War Is Peace
Freedom Is Slavery
Ignorance Is Strength
- George Orwell, 1984
Inscribed on the facade of the Ministry of Truth, these
words summarize the federal medical and scientific policies
in the field of moral pharmacology. With this most recent
groupthink revision of scientific newspeak, cannabis history
now starts in 1981 in response to the introduction of a bill
in Congress (H.R. 4498) "to provide for the therapeutic use
of marijuana in situations involving life-threatening or
sense-threatening illness and to provide adequate supplies of
marijuana for such use," and promises a review of the
literature, which, except for one citation in 1889, one in
1947 and one in 1953, the expunged literature is now
comprised mostly of research conducted in the 1970's. Thus,
the perspective of the Committee is based on minimal
experience in therapeutic applications, deprived of the
practical experience from clinical access enjoyed by their
colleagues of half a century ago when cannabis was available
by prescription.
Most important in therapeutic potential and medical uses
of marijuana are the omissions. Left out was the fact that
cannabis presentations were widely used in Western medicine
from 1839 to the early 1940's. Omitted: concise and accurate
descriptions of the medicinal applications of cannabis that
appeared in the
U.S. Pharmacopoeia and Goodman and Gilman's textbook
of pharmacology, second edition (1955). Forgotten: primary
scientific, structure-activity and pharmacologic studies by
Professor S. Loewe (1950) in the 1940's and early 1950's.
Neglected: comprehensive clinical research by the Mayor's
Committee on Marihuana in 1944.
GLAUCOMA
A reasonably fair assessment of variable results with
different varieties of the illness. Indeed, topical
application would be desirable in nonneurogenic glaucoma, but
solubility characteristics of cannabinoids would appear to be
intrinsically irritating. It would appear that slow titration
with natural or synthetic cannabinoids orally (Reynolds 1890)
would enhance the possibility of favorable results with the
greatest medical safety.
ANTIEMETIC ACTION
Indeed, the discovery of cannabis as an antiemetic is a
most important and truly new discovery that was not known to
medicine when it was available. It is exciting to learn of
the positive results, and one can only wonder why an inhalant
cannot be developed to deliver purified natural and synthetic
cannabinoids. The inhaled route is inherently preferable
especially when nausea and vomiting are inhibiting
gastrointestinal retention and absorption. Autotitration is
also made possible because of this comparatively short
latency period after administration by this route.
ANTICONVULSANT ACTION
Medical practitioners of more than a century ago (e.g.,
McMeens 1856, O'Shaughnessy 1839) would turn over in their
graves to read that a major drug for certain nervous
disorders had retrogressed to a preclinical status of
"showing promise" in a 15-subject seizure disorder study in
1980.
MUSCLE RELAXANT ACTION
As described in the context of utility in spasticity, this
delineation being centrally mediated would correctly fall
within the domain of the anticonvulsant activity.
ANTIASTHMATIC
It is encouraging to see cannabis rediscovered as an
antiasthmatic agent. McMeens (1860) and Waring (1874) noted
cannabis to be useful in some cases of asthma and hay fever
where an "irritable nervous system" seemed to be involved.
Cannabis as a treatment for asthma was mentioned in India in
1954.
ANTIANXIETY-ANTIDEPRESSANT EFFECT
This section by the Committee demonstrates the
methodological problems involved in translating commonly
observed cannabis-use behavior into a scientific presentation
that is oriented to therapeutic utilization. This author's
personal observations of chronic users clearly show cannabis'
applications to closely approximate those of the
benzodiazepines or alcohol. Like other sedatives, the onset
of effects may be an initial stimulation. Alcohol and
cannabis share this property. After the stimulation phase
there is a calming effect. The intensity of the stimulation
(and sedation) is directly dose-related. Low dose (two or
fewer joints/day) chronic use of cannabis appears to have an
effect comparable to five mg of diazepam (Valium®)
twice a day. Chronic cannabis users also show a slight
stimulant effect with a mental lift and an EEG shift from
predominantly alpha/theta (four to 13 Hz) to mostly beta
waves (>14 Hz).
Low and moderate dose cannabis use appears to decrease
affectual reactivity and subjective sense of pressure with
reduction of concomitant multisystem stress. The site of
activity is probably at the thalamo-cortical level, as
postulated by Walton (1938). The reddened eyes of cannabis
users reflect an apparent specific meningeal/vasomotor
response. Cannabis, as compared with other psychotropics, has
remarkably minimal brain stem and other peripheral
effects.
ANALGESIC ACTION
Not referenced nor mentioned: Animal models showing
analgesic effects for cannabis and its derivatives starting
as far back as Hare (1887) and Marshall (1898), as well as
overlooking the extensive bioassay protocol utilized by the
pharmaceutical industry to standardize the strength of
cannabis preparations in reference to U.S.P. standard
preparations available from the U.S. Food and Drug
Administration until 1938.
The "mental clouding" side effect reported in 1976 when
using THC as an analgesic for cancer pain control might have
been avoided by emulating Dr. J. Russell Reynold's protocol
of gradual upward titration of cannabis tincture, as
described in
Lancet in 1890. (Perhaps, using a U.S.P. standard
cannabis tincture might have been more effective than
THC.)
