The Dispensatory of the United States of America

Jacob Bell

New Member
BY JOSEPH P. REMINGTON, Ph.M., F.C.S.,
HORATIO C. WOOD, JR., M.D., ET AL.
CANNABIS. U.S. (Br.)
“The dried flowering tops of the pistillate plants of
Cannabis sativa Linne, or of the variety indica Lamarck
(Fam. Moraceae), freed from the thicker stems and large
foliage leaves and without the presence or admixture of more
than 10 percent of fruits or other foreign matter. Cannabis,
made into a fluid extract in which one hundred mils represent
one hundred grams of the drug, when assayed biologically,
produces incoordination when administered to dogs in
a dose of not more than 0.03 mil of fluid extract per
kilogram of body weight.” U.S. “Indian Hemp consists of
the dried flowering or fruiting tops of the pistillate plant of
Cannabis sativa, Linn., grown in India; from which the resin
has not been removed.” Br.
Cannabis Indicae, Br. ; Hemp, Indian Hemp; Herba Cannabis
Indicae; Chanvre, Fr. Cal. ; Chanvre de l’Inde, Fr. ; Indischer
Hanf, G. ; Cafiamo, Sp.
For many years the official cannabis was restricted to the
drug which was used for centuries in India. The reason for
this was that the Indian cannabis was more uniformly active.
Recently the Indian Government has placed a high tax on
every pound of the drug grown. The result has been that
other markets have been sought and the hemp plant has been
grown in other parts of Asia, Africa and America. While of
course much of this material is not equal to that grown in
India, the fact that it can be grown, as shown by experiments
in the United States (see Hamilton, J. A. Ph. A., 1913, ii;
1915, iv, 389), of a very high quality has caused the framers
of the U. S. Pharmacopoeia to permit the use of a cannabis,
no matter where it may be grown, provided it comes up to
the biological standard as given in the definition. Physiologically
active cannabis is obtained at the present time not only
from India, but Africa, Turkey, Turkestan, Asia Minor, Italy,
Spain and the United States.
The Cannabis sativa, or hemp plant, is an annual, from
four to eight feet or more in height, with an erect, branching,
angular stem. The leaves are alternate or opposite, and
digitate, with five to seven linear-lanceolate, coarsely serrated
segments. The stipules are subulate. The flowers are axillary;
the staminate in long branched, drooping racemes; the pistillate
in erect, simple spikes. The stamens are five, with long
pendulous anthers; the pistils two, with long, filiform, glandular
stigmas. The fruit is ovate and one-seeded. The whole
plant is covered with a fine pubescence, scarcely visible to the
naked eye, and somewhat viscid to the touch. The hemp
plant of India has been considered by some as a distinct
species, and named Cannabis indica; but the most observant
botanists, upon comparing it with the cultivated plant, have
been unable to discover any specific difference. It is now,
therefore, regarded merely as a variety, and is distinguished
by the epithet indica. Pereira states that in the female plant
the flowers are somewhat more crowded than in the common
hemp, but that the male plants in the two varieties are in all
respects the same.
C. sativa is a native of the Caucasus, Persia, and the hilly
regions in Northern India. It is cultivated in many parts of
Europe and Asia, and largely in our Western States. It is from
the Indian variety exclusively that the medicine was formerly
obtained, the heat of the climate in Hindostan apparently
favoring the development of its active principle. H. C. Wood,
many years ago, obtained a parcel of the male plant of C.
americana (C. sativa) from Kentucky, made an alcoholic
extract of the leaves and tops, and upon trying it on the
system, found it effective in less than a grain, and, having
inadvertently taken too large a dose, experienced effects
which left no doubt of the powers of the medicine, and of
the identity of its influence with that of the Indian plant.
(Proc. Am. Philos. Sot., vol. xi, p. 226.) The results obtained
by H. C. Wood have been confirmed by a number of
observers.
