Cannabis for Medicinal Purposes
Compiled by John Malouf, Pharmacist
This paper is written in response to an invitation from the Chair of the Working Party, Professor Wayne Hall, on the Use of Cannabis for Medicinal Purposes.
- Terms of Reference
- Pharmacokinetics: THC in Oral and Inhaled Form
- Cannabinoid Content or Pharmacokinetics? Why might smoking marijuana be helpful?
- Design Issues
- Risks and other Matters to Consider
- Cannabis and the Sick; therapeutic Applications
- Pain Relief
- Nausea and Vomiting from Chemotherapy
- Multiple Sclerosis
- Cannabis & the Brain
- Mental Illness & Acute Toxic Psychosis
- Dependence (Addiction) and Marijuana Use
Terms of Reference
I understand that the terms of reference are the following with a limit of 5000 words excluding references.
- To review the extant medical and scientific literature
- To establish what further research is required
- To establish if and how cannabis can be effectively administered with the least harm to patients
- To establish if and how cannabis, or any cannabinoid substances, should be supplied for medicinal use and how diversion for recreational use or dealing or trafficking could be avoided in these circumstances
- To identify legal, ethical, pharmacological physiological, mental, general health and community implications and issues concerning the use of cannabis for medicinal purposes
- To make recommendations to the Expert Advisory Group on Drugs
- To access the efficacy and safety of cannabis use for medicinal purposes.
- Specific medicinal uses of the plant cannabis sativa or cannabinoid substances, including citation of key evidence,
- Ways in which cannabis products or cannabinoid substances could be provided to those who may benefit from them (eg by prescription).
From a pharmacy perspective, I am doubly surprised that in the year 2000, serious consideration is being given to the medicinal use of any plant in its crude form, instead of a specific alkaloid contained in the plant or synthetic derivatives of it. In addition I am confounded that credibility is being given to the method of administration, namely smoking.
No matter where or when the cannabis plant is examined there will always be reservations about its safety especially because of its psychiatric associations.
The cannabis plant was a source of some medications in the 19th century but finally disappeared from the US Pharmacopoeia in 1942 as it was used with less and less frequency. Later in 1989 the US Drug Enforcement Agency held an official independent investigation as to whether grounds could be established for marijuana to be used medicinally. In his final judgment the administrator expressed his concern.....
"at the misleading accusations and conclusions (of the pro marijuana groups) ... ..these organisations have falsely raised the expectations of many seriously ill persons by claiming that marijuana has medicinal usefulness in treating emesis, glaucoma and other illnesses."
he went on to state
"These are not the Dark Ages. The Congress as well as the medical community, has accepted that drugs should not be available to the public unless they are found by scientific studies to be effective and safe.....(the marijuana apologists) have attempted to perpetuate a dangerous and cruel hoax on the American public by claiming that marijuana has currently accepted medical uses."1
I repeat this statement here, without comment, to demonstrate the strong position held by many in the United States authorities who have reviewed a deal of material on cannabis. The US did not severely restrict the drug till 1937, whereas the League of Nations, on the initiation of Egypt, condemned the drug in 1920 as the damage it was causing and had caused was becoming obvious.
To the best of my knowledge, no crude drug plant is used medically in western medicine today, once the medically active chemicals have been isolated and separated from the useless waste.
Similarly, this writer knows of no drug used in medicine in these times whose preferred route is by smoking. The last substance that I can recall used in this manner was a compound of stramonium leaves which was used over 40 years ago in Australia.
It was marketed under the name of Elliotts Asthma Cigarettes. One hundred years ago, one prescription had leaves of stramonium mixed with tobacco, yarrow and coltsfoot, then smoked. Knowledge took its toll on this product as the dangers of smoke inhalation had become apparent and in addition atropine, hyoscyamine and hyoscine (scopolamine) contained in the stramonium leaves had been isolated and used in other situations and administered differently. One reason the product was abandoned was because the substance caused hallucinations.
Cannabis sativa is not an exception, Why should it be? One can only speculate as to why it should be treated in a different manner to any other drug. There are over 420 different chemicals contained in the plant including over 60 unique chemicals known as cannabinoids. Most of the research, to date, has been given to just one cannabinoid, the psychoactive one, delta-9-tetrahydrocannabinol and to various synthetics developed from this basic molecule.
