Fitness to drive and cannabis: Validation of two blood THCCOOH thresholds to distinguish occasional users from heavy smokers.

Many studies based on either an experimental or an epidemiological approach, have shown that the ability to drive is impaired when the driver is under the influence of cannabis. Baseline performances of heavy users remain impaired even after several weeks of abstinence. Symptoms of cannabis abuse and dependence are generally considered incompatible with safe driving. Recently, it has been shown that traffic safety can be increased by reporting the long-term unfit drivers to the driver licensing authorities and referring the cases for further medical assessment. Evaluation of the frequency of cannabis use is a prerequisite for a reliable medical assessment of the fitness to drive. In a previous paper we advocated the use of two thresholds based on 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) concentration in whole blood to help to distinguish occasional cannabis users (≤3μg/L) from heavy regular smokers (≥40μg/L). These criteria were established on the basis of results obtained in a controlled cannabis smoking study with placebo, carried out with two groups of young male volunteers; the first group was characterized by a heavy use (≥10 joints/month) while the second group was made up of occasional users smoking at most 1 joint/week. However, to date, these cutoffs have not been adequately assessed under real conditions. Their validity can now be evaluated and confirmed with 146 traffic offenders' real cases in which the whole blood cannabinoid concentrations and the frequency of cannabis use are known. The two thresholds were not challenged by the presence of ethanol (40% of cases) and of other therapeutic and illegal drugs (24%). Thus, we propose the following procedure that can be very useful in the Swiss context but also in other countries with similar traffic policies: if the whole blood THCCOOH concentration is higher than 40μg/L, traffic offenders must be directed first and foremost toward medical assessment of their fitness to drive. This evaluation is not recommended if the THCCOOH concentration is lower than 3μg/L and if the self-rated frequency of cannabis use is less than 1 time/week. A THCCOOH level between these two thresholds cannot be reliably interpreted. In such a case, further medical assessment and follow-up of the fitness to drive are also suggested, but with lower priority.

Use of nicotine substitute prescribed at hourly plus ab libitum intake or ad libitum for heavy smokers willing to quit: a randomized controlled trial.

OBJECTIVE: To assess the impact of instructional guidance in the regular use of use nicotine nasal spray (NNS) on the true use of NNS during the first three weeks of smoking cessation for heavy smokers who are willing to quit. METHODS: This randomized, open, controlled trial included 50 patients who were heavy smokers, were willing to quit, and attending an academic outpatient clinic in Western Switzerland. Patients were randomised to instruction on NNS use as "ad libitum" (administration whenever cravings appear; control group) or to use NNS when craving appears and at least every hour when awake (intervention group). Intakes were monitored using an electronic device fixed in the spray unit (MDILog) during the first three weeks of use. Self reported abstinence from smoking at six months was confirmed by expired-air carbon monoxide. Using intention-to-treat analysis, random-effect GLS regression was used to calculate the mean difference of daily doses between groups controlling for lack of independence between measures from the same individual. RESULTS: One patient was lost to follow-up. At baseline randomization, the group receiving instruction to use NNS hourly included more women, patients with previous desires to quit, and patients with more psychiatric comorbidities and less somatic complaints compared to the group instructed to use NNS with cravings (group imbalance). Both groups self-administered more than the daily recommended dosage of 8 uses. Mean daily usage was 13.6 dose/day and 11.1 dose/day for the group instructed to use NNS hourly and with cravings, respectively. Adjusting for baseline imbalance, the increased daily doses in the intervention group (hourly use) remained nonsignificant compared to ad libitum use (-0.5 dose/day; CI 95% -6.2; 5.3, from day 1 to day 7; and 2.3 dose/day; CI 95% -5.4; 10.0, from day 8 to day 21). Instructing patients to use the NNS daily had no effect on smoking cessation at six months (RR = 0.69; CI 95% 0.34; 1.39). CONCLUSION: Heavy smokers willing to quit use NNS frequently, regardless of the instructions given. Recommending the use of NNS only when craving appears for heavy smokers willing to quit seems acceptable compared to prescribing hourly administration. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00861276.