The fruits or “so-called” seeds, though not now official,
have been used in medicine. They are from three to five
millimeters long and about two millimeters broad, roundishovate,
somewhat compressed, of a shining ash-gray color, and
of a disagreeable, oily, sweetish taste. For a comprehensive
monograph on the morphology of cannabis fruits, as well as
their history and chemical composition, see Tschirch, “Handbuch
der Pharmakognosie,” p. 55.5. They yield by expression
about 20 percent of a fixed oil, which has the drying
property, and is used in the arts. They contain also uncrystallizable
sugar and albumen and when rubbed with water form
an emulsion, which may be used advantageously in inflammations
of the mucous membrane, though without narcotic
properties. The seeds are much used as food for birds, as they
are fond of them. They are generally believed to be in no
degree poisonous; but Michaud relates the case of a child in
whom serious symptoms of narcotic poisoning occurred after
taking a certain quantity of them. It is probable that some of
the fruit eaten by the child was unripe, as in this state it
would be more likely to partake of the peculiar qualities of
the plant. (Ann. Thtr., 1860.)
In Hindostan, Persia, and other parts of the East, hemp has
long been habitually employed as an intoxicating agent. The
parts are the tops of the plant, and a resinous product
obtained from it. Bang is the selected, dried and powdered
leaves. Ganjah or pniah is the tops of the cultivated female
plants, cut directly after flowering, and formed into round or
flat bundles from two to four feet long by three inches in
diameter. It is stated that in the province of Bengal great care
is taken to eradicate the male plants from the fields before
fertilization of the female, and that thereby the yield and
quality of the resin is greatly increased. In Bombay this
matter is commonly neglected, so that Bengal ganjah is much
superior to Bombay ganjah. It is recognized in India that
ganjah rapidly deteriorates on keeping, that which is one year
old being not more than one-quarter as potent as the fresh
drug, while two-year-old ganjah is practically inert and is
required by the Indian government to be burned in the
presence of excise officers. It is probable, however, that
much old ganjah finds its way into the markets of the world.
All importations of ganjah or hemp from India should be
made directly after the harvesting of the new crop in April or
May, and the extract should be prepared at once and kept in
hermetically scaled jars. There is on the surface of the plant a
resinous exudation to which it owes its stickiness. According
to Hooper ( P. J., 1909, lxxxi, 347) only small amounts of
charas are raised in India, that which is being consumed there
being mostly imported. The method of collection in Baluchistan
is to gently rub the dried plant between carpets. The dust
which comes off contains the active principle and is known as
“rup.” The second shaking produces an inferior variety,
known as “tahgalim,” and the third shaking is known as
“ganja.” In Nepal the plant is squeezed between the palms of
the hands, and the resin scraped off from the hands. These
balls, and also masses formed out of resin mechanically
separated from the hemp plant are called charas or churrus.
This is the hashish or hasheesh of the Arabs.
Hashish is also produced in considerable quantities in
Persia by rolling and rubbing the flowers, stalks and leaves of
hemp on rough woolen carpets and subsequently scraping off
with a knife and making into balls or sticks the adherent
resinous substance. The carpets are afterwards washed with
water and the extract obtained by evaporation sold at a low
price. The dose for smoking of the best hashish is said to be
one-fourth to one grain (0.016-0.065 Gm.). The fanatics are
affirmed to be generally hashish devotees.
The dealing in hashish in India is said to be a Government
monopoly, and a very heavy license is required for the right
to even purchase it in quantity. The importation of it into
Egypt is so strongly interdicted that the mere possession of it
is a penal offense; H. C. Wood found it, however, readily
procurable. It is said to be brought into the country in pigs’
bladders, in the Indo-European steamers, and thrown out at
night during the passage into the Suez canal, to be picked up
by the boats of confederates. Notwithstanding the Governmental
interdiction, it is largely used by smoking in Egypt, as
an intoxicant. The statement of W. E. Dixon (B. M. J., Nov.,
1899) that the inhalations of hemp smoke produce great
exhilaration and cause muscular fatigue to disappear for the
time being is undoubtedly correct, but his further belief that
the habit is not apt to grow upon the hemp votary is more
doubtful.
