References

B. (1975) Preparation and monitoring of marijuana smoke condensate samples. Bull. Narc. 27, 47-54. 2. Lerner, M. and Zeffert, J. T. (1968) Determination of tetrahydrocannabinol isomers in marihuana and hashish. Bull. Narc. 20, 53-54. 3. Sparacino, C. M., Hyldburg, P. A., and Hughes, T. J. (1990) Chemical and biological analysis of marijuana smoke condensate. NIDA Research Monograph 99, 121-140. 4. Gudzinowicz, B. and Gudzinowicz, M. (1980) Analysis of Drugs and...

Deyo And Musty 2003

E. (2004) Natural cannabinoids interactions and effects, in The Medicinal Use of Cannabis and the Cannabinoids (Guy, G. W., Whittle, B. A., and Robson, R. J., eds.), Pharmaceutical Press, London, pp.165-204. 2. Musty, R. E., Deyo, R. A., Baer, J. L., Darrow, S. M., and Coleman, B. (2000) Effects of SR141716A on animal models of depression. 2000 Symposium on the Cannabinoids, International Cannabinoid Research Society, Burlington, VT, p. 109. 3. Donovan, M. (1845) On the physical and...

Determination of Cannabinoids in Blood or Plasma

Cannabinoid concentrations in urine are not very useful for determining impairment or recent use of marijuana. Therefore, in forensic cases it is important to measure cannabinoid concentrations in blood or plasma, particularly the concentrations of THC and HO-THC, the two psychoactive cannabinoids. However, analysis of cannabinoids in blood or plasma is complicated by the difficulty of separating the cannabinoids from the abundance of endogenous lipophilic and proteinaceous compounds in blood...

Drug Cannabis Breeding

During the early 1960s, marijuana cultivation came to North America. At first, Cannabis seeds found in illicit shipments of marijuana were simply casually sown by curious smokers. Early marijuana cultivators tried any available seed in their efforts to grow potent plants outdoors that would consistently mature before killing frosts. Because most imported marijuana contained seeds, many possibilities were available. Early-maturing northern Mexican varieties proved to be the most favored, as they...

Study of Robbe and OHanlon

The most comprehensive work on marijuana in actual on-road driving has been done at the University of Maastricht in the Netherlands, beginning with this report. The authors first made an assessment of the dose of marijuana preferred by users, so that appropriate doses could the assessed for their effects on driving. Twenty-four subjects who used the drug more than once a month and less than daily and who had driven within an hour of marijuana use within the last year were assessed. Their aver...

Chemometrics

Having had many years of experience in analyzing marijuana and considering the scientific precedents of others' work on a portion of the chemical fingerprint, we determined that GC mass spectrometry (MS) would be the most appropriate methodology to collect test data. GC MS instrumentation would provide not only a chemical fingerprint of a marijuana sample, but also spectral data, which would aid in the identification of each of those components. Law enforcement agencies agreed to provide...

Field Crop Production

When industrial hemp crops are grown for fiber or seed, both male and female plants are usually left standing in the field until harvest. Most medical Cannabis is grown for its psychoactive resin by a different technique. In the early 1970s, a handful Fig. 1. Medical Cannabis cultivars grown in the United Kingdom by GW Pharmaceuticals, which form the basis for GW's development of prescription medicines. The larger inflorescence (A) is a cannabidiol (CBD)-rich cultivar containing only traces of...

Determination of Cannabinoids in Oral Fluids

Analysis of oral fluids to detect recent use of drugs of abuse is of increasing interest because sampling is less invasive than collection of urine or blood. However, unlike most other drugs, THC gets into oral fluids primarily by direct deposition into the oral mucosa during smoking or oral ingestion, rather than being transferred from blood to saliva. Consequently, concentrations of metabolites of THC are very low and difficult to detect in this matrix. Niedbala et al. compared results from...

Experimental Design

The specific goal of the study was to develop a fully operational fingerprint system that could be used to determine the probability that a particular marijuana sample of unknown origin had been grown in one of the target foreign countries or domestic states or other environs in the database. The top priority for the experimental design was to be able to distinguish between foreign and domestically produced marijuana in order to determine the prevalence of foreign material entering the country...

