The most current information will be found toward the end of the document.

Medical Marijuana

The year 1765: from Hemp: Lifeline to the Future, by Chris Conrad, 1994, pp. 192-193, part of Chapter 16, "A World of Cannabis Cultures." Creative Xpressions Publications, Los Angeles, ISBN 0-9639754-1-2, $12.95 from FS Book Company, Sacramento, 1-800-635-8883 American High Society - Did the Founding Fathers of the United States of America smoke cannabis? Some researchers think so. Dr. Burke, president of the American Historical Reference Society and a consultant for the Smithsonian Institute,

Dr. Bradner has published tables of these drugs compiled from the reports of the Massachusetts Health Board and the examination of State chemists in different parts of the country. His paper appeared in the Journal of Inebriety for January, 1890, and the second paper on this subject will be found in the July issue of that journal. These papers bring out the fact, not well known, that nearly all the more prominent proprietary drugs on the market contain large quantities of alcohol.- How far these drugs depend on alcohol to increase their attractiveness and sales is not known, but it is evident that many of the widely used drugs would have no demand if it were not for the alcohol which forms the bases of the combination.

Sears Roebuck & Co.Catalog 1901 - (courtesy of the U.C. Santa Barbara University Library], sears sold the following [note that the first two were sold via house brands]: Sears, Roebuck & Co. [1901] Chicago ILL. U.S.A. Tinctures - No. 8R8936 - Cannabis Indica. - U.S.P. No. 8R8328 Neuralgic, Kenyon Proprietary and Patent Medicines - Battle’s Bromidia Proprietary and Patent Medicines - Piso’s Consumption Cure. ----- (sidebar - Cannabis medicines at one time were as common as aspirin is today] what makes Sears so different is what else they sold -- According to the Sears Encyclopedia): ----- MARIHUANA, the Mexican name for a narcotic drug obtained from the leaves of the hemp plant CANNABIS and generally used in cigarettes. Introduced from Mexico about 1910, probably at New Orleans or in the southwestern states, its use has spread at an alarming rate in the United States Known by a variety of local terms, . . . “The Weed,” it is considered by many authorities to be the most potent drug in common use. - Although the effect of marihuana is often unpredictable, and may range from extreme elation to profound melancholy, the result is almost invariably accompanied by a loss of restraint and self-control, with subsequent erratic behavior. Hallucinations of sight and hearing are not uncommon, and delusions of strength may lead to feats of endurance without sense of fatigue. Although the long-run effects of the continued use of the drug are disputed by medical authorities, it is thought by some that chronic addiction leads to a loss of mental ability, stupor, and indolence, and that in such cases irreparable damage is done to brain tissue and nerve centers, and insanity may be the result. - Marijuana smoking did not become a problem in the United States until about 25 years ago and has caused serious concern only in the past 12 to 15 years. Its use has spread to all sections of the country, being especially prevalent in large cities. In 1937 it was estimated that there were over 100,000 marijuana addicts in the United States, the majority being of high school and college age. An index of the great increase in the use of marijuana since that year is the number of arrests for violation of narcotic drug laws, which more than doubled between 1937 and 1950.

Edited by Tod H. Mikuriya, M.D. (1973) 465 pages Medi-Comp Press, 2633 E. 27th St., Oakland, CA 94601. Library of Congress Catalog Card Number 72-87736 - Table of Contents, Preface and Introduction to "Marijuana: Medical Papers" (1839-1972)

Pictures of Pennsylvania Wild HempSeptember 1940: A Second Synthesis of Cannabinol: Contribution from the Noves Chemical Laboratory, University of Illinois: Structure of Cannabinol. V.

A Second Method of Synthesis of Cannabinol: by Roger Adam's & B.R. Baker: Received July 25, 1940: Urbana, Illinois: pg 2401 - Contribution from the Noyes Chemical Laboratory, University of Illinois, and the School of Medicine, University of Utah: New Analogs of Tetrahydrocannabinol. XIX by Roger Adams, Morton Harfenist and S. Loewe: Volume 71 pg 1624-1628: May 1949 page 4551: Acknowledgment: This work was supported by Grant GP-4931 from the National Science Foundation: MP Cava, RJ Spangler: Department of Chemistry, Wayne State University, Detroit, Michigan, 48202, Received June 5, 1967: Total synthesis of Delta 8 - (Delta 1(6)-Tetrahydrocannabinol, a Biologically Active Constituent of Hashish (Marijuana) - page 4552: Acknowledgments: We thank Dr. P. B. Russell (Wyeth Laboratories Inc.) for his interest and encouragement, Dr. C. Hetzel (Wyeth Laboratories Inc.) for the gas-liquid partition chromatography, Dr. D. Dejonhg (Wayne State University, Detroit, Mich) for the mass spectrum, and Mr. W.C. Jankowski (Varian Analytical Instrument Division , Pittsburgh, PA) for the 100-Mc pmr spectrum (Atlas CH-4)

Psychopharmacologia (Berl.) 11. 184-188 (1967): Effects of (-) Delta 9- Trans-Tetrahydrocannabinol in Man: by Harris Isbell: Department of Medicine, University of Kentucky Medical Center, Lexington, Kentucky: CW Gordoetzsky and D. Jasinski: NIHM Addiction Research Center, USPHS Hospital, Lexington, Kentucky: U. Claussen, FV Spulak and F Korte: Organiseh-Chemisches Institut der Universitat Bonn: Received February 28, 1967

Volume 16, 1968: No 6 page 1157: Chem. Pharm. Bull. 16 (6) 1157 1158 (1968): Cannabichromenic Acid, a Genuine Substance of Cannabichromene 1 Cannabidiolcarbonsaure-tetrahydrocannabitriol-ester: Received Germany: March 1968: Accepted for publication March 14, 19868: Organisch- Chemisches Institut der Universitat Bonn 5379 - 5383

Science: Volume 16: December 13, 1968: Clinical & Psychological Effects of Marihuana in May: by Andrew T. Weil, Norman E. Zinberg, Judith M. Nelson: Mentions LaGuardia Report on page 1235: (i) Smoking in the way nearly all Americans use marijuana. (ii) It is possible to have subjects smoke marijuana cigarettes in such a way that drug dosage is reasonably uniform for all subjects pg 1238 (Safety of marijuana in human volunteers. In view of the apprehension expressed by many persons over the safety of administering marijuana to research subjects, we wish to emphasize that no adverse marijuana reactions occurred in any of our subject. In fact, the five acute nicotine reactions mentioned earlier were far more spectacular than any effects produced by marijuana. In these experiments, observable effects of marijuana were maximum at 15 minutes after smoking. They were diminished between 30 minutes and 1 hour, and they were largely dissipated 3 hours after the end of smoking. No delayed or persistent effects beyond 3 hours were observed or reported. 2) Intoxicating properties of marijuana in a neutral setting: 3) Comparison of naive and chronic user subjects: 4) Recognition of marijuana Placebo Page 1239 5) Effect of marijuana on heart rate: 6) Effect of marijuana on respiratory rate page 1940 7) Effect of marijuana on pupil size 8) Effect of marijuana on conjunctival appearance 9)Effect of Marijuana on blood sugar 10) Effect of marijuana on Continuous Performance Test (11) Effect of marijuana on the Digit Symbol Substitution Test 12) Effect of marijuana on pursuit rotor performance. (13) Effect of marijuana on time estimation 14) Subjective effect of marijuana 15) The effect of marijuana on the self-rating mood scale, the effect of marijuana on a 5 minute verbal sample, and the correlation of personality type and subject -page 1241 Discussion: maintaining effective levels of performance for many tasks - driving, for example (26) - is much easier under the influence of marijuana than under that of other psychoactive drugs. Certainly the surprise that the chronic users expressed when they found they were performing more effectively on CPT, DSST, and pursuit rotor tests than they thought they would is remarkable. ...What might be the basis of this supressibility? Possibly, the actions of marijuana are confined to higher cortical functions without any general stimulatory or depressive effect on lower brain centers. The relative absence of neurological - as opposed to psychiatric - symptoms in marijuana intoxication suggests this possibility....Finally, we would like to comment on the fact that marijuana appears to be a relatively mild intoxicant in our studies. If these results seem to differ from those of earlier experiments, it must be remembered that other experimenters have given marijuana orally, have given doses much higher than those commonly smoked by users, have administered potent synthetics, and have not strictly controlled the laboratory setting. page 1242 Conclusions: 5) Marijuana increases heart rate moderately: 8) Marijuana administration causes dilatation of conjunctival blood vessels.]