THCCOOH concentrations in whole blood: Are they useful in discriminating occasional from heavy smokers?

Some forensic and clinical circumstances require knowledge of the frequency of drug use. Care of the patient, administrative, and legal consequences will be different if the subject is a regular or an occasional cannabis smoker. To this end, 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) has been proposed as a criterion to help to distinguish between these two groups of users. However, to date this indicator has not been adequately assessed under experimental conditions. We carried out a controlled administration study of smoked cannabis with a placebo. Cannabinoid levels were determined in whole blood using tandem mass spectrometry. Significantly high differences in THCCOOH concentrations were found between the two groups when measured during the screening visit, prior to the smoking session, and throughout the day of the experiment. Receiver operating characteristic (ROC) curves were determined and two threshold criteria were proposed in order to distinguish between these groups: a free THCCOOH concentration below 3 µg/L suggested an occasional consumption (≤ 1 joint/week) while a concentration higher than 40 µg/L corresponded to a heavy use (≥ 10 joints/month). These thresholds were tested and found to be consistent with previously published experimental data. The decision threshold of 40 µg/L could be a cut-off for possible disqualification for driving while under the influence of cannabis. A further medical assessment and follow-up would be necessary for the reissuing of a driving license once abstinence from cannabis has been demonstrated. A THCCOOH level below 3 µg/L would indicate that no medical assessment is required. Copyright © 2013 John Wiley & Sons, Ltd.

Use of nicotine substitute prescribed at hourly plus ad libitum intake or ad libitum for heavy smokers willing to quit : a randomized controlled trial

Rapport de synthèse : l .Objectif Evaluer l'effet qu'ont les consignes d'utilisation régulière d'un spray nasal à la nicotine sur leur véritable utilisation durant les 3 premières semaines d'un sevrage tabagique. Un objectif secondaire est d'évaluer l'effet des consignes d'utilisation régulière du spray durant les premières semaines de sevrage tabagique sur le taux de succès à 6 mois par rapport à un groupe pouvant utiliser le spray « ad libitum ». 2. Méthode II s'agit d'une étude ouverte, randomisée contrôlée, incluant 50 patients présentant une dépendance nicotinique forte, se trouvant en phase de préparation selon le modèle transthéorique du changement de Prochaska et Di Clemente, recrutés au sein de la consultation «stop tabac » de la Policlinique Médicale Universitaire de Lausanne. Dans le groupe «contrôle », les patients ont été instruits à utiliser le spray « ad libitum », soit dès qu'apparaissaient des envies irrésistibles de fumer, tandis que le groupe «intervention » a reçu pour consigne d'utiliser le spray au moins 1 fois par heure dès le lever, voire plus en cas d'envie de fumer. L'utilisation du spray nasal a été enregistrée par un dispositif électronique fixé sur le spray (MDILogTM) durant les 3 premières semaines d'utilisation. Durant le suivi, l'abstinence tabagique a été vérifiée par une mesure du taux de CO expiré par un appareil spécifique (Bedfont Smokerlyzer). L'abstinence tabagique a été considérée comme un succès si le taux de CO était s 10 ppm (particules par million). 3. Résultats Un patient a été perdu durant le suivi. Au moment de la randomisation, le groupe «intervention » comprenait plus de femmes, des patients ayant un nombre plus grand de précédentes tentatives d'arrêt du tabagisme, plus de co-morbidités psychiatriques, mais moins de co-morbidités somatiques que le groupe «contrôle ». Dans les 2 groupes, les participants ont utilisé le spray nasal plus de 8 fois par jour (minimum demandé dans le groupe intervention). L'utilisation moyenne du spray était de 13,6 doses/jour pour le groupe «intervention » et de 1 l,l doses/jour pour le groupe contrôle. Ajusté aux différences entre les 2 groupes, la différence entre les doses plus importantes utilisées dans le groupe «intervention »par rapport à celles du groupe « ad libitum »reste non significative durant la première (0.8 ; CI 95% -5.1 ; 6,7), la deuxième (4.0 ; CI 95% -1.9 ; 9.9) et la troisième semaine (3.0 ; CI 95% -2.5 ; 8.5). De même, le fait d'instruire le patient à utiliser chaque heure le spray nasal durant les premières semaines n'a pas eu d'impact sur le taux de succès à 6 mois (RR = 0.69 ; CI 95% 0.34 ; 1.39). 4. Conclusions Cette étude négative montre que les différences d'utilisation du spray nasal nicotinique sont plus dépendantes des caractéristiques individuelles du patient que des recommandations d'utilisation du thérapeute. Les patients présentant un syndrome de dépendance à la nicotine forte utilisent spontanément de manière importante le spray nasal nicotinique, indépendamment des recommandations données. Pour les patients présentant un syndrome de dépendance à la nicotine forte, les recommandations par le thérapeute d'utiliser le spray nasal dès l'apparition d'envies de fumer semblent être la manière de faire la plus adéquate.