Cannabinoid Test System

Cannabis is by far the most widely cultivated, trafficked, and abused illicit drug in the world (1-3). According to the recent Drug Abuse Warning Network update (51), the rate of drug abuse-related emergency department visits involving marijuana rose 139 nationally from 1995 to 2002. As reported in the Drug Testing Index series published by Quest Diagnostics (52), cannabinoid analysis has always had the highest drug positivity rate by drug category among all of the abused drugs tested in...

Immunological Suppression of Alveolar Macrophages in the Lungs of Habitual Marijuana Smokers

The finding that peripheral blood leukocytes collected from marijuana smokers express higher than normal levels of CB1 and CB2 mRNA (65), and that THC mediates distinct immunoregulatory effects when cultured with human leukocytes in vitro (68,86), provide only indirect evidence that marijuana smoking is associated with immunological consequences. The most compelling and direct evidence is provided by studies with AM recovered directly from the lungs of habitual marijuana users (Table 2 refs. 41...

Human Studies

The use of cannabis has been associated with exacerbation of symptoms of schizophrenia (39), but other reports suggest that the use of cannabis helped patients manage their symptoms of schizophrenia, but several studies have shown potential symptom-relieving effects of cannabis use. Peralta and Cuesta (40) studied 95 schizophrenics who had used cannabis in the last year. They found lower scores in the schizophrenics on delusions and alogia scales of Andreasen's Scales for the Assessment of...

Impact of THC on Human Immune Responses and TCell Activation

In addition to animal models, there are several epidemiological studies suggesting that marijuana smoking can predispose to the development of opportunistic infections and cancer. Tindall et al. (83) collected careful drug use histories from 386 HIV-positive individuals and observed a significantly more rapid progression from HIV infection to AIDS in those who smoked marijuana. Similarly, Newell and associates (84) found marijuana use to be associated with the acquisition of opportunistic...

Acute Effects of Marijuana on Airway Physiology

Although anecdotal reports dating back to the 19th century suggested a therapeutic role for marijuana in the relief of asthma, formal experiments first documented this effect in the 1970s. Smoke from marijuana cigarettes was found to produce short-term bronchodilation both in healthy individuals (11,12) and in patients with asthma (13). This bronchodilator effect was clearly attributable to the presence of THC, because oral administration of synthetic THC also produced a dose-dependent...

Cannabinoids and Cardiovascular Effects

Most of the research on cannabinoids has focused on the CNS, yet there are very well-described effects of synthetic and endogenous cannabinoids in the periphery, Fig. 13. Control of blood pressure by baroreceptor reflexes A9-tetrahydrocannabinol causes reflex tachycardia through CB1-mediated vasodilatation. ACh, acetylcholine NE, norepinephrine BP, blood pressure TPR, total peripheral resistance HR, heart rate CNS, central nervous system. Fig. 13. Control of blood pressure by baroreceptor...

Cannabinoid Receptors on Peripheral Blood Leukocytes

Marijuana smoking and purified THC were first proposed as immune modulators in the 1970s when abnormal leukocyte proliferation was observed in spleen cells collected from THC-treated animals (55) and in peripheral blood mononuclear cells collected from a sample of chronic marijuana smokers (56). However, similar findings were not reported in other clinical studies (57,58), and it was not until the discovery of the two different cannabinoid receptors that interactions between cannabinoids and...

Metabolism by FAAH

Endocannabinoid Synapse

Metabolism of endogenous cannabinoids. N-APE, N-arachidonyl phosphatidyl ethanolamine PLD, phospholipase D IDG, inositol-1,2-diacylglycerol PLC, phos-pholipase C 2-AG, 2-arachidonoyl glycerol FAAH, fatty acid amide hydrolase. to a certain extent, 2-AG, but are still unclear for noladin ether. Anandamide and 2-AG are produced from cleavage of two different phospholipid precursors present in the cell membranes of neurons and immune cells in particular. Anandamide is synthesized from the...

Cannabinoids and Immunomodulation

Immune inflammatory responses are at the basis of a number of pathological conditions. CB1 are mainly found centrally and mediate analgesic effects of cannab-inoids. CB2 receptors are mainly found on cells of the immune system, such as macrophages, T-lymphocytes, and natural killer cells (93). High doses of cannabinoids suppress immune responses, whereas low doses cause metabolic stimulation of lymphocytes (94,95). The mechanism of immunomodulation by cannabinoids is still unclear, but evidence...

