Marijuana
Scientific Name(s): Cannabis sativa L. More than a dozen other species names have been used to describe marijuana. Family: Cannabaceae
Common Name(s):A variety of common names have been attributed to the plant. There are, however, specific terms for the various plant parts and extracts. These include: anascha and kif (resinous material and flowering tops mixed with the leaves); banji , hemp , cannabis , shesha , dimba , dagga , suma , vingory and machona (entire plant); bhang and sawi (dried mature leaves); charas (resinous material); ganga (flowering tops); hashish and esrar (resinous material with flowering tops); and marijuana or marihuana (leaves and flowering tops). Names vary with local customs. 1
Clinical Overview
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Uses of Marijuana
Marijuana appears to be medicinally useful as an antiemetic, but its potential for abuse has so far outweighed proposals for its use as a therapeutic agent.
Marijuana Dosing
Marijuana use in cigarette form is typically titrated by the user for its antinausea effects. Doses of pure THC used in clinical studies in analgesia and Tourette syndrome have ranged from 0.4 to 90 mg daily in oral formulations. 2 , 3 , 4 , 5
Contraindications
Contraindications have not yet been identified.
Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use.
Marijuana Interactions
None well documented.
Marijuana Adverse Reactions
Marijuana can be harmful to the heart, lungs, brain, endocrine system and eyes.
Toxicology
Marijuana has a strong potential for abuse and is classified as a schedule Ι drug.
Botany
Cannabis is a leafy annual, some species of which attain heights of more than 10 feet. The stalk may grow 3 to 4 inches thick, is square and hollow and has ridges running along its length. Each leaf has 5 to 11 leaflets radiating from the top of the stalk. These are soft-textured, 7 to 10 inches long, narrow and lance-shaped with regular dentation like a sawblade. The plant is dioecious showing male or female flowers. The female plants have a heavy foliage, while the male plants are sparse. The resin mixture is found in the glandular hairs of the leaflets and floral bracts and is called hashish. Hashish is made up of numerous tetrahydrocannabinol compounds. Cannabis is cultivated worldwide for fiber, seed oil and hashish. The controversy over legitimate and illegal use of cannabis persists. 6 , 7
History
The use of cannabis dates back more than 4,000 years. It has been used for the treatment of catarrh, leprosy, fever, dandruff, hemorrhoids, obesity, asthma, urinary tract infections, loss of appetite, inflammatory conditions and cough. It has been used as a source of fiber for ropes and clothing. The plant's sedative effects were recognized by the ancient Chinese, but the widespread use of the plant for its psychoactive effects most likely began only in the past century. 6 , 8
The history and details of the health hazards of cannabis have been reviewed. 8
Chemistry
More than 420 different compounds have been isolated from cannabis and reported in the chemical literature. The most commonly described compounds are the cannabinoids [delta–9–tetrahydrocannabinol (THC), cannabidiol, and numerous related compounds]. In addition, marijuana contains alkaloids, steroidal compounds and mixtures of volatile components. 5
Feruloyltyramine, a new amide compound, and p-coumaroyltyramine have recently been identified in cannabis seeds. 10 From the fruits, three new acyclic bis-phenylpropane lignan amides have additionally been isolated. 11
The concentration of THC varies in different parts of the plant, being higher in the bracts, flowers and leaves and lower in the stems, seeds and roots. THC concentration varies from 0.1% in Kansas hemp to 4% or more in Jamaican or Vietnamese specimens. 12
Analysis of dried cannabis samples from 1896 to 1905, reported the presence of cannabinol. 13 Additional reports on illicit cannabis samples from Great Britain, Northern Ireland and Denmark exist, evaluating THC content, cannabinoid content and locational differences between regions. 14 , 15 Cannabinoids in hemp (cultivated for fiber production) have also been reported. 16 Analysis of cannabis includes methods such as gas chromatography (GC), high-performance liquid chromatography (HPLC), random amplification of polymorphic DNA (RAPD) and thin layer chromatography (TLC). These methods are of use in sample differentiation, forensic analysis and other applications. 17 , 18 , 19 , 20 Radioimmunoassay of hair for marijuana presence in body systems has also been performed. 21
Marijuana Uses and Pharmacology
The pharmacology of whole marijuana and many of its individual compounds has been investigated in detail. THC appears to contribute most significantly to the pharmacologic effects observed. Cannabinol may potentially contribute to the psychoactivity of the plant. This compound is a degradation product of THC and is not found in the fresh plant. Marijuana exerts its activity following inhalation of the smoke or oral ingestion. When inhaled, THC is absorbed rapidly. The systemic bioavailability of THC following smoking is approximately 18% but higher in heavy users and lower in light users.
THC is distributed rapidly throughout the body, in particular to tissues with high lipid content. Approximately 80% to 90% of an IV dose of THC is excreted in urine and the remainder excreted in the feces via the bile. 9
Cannabinoid metabolites remain detectable in urine for more than 10 days after a single use and for more than 20 days after chronic use. A French report on detection, evaluating newborn infants, suggests not only urine testing of the infant to detect drug exposure, but to also test meconium and hair as well. Testing all three parameters increases sensitivity of analysis for drug exposure detection. 22
Antiemetic effectsAnimal data
Research reveals no animal data regarding the use of marijuana as an antiemetic.
