YOU ARE NOW CONNECTED TO THE TOXLINE (1981 FORWARD, NON-ROYALTY) FILE. ==MARIJUANA USE== 6 AUTHOR Adams IB AUTHOR Martin BR TITLE Cannabis: pharmacology and toxicology in animals and humans. SOURCE Addiction; VOL 91, ISS 11, 1996, P1585-614 (REF: 265) ABSTRACT Cannabis is one of the most widely used drugs throughout the world. The psychoactive constituent of cannabis, delta 9-tetrahydrocannabinol (delta 9-THC), produces a myriad of pharmacological effects in animals and humans. For many decades, the mechanism of action of cannabinoids, compounds which are structurally similar to delta 9-THC, was unknown. Tremendous progress has been made recently in characterizing cannabinoid receptors both centrally and peripherally and in studying the role of second messenger systems at the cellular level. Furthermore, an endogenous ligand, anandamide, for the cannabinoid receptor has been identified. Anandamide is a fatty-acid derived compound that possesses pharmacological properties similar to delta 9-THC. The production of complex behavioral events by cannabinoids is probably mediated by specific cannabinoid receptors and interactions with other neurochemical systems. Cannabis also has great therapeutic potential and has been used for centuries for medicinal purposes. However, cannabinoid-derived drugs on the market today lack specificity and produce many unpleasant side effects, thus limiting therapeutic usefulness. The advent of highly potent analogs and a specific antagonist may make possible the development of compounds that lack undesirable side effects. The advancements in the field of cannabinoid pharmacology should facilitate our understanding of the physiological role of endogenous cannabinoids. 1 AUTHOR Fried PA TITLE Prenatal exposure to marihuana and tobacco during infancy, early and middle childhood: effects and an attempt at synthesis. SOURCE Arch Toxicol Suppl 1995;17:233-60 ABSTRACT Both marihuana and cigarettes appear implicated, in a differential fashion, in the neurobehaviour of infants and children born to women who used these substances during pregnancy. In a low-risk upper middle class sample, marihuana use was associated, in the newborn, with mild withdrawal symptoms and some autonomic disruption of nervous system state regulation. However, between 6 months and 3 years of age no behavioural consequences of marihuana exposure (once confounding factors were controlled) were noted. At four years of age, although global tests of intelligence did not differentiate exposed from non-marihuana exposed children, verbal ability and memory were associated with in utero marihuana exposure. At five and six years of age these general areas were also noted to be associated with maternal cannabis use as was sustained attention. These areas of neurobehavior that appear affected by marihuana exposure during fetal development are ones that are consistent with the cognitive construct of 'executive functioning' which is thought to be a marker of prefrontal lobe functioning. Consistent with the observations derived from these children is that prefrontal functioning may not be apparent until approximately four years of age and that executive functioning is disassociated from measures of global intelligence. Exposure to cigarettes during pregnancy appears to be associated with neurobehavioural deficits in the auditory domain. In the newborn this is manifested by decreased responsivity to sound and altered auditory habituation. Between the ages of one and 11 years the performance on auditory related tasks (verbal memory, language, auditory processing) were consistently the domains that differentiated the cigarette exposed from the non exposed children. The possible role of the cholinergic mediated efferent auditory system is discussed. Also associated with in utero exposure to cigarettes were general cognitive performance and parental reports and objectively derived measures of impulsivity. The striking degree of consistency over the years lends strength to the interpretation that the observations in childhood have, at least as their partial etiology, the prenatal exposure to cigarettes. However, in interpreting the evidence presented it must be recognized that the alterations in the child's behaviour may well affect the parenting behaviour. This potential transactional interaction must remain an integral part of drawing conclusions about both marihuana and cigarette's effects. 8 AUTHOR Nahas G AUTHOR Latour C TITLE The human toxicity of marijuana [see comments] SOURCE Med J Aust 1992 Apr 6;156(7):495-7 ABSTRACT The pathophysiological effects of marijuana smoke and its constituent cannabinoids were reported first from in-vitro and in-vivo experimental studies. Marijuana smoke is mutagenic in the Ames test and in tissue culture and cannabinoids inhibit biosynthesis of macromolecules. In animals, marijuana or delta 9-tetrahydrocannabinol (THC), the intoxicating material it contains, produces symptoms of neurobehavioural toxicity, disrupts all phases of gonadal or reproductive function, and is fetotoxic. Smoking marijuana can lead to symptoms of airway obstruction as well as squamous metaplasia. Clinical manifestations of pathophysiology due to marijuana smoking are now being reported. These include: long-term impairment of memory in adolescents; prolonged impairment of psychomotor performance; a sixfold increase in the incidence of schizophrenia; cancer of mouth, jaw, tongue and lung in 19-30 year olds; fetotoxicity; and non-lymphoblastic leukemia in children of marijuana-smoking mothers. 12 AUTHOR Zimmerman S AUTHOR Zimmerman AM TITLE Genetic effects of marijuana. SOURCE Int J Addict 1990-91;25(1A):19-33 ABSTRACT Marijuana and its constitutive cannabinoids--tetrahydrocannabinol (THC), cannabinol (CBN), and cannabidiol (CBD)--markedly affect mammalian cells. Cytogenetic studies have revealed that cannabinoids induce chromosome aberrations in both in vivo and in vitro studies. These aberrations include chromosomal breaks, deletions, translocations, errors in chromosomal segregation, and hypoploidy, and are due to the clastogenic action of cannabinoids or to cannabinoid-induced disruption of mitotic events or both. Conflicting reports of the cytogenetic effects of cannabinoids are partially explained by the different experimental protocols, cell types, and animals used by investigators. Cannabinoids also suppress macromolecular synthesis (DNA, RNA, and protein) as well as reduce the level of histone gene expression. In general these studies show that cannabinoids are detrimental to the health of an individual. 8 AUTHOR Thomas H TITLE A community survey of adverse effects of cannabis use. SOURCE Drug Alcohol Depend; VOL 42, ISS 3, 1996, P201-7 ABSTRACT This survey estimates the frequency of various adverse effects of the use of the drug cannabis. A sample of 1000 New Zealanders aged 18-35 years were asked to complete a self-administered questionnaire on cannabis use and associated problems. The questionnaire was derived from criteria for the identification of cannabis abuse which are analagous to criteria commonly used to diagnose alcoholism. Of those who responded 38% admitted to having used cannabis. The most common physical or mental health problems, experienced by 22% of users were acute anxiety or panic attacks following cannabis use. Fifteen percent reported psychotic symptoms following use. Problems related to physical and mental health and control of level of intake were more common than social or relationship problems.