"Marijuana: Medical Papers" (1839-1972)

As a psychiatrist, I was tempted to include material from influential and colorful literary origins. Descriptive experiential use started with Dr. Francois Rabelais's "The Herb Pantagruelion" in about 1530; it was re-introduced into European literature through the studies of J.J. Moreau de Tours in the early 1840s; it was popularized by Bayard Taylor, Theophile Gautier, Charles Baudelaire, and Fitz Hugh Ludlow in the 1850s and '60s. Dr. Victor Robinson carried this romantic intellectual tradition into the mid-1940s.

To attempt to include the lesser known but important literary works not published elsewhere would swell this anthology to an unwieldy size and detract from its usefullness as a medical reference.

The introspective accounts of practitioners' and scientists' personal use were influenced by contemporary literary figures who appear in a large proportion, especially in the earlier papers. Personal experimentation and description were once held to be an integral part of drug research.

The accounts of the adventures of the researcher, colleague, and patient serve to remind the reader of the constancy of the human psyche over the years. In the research lab, at the bedside, or at the controls of a locomotive, thoughtful scientists and clinicians describe their experiences and observations.

Despite the advent of technology, these intelligent observations articulately described in the past must not be forgotten. Failure to heed previous insights results in superfluous repetition, stupidity through ignorance and resultant failure.

Browsing through the book one cannot help but be struck by the fact that, althrough scientific tools have become more sophisticated, human nature has not. Ingenuity and clarity of thinking shine beyond the years, making us more humble in the realization that what is contemporary is not necessarily the best or uniquely innovative.

THM
Berkeley, California
1973

Introduction

Analgesia, anticonvulsant action, appetite stimulation, ataraxia, antibiotic properties and low toxicity were described throughout medical literature, beginning in 1839, when O'Shaughnessy introduced cannabis into the Western pharmacopoeia.

As these findings were reported throughout Western medicine, cannabis attained wide use. Cannabis therapy was described in most pharmacopoeial texts as a treatment for a variety of disease conditions.

During the second half of the 1800s and in the present century, medical researchers in some measure corroborated the early reports of the therapeutic potential of cannabis. In addition, much laboratory research has been concerned with bioassay, determination of the mode of action, and attempts to solve the problems of insolubility in water and variability of strength among different cannabis specimens.

"Recreational" smoking of cannabis in the twentieth century and the resultant restrictive federal legislation have functionally ended all medical uses of marijuana.

In light of such assets as minimal toxicity, no buildup of tolerance, no physical dependence, and minimal autonomic disturbance, immediate major clinical reinvestigation of cannabis preparations is indicated in the management of pain, chronic neurologic diseases, convulsive disorders, migraine headache, anorexia, mental illness, and bacterial infections.

Recently declassified secret U.S. Defense Department studies reconfirm marijuana's congeners to have therapeutic utility.

Cannabis indica, Cannabis sativa, Cannabis americana, Indian hemp and marijuana (or marihuana) all refer to the same plant. Cannabis is used throughout the world for diverse purposes and has a long history characterized by usefulness, euphoria or evil - depending on one's point of view. To the agriculturist cannabis is a fiber crop; to the physician of a century ago it was a valuable medicine; to the physician of today it is an enigma; to the user, a euphoriant; to the police, a menace; to the traffickers, a source of profitable danger; to the convict or parolee and his family, a source of sorrow.

This book is concerned primarily with the medicinal aspects of cannabis.

The Chinese emperor Shen-nung is reported to have taught his people to grow hemp for fiber in the twenty-eighth century B.C. A text from the period 1500-1200 B.C. documents a knowledge of the plant in China - but not for use as fiber. In 200 A.D., the use of cannabis as an analgesic was described by the physician Hoa-tho. 44

In India the use of hemp preparations as a remedy was described before 1000 B.C. In Persia, cannabis was known several centuries before Christ. In Assyria, about 650 B.C., its intoxicating properties were noted. 44

