Medicine not marijuana


A summary of recent scientific findings on the real and adverse impacts of marijuana.

For Further information please contact

Michael Robinson
Executive Director
Drug Free Australia
PO Box H135
Hurlstone Park NSW 2193
Phone 02 9591 8850
Email : infodrugfreeaustralia.org.au

The following summary is a collation of material from a wide source of medical reviews and scientific journals with emphasis on reputable scientific studies rather than editorial commentaries. The following has been collated into the following points for a concise guide

The over-riding principle on which to decide what is in the patient’s best interests must be medical science over rumour or anecdotal opinion.

OVERVIEW

While supporters of marijuana use put forward anecdotal stories and psuedo-science of rumours, myths and snake-oil hype,

… the seriously ill, trusting in the care of medical professionals demand the highest standards of medicine be adhered to, not diverted from.

… Medicine must be based on science.

… As a proposed medical substance, marijuana should be subject to the same level of scientific scrutiny as any other new medicine being suggested for use, when it is it fails the test.

In short, modern medicine is based on fact, not fiction!

15 Reasons to reject marijuana use for the seriously ill include

1) Unacceptable Side Effect Profile.

At the symptom level the toxicity of the oral formulation is almost prohibitive with most cannabis naive patients reporting unacceptable side effects including psychological dysphoria “bad trips.”

This study contains the very interesting observations as follows:

“Although there is an aura that marijuana is a “safe” drug, the untoward psychological (eg. panic, anxiety, depression, psychosis) and medical complications (eg. bronchitis, malignancies, sexual dysfunction) associated with its use are well documented.”

Source: Levin FR “Pharmacotherapy for Marijuana Dependence: A Double blind, placebo
controlled pilot study of divalproex sodium.” Am J Addiction 13: 21-23 (2004)

one journal addressed the clinical consequences of marijuana use. The introductory paper stated

… “that in addition to marijuana abuse/dependence, marijuana use is associated in some studies with impairment of cognitive function in the young and old, fetal and developmental consequences, cardiovascular effects…, respiratory/pulmonary complications… impaired immune function…and risk of developing head, neck, and/or lung cancer. ….” The summary stated further that “…research presented at this workshop suggests that marijuana use is not without health hazards and, within the limits of the available data, is associated with significant adverse consequences affecting almost every physiological system.”

Source: Journal of Clinical Pharmacology 2002;42:7S-10S

….a letter from NIDA’s Marijuana Research Center dated January of 2001 stated that

it had more than 15,000 research papers in its marijuana bibliography. However, it must be noted that because of the many negative consequences associated with marijuana smoking there is a reluctance to do clinical trials on humans. Further, because it remains an illicit drug there is also reticence to spend limited research dollars to determine the interaction of an illicit drug with prescription pharmaceuticals. Nevertheless, research on compounds found in marijuana is ongoing and has lead to the development of a number of prescription drugs with several others currently being accessed. However, smoking marijuana as a medicinal remedy is an unnecessary danger to patients …

Source: Reference: J Clin Pharmacol 2002;42:7S-10S, Khalsa et al
Risk of Heart Attacks increase 4 fold within 1 hour of smoking cannabis

Harvard School of Public Health and Boston’s Beth Israel Deaconess Medical Center that smoking “Marijuana Raises Heart Risks.” The study on which this was based was also published in July of 2001.

Source:Mittleman et al, Triggering Myocardial Infarction by Marijuana, Circulation, (103), 2001.

Now, a report in Forensic Science International, by researchers Bachs & Mørland, of the National Institute of Forensic Toxicology in Oslo, Norway, report on six cases of “cardiovascular death in young adults” …….., the authors reference several other cases of cardiovascular incidents related to cannabis use. The studies reported in this article indicate that using marijuana can increase the risk of stroke and bleeding in the brain, which can result in death.

Source: Thomas Geller, MD; Laura Loftis, MD; David S. Brink, MD; Pediatrics, March 2004
Link to Mental Illness including depression and psychotic episodes tripled by cannabis use

There are now more and more research studies that link mental illness to cannabis use. The following studies are all useful sources

Sources: American Journal of Psychiatry, March 2004
Van Us J, Dutch Study, American Journal of Epidemiology, 2002.
“Cannabis Abuse as a Risk Factor for Depressive Symptoms”
Am J. Psychiatry, 158:12, December 2001. Bovasso

Cancers, Lung Infections and Lung Damage.
“The constituents of cannabis and tobacco smoke include a similar range of pro-inflammatory and carcinogenic substances.”
“The way marijuana is inhaled as opposed to the way tobacco is inhaled means that smoking a ‘joint’ of cannabis results in exposure to significantly greater amounts of combusted material than with a tobacco cigarette.” Regarding the use of waterpipes (bongs) to ameliorate smoking hazards, the paper states: “There appears to be no significant reduction in risk with this modified inhalation technique. There is also a link between psychiatric illness and cannabis use, indicating that this particular subgroup may be at particular risk of respiratory disease with prolonged exposure to both tobacco and cannabis smoke.”