Gaoni, Mechoulam \ delta 1 Tetrahydrocannabinol: page 217 - 223 The Isolation and Structure of Delta 1 Tetrahydrocannabinol and Other Neutral Cannabinoids from Hashish: Contribution from the Department of Chemistry, The Weizmann Institute of Science, Rohevoth, and the Laboratory of Natural Products, Hebrew University Pharmacy School, Jerusalem, Israel, Received April 27, 1970

Journal of the American Chemical Society [93:1] January 13, 1971: Studies of the Chymotrypsinogen A Family of Proteins. VIII. Thermodynamic Analysis of Transition I of the Methionine Sulfoxide Derivatives of a-Chymotrypsin 1: by Rodney Biltonen and Rufus Lumry: Contribution from the Laboratory for Biophysical Chemistry, Department of Chemistry, University of Minnesota, Minneapolis, Minnesota, 55455: Received August 15, 1969

The Botany and Chemistry of Cannabis: Proceedings of a Conference organized by The Institute for the Study of Drug Dependence at The Ciba Foundation 9 10, April 1969: Edited by CRB Joyce & SR Curry: Department of Pharmacology and Therapeutics, London Hospital Medical College: The Williams & Wilkins Company Baltimore First Published 1970 International Standard Book Number 0.7000 14 79.9 Implications of Distribution of Hemp, Chapter 3 page 40 Once hemp is growing well, it is believed to control competing weeds, especially annuals (Hackleman and Domingo, 1943). page 41 Royle (1855) simply stated, "Hemp will smother all weeds". Although weed control by hemp was believed to result from shading by the fast growing annual, another mechanism may be operative. Pratt and Youngken (1951) reported that hemp produced volatile oils comprised of terpenes and sesquiterpenes. Most terpenes inhibit germination and growth at high concentrations. For example, Muler et al. (1964), and Muller and Hauge (1967) found that a western shrub, Salvia leucophylla, produced volatile terpenes and greatly restricted the growth of annual grasses. Since hemp seedlings contain little of the narcotic principle (Kingsbury, 1964), the volatile oils, also, may not be produced until the plant is well established. The inability of young hemp to control weed competition, mentioned by Hackleman and Domingo, may simply reflect the lack of development of terpene production. page 43 Figure 3: Distribution of hemp by US of America Counties. A dot indicates that an escaped specimen was collected at least once in the county. page 44 apparently, this variety does not grow in the warmer regions as evidenced by the distinct absence of the species in the southern United States. Finally, there is a good correlation of hemp distribution with alluvial soils along streams. This trend is most apparent in Missouri, Kansas, Nebraska, Iowa, Minnesota, and South Dakota. Alluvial sites usually have soil conditions well suited to the species, they are frequently disturbed by flooding, and seeds of hemp may be carried in flood water. page 45 Hemp is already a major problem in the US as a source of marijuana. Although the variety present throughout most of the country is reportedly low in narcotic derivatives, it is still widely collected and used. Evidence from this study suggests that hemp is spreading in the United States at an increasing rate. Spread is most rapid in the Midwest on alluvial soils and soils relative low in clay; however, the species can and does invade sites less suited. it shows a tremendous ecological amplitude in this respect and has been collected in nearly every conceivable site from lake shores to cracks in concrete walls and upland pine plantations. Although most of the marijuana used in the US at present results from imported material, as that source is controlled the naturalized variety will probably be used much more. Controlling the collection of a weed that occurs in thousands of vacant lots across the country will be a problem of tremendous magnitude.Page 49 Changes with Maturation in the Amounts of Biologically Interesting Substances of Cannabis, Chapter 4: by Zdenek Krejci Another significant question is closely connected with this one. Cannabis sativa, cultivated in a mild climate for industrial use, contains biologically active substances: to what extent does development of the narcotic principle parallel the antibiotic activity? Neither is it known at what degree of maturation of the plant natural biosynthesis of the hashish principle occurs. Our opinion, which is in harmony with that of other groups, is that the antibiotically effect substances of hemp are forerunners of substances of cannavinol type, and that these change at full ripeness under optimal conditions. page 50 In parallel with these analyses, we examined the growth of antibiotic activity in freshly pressed sap, in all standard concentrated extracts and the above- mentioned isolated resin fractions, at 1% concentration in chloroform. The antibiotic effect was determined by cultivation, on a solid culture medium by the modified Oxford method, of the standard B subtilis microorganism. page 51 The target of this part of the research was to find the stage of development and degree of ripeness of the plant at which new spots appeared on the chromatogram. These substances were compared chromatographically with standard cannabidiolic acid, cannabidiol and tetrahydrocannabinol solutions. page 54 Conclusion: It has been confirmed that cannabidiolic acid appears at relatively early stages of development. Increasing amounts are found, especially in fresh material, at all further degrees of development until full ripeness. In dried material especially if stored for a long time, the amount of cannabidiolic acid decreases as a result of decarboxylation and evidently changes to cannabidiol. Cannabidiolic acid is known to have antibiotic activity, which may account for the parallel between the appearance of cannabidiolic acid and that of antibiotic activity traced from the eight week of development. The influence of the quality of the soil upon the growth and quantity of active substances developed is very interesting. The quality of the soil positively influences the growth and the height of plants. But has no perceptible effect upon the production of extractable substances. The amount of IRC and antibiotic activity produced from less fertile localities is greater. The changes that occur in different stages of development are accompanied by large changes in the quantity of substances extractable by alcohol and petroleum ether. The increase in the amount extractable in petroleum ether at later stages of development is especially noteworthy. These observations confirm the occurrence of qualitative changes in the chemical structure of plant constituents. Pharmacological evaluation on experimental animals will follow the physicochemical results reported here, and will be the subject of further communications.

CANNABIS HEMP SEED AS A BASIC WORLD FOOD - Ralph Loziers, general counsel of the National Institute of Oilseed Products, told the congressional committee studying marijuana prohibition in 1937 that, "Hemp seed…is used in all the Oriental nations and also in a part of Russia as food. It is grown in their fields and used as oatmeal. Millions of people every day are using hemp seed in the Orient as food. They have been doing this for many generations, especially in periods of famine. - Now we know hemp seed is the plant kingdom's richest source of life-giving essential fatty acids, and may well be the cure for cancer and heart disease.

HEMP SEED: HUMANITY'S BEST SINGLE FOOD SOURCE

Economic Geography: Hemp: A Monor American Fiber Crop: Page 127 - 128 Figure 1: American Hemp Districts 1900 - 1910 Figure 2: Hemp Mills 1944 Figure 3: The cement block buildings with circular roofs and the tall chimney of the power plant standardize the US Department of Agriculture mills

Synthesis of Various Compounds: T. Petrzilka Page 90 Figure 2: Delta 9 - THC, LSD, Psilocybin, and Mescaline, drawn to demonstrate structural similarities:

Chemical and Pharmacological Studies of Cannabis: by Stig Agurell: Faculty of Pharmacy and Jan-Drik Lindgren of the Department of Toxicology, Karolinska Institute Stockholm. page 175: Analysis of Biological Samples for Cannabis Constituents: page 188 Binding of Delta 1 Tetrahydrocannabinol to Plasma Proteins: Methods of detecting, determination and study of protein binding have also been reviewed by Meyer and Buttman (1968). Protein binding influences drug concentration in tissue fluids, drug excretion, therapeutic activity and toxicity of drugs and penetration through biological membranes. page 190 In this connection, it should be added that electrophoresis of rabbit plasma three hours after i.v. injection of delta 1 thtrahydrocannabinol - H 3 still showed the major part of the activity to be associated with the albumin fraction. At this time very little of the radioactivity is present as the unchanged compound. This indicates that a major metabolite (or several minor ones) are also pound to plasma proteins. Thus, these experiments show that tetrahydrocannabinol is mainly bound to the plasma proteins.