It now appears there is a movement to reintroduce a concept together with a route of administration that was abandoned some 40 years ago. The equivalent would be to reintroduce the plant material from the opium poppy and prescribe it to be smoked for serious pain instead of using its two major alkaloids, codeine for oral use and morphine mainly by the parenteral route. Surely, the same criteria should be applied to all crude plant drugs or are we about to step backward in time? Are we about to see the return to many other crude drugs like digitalis leaves and the ephedra plant and abandon digoxin and ephedrine hydrochloride? I would not think so. Yet, this would be the case if the same logic was applied to cannabis leaves if they were introduced for medical purposes.
For what reason would we disagree with the highly respected peer-review pharmacologist, Dr. Leo Hollister,
"Cannabis and the THC homologs should be treated like any other investigational new drug as the search for a clinical use in medicine goes on. The ingenuity of pharmaceutical chemists in developing THC analogs may yet find a way to exploit some of these potential therapeutic uses without the side effects that make Cannabis, itself, undesirable"2
Cannabis sativa must be one of the most controversial drugs of all time. Botanically it is a very unstable species with over 100 plant varieties of differing strengths. Because of this, hybrids of the plant are constantly in a state of development, especially in Holland, where a ready market exists for its psychoactive properties. This has lead to the development of widely varying strengths of the plant. This basic botanical fact has been ignored by many who discuss the drug as if it were a single substance with mild intoxicant properties. Its unpredictable nature varies immensely from individual to individual and according to the strength of the product used. No longer is it just the mild variety that was once used, 1-2% THC. Canada has just developed a variety of the plant of which 30% of its weight is THC2
Early reports on the medicinal value of cannabis came to the West from India in the early 19th century where it was heralded as being of value for rabies, tetanus, epilepsy3 , rheumatism and many other ailments. About the same time, one of the founding fathers of psychopharmacology, the physician , Moreau, experimented on the mentally ill with hashish in France and was the first to document its effects on the brain.
Members of the pro-pot lobby and the drug-culture promote the medical use of marijuana through their publications, such as HighTimes and the Internet. Their aim of course is normalisation of their activity. The three American organisations who have promoted and continued to promote ³medical marijuana² are the well-funded, Drug Policy Foundation , Norml and the Lindesmith Centre. All three organisations are committed to de-regulation of cannabis . It is well known that major financiers back these organisations. These groups and their adherents see that medical marijuana is an important avenue in getting marijuana and (other drugs) de-controlled.
For example, this author wished to purchase a copy of Lester Grinspoon¹s Marihuana Forbidden Medicine from a medical bookstore in Switzerland, it was not available but easily purchased in a head-shop4 promoting marijuana from Sensi Seeds, Amsterdam promoted in the front of the book.
In Drug Precipice, which was co-authored by two others, and myself, a former Royal Commissioner and retired President of the Court of Appeal (NSW) and a Sydney magistrate, some of the dangers of marijuana are listed5 . I will not repeat them again here but sufficient to say that before any decision can be made on whether cannabis should be available to treat the sick, the known and suspected side effects must be fully understood. These are well set out in a 210 page publication from the Commonwealth , Monograph 25, The health and psychological consequences of cannabis use6 . Your chair, Wayne Hall is one of the co-authors of this review.
Given that each one of us carries a degree of bias, I acknowledge that I am no exception, but I have tried to be as objective as possible in examining the scientific material available relating to cannabis and medicine. In my life time, I have seen many drugs and preparations once thought to be benign, finally abandoned or heavily restricted as their darker side emerged after these products were ³on the market.²
The following are just some of these abandoned or heavily restricted.
- phenacetin topical lead preparations;
- oral and topical mercury products;
- topical use of benzol;
- Drinamyl , Enterovioform ;
- oral dilute solutions of hydrocyanic acid, arsenic and strychnine ( the latter two were used in "tonics");
- Physeptone linctus (for coughs);
- the use of Dover¹s Powders (containing opium) for teething;
- phenmetrazine hydrochloride as an appetite suppressant;
- even camphorated oil.
In all cases we had been originally told how valuable these products were, given the knowledge at the time. The case is completely different with cannabis as a great deal is already known of its dangers. For examining the medical benefits or otherwise of cannabis,the model I have used is simple. Is there any justification for the official endorsement of this drug or any plant of any other type to be smoked? Does cannabis have known medicinal value? Is it superior to any other existing drugs forspecific conditions? Do its benefits outweigh its side effects?
