15 year old girl in BC has MM card for Epilepsy

Click here to go to You Tube to watch this video about 15 year old in BC with MM card for epilepsy

we need to make our children's medicine not illegal. write to Stephen Harper, you MP, and DON'T Vote Conservative next time!

Ottawa's monopoly on pot over

SOURCE: Toronto Sun

Ottawa's monopoly on pot over

Court dismisses federal appeal

Last Updated: 28th October 2008, 3:59am


A court decision that effectively loosens Ottawa’s tight grip on access to medical marijuana has been upheld by the Federal Court of Appeal.



Alison Myrden, who eats, drinks, and smokes 50 grams a day of medical pot, couldn't be happier that the federal government's marijuana monopoly has gone up in smoke.

Myrden, 44, was one of several medicinal marijuana users who yesterday watched as appeal court judges dismissed Ottawa's bid to keep the medical pot supply chain limited to one grower per smoker.

The controversial Health Canada one-grower-per-patient regulation was struck down in January by federal court Justice Barry Strayer, who ruled the restriction was unconstitutional.

Yesterday, federal lawyers Sean Gaudet and James Goreham mounted the government's appeal of Strayer's ruling. Because Strayer's ruling was under appeal, the Health Canada regulation was still in effect until yesterday's decision.

Gaudet and Goreham argued the one-to-one policy was required to ensure against the pot from licensed growers straying illicitly into the open market.

However, the three judges, John Maxwell Evans, Karen Sharlow, and C. Michael Ryers, didn't buy it. They dismissed the appeal after the lunch break, reducing the scheduled one-day hearing to a half-day.

And while the tight-lipped government lawyers -- who declined to comment -- started packing up, the pro-medicinal marijuana advocates cheered and congratulated lawyers Alan Young and Ron Marzel, who were representing 30 patients seeking the right to buy pot from a Smiths Falls grower called Carasel Harvest Supply Corp.

Yesterday's ruling means that licensed medical pot smokers are no longer restricted to getting their weed from a grower who only provides bud to them.

"We all want the same thing ultimately and that's our freedom. That's what it boils down to, the freedom to be able to do what we want without government intervention," Myrden said.

It also means that the much-maligned green grown in Manitoba by a federally contracted grower is no longer the only supplier who can provide weed to more than one person.

Myrden adamantly refuses to smoke the government-issue weed grown in Flin Flon by Prairie Plant Systems.

"I've tried it, it's garbage," said Myrden, a former corrections officer who smokes to combat symptoms of chronic progressive multiple scleroris. "It's absolutely disgusting, it's sticks and seeds and stems, I can't believe they'd make us smoke that as medicine."

Myrden, who also suffers from a rare facial condition she says causes "violent pains," has a government licence to grow her own. She consumes 50 grams a day by eating it, drinking it in tea, and smoking 30 joints.

Outside court yesterday, Young called on Health Canada to adopt more open-minded policies surrounding medicinal marijuana.

"It's time for Health Canada to recognize that medical marijuana is an established part of the regimen of a lot of patients," Young said. "Instead of thwarting patient needs, they should be accommodating patient needs. Hopefully this case will be a signal to them. Quite frankly, they've lost almost every round (in court)."

ADD and marijuana treatment testimonial

SOURCE:http://forum.grasscity.com/recreational-marijuana-use/211163-marijuana-adhd.html


Marijuana and ADHD
I know, it's LONG. If you don't feel like reading it, that's cool. But if you've ever had a problem with ADD or ADHD then this could help you out a lot. PM me or reply to my thread if you have any questions.

Throughout my early school years I knew I was intelligent. I had straight A's up until high school (yeah, not that hard..but w/e). In high school, I lost all drive to do well in school. My disorder finally reared it's ugly head when I was actually required to do my homework at home, weird concept I know. When I got home, I couldn't do it. Too many distractions, not enough motivation, so I gave up.

I would still do well on tests; I could sit in a classroom without taking notes and absorb enough information to ace it. I never really asked myself why I continuously only did enough to slide by. I ended up with a 3.4 GPA even after never doing my homework. The biggest sign that told me something was wrong was the ACT. I scored a 33 on the ACT the second time I took it (first without a calculator, meh.). At that point, I could go to any school I wanted. But I still had to wonder, why didn't I give high school my best? Why couldn't I have just done my homework and got a 4.0. I could have been valedictorian.

So here I am at college. A shitty state university. I procrastinated so much on my college apps that this was the only school I could apply for. I got in easily. I had NO distractions here but my computer first semester (I'm a computer nerd, it's required :P), yet I still didn't do my homework. I was continuously skipping class because I can now and couldn't in high school when I wanted to every day. My grades were suffering, first semester I received a 2.5 gpa. Something had to be done. I thought about getting my adderall prescription filled again, but then I came across an article about cannabis and its uses to remedy ADHD. I was immediately intrigued. I sought out help from some hallmates who were more experienced with the herb .

Something that I found enjoyable during first semester was smoking with my hallmates. After a month of thinking they were just drug addicts, I found myself talking to them more and more and realizing that these guys were actually more intelligent than my current friends who were all self-proclaimed intellectuals. They got me high for my first time ever (it was a bong, by the way ), and since then, I've been smoking marijuana almost every day. At first, I binged. I smoked a lot of pot, way more than needed to get high at my tolerance. I loved the feeling it gave me. I could deal with social situations that were worsened by my ADHD in a much better manner. I could focus better, I was less impulsive, and frustration seemed to just slip away. Things were looking bright...

Until I realized what I was doing. I was continuously smoking throughout the day and basically was high all the time. I realized that people around me were getting the idea that I was this huge stoner. I'd always be stoned and smell like a hint of the herb so people immediately judged me and put me in the "pothead" category. This disgusted me. Just because I smoked, people automatically slotted me as someone who just smokes pot all day and does nothing else. What bothered me most is that people didn't believe that I was intelligent. I was out of it most of the time, so people figured I was a stupid stoner kid. Stereotypes with marijuana are so wrong, but so prevalent within society.

I also found that the reason I was smoking in the first place had been lost. I was smoking to relieve my ADHD. It worked, but I smoked too much. I was blasted all the time so it actually had the reverse effect. I was just as inattentive, obnoxious, and impulsive as I was before smoking. I had a big wakeup call when my hallmates confronted me about these issues. Something had to be changed, and I knew what it was.

