Marijuana: Dose effects on pulse rate,subjective estimates of intoxication,free recall and recognition memory

The effect of marijuana on memory as measured by free recall and recognition, pulse rate and self ratings of intoxication was evaluated in 16 male volunteers. Marijuana containing 0, 5, 10 or 15 mg Δ⁹-THC was evaluated to all subjects by smoking in 4 sessions separated by a 1 week interval. Free recall was reduced in a dose related manner by the drug, but recognition memory was unaffected. A 2 sec word presentation rate produced inferior recall in comparison to a 4 sec rate, but this variable did not interact with drug condition. Intrusion errors increased following intoxication but this effect was not systematically related to dosage of Δ⁹-THC. Both pulse ratings of intoxication increased with dosage.     

Facilitation of brain stimulation reward byΔ 9-tetrahydrocannabinol

The present experiment explored whetherΔ ⁹-tetrahydrocannabinol (Δ ⁹-THC), the psychoactive ingredient in marijuana, shares with other drugs of abuse the ability to facilitate brain stimulation reward acutely, as measured by clectrical intracranial self-stimulation (ICSS). Laboratory rats were implanted with stimulation electrodes in the medial forebrain bundle, and trained to stable performance on a self-titrating threshold ICSS paradigm.Δ ⁹-THC, at a dose believed pharmacologically relevant to moderate human use of marijuana, acutely lowered ICSS thresholds, suggesting that marijuana acts on similar CNS hedonic systems to most other drugs of abuse.     

Ipsilateral turning behavior induced by unilateral microinjections of a cannabinoid into the rat subthalamic nucleus

The subthalamic nucleus contains cannabinoid receptors and cannabinoid receptor mRNA. However, the role of cannabinoid receptors in this nucleus has not been examined. In order to investigate the functional role of cannabinoid receptors in the rat subthalamic nucleus, turning activity was observed following unilateral microinjection of the synthetic cannabinoid CP 55,940. CP 55,940 (10 μg) induced ipsilateral turning. This effect was blocked by coadministration of the cannabinoid receptor antagonist SR141716A (5 μg). These results suggest that cannabinoid receptors in the subthalamic nucleus mediate an inhibition of motor activity.     

Short-term effects of marijuana smoking on cognitive behavior in experienced male users

The effects of smoking marijuana on the ability to use abstract concepts was tested in 12 experienced marijuana users. Each subject was tested three times, after smoking prepared 300 mg cigarettes containing either 0, 1.5 or 2.9% ⁹-THC in different sessions according to a Latin Square design. The same number of whole and/or partial cigarettes was smoked by each subject in each of the three sessions. This was determined for individual subjects by the number of 2.9% ⁹-THC marijuana cigarettes that the subject had been willing to smoke in a pre-experimental session up to a maximum of 1200 mg. The following tests of concept formation and usage were used: 1. a letter series test; 2. a word grouping test; 3. a conceptual clustering memory test; 4. a closure speed test; 5. Witkin's Embedded Figures Test; 6. a size weight illusion test; 7. Luchin's Water Jar Test; 8. Luchin's Hidden Word Test; and 9. an anagram test. Marijuana smoking led to a dose-related impairment on the letter series, word grouping, closure speed, and Embedded Figures test. Performance on the size-weight illusion, Luchin's Water Jar, Luchin's Hidden Word, and the anagram tests were unaffected. Conceptual clustering decreased after marijuana smoking. In most cases only the differences between 0 and 2.9% ⁹-THC marijuana were statistically significant.This study is a partial report of a Ph. D. dissertation of J. H. P. submitted to the University of Michigan while on a USPHS predoctoral traineeship, NIMH, USPHS 5TOI MH-0667-13. Also supported in part by grant USPHS MH-11846.     

An abstinence syndrome following chronic administration of delta-9-tetrahydrocannabinol in rhesus monkeys

Chaired, chronically catheterized rhesus monkeys were administered IV delta-9-tetrahydrocannabinol (THC), 0.5 mg/kg every 6 h for 3 weeks. Following the first THC injection, the animals appeared heavy-lidded, immobile, and unresponsive to observation. Tolerance developed to these behaviors during the 3 weeks of THC administration, although the animals remained subdued compared to baseline. Following discontinuation of THC, animals showed an increase in gross movement, eye contact, and tooth baring of greater frequency and/or duration than observed before THC. This presumably represents a cannabis abstinence syndrome.     