Pharmacokinetics: THC in Oral and Inhaled Form
Because of its lipophylic properties, THC is rapidly distributed throughout the body as it binds to many areas; its excretion rate is also difficult to study because it extends over a long time. A handicap with studying the inhalation of cannabis is the impossibility (to date) of determining the exact dose of THC that is consumed. The inhalation route is a very efficient method of drug absorption when compared to the oral route which is somewhat erratic and much slower. However, the effects vary greatly in smoking, given the different skills of the smoker.
"We can predict within a 95% confidence interval the time a subject smoked and this measurement is used around the world in accidents to determine driving under the influence of the drug.7 "
Cannabinoid Content or Pharmacokinetics? Why might smoking marijuana be helpful?
There is now a great deal known about the pharmacology of THC, but the pharmacology of a smoked marijuana cigarette remains inconclusive. Rosenthal, Mikuriya8 , Grinspoon9 and other proponents for medical marijuana argue of the benefits of the crude plant versus its main psychoactive chemical, THC. They also claim that availability of THC or other cannabinoids in oral form do not satisfy the need to evaluate marijuana itself. A great deal of argument has occurred over whether smoking marijuana has significant therapeutic advantages over oral doses of THC or other derivatives of the plant.
To date it appears that none of the questions have been definitively answered about the benefits of smoked marijuana for any particular disease or condition, using scientific valid methods. There is insufficient data, relating to the exact dose needed, how frequently it needs to be used, its safety, its side effects, when the drug is smoked for medicinal reasons. Although it is recognised that the pharmacokinetics of THC from smoked marijuana varies considerably from oral THC, other proponents of marijuana, Zimmer and Morgan10 argue the pharmacokinetics of smoked marijuana has therapeutical advantages over other routes used. Although there are over 420 chemicals in the plant material, hundreds more (some authorities claim 2000) are formed when it is pyrolysed and smoked directly into the lungs.
With any smoked drug, eg tobacco, it is difficult to measure or control a dose of any of the substances contained. This has been very hard to measure even in controlled studies of cigarette smoking. The same applies to marijuana. Hence a problem! It is essential, when prescribing, to state a measured dose; to date this cannot be done with marijuana smoking. For example a cigarette of marijuana of standard known strength and size will be smoked "recreationally" so as to deliver the smoker¹s desired effect not that as laid down in the protocol of research. Then there is the problem of inexperienced smokers who tend to overdose or underdose. Whereas smoking is hard to administer in a laboratory situation it is impossible to control in a clinical trial of outpatients.
Another problem is that of tolerance11 as well as addiction (dependence), which develops from using the drug. This of course has to be considered. In any study tolerance would be a consideration, as dosage would have to be adjusted as the user would be anticipated to need a higher dosage as time progressed. As far as addiction was concerned, a study in New South Wales in 1997 showed that 57% of long term users of cannabis were dependent on the drug and 75% of these were not aware they had a problem.12
Because of the controversy long surrounding marijuana from those who over emphasise or underemphasise the risks or benefits, the usual problems associated with medical trials of new or unknown drugs are magnified many times, making it very difficult to even have a balanced discussion about it. A random assignment with controls over concurrent pharmacological and non pharmacological therapies is needed. If subjective assessments or self reporting is involved then this is particularly important and should be made under double-blind conditions. Of course, trials with the smoked product produces even more complications. The selection of patients would be problematical. The basic question of whether smoked cannabis has any advantages over the present medications is the real bottom line given the known side effects of the drug. It would have to be determined whether "medical marijuana" was just an excuse for obtaining the drug for long-term users or those dependent on it.
Risks and other Matters to Consider
Given that the vast resources of the tobacco industry have so far been unable to produce a system to deliver tobacco smoke-free, the chances of developing one for marijuana would seem remote.Of course the risks will vary with the disease, the patients and period of treatment. Obviously short term treatment would be a deal less risky than long term treatment. A patient using marijuana for the management of nausea from chemotherapy would be at a lot less risk than those using marijuana for chronic pain, glaucoma, epilepsy or spastic motor diseases. Patients already with damaged immune systems would be at greater risk than other patients because of the negative effects of cannabis on the immune system. Is the claim correct that HIV-positive marijuana smokers progress more rapidly to AIDS than smokers? This is not known to the writer but if this is correct then it should be publicised and if not it should be refuted and put to rest! Some papers suggest this13 .
It would seem that the negative effects on the immune system are irrefutable. eg there are at least 57 separately conducted studies cited that would give warnings on the susceptibility of the immune system to cannabis.
Given the many negative effects from marijuana14 obtaining informed consent would be a complex and lengthy procedure. Yet, if this were not done, then those administering the drug of course would be potentially liable if later it could be proved that the patient had suffered because of the failure to fully explain the effects of the drug.