I've reduced my cannabis consumption down to around 3 times per day on weekdays. Sure, on weekends I'll get blasted every once in a while, but for the most part I smoke much less marijuana than I did before. I found that consumption of cannabis via eating it gave much better results with regards to curing ADHD symptoms. The longer lasting "buzz" I guess you could call it is something that helps me through my school day. I am more attentive, less impulsive, and generally more mellow after eating cannabis rather than smoking it. Smaller amounts, too, showed promise that this could be the answer to all of my problems.

So, I began a routine that I still continue today, and it's done so well to cure my symptoms. In the morning, I eat a piece of toast with cannabis peanut butter. This is excellent for focus and to slow my mind down enough to think throughout the day. I eat a cannabis cookie after dinner. This gives me the ability to focus enough to do my homework throughout the evening. At night, I usually smoke a one hitter or use my vaporizer. This clears my mind enough so that I can lay down and actually fall asleep within 15 minutes, rather than lying in bed for an hour while my mind races about. Really, it reminds me of adderall, without the addictive properties and without the withdrawal if you don't feel like taking it anymore.

So, I would consider the treatment of my ADHD with marijuana to be rather successful. I am attending class daily without any problems. I am able to do my homework and study each night without being distracted. Aside from school, it also helps me in social situations that are made worse by my ADHD. My friends notice that I am no longer as obnoxious or impulsive anymore, and I'm a much more bearable friend. I am very happy with the results, and I suppose the next step is to make this magical herb legal!
__________________
Stay fly.

Marijuana replaces Ritalin in treatment for ADD/ADHD

Marijuana replaces Ritalin in treatment for ADD/ADHD - Video

So it would appear the die is cast and that cannabis is set to be reclassified to a class B drug, bringing with it more arrests, more prison sentences, and more expense.

In the meantime, Dutch Police in Amsterdam are complaining about their rights to use cannabis when off-duty and as if that wasn't enough to prove the futility of trying to outlaw a substance which is a long way safer than either alcohol or tobacco, we now have a consultant pediatrician from the US, claiming marijuana (or cannabis) can be used ON CHILDREN, in the treatment of ADD or ADHD? So who's telling us lies?
Dr Claudia Jenson, who is a consultant pediatrician from USC, has come up with a novel way of treating ADD/ADHD, WITHOUT any of the unwanted side effects which can result from using popularly prescribed medicines.
Attention deficit Disorder, or attention deficit hyperactivity disorder (ADD/ADHD) is a biological, brain based condition that is characterized by poor attention and distractibility and/or hyperactive and impulsive behaviors. It is one of the most common mental disorders that develop in children. Symptoms can continue into adolescence and adulthood. Image
If left untreated, ADHD can lead to poor school/work performance, poor social relationships and a general feeling of low self esteem.

The normal course of treatment for a child diagnosed with ADD/ADHD, is a course of methylphenidate, better known as Ritalin.

Methylphenidate (MPH) is a prescription stimulant commonly used to treat Attention-deficit hyperactivity disorder, or ADHD. It is also one of the primary drugs used to treat the daytime drowsiness symptoms of narcolepsy and chronic fatigue syndrome. The drug is seeing early use to treat cancer-related fatigue.

As always there is a flip-side to these prescription drugs, and in the case of Ritalin, substance abusers have found various ways to ingest the drug recreationally, which gives an effect similar to cocaine or amphetamine so the use of ritalin is to be closely monitored.

For the child diagnosed with ADD/ADHD, the side effects of using Ritalin, are many, including psychosis (abnormal thinking or hallucinations), difficulty sleeping, stomach aches, diarrhea, headaches, lack of hunger (leading to weight loss) and dry mouth. In some cases, the use of Ritalin has led to death.

If Ritalin or its side effects, are causing your children problems, ask your doctor about using marijuana as an alternative.

watch this corresponding video

three of the four national parties have spoken out in favour of decriminalizing the recreational drug.

Federal election could be going to pot
By DAVE MABELL
Sep 5, 2008, 04:22

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Legalizing the use of marijuana will be an election issue if proponents across Canada listen to Neil Magnuson.
In Lethbridge as part of the “2008 Freedom Tour” on Thursday, the long-time activist said three of the four national parties have spoken out in favour of decriminalizing the recreational drug.
For the Green Party, he said, it’s one of the key issues.
“If Elizabeth May is allowed to take part in the debate, she’ll talk about it.”
May, the party’s leader, is battling the reigning Conservatives’ efforts to keep her out of the televised debates. Magnuson, in Alberta as part of the movement’s annual trek to the House of Commons in Ottawa, said he’ll be urging legalization advocates to take full part in the upcoming election.
Pro-pot websites, Facebook and other vehicles will be used to urge advocates to speak up during the campaign and then vote for candidates who support their cause.
Many Liberal and New Democratic Party candidates are also expected to back legalization, he pointed out, though it may not be a platform plank as it is for the nation’s Greens. Not many Conservatives are in favour, he conceded.
“They’re in the pockets of the United States,” a nation where marijuana use is heavily proscribed.
But in Canada today, Magnuson said most adults see the prohibition on marijuana as no more effective as the nation’s generations-ago ban on alcohol.
“I think people across Canada are fairly aware of this issue,” he said. “But they feel helpless about changing the law,” especially when a Tory government is promoting longer jail terms for people caught selling pot.
“Very few Canadians think we should use criminal law against it.”
By refusing to regulate and tax the product — just as provinces do with alcohol — he said the federal government is putting that revenue in the hands of organized crime, just as in Al Capone’s era. So criminal gangs recruit young people to sell their product and run the risk of arrest.
“For youth who are living in poverty, they can’t resist the lure of easy money.”
Magnuson said a Canadian Senate report pegged the costs of policing, prosecuting and jailing those young people at $1 billion or more every year. Because marijuana is so widely grown and used, he added, about 1.5 million Canadians have a drug-related conviction on their court record.
A 25-year activist in metro Vancouver, Magnuson said experience there refutes opponents’ suggestions that using pot becomes a “gateway” to using dangerous “hard drugs.” What researchers there have found, he said, is marijuana’s role in helping addicts quit those narcotics and get on with their lives.
SOURCE: Lethbridge Herald.com

Parents are using marijuana for ODD, OCD, Autism, ADHD and Tourettes and Bi-polar in their kids.

For the Sake of the Children

The Message of Medical Cannabis

Jay R. Cavanaugh, Ph.D.
September 2002

There is a belief system in the United States nurtured by decades of simplistic thinking that says to everyone we must ban cannabis for the sake of the children. Recently, speaking of the DEA raid on the Santa Cruz, California Wo/Men’s Alliance for Medical Marijuana, DEA agent Richard Meyers stated, "what type of message are we sending to our children"? The Alliance, more commonly known as WAMM, is a nonprofit patient cooperative that literally gives medicine away to the sick and dying who qualify for medical cannabis under California State Law. Some of the patients are, in fact, children and a message is most certainly being sent to all of the children of the community and to the rest of us.