Except for Herodotus' report that the Scythians used the smoke from burning hemp seeds for intoxication, the ancient Greeks seemed to be unaware of the psychoactive properties of cannabis. Dioscorides in the first century A.D. rendered an accurate morphologic description of the plant, but made no note of intoxicating properties. 10

In the thirteenth and fourteenth centuries, Arabic writers described the social use of cannabis and resultant cruel but unsuccessful attempts to suppress its non-medical use. 44

Although Galen described the use of the seeds for creating warmth, he did not describe the intoxicating qualities of hemp. Of interest is the paucity of references to hemp's intoxicating properties in the lay and medical literature of Europe before the 1800s. 44

The therapeutic use of cannabis was introduced into Western medicine in 1839, in a forty-page article by W. B. O'Shaughnessy, a thirty-year-old physician serving with the British in India. 27 His discussion of the history of the use of cannabis products in the East reveals an awareness that these drugs had not only been used in medicine for therapeutic purposes, but had also been used for recreational and religious purposes.

O'Shaughnessy is not primarily known for his discovery of hemp drugs, but rather for his basic studies on intravenous electrolyte therapy in 1831, and his introduction of the telegraph into India in the 1850s. 26

After studying the literature on cannabis and conferring with contemporary Hindu and Mohammedan scholars O'Shaughnessy tested the effects of various hemp preparations on animals, before attempting to use them to treat humans. Satisfied that the drug was reasonably safe, he administered preparations of cannabis extract to patients, and discovered that it had analgesic and sedative properties. O'Shaughnessy successfully relieved the pain of rheumatism and stilled the convulsions of an infant with this strange new drug. His most spectacular success came, however, when he quelled the wrenching muscle spasms of tetanus and rabies with the fragrant resin. Psychic effects resembling a curious delirium, when an overdose was given, were treated with strong purgatives, emetics with a blister to the nape of the neck, and leeches on the temples. 27

The use of cannabis derivatives for medicinal purposes spread rapidly throughout Western medicine, as is evidenced in the report of the Committee on Cannabis Indica of the Ohio State Medical Society, published in 1860. In that report physicians told of success in treating stomach pain, childbirth psychosis, chronic cough, and gonorrhea with hemp products. 25 A Dr. Fronmueller, of Fuerth, Ohio, summarized his experiences with the drug as follows:

I have used hemp many hundred times to relieve local pains of an inflammatory as well as neuralgic nature, and judging from these experiments, I have to assign to the Indian hemp a place among the so-called hypnotic medicines next to opium; its effects are less intense, and the secretions are not so much suppressed by it. Digestion is not disturbed; the appetite rather increased; sickness of the stomach seldom induced; congestion never. Hemp may consequently be employed in inflammatory conditions. It disturbs the expectoration far less than opium; the nervous system is also not so much affected. The whole effect of hemp being less violent, and producing a more natural sleep, without interfering with the actions of the internal organs, it is certainly often preferable to opium, although it is not equal to that drug in strength and reliability. An alternating course of opium and Indian hemp seems particularly adapted to those cases where opium alone fails in producing the desired effect. 25

With a wish for speedy effect, it is so easy to use that modern mischief-maker, hypodermic morphia, that they [young physicians] are prone to forget remote results of incautious opiate giving.

Would that the wisdom which has come to their professional fathers through, it may be, a hapless experience, might serve them to steer clear of narcotic shoals on which many a patient has gone awreck.

Indian hemp is not here lauded as a specific. It will, at times, fail. So do other drugs. But the many cases in which it acts well, entitle it to a large and lasting confidence.

My experience warrants this statement: cannabis indica is, often, a safe and successful anodyne and hypnotic. 23

Cannabis products are insoluble in water.

The onset of the effects of medicinal preparations of cannabis takes an hour or so; its action is therefore slower than that of many other drugs.

Different batches of cannabis derivatives vary greatly in strength; moreover, the common procedure for standardization of cannabis samples, by administration to test animals, is subject to error owing to variability of reactions among the animals.

There is wide variation among humans in their individual responses to cannabis.

