23, 2010. (30 refs.)

Caffeine is a silver bullet in neonatology. This ubiquitous trimethylxanthine, pervasively used in the human diet and beverages, significantly impacts on major acute neonatal morbidities including apnea of prematurity, bronchopulmonary dysplasia, patent ductus arteriousus with or without surgical ligation and post-operative apnea. Potential uses in respiratory distress syndrome as suggested by improved lung function in primate models is supported by the decreased time on mechanical ventilation and need for oxygen therapy. Improved later outcomes at 18 to 22 months include clinically significant decreases in cerebral palsy, cognitive impairment, and severe retinopathy of prematurity in those babies who received caffeine during the neonatal period compared to non-caffeine treated placebo neonates. Ongoing and future research studies focus on optimizing current dose regimens to determine whether benefits can be maximized while maintaining an impressive safety profile. Molecular pharmacologic studies focused on the molecular and the biochemical mechanisms underlying the protective effects of caffeine are also being done to optimize treatment regimes and to target potential molecular pathways leading to further decreases in acute and long term neonatal morbidities. Since its use in newborns three decades ago, caffeine is now one of the safest, most cost-beneficial and effective therapies in the newborn.

Altman RD; Lang AE; Postuma RB. Caffeine in Parkinson's disease: A pilot open-label, dose-escalation study. Movement Disorders 26(13): 2427-2431, 2011. (33 refs.)

Introduction: Epidemiologic studies consistently find an inverse association between caffeine use and PD. Numerous explanations exist, but are difficult to evaluate as caffeine's symptomatic effect and tolerability in PD are unknown. Patients and Methods: We designed an open-label, 6-week dose-escalation study of caffeine to establish dose tolerability and evaluate potential motor/nonmotor benefits. Caffeine was started at 200 mg daily and was increased to a maximum of 1,000 mg. Results: Of 25 subjects, 20 tolerated 200 mg, 17 tolerated 400 mg, 7 tolerated 800 mg, and 3 tolerated 1,000 mg. The most common adverse events were gastrointestinal discomfort, anxiety, and worsening/emerging tremor. At 400 mg daily, we found potential improvements in motor manifestations and somnolence (UPDRS III: -4.5 +/- 4.6, P = 0.003; Epworth: -2.0 +/- 3.0, P = 0.015). Conclusion: Maximum dose tolerability for caffeine in PD appears to be 100 to 200 mg BID. We found pilot preliminary evidence that caffeine may improve some motor and nonmotor aspects of PD, which must be confirmed in longer term, placebo-controlled, clinical trials.

Baggott MJ; Erowid E; Erowid F; Galloway GP; Mendelson J. Use patterns and self-reported effects of Salvia divinorum: An internet-based survey. Drug and Alcohol Dependence 111(3): 250-256, 2010. (67 refs.)

Background: There is growing use of Salvia divinorum (SD) a psychoactive plant that produces hallucinogen-like effects through a kappa opioid receptor (KOR) mechanism. Little is known about KOR agonist effects in humans and about users of SD Objectives To characterize the reasons methods and reported consequences of SD use. Methods: Individuals reading SD-related pages of a drug-information website were invited to anonymously complete an online questionnaire if they had used SD. Results: Participants (N=500) were 92 6% male and 23 4 +/- 8 7 (mean +/- s d) years old They had used a median of six times (range 1-250) 80 6% probably or definitely would use SD again Most participants (92 6%) typically smoked or vaporized SD product When smoked the drug s main effects were estimated to last 14 1 +/- 12 8 (range 0 5-120) minutes When asked to compare SD effects to other methods of altering consciousness the most common answer was that SD was unique (38 4%) 25 8% reported persisting (>= 24 h) positive effects (often described as increased sense of well-being) on at least one occasion 4 4% reported persisting negative effects (most often anxiety). Conclusions: SD is typically smoked, acute effects are brief, and persistent adverse effects are uncommon. In addition to acute hallucinogenic effects SD may produce subacute increases in subjective well-being. Such a subacute effect would be unusual for a drug that is used non-medically as withdrawal from other drugs typically either does not affect mood or causes dysphoria. Findings from this convenience sample should be confirmed and extended using surveys of random samples and controlled clinical studies.

Baumrucker S; Mingle P; Harrington D; Stolick M; Carter GT; Oertli KA. Medical marijuana and organ transplantation: drug of abuse, or medical necessity? American Journal of Hospice & Palliative Medicine 28(2): 130-134, 2011. (13 refs.)

This article focuses upon a liver transplant candidate who was removed from the transplant list as the result of a laboratory test indicating his use of marijuana, which was defined as "using drugs of abuse." The ethics team at the hospital was not consulted nor made aware of the case. Of note, the patient was following the state law, allowing him to use marijuana to treat his pain, nausea, and vomiting, which turned out to be the only thing that worked. Despite following state laws, this statefunded university hospital refused to reconsider its decision. This was the case though physicians advocated for the patient and noted that there was no scientific literature showing any increased risk of organ damage or rejection from someone using marijuana. There are commentaries on this case from different members of the referring hospital care team: nurse, social worker, physician, a physician-ethicist, and chaplain.

Beghi E; Pupillo E; Messina P; Giussani G; Chio A; Zoccolella S et al. Coffee and amyotrophic lateral sclerosis: A possible preventive role. American Journal of Epidemiology 174(9): 1002-1008, 2011. (25 refs.)

The relation between coffee intake and risk of amyotrophic lateral sclerosis (ALS) was investigated in 377 newly diagnosed ALS patients from 4 Italian population-based registries in the European ALS Consortium (EURALS Group) (2007-2010). For each patient, 2 age- and sex-matched hospital controls were selected, one from a neurology department and one from a nonneurologic department. Two additional healthy control groups were identified from local general practitioners' (GPs') lists (n = 99) and residents of the same area as a cancer cohort (n = 7,057). Coffee intake was defined in terms of status (ever consuming coffee daily for >= 6 months vs. never), duration, and history (never, former, or current). Ever coffee drinkers comprised 74.7% of ALS patients, 80.4% of neurologic controls, 85.6% of nonneurologic controls (P = 0.0004), 88.9% of GP controls (P = 0.0038), and 86.0% of cancer cohort controls (P < 0.0001). Current coffee drinkers comprised 60.2% of ALS patients, 70.2% of neurologic controls (P = 0.0294), 76.4% of nonneurologic controls (P < 0.0001), and 82.3% of GP controls (P = 0.0002); duration of intake was >= 30 years for 62.3%, 67.7%, 74.7%, and 72.6%. ALS patients had lower lifetime coffee exposure: Odds ratios were 0.7 (95% confidence interval (CI): 0.5, 1.1), 0.6 (95% CI: 0.4, 0.8), and 0.4 (95% CI: 0.2, 0.9) in comparison with neurologic, nonneurologic, and GP controls, respectively. In current (vs. never) coffee drinkers, odds ratios were 0.7 (95% CI: 0.5, 1.0), 0.5 (95% CI: 0.3, 0.7), and 0.4 (95% CI: 0.2, 0.8), respectively. These findings provide epidemiologic evidence of an inverse correlation between coffee intake and ALS risk.

Benson VS; Green J; Pirie K; Beral V. Cigarette smoking and risk of acoustic neuromas and pituitary tumours in the Million Women Study. British Journal of Cancer 102(11): 1654-1656, 2010. (13 refs.)

BACKGROUND: The relationship between cigarette smoking and incidence of acoustic neuromas and pituitary tumours is uncertain. METHODS: We examined the relation between smoking and risk of acoustic neuromas and pituitary tumours in a prospective study of 1.2 million middle-aged women in the United Kingdom. RESULTS: Over 10.2 million person years of follow-up, 177 women were diagnosed with acoustic neuromas and 174 with pituitary tumours. Current smokers at recruitment were at significantly reduced risk of incident acoustic neuroma compared with never smokers (adjusted relative risk (RR) = 0.41, 95% confidence interval (CI) = 0.24-0.70, P = 0.001). Past smokers did not have significantly different risk of acoustic neuroma than never smokers (RR = 0.87, 95% CI = 0.62-1.22, P = 0.4). Smoking was not associated with incidence of pituitary tumours (RR in current vs never smokers = 0.91, 95% CI = 0.60-1.40, P = 0.7). CONCLUSION: Women who smoke are at a significantly reduced risk of acoustic neuromas, but not of pituitary tumours, compared with never smokers. Acoustic neuromas are much rarer than the cancers that are increased among smokers.

Biessels GJ. Caffeine, diabetes, cognition, and dementia. (review). Journal of Alzheimer's Disease 20(Supplement 1): S143-S150, 2010. (94 refs.)

People with diabetes mellitus are at increased risk of cognitive dysfunction. This review explores the relation between caffeine intake, diabetes, cognition and dementia, focusing on type 2 diabetes (T2DM). Epidemiological studies on caffeine/coffee intake and T2DM risk are reviewed. Next, the impact of T2DM on cognition is addressed. Finally, the potential for caffeine to modulate the risk of cognitive decline in the context of diabetes is explored. The conclusion is that, although epidemiological studies indicate that coffee/caffeine consumption is associated with a decreased risk of T2DM and possibly also with a decreased dementia risk, we can at present not be certain that these associations are causal. For now, recommendations for coffee consumption in individuals with T2DM or pre-diabetic stages are therefore difficult to establish, but it should be acknowledged that caffeine does appear to have several properties that warrant further investigations in this field.

Brady KT; Gray KM; Tolliver BK. Cognitive enhancers in the treatment of substance use disorders: Clinical evidence. (review). Pharmacology, Biochemistry and Behavior 99(2, special issue): 285-294, 2011. (140 refs.)

