John C. Kuehnle

Plasma Testosterone Levels before, during and after Chronic Marihuana Smoking

Abstract To test the relation between chronic marihuana use and testosterone levels, we studied 27 men, 21 to 26 years of age. Plasma testosterone was measured daily before, during, and after a 21-...

Experimental analysis of the 'happy hour": effects of purchase price on alcohol consumption.

An experimental analogue of a discount drink policy known as the ‘happy hour’ was used to study the effects of purchase price on drinking behavior. Male volunteers with a prior history of either casual (N=20) or heavy (N=14) drinking were given free access to beverage alcohol during a 20-day period. Approximately half the subjects could purchase alcohol under a single-price condition (50 ¢/drink), while a matched group was given a price reduction daily (25 ¢/drink) during a three-hour period in the afternoon. The results demonstrated that the afternoon price reduction significantly increased alcohol consumption in both casual and heavy drinkers. Reinstatement of the standard purchase price effectively suppressed drinking in both groups. The findings are discussed in terms of the theoretical and research implications of environmental influences on drinking.

Effects of heroin self-administration on cigarette smoking

Cigarette smoking increased during heroin self-administration in comparison to drug-free and methadone detoxification conditions in eight heroin addicts given naltrexone placebo (P<0.01) and three heroin addicts given buprenorphine placebo. Cigarette smoking was stable across conditions for one subject who did not use heroin during naltrexone blockade of heroin effects. Five subjects smoked significantly more (P<0.01) during the hour following a heroin injection than during the preceding hour, and two subjects in the same group smoked significantly less following a heroin injection (P<0.05). Subjects smoked significantly more during the evening and night when self-administering heroin than during baseline conditions (P<0.05), but subjects did not sleep significantly less during heroin self-administration. The peak of the intercigarette interval distribution remained between 16–30 min during baseline and heroin conditions. However, the increased smoking during heroin use appeared to reflect a higher rate of smoking rather than a generalized increase across intercigarette intervals. These data extend previous findings, that alcohol consumption is associated with increased cigarette smoking, to IV heroin self-administration.

Effects of marihuana use on body weight and caloric intake in humans

Body weight and caloric intake were measured in a group of heavy and casual marihuana users prior to, during and following 21 days of marihuana smoking under research ward conditions. A group of control subjects were studied under identical conditions, but they did not smoke marihuana. Both heavy and casual marihuana users had a significant increase in caloric intake and gained weight during the marihuana smoking period. Heavy and casual users gained an average of 3.7 and 2.8 lbs respectively during the first 5 days of marihuana smoking. In contrast, control subjects gained only a small amount of weight (0.2 lbs) during the same time interval. Water retention did not appear to be a major factor in weight gain by the marihuana users. These findings are in agreement with both anecdotal reports and previous experimental data that marihuana use is associated with increased caloric intake and weight gain.

Buprenorphine Effects on Morphine- and Cocaine-Induced Subjective Responses by Drug-Dependent Men

The effects of daily buprenorphine treatment (4 or 8 mg/day, sublingual) on reports of subjective effects after single intravenous doses of morphine (10 mg), cocaine (30 mg), and saline placebo were studied on an inpatient clinical research ward in 26 men concurrently dependent on opioids and cocaine (DSM-III-R). Latency to detection and certainty of a drug effect, as well as drug quality (intensity, euphoria, and dysphoria), were studied before and after 10 to 12 days of buprenorphine maintenance. Saline was accurately identified by all 26 patients during the drugfree baseline and by 25 patients during buprenorphine maintenance conditions. All patients accurately identified morphine during the drugfree period before treatment with buprenorphine, but 18 (69%) of 26 patients were unable to detect morphine during buprenorphine maintenance and 2 misidentified morphine as cocaine. Six men (23%) accurately identified morphine and reported that the intensity and quality of morphines effects were equivalent to drugfree conditions. Cocaine levels in plasma 5 minutes after intravenous cocaine injection were equivalent before and during buprenorphine treatment and averaged 282.8 +/- 43.6 and 295.2 +/- 28.8 ng/ml during 4 and 8 mg/day of buprenorphine maintenance, respectively. All patients accurately identified cocaine before and during buprenorphine maintenance, and there were no significant changes in latency to detection and certainty of a drug effect or reports of cocaine-induced intensity or euphoria during buprenorphine treatment. The concordance between responses to morphine and cocaine during inpatient buprenorphine maintenance and drug use during the first 4 weeks of outpatient buprenorphine treatment was also examined in 16 men. The effects of buprenorphine on individual responses to an acute intravenous dose of morphine or cocaine during the inpatient study did not reliably predict the frequency of heroin or cocaine self-administration during the first 4 weeks of daily outpatient buprenorphine maintenance.