Reference: Internal Medicine Journal 2003;33:310-313, Taylor and Hall.

Smoking marijuana just once or twice a day for a number of years could lead to serious lung disease.

Source: Reported in Join Together March 2000 from Thorax, Journal of British Thoracic Society.
Smoking marijuana can cause cancer

“many people may think marijuana is harmless, but it is not”, Zhang said in a statement. “The carcinogens in marijuana are much stronger than those in tobacco. the big message here is the marijuana, like tobacco, can cause cancer.” Zhang studied 173 patients diagnosed with head and neck cancer, and compared them to 176 cancer free control patients. Those who said they habitually smoked marijuana were more likely to be in the group with head and neck cancers. And the more they smoked , the bigger the risk.

Source: Dr Zhag , Jonsson cancer center University of California,
Reported in journal of cancer Epidemiology Biomarker and prevention Dec 1999.

Researchers report in the July 2000 issue of the “Journal of Immunology” that tetrahydrocannabinol (THC), the major psychoactive component of marijuana, can promote tumor growth by impairing the body’s anti-tumor immunity system.
Source: Roun et al. Biological Psychology Laboratory at Maclean Hospital Limited in haemorrhage Notes Vol. 15, No. 1

Aggravation of pain and muscle spasticity (the opposite of treatment for those suffering AIDS, M.S., Asthma)

Marijuana will not stop Multiple Sclerosis Pain

In findings that contradict earlier research, a team of scientists reports that marijuana does not improve the often painful symptoms of multiple sclerosis (MS). .A previous study in mice indicated that marijuana might help to relieve these painful spasms. However, the amount of the drug used in mice would not be tolerated in humans, the researchers explain. While their study included just 16 patients, it is the largest randomized, controlled clinical trial to investigate the use of marijuana to treat MS.

“Compared to placebo, neither THC nor plant-extract treatment reduced spasticity,” Dr. Joep Killestein from the VU Medical Center in Amsterdam, the Netherlands, told Reuters Health.

Source: Neurology 2002;58:1404-1407.

Smoking can double risk of MS

Smokers are 181 times more likely to develop multiple sclerosis than non smokers according to Dr Trond Riise.

Professor Riise said: “This is the first time that smoking has been established as a risk factor.., hopefully these results will help us learn more about what causes Ms by looking at how smoking affects the onset of the disease.

Source: Dr Trond Riise,University of Bergen Norway reported by ASH Oct 2003

“… since anandamide acts on nerves in the trachea and lungs and is quickly eliminated from the body, an inhaler could potentially control the cough without any side effects. Piomelli says don’t smoke marijuana for asthma, because it could trigger lung constriction and make the problem worse.
Source: Piomelli et al. University of California. Published in Nature . Nov 2000.
2) Inadequate Empirical Evidence

The level of the evidence for its use for the various indications seems to be based at best on preliminary or pilot data. All too often support for marijuana is on anecdotal comment and not scientifically valid data but commonly little more than opinion or anecdotal material.

3) Lack of Comparative Data

This is particularly obvious in the case of the indication for vomiting where there are no comparative trials with the standard serotonin-3 antagonists such as drugs of the ondansetron family. In the case of pain relief, the effects of cannabis appear to be about the same as a moderate dose of codeine, with the notable addition of generally unacceptable side effects.

4) Complexity of the Endocannabinoid System

There are at least two major cannabis receptors and probably three. Their pharmacology is not completely worked out. It is well known that a high concentration of receptors exists on both neurones in the hypothalamus and all of the immune cells of the body. One of the key target groups for whom “medical marijuana” is frequently recommended is AIDS patients. Hence the generally immunosuppressive effects of the cannabinoids should be of major concern in such patients whose immunocompromise is known to be finally lethal.

A third element of this system if the enteric nervous system, which has as many neurones as the brain and spinal cord namely 100 million. Cannabis receptors have been defined in this nervous system, and disorders of bowel function are well known in cannabis addicted patients. This should also worry us – that there is another 100 million neurones whose cannabinoid sensitivies and pharmacology is largely unexplored.