As most past research has been done with cannabis on healthy male volunteers not taking other prescribed drugs, adequate drug interactions will be needed before proposing to use cannabis on the ill. It is known that recent use of cannabis alters the effects of such drugs as the following:
- selective anti-depressants-tricyclics eg amitryptilene, although not enough data is available to date, what has been observed are only in small samples.
- benzodiazepines.....CNS depression and drowsiness can result according to dose. Although, diazepam may be used with care in carefully measured doses as a sedative on a patient with severe agitation due to THC abuse.
- Alcohol. As could be anticipated there is an additive CNS depression, tachycardia, motor performance, and negative effects on perception and cognition.
- Amphetamines and sympathomimetic amines. High doses of drugs, from this group used with THC, caused additive hypertension and tachycardia
- .Serotonin Reuptake Inhibitors. (fluoxetine) Adverse reporting showing severe mania and psychosis.
- Physostigmine. When used with smoked marijuana, psychomotor retardation and very severe depression, have been reported.
- Chlorpromazine. When marijuana is taken by schizophrenic patients taking Largactil an acute psychosis can occur.
- Opioids. Heart rate and cardiac output are increased. THC increases sedation and respiratory depression dependent on dose.
The use of the single synthetic cannabinoid, Marinol, has incurred the following associated warnings for elderly people. Drug abuse or dependence, risky occupations, cardiac disease, mental illness, and concurrent medications are possible difficulties. Pharmacokinetics and cardiovascular toxicity in the elderly is virtually unstudied.
The THC, in cannabis, increases the effects of sedatives and mitigates the effects of stimulants. Severe adverse side effects have been noted when used with barbiturates. Respiratory depression occurs when cannabis is used with alcohol or opioids. Research indicates that marijuana should not be used as an adjunct in anaesthesia.
Cannabis and the Sick; therapeutic Applications
Marijuana, THC and AIDS Wasting The known property of cannabis sativa in stimulating the appetite ("the munchies") has led to the concept that it might have an application in treating AIDS wasting. Anecdotal rep orts of smoking the crude drug have lead to this conclusion. If smoking cannabis was really effective in this manner, there might be a case for using the drug on those affected and risking the immunosupressant properties of cannabis on those whose immune systems which are already damaged. Mattes, Engleman et al., in a paper in 1994, found that 91% of cannabis smokers ate each time they used the drug. 85% thought that their food intake increased when they were under the influence of the drug while 60 % indicated that they would eat, even if they they were not hungry. Other controlled studies have indicated that a group of healthy patients and a group with cancer had their appetites stimulated by using THC15 This was not confirmed by a study by Chang, Shilling and others who studied cancer patients on high doses of methotrexate who were given THC.16 To date there is no acceptable data available for smoked marijuana, except anecdotal, relating to delta-9-THC.
The FDA has approved the cannabis derivative, dronabinol, to be used for Aids Wasting as distinct from smoking the crude drug.
However, three controlled studies17 of dronabinol to date are less than encouraging. These results have to be weighed against treating a sufferer with another agent that further suppresses the immune system, while at the same time increasing the risk of opportunistic infections and neoplasia. In the past, early death from AIDS was anticipated and therefore a possible carcinogenic risk was discounted. Now that the lives of the sufferers are being dramatically lengthened, it would be ironic, and of course tragic, if by making cannabis cigarettes available, the risk of lung cancer would be increased. ( see earlier) It is important to realise that benz(alpha)anthracene and benz(alpha)pyrine have now been identified as both carcinogenic. Meanwhile well-designed case-control studies should be undertaken to examine whether longtime use of cannabis is a risk of the development of lung cancer. What is accepted is that habitual use of marijuana may lead to the following effects on the lungs....... acute and chronic bronchitis; microscopic abnormalities in the bronchial passage cell-linings,pre-malignant increased accumulation of alveolar macrophages; reduction in the ability in these cells to kill microorganisms and tumour cells. It might be expected that AIDS patients or others being treated with chemotherapy who are being given marijuana might be more susceptible to the development of respiratory diseases.
