Effects of smoking marijuana on focal attention and brain blood flow

Using an attention task to control cognitive state, we previously found that smoking marijuana changes regional cerebral blood flow (rCBF). The present study measured rCBF during tasks requiring attention to left and right ears in different conditions. Twelve occasional marijuana users (mean age 23.5 years) were imaged with PET using [15O]water after smoking marijuana or placebo cigarettes as they performed a reaction time (RT) baseline task, and a dichotic listening task with attend-right- and attend-left-ear instructions. Smoking marijuana, but not placebo, resulted in increased normalized rCBF in orbital frontal cortex, anterior cingulate, temporal pole, insula, and cerebellum. RCBF was reduced in visual and auditory cortices. These changes occurred in all three tasks and replicated our earlier studies. They appear to reflect the direct effects of marijuana on the brain. Smoking marijuana lowered rCBF in auditory cortices compared to placebo but did not alter the normal pattern of attention-related rCBF asymmetry (i.e., greater rCBF in the temporal lobe contralateral to the direction of attention) that was also observed after placebo. These data indicate that marijuana has dramatic direct effects on rCBF, but causes relatively little change in the normal pattern of task-related rCBF on this auditory focused attention task.     

Effects of marijuana smoking on subjective ratings and tobacco smoking

Multiple measures of tobacco cigarette smoking and subjective and physiological effect were collected during 90 minute test sessions in volunteer cigarette smokers who also had histories of recreational marijuana use. Before sessions, subjects smoked one marijuana cigarette (placebo or 1.29%, 2.84%, 4.00%) using a standardized puffing procedure. Each dose and placebo was given four times to each subject in a randomized block sequence. Marijuana smoking produced dose-related increases in heart rate, ratings of dose strength and drug liking. However, marijuana produced no significant alterations in tobacco cigarette smoking. Puff duration within each marijuana cigarette varied in a fashion similar to that observed in previous studies of tobacco cigarette smoking: puff duration progressively decreased as the cigarette was smoked. This effect is probably due to progressive decreases in resistance to draw as the cigarette is smoked. Expired air carbon monoxide (CO) levels following marijuana smoking were inversely related to marijuana dose, suggesting the occurrence of some compensatory changes in marijuana smoking in response to dose manipulations. It is concluded that, although marijuana produces dose-related effects on physiological and subjective effects and on marijuana smoking behavior, marijuana differs from a variety of other psychoactive drugs previously studied in this paradigm in that no reliable changes in tobacco smoking were produced.     

Acute effects of marijuana on cognition: relationships to chronic effects and smoking techniques.

A double-blind, placebo-controlled study assessed acute effects on human cognition of marijuana smoking involving long or short durations of inhalation and breath holding. During eight test sessions, 48 adult, male volunteers completed standardized, pencil-and-paper tests of educational development and ability, as well as computerized tests of learning, associative processes, abstraction, and psychomotor performance. Marijuana impaired all capabilities except abstraction and vocabulary. These impairments were more pervasive than those associated with heavy, chronic marijuana use in a previous study involving the same tests, but showed some similarities. Marijuana altered associative processes, encouraging more uncommon associations. Marijuana-induced impairment in learning pairs of words was influenced by associative relationships between the words. There were a few hints that prolonged breath holding increased marijuana's effects under some test conditions, but in general it did not. Prolonged breath holding itself affected performance in four tests, regardless of whether subjects smoked marijuana or placebo. Whether physiological or psychological factors (e.g., exposure to carbon monoxide in smoke or subjects' expectations) produced these effects could not be determined.     