It is also of interest that one of the family of several endocannabinoid molecules 2-acylglycerol, has been noted to change cellular specificity and apparent phenotype of cultured cells from adipocyte to fibroblast. Such radical changes of cellular phenotype imply that usual safety studies will be difficult to guarantee if cellular perturbations of such major degree are involved.

5) Immunosuppression

This immunosuppression is a huge issue in its own right. It is matter of enormous clinical and theoretical interest and implications, and has begun to be explored in great detail in the laboratories of north America. Indeed a senior professional organization has now been formed in the USA to examine this in its own right as it relates to both cannabis and other illicit agents. It is called the Society for Neuroimmune Pharmacology. The effects of this are in fact counter productive indicating that the whole plant marijuana product should never be administered to anyone, let alone someone who is already sick or immune compromised.

Study Finds Marijuana Ingredient Promotes Tumour Growth, Impairs Anti-Tumour Defences

Researchers report in the July 2000 issue of the “Journal of Immunology” that tetrahydrocannabinol (THC), the major psychoactive component of marijuana, can promote tumour growth by impairing the body’s anti-tumour immunity system. While previous research has shown that THC can lower resistance to both bacterial and viral infections, this is the first time that its possible tumour-promoting activity has been reported.

The authors also suggest that smoking marijuana may be more of a cancer risk than smoking tobacco. The tar portion of marijuana smoke, compared to that of tobacco, contains higher concentrations of carcinogenic hydrocarbons, including benzapyrene, a key factor in promoting human lung cancer. And marijuana smoke deposits four times as much tar in the respiratory tract as does a comparable amount of tobacco, thus increasing exposure to carcinogens.

Source: Roun et al. Biological Psychology Laboratory at Maclean Hospital Limited in haemorrhage Notes Vol. 15, No. 1

Cannabis increases tumour growth via several mechanisms including:

1) tars contain many chemicals which are directly tumour stimulating (anthracene’s, nitrosamines, hydrocarbon: higher tar content than
cigarettes);

2) immunosuppressive, reduces immune surveillance and anti-tumour activities of lymphocytes and natural killer cells;

3) altered cytokine production such that permissive cytokines are produced rather than immunostimulatory ones;

4) altered prostaglandin production.

Furthermore these effects occur both by receptor (CB1 and CB2) mediated and receptor independent mechanisms.

All of which means that you CANNOT in good conscience give THC to either AIDS patients or cancer patients, or recommend cannabis for human use.

Source:The PubMed studies

6)
Availability of non-psychoactive congeners

(i.e. there are currently better alternatives and scientific research continues to develop better medicines)

Both cannabidiol and dexanabinol (HU-210) share many of the supposedly beneficial effects of THC but are not psychoactive. As this area is better studied it is likely that many such agents are likely to be made available. With the unacceptably high level of side effects noted in these patients, it would appear to be thoroughly premature to precipitately launch into the making of THC available at this time. A multitude of studies have demonstrated currently available medicines are superior to cannabis.

Source:NeuroReport, Vol. 13, No. 5, 16 April 2002.
Source: Eija Kalso, Associate professor. Pain Clinic, Helsinki University Hospital, Finland BMJ.3212-3.. July 7th 2001

7) Unacceptability of the smoked form of delivery

The toxicity of the smoked form to the aerodigestive tracts, including its association with chronic bronchitis and emphysema and asthma has been agreed upon by major colleges of thoracic medicine worldwide including the Australian and New Zealand Thoracic Society and the British Lung Foundation. Cancer of the mouth, throat, tongue, larynx pharynx have also been noted. Interestingly a high rate of bladder cancer has been noted in some series as cannabinoids are excreted by the urinary route.

Smoking can double risk of MS

Smokers are 181 times more likely to develop multiple sclerosis than non smokers according to Dr Trond Riise.

Source:Dr Trond Riise,University of Bergen Norway reported by ASH Oct 2003
Passive inhalation of cannabis smoke
The blood samples from the passive subjects taken up to 3 hrs. after the start of exposure to cannabis smoke showed a complete absence of cannabinoids. In contrast, their urine samples taken from passive sample up to 6 hrs. after exposure showed significant concentrations of cannabinoid metabolites (less than or equal to 6.8 ng ml-1). These data, taken with the results of other workers, show passive inhalation of cannabis smoke to be possible.