The message is that sick people, with their physicians’ approval, need real nontoxic medicine and programs like WAMM are going to see that they get what they need regardless of their ability to pay. Children are being taught that cannabis is a legitimate medicine that is to be used in the context of an overall medical plan designed to relieve suffering. The children are being taught to love one another and that there is all the difference in the world between legitimate medicine and drug abuse.

Furthermore, some in the medical cannabis community are brave enough to speak out publicly, stating that cannabis can provide unique help with some childhood disorders including cancer but also attention deficit disorder and autism. These latter disorders are currently treated with powerful stimulants such as amphetamine in the first case and with brain numbing toxic preparations such as Haldol in the case of autism. Parents of autistic children and children with severe ADHD often are desperate for help with seemingly insurmountable problems. Behavioral therapies while very helpful often fail to relieve the aggressive, indeed violent, behavior and lack of impulse control sometimes associated with these disorders.

Out of sheer desperation, a number of parents have begun trying adjunctive therapy with cannabis for their children. Most activists within the medical cannabis community are frightened by this development for the very real reason that they believe the use of cannabis with children will only increase the efforts of law enforcement to crush the movement. Nothing could be further from the truth. Some childhood behavioral brain disorders are so resistant to traditional treatment and that treatment is often so toxic that virtually any new method that provides real relief is going to result in a groundswell of support for medical cannabis. This is already happening in the autism community.

Imagine a child being given half a dozen psychotropic drugs from Prozac to Haldol to Valium and who continues to break down doors and assault others seemingly without provocation who now responds to therapy with medical cannabis. Imagine the parents of such children contemplating a lock up for their beloved child who now sees that child calm and functional. Loving parents will demand that cannabis be provided to the arsenal their pediatricians and pediatric neurologists already have.

The message to our sick and suffering children is that we love them. The love is greater than any blind acceptance of the existing wrongful beliefs about cannabis that are merely the propaganda of cultural elitists. As loving parents, these folks are willing to risk the wrath of Child Protective Services, the actions of the DEA, and the ignorance of their own physicians.

Over the past year, thousands of parents and professionals involved in the treatment of children have been reaching out for education on the possible role of cannabis in treating the devastating disorders of their kids. In the words of one parent of a formerly violent autistic boy, "autism took our son away from us and the love of the Lord and cannabis cookies have brought him back". The stories, one might say, are "merely" anecdotal but they are heart wrenching and true.

Brain disorders often involve an imbalance in the brain of key neurotransmitters and/or defects in their receptors. The exact cause of childhood brain disorders is still unknown but seems to involve the way in which brain cells (neurons) communicate with one another. Proper brain function requires an intricate "dance" of just the right concentrations of serotonin, dopamine, GABA, and other chemicals. It is now established that in the human body natural "cannabis", called Endocannabinoids, are active in the brain and play a vital role in regulating brain function. In fact, Endocannabinoids may be the most important chemicals of all in establishing and maintaining homeostasis or balance in key brain systems and other systems elsewhere in the body. Cannabinoids are active in determining when cells die (apoptosis) and when they live. The cannabinoids are neuroprotective. They are powerful anti-oxidants, anti-inflammatories, anti-seizure, and control the production and metabolism of key hormones including psychohormones.

In the decades to come it is certain that pharmaceutical companies will develop and test synthetic medicines based on the naturally occurring cannabinoids. They have already started. These medicines will be very expensive and it will be many decades before they are perfected and in general use. For the sake of the children we can’t wait that long. Nor do we need to. Cannabis has been used safely and medically for thousands of years. Based on the 12,000 year old track record of medical cannabis preparations we can treat our sick children now in the context of comprehensive treatment overseen by qualified physicians.

Currently, we have a virtual epidemic of behavioral problems with children. These problems propel children into self destructive behaviors including drug experimentation, alcoholism, and addiction. These problems destroy our families and fill our institutions and prisons. For the sake of the children we need to more effectively diagnose, intervene, and treat our sick kids. No medicine should be withheld from the effort to treat sick kids based on cultural prejudice and misinformation. For the sake of the children, their parents will not stand for nontoxic and efficacious treatments being denied their babies.

In the near future the American Alliance for Medical Cannabis will be publishing detailed articles on the use of cannabis in the treatment of autism and attention deficit disorders. We have already published articles demonstrating the effectiveness of cannabis with other brain disorders such as Tourette’s Syndrome and Bipolar Disorder. These are terrible illnesses that bring great suffering to many thousands and anguish to a legion of parents. For the sake of the children let’s try medical cannabis.

SOURCE:http://www.letfreedomgrow.com/cmu/for_the_children.htm

Marijuana may be beneficial to ADHD people when driving.

Cannabis normalized impaired psychomotor performance and mood in a patient with hyperactivity disorder

Scientists at the Department for Forensic and Traffic Medicine of the University of Heidelberg, Germany, investigated the effects of cannabis on driving related functions in a 28 year old man with attention-deficit/hyperactivity disorder (ADHD). He had violated traffic regulations several times in recent years and his driving licence was revoked due to driving under the influence of cannabis. He showed abnormal behaviour, seemed to be significantly maladjusted and his concentration was heavily impaired while sober during the first meeting with a psychologist. He was allowed to perform driving related tests under the influence of the cannabis compound dronabinol (THC), which his doctor had prescribed him to treat his symptoms. The examiner expected that he was not able to drive a car under the acute influence of THC.

But at the second visit his behaviour was markedly improved and he performed average and partly above-average in all tests on reaction speed, sustained attention, visual orientation, perception speed and divided attention. A blood sample taken after the tests revealed a high THC concentration of 71 ng/ml in blood serum. He admitted later to have smoked cannabis and not taken dronabinol, because it was too expensive. Researchers noted that "people with ADHD are found to violate traffic regulations, to commit criminal offences and to be involved in traffic accidents more often than the statistical norm" and conclude from their investigation that "it has to be taken into account that in persons with ADHD THC may have atypical and even performance-enhancing effects."