A conclusive study18 in 1997, with Wright,D,Li,N.,Egorin,M.,Enama,M., Mayers,J., Galetto,G., and the DATRI004 and a Study Group of 17 others from 9 facilities examined the effects of the cannabis synthetic dronabinol and the progestin, megestrol, separately and in combination in the treatment of HIV Wasting Syndrome. In this multi centre randomized study the safety of megestrol and dronabinol were studied under an Investigational New Drug Application filed with the FDA, Division of Pilot Drugs. Four treatment arms were developed of the individual drugs in different doses and in combination. Clinical and laboratory evaluations were conducted; the Determination of Plasma Drug Concentrations; Pharmacokinetics Modelling; Statistical Methods evaluated and Results tabulated. They found that both agents were appetite stimulants but only megestrol was associated with significant weight gain as was borne out in two previous independent studies in 1994.
At this time,the treatment of glaucoma is long-term therapy and hence differs from the former condition in treatment modality. When cannabis is introduced this has to borne in mind over short-term therapy as the effects of long-term marijuana use as distinct from occasional use are now well documented. Long term marijuana smoking led to affects resembling emphysema because of the tars, carcinogens and other volatile chemicals present. Continuous use can lead to severe cognitive dysfunction. This assumes greater concern especially due to the age groups where glaucoma develops19 It has been estimated that to control glaucoma 24 hours a day it would be necessary to use between 2,200 and 3,600 cigarettes per year.
On the other hand, the evolvement of non-psychotopic products, such as HU21120 appears to be a major breakthrough in reducing intraocular pressure. This compound shows a lack of binding to the CB 1 receptor. As knowledge increases about this receptor even more analogues will be developed which can be used topically. Of course the topical use of any product has distinct advantages over any other route as low drug masses per delivery volume are possible. The local application of prostaglandin F2-alpha is a major advance in the treatment of glaucoma.
In this area of medicine the cannabinoids offer great hope since synthetic variants, which have no psychoactive properties can, and are, being developed. These compounds could be used con-currently with other available glaucoma treatments.
Other derivatives of Delta-9-THC and other cannabinoids, some of which succeeded in lowering IOL by the oral route have been tested. One of these, nabilone, was successful in treating intraocular pressure, and found to be superior to prochlorperazine in treating nausea as a result of chemotherapy but unwanted psychotropic effects occurred in 28% of patients21 . Clinical trials were discontinued for glaucoma when unfortunately, neurotoxicity in dogs was noted after two months of exposure. Another derivative of THC was known as BW146Y which was very successful but was found to cause orthostatic hypotension as well as psychotropic effects.
Another topical derivative of marijuana, canisol, has been introduced in Jamaica, and it is claimed to decrease aqueous humor formation by 55% in a quarter of an hour. This appears to be contradictory with other studies; possibly only a peer-reviewed panel with independent studies will resolve this situation.
It goes without saying that these analogues are superior in all ways over smoking the crude plant. It is unimaginable that the FDA or equivalent agencies elsewhere would ever approve of the use of non-standard plant material, over superior single drugs.22 Long-time distinguished ophthalomogical researcher, Dr. Keth Green, has authored many published papers since 1973 states that THC, let alone smoked marijuana, has been superseded by other products for the treatment of glaucoma. Even THC, in a light mineral oil base, proved to be not more effective than a placebo even though it would appear to have been effective in animal studies. It seems that THC is not effective when applied topically. It does not compare favourably with topical preparations of beta blockers and pilocarpine nitrate. Of course, none of these treatments offer a cure for glaucoma. The ultimate treatment may possibly come from understanding the cause of this dysfunction on a molecular level.
The major sources of products to give pain relief have been from plants, wintergreen, coca bush, opium poppies. Today, of course, none of these plant materials are used in their crude form. Yet there now is a proposal that plant material be allowed to be smoked as an analgesic. Anecdotal evidence indicates that it has an analgesic property. There seems to be not a deal of research in this area except that of Konig23 and others investigating pain effects on mice. Probably delta-9-THC act through the release of opioid peptides. However, nothing yet has been able to duplicate, or be superior to, the action of the centrally acting opioids. However, the non psychoactive synthetic derivative of delta-9-THC, (DMH-11C) offers possibilities as a non-inflammatory agent in arthritis control. Another derivative from the delta-9-THC molecule was developed in 1980 with far superior analgesic properties as having antiemitic properties, this was levonantradol . Research was done on this product between 1981 and 1985. 20 studies on human subjects were undertaken on its anti-emetic properties. These chemically designed molecules would seem to be the future way to proceed from the basic THC molecule to develop other cannabinoid analogues.