Fitness to drive and cannabis: Experimental and real-life case study validation of two blood THCCOOH thresholds to distinguish occasional users from heavy smokers

Introduction: THC-COOH has been proposed as a criterion to help to distinguish between occasional from regular cannabis users. However, to date this indicator has not been adequately assessed under experimental and real-life conditions. Methods: We carried out a controlled administration study of smoked cannabis with a placebo. Twenty-three heavy smokers and 25 occasional smokers, between 18 and 30 years of age, participated in this study [Battistella G et al., PloS one. 2013;8(1):e52545]. We collected data from a second real case study performed with 146 traffic offenders' cases in which the whole blood cannabinoid concentrations and the frequency of cannabis use were known. Cannabinoid levels were determined in whole blood using tandem mass spectrometry methods. Results: Significantly high differences in THC-COOH concentrations were found between the two groups when measured during the screening visit, prior to the smoking session, and throughout the day of the experiment. Receiver operating characteristic (ROC) curves were determined and two threshold criteria were proposed in order to distinguish between these groups: a free THC-COOH concentration below 3 μg/L suggested an occasional consumption (≤ 1 joint/week) while a concentration higher than 40 μg/L corresponded to a heavy use (≥ 10 joints/month). These thresholds were successfully tested with the second real case study. The two thresholds were not challenged by the presence of ethanol (40% of cases) and of other therapeutic and illegal drugs (24%). These thresholds were also found to be consistent with previously published experimental data. Conclusion: We propose the following procedure that can be very useful in the Swiss context but also in other countries with similar traffic policies: If the whole blood THC-COOH concentration is higher than 40 μg/L, traffic offenders must be directed first and foremost toward medical assessment of their fitness to drive. This evaluation is not recommended if the THC-COOH concentration is lower than 3 μg/L. A THC-COOH level between these two thresholds can't be reliably interpreted. In such a case, further medical assessment and follow up of the fitness to drive are also suggested, but with lower priority.

Serum myeloperoxidase level is Increased in heavy smokers

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Treatment of gingival recessions in heavy smokers using two surgical techniques: a controlled clinical trial

Smokers have small root coverage which is associated with bad vascularity of periodontal tissues. This study evaluated a technique that can increase the blood supply to the periodontal tissues compared with a traditional technique. Twenty heavy smokers (10 males and 10 females) with two bilateral Miller class I gingival recessions received coronally positioned flaps in one side (Control group)and extended flap technique in the other side (Test group). Clinical measurements (probing pocket depth, clinical attachment level, bleeding on probing, gingival recession height, gingival recession width, amount of keratinized tissue, and width and height of the papillae adjacent to the recession) were determined at baseline, 3 and 6 months postoperatively. Salivary cotinina samples were taken as an indicator of the nicotine exposure level. No statistically significant differences (p>0.05) were detected for the clinical measurements or smoke exposure. Both techniques promoted low root coverage (Control group: 43.18% and Test group: 44.52%). In conclusion, no difference was found in root coverage between the techniques. Root coverage is possible and uneventful even, if rather low, in heavy smoker patients with low plaque and bleeding indices.

Comparison of cannabinoid concentrations in oral fluid and whole blood between occasional and regular cannabis smokers prior to and after smoking a cannabis joint.