Attenuation of drug reward has been the major focus of medication development in the addiction area to date. With the growth of research in the area of cognitive neuroscience, the importance of executive function and inhibitory cognitive control in addictive disorders is becoming increasingly apparent. An emerging strategy in the pharmacotherapy of addictions and other psychiatric disorders involves the use of medications that improve cognitive function. In particular, agents that facilitate inhibitory and attentional control, improve abstraction, planning and mental flexibility could be beneficial in the treatment of substance use disorders. Because there are multiple neurotransmitter systems involved in the regulation of cognitive function, agents from a number of drug classes have been tested. In particular, agents acting through the cholinergic, adrenergic and glutamatergic systems have shown potential for improving cognitive function in a number of psychiatric and neurologic disorders, but most of these agents have not been tested in the treatment of individuals with substance use disorders. This manuscript provides a review of clinical data supporting the use of the major classes of cognitive enhancing agents in substance use disorders. Agents that have shown promise in cognitive enhancement in other disorders, and have a theoretical or mechanistic rationale for application to substance use disorders are also highlighted.

Brattwall M; Stomberg MW; Rawal N; Segerdahl M; Houltz E; Jakobsson J. Postoperative impact of regular tobacco use, smoking or snuffing, a prospective multi-center study. Acta Anaesthesiologica Scandinavica 54(3): 321-327, 2010. (18 refs.)

Background: The aim was to study the effects of different tobacco administration routes on pain and post-operative nausea and vomiting (PONV), following three common day surgical procedures: cosmetic breast augmentation (CBA), inguinal hernia repair (IHR) and arthroscopic procedures (AS). We have prospectively investigated the effects of regular tobacco use in ambulatory surgery. Methods: The 355 allocated patients were followed during recovery and the first day at home. Results: Thirty-two percent of the patients used tobacco regularly, 33% of CBA, 27% of IHR and 34% of AS. Pain was well controlled in the post-anesthesia care unit at rest; during ambulation, 37% of all patients reported VAS > 3. Tobacco use had no impact on early post-operative pain. Post-operative nausea was experienced by 30% of patients during recovery while in hospital. On day 1, 14% experienced nausea. We found a significant reduction of PONV among tobacco users (smoking and/or snuffing). Smoking or snuffing reduced the risk of PONV by nearly 50% in both genders on the day of surgery and at the first day at home. The reduction of PONV was equal, regardless of tobacco administration routes. Conclusion: We found that regular use of tobacco, both by smoking and snuffing, had a significant effect on PONV during the early post-operative period. Non-tobacco users undergoing breast surgery were found to have the highest risk for PONV. We could not see any influence of nicotine use on post-operative pain. Thus, it seems of value to identify regular tobacco use, not only smoking, as a part of the pre-operative risk assessment.

Choi HK; Curhan G. Coffee consumption and risk of incident gout in women: the Nurses' Health Study. American Journal of Clinical Nutrition 92(4): 922-927, 2010. (52 refs.)

Background: Coffee is one of the most widely consumed beverages in the world and may affect the risk of gout via various mechanisms, but prospective data on the relation between coffee intake and the risk of incident gout are limited. Design: Over a 26-y period, we prospectively examined the relation between coffee intake and risk of incident gout in 89,433 female participants in the Nurses Health Study. We assessed the consumption of coffee, decaffeinated coffee, tea, and total caffeine in participants every 2-4 y through validated questionnaires. We used a supplementary questionnaire to ascertain whether participants met the survey criteria of the American College of Rheumatology for gout. Results: During the 26 y of follow-up, we documented 896 confirmed incident cases of gout. There was an inverse association between higher coffee intake and the risk of gout. The multivariate relative risks (RRs) for incident gout according to coffee-consumption categories [ie, 0, 1-237, 238-947, and >= 948 mL coffee/d (237 mL one 8-ounce cup)] were 1.00, 0.97, 0.78 (95% CI: 0.64, 0.95), and 0.43 (95% CI: 0.30, 0.61; P for trend < 0.0001), respectively. For decaffeinated coffee, the multivariate RRs according to consumption categories (0, 1-237, and >= 237 mL decaffeinated coffee/d) were 1.00, 1.02, and 0.77 (95% CI: 0.63, 0.95; P for trend = 0.02), respectively. There was an inverse association between total caffeine from all sources and the risk of gout; the multivariate RR of the highest quintile compared with the lowest quintile was 0.52 (95% CI: 0.41, 0.68; P for trend <0.0001). Conclusion: These prospective data suggest that long-term coffee consumption is associated with a lower risk of incident gout in women.

Costa J; Lunet N; Santos C; Santos J; Vaz-Carneiro A. Caffeine exposure and the risk of Parkinson's Disease: A systematic review and meta-analysis of observational studies. (review). Journal of Alzheimers Disease 20(Supplement 1): S221-S238, 2010. (61 refs.)

Several studies conducted worldwide report an inverse association between caffeine/coffee consumption and the risk of developing Parkinson's disease (PD). However, heterogeneity and conflicting results between studies preclude a correct estimation of the strength of this association. We conducted a systematic review and meta-analysis of published epidemiological studies to better estimate the effect of caffeine exposure on the incidence of PD. Data sources searched included Medline, LILACS, Scopus, Web of Science and reference lists, up to September 2009. Cohort, case-control and cross-sectional studies were included. Three independent reviewers selected the studies and extracted the data on to standardized forms. Twenty-six studies were included: 7 cohort, 2 nested case-control, 16 case-control, and 1 cross-sectional study. Quantitative data synthesis of the most precise estimates from each study was accomplished through random effects meta-analysis. Heterogeneity was quantified using the I-2 statistic. The summary RR for the association between caffeine intake and PD was 0.75 [95% Confidence Interval (95% CI): 0.68-0.82], with low to moderate heterogeneity (I-2 = 28.8%). Publication bias for case-control/cross-sectional studies may exist (Egger's test, p = 0.053). When considering only the cohort studies, the RR was 0.80 (95% CI: 0.71-90; I-2 = 8.1%). The negative association was weaker when only women were considered (RR = 0.86, 95% CI: 0.73-1.02; I-2 = 12.9%). A linear relation was observed between levels of exposure to caffeine and the RR estimates: RR of 0.76 (95% CI: 0.72-0.80; I-2 = 35.1%) per 300 mg increase in caffeine intake. This study confirm an inverse association between caffeine intake and the risk of PD, which can hardly by explained by bias or uncontrolled confounding.

de Carvalho M; Marcelino E; de Mendonca A. Electrophysiological studies in healthy subjects involving caffeine. Journal of Alzheimers Disease 20(Supplement 1): S63-S69, 2010. (46 refs.)

We review the electrophysiological studies concerning the effects of caffeine on muscle, lower and upper motor neuron excitability and cognition. Several different methods have been used, such as electromyography, recruitment analysis, H-reflex, transcranial magnetic stimulation (TMS), electroencephalography and event-related potentials. The positive effect of caffeine on vigilance, attention, speed of reaction, information processing and arousal is supported by a number of electrophysiological studies. The evidence in favor of an increased muscle fiber resistance is not definitive, but higher or lower motor neuron excitability can occur as a consequence of a greater excitation of the descending input from the brainstem and upper motor neurons. TMS can address the influence of caffeine on the upper motor neuron. Previous studies showed that cortico-motor threshold and intracortical excitatory and inhibitory pathways are not influenced by caffeine. Nonetheless, our results indicate that cortical silent period (CSP) is reduced in resting muscles after caffeine consumption, when stimulating the motor cortex with intensities slightly above threshold. We present new data demonstrating that this effect is also observed in fatigued muscle. We conclude that CSP can be considered a surrogate marker of the effect of caffeine in the brain, in particular of its central ergogenic effect.

de Mendonca A; Cunha RA. Therapeutic opportunities for caffeine in Alzheimer's disease and other neurodegenerative disorders. Preface. Journal of Alzheimers Disease 20(Supplement 1): S1-S2, 2010. (0 refs.)

DeSantis A; Noar SM; Webb EM. Speeding through the frat house: A qualitative exploration of nonmedical ADHD stimulant use in fraternities. Journal of Drug Education 40(2): 157-171, 2010. (24 refs.)

Qualitative methods were used to investigate the use of nonmedical Attention Deficit Hyperactivity Disorder (ADHD) stimulants by fraternity members. The primary goal of the study was to determine students' levels of understanding and motivations for use of these Schedule II controlled substances. Seventy-nine in-depth interviews were conducted. Key findings highlighted how: a) easy it was for subjects to obtain stimulants; b) little health information nonmedical users have about stimulants; c) academic stress created a fertile context for stimulant use; and d) a small number of prescribed users supply the vast majority of nonmedical users with their stimulants. Most nonmedical users claimed to primarily use ADHD stimulants in periods of high academic stress and believed that they not only reduced fatigue, but also increased reading comprehension, interest, cognition, and memory. These qualitative data have supplied a rich and complex understanding behind nonmedical ADHD stimulant use among fraternity members.

El Ayadi A; Zigmond MJ. Low concentrations of methamphetamine can protect dopaminergic cells against a larger oxidative stress injury: Mechanistic study. PLoS ONE 6(10): e24722, 2011. (103 refs.)

Mild stress can protect against a larger insult, a phenomenon termed preconditioning or tolerance. To determine if a low intensity stressor could also protect cells against intense oxidative stress in a model of dopamine deficiency associated with Parkinson disease, we used methamphetamine to provide a mild, preconditioning stress, 6-hydroxydopamine (6-OHDA) as a source of potentially toxic oxidative stress, and MN9D cells as a model of dopamine neurons. We observed that prior exposure to subtoxic concentrations of methamphetamine protected these cells against 6-OHDA toxicity, whereas higher concentrations of methamphetamine exacerbated it. The protection by methamphetamine was accompanied by decreased uptake of both [(3)H] dopamine and 6-OHDA into the cells, which may have accounted for some of the apparent protection. However, a number of other effects of methamphetamine exposure suggest that the drug also affected basic cellular survival mechanisms. First, although methamphetamine preconditioning decreased basal pERK1/2 and pAkt levels, it enhanced the 6-OHDA-induced increase in these phosphokinases. Second, the apparent increase in pERK1/2 activity was accompanied by increased pMEK1/2 levels and decreased activity of protein phosphatase 2. Third, methamphetamine upregulated the pro-survival protein Bcl-2. Our results suggest that exposure to low concentrations of methamphetamine cause a number of changes in dopamine cells, some of which result in a decrease in their vulnerability to subsequent oxidative stress. These observations may provide insights into the development of new therapies for prevention or treatment of PD.