N 168 r 0919

Predictive mathematical models for estimating the elapsed time in hours of last cannabis use based on plasma A9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-A9-THC (THCCOOH) concentrations by GC MS. (From ref. 70 with permission.) Fig. 5. Predictive mathematical models for estimating the elapsed time in hours of last cannabis use based on plasma A9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-A9-THC (THCCOOH) concentrations by GC MS. (From ref. 70 with permission.) crashes that...

Cannabis s Origin Domestication and Dispersal

Cannabis originated either in the riverine valleys of Central Asia or in northern South Asia along the foothills of the Himalayas and was first cultivated in China on a large scale for fiber and seed production and soon after in india for resin production. Various cultures have traditionally used Cannabis for different purposes. European and East Asian societies most often used Cannabis for its strong fibers and nutritious seeds. Species of Cannabis from these regions are usually relatively low...

Resin Gland Anatomy and Development

Gland Heads Cannabis

As resin gland development commences, the medically important cannabinoids and the associated terpenes begin to appear. Although the cannabinoids are odorless, terpenes are the primary aromatic principles found in the essential oil of Cannabis (9,10). Most interesting economically and medically are the cannabinoid-rich terpenoid secretions of the head cells of glandular hairs densely distributed across the myriad surfaces of the female flowers. Male plants are of no consequence in medicine...

Hypothalamus and Neuroendocrine Effects

The hypothalamus is the principal brain region controlling feeding and regulation of body weight. Several neurotransmitters are involved in the control of food intake. Serotonin and norepinephrine tend to inhibit feeding peptides such as NPY and orexins A and B tend to stimulate eating behaviors, whereas cocaine- and amphetamine-regulated transcripts and proopiomelanocortin-derived peptides are anorectic hormones such as insulin and leptin also play a role, with leptin preventing body weight...

Endocrine Effects

Marijuana use affects endocrine and reproductive functions as well, inhibits the secretion of gonadotropins from the pituitary gland, and may act directly on the ovary or testis. Although the effects are subtle, it is important to determine the true incidence of hypothalamic dysfunction, metabolic abnormalities, and mechanism of action of marijuana from well-designed studies (35). Cannabinoids affect multiple reproductive functions, from hormone secretion to birth of offspring (36). Schuel and...

Effects on the Brain Cognitive Psychological and Mental Consequences

Research by Pope and Yurgelum-Todd (52), Kouri et al. (53), Solowij et al. (54), and Block and Ghoneim (55) has shown that chronic use of marijuana was associated with impairment of cognition, particularly affecting short-term memory and executive functioning in humans and this impairment did not recover after abstaining from heavy use of marijuana (up to 5000 times in a lifetime) for at least 24 hours (52), 7 days (56), or 6 weeks (54). However, in the study of Pope and colleagues (57), the...

Cannabinoids and Analgesia

Dopamine Adrenaline Synthesis

Pain pathways are described at three levels in the periphery, where it originates at the level of the spinal cord, where some control gating the transmission of pain exists and in the CNS, particularly at the level of the periaqueductal gray. CBj receptors are found on peripheral nerves (59), and injection of anandamide into tissues swollen from carageenan-induced inflammation has been shown to reduce pain in rats (60). But there is much more evidence for a spinal and a central site of action...

Stability of Cannabinoids in Biological Matrices

Different stability studies have been conducted to investigate the stability of THC-COOH in urine or the stability of THC and THC-COOH in blood (84,85,129-134). The hydrophobic nature of cannabinoid molecules may lead to the loss of drugs in the specimen caused by surface adsorption to the specimen-handling and storage devices and containers. The loss of analyte from calibrator solutions can lead to inaccuracy of the analytical system (129). The stability of cannabinoids in immunoassay...

Determination of Cannabinoids in Hair

Determination of drugs in hair has continued to grow in importance its advantages over analysis of other matrices are that it is relatively noninvasive, and drugs can be detected in hair for a much longer time period. However, cannabinoids in blood are not taken up in hair nearly as efficiently as most other drugs are. As a result, concentrations of cannabinoids in hair after smoking or ingestion of marijuana are very low and can only be detected with extremely sensitive analytical methods....