Despite these problems regarding the uncertainty of potency and dosage and the difficulties in mode of administration, cannabis has several important advantages over other substances used as analgesics, sedatives, and hypnotics:

The prolonged use of cannabis does not lead to the development of physical dependence. 11, 13, 14, 24, 39, 44

There is minimal development of tolerance to cannabis products. * 11, 13, 14, 24, 44

Cannabis products have exceedingly low toxicity. 9, 21, 22, 24 (The oral dose required to kill a mouse has been found to be about 40,000 times the dose required to produce typical symptoms of intoxication in man.) 21

Cannabis produces no disturbance of vegetative functioning, whereas the opiates inhibit the gastrointestinal tract, the flow of bile and the cough reflex. 1, 2, 24, 44, 46

Besides investigating the physical effects of medicinal preparations of cannabis, nineteenth-century physicians observed the psychic effects of the drug in its therapeutic applications. 4, 27, 33 They found that cannabis first mildly stimulates, and then sedates the higher centers of the brain. Hare suggested in 1887 a possible mechanism of cannabis' analgesic properties:

During the time that this remarkable drug is relieving pain a very curious psychical condition manifests itself; namely, that the diminution of the pain seems to be due to its fading away in the distance, so that the pain becomes less and less, just as the pain in a delicate ear would grow less and less as a beaten drum was carried farther and farther out of the range of hearing.

This condition is probably associated with the other well-known symptom produced by the drug; namely, the prolongation of time. 16

Reynolds stressed the necessity of titrating the dose of each patient, increasing gradually every third or fourth day, to avoid "toxic" effects:

The dose should be given in minimum quantity, repeated in not less than four or six hours, and gradually increased by one drop every third or fourth day, until either relief is obtained, or the drug is proved, in such case, to be useless. With these precautions I have never met with any toxic effects, and have rarely failed to find, after a comparatively short time, either the value or the uselessness of the drug. 33

In his definitive survey of the literature and report of his own studies, deceptively titled Marihuana, America's New Drug Problem, Walton notes that cannabis was widely used during the latter half of the nineteenth century, and particularly before new drugs were developed:

This popularity of the hemp drugs can be attributed partly to the fact that they were introduced before the synthetic hypnotics and analgesics. Chloral hydrate was not introduced until 1869 and was followed in the next thirty years by paraldehyde, sulfonal and the barbitals. Antipyrine and acetanilide, the first of their particular group of analgesics, were introduced about 1884. For general sedative and analgesic purposes, the only drugs commonly used at this time were the morphine derivatives and their disadvantages were very well known. In fact, the most attractive feature of the hemp narcotics was probably the fact that they did not exhibit certain of the notorious disadvantages of the opiates. The hemp narcotics do not constipate at all, they more often increase than decrease appetite, they do not particularly depress the respiratory center even in large doses, they rarely or never cause pruritis or cutaneous eruptions and, most important, the liability of developing addiction is very much less than with opiates. 44

Cannabis preparations were still widely available in legend and over-the-counter forms in the 1930s. Crump * in 1931 mentioned the proprietaries "Piso's Cure," "One Day Cough Cure" and "Neurosine" as containing cannabis. 44 In 1937 Sasman listed twenty-eight pharmaceuticals containing cannabis. 36 Cannabis was still recognized as a medicinal agent in that year, when the committee on legislative activities of the American Medical Association concluded as follows:

. . . there is positively no evidence to indicate the abuse of cannabis as a medicinal agent or to show that its medicinal use is leading to the development of cannabis addiction. Cannabis at the present time is slightly used for medicinal purposes, but it would seem worthwhile to maintain its status as a medicinal agent for such purposes as it now has. There is a possibility that a re-study of the drug by modern means may show other advantages to be derived from its medicinal use. 32

The recreational smoking of marijuana may have started in this country in New Orleans in about 1910, and continued on a small scale there until 1926, when a newspaper ran a six-part series on the use of the drug. 44 The fad subsequently spread up the Mississippi and throughout the United States, faster than local and state laws could be passed to discourage it. The use of "tea" or "muggles" blossomed into a minor "psychedelic revolution" of the 1920s. Narcotics officers encouraged the enactment of local prohibitory laws and eventually succeeded in bringing about restrictive Federal legislation. In 1937 Congress passed the Marihuana Tax Act, the finale to a series of prohibitory acts in the individual states. Under the new laws, the already dwindling use of cannabis as a therapeutic substance in medicine was brought to a virtual halt. In 1941, cannabis was dropped from the National Formulary and Pharmacopoeia.