Souce:Law B, Mason PA, Moffat AC, King LJ, Marks V. PMID: 6149279 [PubMed – indexed for MEDLINE]
Cannabis Poisoning
A paediatrician Dr John Goldsmith has come out publicly with a survey he has done in North Island Hospital in NZ. emergency units where babies under the age of 2.5 years are admitted for cannabis poisoning .

Source: Dr John Goldsmith North Island Hospital ,New Zealand, 2002

8) Unacceptability of the oral form of Delivery
As it is not easily possible to titrate the oral dose exactly a very high rate of unpleasant and dysphoric side effects has been noted. This would appear also to be a sub-optimal route of delivery.

9) The Complexity of bringing drugs to market

The complexity and cost of bringing drugs to market has been noted many times, and is said to cost up to the billions of dollars. Furthermore this is understood never to have been done in Australia. Hence it is only prudent for Australian regulatory authorities including Governments to await formal pharmaceutical trials in nations and entities which have recognized pharmaceutical industries such as Europe and North America. It is prudent not to attempt to bypass this process for litigant as well as compassionate reasons. To inflict upon sick people, the adverse effects of marijuana could be interpreted by the public and the courts as a negligent act of the government who have an over riding responsibility to protect the public from claims that cannot and have not been sustained in evidence.

10) Aging and Stem Cells

With all the recent debate in relation to embryonic stem cells, the central, pivotal and essential role of stem cells which occur in the adult organism appears to have been radically overlooked. Obviously patients addicted to many drugs look prematurely and severely aged. Experimental studies have established for many years that all the illicit drugs of abuse cause single cell programmed death. This appears to occur in an additive and indeed multiplicative manner. One of the worst offenders is THC. It is also established that all the illicit drugs cause an inhibition of stem cell growth. This is well described in the brain and hypothalamus, but also affects other tissues. The combined effects of increased rate of cell death, and reduced rate of cell renewal may potentially be very serious and urgently require further study. This should concern many Governments given the increasing burden of aging on health budgets in many nations. The very real prospect of accelerated aging – especially of vulnerable patients such as those suffering from AIDS should precipitate a major community outcry against all but the most scrupulous clinical use of the appropriately researched cannabinoids.

11) Basic Neuropharmacophysiology

THC actually acts to inhibit synaptic transmission. Receptors exist on the PRE-synaptic side of the synapse and appear to act to turn off neurotransmission. This is known to scientists as “retrograde neurotransmission.” This is of course entirely consistent with the clinical syndrome we see of so-called “dope-heads.” This of course is the major reason it is used – the “downer” or sedative effect.

But the basis of its neuropharmacology should give us great pause indeed, for we appear to be shutting down the brain functions. It should also be added that there is a very close relationship between the opiate and cannabinoid receptor at the molecular level on the cell membrane. Both are 7-transmembrane loop-helix-loop GTP coupled plasma membrane receptors, coupled to inhibitory effects on adenyl cyclase and DNA transcription in the cell nucleus via similar intracellular transduction cascades.

Both are associated with immunosuppression, programmed cell death, and stem cell inhibition. Both occur in similar parts of the brain particularly in the hypothalamus and limbic circuits; both appear to share significant cross-talk at the plasma membrane level. In other words the so-called “gateway hypothesis” which was demonstrated and proven in the Christchurch New Zealand cohort, and was thought to be based on social and values based activities, almost certainly extends also to the molecular and cell membrane level.

12) Sundry Toxicities

Toxic effects on the following systems are accepted even by major cannabis advocates such as Wayne Hall.:

‘In fact the serious adverse effects of Cannabis have been known for some time now. Including adolescent developmental problems, permanent cognitive impairment as well as involvement in and the development of psychosis’.

Source:Hall W, Solowij N, “Long-term Cannabis use and Mental Health” 1997 British Journal of Psychiatry, August,1997 171:107-8

‘Caused disturbance to neural connectivity. However, it seems Cannabis can precipitate or exacerbate a schizophrenic tendency in a characteristic manner’.
Source:Hall W, Solowij N, “Long-term Cannabis use and Mental Health” 1997 British Journal of Psychiatry, August, 171:107-8
Hall A, Degenhardt, “Cannabis and Psychosis” Australian National Drug and Alcohol Research Centre, Presented
at The Inaugural International Cannabis and Psychosis Conf. 1999, Melbourne 16-17 February 1999

Chronic Symptoms of Cannabis Psychosis
‘Patients are left with the well-recognised and permanent symptoms of memory loss, apathy, loss of motivation and, paranoid ideation. ….. there is accumulating evidence of the psychological consequences of using Cannabis’.

