Pharm 100 - Lesson B.9
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Introduction to cannabis
- The term “cannabis” refers to the drug-containing forms of the hemp plant, Cannabis sativa, whichis an herbaceous annual. There are two varieties of
- Cannabis sativa – resin-producing and fibreproducing. In Cannabis sativa, there are 420 chemical compounds, many of which are common to otherplants. There are 60 compounds that are found only in Cannabis sativa, and these compounds arereferred to as cannabinoids. Of these compounds, l-trans-)9-tetrahydrocannabinol (THC) is the most potent psychoactive agent in cannabis, and THC accounts for most, but not all, of the psychoactive effects of cannabis. Common names for cannabis or its products include marijuana, hashish, hashish oil,charas, bhang, ganja, and dagga. Marijuana, hashish and hashish oil are the cannabis preparations mostcommon to North America.
- 2700 BC – 1800’s Cannabis plant was used for manufacturing rope; marijuana was used for its mildintoxicating effects as it was considered less harmful than alcohol.
- 1920’s – 1930’s Public concern was raised over the effects of marijuana on individuals and society (“menace of marijuana”). Legislation was enacted to outlaw the use of marijuana,which was considered to be a narcotic.
- 1960’s – 1970’s Increased use of cannabis, primarily in the form of marijuana. Survey in 1972- more than two million people in the U.S.A. reported daily use of marijuana. Survey in 1977- 60% of young adults in the U.S.A. reported some experience (?)with marijuana. A 1979 survey in Ontario revealed that approximately 50% ofstudents aged 16 or over reported some use of marijuana in the preceding 12months.
- 1978 U.S.A.-sponsored project using the herbicide, paraquat, was initiated in an attemptto destroy cannabis crops in Mexico. It failed. U.S.A. citizens were smokingcannabis products containing paraquat, which can produce lung toxicity.
- 1980’s In the early 1980’s, the use of marijuana began to stabilize. In 1982, 42% of highschool students in the U.S.A. reported use of the drug in the previous year and 5.5% used it daily. The figures in Ontario were similar.
- 1990’s The decline in the use of marijuana in the 1980’s was followed by an increase in use in the 1990’s. Marijuana is currently the third most popular psychoactive drug,after alcohol and tobacco (fourth if one includes caffeine).
In November 1996, voters in Arizona and California approved the legal use of marijuana formedical purposes. Other states are likely to follow the same pattern. This change in the use of marijuanareflects the changing public (societal) attitudes towards the use of this drug. In Canada, society mustexpress its views through different mechanisms, e.g. lobby groups. The changes which occurred inArizona and California are troublesome, at least from a pharmacological point of view. The medical useof drugs should be based on the scientific evidence which balances benefit and risk, i.e. evidence-basedmedicine. Society can decide on the societal risks that are acceptable, but not on the scientific validity ofdata.
- In 1997, an Ontario court dismissed charges related to possession and cultivation of cannabis on thebasis that the individual was using the drug to control epilepsy, which was not controlled by conventionaldrug therapy.
- In 1997, Canada changed the law to allow the cultivation of some varieties of cannabis that containvery small amounts of THC for use in the manufacture of rope, clothing and other hemp products. Farmers must obtain a special license to grow hemp, as the crop is called.
- In 2002 to 2005 Health Canada supported trials on the medical use of marijuana. Currently the program has been suspended
Classification of Marijuana
- Legal: Marijuana is classified as a narcotic and controlled under the Narcotic Control Act.
- Pharmacological: Marijuana is classified as a central nervous system depressant, euphoriant and hallucinogen, although the hallucinogenic properties only occur at high doses
Pharmacology of mamma J
- The mechanism of action of marijuana is not fully understood. The active ingredient in marijuana,)9-tetrahydrocannabinol (THC), binds specifically to receptors located in the cerebral cortex, cerebellum,hippocampus, hypothalamus, and other areas of the brain and spinal cord. These receptors have beendesignated CB1 or Type 1 cannabinoid receptors. A second receptor, CB2, is found only in the periphery. CB2 receptors do not appear to be involved in the psychotomimetic effects of THC, but may mediatesome of its effects on the immune system.