Around the time of the passage of the Marihuana Tax Act, Walton postulated sites of action for cannabis drugs. Cortical areas, he found, are affected at low dosage, while at high dosage there seems to be a depressant effect on the thalamo-cortical pathways. Hyperemia of the brain appears to be a local phenomenon, unless centers controlling vasodilation might be located in the thalamo-cortical region. Similar possible mechanisms are suggested for the phenomenon of mild hypoglycemia, usual hunger and thirst and occasional lacrimation and nausea. 44

Despite restrictive legislation, a few medical researchers have had the opportunity to continue the investigation of the therapeutic applications of cannabis in recent years. In his study of the medical applications of cannabis for Mayor La Guardia's committee, Dr. Samuel Allentuck reported, among other findings, favorable results in treating withdrawal of opiate addicts with tetrahydrocannabinol (THC), a powerful purified product of the hemp plant. 1, 24

An article in 1949, buried in a journal of chemical abstracts, reported that a substance related to THC controlled epileptic seizures in a group of children more effectively than diphenylhydantoin (Dilantin ®), a most commonly prescribed anticonvulsant. 9

A number of experimenters, believing that cannabis products might be of value in psychiatry, have investigated the applications of various forms of them in the treatment of mental disorders. Cannabis had been used in the nineteenth century to treat mental illness. 19, 25, 45, 46 However, aside from some rather equivocal clinical studies, primarily in the treatment of depression, 29, 30, 35, 39 and another report of success in treating withdrawal from alcohol and opiate addiction, 42 no significant contemporary psychiatric studies involving cannabis therapy have been reported to date.

Many current "authoritative" publications unequivocally state that there is no legitimate medical use for marijuana. As compared with the 1800s, this century has seen very little medical research on the array of some twenty chemicals that are found in the hemp plant. 37

Today's readers may tend to be skeptical about a report of a cure for gonorrhea published over a century ago. 19, 25 Such findings may bear reinvestigation, however, in the light of a report from Czechoslovakia in 1960 that cannabidiolic acid, a product of the unripe hemp plant, has bacteriocidal properties. 7 Some of the therapeutic applications reported in the early medical papers have been corroborated by later investigators, but for the most part the therapeutic aspects of cannabis remain to be re-explored under modern clinical conditions.

In the past twenty years, clinical and basic research on cannabis have dwindled to practically nothing. The record of tax stamps issued by the Federal Bureau of Narcotics for cannabis research, as compared with those for research on narcotic drugs, tells the story of the twenty-year "drought" in the investigation of cannabis products: 43

                                          Users for Purposes of Research,
                                                Instruction, or Analysis

Year                                 Narcotic Drugs              Marijuana

1938 . . . . . . . . . . . . .              ....                      5 
1941 . . . . . . . . . . . . .                94                     ..
1943 . . . . . . . . . . . . .              ....                     43
1946 . . . . . . . . . . . . .               323                     ..
1948 . . . . . . . . . . . . .              ....                     87
1951 . . . . . . . . . . . . .              1078                     ..
1953 . . . . . . . . . . . . .              ....                     18
1956 . . . . . . . . . . . . .               284                     ..
1958 . . . . . . . . . . . . .              ....                      6
1961 . . . . . . . . . . . . .               344                     ..
1965 . . . . . . . . . . . . .               431                     16

The rising non-medical use of marijuana both floated and was buoyed by the "psychedelic revolution" of the mid 1960s. The panicked reaction included a renewed scientific interest in the drug.

Eleven studies funded by the National Institute of Mental Health 1967 concerning cannabis were either specialized animal experiments, part of an observational sociologic study of a number of drugs, or explorations of chemical detection methods. No human studies were included.