A cross-over controlled administration study of smoked cannabis was carried out on occasional and heavy smokers. The participants smoked a joint (11 % Δ9-tetrahydrocannabinol (THC)) or a matching placebo on two different occasions. Whole blood (WB) and oral fluid (OF) samples were collected before and up to 3.5 h after smoking the joints. Pharmacokinetic analyses were obtained from these data. Questionnaires assessing the subjective effects were administered to the subjects during each session before and after the smoking time period. THC, 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THCCOOH) were analyzed in the blood by gas chromatography or liquid chromatography (LC)-tandem mass spectrometry (MS/MS). The determination of THC, THCCOOH, cannabinol (CBN), and Δ9-tetrahydrocannabinolic acid A (THC-A) was carried out on OF only using LC-MS/MS. In line with the widely accepted assumption that cannabis smoking results in a strong contamination of the oral cavity, we found that THC, and also THC-A, shows a sharp, high concentration peak just after smoking, with a rapid decrease in these levels within 3 h. No obvious differences were found between both groups concerning THC median maximum concentrations measured either in blood or in OF; these levels were equal to 1,338 and 1,041 μg/L in OF and to 82 and 94 μg/L in WB for occasional and heavy smokers, respectively. The initial WB THCCOOH concentration was much higher in regular smokers than in occasional users. Compared with the occasional smokers, the sensation of confusion felt by the regular smokers was much less while the feeling of intoxication remained almost unchanged.

Socio-demographic factors, smoking, symptoms, morbidities and pulmonary function and quality of life in individuals with a heavy smoking history

Objective: To determine which socio-demographic, exposure, morbidity and symptom variables are associated with health-related quality of life among former and current heavy smokers. Methods: Cross sectional data from 2537 participants were studied. All participants were at ≥2% risk of developing lung cancer within 6 years. Linear and logistic regression models utilizing a multivariable fractional polynomial selection process identified variables associated with health-related quality of life, measured by the EQ-5D. Results: Upstream and downstream associations between smoking cessation and higher health-related quality of life were evident. Significant upstream associations, such as education level and current working status and were explained by the addition of morbidities and symptoms to regression models. Having arthritis, decreased forced expiratory volume in one second, fatigue, poor appetite or dyspnea were most highly and commonly associated with decreased HRQoL. Discussion: Upstream factors such as educational attainment, employment status and smoking cessation should be targeted to prevent decreased health-related quality of life. Practitioners should focus treatment on downstream factors, especially symptoms, to improve health-related quality of life.

Mucociliary clearance and its relation with the level of physical activity in daily life in healthy smokers and nonsmokers

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Periodontal status in smokers and never-smokers: Clinical findings and real-time polymerase chain reaction quantification of putative periodontal pathogens

Background: Smoking is a well-known risk factor for destructive periodontal disease, but its relationship with periodontal status and subgingival microbiota remains unclear. Inherent limitations of microbiological methods previously used may partly explain these mixed results, and real-time polymerase chain reaction (PCR) has been presented as a valid alternative. The aim of the present study was to investigate the clinical condition and microbiological profile of patients with chronic periodontitis as related to the habit of smoking.Methods: Fifty patients (33 to 59 years old), 25 smokers and 25 never-smokers, constituted the sample. The visible plaque index (VPI), gingival bleeding index (GBI), bleeding on probing (BOP), periodontal probing depth (PD), clinical attachment loss (CAL), and gingival crevicular fluid (GCF) volume were recorded. Real-time PCR quantified Porphyromonas gingivalis, Micromonas micros, Dialister pneumosintes, Actinobacillus actinomycetemcomitans and total bacteria in subgingival samples.Results: Smokers and never-smokers showed similar values for VPI, GBI, and BOP. Smokers had deeper PD in buccal/lingual sites and higher CAL independently of the tooth surface. The GCF volume was smaller in smokers, independent of the PD. Similar amounts of total bacteria and P. gingivalis were observed for both groups. Significantly higher numbers of D. pneumosintes and M. micros were present in smokers and associated with moderate and deep pockets. When heavy smokers were considered, higher counts of total bacteria, M. micros, and D. pneumosintes were observed.Conclusions: Smoking seems to have a detrimental impact on the periodontal status and microbiological profile of patients with periodontitis. Compared to never-smokers, smokers had deeper pockets, greater periodontal destruction, and higher counts of some putative periodontal pathogens.