Toxicological Tests

Marijuana use can be demonstrated by a chemical or toxicological test. Toxico-logical tests for detection of marijuana use currently include hair, urine, blood, sweat, and oral fluid. Hair marijuana tests offer the possibility of looking at marijuana exposure over the time period during which the hair was growing. Hair grows at a rate of about 1 cm a month, and most commercial vendors offering hair testing will test a 3-cm ( 3 month) section closest to the scalp. Upon request, a longer length...

Determination of Cannabinoids in Adipose Tissue and Other Tissues

Quantitative determination of cannabinoids in adipose tissue is even more challenging than analysis of cannabinoids in blood. Johansson et al. developed a lengthy assay for measurement of THC in human fatty tissue (53). The procedure included homogenization of the fat samples with hexane isopropanol (3 2) and sequential SPEs with Lipidex 5000 gel and a C18 resin. The extracted THC was derivatized with (MTBSTFA), and the derivatized THC was purified by preparative HPLC using a C18 column....

Basal Ganglia and Cerebellum

Basal Ganglia Cerebellar Pathways

The basal ganglia and the cerebellum interact with the cortex through a series of feedback circuits. The basal ganglia, a group of midbrain nuclei, are involved mainly with the initiation and execution of a movement, whereas the cerebellum tends to modulate ongoing movement (Fig. 5). Again, pathology clearly describes the role played by these structures in motor coordination. The most relevant disorders are the dyskinesias, or abnormal movements. Basal ganglia degeneration results in movement...

Life Cycle and Ecology

Cannabis is an annual crop plant propagated from seed and grows vigorously when provided an open sunny location with light well-drained soil, ample nutrients, and water. Cannabis can reach up to 5 m (16 ft.) in height in a 4- to 8-month spring-to-autumn growing season. Feral Cannabis populations are frequently found in association with human habitation. Disturbed lands such as active and disused farm fields, roadsides, railways, trails, trash piles, and exposed riverbanks are ideal habitats for...

Cannabinoids

Herbal Products Toxicology and Clinical Pharmacology, Second Edition, edited by Richard L. Kingston and Timothy S. Tracy, 2007 Criminal Poisoning Investigational Guide for Law Enforcement, Toxicologists, Forensic Scientists, and Attorneys, Second Edition, by John H. Trestrail, III, 2007 Forensic Pathology of Trauma Common Problems for the Pathologist, by Michael J. Shkrum and David A. Ramsay, 2007 Marijuana and the Cannabinoids, edited by Mahmoud A. ElSohly, 2006 Sudden Deaths in Custody,...

The Cannabis Species Debate

Twentieth-century taxonomists have variously characterized Cannabis. Although all taxonomists recognize the species Cannabis sativa, Small and Cronquist (20) subdivided C. sativa into two subspecies, each with two varieties based largely on can-nabinoid content and traditional usage. Schultes et al. (21) divided Cannabis into three separate species C. sativa, C. indica, and C. ruderalis. Several other researchers do not preserve C. ruderalis, but recognize both C. sativa and C. indica (22,23)....

Determination of Cannabinoids in Meconium

Clinicians are increasingly interested in determining when a newborn infant has been prenatally exposed to marijuana or other drugs of abuse. Meconium is the preferred matrix for analysis in these cases because it retains drugs and drug metabolites for a longer time than does an infant's blood or urine (55). GC MS confirmation of THCA in meconium was first reported by Moore et al. (56). The meconium was initially screened by fluorescence polarization immunoassay (Abbott Laboratories, Abbott...

Behavioral Activity

Whole smoke condensate from female Mexican marijuana was solvent-fractionated into four fractions using pentane, ether, methylene chloride, and ethanol. These fractions were tested in the rat (iv via leg or tail veins) for spontaneous posture, catatonic, locomotion, and coordination as well as evoked responses of arousal, startle, vocalization, and biting. The smoke condensate of marijuana (6 mg mL, 0.44 mg mL of A9-THC) and the pentane fraction (3 mg mL, 0.5 mg mL of A9-THC) had less...