- Once these receptors were identified, the search began for an endogenous ligand (an endogenoussubstance which acts by binding to this receptor). Anandamide was isolated and meets the criteria to be classified as the endogenous ligand. Anandamide may be involved in learning and memory processes. The structures of THC and anandamide are shown in A Primer of Drug Action, Chapter 18, page 557. The CB1 receptor, when activated by anandamide or THC, inhibits the release of excitatoryneurotransmitters. This would explain the reduction in cognitive function seen with THC. It alsoexplains the CNS depressant properties of the drug (the terms “THC” and “marijuana” are usedsynonymously). THC produces most of its effects by inhibiting the release of transmitters; it may wellhave other actions.
- In the periphery, THC binds to CB2 receptors on lymphocytes (cells involved in the immuneresponse) and it is thought that the immunosuppressive properties of THC are mediated via this receptor
- The absorption of THC from marijuana smoke is rapid and the onset of action is almost immediate. The effect lasts up to three to four hours and more must be inhaled to continue the “high”. THC is alsoabsorbed after oral administration, but the absorption occurs slowly and is incomplete. The onset ofaction will be delayed 30 to 60 minutes. The effect is less than that from smoking the material
- THC is slowly metabolized, having a half-life of approximately 30 hours, but elimination from adipose tissue may take longer. It is the metabolites of THC that are measured in drug tests. Chronic users will be positive, for the metabolites, for several weeks after use has stopped. This does not meanthat they were under the influence of THC at the time of the testing.
Medical Uses of Marijuana
- Cannabis extracts were once widely used, on medical prescription, as sedatives and hypnotics. There are a number of possible uses for cannabinoids: nausea and vomiting, anorexia (loss of appetite),epilepsy, glaucoma, spasticity, and migraine. One of the few applications that has found some measureof medical acceptance is in the prevention of nausea and vomiting associated with anticancer drugs. Even in this application, other anti-nausea drugs were superior in studies. It must be recognized that, inthe past fifteen years, very effective and selective drugs have been developed to treat nausea associatedwith cancer chemotherapy. There are two synthetic THC derivatives used as anti-nauseants – dronabinaland nabilone. These agents are more selective in their actions than THC. As more information is obtained on the functions of anandamide and its receptors, it is likely that drugs that bind to the CB1 andCB2 receptors will be developed that are more effective and less toxic than THC.
- Recently a metered dose inhaler containing THC has been approved for the treatment of neuropathicpain. It is hoped that this means of administration of THC will be more effective than administering it inthe form of a tablet
Non-Medical Use of Cannabis and Cannabis Products
- Cannabis products are available, on the street, in several forms. Marijuana is the dried flowering tops and leaves of the harvested plans.
- Hashish consists of dried resin, usually from the flowers and compressed flowers.
- Hashish oil is obtained by extracting the cannabinoids from hashish.
- In most cases,the product is smoked or inhaled. Hashish may be baked into foods and eaten
Effects of Short-Term Use – Low to Moderate Doses
- CNS: Early effects will be seen as relaxation and drowsiness; there is disinhibition and talkativeness.
- A feeling of well-being, exhilaration and euphoria.
- They experience distortions in perception of time, body image and distance. Sense of hearing and vision are enhanced.The perception of the senses of touch, smell and taste are enhanced (this may be useful as an appetite stimulant).
- There is spontaneous laughter, impairment of short-term memory and concentration, and confusion. The attention span may be reduced.
- Balance and stability on standing and walking can be impaired. The user may have decreasedmuscle strength.
- Motor coordination is impaired (driving).
- The occasional user may experience fearfulness, anxiety and mild paranoia. Violent behaviour israre.
- The user may experience flashbacks, especially if they abused hallucinogens.
- Cardiovascular: The smoker experiences an increased heart rate and increased blood flow to theextremities. Their blood pressure may not accommodate when moving from a sitting to a standingposition (orthostatic hypotension).
- Respiratory: The smoke and ingredients in the smoke irritates the mucous membranes lining the respiratory system. There is also bronchodilation.
- Gastrointestinal: There is increased appetite and dryness of the mouth and throat.
- Other effects: Sex drive may be reduced in males, as THC may reduce testosterone levels. In females,THC can disrupt the ovarian cycle. In utero exposure may be associated with “behavioural problems” inchildren. As the drug wears off, there is an experience of a “hangover” similar to that with alcohol.