In an informal study of 60 patients at James Paget Hospital at Great Yarmouth, the synthetic cannabinoid, Nabilone was used in trials to study its analgesic effects on chronic pain associated with multiple sclerosis and osteoarthritis. In this study of 60 patients it was found that 30% reported a benefit while 25% reported significant side effects, 45% obtained no benefit. Clearly a more developed study could be of value. Although a classical double-blind, with placebo-contols would according to the researchers, prove to be difficult. They feel that various modes of delivery should be studied including, suppositories, rapid inhalers and slow-acting oral forms. Dependency remains a major concern. Significantly, those conducting the trial concluded that using marijuana was unnecessary, scientifically almost impossible to conduct and medically unacceptable.24
Nausea and Vomiting from Chemotherapy
Great progress has been made over the last 30 years in developing potent antiemetics in controlling chemotherapy induced emesis.25 In the 1970s there was near a 100% risk of being ill due directly as a result of the treatment. In the 1990s this figure had fallen to between 20-30% and in the case of treatment for lymphomas and breast cancer, this figure has fallen to only a 10% chance of vomiting with the best available regimes.26 (Dr.Gralla has been presenting published research papers on the subject for over 17 years).
Clinical trials are now being conducted with NK-1-receptor antagonists which initially are promising.
Combinations of corticosteroids with either metoclopramide or a serotinin-receptor antagonist are more effective than when either of these drugs are used alone.
Cannabinoids possess antiemetic properties but not as high as with other groups of drugs such as serotonin-receptor antagonists, corticosteroids and substituted benzamides. The side effects of the cannabinoids are higher than this group of compounds. The synthetic cannabinoids such as nabilone and levonantradol do not appear to have antiemetic properties superior to the cannabinoids. From what data exists there is no advantage of either inhaled or oral THC over this cannabinoid group.
Cannabis has been promoted as a treatment for the symptoms of spasticity, pain, bladder dysfunction, tremor and ataxia. Controlled clinical trials are lacking but some observations show that ataxia and tremor worsen with marijuana. Studies on the dysfunction of the baldder are inconclusive. Thorough double blind studies are needed before any deductions can be drawn from cannabis used to lessen MS symptoms. Research is needed to ascertain whether the new synthetic congeners of THC or other cannabinoids are useful.
No well controlled studies are available that show a reduction or increase in seizures. There has been little interest in this area since 1937 with the advent of phenytoin which was the forerunner of many effective drugs to treat grand and petit mal seizures.
Cannabis & the Brain
No discussion on cannabis anywhere is complete without looking at its neuropsychiatric properties. Indeed any thought of using the many different forms and strengths of the plant, cannabis sativa , for treatment must have at least a basic understanding of its psychiatric draw backs.
The most common effects of cannabis intoxication are anxiety and panic attacks. Other related conditions include, inability to drive a car competently. sense of loss of control, depersonalisation and restlessness. Hallucinations may occur and feelings of paranoia are quite common. Vomiting, diarrhoea and dizziness are sometimes present.
It is important to distinguish between post-drug impairment syndrome (PDIS) and the temporary brain dysfunction from using cannabis sativa. Given the unpredictability of the response by certain individuals, its effects and actual degree of impairment (as distinct from intoxication) are hard to define. Psychiatrists still argue over the classification of the condition closely implicated from the use of the drug. Be it a cannabis psychosis or schizophrenia or something else, the dispute continues. There is no dispute, however, that the mental stability of many users (not necessarily abusers) is linked to their use of marijuana. Maybe the developing science of PET scanning in combination with the study of the cannabis receptor and brain cell physiology and chemistry will eventually clarify the mode of action and just why some individuals are not as adversely affected as others. The higher the THC potency, the greater is the risk of adverse effects. There is concern that cannabis use leads progressively to distractibility and hence impairment in any situation where concentration and focused attention are essential. The question remains as to what extent are these changes reversible after cannabis use is discontinued?27
Mental Illness & Acute Toxic Psychosis
It is only of recent years that the adverse effects of cannabis have been observed in Western Culture. Such reports were formerly from India, the Middle East and Africa. However, chronic mental reactions have unfortunately become apparent in the West over the last 30 years. Yet in Egypt, in the 1950s, it was observed that impairment of the brain function by marijuana users lasted well after the period of acute intoxication.28 The term hashishats is used by some Egyptian psychiatrists to describe those affected by marijuana. "Hallucinations, paranoid delusions, and feelings of depersonalisation and derealisation are not uncommon and are seen in acute intoxicated states as well as acute or chronic psychoses."29
The following relate to some of the effects that may occur in some individuals resulting from their marijuana abuse. Paranoid reactions are common, but usually transitory. However, anxiety associated with this may, at times, deepen into a panic state. This is followed by acute episodes of delusions and hallucinations. These conditions may be triggered by marijuana. Ordinary thought processes become confused. Anxiety may reach panic proportions because the susceptible user feels that the drug induced state will never end. If the dose is large enough, hallucinations from a toxic psychosis condition may result. One source claims that THC of 6% strength can trigger hallucinations. Psychiatric emergencies, arising from smoking marijuana, are not a rare event in many hospitals. It is believed that cannabis use may trigger an underlying psychosis. Such episodes have occurred also in users who have not previously suffered from the disease who had been stabilised until using cannabis. Researcher observe that it can be an independent risk factor for the development of schizophrenia. In a paper presented at the Second Paris Conference on Cannabis and Cocaine in 1992, the psychiatrist and researcher, Dr. Juan Negrete, from McGill University Addictions Unit in Montreal, delivered a paper entitled the
Effects of Cannabis on Schizophrenia. In extracts from this paper, Negrete states...............