Of the fifty-six projects funded during the next fiscal years 1968-69 only two used humans. 52 The next year was somewhat less cautious with eight out of thirty-five projects devoted to clinical studies. 53

Some of the preliminary results are in from these studies. Much is still unpublished.

According to Harris, the toxicity factor of marijuana derivatives is over two hundred and that chronic smoking of marijuana is less harmful to the lungs than tobacco cigarettes. 49

Domino described the cross tolerance of THC and alcohol in pigeons 47 corroborating Jones' clinical observations. 50, 51 These rediscoveries demand therapeutic trial.

In August 1971 certain secret Defense Department documents were declassified. While at NIMH as a consulting research psychiatrist in 1967 I had become aware of the existence of clandestine research at Edgewood Arsenal in Maryland.

From 1954-59 Dr. Van M. Sim was in charge of the project. He reported to Medical World News: "Marijuana . . . is probably the most potent anti-epileptic known to medicine today." 49

Dr. Harold F. Hardman, then with the Defense contracting group at the University of Michigan's Department of Pharmacology reported effects of profound hypothermia and felt marijuana derivatives to be potentially quite useful in brain and traumatic surgery. 48

The principal focus was, however, on the possible use of THC homologs as incapacitating agents. Besides the aforementioned government agency and university, the private sector was represented by the Arthur D. Little Company of Cambridge, Massachusetts. 55

Recently in the course of a study of effects on driving, it was incidentally discovered that cannabis lowers intraocular pressure, thus being possibly useful in the treatment of glaucoma. 56

Thus, a helix is made. Modern technologic methods confirm O'Shaughnessy's observations 130 years ago. After swinging away from the knowledge of marijuana's properties through the worship of new synthetics, an unrelated rise of marijuana use socially, illegalization and removal from availability for clinical use, medicine rediscovers marijuana.

The flame of knowledge is at a low ebb, kept alive by isolated scientists and clinicians; it is now being rekindled by these recent circumscribed revelations.

Unless existing restrictive state and federal laws governing marijuana are changed, there will be no future for either modern scientific investigation or controlled clinical trial by present-day methods.

The tide is turning. The Federal Bureau of Narcotic and Dangerous Drugs, National Institute of Mental Health and The Food and Drug Administration Joint Committee recently authorized human therapeutic trial of cannabis products. We may now look forward to reinvestigation of the numerous possible medical uses of marijuana. 54

A concerted effort is indicated for full-scale investigations where knowledge is lacking. Acute and chronic effects of cannabis should be restudied by modern methods. Metabolic pathways of action and detoxification need exploration by the pharmaceutical means of today. Chronic toxicity studies must be undertaken to examine possible long-term effects of cannabis use. *

Medical science must again confront the problems of cannabis' insolubility in water and its variable strength. Since human and animal responses vary a great deal, individual doses must be titrated. The popular "double blind" type of study methods will require revision. The reporting of personal drug experience was once acceptable to the scientific community. 15, 22, 25, 29, 34, 39, 44 Humans who are drug "sophisticates" will again become indispensable to psychoactive drug research, as wine tasters are to the wine industry, for only humans can verbally report the subtle and complex effects of these substances.

Government agencies having stimulated little significant clinical research in this field, the pharmaceutical industry should take the initiative in starting basic research and clinical studies into the purified congeners of cannabis for their chemical properties, pharmacologic qualities and therapeutic applications.

Possible Therapeutic Applications of
Tetrahydrocannabinols and Like Products

Analgesic-hypnotic 16, 18, 19, 23, 25, 27, 33, 45
Appetite stimulant 18, 25, 27
Antiepileptic-antispasmodic 9, 18, 27, 33, 40, 45, 49
Prophylactic and treatment of the neuralgias, including migraine and tic douloureux 3, 16, 17, 18, 19, 23, 25, 28, 31, 33, 38, 40, 45
Antidepressant-tranquilizer 6, 16, 18, 19, 23, 25, 31, 33, 40, 45
Antiasthmatic 18, 25, 45
Oxytocic 25, 45
Antitussive 3, 16, 25, 38, 45
Topical anesthetic 8
Withdrawal agent for opiate and alcohol addiction 5, 23, 24, 38, 42, 45, 47, 50, 51
Childbirth analgesic 12
Antibiotic 7
Intraocular hypotensive 56
Hypothermogenic 48

* Loewe notes a slight "beginner's habituation" in dogs, during the first few trials with the drug, as the only noticeable tolerance effect. 20

* Chairman, Investigating Committee, American Medical Association.