Momea or mimea is a hemp preparation said to be made in
Tibet with human fat. From gunjah the Messrs. Smith, of
Edinburgh, obtained a purer resin by the following process:
Bruised ganjah is digested, first in successive portions of
warm water, until the expressed liquid comes away colorless;
and afterwards for two days, with a moderate heat, in a
solution of sodium carbonate, containing one part of the salt
for two of the dried herb. It is then expressed, washed, dried,
and exhausted by percolation with alcohol. The tincture,
after being agitated with milk of lime containing one part of
the earth for twelve of the gunjah used, is filtered; the lime is
precipitated by sulphuric acid; the filtered liquor is agitated
with animal charcoal, and again filtered; most of the alcohol
is distilled off, and to the residue twice its weight of water is
added; the liquor is then allowed to evaporate gradually; and,
finally, the resin is washed with fresh water until it ceases to
impart a sour or bitter taste to the liquid, and is then dried in
thin layers. Thus obtained, it retains the odor and taste of
gunjah, which yields from 6 to 7 percent of it.
Properties.-Fresh hemp has a peculiar narcotic odor,
which is said to be capable of producing vertigo, headache,
and a species of intoxication. It is much less in the dried tops,
which have a feeble bitterish taste. According to Royle,
churrus is, when pure, of a blackish-gray, blackish-green, or
dirty olive color, of a fragrant and narcotic odor, and a
slightly warm, bitterish and acrid taste. Cannabis is officially
described as “in dark green or greenish-brown and more or
less agglutinated fragments, consisting of the short stems with
their leaf-like bracts and pistillate flowers, some of the latter
being replaced with more or less developed fruits; stems
cylindrical, of varying length, not more than 3 mm. in
diameter, longitudinally furrowed, light green to light brown,
strigose-pubescent; leaves digitately compound; leaflets, when
soaked in water and spread out, linear-lanceolate, nearly
sessile, margin deeply serrate, bracts ovate, pubescent, each
enclosing one or two pistillate flowers, or more or less
developed fruits; calyx dark green, pubescent and somewhat
folded around the ovary or fruit; styles two, filiform and
pubescent; ovary with a single campylotropous ovule; fruit
light green to light brown, broadly ellipsoidal, about 3.5 mm.
in length, finely wrinkled and slightly reticulated; odor
agreeably aromatic; taste characteristic. The powder is dark
green, giving a strong effervescence on the addition of dilute
hydrochloric acid; numerous sharp pointed fragments of
upper portion of non-glandular hairs and fragments of bracts
and leaves showing yellowish-brown laticiferous vessels, rosette
aggregates of calcium oxalate from 0.005 to 0.025 mm.
in diameter; non-glandular, with a very slender pointed apex
and a considerably enlarged base containing, usually in the
lumen, some calcium carbonate; glandular hairs of two kinds,
one with a short, one-celled stalk and the other with a
multicellular, long, tongue-shaped stalk, the glandular portion
being globular and consisting of from eight to sixteen cells,
fragments of fruits with palisade-like, non-lignified sclerenchymatous
cells, walls yellowish-brown, finely porous, the
lumina usually containing air; tissues of embryo and endosperm
with numerous oil globules and aleurone grains, the
latter from 0.005 to 0.01 mm. in diameter and consisting of
large crystalloids and globoids. The yield of alcohol extractive
is not less than 8 percent and the alcoholic solution is of
a bright green color. Cannabis yields not more than 15
percent of ash.” U.S.
The British Pharmacopoeia describes Indian cannabis as
follows :
“In compressed, rough, dusky-green masses, consisting of
the branched upper part of the stem, bearing leaves and
pistillate flowers or fruits, matted together by a resinous
secretion. Upper leaves simple, alternate, l-3 partite; lower
leaves opposite and digitate, consisting of five to seven
linear-lanceolate leaflets with distantly serrate margins. Fruit
one-seeded and supported by an ovate-lanceolate bract. Both
leaves and bracts bear external oleo-resin glands and onecelled
curved hairs, the bases of which are enlarged and
contain cystoliths. Strong, characteristic odor; taste slight.
