J. F. O'Hanlon

Marijuana, alcohol and actual driving performance

The objective of the current study was to assess the separate and combined effects of marijuana and alcohol on actual driving performance. Eighteen subjects were treated with drugs and placebo according to a balanced, 6‐way, crossover design. On separate evenings they were given weight calibrated Δ9‐tetrahydrocannabinol (THC) doses of 0, 100 and 200 μg/kg with and without an alcohol dose sufficient for achieving blood alcohol concentrations (BAC) of 0·04 g/dl while performing a Road Tracking and Car Following Test in normal traffic. Main outcome measures were standard deviation of lateral position (SDLP), time driven out of lane (TOL), reaction time (RT) and standard deviation of headway (SDH). Both THC doses alone, and alcohol alone, significantly impaired the subjects performances in both driving tests. Performance deficits were minor after alcohol and moderate after both THC doses. Combining THC with alcohol dramatically impaired driving performance. Alcohol combined with THC 100 and 200 μg/kg produced a rise in SDLP the equivalent of that associated with BAC=0·09 and 0·14 g/dl, respectively. Mean TOL rose exponentially with SDLP. Relative to placebo mean RT lengthened by 1·6 s under the combined influence of alcohol and THC 200 μg/kg. Changes in SDH ranged between 0·9 and 3·8 m. Low doses of THC moderately impair driving performance when given alone but severely impair driving performance in combination with a low dose of alcohol. Copyright

Antihistamine effects on actual driving performance in a standard test: a summary of Dutch experience, 1989-94

The review summarizes the major results of eight double‐blind, placebo‐controlled, volunteer studies undertaken by three independent institutions for showing the effects on actual driving performance of “sedating” and “nonsedating” antihistamines (respectively, triprolidine, diphenhydramine, clemastine and terfenadine, loratadine, cetirizine, acrivastine, mizolastine, and ebastine). A common, standardized test was used that measures driving impairment from vehicular “weaving” (i.e., standard deviation of lateral position (SDLP)). Logical relationships were found between impairment and dose, time after dosing, and repeated doses over 4–5 days. The newer drugs were generally less impairing, but differences existed among their effects, and none was unimpairing at doses 1–2 × the currently recommended levels. One or possibly two of the newer drugs possessed both performance‐enhancing and ‐impairing properties, depending on dose, suggesting two mechanisms of action.

Effects of loratadine and cetirizine on actual driving and psychometric test performance, and EEG during driving

SummarySixteen healthy male and female volunteers took part in a 6-way, double-blind cross-over trial to compare the effects of single doses of cetirizine 10 mg, loratadine 10 mg and placebo, with and without alcohol (0.72 g·kg−1, lean body mass). Performance was measured in two repetitions of a psychometric test battery, and a standard, over-the-road driving test. EEG was also measured during driving. Alcohol significantly affected almost every performance measure and altered the EEG energy spectrum during driving whilst the blood concentrations declined from 0.37 to 0.20 mg·ml−1. The effects of cetirizine of on driving performance resembled those of alcohol. It caused the subjects to operate with significantly greater variability in speed and lateral position (‘weaving’ motion). The effects of alcohol and cetirizine appeared to be additive. Certain cetirizine-placebo differences in subjective feelings and test battery performance were also significant. Loratadine had no significant effect on any performance parameter. It was concluded that cetirizine, but not loratadine, generally caused mild impairment of performance after a single 10 mg dose.

Fexofenadine's effects, alone and with alcohol, on actual driving and psychomotor performance

BACKGROUND Fexofenadine is the hydrochloride salt of terfenadines active metabolite. OBJECTIVE Fexofenadines effects on performance were assessed in this study for the purpose of determining its safety of use by patients who engage in potentially dangerous activities, especially car driving. METHODS Fexofenadine was administered in daily doses of 120 or 240 mg, each in single and divided units given over 5 days. Two milligrams of clemastine given twice daily and placebo were given in similar series. Twenty-four healthy volunteers (12 men, 12 women; age range, 21 to 45 years) participated in a double-blind six-way crossover study. Psychomotor tests (critical tracking, choice reaction time, and sustained attention) and a standardized actual driving test were undertaken between 1.5 to 4 hours after administration of the morning dose on days 1, 4, and 5 of each series. On day 5, subjects were challenged with a moderate alcohol dose before testing. RESULTS Fexofenadine did not impair driving performance. On the contrary, driving performance was consistently better during twice daily treatment with 120 mg fexofenadine than during treatment with placebo, significantly so on day 4. Both of the 240 mg/day regimens significantly attenuated alcohols adverse effect on driving on day 5. Effects in psychomotor tests were not significant, with the exception of the critical tracking test in which the first single doses of fexofenadine, 120 and 240 mg, had significantly impairing effects. CONCLUSION It was concluded that fexofenadine has no effect on performance after being taken in the recommended dosage of 60 mg twice daily.