Ignored: Numerous descriptions of cannabis as the
treatment of choice for migraine headache, as listed in
materia medica, journals and texts with the latest (and
unfortunately last) in the
Journal of the American Medical Association by Morris
Fishbein (1942) 4O years, ago.
ALCOHOLISM
In this author's limited clinical and social
experience, the substitution of cannabis as a
euphoriant/sedative is possible in some cases. The success of
substitution depends on support groups of other cannabis
users. Failure is usually due to denial and rigidly
habituated behavior patterns usually involving other
alcoholics or alcohol abusers. Another significant source of
failure is the deterrence by its illegal status and uncertain
supply of the drug.
OPIATE WITHDRAWAL
It should be said that the reason there are no efforts to
follow up on Birch's (1889) and Mattison's (1891) early
clinical experiences is because of the excessively
restrictive multiagency federal involvement. In the moral
pharmacologic regulatory reality, the treatment of discomfort
brought on by the abuse of another illegal drug is low
priority.
ANTITUMOR ACTION
It might be construed to be antitumor in the enhancement
of appetite and suppression of nausea, but, as such, specific
antioncologic activity seems unlikely.
SUMMARY
The lack of clinical experience is a serious impediment to
a realistic appraisal of the therapeutic potential of
cannabinoids. The federal bias toward pushing THC for
scientific "purity" and the inability to grow or process
cannabis would appear to constitute another negative
influence. It is gratifying that despite these difficulties
the Committee is in favor of further research into the
medicinal applications of cannabis.
There is sufficient clinical data, both recently and
historically, to warrant the restoration of cannabis products
for general prescribing. The Committee is generally correct
in their favorable findings in glaucoma and antiemetic
applications, but grossly underestimates the utility of
cannabinoids as sedative, anticonvulsant and antimigraine
agents because of inadequate experimental protocol, a less
than thorough review of the medical literature and
dog-in-the- manger interagency conflict-based federal
policy.
RECOMMENDATIONS FOR RESEARCH
The development of nonirritating purified natural
cannabinoid aerosol preparations should be a top priority
effort. The reality is that because the smoked route is used,
there will be huge numbers of chronic cannabis smokers
subjecting their tracheobronchial trees to irritation from
pyrrolized impurities that technology could prevent.
Precisely how much morbidity and mortality, which could have
been prevented through appropriate research and development,
remains to be answered in the distant future.
Cannabis homologues have been studied since the late
1930's. The compounds synthesized and studied by Loewe (1950)
have yet to be adequately reevaluated and would be of
potential benefit to the present knowledge of chemical
structure-activity relationships in cannabinoids - the only
complex nonnitrogenous water insoluble psychotropic agents
known.
REFERENCES
Birch, E.A. 1889. The use of Indian hemp in the treatment
of chronic chloral and chronic opium poisoning.
Lancet Vol. 1:625.
Fishbein, M. 1942. Migraine associated with menstruation.
Journal of the American Medical Association Vol. 120:
4, 326.
Goodman, L.S. & Gilman, A. (Eds.). 1955.
The Pharmacological Basis of Therapeutics. New York:
Macmillan.
Hare, H.A. 1887. Clinical and physiological notes on the
action of cannabis indica.
Therapeutic Gazette Vol. 11; 225-228.
Loewe, S. 1950. The active principles of cannabis and the
pharmacology of the cannabinols.
Archiv fur Experimentale Pathologie und Pharmakologie
Vol. 211: 175-193.
Marshall, C.R. 1898. A contribution to the pharmacology of
cannabis indica.
Journal of the American Medical Association Vol. 31:
882-891.
Mattison, J.B. 1891. Cannabis indica as an anodyne and
hypnotic.
St. Louis Medical and Surgical Journal Vol. 61:
265-271.
Mayor's Committee on Marihuana. 1944.
The Marihuana Problem in the City of New York.
Lancaster, Pennsylvania: Jacques Cattell Press.
McMeens, R.R. 1860. Report of the Ohio State Medical
Committee on cannabis indica.
Transactions of the Fifteenth Annual Meeting of the Ohio
State Medical Society. Columbus: Follett, Foster &
Co., pp. 75-100.
Nadkarni, A. (Ed.). 1954.
Indian Materia Medica. Bombay: Popular Book Depot.
Orwell, G. 1949.
1984. New York: Harcourt Brace Jovanovich.
O'Shaughnessy, W.B. 1838-40. On the preparations of the
Indian hemp, or gunjah.
Transactions of the Medical and Psychical Society of
Bengal. pp. 71-102.
Reynolds, J.R. 1890. Therapeutic uses and toxic effects of
cannabis indica.
Lancet Vol. 1: 637-638.
Walton, R.P. 1938. Marihuana: America's New Drug
Problem. Philadelphia: J.B. Lippincott.
Waring, E.J. 1874.
Practical Therapeutics: Articles of the Materia
Medica. Philadelphia: Lindsay & Blakiston. pp.
157-161.
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