Numbering Systems, Formulae, Trivial Names and Suggested Abbreviations for Various Cannabinoids: by L. Crombie Page 209 - 213 Nature: Volume 232: August 20, 1971: Cannabivarin and Tetrahydrocannabivarin, Two New Constituents of Hashish: by Frans W. H. M. Merkus: RC Hospital: Sittard: The Netherlands: Received April 18, 1971

Ritual Use of Cannabis Sativa L: A Historical-Ethnographic Survey: William A. Emboden, Jr. pg. 214 - 237 page 219 Cannabis is also the plant which Democritus (ca. 460 B.C.) knew as potamaugis, and which he said was drunk with wine and myrrh to produce delirium and visionary states. Democritus observed the "immoderate laughter: that occurred erratically following a draught of this decoction. The first Greek botanist, Theophrastus (371-287 B.C.), wrote of Cannabis under the name dendramalache and gave one of the first accurate accounts of the plant. page 236 Cannabis is rapidly becoming a "social drug", but historically in societies that have focused on Cannabis (and other psychotropic substances) in a ritual way. In the meantime, it is not obvious that the social costs of enforcing laws based essentially on the hysteria of the 1930's rather than on dispassionate scientific research are out of proportion to the actual or presumed harm done by this ancient euphoriant? Surely one of the most deleterious results of the law - modified recently, to be sure, but still punitive - is precisely a cause - and - effect relationship so often charged to Cannabis: that it leads to the use of other, more dangerous, and truly addictive drugs. The cause - and - effect relationship is not physiological, however, but social, because by having driven Cannabis underground the law forces young people into contact with criminal elements whose motivation is neither ritual nor altruistic but commercial. There is an additional factor, which touches on the relationship of the dominant white society to its minorities. On a television program on drug abuse produced by KNXT, the CBS station in Los Angeles, in 1970, a young female participant from the Spanish-speaking community observed that marijuana had become so expensive that only affluent middle- class whites could afford it, while minority youth seeking momentary relief from unbearable pressures were forced by economics to resort to more readily available and cheaper amphetamines and other potentially far more harmful drugs. To an ethnobotanist concerned with the complex interrelationship, through time, between man and the plant kingdom, especially its numerous intoxicants and euphoriants, it is ironic that Cannabis, which only a few years ago was associated in the public mind exclusively with the poor black and brown minorities, should have joined the long list of social drugs of our drug- oriented, affluent, white middleclass society, while being priced out of reach of those on the bottom rung of the economic ladder. it is doubly ironic if we speculate that some of the remote Mediterranean, Near Eastern, and African ancestors of these minorities might have been among those who long ago used Cannabis as a divine plant and "guide to heaven". Page 237: Tabernanthe Iboga: Narcotic Ecstasies and the Work of the Ancestors: Right at the start I am going to impose upon the reader a conceptual continuum and a confession. At least he is forewarned where certain habits of thought may reach. The continuum is the familiar one between instrumental behavior on the one hand and expressive behavior on the other. Instrumental behavior is behavior in which we seek to change things in the object world by manipulating them in some way, usually to the benefit of ourselves. Expressive behavior is behavior in which we seek to change things within ourselves by giving outward expression to inward states. In instrumental behavior we interiorize. We make as accurate a model as we can of the external world and, conforming our behavior to that model, we hope to influence the world. We have been more successful in this than Francis Bacon, the great interiorizer, could have ever hoped. In expressive behavior we exteriorize. We bring forth the lights and shadows of interior weather and let them play willy-nilly upon the object world, often to creative effect. The distinction we are making is sometimes made, as is appropriate in the age of polymers, between autoplastic and alloplastic action: that is, action that seeks to change the self, and the action that seeks to change everything else. There are undoubtedly philosophic and behavioral difficulties with such a clean distinction. But we hope our discussion of an African narcotic will be of enough interest to carry us beyond the abuse of terms.

Pharmacological Reviews: Volume 23, No 4, Biological Disposition of Tetrahydrocannabinols 1,2: by Edward B. Truitt, Jr: Columbus Laboratories, Battelle Memorial Institute, Columbus, Ohio,: January 1971: page 273 - 278 page 275 Distribution: 3. The ability of THC and \ or metabolites to cross the placenta;...In plasma, 80 to 95% of the delta 9 - THC migrates in association with lipoprotein. page 276 Thus, induction of hepatic microsomal enzymes may explain in part the increasing pharmacological effect of the drug during the first several exposures in addition to improved smoking technique and better recognition of the euphoric effect. Induction of microsomal non-specific oxidases is implied by the finding of a shortened barbiturate sleeping time in mice treated chronically with THC. Finally, a significant relationship may exist between persistence of dihydroxy-THC and hydroxy cannabinol derivatives and the after-effects of THC on mood, motivation and thought processes. page 277 In rats, the persistence of excretory products in the feces suggested an enterohepatic circulation which has been confirmed by Klausner and Dingell who showed reabsorption of the metabolites after an introduodenal injection of bile in an untreated recipient rat. Recycling of THC metabolites in this manner is reminiscent of the macrolide antibiotics and may also be related to the occurrence of gastrointestinal side effects by both groups of compounds.

Nature: Volume 232 August 20, 1971 pg. 579-580: Cannabivarin and Tetrahydrocannabivarin, Two New Constituents of Hashish: pg. 580 It is also likely that tetrahydrocannabivarin will have an additive or a synergistic effect to the tetrahydrocannabinol effect. We have found that in many samples of hashish a considerable quantity of cannabidivarin, tetrahydrocannabivarin and cannabivarin is present. The identification and the quantitative determination contribute to a more exact chemical knowledge of the constituents and their biosyntheses and allow a better understanding of the different biological activities of hashish samples.

Pharmacological Review: Volume 23. No 4: Session I Cannabis Prelude: by E. Leong Way: Department of Pharmacology, University of California, San Francisco Medical Center, San Francisco, California: page 263 - 271 page 267: copy page 27 Pure Delta 8 and Delta 9 THC are thick, viscours oily materials at room temperature, and resinous solids when cold. They are soluble in organic solvents and insoluble in water. Though they are soluble in alcohol, they oil-out on diluting with water. Aqueous suspension can be made with Tween 80.

The Identification and Misidentification of Marijuana: by Dwight S. Fullerton, PHD., RPH: Dr. Fullerton is Assistant Professor of Medicinal Chemistry at the College of Pharmacy, University of Minnesota, Minneapolis. about 1974 pages 291 - 345 page 291 In 1972, there were 292,179 people arrested in the US for crimes involving marijuana. In 1973, marijuana arrests numbered 420,700, or 43% more than the previous year. During 1974, over 500,000 people pg 315 "Cystoliths" are defined as "clustered bodies formed by the thickening of the cell wall at a certain point and subsequent ingrowth which later forms a cellulose skeleton consisting of a stalk and body. . . calcium carbonate is pilled up on the body in layers, forming an irregular spheroidal deposit." More simply stated, the cystolith hairs being looked for in marijuana are multicellular, nonglandular hairs which are usually shaped like bear-claws.