Tuberculosis outbreak in marijuana users, Seattle, Washington, 2004

Matching Mycobacterium tuberculosis isolates were noted among 11 young tuberculosis patients socially linked through illicit drug-related activities. A large proportion of their friends, 14 (64%) of 22, had positive tuberculin skin-test results. The behavior of "hotboxing" (smoking marijuana inside a closed car with friends to repeatedly inhale exhaled smoke) fueled transmission.     

Voucher-based contingent reinforcement of marijuana abstinence among individuals with serious mental illness

Previous studies by our group have used money given contingent on abstinence to reduce drug use by individuals with schizophrenia. In this study, we examined the sensitivity of marijuana use by individuals with serious mental illness to voucher-based contingent reinforcement, which represents the first study to date investigating the efficacy of voucher incentives with this population. This within-subject reversal design consisted of three conditions: 4-week baseline, 12-week voucher intervention, and 4-week baseline. During baseline periods, subjects received US$10 vouchers per urine specimen, independent of urinalysis results. During voucher intervention, only specimens testing negative for marijuana earned vouchers, with total possible earnings of US$930. Seven adults with schizophrenia or other serious mental illnesses participated in the study. The percentage of marijuana-negative specimens was significantly greater during voucher intervention than during baseline periods. These results provide evidence that marijuana use among individuals with serious mental illness is sensitive to voucher-based incentives and further support the potential feasibility of using voucher-based contingency management to reduce substance abuse in this challenging population.     

Δ1-Tetrahydrocannabinol,synhexyl and marijuana extract administered orally in man: Catecholamine excretion,plasma cortisol levels and platelet serotonin content

Measurements of catecholamine excretion, plasma cortisol and platelet serotonin concentration were done in the course of experiments in which human volunteers were given sizable oral doses of -tetrahydrocannabinol, synhexyl or marijuana extracts. A transient rise in epinephrine excretion was observed following THC but seemed best explained by the anticipatory stress of the experiment or the rapid onset of unfamiliar symptoms. A decreased turnover of catecholamines or a shift in the degradative pathways of catecholamines from the oxidative to the reductive route was suggested by the decrease in VMA excretion following synhexyl. Plasma cortisol was unchanged except in the presence of clinically obvious psychological distress on the part of the patient. Platelet serotonin was unchanged.The lack of major effects of marijuana-like drugs on these and other clinical measurement of stress corroborates the clinical observation that drugs of this type seem to be less stressful than the usual psychotomimetics. The pronounced euphoriant and sedative effect of marijunana may ameliorate the stress of the psychotomimetic experience.Supported by grant MH-03030, USPHS.     

An affective and cognitive model of marijuana and alcohol problems

This study examined a six-month prospective model of marijuana and alcohol problems among college students. Among marijuana users, there was an indirect positive association between use utility and Time 1 (T1) marijuana-related problems through T1 marijuana use, whereas there was a direct positive association between affect lability and T1 marijuana-related problems. A multi-group analysis of alcohol problems compared models for users of alcohol and marijuana and users of alcohol only. For both groups, there was a direct positive association between T1 use utility and T2 alcohol consumption and an indirect association with T2 alcohol problems via alcohol consumption. Impulsivity was directly and positively associated with T1 alcohol problems among the alcohol-only group. For the alcohol-only group, impulsivity moderated the association between T2 consumption and problems, making it stronger. Associations between affect lability and alcohol problems as well as alcohol consumption and problems were stronger in the alcohol and marijuana group. Results support differential pathways to substance-related problems, an indirect pathway, in which problems are an unintended consequence of goal-directed use activity, as well as direct and interactive pathways in which problems may be viewed as consequences of broader regulatory problems.     

A content analysis of personal strivings: associations with substance use

This study examined relations between personal strivings and frequency of alcohol, marijuana, and any drug use among college students. Personal strivings are ongoing goals that an individual is characteristically trying to achieve through their behavior. Participants generated lists of personal strivings following standard instructions and then completed an assessment of alcohol and marijuana use and days used any drug (aside from tobacco or medication as prescribed). Personal strivings were coded into content categories by trained raters using a coding manual. Four content categories were examined for this study: achievement, affect regulation, self-presentation, and interpersonal. A series of t-tests revealed that participants' achievement strivings were unrelated to substance use. In contrast, participants endorsing more affect regulation goals used all drugs more frequently. Self-presentation goals were positively associated with alcohol use but unrelated to marijuana or other drug use. Finally, interpersonal goals were associated with higher rates of alcohol use, lower rates of marijuana use, and not related to total use days.