Source: Hall W, Solowji N, Lemon J, The health and psychological consequences Monograph Series no 25.
Canberra:Australia Government Publishing Service, 1994 of Cannabis use. Nat. Drug Strategy
a) Driving

More than one in five drivers who died on NZ roads 1995-1997 had been smoking cannabis in the-hours before they crashed. The study found 82 of a sample of 386 drivers had cannabis in their bloodstreams and 54 per cent of the cannabis smokers were over the legal alcohol limit.

Source: Institute of Environmental Science and Research (ESR) in New Zealand. Jan 2000.

Marijuana use can render the user unfit to drive for more than 24 hours and adversely affect cognitive impairment for up to 28 days
Source: Bolla, K.I., et al. Dose-related neurocognitive effects of marijuana use. Neurology 59(9):1337-1343, 2002.

b) Gene toxicity
Genetic anomalies tied with marijuana—activated brain chemicals appear linked to schizophrenia, Japanese researchers report.
This result provides genetic evidence that marijuana use can result in schizophrenia or a significantly increased risk of schizophrenia.
The researchers described their findings in the scientific journal Molecular Psychiatry.

Source:Hiroshi Ujike,Okayama university Japan- Reported in UPI Science News, New York 2002

c) Hormonal and reproductive toxicities
d) Likely effect on cancer

e) Amotivational syndrome

f) Depression

Frequent Marijuana Use Associated With Depression and Anxiety in Teen Girls

Teens, especially girls, who use marijuana frequently are more likely to suffer from depression and anxiety, say Australian researchers.
Teens who used marijuana weekly or more often had twice the risk of experiencing depression and anxiety. The risk of depression and anxiety was greatest among females who used marijuana daily – they had five times the risk of being depressed or anxious than their non-using peers.

Source: George C. Patton; Carolyn Coffey; John B. Carlin; Louisa Degenhardt; Michael Lynskey; Wayne Hall;
British Medical Journal, November 23, 2002
g) Psychosis
its effect to exacerbate supposedly underlying tendencies is agreed upon: several recent papers, including some from Netherlands, also document the occurrence of this severe disorder in patients without pre-existing personal or family history. In this connection it is worth noting that in the laboratory psychosis can be predictably produced in 100% of animals by the combined use of amphetamines and cannabis.

Marijuana and Schizophrenia

In one of the earliest studies that associates marijuana use with schizophrenia, 45,570 Swedish conscripts were asked to report their frequency of cannabis use. Over the 15 year follow up period, conscripts who had used cannabis more than 50 times before conscription had a six times higher risk for development of schizophrenia than non-users. Those who used cannabis 11 to 50 times had a three-fold increase in risk.

Source: Quoted in Taylor H: Analysis of the Medical Use of Marijuana and its Societal Implications.
Journal of the American Pharmaceutical Association 1998; 38: 220-7
h) Cardiovascular

Vasoconstriction occurs in many tissue beds, along with a faster heart rate. This has been associated with heart attack in some recent series, and organ infarction. It is of particular concern in the long term to think that such changes are likely occurring in the brain, along with accelerated cell death. The studies reported in this article indicate that using marijuana can increase the risk of stroke and bleeding in the brain, which can result in death.

Source: Thomas Geller, MD; Laura Loftis, MD; David S. Brink, MD; Pediatrics, March 2004
13) Comments on specific indications:

a) Where it is recommended to be used with prochlorperazine for vomiting. It is likely inferior to ondansetron etc. Side effect profile unacceptable. Seldom used clinically even where it is available to be prescribed.

b) Pain relief. Equal to codeine, plus the nasty side effects. codeine and other alternatives preferred.

c) Appetite stimulation. Minimal effect in published studies. However may be associated with other functions later on. Seems to be associated with morbid obesity developing in a number of heavy users in later decades. (This would appear to include several well-known cannabis advocates). Given that we known that obesity itself is a terrible health disadvantage, this alone should give us great cause. Overweight is also associated with at least 12 cancers, and according to a New England Med J article in 2003, the overall elevated cancer risk in the overweight is 156% of normal, with up to 450% for some tumours such as liver.

The authors reported that “participants reported ‘negative’ subjective effects… [irritable, miserable, bad drug effects, negative mood states] during days after smoking marijuana, but not after oral THC.” They noted that previous studies had found that both dronabinol and smoked marijuana increased “total daily calorie intake and produced abstinence symptoms upon discontinuation of their use.” [NOTE: caloric intake does not remedy wasting syndrome]
The doses of dronabinol and smoked marijuana used in the study were based on the researchers’ previous studies in which they found 20 mg of dronabinol had similar effects to marijuana cigarettes with a potency of 3.1% THC.