Mutagenicity

A study by Novotny et al. (24) has shown a possible chemical basis for the higher mutagenicity of marijuana smoke as compared to tobacco smoke. The total weights of polynuclear aromatic fractions containing three rings or more were significantly higher in MSC than in high-tar cigarette smoke condensate. The well known carcinogen benzo a pyrene was present in MSC by a 70 higher amount than in TSC. It was suggested that the pyrolysis products of A9-THC and other cannabinoids are major...

Pharmacological Characteristics of Cannabinoids and Other Cannabis Constituents

THC is the pharmacologically and toxicologically most relevant and best studied constituent of the Cannabis plant, responsible for most of the effects of natural Cannabis preparations (42). (A MEDLINE search covering the period 1993-2003 and using the keywords tetrahydrocannabinol and pharmacology produced about 1000 citations.) THC mainly acts through binding to the CB-1 receptor (see Chapter 6). The natural (-)-trans isomer of THC is 6- to 100-fold more potent than the (+)-trans isomer. A...

Medical Values of Terpenes

The terpenoid compounds found in Cannabis resin are numerous, vary widely among varieties, and produce aromas that are often characteristic of the plant's geographic origin. Although more than 100 different named terpenes have been identified from Cannabis, no more than 40 known terpenes have been identified in a single plant sample, and many more remain unnamed (11). Terpenes are produced via multibranched biosynthetic pathways controlled by genetically determined enzyme systems. This...

Rimonabant and the Endocannabinoid System

The Endocannabinoid (EC) System is a newly discovered physiological system in the body that is believed to play a key role in the central and peripheral regulation of energy balance, glucose and lipid metabolism, as well as in the control of tobacco dependence. CB1 receptors are found in the brain as well as in peripheral tissues of the body, such as adipocytes (or fat cells), which are associated with lipid and glucose metabolism. Excessive food intake or chronic tobacco use results in an...

Specimen Validity Testing

The normalization of THC metabolite concentration to urine creatinine concentration has been proven to help address the issue of fluctuating THC-COOH concentration as a result of specimen donor hydration status. In addition to physiological fluctuation, intentional dilution of urine specimens in vivo or in vitro may lower the levels of drug below the threshold for a positive screen result and thus avoid further testing (151-154). Moreover, attempts to conceal drug abuse by water dilution are...

Fractionation and Analysis of Marijuana Smoke Condensate

MSC is a highly complex matrix containing several thousand compounds that may vary over several orders of magnitude (4). A liquid-liquid fractionation scheme (5,6) allowed the separation of these components into different classes of compounds (i.e., acidic, basic, and neutral nonpolar, polar, and polyaromatic hydrocarbons see Fig. 1). In 1975, Jones and Foote (7) reported acids, phenols, and bases that were chemically separated from the smoke condensate of 2638 marijuana cigarettes and...

Correlation of Results From Cannabinoid Immunoassay and GCMS Analysis

Thc Cooh Half Life

A number of studies have been conducted to investigate how well results from cannabinoid immunoassays can correlate to GC MS analysis and or to select an appropriate cutoff value for each of the initial test methods (99-105). In all cases the general correlations exist, yet the data points could be rather scattered. Generally speaking, the correlation coefficients are more sensitive to the change of sample groups, in which the distributions in the relative concentrations of THC-COOH and other...

Skin Sweats

The substance collected for sweat testing is actually a combination of secretions onto the skin. Cannabinoids and other drugs are transported into sweat by diffusion from blood and other depots. Sweat from eccrine glands and sebum from apocrine sweat glands and sebaceous glands are the main constituents. Eccrine glands are located throughout the body near the surface of the skin, and the sweat they produce is aqueous, contains salts, is usually in the pH range of 4.0-6.0, and is produced at...

Determination of Other Cannabinoids in Urine

Although detection of THCA in urine continues to be the primary method for identifying recent use of marijuana, Manno and Manno and their co-investigators have shown that THC and other metabolites of THC are also excreted in urine as glucuronide conjugates that are not, however, as easily hydrolyzed as THCA glucuronide (38,39). THC and its hydroxylated metabolites are excreted in urine primarily as ether-linked glucuronide conjugates that do not undergo hydrolysis under alkaline conditions....