BEHAVIORAL AND BIOLOGIC ASPECTS OF MARIJUANA USE

Before the current decade, only three comprehensive studies of the effects of repeat-dose marijuana administration had been conducted.zs45,52 Our current data base has been expanded considerably and has been reviewed in part in several comprehensive publicatiorsz53 Yet, despite an exponential increment in our fund of information about the effects of marijuana on human biologic function and behavior, we are still far from certain about the type and nature of any subtle, and perhaps disastrous, consequences that may be associated with long-term marijuana use. Data presented in this paper reprint an overview of a series of multidisciplinary studies conducted in our laboratory. The major questions that we addressed in this research were similar to those we have posed in previous These questions were: “Does chronic use of marijuana systematically affect motivation to engage in a variety of social and goal-directed activities? Are there constant relationships between free-choice marijuana intake and antecedent and consequent mood states? What are the relationships between free-choice marijuana intake and patterns of verbal interaction? What are the relationships between free-choice marijuana intake and performance on psychologic tasks that assess such functions as problem solving and risk taking, memory, time estimation, and cognitive function? And, finally, are physiologic and biochemical changes associated with repeated doses of marijuana?” Some answers for these questions are provided in each of the topical sections of this manuscript. This report is a summary of the current “state of science” for ongoing research in our laboratory and clinical research facility. More detailed presentations of data obtained in studies of behavorial and social reactions, group interaction, and tolerance will be published by Dr. Babor and his associates. Dr. A. Michael Rossi and his colleagues will report in subsequent publications on studies of mood, short-term memory, vigilance, and reaction time. Drs. Kuehnle and Bernstein have submitted data for publication on psychiatric aspects and cardiac and pulmonary function. Drs. Greenberg and Mello and their associates have presented a detailed description of studies of operant behavior elsewhere in this monograph. One of the most important joints we would like to emphasize is the 35, 37.

Acute interactions of buprenorphine with intravenous cocaine and morphine : an investigational new drug phase I safety evaluation

Recent preclinical and clinical studies suggest that buprenorphine, an opioid mixed agonist-antagonist, may be useful for the treatment of dual dependence on cocaine and opiates. This report describes an inpatient clinical evaluation of the safety of buprenorphine alone and in combination with single doses of cocaine and morphine. Twenty subjects with a DSM-III-R diagnosis of concurrent cocaine and opioid dependence were randomly assigned to maintenance treatment with single daily doses of 4 or 8 mg of sublingual buprenorphine for 21 days. Side effects and vital signs were evaluated every day once every 8 hours and for 2 hours after daily buprenorphine administration. The physiologic effects of a single-blind challenge dose of cocaine (30 mg intravenously), morphine (10 mg intravenously), and intravenous saline placebo were measured before and during buprenorphine maintenance. Before buprenorphine maintenance, subjects underwent methadone detoxification followed by a 9-day drugfree period. Three baseline single-blind challenge dose studies were conducted on study days 7, 8, and 9 during the drug-free period. Cardiovascular responses to cocaine and to morphine were equivalent under drugfree and buprenorphine maintenance conditions. Respiration and temperature changes in response to cocaine were also equivalent before and during buprenorphine maintenance. Respiratory rates were slightly lower after morphine administration during maintenance on 8 mg of buprenorphine, but this was not statistically significant. Mild opioid agonist-like side effects were reported during buprenorphine induction and maintenance. These included headache, sedation, nasal discharge, abdominal discomfort, and anxiety. Most opioid agonist side effects decreased within 12 to 14 days. An electrocardiogram and blood chemistry measures were normal before and during buprenorphine maintenance. These data suggest that daily maintenance on buprenorphine is not associated with adverse side effects or toxic interactions with a single acute dose of intravenous cocaine or morphine.

Effect of acute ethanol ingestion on integrated plasma prolactin levels in normal men

Healthy male subjects ingested 1.0 g ethanol/kg (Alcohol Day) and caloric equivalents of sucrose (Control Day). Plasma prolactin was determined on samples collected at 20-min intervals by serial constant blood exfusion, from 2 hr before to 4 hr after the drink. In 14 of the 15 men studied, plasma prolactin levels during the 2-hr period after alcohol administration were elevated an average of 31% above values for the preceding 2-hr period. Data pooled for all subjects revealed a small but statistically significant increase in prolactin coinciding with ascending and peak concentrations of blood alcohol. A significant increment in prolactin was associated with peak blood alcohol levels when values were compared between control and alcohol treatment days. Although of statistical significance, these transient and variable increases were within the normal range of basal prolactin levels for most subjects and are unlikely to be physiologically meaningful.

Marihuana and mood in human volunteers.

Fifteen adult male marihuana smokers volunteered to live on a hospital research ward for a 31-day study which included a five-day baseline, a 21-day marihuana smoking period and a concluding five-day baseline. Subjects rated their moods and level of intoxication each day at scheduled occasions. Analyses of variance indicated a significant trend in the mood ratings which increased slightly in the euphoric direction just before smoking marihuana (compared to routine ratings) and further increased slightly after smoking marihuana. Level of intoxication ratings and mood ratings were not significantly correlated, but an intoxicated subjects mood ratings were significantly correlated with the average mood ratings of other subjects intoxicated or not. The results suggest that marihuana may increase a persons susceptibility to the moods of others and the feeling of being in harmony with others may be a positive reinforcer.

Propranolol and behavior of alcohol addicts after acute alcohol ingestion.

Sixty‐four adult male chronic alcoholic addicts were studied to assess the effects of propranolol pretreatment on behavioral changes induced by acute ingestion of alcohol. The study was carried out under controlled research ward conditions with a double‐blind technique. Pretreatment with 10, 20, and 40 mg of propranolol 4 times a day for 3 consecutive days prior to alcohol administration failed to block or attenuate cognitive, perceptual, motor, and affective changes induced by acute alcohol intoxication.