Chem. Pharm. Bull. 20 (9): page 2072: (Received May 22 1972):Toyko: UDC 547 597 02 581 192 615 322: Volume 20: Cannabidiol Monomethyl Ether. A New Neutral Cannabinoid

J. Pharm. Pharmac., 1974, 26,: pages 413-419: Received November 14, 1973: The Cannabinoid Content of Cannabis Sativa L Grown in England: by J.W. Fairbairn and JA Liebmann: Department of Pharmacognosy, The School of Pharmacy, University of London, Brunswick Square, London WC1 1AX, UK:

Tetrahedron: Volume 30: Pages 237 to 2446: Pergamon Press 1974: Printed in Great Britain: Cannabielsoic Acids Isolation and Synthesis by a Novel Oxidative Cyclization: by A Shani: Department of Chemistry, University of Negev, Beer Sheva, Israel: Received in the UK December 5, 1973: Accepted for publication February 25, 1974 Summary: Freezing, or sitting in sun in vacuum sealed containers does not change, but to let the air get to it changes a lot:

Journal of Pharmaceutical Sciences: Volume 60, No. 8, August 1971: page 1246 - 1249: Mississippi-Grown Cannabis Sativa L: Preliminary Observation on Chemical Definition of Phenotype and Variations in Tetrahydrocannabinol Content versus Age, Sex, Plant Part: by Patricia S. Fetterman Abstract: Nine Strains of Cannabis Sativa L Iowa, Minnesota, Mexico, Turkey, Italy, France, & Sweden page 1248 has Table I - GLC Analysis of Phenotype Classification of Various Samples of Marijuana

from The Consumers Union Report on Licit & Illicit Drugs, pp. 294-298, by Edward M. Brecher - and the editors of Consumer Reports (Little, Brown and Company, Boston, 1972), ISBN 0-316-10717-4, The Swedish Experience

Psychoses, Adverse Reactions, and Personality Deterioration - Chapter 10 from Marihuana Reconsidered, pp. 253-290, by Lester Grinspoon, M.D., 1971, 1977, - Harvard University Press, ISBN 0-674-54834-5, Library of Congress Catalog Card Number - 77-76767

Pharmacological Reviews: Volume 23 No. 4: pages 265 -271: Chemistry of Marijuana: by Coy W. Waler: Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi

American Review of Respiratory Disease, Volume 112, 1975. - Effects Of Smoked Marijuana In Experimentally Induced Asthma (Summary) - By Donald P. Tashkin Bertrand J. Shapiro Y. Enoch Lee and Charles E. Harper

Chemical Reviews, 1976, Volume 76, No 1 77: Chemistry and Biochemistry of Cannabis:Recent advances in the Chemistry and Biochemistry of Cannabis: Raphael Mechaulam: Department of Natural Products: Hebrew University School of Pharmacy, Jerusalem, and The Wrocester Foundation for Experimental Biology: Revised March 18, 1975: page 75 - 112: page 95 The difference between quantitative analyses of silylated and unsilylated extracts enables the determination of cannabinoidic acids in samples to be administered by routes other than smoking. However, if the sample is to be smoked, there is a case for quoting the apparent cannabinoid amounts determined as the unsilylated xtract, since any acids present in the sample will be decarboxylated by the smoking process. In these samples, cannabinoid losses during smoking commonly 50 or even higher, depending on the method of sample preparation and combustion conditions. Thus although it is desirable to administer cannabinoids experimentally in a manner closely approximating to page 105 The effect of delta 1 - THC on potassium ion influx in rat erythrocytes has been studied by Gibermann et al. They concluded that it was an inhibitor which was ph dependent in a manner similar to certain anesthetics. Schurr et al. have reported that glucose efflux from erythrocytes is inhibited in cannabinoids. The production of bone marrow cells in rats can be disturbed by injection of delta 1 THC./ While these results suggest that the use of cannabis may diminish defense against injection, the authors also point out that the drug may be beneficial in combating certain forms of leukemia. Kubena et al. reported that corticosterone plasma levels were significantly raised in rats given delta 1 THC. The response was dose related in the range of 1-4 mg\kg and could not be evoked in hypophysectomized animals. The authors, therefore, conclude that the effect was mediated through the central nervous system. Delta 1 THC can alter hypothalamo-pituitary function. Effects have been reported on both male and female reproductive systems which might be expected from the results of the studies on THC distribution (vide supra). Nir et al. found that the characteristic cyclic luteinizing hormone peak in female rats was completely abolished by two 10 mg injections of delta 1 THC. They also observed that ovulation had been greatly reduced, an effect which they had also seen with indomethacin. the latter drug is a potent inhibitor of prostaglandin biosynthesis, a property which has also been found for a number of cannabinoids including delta 1 THC. This suggests that the two drugs may be acting on the ovary by similar mechanisms; however, more evidence is needed. ***It should be noted they used only synthetics and injection was by needle in laboratory animals.

Journal of Pharmaceutical Sciences: Volume 64, No. 5, May 1975: Constituents of Cannabis Sativa L. XI: Cannabidiol and Cannabichromene in Samples of Known Geographical Origin: pages 892 - 895: These are seed samples & graphs showing US Cannabis usually has no THC content: Page 1084: Isolation of Cannabisativine, an Alkaloid, from Cannabis Staiva L. Root: By Carlton E. Turner: Cannabisativine (new spermidine alkaloid) isolated from roots of Cannabis Sativa: Cannabis Sativa L. has several low molecular weight nitrogen - containing substances including choline (1-4), trigonelline (2,3), muscarine (5), piperidine (6), N-(p-hydroxy-B-phenylethyl) - p - hydroxy-trans-cinnamamide (7), nurine (8), L-proline (8), and L-(+) - isoleucine betaine (9).

Phytochemistry, 1975: Volume 14, page 2304: Pergamon Press: Printed in England: Alkaloids of Cannabis Sativa Leaves: Received April 4, 1975: Key Word Index: Cannabis Sativa: Cannabinaceae, marijuana leaves; alkaloids; 4-(B-dimethylaminethyl-phenol; hordenine. Plant Medica: Volume 28, 1975: Malingre, Hendriks, Batterman, Bos & Visser Laboratory of Pharmacognosy and Galenical Pharmacy, University of Groningen, The Netherlands: Essential Oil of Cannabis Sativa: pages 56 -61

Journal of Medicinal Chemistry: 1976: Volume 19 No 4: page 552 - 554: Drugs Drived From Cannabinoids: 4. Effect of Alkyl Substitution in Sulfur and Carbocyclin Analogs: by RK Razdan, SISA Incorporated, Cambridge, Massachusetts, 02138: Abbott Laboratories page 554 Pharmacology: All compounds were administered orally as a suspension of 0.5% methylcellulose. The compounds for the sedative - hypnotic study (cat) were mixed with food. Mice were used for the Dopa potentiation, mouse fighting, audiogenic seizure, writhing, and hot-plate tests, rats for the motor activity and tail-flick tests, dogs for ataxia, and cats for the sedative-hypnotic studies.Journal of Medicinal Chemistry, 1976, Volume 19, No. 4. pages 454 to 461: Drugs Derived from Cannabinoids: Basic Esters of Nitrogen and Carbocyclic Analogs: by: Raj K. Razdan, SISA Incorporated, Cambridge, MSS Drugs Derived from Cannabinoids. 5. Tetrahydrocannabinol and Heterocyclic Analogs Containing Aromatic Side Chains: Page 461 "They found that the nitrogen analog 4a (R' = CHxC=CH) had analgesic activity ranging between that of codeine and morphine with no physical dependence liability."