SOURCE:http://bbsnews.net/article.php/20071001105829361

Health Canada info on medical marijuana

Information for Health Care Professionals
(Revised)
Marihuana (marijuana, cannabis)
dried plant for administration by ingestion or other means
Psychoactive agent
Prepared by Health Canada, July 2003
Presented in present format by CPhA, June 2004
This document has been prepared for the Drug Strategy and Controlled
Substances Programme to provide information on the use of marihuana for
medical purposes. Marihuana is not an approved therapeutic product and
the provision of this information should not be interpreted as an
endorsement of the use of this product, or marihuana generally, by Health
Canada.
Despite the similarity of format, it is not a Drug Product Monograph, which is
a document which would be required if the product were to receive a Notice of
Compliance authorizing its sale in Canada. This document is a summary of
peer reviewed literature and international reviews concerning potential
therapeutic uses and harmful effects of marihuana. It is not meant to be
comprehensive and should be used as a complement to other reliable sources
of information.
This document should not be construed as expressing conclusions from
Health Canada about the appropriate use of marihuana for medical
purposes.
Marihuana (marijuana, cannabis) is not an approved therapeutic
substance in Canada and no marihuana product has been issued a
notice of compliance by Health Canada authorizing sale in
Canada.
Health
Canada
Santé
Canada
TABLE OF CONTENTS
Page
1.0 Chemistry.................................................................................................................................1
1.1 Composition..............................................................................................................................1
1.2 Other ingredients.......................................................................................................................1
1.3 Stability and storage...................................................................................................................1
2.0 Clinical Pharmacology.............................................................................................................2
2.1 Pharmacodynamics ....................................................................................................................2
2.2 Pharmacokinetics .......................................................................................................................5
2.2.1 Absorption...................................................................................................... 5
2.2.1.1 Smoked cannabis ............................................................................ 5
2.2.1.2 Oral THC .........................................................................................6
2.2.1.3 Rectal THC ......................................................................................7
2.2.2 Distribution .....................................................................................................7
2.2.3 Metabolism .................................................................................................... 8
2.2.3.1 Inhalation ..........................................................................................8
2.2.3.2 Oral ...................................................................................................9
2.2.4 Excretion .......................................................................................................10
2.3 Pharmacokinetic-pharmacodynamic relationships ................................................................. 10
3.0 Dosing.................................................................................................................................... 11
3.1 Smoking ................................................................................................................................. 11
3.2 Oral .........................................................................................................................................12
4.0 Purported Indications and Clinical Use.............................................................................. 12
4.1 Nausea and vomiting................................................................................................................13
4.2 Wasting syndrome and loss of appetite in AIDS and cancer patients .....................................13
4.2.1 To stimulate appetite and produce weight gain in AIDS patients ................13
4.2.2 To stimulate appetite and produce weight gain in cancer patients ...............14
4.2.3 Anorexia nervosa ..........................................................................................15
4.3 Multiple sclerosis, spinal cord injury or disease......................................................................15
4.3.1 Multiple sclerosis .........................................................................................15
4.3.2 Spinal cord injury..........................................................................................15
4.4 Epilepsy...................................................................................................................................16
4.5 Pain .........................................................................................................................................16
4.5.1 Cancer pain ...................................................................................................16
4.5.2 Other pain categories ....................................................................................17
4.6 Other diseases and symptoms..................................................................................................18
4.6.1 Movement disorders......................................................................................18
-iii-
4.6.1.1 Dystonia .........................................................................................18
4.6.1.2 Huntington’s disease......................................................................18
4.6.1.3 Parkinson’s disease ........................................................................18
4.6.1.4 Tourette’s syndrome ......................................................................19
4.6.2 Glaucoma ......................................................................................................19
4.6.3 Bronchial asthma ..........................................................................................19
4.6.4 Hypertension .................................................................................................20
4.6.5 Psychiatric disorders .....................................................................................20
4.6.6 Alzheimer’s disease ..................................................................................... 21
5.0 Contraindications................................................................................................................. 21
6.0 Warnings................................................................................................................................21
7.0 Precautions ............................................................................................................................ 22
7.1 General....................................................................................................................................22
7.2 Dependence and withdrawal ....................................................................................................22
7.3 Special populations ..................................................................................................................22
7.4 Drug interactions.....................................................................................................................22