Cannabinoids Pharmacokinetics and Drug Analysis

Metabolic Transformations

Cannabinoids immunoassays for each type of biological matrix have to be designed and interpreted in the context of A9-THC absorption and metabolism. The Fig. 1. Chemical structure of naturally occurring cannabinoids. 21 CFR 862.3870 defines a cannabinoid test system as a device intended to measure any of the cannabinoids, hallucinogenic compounds endogenous to marihuana, in serum, plasma, saliva, and urine. Cannabinoid compounds include A9-tetrahydrocannabinol, cannabidiol, cannabinol, and...

Urine

Many governmental and private organizations in the United States employ drug testing as part of their drug use-prevention programs. Urine is the biological matrix most commonly tested to identify individuals who use drugs. In 2003 it was estimated that more than 20 million urine specimens were collected for drug testing in United States programs. Drug testing is also an important objective outcome measure of drug treatment, drug research investigating efficacy of new behavioral therapies,...

Inhibition of Dihydrotestosterone Binding to the Androgen Receptor

MSC and two constituents of Cannabis, A9-THC and cannabinol, were tested for their ability to interact with the androgen receptor in rat prostate cytosol (32). The above-mentioned materials competitively inhibited the specific binding of dihydrotestosterone to the androgen receptor with a dissociation constant (Ki) of 2.1 x 10-7 M for CBN, 2.6 x 107 M for A9-THC, and 5.8 x 107 M for MSC. The data indicate that the antiandrogenic effects associated with marijuana use result, at least in part,...

Hemp Seed Oil Products Synthetic THC Medication and Drug Testing

The question of whether the consumption of cannabinoid-containing foodstuffs or cannabinoid-based therapeutics could be used to justify the presence of urinary THC-COOH has been extensively investigated and reported in the literature (70,110,136-144). A number of studies in 1997 clearly showed that ingestion of what were commercially available hemp seed oils could produce positive cannabinoid immunoassay results for several days (137-140). These screen-positive specimens were shown to contain...

Introduction

This chapter describes the published mass spectrometric (MS) methods that have proven most effective for quantitative measurement of A9-tetrahydrocannabinol (THC) and its major metabolites in physiological specimens. Because determination of 11-nor-9-carboxy- A tetrahydrocannabinol (THCA) in urine continues to be the most frequently used indicator of marijuana use, the first portion of the chapter will discuss methods for measurement of THCA in urine. However, the major portion of the chapter...

Preparation of Marijuana Smoke Condensate

Patel and Gori (1) described the preparation of marijuana cigarettes and the production of MSC. Various analytical parameters of blended marijuana (i.e., ash, hex-ane solubles, nitrate, reducing sugars, citric acid, malic acid, oxalic acid, potassium, sodium, calcium, magnesium, cadmium, chromium, and A9-tetrahydrocannabinol THC ) and marijuana cigarettes (average weight, average moisture content, static burning rate, fire zone temperature at 15- and 55-mm marks) were determined.

Cutoff Concentrations and Immunoassay Evaluations

Because a cutoff is the concentration of drug below which all specimens are considered to be negative, the cutoff decision has a direct impact on the detection time window and the positive rate. The most commonly used method for immunoassay performance comparisons is to evaluate the so-called true-positive TP , true-negative TN , false-positive FP , and false-negative FN of the assay. These results can then be used to calculate the specificity TN TN FP x 100 , sensitivity TP TP FN x 100 ,...

Chemistry and Classification

So far, 66 cannabinoids have been identified. They are divided into 10 subclasses 8-10 see Table 1 . From Forensic Science and Medicine Marijuana and the Cannabinoids Edited by M. A. ElSohly Humana Press Inc., Totowa, New Jersey Main pharmacological characteristics 1. Cannabigerol CBG type CBG was the first cannabinoid identified 11 , and its precursor cannabigerolic acid CBGA was shown to be the first biogenic cannabinoid formed in the plant 12 . Propyl side-chain analogs and a monomethyl...

Study of Lamers and Ramaekers

In this study, performed at the same institute and using the same methodology, researchers assessed the combined effects of alcohol and marijuana using 0.04 g 100 mL BAC and 100 Mg kg THC on urban city driving. Additionally, using a head-mounted eye movement-recording system, the subjects' visual search or side glances were assessed. This study confirmed that low doses of marijuana, or alcohol at the 0.04 g 100 mL concentration, when taken alone, did not impair city driving or performance or...