Eskelinen MH; Kivipelto M. Caffeine as a protective factor in dementia and Alzheimer's disease. Journal of Alzheimers Disease 20(Supplement 1): S167-S174, 2010. (33 refs.)

Caffeine has well-known short-term stimulating effects on central nervous system, but the long-term impacts on cognition have been less clear. Dementia and Alzheimer's disease (AD) are rapidly increasing public health problems in ageing populations and at the moment curative treatment is lacking. Thus, the putative protective effects of caffeine against dementia/AD are of great interest. Here, we discuss findings from the longitudinal epidemiological studies about caffeine/coffee/tea and dementia/AD/cognitive functioning with a special emphasis on our recent results from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study. The findings of the previous studies are somewhat inconsistent, but most studies (3 out of 5) support coffee's favorable effects against cognitive decline, dementia or AD. In addition, two studies had combined coffee and tea drinking and indicated some positive effects on cognitive functioning. For tea drinking, protective effects against cognitive decline/dementia are still less evident. In the CAIDE study, coffee drinking of 3-5 cups per day at midlife was associated with a decreased risk of dementia/AD by about 65% at late-life. In conclusion, coffee drinking may be associated with a decreased risk of dementia/AD. This may be mediated by caffeine and/or other mechanisms like antioxidant capacity and increased insulin sensitivity. This finding might open possibilities for prevention or postponing the onset of dementia/AD.

Esra YE; Aziz Y; Zeki U; Gulsah G; Mert B; Yesim E et al. Is chemotherapy-induced nausea and vomiting lower in smokers? International Journal of Clinical Pharmacology and Therapeutics 49(12): 709-712, 2011. (24 refs.)

Aim: Chemotherapy-induced nausea and vomiting (CINV) is not understood completely. The aim of this study is to investigate the effects of smoking on CINV. Methods. 121 consecutive patients who received cisplatin (>= 50 mg/m(2)) based chemotherapy were included in the study. The patients who reported motion sickness, pain, emesis during past pregnancy, emesis history of previous chemotherapy, with Karnofsky score < 70, peptic ulcer, gastroesophageal reflux, migraine, central nervous system metastasis and patients scheduled to receive radiation therapy were excluded from the study. A standard antiemetic treatment was given to all patients. The nausea and vomiting was assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire. After first cycle of chemotherapy, Grade 2 - 3 nausea and vomiting were questioned. Results: Grade 2 - 3 nausea and vomiting was higher in non-smokers (p < 0.001). We found that nausea and vomiting in women is more frequent than in men (p < 0.001). Conclusion: In our study we found that smokers had a lower incidence of CINV. Further investigations are needed to confirm the findings of this pilot study.

Garia AM; Ramon-Bou N; Porta M. Isolated and joint effects of tobacco and alcohol consumption on risk of Alzheimer's disease. Journal of Alzheimer's Disease 20(2): 577-586, 2010. (32 refs.)

The roles of smoking and alcohol on the development of Alzheimer's disease (AD) remain unclear. We performed a case-control study on the effects of both exposures before the age of onset of the disease in the cases (and same reference age for their age-matched controls) on disease risk. Interviews were conducted with population controls (n = 246) and relatives of cases (n = 176) identified through local Alzheimer's Disease Associations. Logistic regression models were built adjusting by gender, age, residence, education, economic situation, employment, and history of dementia in close relatives. Risk of AD was unaffected by any measure of tobacco consumption. Alcohol consumers showed a lower risk of AD than never consumers (adjusted odds ratio, aOR = 0.53, 95% CI 0.32, 0.88), with differences by gender (women aOR = 0.48, 95% CI 0.27, 0.84; men aOR = 0.80, 95% CI 0.23, 2.80). Mean daily total consumption of alcohol and time consuming alcohol showed increasingly protective dose-response relationships in women. Lower AD risk was observed in alcohol drinkers of both genders who never smoked (aOR = 0.37, 95% CI 0.21, 0.65). All these associations were independent of the presence of apolipoprotein E4 allele(s) in the cases. Although the sample was small for some analyses addressing these interactions, our results suggest a protective effect of alcohol consumption, mostly in non-smokers, and the need to consider interactions between tobacco and alcohol consumption, as well as interactions with gender, when assessing the effects of smoking and/or drinking on the risk of AD.

Gelber RP; Petrovitch H; Masaki KH; Ross GW; White LR. Coffee intake in midlife and risk of dementia and its neuropathologic correlates. Journal of Alzheimer's Disease 23(4): 607-615, 2011. (29 refs.)

While animal data suggest a protective effect of caffeine on cognition, studies in humans remain inconsistent. We examined associations of coffee and caffeine intake in midlife with risk of dementia, its neuropathologic correlates, and cognitive impairment among 3494 men in the Honolulu-Asia Aging Study (mean age 52 at cohort entry, 1965-1968) examined for dementia in 1991-1993, including 418 decedents (1992-2004) who underwent brain autopsy. Caffeine intake was determined according to self-reported coffee, tea, and cola consumption at baseline. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for overall dementia, Alzheimer's disease (AD), vascular dementia (VaD), cognitive impairment (Cognitive Abilities Screening Instrument score <74), and neuropathologic lesions at death (Alzheimer lesions, microvascular ischemic lesions, cortical Lewy bodies, hippocampal sclerosis, generalized atrophy), according to coffee and caffeine intake. Dementia was diagnosed in 226 men (including 118 AD, 80 VaD), and cognitive impairment in 347. There were no significant associations between coffee or caffeine intake and risk of cognitive impairment, overall dementia, AD, VaD, or moderate/high levels of the individual neuropathologic lesion types. However, men in the highest quartile of caffeine intake (>277.5 mg/d) were less likely than men in the lowest quartile (<= 115.5 mg) to have any of the lesion types (adjusted-OR, 0.45; 95% CI, 0.23-0.89; p, trend = 0.04). Coffee and caffeine intake in midlife were not associated with cognitive impairment, dementia, or individual neuropathologic lesions, although higher caffeine intake was associated with a lower odds of having any of the lesion types at autopsy.

Glade MJ. Caffeine: Not just a stimulant. (review). Nutrition 26(10): 932-938, 2010. (101 refs.)

Objective: The beneficial effects of human caffeine consumption deserve clarification. Methods: A detailed literature review was conducted and summarized. Results: A large body of scientific evidence describes the beneficial effects of human caffeine consumption on a number of physiologic systems. Conclusion: The consumption of moderate amounts of caffeine 1) increases energy availability, 2) increases daily energy expenditure, 3) decreases fatigue, 4) decreases the sense of effort associated with physical activity, 5) enhances physical performance, 6) enhances motor performance, 7) enhances cognitive performance, 8) increases alertness, wakefulness, and feelings of "energy," 9) decreases mental fatigue, 10) quickens reactions, 11) increases the accuracy of reactions, 12) increases the ability to concentrate and focus attention, 13) enhances short-term memory, 14) increases the ability to solve problems requiring reasoning, 15) increases the ability to make correct decisions, 16) enhances cognitive functioning capabilities and neuromuscular coordination, and 17) in otherwise healthy non-pregnant adults is safe.

Greenberg JA; Owen DR; Geliebter A. Decaffeinated coffee and glucose metabolism in young men. Diabetes Care 33(2): 278-280, 2010. (12 refs.)

OBJECTIVE - The epidemiological association between coffee drinking and decreased risk Of type 2 diabetes is strong. However, caffeinated coffee acutely impairs glucose metabolism. We assessed acute effects of decaffeinated coffee on glucose and insulin levels. DESIGN and METHODS - This was a randomized, cross-over, placebo-controlled trial of the effects of decaffeinated coffee, caffeinated coffee, and caffeine on glucose, insulin, and glucose-de pendent insulinotropic poly-peptide (GIP) levels during a 2-h Oral glucose tolerance test (OGTT) in 11 young men. RESULTS - Within the first hour Of the CGTT, glucose and insulin were higher for decaffeinated coffee than for placebo (P < 0.05). During the whole OGTT, decaffeinated coffee yielded higher insulin than placebo and lower glucose and a higher insulin sensitivity index than caffeine. Changes in GIP could not explain any beverage effects on glucose and insulin. CONCLUSIONS - Some types of decaffeinated coffee may acutely impair glucose metabolism but less than caffeine.

Grinshpoon A; Barchana M; Lipshitz I; Rosca P; Weizman A; Ponizovsky AM. Methadone maintenance and cancer risk: An Israeli case registry study. Drug and Alcohol Dependence 119(1-2): 88-92, 2011. (43 refs.)

Objectives: This study explored cancer incidence rates in a large cohort of Israeli (Jewish and Arab) opioid-dependent individuals receiving methadone maintenance treatment (MMT), and how the incidences vary by ethnicity and sex. Method: The record linkage between the Israel National Addiction Registry (INAR) and the Israel National Cancer Registry (INCR) was performed. Information about the Israeli general population from the Central Bureau of Statistics was used for comparison to match sex and year of birth to the cohort under study. Age standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated. Results: Though the SIR values for aggregated cancer sites for both men and women on MMT did not differ significantly from the corresponding figures in the general population (0.88, 95% CI 0.76-1.00, and 1.06, 95% CI 0.76-1.36, respectively), the risks were substantially increased for lung (1.97, 95% CI 1.13-2.82), larynx (3.62,95% CI 1.11-6.13) and liver (6.8, 95% CI 1.76-11.83) cancers among Jewish men and for cervix uteri cancer among Jewish women (2.41.95% CI 0.99-3.84). By contrast, the SIR values for colorectal cancer among Jewish men (0.46.95% CI 0.09-0.82) and for breast cancer among Jewish women (0.36, 95% CI 0.00-0.71) were significantly lower than expected. Conclusions: The results suggest that the increased and reduced site-specific cancer risks are counterbalanced, resulting in the absence of the expected excess cancer risk for the entire cohort. The reduced risks for colorectal and breast cancers suggest a protective effect of MMT, warranting further investigation.