Residual effects of evening and middle-of-the-night administration of zaleplon 10 and 20 mg on memory and actual driving performance

Zaleplon, a new pyrazolopyrimidine hypnotic, possesses an unusually short elimination half‐life (ca 1 h). This study was conducted to determine whether middle‐of‐the‐night administration of zaleplon affects memory or driving performance the following morning. Twenty‐eight healthy volunteers participated in a double‐blind, 7‐way, crossover study. They ingested capsules twice on each treatment night; once before initiating sleep and again after being briefly awakened 5 h later. Treatments were: placebo at both times, zaleplon 10 or 20 mg, or zopiclone 7·5 mg followed by placebo, or the same in reverse order. Subjects arose 3 h after the second dose. One hour later, sleep quality and mood were assessed by questionnaires and balance and memory in a test battery. A standardized actual driving test was undertaken between 5 and 6 h after the second dose. All drugs similarly improved sleep quality, but only zopiclone hindered awakening. Evening zaleplon doses were without significant effects. Late‐night zaleplon had minor effects in one memory test. Evening zopiclone shared these effects and also significantly impaired driving performance. Late‐night zopiclones effects were significant in every test. Its effects on driving were severe. The results suggest that zaleplon 10 mg certainly, and 20 mg probably, can be taken at bedtime or later in the night, up to 5 h before driving with little risk of serious impairment.

Acrivastine, terfenadine and diphenhydramine effects on driving performance as a function of dose and time after dosing

The study was conducted according to a nineway, observer- and subject-blind, cross-over design. Its purpose was to compare the single-dose effects of the following drugs on driving performance: acrivastine (8, 16 and 24 mg); the combination of acrivastine (8 mg) with pseudoephedrine (60 mg); terfenadine (60, 120 and 180 mg); diphenhydramine-HCL (50 mg); and placebo. The subjects were 18 healthy female volunteers. Drug effects were assessed in two repetitions of two driving tests (highway driving and car-following) after each treatment.Acrivastines impairing effects in both driving tests were similarly dose-related. The 8-mg dose had a small, but significant, effect on highway driving in the first trial. The 16-mg and 24-mg doses significantly impaired driving in both tests during the first trial and the 24-mg dose did so again during the second trial.Neither the combination of acrivastine with pseudoephedrine nor terfenadine caused any significant impairment of performance.Diphenhydramine significantly impaired driving in both tests during every trial.In conclusion, the normal therapeutic dose of acrivastine (8 mg) had little effect on driving performance, and virtually none when that dose was given in combination with pseudoephedrine (60 mg). Higher doses of acrivastine severely impaired driving performance. Terfenadine had no significant effect on driving performance after any dose while diphenhydramine strongly impaired every important driving parameter.

Effects of emedastine and cetirizine, alone and with alcohol, on actual driving of males and females

Emedastine is registered in its country of origin (Japan) as an antihistamine for the indication of seasonal allergic rhinitis. Further research on the drugs sedating properties was needed to secure its registration elsewhere. The present study was designed to compare the effects of emedastine 2 mg and 4 mg twice daily after single and repeated doses, on actual driving performance versus those of cetirizine 10 mg once daily and placebo; and to determine how repeated doses of each drug interact with alcohol to affect driving. Each treatment was administered for 5 days to 19 healthy volunteers (nine men and ten women, aged 21–45 years) according to a four-period double-blind cross-over design. Driving performance was measured in a standardized test between 3 and 4 h after administration of the morning dose on days 1, 4 and 5. Alcohol, sufficient for achieving a blood alcohol concentration of 0.05 g/dl was given before driving on day 5 of each period. Both emedastine doses similarly and significantly impaired driving in every test. The effects of cetirizine were less. They were significant over days 1, 4 and 5 combined, although not separately. Women were more impaired by both drugs. Alcohol increased driving impairment similarly in every condition. Subjects were only able to discriminate the sedating and impairing effects of the first dose of emedastine 4 mg from placebo. Emedastine, in oral doses of 2mg and 4 mg twice daily, is sedating and impairs driving. The drug could therefore constitute a traffic hazard and its users should be warned accordingly.