Effects of chronic marijuana use on human cognition

Impairments of human cognition and learning following chronic marijuana use are of serious concern, but have not been clearly demonstrated. To determine whether such impairments occurred, this study compared performance of adult marijuana users and non-users (N=144 andN=72, respectively) matched on intellectual functioning before the onset of drug use, i.e., on scores from standardized tests administered during the fourth grade of grammar school (Iowa Tests of Basic Skills). Subjects were given the twelfth grade versions of these tests (Iowa Tests of Educational Development) and other, computerized cognitive tests in successive test sessions. Heavy marijuana use (defined by use seven or more times weekly) was associated with deficits in mathematical skills and verbal expression in the Iowa Tests of Educational Development and selective impairments in memory retrieval processes in Buschke's Test. The retrieval impairments were restricted to words that were easy to visualize. Impairments depended on the frequency of chronic marijuana use, i.e., light and intermediate marijuana use (defined by use one to four and five to six times weekly, respectively) were not associated with deficits. Intermediate use was associated with superior performance in one condition (fuzzy concepts) of a Concept Formation test.     

Effects of acute marijuana smoking in post-menopausal women

Acute effects of marijuana and placebo cigarette smoking on pulse rate and self-estimations of mood and level of intoxication were studied in ten post-menopausal women. Six women had no prior experience with marijuana. Four subjects had a total of seven marijuana smoking experiences, none of which occurred during the past year. Statistically significant increases in pulse rate and level of intoxication followed marijuana but not placebo cigarette smoking. Marijuana smoking also induced a significant increase in symptoms of confusion and a decrease in self-report indices of arousal.     

Effects of acute marijuana smoking on pulse rate and mood states in women

The effects of marijuana cigarette (1.8% THC) smoking on pulse rate and mood were studied under double-blind placebo-controlled conditions in 28 adult female volunteers during the follicular, luteal, and ovulatory phases of the menstrual cycle. Statistically significant increases in pulse rate, subjective levels of intoxication, and the POMS confusion factor occurred after marijuana smoking. However, no statistically significant differences for any measure were observed following marijuana smoking as a function of menstrual cycle phase. Subjects with a past history of intermittent marijuana use (five or less times weekly) had significantly higher pulse rates, subjective levels of intoxication, and POMS confusion factor scores than did subjects with a past history of regular (six or more times weekly) marijuana use. Persistence of marijuana-induced changes in pulse rate, intoxication, and confusion were also of longer duration for subjects with a past history of intermittent marijuana smoking. The influence of past history of marijuana use on marijuana-induced alterations in pulse rate, intoxication, and mood for females appears to be similar to males. These similarities are not attenuated as a function of the menstrualcycle phase of females.     

Kinetic study of smoking marijuana

Six subjects each smoked a 1% marijuana cigarette and 2 hr later smoked a second one. Plasma levels of delta-9-tetrahydrocannabinol were measured for 9 hr with a radioimmunoassay. Heart rate and self-reported high were measured for 2 hr after each cigarette. All three measures showed a rapid increase after the start of smoking with C_max occurring before the end of smoking. There was a strong correlation between decrease in heart rate and plasma levels from 10 min after smoking until 120 min. All pharmacodynamic response measures returned to baseline values within approximately 2 hr.     

Kinetic study of smoking marijuana

Six subjects each smoked a 1% marijuana cigarette and 2 hr later smoked a second one. Plasma levels of delta-9-tetrahydrocannabinol were measured for 9 hr with a radioimmunoassay. Heart rate and self-reported "high" were measured for 2 hr after each cigarette. All three measures showed a rapid increase after the start of smoking with Cmax occurring before the end of smoking. There was a strong correlation between decrease in heart rate and plasma levels from 10 min after smoking until 120 min. All pharmacodynamic response measures returned to baseline values within approximately 2 hr.     

Effects of tetrahydrocannabinol content on marijuana smoking behavior, subjective reports, and performance

This study investigated the smoking topography of marijuana and its effect on heart rate, subjective reports, and cognitive/psychomotor task performance. Male subjects (N = 12) with histories of moderate marijuana use smoked ad lib one cigarette containing 0, 1.3, or 2.7% delta 9-THC on separate days. Smoking topography measures revealed smaller puff and inhalation volumes and shorter puff duration for the high marijuana dose compared to the low dose. No other smoking behavior differed between the active doses. Heart rate was increased dose dependently over placebo levels. Active marijuana also increased subjective reports of drug effect over placebo, but not dose dependently. Significant memory impairment was observed on a forward and reverse digit span task, and performance was impaired on the digit symbol substitution task by the high, but not low, dose of marijuana. Performance on a divided attention task was not affected by marijuana. Thus, although subjects adjusted their smoking of cigarettes varying in THC content, dose-related effects of marijuana were obtained on several measures. The observed differences and individual variation in smoking topography measures suggest that precise control of smoking behavior would improve the accuracy of marijuana dose delivery.     