When a mixture of ten grams of finely powdered Indian
Hemp and one hundred millilitres of alcohol (90 percent) is
shaken occasionally during twenty-four hours and then filtered,
twenty millilitres of the filtrate, evaporated in a
flat-bottomed dish, yield a residue weighing when dried at
100” C. (212” F.), not less than 0.250 gram. Ash not more
than 15 percent.” Rr.
For a histological description of the leaf by A. R. L.
Dohme, see Proc. A. Ph. A., 1897, 569. The Cannabis of the
market may consist of fruiting tops and stems and occasionally the staminate tops are admixed with it.
Hooper (P. J., lxxxi, p. SO) describes a method for the
chemical standardization of cannabis indica based upon its
iodine value. He finds that the alcoholic extract of old
samples has a lower iodine value than that from recent
specimens, and there is more or less constancy of relation
between the age and the iodine value.
For description of the U.S. method of physiological assay,
see page 279.
Indian churrus or hasheesh is a hard resinous mass of a
greenish-gray color, containing much gritty earth, and, as it
occurs in Egypt, of a feeble, hemp-like odor and taste.
Schlesinger found in the leaves a bitter substance, chlorophyll,
green resinous extractive, coloring matter, gummy
extract, extractive, albumen, lignin, and salts. The plant also
contains volatile oil in very small proportion, which probably
has narcotic properties. The resin obtained by T. & H. Smith
of Edinburgh, in 1846, has been thought to be the active
principle, and received the name of cannabin. By repeated
distillation of the same portion of water from relatively large
quantities of hemp renewed at each distillation, M. J. Personne
obtained a volatile oil, of a stupefying odor, and an
action on the system such as to dispose him to think that it
was the active principle of the plant. As the water distilled
was strongly alkaline, he supposed that his volatile principle
might be a new alkaloid; but the alkaline reaction was found
to depend on ammonia; and the liquid obtained proved to be
a volatile oil, lighter than water, of a deep amber color, a
strong odor of hemp, and composed of two distinct oils, one
colorless, with the formula C,, H,, , the other a hydride of
the first, C,, H,, , which was solid, and separates from alcohol
in platelike crystals. For the former Personne proposes the
name of cannabene. It is affirmed that when this is inhaled,
or taken into the stomach, a singular excitement is felt
throughout the system, followed by a depression, sometimes
amounting to syncope, with hallucinations which are generally
disagreeable, but an action on the whole slighter and
more fugitive than that of the resin. The various substances
of alkaloidal nature that have been described by different
investigators as found in Indian hemp are now recognized as
due to decomposition products of choline, which was identified
as present by Jahns (P.J,, 1887, xvii, 1049). Cannabindon, C,H,, 0, is a dark red syrupy liquid obtained by Kobert
(Chew. Ztg., 1894, 741) from Cannabis Indica; it is soluble in
alcohol, ether and oils; it is affirmed to be a narcotic in doses
of from half a grain to two grains (0.032-0.13 Gm.). As a
result of a reinvestigation of charras (churrus) from Indian
hemp, Wood, Spivey, and Easterfield (J. Chem. S., vol. lxix,
539) have found the following principles: (1) a terpene,
boiling between 150” and 180” C. (302” and 356” F.); (2) a
sesquiterpene, boiling at 258” to 259” C. (496.4”-498.2” F.);
(3) a crystalline paraffin of probable formula C,, H,, , melting
at 63.5” C. (146.3” F.); and (4) a red oil, boiling at 265”
to 270” C. (509”-518” F.) under a pressure of 20 mm., to
which they give the name cannabinol, and the formula
Cl8 H,, 0,. This latter constituent they consider the only
active ingredient. It is probably the same substance as the
dark red syrup of Kobert, mentioned above under the name
cannabindon. The authors found that cannabinol readily
underwent superficial oxidation, at the same time losing its
toxic activity. Famulener and Lyons (A. Pbarm., 1904)
believe that the only reliable preparation of cannabis is a
fluid extract made from the fresh drug. I. Ronx (A. Pharm.,
1887) has experimented upon extracts made by treating
purified extract of hemp with petroleum benzin and ether.