- "Cannabis use is associated with an increased risk of developing schizophrenia."
- "Data gathered through clinical and Epidemilogical studies consistently suggest the probability that cannabis could act as a trigger, prompting the overt expression of schizophrenia in individuals who suffer pathophysiological anomalies."
- It would appear that some individuals, by a genetic influence or other predispositions, are vulnerable to schizophrenia, but that another factor, a trigger, is needed to start the schizophrenic process. Such a trigger is marijuana.
Acute psychosis in heavy or susceptible users of marijuana may progress to a chronic psychosis resembling a schizophrenic reaction. Longitudinal research studies in Sweden involving over 50,000 subjects over 15 years have shown that for those who have used cannabis 50 times or more have a risk factor of schizophrenia much higher than the non users.30
The same researchers stated that:
"Among the causes of death a strong predominance was found for violent death, suicide or uncertain suicide being the single most important factor accounting for 34% of all deaths. The proportion of suicides increased sharply with the level of cannabis consumption."
Other researchers in Scandinavia state
"..information has appeared that indicates a connection between cannabis use and some of the more spectacular murder cases. In these cases the perpetrators were cannabis users. Use of cannabis may have a stronger association to violent crimes than what is presently acknowledged. One possible explanation of these violent and impulsive misdeeds could be the confusional states of cannabis psychosis giving rise to rapid fluctuations in mood, panic attacks and paranoid delusions. This seems to make the cannabis-related deaths different from deaths related to alcohol, amphetamine and heroin. Another difference, is the high incidence of suicides among cannabis users. Though occurring unexpectedly, these acts were in most instances preceeded by a history of mental depression and explicit suicidal intent."31
Research needs to be done in Australia concerning the relationship between crime and marijuana use. The plea of "diminished responsibility" associated with cannabis psychosis is commonly used in the legal system, when a senseless death has resulted.
"Suicide attempts among young drug users" was the title of an article published in the American Journal of Diseases of Children32 which showed that substance abuse was a significant risk factor in suicide attempts and fatal suicides during adolescence. A study released on schizophrenia and substance abuse released in 1990, concluded that 42% of schizophrenics had used cannabis at sometime in their lives.33 Various studies have consistently elicited a younger age of onset of schizophrenia in patients who are cannabis users when compared with those who are not.34
Dependence (Addiction) and Marijuana Use
Despite the protestations of some, there is no longer any debate35 about this property of cannabis. It was originally denied that it was a drug of dependence. Later it was recognised as being psychologically addicting, but now is recognised as being physically addicting also. There is now conclusive clinical and epidemilogical evidence that some marijuana users experience a problem in controlling their use as tolerance develops and dependence develops. It is estimated that at least 10% of users are addicted to the drug. Some users suffer a withdrawal syndrome when they abruptly cease using. It is recognised to be a larger problem than once believed and that heavy cannabis users experience problems controlling their use despite difficulties arising from their use of the drug.