Toxicity of marijuana and tobacco smoking in the beagle.

Four cigarettes of marijuana or tobacco in the form of smoke inhaled into the trachea were administered to dogs daily over a period of nine months. Marijuana caused a slowing of body weight gain. Food consumption increased at first and was accompanied by diarrhea; then it decreased. This suggests a malabsorption of food or a more fundamental metabolic disturbance. The tobacco smoking group consumed much less food without showing any significant change in body weight gain in 3 and 6 months, but it did in 9 months only. In marijuana smoking dog, blood pressure remained unchanged. The resting heart rate was increased (by 32% at 3, 30% at 6, and 15% at 9 months). Alpha1-globulin, eosinophils and lymphocyte count were significantly decreased. A decrease in serum triglycerides was noted. In addition, a behavioral study permitted us to note a general perturbation in the behaviour of the marijuana smoking dogs. The dogs showed impairment of learning, probably due to these behavioral perturbations.     

Effects of cigarette smoking and nicotine nasal spray on psychiatric symptoms and cognition in schizophrenia.

Schizophrenic patients have among the highest rates of smoking of any group of patients. Previous studies have identified psychophysiological and potential nicotinic receptor abnormalities which may be associated with this phenomenon. The effects of acute smoking or acute administration of nicotine nasal spray, after smoking abstinence, on negative symptoms and neurocognitive function have been less extensively studied in experimental designs. This study investigated the effects of smoking of high nicotine or denicotinized cigarettes, and receiving active or placebo nicotine nasal sprays, on positive and negative symptoms and cognitive functions in schizophrenic patients. The study utilized a placebo controlled crossover experimental design with pre- and post-drug evaluations on each experimental day. Smoking high nicotine cigarettes decreased negative symptoms more than denicotinized cigarettes, but smoking neither cigarette changed scores of positive symptoms, anxiety, or depression. Active nicotine nasal spray did not differentially decrease negative symptoms compared with placebo, but did improve performance on a spatial organization task, and tended to improve some measures of verbal memory and two-choice reaction time in schizophrenic patients. Both high and denicotinized cigarettes improved performance on the spatial processing task, but there was no statistically significant differential drug (Cigarette type) effect. These results suggest that acute smoking of cigarettes may transiently decrease negative symptoms in patients with schizophrenia, but it is unclear whether this effect is attributable to nicotine, other components of cigarettes, or the act of smoking. Nicotine nasal spray may modestly improve some selected aspects of cognitive function in schizophrenia.     

Effects of varying marijuana smoking profile on deposition of tar and absorption of CO and delta-9-THC.

We investigated the effects of previously observed differences in smoking technique for marijuana (M) versus tobacco (T) on the amount of inhaled tar, the percentage retention of inhaled tar in the lung, the pre- to postcigarette boost in blood carboxyhemoglobin (COHb) and in serum delta-9-tetrahydrocannabinol (THC concentrations), and psychophysiologic responses to THC (increased heart rate and subjective "high"). Ten healthy, habitual smokers of M were studied on 6 separate days. On each day, subjects smoked a single M cigarette (approximately 900 mg, 1.24% delta-9-THC) using one of 6 different smoking profiles typical for marijuana [puff volume (PV) approximately 70 ml; breathholding time, (BHT) 14-16 s] or tobacco (PV approximately 45 ml; BHT 4-5 s) or a combination of the two techniques (PV approximately 70 ml and BHT 4-5 s; or PV approximately 45 ml and BHT 14-16 s). Inhaled volume (1.5 liters), interpuff interval (30 s) and number of puffs (6) were all fixed, except that for the approximately 45-ml PV condition, the number of puffs was increased to 10 in 2 additional sessions to standardize the total amount of cigarette consumed to that of the approximately 70-ml PV condition. The longer BHT significantly increased both percent retention of tar in the lung and the pre- to postsmoking rise in blood COHb, serum THC and heart rate, independent of puff volume and number. In contrast, the larger PV had no significant influence on these variables for the same amount of cigarette consumed.(ABSTRACT TRUNCATED AT 250 WORDS)     

The pharmacologic effects of daily marijuana smoking in humans.