J. Pharm. Pharmac., 1976, 28, pages 280 - 285: Received July 22, 1975: Characterization of the butyl homologues of delta 1 tetrahydrocannabinol, cannabinol and cannabidiol in samples of cannabis by combined gas chromatography and mass spectrometry: *** One of the samples in this experiment was 140 years old sealed in a bottle

Economic Botany, 38 (2), 1984 . PP 256 -271: by the New York Botanical Garden, Bronx, NY, 0458: Book Reviews: by John W. Thieret, Book Review Editor: Marijuana and Health: National Academy of Sciences, Institute of Medicine Division of Health Services Policy: 188 pages National Academy Press, Washington, DC, 1982: ***Compares this to the British Hemp Enquiry done 100 years ago. "The volume is divided into eight sections: "Chemistry and Pharmacology of Marijuana", Use of Marijuana in the United States". "Effects of Marijuana on the Respiratory and Cardiovascular Systems: Effects of Marijuana on the Brain," "Effects of Marijuana on Other Biological Systems,: :Behavioral and Psychosical Effects of Marijuana Use," Therapeutic Potential and Medical Uses of Marijuana," and "Federal Support of Research on Marijuana"

Botany Gaz. 144 (1) pages 43 - 48, 1983: Effect of Light Quality of Cannabinoid Content of Cannabis Sativa L. (Cannabaceae): Paul G. Mahlberg:

Department of Biology, Indiana University, Bloomington, Indiana, 47405: Journal of Natural Products: Vol 47, No 3 pages 445 - 452: May- June 1984: Constituents of Cannabis Sativa. XXV. Isolation of Two New Dihydrostilbenes from a Panamanian Variant: By Hala N. Elsohly: Visiting professor from the Shangai Institute of Materia Medica, Chinese Academy of Sciences, People Republic of China at the University of Mississippi:

Bot. Gaz. 146 (2) pages 32 - 38. 1985: A Temporal Study of Cannabinoid Composition in Continual Clones of Cannabis Sativa L. (Cannabaceae) by Jocelyn C. Turner: Department of Biology: Indiana University.

Botanical Gaz 148 (3): pages 468 to 474: December 1987: Cannabinoid Occurrence in Seedlings of Cannabis Sativa L: Quantitation In Seedlings of Known Age and Primary Leaf Length: by Ann F. Vogelmann: Jet Propulsion Laboratory MS 183-501, California Institute of Technology, Pasadena, CA, 91109:

Journal of Natural Products: Volume 51, No. 6, pages 1075 - 1079, Nov - Dec 1988: Cannabinoid Composition in Seedlings Compared to Adult Plants of Cannabis Sativa: Ann Vogelmann,: Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA, 91109:

Phytochemistry: Volume 30, No. 9 Pages 3013 to 3016: 1991: Printed in Great Britain: Cannabisin A, An Arylnaphthalene Lignanamide From Fruits of Cannabis Sativa: Iwao Sakakibara, : Tsumura Research Institute for Biology and Chemistry: Japan: Received Feb 25, 1991: Page 3013: Introduction: Fruits of Cannabis Sativa have been used as purgatives in China and Japan. Previously, several fatty acids [1], choline, and torigonelline [2] were isolated from this material. We have now isolated a new lignanamide, cannabisin A, together with a known lignanamide and three amides: Result & Discussion: Cannabisin A (1) was isolated from an aqueous ethanol extract of C. Sativa, Together with a lignanamide, grossamide (2) [3] and three amides: N-trans-caffeoyltyramine (3), N-trans-feruloyltyramine (4) and N-p- coumaroyltyramine (5) [4]

The Economists: July 6, 1991: Science & Technology: Medical Marijuana: Cross-eyed and painless: Cambridge, Massachusetts: last year almost 100,000 doses of Marinol were prescribed:

Life Sciences, Volume 48, Pages 507 - 515: Pergamon Press: Antagonism of Marihuana Effects by Indomethacin in Humans: by Mario Perez-Reyes: Department of Psychiatry, University of North Carolina, School of Medicine: Received in final form November 28, 1990: page 511 Free Recall: Mean free recall performance decreased and partially recovered across time after smoking. Whereas the memory impairment appears to be worse in the placebo condition than in the indomethacin condition. ***Indomethacin must be a drug to keep you from liking or getting high off pot.

American Journal of Botany 78 (8) pages 1113 - 1122: August 1991: Cuticle Development on Glandular Trichomes of Cannabis Sativa (Cannabaceae): By Paul Mahlberg: Department of Biology, Indiana University, Bloomington, Indiana:

American Journal of Botany 78 (2) pages 220-229, February 1991: Secretory Cavity Development in Glandular Trichomes of Cannabis Sativa L (Cannabaceae) by Eun-Soo Kim: Department of Biology, Indiana University:

Chemistry & Engineering: August 24, 1992: page 25: Photoaffinity label for cannabinoid receptor: "Effects mediated by THC at the receptor include antiiasthma effects, increased heart rate, reduced eye pressure, pain relief, antinausea properties, body temperature changes, mood-altering effects...The THC receptor was recently cloned and expressed, and its amino acid sequence was determined.

Euphyytica 62: 187-200,1992: Chacterisation of Cannabis accessions with regard to cannabinoid content in relation to other plant characters: by EOM de Meijer: Center of Plant Breeding and Reproduction Research: The Netherlands: page 196 has a Table with average content of THC and CBD & THC\CBD ratio

Euphytica 62: pages 201 - 211: 1992: The CPRO Cannabis germplasm collection: by EPM de Meijer: Center of Plant Breeding: The Netherlands: page 203: Seeds currently used for experiments were stored in paper bags in a dark coldroom at 4oC and relative air humidity of 30%. Under such conditions seed moisture content reaches an equilibrium of about 6%: Page 209 Drug cultivars: The drug strains in the collection are poorly documented. "Skunk" is a hybrid between indigenous strains from Afghanistan, Mexico and Colombia. The Hybridization work took place in 1976 in California, USA and ten years of inbreeding a selection of the progency resulted in a consistently true breeding cultivar. Skunk is currently commercialized for indoor cultivation in the Netherlands.

Discover 12: August 1992: Sex: Stoned Sperm: The active ingredient in Marijuana is a molecule called THC, which binds to a receptor on the surface of brain cells. Mood elevation often ensues, as well as a heightened ability to find interest in very silly things. ...our distant cousins the spiny sea urchins have THC receptors too - not in their brains, but on their sperm. ...Echinoderms, the phylum that includes sea urchins, and chordates, the phylum that includes vertebrates like us, are believed to have diverged from a common ancestor some 600 to 800 million years ago. Thus the THC receptor seems to be at least that old - which only makes researchers all the more eager to find out what it does for organisms that don't smoke pot. "It's survived over this enormous time," says Schuel. "Whatever it's doing it must be tremendously important. ***There is also a article about The Country Leaf & the City Leaf: Holy, growing Ketteringham, England. A holly leaf has thousands of stomata covering every square inch of its surface. On the city- bred leaf, however, many of the stomata are clogged by grit, mostly carbon and lead from car exhaust. The pollutants not only clog the plant's vital pores but also prevent sunlight from reaching much of the leaf's surface. The color of the leaf was gray.

Phytochemistry: Volume 31, No. 9 pages 3219 - 3223, 1992: Printed in Great Britain: Three Phenyldihydronaphthalene Lignanamides From Fruits of Cannabis Sativa: Iwao Sakakibara: Tsumura Research Institute for Biology & Chemistry: Abstract: Three new lignanamides, names Cannabisin B, C, & D, were isolated from the fruits of Cannabis Sativa.

American Journal of Botany 79 (2): pages 166 - 173: February 1992: Secretory Vesicle Formation in Trichomes of Cannabis Sativa (Cannabaceae) by Paul G. Mahlberg: Department of Biology, Indiana University: page 172: The continued production of lipophilic secretory vesicles at the plasma membrane-wall interface relates to the composition and role of vesicle contents. Vesicles probably contain fatty acids associated with cuticle formation: which thicken the cuticle of the developing gland. There are also present in the gland volatile monoterpenes and sesquiterpenes. ...It also provides insight into the mechanism for secretion of cuticular and waxy components in dermal and other cells. This study supports the interpretation that such lipophilic components are secreted directly into and through the wall from the plasma membrane surface.