Heishman SJ; Kleykamp BA; Singleton EG. Meta-analysis of the acute effects of nicotine and smoking on human performance. (review). Psychopharmacology 210(4): 453-469, 2010. (103 refs.)

Empirical studies indicate that nicotine enhances some aspects of attention and cognition, suggesting a role in the maintenance of tobacco dependence. The purpose of this review was to update the literature since our previous review (Heishman et al. Exp Clin Psychopharmacol 2:345-395, 1994) and to determine which aspects of human performance were most sensitive to the effects of nicotine and smoking. We conducted a meta-analysis on the outcome measures of 41 double-blind, placebo-controlled laboratory studies published from 1994 to 2008. In all studies, nicotine was administered, and performance was assessed in healthy adult nonsmokers or smokers who were not tobacco-deprived or minimally deprived (a parts per thousand currency sign2 h). There were sufficient effect size data to conduct meta-analyses on nine performance domains, including motor abilities, alerting and orienting attention, and episodic and working memory. We found significant positive effects of nicotine or smoking on six domains: fine motor, alerting attention-accuracy and response time (RT), orienting attention-RT, short-term episodic memory-accuracy, and working memory-RT (effect size range = 0.16 to 0.44). The significant effects of nicotine on motor abilities, attention, and memory likely represent true performance enhancement because they are not confounded by withdrawal relief. The beneficial cognitive effects of nicotine have implications for initiation of smoking and maintenance of tobacco dependence.

Herman AI; Sofuoglu M. Cognitive effects of nicotine: Genetic moderators. (review). Addiction Biology 15(3): 250-265, 2010. (216 refs.)

Cigarette smoking is the main preventable cause of death in developed countries, and the development of more effective treatments is necessary. Cumulating evidence suggests that cognitive enhancement may contribute to the addictive actions of nicotine. Several studies have demonstrated that nicotine enhances cognitive performance in both smokers and non-smokers. Genetic studies support the role of both dopamine (DA) and nicotinic acetylcholine receptors (nAChRs) associated with nicotine-induced cognitive enhancement. Based on knockout mice studies, beta 2 nAChRs are thought to be essential in mediating the cognitive effects of nicotine. alpha 7nAChRs are associated with attentional and sensory filtering response, especially in schizophrenic individuals. Genetic variation in D2 type DA receptors and the catechol-O-methyltransferase enzyme appears to moderate cognitive deficits induced by smoking abstinence. Serotonin transporter (5-HTT) gene variation also moderates nicotine-induced improvement in spatial working memory. Less is known about the contribution of genetic variation in DA transporter and D4 type DA receptor genetic variation on the cognitive effects of nicotine. Future research will provide a clearer understanding of the mechanism underlying the cognitive-enhancing actions of nicotine.

Holmes AD; Copland DA; Silburn PA; Chenery HJ. Acute nicotine enhances strategy-based semantic processing in Parkinson's disease. International Journal of Neuropsychopharmacology 14(7): 877-885, 2011. (49 refs.)

Nicotinic mechanisms may play a role in the cognitive deficits of Parkinson's disease (PD). Recently, on a cognitively demanding strategy-based priming task, nicotine selectively affected controlled semantic processing in young adult non-smokers as reported by Holmes et al. (International Journal of Neuropsychopharmacology 11, 389-399, 2008). Such controlled semantic processing is compromised in PD. This study investigated the effects of acute transdermal nicotine on controlled semantic processing in nonsmokers with PD (n = 10) and non-smoking matched controls (n = 16) using a strategy-based semantic priming paradigm. Transdermal nicotine patches (7 mg/24 h) were administered in a double-blind, placebo-controlled, crossover design. Participants were instructed to expect target words from specified semantic categories based on the primes, while unexpected targets were also presented. Priming conditions included those concurring with trained expectations (expected-related and expected-unrelated), those which did not (unexpected-related and unexpected-unrelated), and neutral-baseline conditions. Controls evidenced significant expectancy effects (i.e. reaction-time differences for expected vs. unexpected conditions) under both drug states. An expectancy effect was not evident for PD under placebo due to a lack of reaction-time slowing for unexpected conditions. However, under nicotine an expectancy effect was present for PD at a level comparable to controls. Overall the findings indicate that nicotine can improve impaired controlled semantic processing in PD possibly via enhanced expectancy or inhibitory mechanisms.

Hong LE; Schroeder M; Ross TJ; Buchholz B; Salmeron BJ; Wonodi I et al. Nicotine enhances but does not normalize visual sustained attention and the associated brain network in schizophrenia. Schizophrenia Bulletin 37(2): 416-425, 2011. (47 refs.)

Sustained attention abnormality in schizophrenia is usually refractory to available treatment. Nicotine can transiently improve sustained attention in schizophrenia patients, although its neural mechanisms are unknown. Understanding the neural basis of this effect may lead to new treatment strategies for this cognitive deficit. Twenty schizophrenia patients and 24 healthy comparison smokers participated in a double-blind, placebo-controlled, crossover, randomized functional magnetic resonance imaging study comparing nicotine vs placebo patch on sustained attention, using the rapid visual information-processing task. Schizophrenia patients had impaired visual sustained attention accuracy and processing speed (all P's <.001) and showed significantly reduced activation in the frontal-parietal-cingulate-thalamic attention network compared with healthy comparison subjects. Nicotine administration enhanced accuracy and processing speed compared with placebo (all P's <.006), with no drug x diagnosis interactions. However, schizophrenia patients' task performance remained impaired during the nicotine condition, even when compared with healthy comparison subjects in the placebo condition (all P's <.01). Nicotine exerted no significant reversal of the impaired attention network associated with schizophrenia. Activations in brain regions associated with nicotine-induced behavioral improvement were not significantly different between patients and comparison subjects. Thus, nicotine transiently enhanced sustained attention similarly in schizophrenia patients and in healthy comparison smokers. The neural mechanisms for this nicotinic effect in schizophrenia appear similar to those for healthy comparison subjects. However, nicotine, at least in a single sustained dose, does not normalize impaired sustained attention and its associated brain network in schizophrenia. These findings provide guidance for developing new treatment strategies for the sustained attention deficit in schizophrenia.

Johnson S; Koh WP; Wang RW; Govindarajan S; Yu MC; Yuan JM. Coffee consumption and reduced risk of hepatocellular carcinoma: Findings from the Singapore Chinese Health Study. Cancer Causes & Control 22(3): 503-510, 2011. (39 refs.)

Background: Coffee consumption has been associated with reduced markers of hepatic cell damage, reduced risk of chronic liver disease, and cirrhosis across a variety of populations. Data on the association between coffee consumption and risk of hepatocellular carcinoma (HCC), especially in high-risk populations, are sparse. Methods: This study examines the relationship between coffee and caffeine consumption, and the risk of developing HCC within the Singapore Chinese Health Study, a prospective cohort of 63,257 middle-aged and older Chinese men and women, a relatively high-risk population for HCC. Baseline data on coffee consumption and other dietary and lifestyle factors were collected through in-person interviews at enrollment between 1993 and 1998. Results: As of 31 December 2006, 362 cohort participants had developed HCC. High levels of coffee or caffeine consumption were associated with reduced risk of HCC (p for trend < 0.05). Compared with non-drinkers of coffee, individuals who consumed three or more cups of coffee per day experienced a statistically significant 44% reduction in risk of HCC (hazard ratio 0.56, 95% confidence interval, 0.31-1.00, p = .049) after adjustment for potential confounders and tea consumption. Conclusion: These data suggest that coffee consumption may reduce the risk of developing HCC in Chinese in Singapore.

Karumanchi SA; Levine RJ. How does smoking reduce the risk of preeclampsia? (editorial). Hypertension 55(5): 1100-1101, 2010. (14 refs.)

Koppelstaetter F; Poeppel TD; Siedentopf CM; Ischebeck A; Kolbitsch C; Mottaghy FM et al. Caffeine and cognition in functional magnetic resonance imaging. (review). Journal of Alzheimers Disease 20(Supplement 1): S71-S84, 2010. (76 refs.)

Caffeine has been consumed since ancient times due to its beneficial effects on attention, psychomotor function, and memory. Caffeine exerts its action mainly through an antagonism of cerebral adenosine receptors, although there are important secondary effects on other neurotransmitter systems. Recently, functional MRI (fMRI) entered the field of neuropharmacology to explore the intracerebral sites and mechanisms of action of pharmacological agents. However, as caffeine possesses vasoconstrictive properties it may interfere with the mechanisms underlying the functional contrast in fMRI. Yet, only a limited number of studies dealt with the effect of caffeine on measures in fMRI. Even fewer neuroimaging studies examined the effects that caffeine exerts on cognition: Portas and colleagues used fMRI in an attentional task under different levels of arousal (sleep deprivation or caffeine administration), concluding that the thalamus is involved in mediating the interaction of attention and arousal. Bendlin and colleagues found caffeine to stabilize the extent of neuronal activation in repetitive word stem completion, counteracting the general task practice effect. Recently, Koppelstaetter and colleagues assessed the effect of caffeine on verbal working memory demonstrating a modulatory effect of caffeine on brain regions (medial frontopolar and anterior cingulate cortex) that have been associated with attentional and executive functions. This review surveys and discusses neuroimaging findings on 1) how caffeine affects the contrast underlying fMRI techniques, particularly the blood oxygen level dependent contrast (BOLD fMRI), and 2) how caffeine operates on neuronal activity underlying cognition, to understand the effect of caffeine on behavior and its neurobiological underpinnings.