Clinical dataConsiderable attention has been given to the evaluation of THC as an antiemetic agent. THC administered as oral capsules appears to be at least as effective as prochlorperazine but may have more CNS side effects. THC is effective in patients refractory to other agents and the drug appears to be particularly useful against the side effects of high-dose methotrexate, BCNU (carmustine) or radiotherapy. Only nine cases of serious adverse effects caused by THC therapy were reported in 1565 patients who received THC treatment. These have ranged from agitation and panic to seizure and tachycardia. One analog, nabilone ( Cesamet ) has been found to be effective but may be difficult to use clinically because of the potential for accumulation. 12 Several publications in the popular press have shown that there is a continued conflict between marijuana's schedule Ι status vs the rights of physicians to prescribe it for medical purposes.
Dosage
Marijuana use in cigarette form is typically titrated by the user for its antinausea effects. Doses of pure THC used in clinical studies in analgeia and Tourette syndrome have ranged from 0.4 to 90 mg daily in oral formulations. 2 , 3 , 4 , 5
Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use.
Interactions
None well documented.
Adverse Reactions
Marijuana can be harmful to the heart, lungs, brain, endocrine system, and eyes.
Toxicology
Marijuana has a strong potential for abuse and is classified as a schedule Ι drug.
Cardiovascular effectsIngestion or inhalation of marijuana often results in tachycardia (especially supraventricular). ECG changes are not observed regularly in healthy young adults. 23 The drug may reduce exercise tolerance in anginal patients. Although marijuana may raise blood pressure, there is no evidence that the drug may cause permanent deleterious effects on the normal cardiovascular system. 24
Pulmonary effectsBronchial and pulmonary irritation are well-documented following smoking of marijuana. Although short-term inhalation has been found to increase bronchodilation and to reduce bronchospasm in asthmatics, long-term administration impairs lung function. Chronic use may result in constrictive lung disease such as interstitial fibrosis. In one study comparing the adverse effects of marijuana and tobacco, smoking less than one marijuana cigarette a day diminished vital capacity as much as smoking 16 tobacco cigarettes. 25 A later report also evaluating marijuana and tobacco smoke, finds that the gas-phase cytotoxins that are present may have no cytotoxic potential when inhaled by humans. 26
Various types of marijuana may contain up to 50% more polyaromatic hydrocarbons in its smoke than tobacco does, high levels of which are associated with susceptibility to bronchial carcinoma. Marijuana appears to be frequently contaminated with aspergillus mold. In one study, 11 of 12 samples tested were contaminated. Spores of aspergillus pass readily through marijuana cigarettes into smoke, 27 and can result in fungal sensitization. 28 This is important in light of the use of marijuana by immunocompromised patients. Paraquat (a herbicide sprayed to control marijuana growth) toxicity was identified several years ago, but does not appear to be a clinically important problem. 29
Neoplastic effectsMouse skin painted with marijuana smoke particles produced metaplasia of the sebaceous glands. In another study, tobacco tar applied to the skin of mice was more carcinogenic than marijuana tar. Bronchial biopsies from humans have identified atypical cells, basal cell hyperplasia and squamous cell metaplasia to the greatest degree in subjects who used both marijuana and tobacco. 23
Psychomotor/CNS effectsMarijuana intoxication impairs reaction time, motor coordination and visual perception. Marijuana can produce panic reactions, “flashbacks” and other emotional disturbances for which children and adolescents appear to be at highest risk. Distortion of time and distance and visual and auditory hallucinations have been reported. 1 Marijuana's high potential for abuse explains its classification as a schedule Ι drug under the jurisdiction of the Controlled Substances Act. 30 Humans and other species prefer higher doses (over lower doses) with many drugs of abuse. Subjects choose high-potency marijuana (1.95% THC) more than low-potency (0.63% THC), linking the drug's abuse liability to the content. 31 “Drug liking” and higher THC dose choice in marijuana cigarettes over placebo has similarly been reported. 32
A structural relationship has been identified between cannabidiol and phenytoin, suggesting that cannabidiol meets the steriochemical requirements suggested for anticonvulsant drug action. 33 At least one report suggests that marijuana smoking can assist in the control of epileptic seizures; 34 however, marijuana use has also been shown to exacerbate grand mal convulsions. 35 THC has induced catalepsy (abnormal maintenance of posture associated with mental state) in mice, but cannabis oil and related cannabinoids have not. 36
Endocrine effectsLong-term use of marijuana in females may cause abnormal menstruation, including anovulatory cycles. Fetal damage has been reported in animals and appears to occur in humans. THC mediates the secretion of pituitary gonadotropins. In ovariectomized rats, injected THC in relatively low doses suppressed the release of leuteinizing hormone by up to 68%. 37 In males, conflicting data have been reported regarding the lowering of testosterone levels. Although reduced sperm counts have been reported in controlled trials, these are probably less important than the development of sperm structural abnormalities and motility changes induced by marijuana.
Ocular effectsIncreased conjunctival vascular congestion is a common feature of marijuana use. Marijuana and THC have been investigated for the reduction of intraocular pressure in glaucoma. Although some studies indicate that the drug is effective, it is not clear whether treatment preserves visual function. 36
Miscellaneous effectsMarijuana has been associated with xerostomia, nausea and vomiting. The cannabinoids are highly allergenic when evaluated in the guinea pig. 38 Some fractions of marijuana may have trypanocidal effects, 39 and immune system effects. 40
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