Six healthy male, paid volunteers smoked one NIDA cigarette containing 1.0% THC each day for 13 consecutive days. They were tested before and after the period of drug administration by the following procedure: the subjects smoked one NIDA marijuana cigarette containing 1.0% THC followed 15 minutes later by the intravenous infusion of 52 micrograms/min of deuterated THC for 50 minutes. The THC plasma concentrations, ratings of "high" and heart rate effects produced by the combined drug administration were measured, and absolute bioavailability of smoked THC was calculated on Days 1 and 22. Statistical analyses indicate that the only significant changes induced by daily marijuana exposure were in cardioacceleration.     

Cigarette smoking among marijuana users in the United States.

The vast majority of drug users smoke cigarettes. Most use marijuana and no other illicit drug. We analyzed adult responses to the 1997 NHSDA (n = 16,661) to explore relationships between marijuana use and cigarette smoking. Multivariate analyses controlled for other illicit drug use and other potential covariates. Nearly three-quarters of current marijuana users (74%) smoked cigarettes. Compared to nonusers, the adjusted odds of being a smoker were 5.43 for current marijuana users, 3.58 for past year marijuana users, and 2.02 for former marijuana users. Odds for cigarette smoking among current poly-drug users, compared to nonusers, were 2.3 to 1. Level of cigarette smoking was directly associated with frequency of marijuana use. Nationwide, an estimated 7 million adults smoke both substances and are at increased risk for respiratory illnesses and mortality. Cigarette smoking is a major co-morbidity of marijuana use and smoking cessation should be addressed among marijuana users in addition to their other illicit drug involvement.     

Sex, drugs, and cognition: effects of marijuana

Despite the knowledge that many drugs affect men and women differently, few studies exploring the effects of marijuana use on cognition have included women. Findings from both animal and human studies suggest marijuana may have more marked effects in women. This study examined sex differences in the acute effects of marijuana on cognition in 70 (n=35 male, 35 female) occasional users of marijuana. Tasks were chosen to tap a wide variety of cognitive domains affected by sex and/or marijuana including attention, cognitive flexibility, time estimation, and visuospatial processing. As expected, acute marijuana use impaired performance on selective and divided attention, time estimation, and cognitive flexibility. While there did not appear to be sex differences in marijuana's effects on cognition, women requested to discontinue the smoking session more often than men, likely leading to an underestimation of differences. Further study of psychological differences in marijuana's effects on men and women following both acute and residual effects of marijuana is warranted.     

Tetrahydrocannabinol content and differences in marijuana smoking behavior

Changes in smoking behavior in response to a change in marijuana potency were measured in marijuana users. A marijuana cigarette containing 1.2% or 3.9% tetrahydrocannabinol (THC) was smoked on separate days by ten experienced users. Puff volume, duration and number, interpuff interval, inhalation volume and duration were averaged for each cigarette. The high potency cigarettes were smoked with more puffs and longer interpuff intervals, but also with greater inhaled volumes of air, thereby diluting the marijuana smoke.     

Effects of attitude change on behavior for highly involving issues: The case of marijuana smoking

Two studies investigated the immediate effects of persuasive communications on marijuana attitudes, intentions and behavior as well as delayed impact over a 6-week follow-up period. The persuasive appeals were directed at beliefs that were the most important predictors of behavior. Results indicated that certain beliefs (e.g., hedonism) were highly resistant whereas others (e.g., control of actions) were somewhat more amenable to influence attempts. However, even when attitude change was successful, correspondent changes in intentions and behavior did not necessarily follow. The need to further study resistance factors and the apparent complexity of the attitude-behavior relationship for the real-life, highly involving topics of marijuana use in particular and addictive behaviors more generally was discussed.