Recent progress in the neurotoxicology of natural drugs associated with dependence or addiction, their endogenous agonists and receptors.
Nicotine in tobacco, tetrahydrocannabinol (delta 9-THC) in marijuana and morphine in opium are well known as drugs associated with dependence or addiction. Endogenous active substances that mimic the effects of the natural drugs and their respective receptors have been found in the mammalian central nervous system (CNS). Such active substances and receptors include acetylcholine (ACh) and the nicotinic ACh receptor (nAChR) for nicotine, anandamide and CB1 for delta 9-THC, and endomorphins (1 and 2) and the mu (OP3) opioid receptor for morphine, respectively. Considerable progress has been made in studies on neurotoxicity, in terms of the habituation, dependence and withdrawal phenomena associated with these drugs and with respect to correlations with endogenous active substances and their receptors. In this article we shall review recent findings related to the neurotoxicity of tobacco, marijuana and opium, and their toxic ingredients, nicotine, delta 9-THC and morphine in relation to their respective endogenous agents and receptors in the CNS. (+info)
Cannabis use and cognitive decline in persons under 65 years of age.
The purpose of this study was to investigate possible adverse effects of cannabis use on cognitive decline after 12 years in persons under age 65 years. This was a follow-up study of a probability sample of the adult household residents of East Baltimore. The analyses included 1,318 participants in the Baltimore, Maryland, portion of the Epidemiologic Catchment Area study who completed the Mini-Mental State Examination (MMSE) during three study waves in 1981, 1982, and 1993-1996. Individual MMSE score differences between waves 2 and 3 were calculated for each study participant. After 12 years, study participants' scores declined a mean of 1.20 points on the MMSE (standard deviation 1.90), with 66% having scores that declined by at least one point. Significant numbers of scores declined by three points or more (15% of participants in the 18-29 age group). There were no significant differences in cognitive decline between heavy users, light users, and nonusers of cannabis. There were also no male-female differences in cognitive decline in relation to cannabis use. The authors conclude that over long time periods, in persons under age 65 years, cognitive decline occurs in all age groups. This decline is closely associated with aging and educational level but does not appear to be associated with cannabis use. (+info)
Nail analysis for drugs of abuse: extraction and determination of cannabis in fingernails by RIA and GC-MS.
Fingernail clippings were evaluated as analytical specimens for the detection and quantitation of cannabinoids. Specimens were obtained from consenting adults attending a drug clinic, along with information concerning the drugs which they had used over the previous six months. Methods for the surface decontamination and extraction of the specimens were evaluated. Detergent, water, and methanol washes followed by alkaline hydrolysis and liquid-liquid extraction were selected for use in the study. Extracts were analyzed by radioimmunoassay (RIA) and gas chromatography-mass spectrometry (GC-MS) to detect and quantitate cannabinoids present in fingernail clippings. Positive RIA results were obtained from specimens from six known cannabis users. The mean cannabinoid concentration in fingernail clippings determined by RIA was 1.03 ng/mg. Using GC-MS, the mean delta9-tetrahydrocannabinol concentration in fingernail clippings from a further 14 known cannabis users was 1.44 ng/mg. Using GC-MS, the average 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid concentration in fingernail clippings from three known cannabis users extracted in acidic pH was 19.85 ng/mg. Based on these results, fingernails are potentially useful biological specimens for the detection of past cannabis use in cases of medicolegal interest. (+info)
Urinary excretion profiles of 11-nor-9-carboxy-delta9-tetrahydrocannabinol: a delta9-THCCOOH to creatinine ratio study.
Monitoring the major cannabinoid metabolite (delta9-THCCOOH) to creatinine ratio (M/C) has been used to predict new drug use. According to Huestis and Cone, the best accuracy (85.4%) for predicting new marijuana use was a ratio > or = 0.5 from two urine specimens collected at least 24 h apart. Manno et al. recommended an M/C ratio of > or = 1.5. Subjects with a history of chronic marijuana use were screened for cannabinoid use by immunoassay (50-ng/mL cutoff), and presumptive positives were confirmed by gas chromatography-mass spectrometry for delta9-THCCOOH (15-ng/mL cutoff). Creatinine was analyzed with a cutoff concentration of 25 mg/dL. The study objective was to apply the criteria from both groups of workers to determine if consecutive urine specimens (collected at least 24 h apart) positive for cannabinoids could be used to differentiate new marijuana use from the excretion of residual cannabinoid metabolite (delta9-THCCOOH) in an uncontrolled setting. Serial urine specimens (826) were collected from 26 individuals. Huestis and Cone and Manno et al. ratios indicated new drug use in 83% and 33% of serial urine specimens collected at least 24 h apart, respectively. Clinically, the Huestis and Cone ratio is recommended because of a lower false-negative rate (7.4%) than the Manno et al. false-negative rate (24%). In legal situations, we recommend using the Manno et al. ratio because of its lower false-positive rate (0.1%) as stated by Huestis and Cone. (+info)
Marijuana: medical implications.
Over 50 percent of people will use marijuana sometime in their life. While intoxication lasts two to three hours, the active ingredient in marijuana, delta-9-tetrahydro-cannabinol, can accumulate in fatty tissues, including the brain and testes. Adverse effects from marijuana use include decreased coordination, epithelial damage to the lungs, increased risk of infection, cardiovascular effects and cognitive deficits. Unexplained behavior changes, altered social relationships and poor performance at school or work can signify a drug problem. Treatment requires a combination of education, social support, drug monitoring and attention to comorbid medical and psychiatric conditions. (+info)
Detection of drug misuse--an addictive challenge.
It is now accepted that drug misuse is a large and growing problem in the United Kingdom, some estimates of the number of regular illicit drug users being as high as three million. The aim of this paper is to provide insight into the methods used to detect drug misuse. The strategy adopted by one laboratory is described and methods of screening for, and identification of, a wide range of compounds are provided. No claim is made that this is the best approach or that the list of drugs detected is comprehensive; the range of drugs encountered is always increasing and the lists are constantly updated. It is hoped that users of toxicology laboratory services will gain an appreciation of the capabilities and limitations of the techniques available; and that those who may wish to provide such a service will find the necessary information in a readily accessible format. (+info)
Purification and some properties of an aminopeptidase from the seeds of Cannabis sativa.
An aminopeptidase (HSA) with a molecular mass of 78 kDa was purified from hemp (Cannabis sativa) seeds. The activity was inhibited by monoiodeacetic acid, p-chloromercuri-phenylsulfonic acid, and Zn2+ ion. The specificity of HSA was similar to that of a leucyl aminopeptidase [EC 22.214.171.124] from mammalian cytosol. However, other enzyme properties were different from these of leucyl aminopeptidase. (+info)
Marijuana smoking and reduced pressure in human eyes: drug action or epiphenomenon?
Normal pressure within the human eye was reduced after smoking a socially relevant dose of marijuana (12 mg. delta9-9-tetrahydrocannabinol), but only for light to moderate users who experienced a substantial "high" and a state of peaceful relaxation from the experimental dose. Analysis suggests an indirect effect of the drug associated with relaxation-a psychophysiologic state that can be produced by drug and nondrug means. (+info)