Effects of Cigarette Smoking Intensity on the Mucociliary Clearance of Active Smokers

Background: Smoking impairs mucociliary clearance and increases respiratory infection frequency and severity in subjects with and without smoking-related chronic lung diseases. Objective: This study evaluated the effects of smoking intensity on mucociliary clearance in active smokers. Methods: Seventy-five active smokers were grouped into light (1-10 cigarettes/day; n = 14), moderate (11-20 cigarettes/day; n = 34) and heavy smokers (≥21 cigarettes/day; n = 27) before starting a smoking cessation programme. Smoking behaviour, nicotine dependence, pulmonary function, carbon monoxide in exhaled air (exCO), carboxyhaemoglobin (COHb) and mucociliary clearance measured by the saccharin transit time (STT) test were all evaluated. An age-matched non-smoker group (n = 24) was assessed using the same tests. Results: Moderate (49 ± 7 years) and heavy smokers (46 ± 8 years) had higher STT (p = 0.0001), exCO (p < 0.0001) and COHb (p < 0.0001) levels compared with light smokers (51 ± 15 years) and non-smokers (50 ± 11 years). A positive correlation was observed between STT and exCO (r = 0.4; p < 0.0001), STT and cigarettes/day (r = 0.3, p = 0.02) and exCO and cigarettes/day (r = 0.3, p < 0.01). Conclusion: Smoking impairs mucociliary clearance and is associated with cigarette smoking intensity. Copyright © 2013 S. Karger AG, Basel.

Active and passive smoking and the risk of subarachnoid hemorrhage - An international population-based case-control study

Background and Purpose - This study was undertaken to better clarify the risks associated with cigarette smoking and subarachnoid hemorrhage (SAH). Methods - The study included 432 incident cases of SAH frequency matched to 473 community SAH-free controls to determine dose-dependent associations of active and passive smoking ( at home) and smoking cessation with SAH. Results - Compared with never smokers not exposed to passive smoking, the adjusted odds ratio for SAH among current smokers was 5.0 (95% confidence interval [CI], 3.1 to 8.1); for past smokers, 1.2 ( 95% CI, 0.8 to 2.0); and for passive smokers, 0.9 ( 95% CI, 0.6 to 1.5). Current and lifetime exposures showed a clear dose-dependent effect, and risks appeared more prominent in women and for aneurysmal SAH. Approximately 1 in 3 cases of SAH could be attributed to current smoking, but risks decline quickly after smoking cessation, even among heavy smokers. Conclusions - A strong positive association was found between cigarette smoking and SAH, especially for aneurysmal SAH and women, which is virtually eliminated within a few years of smoking cessation. Large opportunities exist for preventing SAH through smoking avoidance and cessation programs.

Respiratory health effects of cannabis: Position statement of the Thoracic Society of Australia and New Zealand

Both the gaseous and the particulate phases of tobacco and cannabis smoke contain a similar range of harmful chemicals. However, differing patterns of inhalation mean that smoking a 'joint' of cannabis results in exposure to significantly greater amounts of combusted material than with a tobacco cigarette. The histopathological effects of cannabis smoke exposure include changes consistent with acute and chronic bronchitis. Cellular dysplasia has also been observed, suggesting that, like tobacco smoke, cannabis exposure has the potential to cause malignancy. These features are consistent with the clinical presentation. Symptoms of cough and early morning sputum production are common (20-25%) even in young individuals who smoke cannabis alone. Almost all studies indicate that the effects of cannabis and tobacco smoking are additive and independent. Public health education should dispel the myth that cannabis smoking is relatively safe by highlighting that the adverse respiratory effects of smoking cannabis are similar to those of smoking tobacco, even although it remains to be confirmed that smoking cannabis alone leads to the development of chronic lung disease.