Kyle J; Fox HC; Whalley LJ. Caffeine, cognition, and socioeconomic status. Journal of Alzheimers Disease 20(Supplement 1): S151-S159, 2010. (31 refs.)

There is interest in age-related cognitive decline and environmental risk factors for Alzheimer's disease (AD). This interest is focused on individual differences in exposure to agents that may harm or protect cognitive function. Caffeine is used as a short acting mental stimulant and may possess longer-term properties that protect against age-related decline and, possibly, AD. The current study aimed to: 1) examine current cognitive function in a narrow age range sample (n = 351) without dementia (MMSE > 25) who are, by reason of age, entering the period of increased risk of AD; and 2) link cognitive function to self-reported intake of caffeine and socioeconomic status (SES). Possible confounding by gender, childhood intelligence, education, and symptoms of anxiety and depression was introduced into the statistical model. There were significant differences between SES groups in caffeine intake (p < 0.05) and cognitive performance (p < 0.001). Higher quartiles of caffeine intake were associated with slower digit symbol speed (F = 3.38, p < 0.02) but this finding was removed after allowing for SES. The results are discussed in terms of the withdrawal effects of caffeine during cognitive testing and strong links between SES and cognitive performance. No evidence in support of cognitive enhancing effects of caffeine was found.

Lamina S. Khat (catha edulis): The herb with officio-legal, socio-cultural and economic uncertainty. (review). South African Journal of Science 106(3-4): 28-31, 2010. (51 refs.)

Khat (Catha edulis) is a plant of uncertain and highly controversial status grown in the countries around the Red Sea and on the eastern coast of Africa. The chewing of khat leaves has a deep-rooted religious and socio-cultural tradition. Khat is considered a cash crop and its cultivation is a source of economic value to the societies and nations involved. There have, however, been reports of negative economic effects on the individuals engaging in the habit of khat chewing. The increasing use of khat worldwide, along with the negative international attention that this has garnered, has led to the present status of uncertainty of the once indigenous practice of khat chewing. Scientists, mostly western Europeans, have tended to focus on problems related to khat with little attention to the positive role of khat chewing in society and the world at large. In addition, no report has directly associated khat with any organised crime, violence or antisocial activity, particularly in countries where khat is legalised. This paper reviewed the various areas of uncertainty and controversy relating to khat. Based on the findings of the review, further qualitative and quantitative research is required and a positive international approach to khat use at economic, religious and socio-cultural levels is advocated.

Lara DR. Caffeine, mental health, and psychiatric disorders. (review). Journal of Alzheimers Disease 20(Supplement 1): S239-S248, 2010. (126 refs.)

Caffeine intake is so common that its pharmacological effects on the mind are undervalued. Since it is so readily available, individuals can adjust their own dose, time of administration and dose intervals of caffeine, according to the perceived benefits and side effects of each dose. This review focuses on human studies of caffeine in subjects with and without psychiatric disorders. Besides the possibility of mild drug dependence, caffeine may bring benefits that contribute to its widespread use. These benefits seem to be related to adaptation of mental energy to the context by increasing alertness, attention, and cognitive function (more evident in longer or more difficult tasks or situations of low arousal) and by elevating mood. Accordingly, moderate caffeine intake (< 6 cups/day) has been associated with less depressive symptoms, fewer cognitive failures, and lower risk of suicide. However, its putative therapeutic effects on depression and ADHD have been insufficiently studied. Conversely, in rare cases high doses of caffeine can induce psychotic and manic symptoms, and more commonly, anxiety. Patients with panic disorder and performance social anxiety disorder seem to be particularly sensitive to the anxiogenic effects of caffeine, whereas preliminary data suggests that it may be effective for some patients with obsessive compulsive disorder (OCD). The threshold for the anxiogenic effect of caffeine is influenced by a polymorphism of the A2A receptor. In summary, caffeine can be regarded as a pharmacological tool to increase energy and effortful behavior in daily activities. More populational (cross-sectional and prospective) and experimental studies are necessary to establish the role of caffeine intake in psychiatric disorders, especially its putative efficacy on depressive mood and cognitive/attentional disorders.

Larsson SC; Orsini N. Coffee consumption and risk of stroke: A dose-response meta-analysis of prospective studies. (review). American Journal of Epidemiology 174(9): 993-1001, 2011. (38 refs.)

Coffee consumption has been inconsistently associated with risk of stroke. The authors conducted a meta-analysis of prospective studies to quantitatively assess the association between coffee consumption and stroke risk. Pertinent studies were identified by searching PubMed and Embase from January 1966 through May 2011 and by reviewing the reference lists of retrieved articles. Prospective studies in which investigators reported relative risks of stroke for 3 or more categories of coffee consumption were eligible. Results from individual studies were pooled using a random-effects model. Eleven prospective studies, with 10,003 cases of stroke and 479,689 participants, met the inclusion criteria. There was some evidence of a nonlinear association between coffee consumption and risk of stroke (P for nonlinearity = 0.005). Compared with no coffee consumption, the relative risks of stroke were 0.86 (95% confidence interval (95% CI): 0.78, 0.94) for 2 cups of coffee per day, 0.83 (95% CI: 0.74, 0.92) for 3-4 cups/day, 0.87 (95% CI: 0.77, 0.97) for 6 cups/day, and 0.93 (95% CI: 0.79, 1.08) for 8 cups/day. There was marginal between-study heterogeneity among study-specific trends (I(2) = 12% and I(2) = 20% for the first and second spline transformations, respectively). Findings from this meta-analysis indicate that moderate coffee consumption may be weakly inversely associated with risk of stroke.

Lee Y; Back JH; Kim J; Kim SH; Na DL; Cheong HK et al. Systematic review of health behavioral risks and cognitive health in older adults. (review). International Psychogeriatrics 22(2): 174-187, 2010. (57 refs.)

Background: An increasing body of evidence suggests that health behaviors may protect against cognitive impairment and dementia. The purpose of this study was to summarize the current evidence on health behavioral factors predicting cognitive health through a systematic review of the published literature. Methods: PubMedicine, Embase, and PsycINFO databases were searched for studies on community representative samples aged 65 and older, with prospective cohort design and multivariate analysis. The outcome - cognitive health - was defined as a continuum of cognitive function ranging from cognitive decline to impairment and dementia, and health behaviors included physical activity, smoking, alcohol drinking, body mass index, and diet and nutrition. Results: Of 12,105 abstracts identified, 690 relevant full-texts were reviewed. The final yield amounted to 115 articles of which 37 studies were chosen that met the highest standards of quality. Leisure time physical activity, even of moderate level, showed protective effects against dementia, whereas smoking elevated the risk of Alzheimer's disease. Moderate alcohol consumption tended to be protective against cognitive decline and dementia, but nondrinkers and frequent drinkers exhibited a higher risk for dementia and cognitive impairment. Midlife obesity had an adverse effect on cognitive function in later life. Analysis showed vegetable and fish consumption to be of benefit, whereas, persons consuming a diet high in saturated fat had an increased dementia risk. Conclusion: The review demonstrates accumulating evidence supporting health behavioral effects in reducing the risk of cognitive decline and dementia. Results indicate potential benefits of healthy lifestyles in protecting cognitive health in later life.

Lin WY; Pi-Sunyer FX; Chen CC; Davidson LE; Liu CS; Li TC; Wu MF. Coffee consumption is inversely associated with type 2 diabetes in Chinese. European Journal of Clinical Investigation 41(6): 659- 666, 2011. (35 refs.)

Background: Coffee consumption has been shown to be inversely associated to type 2 diabetes mellitus (T2DM), but evidence in Chinese populations is limited. We investigated the relationship between coffee consumption and T2DM in a population-based cohort of middle-aged Chinese. Materials and methods: We studied 2332 subjects who participated in the Taichung Community Health Study in Taiwan in 2004. The relationships between coffee consumption, T2DM and fasting glucose were assessed. Results: The prevalence of T2DM was 14 center dot 0% and 10 center dot 4% in men and women. After adjustment for age, body mass index, blood pressure, smoking, alcohol drinking, betel nut chewing, physical activity, income, education level, fat%, protein%, carbohydrate% and magnesium, coffee intake was inversely associated with T2DM. Habitual coffee drinkers had 38-46% lower risk of T2DM than nondrinkers. Compared to nondrinkers, the adjusted odds ratios (ORs) for T2DM according to subjects with habitual coffee consumption (< 1, 1-6, >= 7 times per week) were 0 center dot 77 (0 center dot 52-1 center dot 13), 0 center dot 46 (0 center dot 28-0 center dot 76) and 0 center dot 37 (0 center dot 16-0 center dot 83), respectively. The decreasing ORs indicate a dose-response effect of coffee consumption on the likelihood of having T2DM (P < 0 center dot 001). A similar relationship was also evident in newly diagnosed T2DM (P < 0 center dot 05). The adjusted mean fasting glucose levels gradually decreased as the frequency of coffee consumption increased (P < 0 center dot 05). Conclusions: Coffee intake is inversely associated with T2DM in Chinese. Coffee may be a protective agent for T2DM in Chinese.

Miller EC; Cao HL; Wen SW; Yang QY; Lafleche J; Walker M. The risk of adverse pregnancy outcomes is increased in preeclamptic women who smoke compared with nonpreeclamptic women who do not smoke. American Journal of Obstetrics and Gynecology 203(4): 334.e1, 2010. (36 refs.)