Science: Volume 258: December 18, 1992: pages 1882 & 1884 Pot, Heroine Unlock New Areas for Neuroscience: by Marcia Barina: This is the story of Anandamide:

Science: Volume 260: April 2 1993: page 16: Drug Abuse Research: by Richard A. Millstei: Acting Director, National Institute of Drug Abuse: Rockville, MD, 2085: Congratulate Science for Pot, Heroin Unlock article above:

Proc. Natl. Acad. Sci, USA: Volume 90 pages 7656 - 7660: August 1993: Cell Biology: Anandamide, an endogenous cannabimimetic eicosanoid, binds to the cloned human cannabinoid receptor and stimulates receptor-mediated signal transduction: by Christian C. Felder: Laboratory of Cell Biology, and Laboratory of Clinical Science, Section on Analytical Biochemistry, National Institute on Mental Health, Bethesda, MD: Abstract: (arachidonylethanolamide/adenylate cyclase / phosphosipase A2/calcium/calcium current): Anandamide inhibited forskolin-stimulated cAMP accumulation in CHO-HCR cells, but not in CHom5 cells, and this response was blocked with pertussis toxin. N-type calcium channels were inhibited by anandamide and several active congeners in N18 neuroblastoma cells. Anandamide stimulated arachidonic acid and intracellular calcium release in both CHOm5 and CHO-HCR cells and had no effect on the release of inositol phosphates or phosphatidylethanol, generated after activation of phospholiphase C and D, respectively. Anandamide appears to exhibit the essential criteria required to be classified as a cannabinoid/anandamide receptor agonist and shares similar nonreceptor effects on arachidonic acid and intracellular calcium release as other cannabinoid agonist. Abbreviations: HCR, human cannabinoid receptor: THC delta 9: G protein, guanine nucleotide binding protein THC bind to specific cannabinoid receptors and couple functionally to inhibit adenylate cyclase and inhibit N- type calcium channels via a pertussis toxin-sensitive guanine nucleotide binding protein (G protein). The cannabinoid receptor is found primarily in brain tissue with the highest concentrations in the substantia nigra pars reticulata, globus palidus, and molecular layer of the cerebellum. Cannabinoid receptors have also been identified in testis and in spleen cells. In a variety of cell types, cannabinoid agonists cause a concentration-dependent increase in arachidonic acid release presumably through a combination of phospholipase A2activation and acyltransferase inhibition. We have demonstrated both receptor and non-receptor mediated activation of signal transduction pathways by cannabinoid agonists in mammalian cell lines transfected with and stably express the cannabinoid receptor. In these cells, cannabinoid-receptor-coupled signaling utilized adenylate cyclase as an effector enzyme, whereas noncannabinoid receptor effects included activation of phospholipase A2 and intracellular calcium release. Expression of cannabinoid receptors in the brain suggested the presence of an endogenous ligand and a normal physiological role for the receptor in brain function. Arachidonylethanolamide (anandamide), a candidate endogenous cannabinoid ligand, has recently been isolated from porcine brain and inhibited cannabinoid-agoinst-specific binding to synaptosomal membrane preparations. Anandamide mimicked cannabinoid-induced inhibition of the twitch response in isolated murine vas deferens, suggesting it may be functionally similar to THC. However, functional activity of anandamide at the cannabinoid receptor and stimulation of one or more second messenger responses have been definitely demonstrated. In this study, mammalian cells stablyt expressing the transfected human cannabinoid receptor were used to determine whether anandamide bound specifically to the cannabinoid receptor and coupled to the inhibition of cAMP accumulation. In addition, chemical modification were made to both the arachidonyl and ethanolamide moieties of anandamide to establish the structurally important elements of anandamide required for activity. The efficacy of these analogs in inhibiting high-voltage-activated calcium currents (N-type calcium channels) in N18 neuroblastoma cells was also assessed. Finally, selectivity of the cannabinoid receptor for coupling to various signal transduction pathways was evaluated and comparison was made to the action of anandamide on muscarinic m5 receptor-transfected control cells. Page 8758 Fatty acids were purchased from Cayman Chemicals (Ann Arbor, MI) fetal bovine serium and "differentiated" in DMEM/0.5% fetal bovine serum/2% page 7658 Anandamide is a combination of arachidonic acid and ethanolamine coupled through an amide linkage. Thus, for the compounds examined. The ability of the anandamide congeners to inhibit calcium currents closely parallels their activity in binding to the cannabinoid receptor and inhibiting adenylate cyclase, suggesting common receptor interaction. In the absence of forskol anandamide stimulated a more modest cAMP accumulation in pertussis toxin- treated CHO-HCR cells. page 7660 Anandamide fits essential criteria to establish it as an endogenous agonist for the cannabinoid receptor. Anandamide has been shown to display saturable and specific binding, to stimulate functional second messenger responses, and to mimic the action of cannabinoid agonists in several behavioral paradigms. G-protein-coupled receptors can be generalized to belong to either the inhibitory group of receptors, which inhibit adenylate cyclase, or to the calcium mobilizing group of receptors, which can activate membrane associated phospholipases leading to changes in intracellular calcium. The cannabinoid/anandamide receptor appears to exhibit the properties of an inhibitory receptor except for its inability to modulate the release of arachidonic acid in the CHO cell model as shown for other inhibitory receptors.

Nature September 2, 1993: Volume 365 Issue No. 6441 v Peripheral vision: The cannabinoids can exert a wide range of effects which could be useful clinically, including analgesic, anti-inflammatory, antiemetic, and immunosuppressive activity. But the better-known psychoactive properties limit clinical applications. So the discovery of a cannabinoid receptor located in peripheral tissue rather than the central nervous system has implications not only for our understanding of the action of cannabinoids, but also suggests potential pharmaceutical uses.

American Journal of Botany: Volume 78: Secretory Cavitry Development: by Kim and Mahlberg: February 1991: page 223 - 229

Plant Disease/Volume 75 No3 Diseases of Cannabis Sativa L. by JM McPartland, Primary Collator: page 226 - 227