The ether extract produced insignificant results. The petroleum
extract was excitant and convulsant. The alcoholic
extract was a feeble narcotic. The resin “cannabin” of which
cannabinol is the chief constituent, appears to be active.
Frankel (A, E. P. P., 1903, p. 266) claims to have isolated the
active principle of hashish as a pure and chemically well
defined body. It has the formula C,, H,, 0,) and is a
phenol-aldehyde. It is of a pale yellow color and of a thick
consistency. When heated it becomes quite fluid and distills
at 0.5 mm. It oxidizes in the air, acquiring a brown tint. It
responds to Millon’s reaction, and can be acetylized, showing
thus its phenol character. Frankel proposes that the name
cannabinol be given to it and that the term pseudocannabinol
be given to the inactive substance of Wood,
Spivey and Easterfield.
Assay. -“Prepare a fluid extract and proceed as directed
below.” U.S.
Attempts have been made to apply physiological tests to
the standardization of cannabis indica. Up to the present no
means have been suggested for determining the relative
potency of different samples of cannabis indica, the physiological
test simply demonstrating that the drug possesses a
certain indefinite amount of physiological action. This test is
carried out upon dogs in the following manner: It is advisable
to use the same animal for repeated tests, because the
individual susceptibility of the dog varies so greatly, and the
experimenter gradually learns the degree of reaction to be
expected from a certain dog. A tincture of the specimen to
be tested is either evaporated into a soft extract and given in
the form of a pill or mixed with an inert absorbing powder
and enclosed in a capsule; it must not be given hypodermically.
The symptoms caused by cannabis indica in the dog
recall those of alcoholism in the human being. There is at
first a slight loss of control in the hind legs so that the animal
staggers as he walks, later the ataxia becomes so marked that
the dog is unable to stand up without leaning against some
object, and about this time begins to show distinct drowsiness,
and may eventually pass into a heavy sleep.
The details of assay as directed by the U.S. are as follows:
“The assay of Cannabis and its preparations has been made a
requirement and is based upon the fact that this drug
produces certain symptoms of muscular incoordination. The
method consists of ascertaining the dose of the preparation
to be tested which will produce these symptoms of incoordination
in dogs and then adjusting its strength by comparison
with a standard preparation.
“Dogs. -The animals differ considerably in susceptibility
to the drug and therefore it is best to make preliminary tests
upon several dogs with average-sized doses and select from
among them the animals which react easily to the drug. As a
rule, fox terriers serve very well for the purpose, but any dog
may prove satisfactory. It is best to provide at least two dogs
for each assay, but if many samples are to be examined more
dogs will be needed. The dogs should be at least one year old
and in normal health and must be kept under the best
sanitary conditions. They may be used repeatedly for the
purpose but not at shorter intervals than three days. Each
series of tests should be conducted by the same person, who
should be perfectly familiar with the peculiarities of each
animal in order that he may recognize more certainly deviations
from the normal. While the tests are being made the animals should be kept in a perfectly quiet room, free from
disturbance and separated so that they cannot see each other.
“Preparation of the Drug.-The drug may be given most
conveniently in the form of the fluid extract which is
administered in gelatin capsules, or the extract made into soft
pills may be used; but whichever form is chosen the same
should be used for both the standard and the preparation
that is to be tested.
“Before administration the animal should not be fed for
twenty-four hours in order to hasten absorption. The head of
the animal being held, its mouth is opened and the capsule or
pill is placed upon the back of the tongue. Usually the drug is
easily swallowed when given in this way, but this may be
facilitated by giving the animal a small amount of water to
drink.