OBJECTIVE: Maternal smoking and preeclampsia independently increase the risk of adverse pregnancy outcomes; however, smoking decreases the risk of preeclampsia. We sought to estimate the risk of adverse pregnancy outcomes among preeclamptic women who smoke and hypothesized that this risk would be increased, compared with nonpreeclamptic women who smoke or preeclamptic women who do not smoke. STUDY DESIGN: With the use of the Niday Perinatal Database and multiple logistic regressions, we estimated the risk of adverse pregnancy outcomes in nonpreeclamptic women who smoke, preeclamptic women who do not smoke, and preeclamptic women who smoke in relation to nonpreeclamptic women who do not smoke. RESULTS: The incidence of adverse pregnancy outcomes was more than twice as high among preeclamptic women who smoke as among nonpreeclamptic women who do not smoke. The following data were observed: small-for-gestational-age infant (odds ratio [OR], 3.40; 95% CI, 2.27-4.89), preterm birth (OR, 5.77; 95% CI, 4.50-7.35), very preterm birth (OR, 5.44; 95% CI, 3.51-8.11), abruption (OR, 6.16; 95% CI, 3.05-11.01), Apgar <4 at 5 minutes (OR, 3.11; 95% CI, 1.48-5.72), and stillbirth (OR, 3.39; 95% CI, 1.33-6.99). CONCLUSION: Smoking decreases the risk of preeclampsia, but smokers with preeclampsia have an increased risk for adverse pregnancy outcomes.

Morelli M; Simola N. Can dietary substances protect against Parkinson's disease? The case of caffeine. (editorial). Experimental Neurology 225(2): 246-249, 2010. (33 refs.)

Morgan CJA; Muetzelfeldt L; Muetzelfeldt M; Nutt DJ; Curran HV. Harms associated with psychoactive substances: Findings of the UK National Drug Survey. Journal of Psychopharmacology 24(2): 147-153, 2010. (6 refs.)

Nutt and colleagues' 'rational' scale to assess the harms of commonly used drugs was based on ratings by a panel of experts. This survey aimed to assess drug users' views of the harms of drugs using the same scale. As users' drug choices are not solely based on harms, we additionally assessed perceived benefits. The survey was hosted at http: www.nationaldrugsurvey.org. UK residents reported their experience of 20 commonly used substances; those with direct experience of a substance rated its physical, dependence-related and social harms as well as benefits. A total of 1501 users completed the survey. There was no correlation between the classification of the 20 drugs under the Misuse of Drugs Act and ranking of harms by users. Despite being unclassified substances, alcohol, solvents and tobacco were rated within the top ten most harmful drugs. There was a remarkably high correlation (r = 0.896) overall between rankings by users' and by experts. Ecstasy, cannabis and LSD were ranked highest by users on both acute and chronic benefits. These findings imply that users are relatively well informed about the harms associated with the drugs they use. They also suggest that the current UK legal classification system is not acting to inform users of the harms of psychoactive substances.

Mueller U; Sauer T; Weigel I; Pichner R; Pischetsrieder M. Identification of H2O2 as a major antimicrobial component in coffee. Food & Function 2(5): 265-272, 2011. (31 refs.)

Coffee shows distinct antimicrobial activity against several bacterial genera. The present study investigated molecular mechanisms and active ingredients mediating the antimicrobial effect of coffee. Depending on concentration, roasted, but not raw coffee brew inhibited the growth of Escherichia coli and Listeria innocua. Several coffee ingredients with known antibacterial properties were tested for their contribution to the observed effect. In natural concentration, caffeine, ferulic acid and a mixture of all test compounds showed very weak, but significant activity, whereas trigonelline, 5-(hydroxymethyl) furfural, chlorogenic acid, nicotinic acid, caffeic acid, and methylglyoxal were not active. Antimicrobial activity, however, was completely abolished by addition of catalase indicating that H2O2 is a major antimicrobial coffee component. In accordance with this assumption, bacterial counts during 16 h of incubation were inversely related to the H2O2 concentration in the incubation solution. Pure H2O2 showed slightly weaker activity. The H2O2 dependent antimicrobial activity of coffee could be mimicked by a reaction mixture of D-ribose and L-lysine (30 min 120 degrees C) indicating that H2O2 is generated in the coffee brew by Maillard reaction products. Identification of H2O2 as major antimicrobial coffee component is important to evaluate the application of coffee or coffee extracts as natural preservatives.

Nebes RD; Pollock BG; Halligan EM; Houck P; Saxton JA. Cognitive slowing associated with elevated serum anticholinergic activity in older individuals is decreased by caffeine use. American Journal of Geriatric Psychiatry 19(2): 169-175, 2011. (32 refs.)

Objectives: This study examined whether some of the age-associated decrements in basic cognitive resources (information-processing speed and working memory) result from anticholinergic medication use (as measured by serum anticholinergic activity [SAA]) and whether such decrements are lessened by caffeine. Design: Cross-sectional observational study. Setting: University medical center. Participants: One hundred fifty-two normal-elderly community volunteers. Measurements: Two tests each of information-processing speed and of working memory were administered, and blood samples were drawn before and after cognitive testing to determine serum levels of anticholinergic activity and of paraxanthine-a caffeine metabolite. Results: Elevated SAA was associated with a significant but modest slowing in information-processing time but only in those individuals who had low levels of serum paraxanthine. SAA did not correlate with performance on tests of working memory. Conclusions: These results suggest that anticholinergic medications are a relatively minor contributor to the decrements in basic processing resources commonly found in studies of normal aging.

Nehlig A. Is caffeine a cognitive enhancer? (review). Journal of Alzheimers Disease 20(Supplement 1): S85-S94, 2010. (91 refs.)

The effects of caffeine on cognition were reviewed based on the large body of literature available on the topic. Caffeine does not usually affect performance in learning and memory tasks, although caffeine may occasionally have facilitatory or inhibitory effects on memory and learning. Caffeine facilitates learning in tasks in which information is presented passively; in tasks in which material is learned intentionally, caffeine has no effect. Caffeine facilitates performance in tasks involving working memory to a limited extent, but hinders performance in tasks that heavily depend on working memory, and caffeine appears to rather improve memory performance under suboptimal alertness conditions. Most studies, however, found improvements in reaction time. The ingestion of caffeine does not seem to affect long-term memory. At low doses, caffeine improves hedonic tone and reduces anxiety, while at high doses, there is an increase in tense arousal, including anxiety, nervousness, jitteriness. The larger improvement of performance in fatigued subjects confirms that caffeine is a mild stimulant. Caffeine has also been reported to prevent cognitive decline in healthy subjects but the results of the studies are heterogeneous, some finding no age-related effect while others reported effects only in one sex and mainly in the oldest population. In conclusion, it appears that caffeine cannot be considered a 'pure' cognitive enhancer. The indirect action of caffeine on arousal, mood and concentration contributes in large part to its cognitive enhancing properties.

Oksenberg A. Alleviation of severe restless legs syndrome (RLS) symptoms by cigarette smoking. Journal of Clinical Sleep Medicine 6(5): 489-490, 2010. (12 refs.)

Cigarette smoking is in general considered an aggravating factor for restless legs syndrome (RLS). The author presents a case in which cigarette smoking has produced for many years a consistent and effective alleviation of RLS symptoms.

Potera C. Tobacco bio-oil kills agricultural pests. (editorial). Environmental Health Perspectives 119(1): A18-A18, 2011. (3 refs.)

Cigarette smoking continues to be the leading cause of preventable death and disease in the United States but tobacco has potentially beneficial uses as well as deadly ones. Gardeners have long known that homemade mixtures of tobacco and water can kill insect pests. But these homemade brews kill desirable insects, too, and could poison animals that ingest them. Now researchers at the University of Western Ontario are finding new ways to turn tobacco into a more selective eco-friendly pest control agent. A team led by chemical engineer Cedric Briens heated finely ground tobacco leaves to 500�C in a vacuum, a process called pyrolysis, then collected the condensate. (Since publishing the paper, the team has found they can use the entire plant�leaves and stalks�which makes it easier and cheaper to harvest the tobacco.) The bio-oil was tested against the Colorado potato beetle (Leptinotarsa decemlineata), 11 fungi, and 4 bacteria, all of which are agricultural pests. The bio-oil blocked the growth of the bacteria Streptomyces scabies and Clavibacter michiganensis and the fungus Pythium ultimum. S. scabies causes a common potato scab disease that makes potatoes unmarketable, C. michiganensis kills young plants and deforms fruits, especially tomatoes, and P. ultimum kills seedlings of eggplant, peppers, lettuce, tomatoes, and cucumbers. The bio-oil also killed 100% of Colorado potato beetles, a resistant pest that can destroy potato crops. The other organisms were unaffected. Nicotine, a key toxin in tobacco, has known insecticidal properties on its own. But even after removing nicotine from the bio-oil, it still potently killed these few pests.

Reis JP; Loria CM; Steffen LM; Zhou X; van Horn L; Siscovick DS et al. Coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood and atherosclerosis later in life: The CARDIA Study. Arteriosclerosis, Thrombosis, and Vascular Biology 30(10): 2059-2066, 2010. (53 refs.)

Objective-To determine the association of coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood with the presence and progression of coronary artery calcified (CAC) plaque and carotid intima-media thickness later in life. Methods and Results-The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a cohort of 5115 white and black adults who were aged 18 to 30 years when they completed a baseline clinic examination from 1985 to 1986. Subsequent examinations were conducted 2, 5, 7, 10, 15, and 20 years later. After multivariable adjustment, no association was observed between average coffee, decaffeinated coffee, or caffeine consumption (years 0 and 7) and presence of CAC (score, >0 Agatston units at year 15 or 20), CAC progression (incident CAC at year 20 or increase in CAC score by >= 20 Agatston units), or high carotid intima-media thickness (>80th percentile, year 20). However, tea consumption displayed a nonsignificant trend for an inverse association with CAC (P = 0.08 for trend) and an inverse association with CAC progression (P = 0.04 for trend) but no association with high carotid intima-media thickness (P > 0.20 for trend). Stratification of the coffee analyses by sex, race, or smoking yielded similar nonsignificant patterns. Conclusion-We observed no substantial association between coffee or caffeine intake and coronary and carotid atherosclerosis. However, our results suggested an inverse association between tea and CAC but not carotid atherosclerosis.

Ringen PA; Vaskinn A; Sundet K; Engh JA; Jonsdottir H; Simonsen C et al. Opposite relationships between cannabis use and neurocognitive functioning in bipolar disorder and schizophrenia. Psychological Medicine 40(8): 1337-1347, 2010. (54 refs.)