7.5 Drug screening tests.................................................................................................................23
8.0 Adverse Effects...................................................................................................................... 23
8.1 Carcinogenesis, mutagenesis and respiratory tract ..................................................................23
8.2 Immune system ........................................................................................................................24
8.3 Reproductive and endocrine systems.......................................................................................24
8.4 Cardiovascular effects..............................................................................................................25
8.5 Central nervous system............................................................................................................27
8.5.1 Cognition......................................................................................................27
8.5.2 Psychomotor performance ...........................................................................27
8.5.3 Behavioural effects ......................................................................................28
8.5.3.1 Psychiatric disorders ............................................................................28
8.5.3.2 Schizophrenia.......................................................................................29
8.5.3.3 Amotivational syndrome......................................................................29
8.5.3.4 Dependence and tolerance ...................................................................30
9.0 Overdose and toxicity ........................................................................................................... 31
-1-
1.0 Chemistry
1.1 Composition
Marihuana (Marijuana) is the common name for Cannabis, a hemp plant that grows
throughout temperate and tropical climates in almost any soil condition. Delta-9-
tetrahydrocannabinol ( Δ9-THC, THC) is the main psychoactive ingredient of cannabis.
The flowering tops and leaves are used to produce cannabis for smoking. Marihuana is
most commonly smoked in hand-rolled cigarettes (“joints”) containing marihuana plant
material.
Although the leaves and flowering tops of Cannabis plants yield more than 60
cannabinoids, the major active components are Δ9-THC, cannabinol (CBN) and
cannabidiol (CBD) (British Medical Association, 1997, p 7).
1.2 Other ingredients
There are other components in marihuana joints which are common to tobacco and the
smoke from them is considered chemically similar to that from tobacco cigarettes
(Iverson, 2000, p 191; British Medical Association, 1997, p 14). However, some
investigators report that two potent carcinogens in tobacco smoke, benzanthracene and
benzpyrene, are present in higher amounts in marihuana smoke (Novotny, et al., 1976).
Differences in the smoking techniques used by marihuana and tobacco smokers are
reported to result in three-fold higher levels of tar and five-fold higher levels of carbon
monoxide being retained in the lungs during cannabis than during tobacco smoking (Wu,
et al., 1988). This greater retention of tar and carbon monoxide from cannabis smoke
may offset the fact that a marihuana smoker typically smokes fewer cigarettes per day
than a tobacco smoker (i.e., the exposure to tar and carbon monoxide could be similar for
both groups of smokers) (Peterson, 1979; Tashkin, et al, 1987).
1.3 Stability and storage
Most of the information on stability of marihuana does not distinguish between THC and
its carboxylic acid analogue (THCA). The latter is degraded to THC by pyrolysis during
smoking or in the inlet of gas chromatographs used in forensic analysis (Baker, et al.,
1981). Heat, light, humidity, acidity and oxidation all affect the stability of cannabis
(Garrett, et al., 1974; Mechoulam, et al., 1981). Available information suggests that THC
in recently harvested plant material stored in dry, tightly- closed, refrigerated containers
would be stable for several months. The National Institute of Drug Abuse (NIDA) reports
(Thomas, et al., 1999) that retention samples of their carefully prepared and standardized
cigarettes are stable for months, particularly when stored below 0oC. However, even at
18oC, there is a loss of only a third of the THC potency (from 2.87 to 1.8% THC) over 5
years, with some increase in the concentration of CBN.
2.0 Clinical Pharmacology
2.1 Pharmacodynamics
Most of the pharmacodynamic information on marihuana in humans refers to the effects
of the major constituent THC. CBD does not appear to be psychoactive; its principle
-2-
action is inhibition of cytochrome P450 enzymes, which decreases the metabolism of
TCH and other drugs. CBN, while only weakly active compared to THC in the brain,
appears to have activity in isolated immune cells (National Academy of Sciences, 1999, p
2.5).
Cannabinoid receptors have been discovered in neural tissue. Two types of cannabinoid
receptors, CB1 and CB2, have been identified. Table 1, adapted from the British Medical
Association Report (British Medical Association, 1997, p 19), notes some of the effects
of cannabis. Many of the effects are biphasic, e.g., increased activity with acute or
smaller doses, decreased activity with larger doses or chronic use. Effects differ greatly
among individuals and may be greater in severely ill and elderly patients.
-3-
Table 1: Pharmacologic actions of cannabis in man
Body System/Effect Detail of Effects
CNS
Psychological Euphoria (“high”), dysphoria, anxiety, depersonalization,
precipitation or aggravation of psychosis.
Perception Heightened sensory perception, distortion of space and time, sense,
hallucinations, misperceptions.
Sedative Generalised CNS depression, drowsiness, somnolence; additive
with other CNS depressants.
Cognition, psychomotor
performance
Fragmentation of thoughts, mental clouding, memory impairment,
global impairment of performance especially in complex
demanding tasks.
Motor function Increased motor activity followed by inertia and in coordination,
ataxia, dysarthria, tremulousness, weakness, muscle twitching.
Analgesic Currently available oral cannabinoids are similar in potency to
codeine (but from a different mechanism).
Anti-emetic, increased
appetite
With acute doses; effect reversed with larger doses or chronic use
(tolerance).
Tolerance To most behavioural and somatic effects, including the “high”.
Dependence, abstinence
syndrome
Has been produced experimentally following prolonged
intoxication: symptoms include disturbed sleep, decreased appetite,
restlessness, irritability and sweating. Information from therapeutic
use lacking.
Cardiovascular System
Heart rate Tachycardia with acute dosage, bradycardia with chronic use.
Peripheral circulation Vasodilation, conjunctival redness, postural hypotension.
Cardiac output Increased output and myocardial oxygen demand.
Cerebral blood flow Increased with acute dose, decreased with chronic use.
Respiratory system
Ventilation Small doses stimulate; larger doses depress.
Bronchodilation Coughing, but tolerance develops.
Airways obstruction From chronic smoking.
Eye Decreased intraocular pressure.
Immune system Chronic use: impaired bactericidal activity of macrophages in lung
and spleen.
Reproductive System
Males Antiandrogenic, decreased sperm count and sperm motility (chronic
use, but tolerance may develop).
Females Suppression of ovulation, complex effects on prolactin secretion;
chronic use: increased obstetric risk.
-4-
The acute effects of smoking marihuana include almost immediate euphoria (the
marihuana “high”) as well as cardiovascular, bronchopulmonary, ocular, psychological
and psychomotor effects. Maximum euphoria occurs within 15 minutes after smoking;
the psychological effects (see Table 1) reach a plateau which can last for several hours.