Nature: Volume 365: September 2, 1993: Medical uses of marijuana? by Leslie L Iversen: ...Its diverse uses include the treatment of pain and inflammation, the lowering of intraocular pressure in glaucoma, the relief of nausea associated with cancer chemotherapy, and the relief of muscle spasms associated with multiple sclerosis. ...cannabinoid receptor...is not present in brain but only in peripheral tissues. six classes of clones expressed in a human leukaemic cell line with homology to G protein-coupled receptors. Some of these appeared to correspond to known G-protein-coupled receptors. Some of these appeared to correspond to known G-protein-coupled receptors but others were novel. One of these, termed CX5 showed some homology with the cannabinoid receptor, whose identification and ...when the CX5 complementary DNA was transfected into tissue culture cells and expressed, its identity as a cannabinoid receptor gene was confirmed by the high-affinity binding of the synthetic high-affinity cannabinoid receptor radioligands CP 55940 and Win 55212-2. Furthermore, Delta 9 THC displaced these radioligands with high affinity, whereas the biologically interactive analogue cannabidiol was much less effective. Further experiments revealed that expression of messenger RNA for the CX5 gene could only be detected in rat spleen,...Within the spleen, in situ hybridization experiments revealed the presence of high densities of CX5 in the marginal zones around the periarteriolar lymphoid sheths. Many questions remain unanswered. Is the second cannabinoid receptor expressed only in the spleen? The high level of expression, probably in the highly active macrophages, in a region where the outside world meets the immune system, suggests a possible role in inflammatory and immune responses to infection or other foreign antigens. Might CX5 be found more widely in macrophages elsewhere? The inducibility of CX5 by dimethylformamide reported by the authors in the human cell line may suggest macrophage expression of CX5 will prove similarly inducible. Among other tissues that might be examined, the testis is important as this is the only peripheral tissue that exhibits some expression of the brain-type cannabinoid receptor. An issue raised by the therapeutic use of cannabinoids has been there effects on male fertility and ability to lower testosterone levels. The delta 9 THC analogue cannabinol showed some selectivity for the CX5 site compared with the brain receptor. Further medicinal chemistry efforts could no doubt yield highly selective ligands. It is possible that such compounds might represent novel anti-inflammatory or immunosuppressant agents. The discovery by Munro highlights yet again the ability of molecular biology to discover new receptors at a rate much faster than pharmacologists can handle. Page 61- 65: Molecular characterization of a peripheral receptor for cannabinoids: Sean Munro: MRC Laboratory of Molecular Biology: Hills Road, Cambridge: UK Delta 9 THC also exert a wide range of other effects including analgesia, anti-inflammation, immunosuppression, anticonvulsion, alleviation of intraocular pressure in glaucoma, and attenuation of vomiting. ...The marginal zone in the site through which blood-borne cells and antigens enter the spleen, and the marginal zone macrophages comprise a distinct population of highly phagocytic cells thought to play a role in both digesting and processing bacterial antigens and in directing lymphocyte recirculation. ...The in vivo function of CX5 is presumably to tranduce a signal through a G protein in response to an endogenous ligand, although we do not yet have direct evidence for such coupling. ... Anandamide is able to cross the blood brain barrier rapidly but worthwhile speculation as to its function, and possible interactions between the neural and immunological systems, will require the identification of all the sources of this intriguing molecule. ... We suggest that in the future the two receptors be distinguished by calling the brain receptor CB1 and the CX5 receptor CB2. It has been proposed that the peripheral effects of cannabinoids are either indirect effects of central actions, or reflect interactions with non-receptor proteins such as lipoxygenases. It is clearly possible that some of these peripheral effects are in fact medicated through the CB2 receptor and it will be interesting to determine the activities of any cannabinoids specific for this receptor.

Nature: Volume 366: December 16, 1993: Decriminalizing Drugs: The US Surgeon-General has revived a long-simmering debate about existing legal restraints on drug abuse.

Science: Volume 263: February 4, 1994: pg 599 Reefer Madness at FDA: about a 40 person pilot study comparing Marinol to a range of marijuana doses. If FDA approves the new protocol, the trial will start this summer.

Nature: Volume 364: August 19, 1993: by Plinio Prioreschi: Division of History of Medicine: Department of Pharmacology, Creighton University University School of Medicine: page 680: Ancient use of cannabis: ...Rather it was used for such disparate conditions as empyema, "phthisis", "typhus", leucorrhoea, habitual abortion, "dropsy of the uterus", metrorrhagia and "displacement of the uterus." In all these cases there is no mention of cannabis use for pain. On only three occasions is the relief of pain mentioned and , in these, poppy is used as one ingredient in a mixture with other drugs.

Nature: Volume 363: May 20, 1993: Early Medical Use Of Cannabis: Joe Zias: Israel Antiquities Authority: Jerusalem, Israel: Page 215: This procedure would usually have been carried out by a midwife as physicians were by law prohibited from attending women in labour. In the nineteenth century, its use in obstetrics is cited in several medical publications, one of which indicated that C. sativa had the remarkable power to increase the force of uterine contractions, concomitant with a significant reduction of labor pain.

Nature: September 11, 1993: Page 165: Immune cells sport marijuana receptor: E. Pennisi: ...this newly identified receptor, which is located on cells Called macrophages that lie in the parts of the spleen where substances in the blood first encounter the immune system. ... In the spleen, THC like compounds seem to affect the ability of cells to generage a messenger molecule that helps activate white blood cells, says Norbert E. Kaminski at Michigan State University in East Lansing. ... Because the spleen and brain receptors are different and because other researchers have discovered marijuana receptors in fish and sea urchins, Munro suspects that this ancient psychoactive agent ties into an ancient and wide spread internal signaling system for organisms.

Science News: Volume 143: February 6, 1993 Page 88: Marijuana and the Brain: Scientist discover the brain's own THC: by Kathy A. Fackelmann: Many scientists speculate that such internal compounds help humans cope with stress and pain. The findings may help neuroscientists figure out how these brain-made substances work at the molecular level. page 89: The researchers labored for two more years to get enough of the purified compound - a drop of lear, oily fluid - to examine in detail. Using a technique called mass spectrometry, they determined the structure of the substance. Devane, of course, had no trouble coming up with a name, anandamide. Anandamide is derived from arachinodic acid, a 20-carbon carboxylic acid that is the starting point for a cascade of complex biochemical reactions. One branch of that cascade leads to the production of the leukotrienes, key substances in the inflammation process. Another branch leads to substances known as prostaglandins, which play role in mediating pain. Devane believes another, as yet uncharted branch of this cascade leads to anandamide. In smaller doses that occur naturally in the body, anandamide may be involved in the regulation of mood, memory, pain, movement, and other activities, Devane says. ... This observation suggests that a defect in anandamide or its receptor may cause certain diseases characterized by loss of motor control. For example, some scientists speculate that the natural marijuana-like substance may play a role in Huntington's chorea, a progressive hereditary disease that interferes with muscular control. There's no proof that anandamide is connected to Huntington's disease, however Herkenham's preliminary data suggest that people with Huntington's lose lots of THC receptors early in the disease process, even before symptoms start to surface. ... Such evidence suggests that anandamide is involved in appetite control Brownstein says. ... Several decades ago, neuroscientists identified endorphines and enkephalins, opium- like compounds manufactured by the human brain. . page 94 . Evans & his co-workers have identified and described the messenger RNA that carries the genetic blueprint for one type of opiate receptor from the DNA of a cell's nucleus to the receptor's production site. ... The messenger RNA for opiate receptors is very rare and difficult to isolate. But once they had the messenger RNA, the team could determine the amino acid that make up the receptor. ...The opite receptor and the THC receptor belong to a family of proteins that do their work via molecules called G-proteins. Evans says such receptors work this way: An opiate or THC like drug binds with the receptor on the outer surface of the cell. Once activated, the receptor acts on G-proteins inside the cell, a process that leads to a cascade of bio-chemical reactions and a feeling of euphoria....Like anandamide, the endorphins and enkephalins play a role in a healthy brain and are probably involved in immune function, motor control, and pain relief, Evans speculates.