* Cunningham in 1893 found no gross central nervous system changes with chronic administration of hemp drugs to primates over several months. 8

* Morton "discovered" ether for anesthetic purposes after observing medical students at "ether frolics" in 1846 (Howard W. Haggard: Devils, Drugs and Doctors, Harper and Row, New York, 1929, p. 99)

REFERENCES

2. Ames, Frances: A clinical and metabolic study of acute intoxication with cannabis sativa and its role in the model psychoses, J. of Mental Science, 104:972-99, Oct. 1958.

3. Anderson, G. S. D.: Remarks on the remedial virtues of cannabis indica, or Indian hemp, Boston Med. and Surg. J., 67:427-30, 1863.

4. Bell, John: On the haschisch or cannabis indica, Boston Med. and Surg. J., 56:209-16, 229-36, 1857.

5. Birch, Edward A.: The use of Indian hemp in the treatment of chronic chloral and chronic opium poisoning, Lancet, 1:625, 30 Mar. 1889.

6. Boyd, E. S., and Merritt, D. A.: Effects of a tetrahydrocannabinol derivative on some motor systems in the cat, Arch. Internat. de Pharmacodynamie et de Therapie, 153:1-12, 1965.

7. CIBA Foundation Study Group, Hashish - Its Chemistry and Pharmacology, 1964, pp. 45, 49.

8. Cunningham, D. D.: Report by Brigade-Surgeon - Lieut. Col. D. D. Cunningham, F.R.S., C.I.E., on the nature of the effects accompanying the continued treatment of animals with hemp drugs and with dhatura; from Report of the Indian Hemp Drugs Commission, 1893-4, Government Central Printing Office, Simla, India, 1894, Vol. 3, pp. 192-96.

9. Davis, J. P., and Ramsey, H. H.: Antiepileptic action of marihuana-active substances, Federat. Proc., 8:284-85, Mar. 1949.

10. Dioscorides, Pedanius: The Greek Herbal of Dioscorides, Edited by Robert T. Gunther, Hafner Publishing Co., New York, 1959, pp. 390-91.

11. Eddy, N. B., Halbach, H., Isbell, H., and Seevers, M. H.: Drug dependence: its significance and characteristics. Psychopharmacology Bull., 3:1-12, July 1966.

12. Effects of alcohol and cannabis during labor, JAMA, 94:1165, 1930.

13. Goodman, L. S., and Gilman, A.: The Pharmacological Basic of Therapeutics, 2nd Edition, Macmillan, New York, 1955.

14. Goodman, L. S., and Gilman, A.: The Pharmacological Basis of Therapeutics, 3rd Edition, Macmillan, New York, 1965.

15. Hamilton, H. C., Lescohier, A. W., and Perkins, R. A.: The physiological activity of cannabis sativa. Comparison of extracts from Indian and American-grown drug upon human subjects, J. Amer. Pharm. Assoc., 2:22-30, 1913.

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18. Indian Materia Medica, edited by A. K. Nadkarni, Popular Book Depot, Bombay, 1954.

19. Lilly's Hand Book of Pharmacy and Therapeutics, Eli Lilly and Co., Indianapolis, 1898, p. 32.

20. Loewe, S.: The active principles of cannabis and the pharmacology of the cannabinols, Archiv fur Experim. Pathologie und Pharmakologie, 211:175-93, 1950.

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25. McMeens, R. R.: Report of the committee on cannabis indica; from Transactions of the Fifteenth Annual Meeting of the Ohio State Medical Society, Follett, Foster and Co., Columbus, Ohio, 1860, pp. 75-100.