In conclusion, the authors note “This finding may have important clinical implications because it suggests that oral delta-9 THC is as effective as smoked marijuana…”

d) M.S. Likely to be acting as an immunosuppressant which should worry us enormously especially in AIDS patients.

e) Epilepsy. Some studies demonstrate also pro-epileptic effects. However there are lots of anticonvulsant drugs on the market currently which have a lesser side effect profile than THC.

f) Glaucoma. It is said that the intra-ocular pressure is lowered after systemic administration only at doses which depress the heart action. Very good drugs already exist for this disorder. A topically applied eye drop may have a role. Whether THC or one of the non-psychoactive cannabinoids would be most suitable remains to be determined.

Reference: Hart et al, Psychopharmacology (2002) 164:407-415

MARIJUANA SMOKING VS. CANNABINOIDS FOR GLAUCOMA THERAPY: A REVIEW

Abstract

This review encompasses the clinical effects, including toxicological data, of marijuana and many constituent compounds on the eye and the remainder of the body.

A perspective is given on the use of marijuana and the cannabinoids in the treatment of glaucoma. The conclusion is reached that although it is undisputed that smoking of marijuana plant material causes an intraocular pressure fall in 60 to 65% of users, continued use at a rate needed to control glaucomatous intraocular pressure leads to substantial systemic pathological changes. Development of drugs based upon the cannabinoid molecule or its agonists, for use as topical or oral antiglaucoma medications, seems to be worthy of further pursuit. Among the latter chemicals are some that have no known adverse psychoactive side effects.

Source: Keith Green, Ph.D., D.Sc., Department of Ophthalmology, Department of Physiology & Endocrinology,
Medical College of Georgia, Augusta, Georgia
14) Addictive and Habit Forming Potential
The addictive capacity of cannabis is now accepted and has been established in the scientific literature at least since the publication of the DSM IV of the American Psychiatric Association in 1994; and has been verified many times in papers since that time. The fact that this is now accepted throws into question its clinical use, for the drug itself is associated with uncontrolled use. Combined with its gateway action in terms of introducing the user to other drugs, this should be a point of major concern for all regulatory authorities, simply because addiction implies that it is not able to be regulated in the normal manner of other therapeutic agents.

15) The T.G.A.

If marijuana is in fact effective, economical and ultimately appropriately suitable to be prescribed to patients then it should pass the demands of Australia’s medical regulatory bodies …. including The Therapeutic Administration. Botanical or crude plant marijuana has not.

Refer to Cannabis with care? Booklet for further details on this concern as well as others

Copies available from Drug Free Australia. PO Box H135 Hurlstone Park NSW 2193
Or email infodrugfreeaustralia.org.au

Here is just one of the many examples of Australian and International professional bodies who oppose marijuana use.

AMERICAN ACADEMY PEDIATRICS STATEMENT

American Academy of Pediatrics Vol. 113 No. 6 June 2004 p.1825 – 1826

Recommendations

1. The American Academy of Pediatrics opposes the legalization of marijuana.

2. The American Academy of Pediatrics supports rigorous scientific research regarding the use of cannabanoids for the relief of symptoms not currently ameliorated by existing legal drug formulations.

CONCLUSION.

In short true compassion for our ill patients necessitates and indeed morally obliges appropriate and disciplined medical care for them.

The normal physiological action of cannabinoids in terms of the inhibition of brain function by retrograde neurotransmission is of major concern to all those concerned with preserving and promoting the neurological and normal brain function of adolescents and young adults, and thus maximizing the neurological potential and intellectual property of the on-coming generation.

If cannabinoids are shown to have a place in evidence based medical therapeutics in the future then, given the well established high side effect profile of these agents, and their horrific long term cumulative toxicities, it is appropriate that patients only be exposed after careful and replicated disciplined and independently controlled clinical trials with appropriate dose forms, or appropriate agents, most likely not THC itself.

It is also appropriate that comparative studies with established and accepted safe agents also be performed.

Issues of genotoxicity, weight gain, immunosuppression, impaired concentration while driving, gateway action at both the molecular and social level, premature aging including suppression of stem cell activity and renewal, and depression of brain function and neurogenesis and psychological toxicity appear to be particularly germane and of very real clinical concern, and the subject of on-going research at this time.

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