of Psychoactive Drugs 14 (1982): 239-241
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.
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.
II. 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.
III. 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.
IV. 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.
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.
VI. 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.
VII. 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.
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.
IX. 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.
X. 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.
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.
XII. 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.
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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.
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