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27. O'Shaughnessy, W. B.: On the preparations of the Indian hemp, or gunjah, Trans. Med. and Phy. Soc., Bengal, 71-102, 1838-40; 421-61, 1842.

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32. Report of the Committee on Legislative Activities, JAMA, 108:2214-15, 1937.

33. Reynolds, J. Russell: Therapeutical uses and toxic effects of cannabis indica, Lancet, 1:637-38, 22 Mar. 1890.

34. Robinson, Victor: An Essay on Hasheesh - Historical and Experimental, L. H. Ringer, New York, 1912.

35. Rolls, E. J., and Stafford-Clark, D.: Depersonalization treated by cannabis indica and psychotherapy, Guy's Hospital Report, 103:330-36, 1954.

36. Sasman, Marty: Cannabis indica in pharmaceuticals, J. of the N.J. Med Soc., 35:51-52, Jan. 1938.

37. Shulgin, Alexander T.: personal communication, 1968.

38. Stevens, A. A.: Modern Materia Medica and Therapeutics, W. B. Saunders and Co., Philadelphia, 1903, pp. 77-78.

39. Stockings, G. Taylor: A new euphoriant for depressive mental states, Brit. Med J., 1:918-22, 28 June 1947.

40. Suckling, C. W.: On the therapeutic value of Indian Hemp, Brit. Med. J., 2:12, 1881.

41. Terry, C. E., and Pellens, M.: The Opium Problem, Bureau of Social Hygiene, Inc., New York, 1928, pp. 53-93.

42. Thompson, L. J. and Proctor, R. C.: The use of pyrahexyl in the treatment of alcoholic and drug withdrawal conditions, N. Carolina Med. J., 14:520-23, Oct. 1953.

43. U.S. Treasury Dept., Bureau of Narcotics, Traffic in Opium and Other Dangerous Drugs for the Year Ended Dec. 31, 1965, U.S. Printing Office, Washington, 1966, pp. 55-56.

44. Walton, Robert P.: Marihuana: America's New Drug Problem, J. B. Lippincott, Philadelphia, 1938, pp. 1-18, 86-157.

45. Waring, Edward John: "Practical Therapeutics," Lindsay and Blakiston, Philadelphia, 1874, pp. 157-61.

46. Wood, G. B., and Bache, F.: The Dispensatory of the United States of America, 12th Edition, J. B. Lippincott, Philadelphia, 1866, pp. 379-82.

47. Domino, Edward F., Neuropharmacological Studies of Marijuana - Some Synthetic and Natural THC Derivatives in Animals and Man, 1971. Unpublished. 54 pp.

48. Hardman, Harold F., Domino, Edward F. and Seevers, Maurice T., General Pharmacological Actions of Synthetic Tetrahydrocannabinol Derivatives, 1971. Unpublished.

49. Berger, Alfred D., Marijuana. Med. World News, July 16, 1971, pp. 37-43.

50. Jones, Reese T., Psychological Studies of Marijuana and Alcohol in Man, Psychopharmacologia, 18, 108-117, 1970.

51. Jones, Reese T ., Tetrahydrocannabinol and the Marijuana Induced Social "High" or the Effects of the Mind on Marijuana. Ann. N.Y. Acad. Sci., 1972. In press.

52. Grants Active During Fiscal Years 1968 and 1969 Center for Studies in Narcotics and Drug Abuse, National Institute of Mental Health, 1969. Unpublished.

53. Ibid., 1970.

54. Bozetti, Louis: personal communication, January, 1972.

55. Arthur D. Little Company, New Incapacitating Agents - Quarterly Report 15/16 Supplement. Preclinical Pharmacology and Toxicology of Candidate Agent 226, 169. Papers on Tetrahydrocannabinols - Cleared for public release. The National Technical Information Service, Department of Commerce, 1971.

56. Hepler, R. S. and Frank, I. R. Marihuana Smoking and Intraocular Pressure, JAMA, Sept. 6, 1971. Vol. 217, no. 10.

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