However, on first dosing, some people experience dysphoria and anxiety. The effects on
the cardiovascular system (tachycardia, etc.) decline much faster as THC is distributed
out of the circulatory system. Tachycardia is the most consistent of the physiological
effects of marihuana (Beaconsfield, et al., 1972; Perez-Reyes, 1990).
The short-term psychoactive effects of marihuana smoking include euphoria, relaxation,
time-distortion, perception of enhanced sensory experiences (such as music) and loss of
inhibitions that may result in laughter (Hall, et al., 1998). This is followed by a
depressant period (Ameri, 1999). While there is some inconsistency in reports of the
acute effects on memory and motor skills (Fant, et al., 1998; Kelly, et al., 1993; Barnett,
et al., 1985), most reviews note that marihuana use is associated with impaired function
of a variety of cognitive tasks and short-term memory (Ameri, 1999; National Academy
of Sciences, 1999, p 2.27; Hollister, 1998; Miller, Ch. 15 p 227-231).
A major concern
from such an acute effect is impairment affecting driving or operation of intricate
machinery (Hansteen, et al., 1976; Smiley, et al., 1999; O’Kane, et al., 2002). There are
reports of reduced skills on flight simulators by experienced pilots 24 h after smoking one
marihuana cigarette (Leirer, et al., 1991). Plasma THC levels attained after smoking seem
to have a dose and concentration dependent effect on cognitive function (Heishman, et
al., 1990).
2.2 Pharmacokinetics
This section will be restricted to human pharmacokinetics, mainly of smoked cannabis,
but with some comparisons to oral THC, including dronabinol (Marinol®).
2.2.1 Absorption
2.2.1.1 Smoked cannabis
The estimation of dose administered by the smoking route is a major variable in
the assessment of absorption of cannabinoids (mainly THC) in humans. The
source of the plant material and the composition of the cigarette, together with the
efficiency of smoking by the subject, are additional uncontrolled factors. It might
be reasonable to consider about 10% (range 3-30%) as an average for THC
content in Canadian marihuana. It appears that habitual (heavy) marihuana
smokers can increase the amount absorbed, which is attributed to more efficient
smoking techniques (Agurell, et al., 1986).
THC absorption by inhalation is extremely rapid, with a bioavailability of 18 to
50% from the cigarette (Huestis, 1999), and is the main reason this route is
preferred by many people (Iverson, 2000, p 46-47).
Standardised cigarettes have been developed by NIDA, and the relationships
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among cannabis (THC) content, dose administered and resultant plasma levels
have been investigated. Smoking cannabis containing 1.64% THC (mean dose
13.0 mg THC) resulted in mean peak THC plasma levels of 77 ng/mL (Ohlsson,
et al., 1980).
THC levels in plasma decreased rapidly after cessation of smoking and were
below 5 ng/mL, 2 hours after smoking; mean concentrations declined by about
50%, 15 minutes after (Huestis, et al., 1992) reaching the maximum (Huestis,
1999). However, THC from a single dose can be detected in plasma for at least a
day using modern sensitive analytical techniques and for 13 days in chronic users
(Johansson, et al., 1988). The decline of THC in plasma is multiphasic and as
Harvey (Harvey, 1999) notes, the estimates of the terminal half-life of THC in
humans have increased as analytical methods have become more sensitive. There
is still no consensus. It is probably safe to say that the terminal half-life of THC
averages at least a week and could be considerably longer. The half-life in plasma
does not appear to be different between heavy and light users (Agurell, et al.,
1971).
2.2.1.2 Oral THC
Absorption from an oral dose of 20 mg THC in a chocolate cookie was described
as slow and unreliable (Agurell, et al., 1986), with a systemic availability of only
4 to 12% (Ohlsson, et al., 1980). While most subjects had peak plasma THC
concentrations between 1 to 2 hours, some of the 11 subjects only peaked at 6
hours and many had more than one peak.
Only 10-20% of synthetic THC (dronabinol, Marinol®) administered in capsules
with sesame oil enters the systemic circulation indicating extensive first-pass
metabolism (Compendium of Pharmaceuticals and Specialties, 2003). The
psychotropic effect or “high" is observed to occur more quickly by the smoking
than the oral route, which has been characterized by Iversen (Iverson, 2000, p 46-
47) as the reason “smoking is the preferred route of cannabis for many people”.
2.2.1.3 Rectal THC
Limited evidence suggests a higher bioavailability of THC by the rectal route than
by the oral route (Mattes, et al., 1993 p 745-747; Brenneisen, et al., 1996).
2.2.2 Distribution
Distribution of THC begins immediately after absorption. The plasma protein binding
of THC and its metabolites is approximately 97% (Garrett, et al., 1977; Widman, et
al., 1974). THC is mainly bound to low-density lipoproteins, with up to 10% present
in red blood cells (Walqvist, et al., 1970), while the metabolite, 11-hydroxy THC, is
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even more strongly bound with only 1% found in the free-fraction (Widman, et al.,
1973).
THC has a large apparent volume of distribution, approximately 10 L/kg, because of
its high lipid solubility. Animal studies show that it is sequestered to fatty tissues
including brain (Harvey, 1999). The highest concentrations are found in the heart and
in adipose tissue, with levels reaching 10 and 1000 times that of plasma, respectively
(Truitt Jr., 1971). THC readily crosses the blood brain barrier and the slight delay in
correlating peak plasma concentration to effects is assumed to reflect this distribution
(Agurell, et al., 1986). While immediate distribution is high in liver, spleen and body
fat are the major sites of distribution after 72 h. Spleen and body fat are the long-term
storage sites (Harvey, 1999).
There has been concern about the possible consequences of the long persistence of
THC in fatty tissues. There is no evidence that the THC residues persist in the brain.
Release from the fatty storage sites into blood is slow; levels attained are not high
enough to cause psychological effects.
2.2.3 Metabolism
Most metabolism of cannabinoids occurs in the liver and different metabolites
predominate when different routes of administration are used. The complex
metabolism of THC involves allylic oxidation, epoxidation, decarboxylation and
conjugation (Agurell, et al., 1986). Cannabinoids are good substrates for cytochrome
P450 mixed-function oxidases, mainly CYP 2C9. The major initial metabolites of
THC are 11-hydroxy THC and 11-nor-9-carboxy THC. 11-hydroxy THC is rapidly
formed by action of hepatic microsomal oxidases, and plasma levels parallel the
duration of observable drug action. 11-hydroxy THC has been found to have
psychotomimetic properties equal to THC (Christensen, et al., 1971; Perez-Reyes, et
al., 1972).
2.2.3.1 Inhalation
After smoking (1.75 and 3.55% THC cigarettes) 11-hydroxy THC (Huestis, et al.,
1992) appears rapidly and peaks shortly after THC, at about 15 minutes after the
start of smoking. It exhibited peak plasma concentrations of about 7.5 ng/mL
(about 5% of parent THC) and the AUC profile of this metabolite averaged 20%
of the parent. Similar results were obtained with intravenous administration
(Agurell, et al., 1971).
The psycho-inactive 11-nor-9-carboxy THC is the primary acid metabolite of
THC excreted in urine (Huestis, et al., 1996) and it is the cannabinoid often
screened for in forensic analysis of body fluids (Martin, et al., 1999). Peak
plasma values of this metabolite occur 1.5 to 2.5 h after smoking and are about
one third the concentration of parent THC. Following oxidation, the phase II
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metabolites of the free drug or hydroxy-THC appear to be glucuronide conjugates
(Agurell, et al., 1986).
