References

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Acknowledgment

This work was supported by National Institute on Drug Abuse intramural funds. References 1. United Nations Office on Drugs and Crime. (2003) Global Illicit Drug Trends, 2003, United Nations Office on Drugs and Crime,New York. 2. Substance Abuse & Mental Health Services Administration. (2002) National Survey on Drug Use and Health, 2002, Substance Abuse & Mental Health Services Administration, Rockville MD. 3. McPartland J. M. and Pruitt P. L. (1999) Side effects of pharmaceuticals not...

TCD Sonography

The routine TCD evaluation of cerebral blood flow velocity began in the 1980s (41). TCD provides clinically useful information in assessing abnormal hemodynamics in cerebral arteries. Current clinical applications of TCD include screening children 2-16 yr of age with sickle cell disease for stroke risk, the detection and monitoring vasospasm after subarachnoid hemorrhage, detection of intracranial steno-occlusive disease, monitoring vasomotor reactivity, detection cerebral circulatory arrest,...

Stephen J Heishman and Edward G Singleton

Cannabis is the most widely used illicit drug in the United States, with 14.6 million current users. Cannabis-dependent individuals presenting for treatment typically report cannabis craving however, the phenomenon has received little research attention. In the absence of a valid, multidimensional questionnaire to assess cannabis craving, we developed the Marijuana Craving Questionnaire (MCQ). The MCQ consists of four constructs or factors that characterize cannabis craving compulsivity,...

Modification of Gene Expression in Xenopus laeves Oocytes

Electrophysiology Oocyte

3.6.1. cRNA Synthesis and Oocyte Expression Complementary RNAs (cRNAs) are synthesized from corresponding complementary DNAs (cDNAs) coding for the receptor gene of interest such as the glutamate receptor and are individually injected into Xenopus laeves oocytes individually or in desired receptor subunit combinations of 16-20 ng per subunit using a microinjector and prepared for electrophysiological recording. 3.6.2. Electrophysiological Recording 1. After detecting receptor expression,...

Orexigenic and Anorexigenic Studies

A combination of central and peripheral mechanisms control food intake. Indeed, hypothalamic nuclei and the brainstem act as input stations for hormonal and gastrointestinal information (10,11). Furthermore, peripheral satiety factors such as cholecystokinin (CCK) activate CCK1 receptors on vagal afferents, which transmit signals to hindbrain nuclei such as the nucleus tractus soli-tarius (NTS). The NTS in turn communicates with several hypothalamic nuclei, which play critical roles in appetite...

Future Directions

This chapter has described methods for the assessment of cannabinoid-induced behavioral changes. In view of the widespread presence of cannabinoid receptors and their ligands (see for example refs. 84a, 84b), it is hardly surprising that the cannabinoids are involved in virtually every mode of behavior. Moreover, it has recently become evident that the endocannabinoids play a pivotal role as the retrograde messengers in glutamatergic and GABA-ergic synapses in a number of brain structures...

Phagocytosis Assay

Phagocytosis is one of the first lines of defense against invading microorganisms. Macrophages play a central role in this process as a host defends against intruding foreign bodies. This phagocytosis assay was developed in order to further elucidate the level at which macrophage function is compromised, if at all, in the presence of cannabinoids. 3.4.1. Macrophage Treatment With Foreign Antigen 1. Thioglycolate-elicited peritoneal macrophages from CB2R+ + or CB2R- - are plated and treated with...

Hybrid Cannabinoids

Hybrid cannabinoids, as the name indicates, were generated by combining the pharmacophoric features of classical and nonclassical cannabinoids (Fig. 3). The Fig. 3. Evolution of hybrid cannabinoids. Fig. 3. Evolution of hybrid cannabinoids. Fig. 4. Novel CC NCC hybrid ligands. Fig. 4. Novel CC NCC hybrid ligands. objective behind their design was to study more precisely the stereochemical requirements of the SAH pharmacophore, which was discovered during the development of NCCs. These hybrid...

Methods for the Synthesis of Cannabinergic Ligands

Nikas, Richard I. Duclos, Jr., and Alexandros Makriyannis During the last decade, numerous cannabinergic ligands with high affinity and selectivity profiles for cannabinoid receptors (CB1 and CB2) emerged from rigorously pursued structure-activity relationship studies. This chapter focuses on the synthetic aspects of key cannabi-noid receptor probes representing the different classes of cannabinergic ligands that encompasses classical cannabinoids (CCs) including...

Nonclassical Cannabinoids

A second class of cannabinergic ligands possessing close similarity with CCs was developed at Pfizer in an effort to simplify the CC structure, while maintaining or improving biological activity (52-56). This group of compounds is generally designated as nonclassical cannabinoids and includes AC-bicyclic (e.g., 26 and 27, Fig. 2) and ACD-tricyclic (e.g., 28, Fig. 2) ligands lacking the pyran Bring of CCs. NCCs share some of the key pharmacophores of the CCs, namely, the phenolic hydroxyl, the...

Adverse Events From Cannabis Administration

Acute cardiovascular effects of cannabis administration include tachycardia, slightly increased blood pressure when supine, orthostatic hypotension, increased cardiac output, and decreased left ventricular ejection fraction (32,33). These effects increase myocardial oxygen demand at the same time that oxygen delivery to tissues may be decreased because of the increased car-boxyhemoglobin from smoking. As a result, smoking one marijuana cigarette significantly reduces maximal exercise...

The Mouse Tetrad Test

The mouse tetrad consists of four simple evaluations, which may be measured in sequence in the same animal. 1. Motor activity in an open field is measured for various lengths of time, but typically for 10 min, by digitized or manual observation. 2. The amount of time in which the mouse is immobile after placement on a metal ring of 5.5 cm diameter, fixed at approx 16 cm above a table top, is recorded for 4-5 min. This method was developed by Pertwee (13) and is taken as a measure of catalepsy....

Acknowledgments

Supported by grants from National Institutes on Drug Abuse (DA9158, DA03801, and DA07215). Scheme 17. Synthesis of tail-modified analog 73 (95). Reagents and conditions (a) I2, PPh3, imidazole, Et2O CH3CN, 0 to 23 C, 1 h, 98 (b) PPh3, CH3CN, reflux, 18 h, 90 (c) NaHMDS, THF HMPA, 80, -78 to 23 C, 2 h, 61 (d) LiOH, MeOH H2O, 23 C, 18 h, 94 (e) oxalyl chloride, CH2Cl2, 0 C, 2 h, 100 (f) 2-ethanolamine, CH2Cl2, 0 to 23 C. Methyl iodide (79). To a stirred solution of triphenylphosphine (456 mg,...

Nancy E Buckley Diep Burbridge Manop Buranapramest Tanya Ferguson and Renee Y Paau

Marijuana components, such as A-9-tetrahydrocannabinol, and endogenous cannabinoids, such as anandamide and 2-arachydonoylglycerol, alter diverse immune functions. Two cannabinoid receptors have been discovered to date, the central cannabinoid receptor CB1R and the peripheral cannabinoid receptor CB2R . The CB1R is expressed predominantly in the central nervous system. The CB2R is expressed mainly in cells of the immune system, suggesting that the CB2R is involved in immunoregulatory events....

Statistics

Six to nine separate immunocytochemical experiments were run for each primary antibody. Individual experiments were composed of at least two or three tissue sections of each animal from each group. Ten to 14 fields were analyzed for each brain region. Interexperimental differences were not statistically significant. Values represent the mean SD of experiments performed for each marker and treatment. The statistical study was performed by applying a two-tailed Student's i-test to the results of...