Life Sciences: Volume 52: 1993 Pages 757-767: Pergamon Press: Acute Changes in Cerebral Blood Flow After Smoking Marijuana: Roy J. Mathew: Department of Psychiatry: Duke University Medical Center: Box 3972: In experienced marijuana smokers, marijuana smoking was accompanied by a significant bilateral increase in cerebral blood flow (CBF) especially in the frontal regions and cerebral blood velocity. Similarly, the CBF increase was unrelated to plasma levels of THC and extracranial circulation. ... It is conceivable that the behavioral manifestations are mediated through activation and deactivation of different brain regions. In normal subjects, cerebral blood flow (CBF) and cerebral metabolism (CMR) which are closely coupled with brain function can be used as indices of brain function. Experienced Smokers (ES). on the Profile of Mood States (POMS) reported no dysphoria, or severe anxiety, their score dropped from 9.8 to 6.9, and the Cerebral blood flow (global) increased significantly. The CBF increase after marijuana, in ES, reached significance in left and right frontal regions and left temporal region. pg. 759 CBF Measurements: brain was analyzed with a bicompartmental model which separated the fast grey matter perfusion from slower white matter and extra-cranial tissue perfusion. Depersonalization Inventory (DPI) and Temporal Disintegration Inventory (TDI) CO2 is a potent cerebral vasodilator Xenon inhalation technizue measures grey matter perfusion to the cerebral cortex in the in each hemisphere. It is possible to separate blood flow to large brain regions. page 760 We calculated flow to the anterior (frontal and central) and posterior (temporal, perietal and occipital) regions for each hemisphere and submitted these to a drug by time by hemisphere and by anterior, posterior (A-P) model. CBR increases were stronger in the anterior part of each hemisphere. page 761 Analysis of THC plasma levels indicated peak plasma levels were at 5 minutes for both doses of THC. Analyses conducted for the systolic blood pressures indicated slight by statistically significant drug by time effects. page 762 slight decrease in systolic pressure over the first forty minutes following 3.55% THC - slight rise in pulse rate: page 763 CBF side of the equation the structure coefficients (correlation's of the variable with the canonical variable which indicates which variables or regions define the canonical variable) were highest for (rank order): frontal right, temporal right, and frontal left and smallest for parietal left. On the rating scale side, the self rating of "high" was greatest followed by depersonalization, confusion and temporal disintegration. Thus, changes in CBF in the frontal and temporal regions particularly on the right side were most heavily correlated with a pattern of psychological changes assessed by these four rating scales: Changes in CBF are accompanied by parallel changes in flow velocity in the middle cerebral artery which carries 80 % of the hemispheric flow. We measured cerebral blood velocity (CBV) after marijuana smoking with page 764 CBV increased during and after the smoking...but there were no significant changes in blood pressure. It should be noted the middle cerebral artery CBV does not represent changes in global CBF and that changes in the middle cerebral artery caliber (in addition to cerebral capillary perfusion) can also explain the findings. page 765 (Carbon monoxide can limit oxygen delivery to the brain and cause a CBF increase. ... CBF is autoregulated from moderate changes in perfusion pressure which were minimal after marijuana. Conditions characterized by increased brain arousal such as epileptic seizures and moderate degrees of anxiety are associated with CBF increase while low arousal states such as slow wave sleep and coma are accompanied by decreased CBF. Depersonalization and altered time sense are associated with temporal lobe pathology which might explain Canonical correlation's between right hemispheric temporal flow and behavioral changes. marijuana is known to increase sensory awareness which may account for the increase in pariental flow after marijuana especially on the left side. This work was supported by a grant from the National Institute on Drug Abuse (DA 04985)

Therapeutic Hemp Oil: The nutritional composition of oil from the marijuana plant could be beneficial to your health. by Andrew Weil, M.D: Professor at University of Arizona College of Medicine, and is the author of Natural Health, Natural Medicine, 1990: Hemp oil contain 57 percent linoleic (LA) and 19 percent linolenic (LNA) acids, in the three to one ration that matches our nutritional needs. These are the essential fatty acids (EFA's) so called because the body cannot make them and must get them from external sources. The best sources are oils from freshly ground grains and whole seeds, but EFA's are fragile and quickly lost in processing. EFA's are the building blocks of longer chain fats, such as eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), that occur naturally in the fat of cold-water fish like sardines, mackerel, salmon, bluefish, herring, and, to lesser extent, tuna. Adding these foods to the diet seems to lower risks of heart attacks because omegas- 3 fatty acids reduce the clotting tendency of the blood to improve cholesterol profiles. They also have a natural anti-inflammatory effect that makes them useful for people with arthritis and autoimmune disorders. Hemp oil also provides 1.7 percent gamma-linolenic acid (GLA) My experience is that it stimulates growth of hair and nails, improves the health of the skin, and can reduce inflammation.

The Drug Policy Letter: Number 22: New Ways of Thinking About Drugs: Spring 1994: page 8: One reason to consider legalization is the notion of desert, of fairness. Traffickers do not deserve the profits we are helping them to gain. Our efforts to curtail production and impede the sale of drugs keep in place a complex set of institutions - from the local police to international organizations - that consume billions of dollars and imperil the lives of thousands in both the US & Colombia and whose chief effect, judging from the results we have, is to reward the traffickers and their associates, by keeping the price of their deadly merchandise artificially high. Our present approach offers criminals, large and small, a profit margin that no honest business ordinarily yields. In the process, we may be contribution to the generation of all the problems and vices that accompany drugs, i.e., violence, corruption and a generalized disregard for law, both on the part of those who intentionally flaunt it by engaging in drugrelated activities, and sadly, on the part of those who erode constitutional protections in their efforts to strike a blow a the drug business.

Senator John Kerry: D. Mass - condemnation of the Colombian Attorney General's positions for ending the drug war, we will never win. 421 Russell Senate Office Building, Washington, DC, 20510

The New York Times: February 27, 1993: Drug Policy Action: The Drug Policy Letter: Foundation Funs Full-Page Ad Demanding Change in Drug Policy: 108 signatories from a variety of background lent their support to the ad. 25 were medical doctors, 10 current and former law enforcement officials, ***Pull this for names of prominent individuals who help pay for the ad.Drug Policy Foundation: - has phone number listed: does not have address:

Nature: Volume 351: June 27, 1991: M. E. West: Department of Pharmacology, Faculty of Medical Sciences, University of West Indies, Mona Campus, Kingston 7, Jamaica The fishermen have claimed for many years that their vision at night is much better after taking the run-cannabis extract. University of West Indies laboratory facilities, we prepared a non- psychoactive substance from cannabis, which showed a marked ocular hypotensive effect. This preparation, Canasol, is now used to treat glaucoma, and many patients have reported significant improvement in night vision after taking it. From our findings, some of which are unpublished, it would seem that adrenoreceptors are involved and that they may be located in the ciliary epithelium. The ocular responses can be antogonized by alpha- adrenoreceptor blocking agents, ligation of the ascending cervical (sympathetic) nerve, and retrobulbar anesthesia.

Scientific America: December 1990: Going to Pot: A grassroots movement touts hemp's environmental virtues. by John Horgan

The Way of Herbs: by Michael Tierra, C.A., N.D.,: Pocket Books: page 131: Calamus: (Sweet flag, Sweet sedge: Biochemical Constituents: essential oil, amino acid, organic acid, sugars: Properties: Stimulant, carminative, antispasmodic, expectorant, emetic. Ayurvedic medicine emphasizes the use of calamus root in increase mental focus, and as such it is used as an antidote to smoking marijuana. The combination of gotu kola for cleaning the mind and relieving mental tension and calamus for helping to focus it is standard treatment for the central nervous system in Ayurveda.

Ayurveda: The Science of Self Healing: by Dr. Vasant Lad: A Practical Guide: Lotus Press: Santa Fe, New Mexico: According to Ayurveda, calamus is anticonvulsive. It is used for epileptic seizures. It acts on the higher cerebral functions and brain tissue to help expand and bring clarity to the consciousness. Calamus root is the best antidote for the illeffects of marijuana. Marijuana is toxic to the liver and the brain cells; however, if one smokes a pinch of calamus root powder with the marijuana, the herb will completely neutralize the toxic side effects of the drug. In fact, the side effects of all psychedelics can be neutralized by calamus root. Calamus root helps the circulation and provides nutrition for the muscle tissue. Calamus root is also used to improve the memory. Each morning and evening, take a pinch of the powdered root with on-fourth to one-half teaspoonful of honey. If one drinks two to three glasses of calamus root tea, it will cause vomiting. This action is therapeutic for chronic cough and asthma. Calamus root is also a broncho-dilator and acts as a chest decongestant. 18

NATURAL VERSUS SYNTHETIC THE DEBATE CONTINUES

Breast Milk - Anadamide-endogenous cannabinoid

As beings of Planet Earth, we are bio-chemically engineered to process cannabis - Cannabinoid Receptors

The Papers - Used by Scientists in Great Britain to research the probability or medical usages of Cannabis Sativa. The date of The Papers do happen to correspond with the above publication. 2001

HEALING HAZE? - As Politicians Debate The Potential Merits Of Medical Marijuana, Scientists Search For New Ways To Deliver This Old Drug - Synthetic vs Natural - June 2001

Anadamide - Breast Milk - Endogenous cannabinoid

More recent research http://www.hempforus.com/9.htm