It is known that polyaromatic hydrocarbons found in tobacco and cannabis smoke
induce the action of CYP1A2. If it is shown that the metabolism of THC also
involves this cytochrome P450 isoenzyme, then repeated exposure to cannabis
could cause the more rapid disappearance of THC via this specific enzyme
(Valjent, et al., 2002). Various other cytochrome P450, enzymes are of interest for
potential drug interactions. In human liver microsome preparations, CBD has been
shown to inhibit formation of THC metabolites catalyzed by CYP 3A, with less
effect on CYP 2C9 (Harvey, 1999). However, others suggest that CBD decreases
formation of 11-hydroxy THC by inhibition of CYP 2C9 (Bornheim, et al., 1993).
Observed and potential interactions of cannabis with other drugs are discussed
later.
2.2.3.2 Oral
After oral doses of THC, parent THC and its active metabolite, 11-OH-THC, are
present in approximately equal concentrations in plasma (Wall, et al., 1981; Cone,
et al., 1988). Concentrations of both parent drug and metabolite peak at
approximately 2 to 4 hours after oral dosing and decline over several days.
Clearance averages about 0.2 L/kg-h, but is highly variable, due to the complexity
of cannabinoid distribution (Marinol US monograph). The larger amount of 11-
hydroxy THC metabolite, from first pass metabolism by this route, which is
similar in potency to THC, complicates interpretation of potential effects. With
oral THC dosing, the absorption is slow and variable, and peak concentrations of
THC may be considered one tenth those from efficiently smoked administration
but the plasma levels of active 11-hydroxy metabolite are about 3 times higher
than observed in the plasma from smoking (Wall, et al., 1983).
2.2.4 Excretion
Following inhalation, elimination of THC and its metabolites occurs via the faeces
(65%) and the urine (20%). After five days, 80% to 90% of the total dose is excreted.
Similarly, following oral doses, THC and its biotransformation products are excreted
in both faeces and urine. Biliary excretion is the major route of elimination with
about half of a radiolabelled oral dose being recovered from the faeces within 72
hours as contrasted with 10 to 15% recovered from urine. Less than 5% of an oral
dose is recovered unchanged in the faeces. Following administration of a single oral
dose, low levels of THC metabolites have been detected for more than 5 weeks in the
urine and faeces (Harvey, 1999, p 91-103; Compendium of Pharmaceuticals and
Specialties,2003).
Traces of marihuana can be detected in urine even for weeks (Ohlsson, et al., 1980)
after dosing in forensic or employment situations when such testing may be applied.
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2.3 Pharmacokinetic-pharmacodynamic relationships
Though it is of major forensic interest, the temporal relationship between plasma
concentrations of TCH and its psychotropic, cognitive and motor effects is unclear
(Harder, et al., 1997; Cone, et al., 1993). Dose and plasma concentration vs. response for
possible therapeutic applications are ill-defined, except for some information obtained for
oral dosing with dronabinol (synthetic THC) for its limited indications (Compedium of
Pharmaceuticals and specialties, 2003). Interpretations of THC pharmacokinetics is also
complicated by the emergence of active metabolites, particularly 11-hydroxy THC (Wall,
et al., 1981; Cone, et al., 1988), which attains higher concentrations after oral than
inhalation doses. Pharmacodynamic modelling (Barnett, et al., 1982) supports a 10
ng/mL cutoff as evidence of functional impairment (McBay, 1985) which is in agreement
with the estimate of 25 – 29 ng/mL for the steady state plasma concentration at 50% of
the maximum “high” effect, or Css(50). The model was also used to simulate multiple
dosing with a 1% cigarette containing 9 mg THC (Harder, et al., 1997). The duration of
maximal “high” for this dose was estimated at about 45 minutes after dosing and declined
to 50% of this peak effect at about 100 minutes following smoking. A dosing interval of
1h with this dose would give a “continuous high” and the recovery after the last dose
would be 150 minutes. The peak plasma concentration during this dosage is estimated at
about 70 ng/mL and the Css(50) at about 30 ng/mL THC.
Target THC plasma concentrations have been derived based on the subjective “high”
response that may or may not be related to the potential therapeutic applications.
However, it is likely that the psychoactivity that elicits this response from the central
nervous system is receptor derived and the concentrations are useful for suggesting doses
from smoking.
3.0 Dosing
3.1 Smoking
The actual dose of THC absorbed when smoked is not easily quantified (see section
2.2.1). According to the World Health Organization (World Health Organization, 1997),
a typical joint contains between 0.5 and 1.0 g of cannabis plant matter (average 750 mg)
which may vary in THC content between 7.5 and 225 mg (i.e., typically between 1 and
30%; see Table 2. The actual amount of THC delivered in the smoke has been estimated
at 20 to 70%, the remainder being lost through combustion or side stream smoke. The
bioavailability of THC (the fraction of THC in the cigarette which reaches the
bloodstream) from marihuana cigarettes in human subjects has been reported from 5 to
24%. The amount of other cannabinoids present, mainly CBN and CBD, is usually much
lower, but the amount delivered and absorbed parallels that of THC.
Table 2 shows some relationships between percentage of THC in cannabis plant material
and the amount in average joints. Bioavailability of cannabinoid depends greatly on
smoking technique (likely maximum approximately 50%).
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Table 2: Relationship of THC percent in plant material to
available dose in a joint
%THC (mg per 100 mg cannabis) mg THC per 750 mg*
(“ average joint”)
1 7.5
2.5 18.75
5 37.5
10 75
15 112.5
20 150
30 225
* WHO average weight
Assuming the desired peak plasma concentration of smoked THC is in the 50-100 ng/mL
range, (see Section 2.3) it has been shown (Huestis, et al., 1992) that this can be readily
achieved with smoke from a single 3.55 % marihuana cigarette with about 900 mg plant
material (approximately 32 mg THC).
A 750 mg joint of 5% strength (i.e., 37.5 mg THC) would yield slightly higher plasma
levels. If the current average “street” marihuana contains 10% THC, then plants yielding
joints from such a source might have an available 75 mg dose and could result in rapid
attainment of plasma concentrations above 300 ng/mL. Clearly even more potent strains
of cannabis have been reported. Patients initiating smoked marihuana therapy should
be cautioned to begin slowly and to stop smoking if tachycardia occurs.
3.2 Oral
The pharmacokinetic information described in section 2.2 reports the erratic and slow
absorption from the oral route and doses are estimated from the information for Marinol®.
4.0 Purported Indications and Clinical Use
The oral form of synthetic THC, dronabinol (2.5, 5 or 10 mg, dissolved in sesame oil) in
capsules is marketed in the US and Canada as Marinol®. It is indicated for treatment of
chemotherapy-induced emesis and for appetite stimulation in AIDS- related anorexia associated
with weight loss (Compendium of Pharmaceuticals and Specialties, 2003; Marinol US
monograph).
While there are many anecdotal reports of the therapeutic value of smoked marihuana, scientific
studies supporting the safety and efficacy of marihuana for therapeutic claims are inconclusive.
The existing scientific evidence for various symptoms is summarized in the following sections.
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4.1 Nausea and vomiting
The IOM (National Academy of Sciences, 1999, p 4.17) and other committees (Health
Department, NSW, Australia, 2000, p 41) consider that the place (if any) for smoked