“Assay.-An average dose of the known or standard preparation
is given to one of the dogs and a like dose of the
preparation to be standardized is given the second dog. After
one hour both dogs are observed very carefully for symptoms
of muscular incoordination. The incoordination is manifested
differently in different animals, but in small doses it shows
itself most frequently in slight swaying, when the animal is
standing quietly, or in some ataxia when it runs about. The
observation should be made frequently during the second
hour following the administration of the drug.
“The results obtained from the first test should be confirmed
after an interval of not less than three days by
repeating the administration, but reversing the order, that is,
giving the known strength drug to the dog which received
that of unknown strength before and vice versa.
“In subsequent tests which are carried out, the dose of the
preparation of unknown strength is modified so as to produce
similar symptoms to those produced by the standard. If
the preparation to be tested is below the standard in strength,
its dose must be increased, or if it is above strength its dose is
lessened until equivalent doses of the two are found. Dogs
may be used over long periods of time, even for some years,
but occasionally they have to be discarded, as in some cases
they seem to learn the effects of the drug and so refuse to
stand up. A certain degree of tolerance is sometimes gained
which necessitates larger doses.
“Standard,-As there is no chemical substance of definite composition which can be adopted as a standard, a fluid
extract of Cannabis or an extract which has been carefully
prepared and suitably preserved may be utilized for this
purpose. A standard fluid extract will produce incoordination
when administered to dogs in the dose of 0.03 mil for each
kilogram of body weight of dog. When administered in the
form of the Extract a dose of 0.004 Gm. for each kilogram of
body weight of dog should produce similar symptoms, and
the requirement for a standard tincture is a dose of 0.3 mil
for each kilogram of body weight of dog.” U.S. IX.
Uses.-Aside from a slight local irritant effect the action of
cannabis seems to be limited almost exclusively to the higher
nerve centers. In man this is first manifested by a peculiar
delirium which is accompanied with exaltation of the imaginative
function and later by a remarkable loss of the sense of
time. The delirium is often accompanied with motor weakness
and diminished reflexes and generally followed by
drowsiness. In the dog the earliest manifestation of the drug’s
action is a slight degree of restlessness which is soon followed
by disturbances of equilibrium and later weakness of the legs
and drowsiness.
Cannabis is used in medicine to relieve pain, to encourage
sleep, and to soothe restlessness. Its action upon the nerve
centers resembles opium, although much less certain, but it
does not have the deleterious effect on the secretions. As a
somnifacient it is rarely sufficient by itself, but may at times
aid the hypnotic effect of other drugs. For its analgesic
action it is used especially in pains of neuralgic origin, such as
migraine, but is occasionally of service in other types. As a
general nerve sedative it is used in hysteria, mental depression,
neurasthenia, and the like. It has also been used in a
number of other conditions, such as tetanus and uterine
hemorrhage, but with less evidence of benefit. One of the
great hindrances to the wider use of this drug is its extreme
variability. Formerly many of the preparations of cannabis
were inert before they left the manufacturers’ hands, and the
present requirements of the U.S.P. that the drug be tested
upon dogs to insure its activity is an important step in the
right direction. But even granted an active preparation when
manufactured, so rapidly does the drug deteriorate that by
the time the drug reaches the patient it has lost a large proportion of its activity. The only way of determining the
dose of an individual preparation is to give it in ascending
quantities until some effect is produced. The fluid extract is
perhaps as useful a preparation as any; one may start with
two or three minims of this three times a day, increasing one
minim every dose until some effect is produced. According to
C. R. Marshall (L. L., 1897, i, also J. A. M. A., Oct., 1898)
the deterioration of cannabis is due to the oxidation of
cannabinol, which he has found to act upon dogs and cats as
the crude drug.
Dose, of cannabis, one to three grains (0.065-0.2 Gm.).
Official Prep.-Extractum Cannabis, U.S. (Br.);-Fluid extractum
Cannabis, U.S.; Tinctura Cannabis (from Extract),
US. (Br.); Collodium Sidicylici Composita (from fluid extract),
N. F. ; Tinctura Chlorali et Potassii Bromidi Composita
(from Extract) IV. F.


Source: The Dispensatory of the United States of America
 
Back
Top Bottom