Effects of Short-Term Use – Higher Doses
- As the dose of cannabis (THC) is increased, the effects described above for low doses will beaccentuated. In addition, the following responses may be observed.
- CNS: Users may experience pseudohallucinations (hallucinations that the person knows are notreal). There is a running together of senses, e.g. seeing music. Judgement will be impaired, as iscoordination; reaction time is slowed and performance in simple motor tasks is impaired. There is often confusion of events; true hallucinations may occur as well as delusions. Mentation becomes confusedand disorganized. The user may become paranoid, agitated and panic stricken. Occasionally, there is atoxic psychosis manifested as hallucinations, paranoid delusions, disorientation, sever agitation, and afeeling of de-personalization (I really don’t exist).
- Cannabis and impaired driving: Tests conducted have demonstrated that THC interferes withfunctions required for the safe operation of a motor vehicle. These are motor coordination, tracking,perception, and vigilance. The actual performance on the road is impaired. The degree of disruption is dose-dependent, as little as one joint can be found to cause an impairment in some individuals. Alcoholand THC, used simultaneously, will intensify the adverse effects of each other on driving performance.
Effects of Long-Term Use
- Psychological effects: The occasional low-dose use of cannabis does not appear to be associatedwith harmful psychological effects. The risk of psychological dependence is more evident in users whohave emotional problems and use cannabis to control psychological stress.
- Very high doses of cannabisover a long period may be associated with significant problems in some users. There is an“amotivational syndrome” associated with high-dose use. This is characterized by mental slowing, loss of memory, difficulty with abstract thinking, loss of drive, and emotional flatness. The syndrome usuallydisappears upon cessation of drug use, suggesting that it represents chronic intoxication. The mostcommon long-term effects seen are: loss of short-term memory, lack of concentration, and loss of abilityin abstract thinking. The issue of permanent effects from long-term use has not been settled, but somedata suggests that structural changes do occur in the brain and these changes may be associated withimpairment of memory and learning.
- The cardiovascular effects of cannabis are usually reversible. The changes in blood pressure do not appear to be serious. The increase in heart rate can be a potential problem for the user with heartdisease.
- The respiratory system is a major target for the adverse effects of smoking marijuana. Bronchitis,asthma, sore throat and chronic irritation of and damage to membranes of the respiratory tract are allhigher in heavy users of marijuana. These adverse events are additive with the simultaneous use of tobacco and marijuana. Marijuana smoke contains a higher amount of tars and carcinogens (cancercausing compounds) than tobacco smoke and is most likely to be a cancer-causing product. Currentstudies suggest that cancers may occur more rapidly with marijuana than tobacco. Cancers due tosmoking tobacco have a latency period of 20-25 years. Not only are there higher concentrations ofcarcinogens in marijuana smoke than in tobacco smoke, but the method of smoking is different. The marijuana user inhales deeply and holds the smoke in the lungs in order to maximize the absorption ofTHC and other cannabinoids. Unfortunately, this process also enhances the amount of tars and carcinogens absorbed.
- Other areas of concern are the long-term effects of cannabis products on human male fertility. While there is a decrease in sperm count, fertility does not appear to be affected. The other area ofconcern is the effects on the developing fetus. Developmental delays have been observed, but it is difficult to distinguish the effects of THC from those of other drugs, diet, and overall poor prenatal care.
Tolerance and Dependence
- Tolerance does occur to the cannabinoids upon long-term use. Tolerance occurs to the psychoactiveproperties of THC, but also to the effects on the cardiovascular system, the impairment of performance,and cognitive function.
- Physical dependence can occur with high-dose use. Upon termination, there is a mild withdrawalsyndrome. This is characterized by sleep disturbances, irritability, loss of appetite, nervousness, mildagitation, upset stomach, and sweating.
- With regular use, psychological dependence does develop. There is often a persistent craving forthe drug and the drug is the most important component in their life.
Potential for Abuse
- The dependence liability of cannabis products is low to moderate. The euphoria (high) is not asintense as some other drugs (e.g. cocaine) and the reinforcement is much less.
- The inherent harmfulness of cannabis products is low, especially for low doses of the drug(infrequent use). The greatest danger may possibly be an automobile accident, which is becoming asignificant problem. The major long-term effects are the adverse effects on the respiratory tract, althoughthe effects of high-dose, chronic use on the CNS should not be discounted.
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