Effects of mizolastine and clemastine on actual driving and psychomotor performance in healthy volunteers

The acute effect of doses of mizolastine 5, 10, 20 and 40 mg, an active control (clemastine 2 mg) and placebo on actual car driving and psychomotor performance have been compared. Twenty four healthy volunteers were treated according to a double-blind, 6-way cross-over design. In the driving test, lasting about 1 h, lateral position control and speed were continuously measured; the psychomotor test battery, lasting 50 min, comprised critical flicker-fusion frequency, critical instability tracking, divided attention, memory search and choice reaction time, and vigilance studies; and mood changes and possible adverse-effects were rated on visual analogue scales.The results showed a dose-response relationship: mizolastine 40 and 20 mg impaired driving and psychomotor performance. The effect of mizolastine 40 mg on driving was strongly correlated with that of clemastine (r=0.78) and was comparable to the effect of a blood ethanol level of 0.8 mg·ml−1. Mizolastine 5 mg and 10 mg did not have a significant effect on driving performance and psychomotor tests.It was concluded that at a 10 mg dose of mizolastine, the therapeutic dose, it could be considered a safe antihistamine, although individual adverse reactions cannot be completely ruled out.

Effects of mefloquine alone and with alcohol on psychomotor and driving performance

Objective: To determine whether mefloquine, a quinoline antimalarial drug, affects psychomotor and actual driving performance when given in a prophylactic regimen, alone or in combination with alcohol.Methods:Forty male and female volunteers were randomly assigned in equal numbers to two groups, and were treated double-blind for one month with mefloquine and placebo. The medication was taken in a 250 mg dose on the evenings of Days 1, 2, 3, 8, 15, 22 and 29. Testing was done on Days 4, 23 and 30, the latter after repeated doses of alcohol sufficient to sustain a blood concentration of about 0.35 mg ⋅ml−1. Two real driving tests were used to measure prolonged (1 h) road tracking and car following performance. Critical Flicker/Fusion Frequency (CFF), critical instability tracking and body sway were also measured in the laboratory.Results:Mefloquine caused no significant impairment in any test at any time relative to placebo. It significantly improved road tracking performance on Day 4. A significant interaction between prior treatment and alcohol was found in the body sway test, as the alcohol-induced change was less after mefloquine than placebo. The sensitivity of the driving test and the CFF test were shown by the significant overall effect of alcohol which did not discriminate between the two prior treatments.Conclusion:Mefloquine did not impair driving performance but rather improved it in the longer test, suggesting that the drug may possess psychostimulating properties.

Considering the P450 cytochrome system as determining combined effects of antidepressants and benzodiazepines on actual driving performance of depressed outpatients.

Parallel groups of depressed (DSM III-R) outpatients received moclobemide (n = 22) and fluoxetine (n = 19), double blind, for 6 weeks. Respective starting doses were 150 mg twice a day and 20 mg q.a.m. These could be doubled after 3 weeks for greater efficacy. Chronic users of benzodiazepine anxiolytics continued taking them as comedication. Therapeutic and side effects were assessed using conventional rating scales. Actual driving performance was assessed during the week before therapy and at 1, 3 and 6 weeks thereafter using a standardized test that measures standard deviation of lateral position (SDLP). Similar remissions in depressive symptoms and side effects occurred in both groups. Patients drove with normal and reliable (r = 0.87) SDLPs before treatments. Most continued to do so but a few drove with progressively rising SDLPs and the overall trends were significant in both groups (p < 0.03). A post-hoc multiple regression analysis was applied for identifying factors that correlated with SDLP in separate tests after the beginning of therapy. At 3 and 6 weeks there were significant (p < 0.03) relationships involving the same factor; patients who drove with progressively higher SDLPs appeared to be those using benzodiazepines that are metabolized by a P450 isozyme subject to inhibition by their particular antidepressant.