Background. Cannabis use is associated with altered neurocognitive functioning in severe mental disorders, but data are still inconclusive and there are no studies of bipolar disorder. The aim of this study was to investigate the association between cannabis use and neurocognition in bipolar disorder compared with schizophrenia in a naturalistic setting. Method. A total of 133 patients with bipolar disorder and 140 patients with schizophrenia underwent neuropsychological assessments and clinical characterization including measures of substance use. Relationships between cannabis users and neurocognitive function were explored in the two diagnostic groups. Possible interactions between diagnosis and cannabis use were investigated, and findings were controlled for possible confounders. Results. In bipolar disorder subjects, cannabis use was associated with better neurocognitive function, but the opposite was the case for the schizophrenia subjects. There was a statistically significant interaction effect of diagnosis and cannabis use on focused attention (p = 0.019), executive functioning (verbal fluency - set shifting) (p = 0.009), logical memory-learning (p = 0.007) and on logical memory-recall (p = 0.004). These differences in neurocognitive function could not be explained by putative confounders. Conclusions. The findings suggest that cannabis use may be related to improved neurocognition in bipolar disorder and compromised neurocognition in schizophrenia. The results need to be replicated in independent samples, and may suggest different underlying disease mechanisms in the two disorders.f

Santini A; Ferracane R; Mikusova P; Eged S; Srobarova A; Meca G et al. Influence of different coffee drink preparations on ochratoxin A content and evaluation of the antioxidant activity and caffeine variations. Food Control 22(8): 1240- 1245, 2011. (34 refs.)

Coffee is one of the most frequently consumed beverages in North America and Europe. It is well known that coffee contains caffeine and that coffee beans can be contaminated by Ochratoxin A (OTA). The operating conditions however affect OTA and caffeine extraction from the roasted coffee. OTA content found in the beverages can be greater than that found in the roasted coffee used to prepare it, representing a potential OTA related risk factor for the human health. Moreover the coffee beans and coffee based beverages have an anti oxidant activity. This study investigates the OTA content, the amount of caffeine, and the antioxidant activity in five different preparations: American coffee, Moka, Italian Espresso, Neapolitan and Turkish coffee. Artificially OTA spiked samples were prepared using artificially contaminated roasted coffee beans. High Pressure Liquid Chromatography with fluorimetric detector was used (LC-FLD). The OTA amount, in all preparations, was 85% lower then the spiking level. Quantitative analysis of the caffeine content in the five coffee preparations was determined by spectrophotometry, and the antioxidant lipophilic and hydrophilic activities of the different coffee preparations were investigated and compared. The caffeine content was directly related to its antioxidant activity; no relation was found between OTA, antioxidant activity and caffeine.

Santos C; Costa J; Santos J; Vaz-Carneiro A; Lunet N. Caffeine intake and dementia: Systematic review and meta-analysis. (review). Journal of Alzheimers Disease 20(Supplement 1): S187-S204, 2010. (40 refs.)

A recent meta-analysis of 4 studies published up to January 2004 suggests a negative association between coffee consumption and Alzheimer's disease, despite important heterogeneity in methods and results. Several epidemiological studies on this issue have been published since then, warranting an update of the insights on this topic. We conducted a systematic review and meta-analysis of published studies quantifying the relation between caffeine intake and cognitive decline or dementia. Data sources searched included Medline, LILACS, Scopus, Web of Science and reference lists, up to September 2009. Cohort and case-control studies were included. Three independent reviewers selected the studies and extracted the data on to standardized forms. Nine cohort and two case-control studies were included. Quantitative data synthesis of the most precise estimates from each study was accomplished through random effects meta-analysis. Heterogeneity was quantified using the I-2 statistic. The outcomes of the studies considered for meta-analysis were Alzheimer's disease in four studies, dementia or cognitive impairment in two studies, and cognitive decline in three studies. The summary relative risk (RR) for the association between caffeine intake and different measures of cognitive impairment/decline was 0.84 [95% Confidence Interval (95% CI): 0.72-0.99; I-2 = 42.6%]. When considering only the cohort studies, the summary RR was 0.93 (95% CI: 0.83-1.04, I-2 = 0.0%), and 0.77 (95% CI: 0.63-0.95, I-2 = 34.7%), if the most influential study was excluded. This systematic review and meta-analysis found a trend towards a protective effect of caffeine, but the large methodological heterogeneity across a still limited number of epidemiological studies precludes robust and definite statements on this topic.

Santos C; Lunet N; Azevedo A; de Mendonca A; Ritchie K; Barros H. Caffeine intake is associated with a lower risk of cognitive decline: A cohort study from Portugal. Journal of Alzheimers Disease 20(Supplement 1): S175-S185, 2010. (54 refs.)

Alzheimer's disease has emerged in recent decades as a major health problem and the role of lifestyles in the modulation of risk has been increasingly recognized. Recent epidemiological studies suggest a protective effect for caffeine intake in dementia. We aimed to quantify the association between caffeine dietary intake and cognitive decline, in a cohort of adults living in Porto. A cohort of 648 subjects aged >= 65 years was recruited between 1999-2003. Follow-up evaluation (2005-2008) was carried out on 58.2% of the eligible participants and 10.9% were deceased. Caffeine exposure in the year preceding baseline evaluation was assessed with a validated food frequency questionnaire. Cognitive evaluation consisted of baseline and follow-up Mini-Mental State Examination (MMSE). Cognitive decline was defined by a decrease >= 2 points in the MMSE score between evaluations. Relative risk (RR) and 95% confidence interval (95% CI) estimates adjusted for age, education, smoking, alcohol drinking, body mass index, hypertension, and diabetes were computed using Poisson regression. Caffeine intake (>62 mg/day [3rd third] vs. <22 mg/day [1st third]) was associated with a lower risk of cognitive decline in women (RR = 0.49, 95% CI 0.24-0.97), but not significantly in men (RR = 0.65, 95% CI 0.27-1.54). Our study confirms the negative association between caffeine and cognitive decline in women.

Sarne Y; Asaf F; Fishbein M; Gafni M; Keren O. The dual neuroprotective-neurotoxic profile of cannabinoid drugs. (review). British Journal of Pharmacology 163(7, special issue): 1391-1401, 2011. (137 refs.)

Extensive in vitro and in vivo studies have shown that cannabinoid drugs have neuroprotective properties and suggested that the endocannabinoid system may be involved in endogenous neuroprotective mechanisms. On the other hand, neurotoxic effects of cannabinoids in vitro and in vivo were also described. Several possible explanations for these dual, opposite effects of cannabinoids on cellular fate were suggested, and it is conceivable that various factors may determine the final outcome of the cannabinoid effect in vivo. In the current review, we focus on one of the possible reasons for the dual neuroprotective/neurotoxic effects of cannabinoids in vivo, namely, the opposite effects of low versus high doses of cannabinoids. While many studies reported neuroprotective effects of the conventional doses of cannabinoids in various experimental models for acute brain injuries, we have shown that a single administration of an extremely low dose of Delta(9)-tetrahydrocannabinol (THC) (3-4 orders of magnitude lower than the conventional doses) to mice induced long-lasting mild cognitive deficits that affected various aspects of memory and learning. These findings led to the idea that this low dose of THC, which induces minor damage to the brain, may activate preconditioning and/or postconditioning mechanisms and thus will protect the brain from more severe insults. Indeed, our recent findings support this assumption and show that a pre- or a postconditioning treatment with extremely low doses of THC, several days before or after brain injury, provides effective long-term cognitive neuroprotection. The future therapeutical potential of these findings is discussed.

Segarra R; Zabala A; Eguiluz JI; Ojeda N; Elizagarate E; Sanchez P et al. Cognitive performance and smoking in first-episode psychosis: the self-medication hypothesis. European Archives of Psychiatry and Clinical Neuroscience 261(4): 241-250, 2011. (46 refs.)

The self-medication hypothesis attempts to explain the extraordinary high levels of cigarette smoking in schizophrenia; patients may smoke in an attempt to reduce their cognitive deficits, symptoms, or the side effects of antipsychotics. In a previous report, we detected beneficial performance in attention and working memory in patients with first-episode psychosis who smoked compared to non-smoking patients soon after stabilization. In the present study, we examine differences in the course of those deficits 12 months after the initiation of antipsychotic treatment. We also explore the association between smoking and symptoms and side effects of medication. Neuropsychological assessments were performed at baseline, month 6 and month 12 using a computerized battery that included measures of sustained attention (Continuous Performance Test CPT-O), selective attention (Stroop interference task) and working memory (CPT-XO). Patients met the criterion of fitting in the same smoking category throughout the study: non-smoker (n = 15; 0 cigarettes/day) and smoker (n = 26; > 15 cigarettes/day). The non-smoking patients showed significant cognitive improvements, whereas smoking patients lost their superior baseline performance, which was probably obtained through nicotinic stimulation, at the 6- and 12-month assessments due to a static course of deficits. Smokers did not obtain any cognitive benefit after instauration of treatment and worsen their symptoms over the first year. These results suggest that smoking may constitute a marker of a more severe illness. Smoking was not associated with fewer extrapyramidal side effects. Smoking might improve attention and working memory to a similarly modest extent as atypical antipsychotics and could reflect an effort to ameliorate these cognitive dysfunctions previous to treatment instauration.

Uritsky TJ; McPherson ML; Pradel F. Assessment of hospice health professionals' knowledge, views, and experience with medical marijuana. Journal of Palliative Medicine 14(12): 1291-1295, 2011. (10 refs.)

The medicinal and recreational use of cannabis has been controversial, especially in the United States. Marijuana for medicinal use is approved in 14 U.S. states and has recently been considered for legalization in several additional states. Given its demonstrated efficacy in symptom management, marijuana has a potential role in palliative care. This study utilized a 16-item questionnaire to assess the knowledge, experience, and views of hospice professionals regarding the use of marijuana in terminally ill patients. The study results revealed that, like the general public, hospice health care providers are generally in favor of legalization of marijuana and, if legalized, would support its use in symptom management for their terminally ill patients.