Unless the research and the warnings are ignored, there is no doubt that cannabis plant material has no place in modern medical practice. However, some of the original chemicals present in the plant may be of benefit as chemistry can manipulate and modify the basic molecules in search of superior benefits with fewer side effects. The search for effective methods of treating the conditions before mentioned will of course proceed. Maybe the answers are contained in one or more of the 400 odd chemicals in the crude plant or its synthetic derivatives. Maybe the answers will be found elsewhere. Whatever the result, modern medicine and research will reveal improved treatments. If by the remotest chance cannabis leaf in cigarette form was allowed for certain types of medication, what should be measured then for a dose. Almost exclusively, in the past this has been the THC content. But in the 21st century if marijuana is sanctioned to be smoked medically, then the "safe" dose levels of cannabinol, CBD, CBN, CBG, cannabinochromene and the other remaining 56 cannabinoid should be known, otherwise the sanctioning of use of a product of unknown dosage and concentration of these chemicals will be granted opening the gates to potential future liabilities. This is further complicated by the sanctioning of a substance with damaging potential high levels of tar and other contaminates, such as salmonella and aspergillus. These bacteria and fungi could be eliminated by sterilisation of the cigarettes.36 However, this would not, of course, affect the higher levels of tar (compared to tobacco) contained in marijuana. The tar would remain unless a way could be found to eliminate it. Cannabis contains 400% more carbon particulates than tobacco. The carcinogens, benzopyrene, and the aromatic hydro carbons such as benzanthrecene are present in the plant in concentrations that are 50-80% higher than tobacco. As this is now known and accepted, any medical sanctioning of cannabis might open the door to any potential class actions against those implicated. At one time some members of the tobacco industry showed interest in marketing cannabis cigarettes in Australia but this has now been abandoned for obvious reasons of potential litigation as the "soft" image of the drug has proved to be a fiction. The pressure for deregulation comes from different sources. It originates from those who genuinely believe that deregulation of cannabis sativa, is inhibiting sound medical practice. It also comes from ailing long term smokers of it who also believe it will help them. Please do not discount or overlook the drug culture and their strident calls for controls to be lifted under the guise that it will help the sick. If this were so, I would support them all the way, but on the overwhelming evidence available, there is no way that I could do so, professionally or ethically. In the end, history will be the judge as to whether a progressive stance was adopted towards the development of newer and better treatments for the chronically ill and for those being treated with chemotherapy or whether we will be pressured into a regressive stance of deregulation of smoking a crude psychoactive plant under the guise of medicine.
Australian Pharmacists Against Drug Abuse
1 Drug Precipice 1998 University of NSW Press, Moffitt, Malouf, & Thompson
2 Developed in Vancouver it is sold as "BC Bud", double the strengths from Oregon and northern California and six times stronger than that developed in Mexico. The Australian Average is 5 to 6 %.
3 THC can precipitate Epiliptic fits while another cannabinoid, cannabidiol has anti epileptic properties.
4 A store selling marijuana paraphenelia and linked to the drug culture
5 Drug Precipice 1998 University of NSW Press, Moffitt, Malouf, & Thompson
6 ISBN 0 644 35085 7, published in 1994 Australian Government Publishing Service
7 Huestis M, Mithcell J, Cone E. 1995. Detection times of marijuana metabolites in urine by immunoassay & GC MS. J Anal Tocixol. 19.
Huestis M, Mithcell J, Cone E. 1996. Urinary excretion profiles of 11-nor-9 carboxy-delta9-tetrahydrocannabinol in humans after single smoked doses of marijuana. J Anal Tocixol. 20.
8 Marijuana Medical Handbook 1997, Quick American Archives. Oakland
9 Marihuana: the Forbidden Medicine, 1997 Yale University Press
10 Marijuana Myths, Marijuana Facts, 1997. Lindesmith Centre NY.
11 Drug Precipice
12 Connexions Aug 1997. Decades of Dope and Study raises more Questions. Didcott, Pet al. & Swift W.
13 Epidemilogical data suggests that HIV positive marijuana smokers progress to symptomatic AIDS more repidly than those who do not smoke marijuana. Epidemilogical reporting of frequency of marijuana use and incidence of physiopathological and infectious markers would be beneficial
14 National Institute of Drug Abuse Bethesda, MD, USA Warnings in public Health Documents 1995.
15 Regelson W, Butler J, et al. 1976 in Pharmacology of Marijuana (Braude and Szara) Raven Press
Sallan S & Cronin C et al. 1980 Antimetics in patients receiving chemotherapy for cancer: a randomised comparison of delta-9- tetrahydrocannabinol and prochlorperazine <N Eng J Med 30, 135-138
16 Chang A, Shilling D et al. delta-9-9tetrahydrocannabinol : A prospective randomised evaluation 1979.
17 Beal J and 8 others (1995) Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDs. J.Pain Symptom Management 10(2), 89-97
Beal J and 10 others (1997) Long Term Efficacy and safety of dronabindol for acquired immunodeficiency syndrome associated anorexia
Timpone J and 6 others and a study group (1997). The safety and the pharmacokinetics of single agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wast