Wang CC; Lu TH; Liao WC; Yuan SC; Kuo PC; Chuang HL et al. Cigarette smoking and cognitive impairment: A 10-year cohort study in Taiwan. Archives of Gerontology and Geriatrics 51(2): 143-148, 2010. (43 refs.)

The relationship between cigarette smoking and cognitive impairment is not a simple one. Some studies have demonstrated that cigarette smoking is a risk factor for cognitive impairment in the elderly, whereas other studies have shown cigarette smoking to be protective against dementia. This study aims to explore the relationship between cigarette smoking and cognitive impairment in elderly persons without dementia, during a 10-year period. Data were derived from a population-based cohort study of 1436 elderly Taiwanese. Cognitive function was measured by the SPMSQ both in 1993 and in 2003. A total of 1436 participants free of cognitive impairment at baseline (SPMSQ >= 6 in 1993) were included in these analyses. Subsequently, participants were divided into three groups: never, past, and current smokers. The effect of cigarette smoking on cognitive function was assessed using logistic regression. In the logistic regression model adjusted for age, education, hypertension, diabetes, heart disease, and stroke at baseline, persons who had quit smoking (Odds ratio = OR = 0.31; 95% CI = 0.18-0.53; p < 0.001) and those who continued to smoke (OR = 0.37; 95% CI = 0.20-0.70; p < 0.001) were about one-third as likely to develop cognitive impairment as were those who never smoked. However, no dose-response relationship was observed between pack-years and cognitive impairment. Past and current smokers were less likely to develop cognitive impairment during a 10-year follow-up than were those who had never smoked. The present study suggests that smoking may be protective for cognitive function.

Wang YJ; Tuomilehto J; Jousilahti P; Antikainen R; Mahonen M; Mannisto S et al. Coffee consumption and the risk of heart failure in Finnish men and women. Heart 97(1): 44-48, 2011. (30 refs.)

Objectives: To evaluate the association of coffee consumption with the risk of heart failure (HF) in the Finnish population. Design Prospective population-based cohort study. Setting This study, which is a part of FINRISK study, was carried out in Finland. Subjects: Study cohorts included 59 490 Finnish participants aged 25-74 years who were free of HF at baseline. Main outcome measures HF (2020 men and 1807 women) during a mean follow-up of 19.2 years. Results: Multivariable-adjusted (age, study year, body mass index, smoking, education, alcohol consumption, tea consumption, physical activity, systolic blood pressure, history of myocardial infarction, history of valvular heart disease, history of diabetes and total cholesterol) HRs (with 95% CI) of HF associated with the amount of coffee consumption daily (0, 1-2, 3-4, 5-6, 7-9 and >= 10 cups) were 1.00, 0.91 (0.71 to 1.16), 0.88 (0.70 to 1.10), 0.91 (0.73 to 1.13), 0.96 (0.76 to 1.22) and 1.02 (0.80 to 1.30) (p(trend)=0.485) for men and 1.00, 0.73 (0.56 to 0.97), 0.77 (0.60 to 0.98), 0.68 (0.53 to 0.88), 0.80 (0.61 to 1.04) and 0.88 (0.65 to 1.19) (p(trend)=0.007) for women, respectively. Stratification by age, smoking status, alcohol consumption, history of type 2 diabetes mellitus and body mass index gave similar results. Conclusion: Coffee consumption does not increase the risk of HF in Finnish men and women. In women, an inverse association was observed between low to moderate coffee consumption and the risk of HF.

Wikstrom AK; Stephansson O; Cnattingius S. Tobacco use during pregnancy and preeclampsia: Risk effects of cigarette smoking and snuff. Hypertension 55(5): 1254-1259, 2010. (30 refs.)

Preeclampsia is a leading cause of maternal and infant mortality and morbidity worldwide. Both Swedish snuff and cigarette smoke include nicotine, but combustion products accompany only smoking. The aims of this study were to compare the effects of Swedish snuff and cigarette smoking on preeclampsia risk and to estimate whether changes in tobacco habits during pregnancy affect the risk of developing term preeclampsia. We used information from the Swedish Birth Register on all singleton births in Sweden during the years 1999-2006 (n=612 712). Compared with nontobacco users, women who used snuff in early pregnancy had an adjusted odds ratio (OR) for preeclampsia of 1.11 (95% CI: 0.97 to 1.28). The corresponding ORs for light and heavy smokers were 0.66 (95% CI: 0.61 to 0.71) and 0.51 (95% CI: 0.44 to 0.58), respectively, with ORs lower for term than preterm preeclampsia. Compared with nontobacco users, women who smoked in early pregnancy but had quit smoking before late pregnancy (weeks 30 to 32) had an adjusted OR for term preeclampsia of 0.94 (95% CI: 0.83 to 1.08). The corresponding OR for women who did not use tobacco in early pregnancy but had started to smoke before late pregnancy was 0.65 (95% CI: 0.50 to 0.85). We conclude that tobacco combustion products rather than nicotine are the probable protective ingredients against preeclampsia in cigarette smoke. Because change of smoking habits during pregnancy influence risk, we further conclude that it is the smoking habits in the middle or late rather than in the beginning of pregnancy that seem to affect the risk of preeclampsia.

Yu XF; Bao ZJ; Zou JA; Dong J. Coffee consumption and risk of cancers: A meta-analysis of cohort studies. (review). BMC Cancer 11: article 96, 2011. (89 refs.)

Background: Coffee consumption has been shown to be associated with cancer of various sites in epidemiological studies. However, there is no comprehensive overview of the substantial body of epidemiologic evidence. Methods: We searched MEDLINE, EMBASE, Science Citation Index Expanded and bibliographies of retrieved articles. Prospective cohort studies were included if they reported relative risks (RRs) and corresponding 95% confidence intervals (CIs) of various cancers with respect to frequency of coffee intake. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with 1 cup/day increment of coffee consumption. Results: 59 studies, consisting of 40 independent cohorts, met the inclusion criteria. Compared with individuals who did not or seldom drink coffee per day, the pooled RR of cancer was 0.87 (95% CI, 0.82-0.92) for regular coffee drinkers, 0.89 (0.84-0.93) for low to moderate coffee drinkers, and 0.82 (0.74-0.89) for high drinkers. Overall, an increase in consumption of 1 cup of coffee per day was associated with a 3% reduced risk of cancers (RR, 0.97; 95% CI, 0.96-0.98). In subgroup analyses, we noted that, coffee drinking was associated with a reduced risk of bladder, breast, buccal and pharyngeal, colorectal, endometrial, esophageal, hepatocellular, leukemic, pancreatic, and prostate cancers. Conclusions: Findings from this meta-analysis suggest that coffee consumption may reduce the total cancer incidence and it also has an inverse association with some type of cancers.

Zajicek JP; Apostu VI. Role of cannabinoids in multiple sclerosis. (review). CNS Drugs 25(3): 187-201, 2011. (107 refs.)

Although extracts from the cannabis plant have been used medicinally for thousands of years, it is only within the last 2 decades that our understanding of cannabinoid physiology and the provision of evidence for therapeutic benefit of cannabinoids has begun to accumulate. This review provides a background to advances in our understanding of cannabinoid receptors and the endocannabinoid system, and then considers how cannabinoids may help in the management of multiple sclerosis (MS). The relative paucity of treatments for MS-related symptoms has led to experimentation by patients with MS in a number of areas including the use of cannabis extracts. An increasing amount of evidence is now emerging to confirm anecdotal reports of symptomatic improvement, particularly for muscle stiffness and spasms, neuropathic pain and sleep and bladder disturbance, in patients with MS treated with cannabinoids. Trials evaluating a role in treating other symptoms such as tremor and nystagmus have not demonstrated any beneficial effects of cannabinoids. Safety profiles of cannabinoids seem acceptable, although a slow prolonged period of titration improves tolerability. No serious safety concerns have emerged. Methodological issues in trial design and treatment delivery are now being addressed. In addition, recent experimental evidence is beginning to suggest an effect of cannabinoids on more fundamental processes important in MS, with evidence of anti-inflammation, encouragement of remyelination and neuroprotection. Trials are currently under way to test whether cannabinoids may have a longer term role in reducing disability and progression in MS, in addition to symptom amelioration, where indications are being established.

Zhang Y; Lee ET; Cowan LD; Fabsitz RR; Howard BV. Coffee consumption and the incidence of type 2 diabetes in men and women with normal glucose tolerance: The Strong Heart Study. Nutrition, Metabolism and Cardiovascular Diseases 21(6): 418-423, 2011. (39 refs.)

Background and aims: It was reported that high coffee consumption was related to decreased diabetes risk. The aim of this study is to examine the association between coffee consumption and the incidence of type 2 diabetes in persons with normal glucose tolerance in a population with a high incidence and prevalence of diabetes. Methods. and results: In a prospective cohort study, information about daily coffee consumption was collected at the baseline examination (1989-1992) in a population-based sample of American Indian men and women 45-74 years of age. Participants with normal glucose tolerance (N = 1141) at the baseline examination were followed for an average of 7.6 years. The incidence of diabetes was compared across the categories of daily coffee consumption. The hazard ratios of diabetes related to coffee consumption were calculated using Cox proportional hazards models, adjusted for potential confounders. Levels of coffee consumption were positively related to levels of current smoking and inversely related to body mass index, waist circumference, female gender, and hypertension. Compared to those who did not drink coffee, participants who drank 12 or more cups of coffee daily had 67% less risk of developing diabetes during the follow-up (hazard ratio: 0.33, 95% confidence interval: 0.13, 0.81). Conclusion: In this population, a high level of coffee consumption was associated with a reduced risk of deterioration of glucose metabolism over an average 7.6 years of follow-up. More work is needed to understand whether there is a plausible biological mechanism for this observation.