marihuana would be as an adjunct to other antiemetics, when they are not fully successful
in treatment. However, there are no trials available for guidance. The BMA report
(British Medical Association, 1997, p 27) indicates the research needed to evaluate
marihuana in chemotherapy-induced emesis. This includes establishing dose ranges for
cannabinoids and clinical trials to differentiate optimum cannabinoid treatment for
specific anticancer agents and patient groups.
The IOM report suggests that, since there are now more effective antiemetic agents
available than were available in the 1980s (especially the 5-HT3 receptor antagonists),
patients are less in need of THC.
4.2 Wasting syndrome (cachexia, e.g., from tissue injury by infection or tumor) and
loss of appetite (anorexia) in AIDS and cancer patients
4.2.1 To stimulate appetite and produce weight gain in AIDS patients
The reports that marihuana is beneficial for patients with AIDS wasting syndrome
are anecdotal, although it appears to be very popular with AIDS patients
(Grinspoon et al., 1993). Studies with healthy subjects confirm an appetite
stimulating effect of smoked marihuana together with increases of food
consumption and body weight (Mattes, et al., 1994; Foltin, et al., 1988). In a
controlled, residential laboratory study in which food consumption was carefully
monitored and cannabis cigarettes were smoked with a standardized procedure,
subjects consumed significantly more calories daily compared to placebo (Foltin,
et al., 1988). There are, however no clinical trials of the smoked drug for this
indication (National Academy of Sciences, 1999, p 4.19).
Oral synthetic THC, dronabinol, administered as capsules (Marinol®) has been
approved for this indication. The Marinol product monograph summarizes a
randomized double-blind, placebo controlled-trial in 139 patients (Beal, et al.,
1995) with the 72 patients in the treatment group initially receiving 2.5 mg
dronabinol twice a day, but then having the dose reduced to 2.5 mg at bedtime
due to side effects (feeling high, dizziness, confusion and somnolence). Over the
six week treatment period dronabinol significantly increased appetite, with a trend
towards improved body-weight, and mood, and a decrease in nausea. After the six
weeks, patients were allowed to continue receiving dronabinol, during which the
appetite improvement continued.
A major concern with marihuana smoking in HIV-infected patients is that they
might be more vulnerable than other marihuana users to immunosuppressive
effects of marihuana or to the exposure of infectious organisms associated with
marihuana plant material (National Academy of Sciences, 1999, p 4.19). There
are also drug interaction concerns that are reviewed later.
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4.2.2 To stimulate appetite and produce weight gain in cancer patients
Smoked marihuana has not been studied in patients with cancer cachexia. Oral
THC (dronabinol) has been shown to improve appetite and food intake from
observations during the investigations of the anti-nausea effect (Ekert, et al., 1979;
Sallan, et al., 1980). Improved appetite and increased food intake was reported in
patients with unresectable or advanced cancer treated with open-label dronabinol
2.5 mg 2 to 3 times daily for 4 to 6 weeks, but weight gain was achieved in only a
few patients (Plasse, et al., 1991; Wadleigh, et al.,1990, p 331; Nelson, et al.,
1994). Modest weight gain was obtained with a larger dose regimen of dronabinol
(5 mg, 3 times daily), but the CNS side effects including dizziness and
somnolence were limiting (Regelson, et al., 1976). Cancer cachexia is not an
approved indication for dronabinol either in Canada or the U.S.
The immunomodulating effects of some cannabinoids could be contraindicated in
some cancer patients (both the chemotherapy and the cancer can be
immunosuppressive) (National Academy of Sciences, 1999, p 4.21).
4.2.3 Anorexia nervosa
A randomized trial of oral THC (Gross, et al., 1983) was unsuccessful for weight
gain and three of the eleven patients administered THC reported severe dysphoric
reactions. Both the British Medical Association (British Medical Association,
1997, p 46) and IOM (National Academy of Sciences, 1999, p 4.21) conclude that
marihuana is unlikely to be effective in this group of patients.
4.3 Multiple sclerosis, spinal cord injury or disease
The common symptom of these diseases is muscle spasticity. There are many anecdotal
reports that marihuana can ameliorate spasticity associated with multiple sclerosis or
spinal cord injury when other drugs fail or produce unacceptable side effects (American
Medical Association, 1997, p 10; British Medical Association, 1997, p 30; National
Academy of Sciences, 1999, p 4.23).
4.3.1 Multiple sclerosis (MS)
Published reports spanning one hundred years suggest that people with spasticity may
experience relief with cannabis (Consroe, et al., 1986). As many as 4% of MS
patients in the UK already smoke cannabis to relieve symptoms (Iverson, 2000, p
157) and in a mail survey of 233 MS patients in the UK and US, 112 (48%) reported
(Consroe, 1997) that cannabis was used to ameliorate symptoms.
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4.3.2 Spinal cord injury
Patients surviving spinal cord injuries are usually young (60% are less than 35 years
old (National Academy of Sciences, 1999, p 4.28)), and require long-term or even
life-long care. While there are no clinical trials of smoked marihuana for treatment of
muscle spasms, spinal patients reported to the IOM workshops that muscle spasms,
nausea and sleeplessness were alleviated by smoking marihuana.
4.4 Epilepsy
While some work in animals suggests that cannabinoids could have a role in treatment of
some types of epileptic seizures (Consroe, et al., 1992), (in particular CBD appeared to
have anticonvulsant without psychoactive properties (Hollister, 1986)), there are only
anecdotal and individual case reports that marihuana controls seizures in epileptics.
The potential antiepileptic activity of cannabidiol (CBD) in epileptic patients who were
poorly controlled with conventional anticonvulsants, has been investigated but is not
promising (Ames, et al., 1986, p 14; Trembly, et al., 1997, p 51; Cunha, et al., 1980).
4.5 Pain
4.5.1 Cancer pain
There are no controlled clinical trials of smoked marihuana in treatment of pain.
There are two double-blind, controlled studies of oral THC (dronabinol,
Marinol®) in cancer pain. The first (Noyes Jr., et al., 1975) was a dose ranging
study of 5, 10, 15 and 20 mg THC, given in successive days, to ten cancer
patients. Significant pain relief was found at the 15 and 20 mg dose levels, but at
these higher doses patients were heavily sedated with mental clouding common. A
second, placebo-controlled, study (Noyes, et al., 1975) compared oral 10 and 20
mg THC with 60 and 120 mg codeine in 36 patients with cancer pain. The 10 and
20 mg THC were equivalent in analgesic potency with 60 and 120 mg codeine
respectively. The 10 mg THC dose was well tolerated and, despite its sedative
effect, may have analgesic potential, but the 20 mg THC dose induced side effects
including somnolence, dizziness, ataxia, and blurred vision. Alarming extreme
anxiety was also observed at this dose. This side effect profile is supported by a
report concerning a synthetic analogue of THC also tested in controlled trials
(Staquet, et al., 1978). While it was equivalent in efficacy to codeine, it was not
considered clinically useful because of the frequency of side effects.
4.5.2 Other pain categories
Intravenous THC (0.22 mg/kg and 0.44 mg/kg) administered to patients
undergoing tooth extraction (Raft, et al., 1977) was compared to diazepam (0.157
mg/kg). High dose THC was least effective and diazepam most effective. Four
patients preferred placebo to low dose THC. A study of oral CBD, 450 mg/day in
divided doses, in 10 patients with chronic neuropathic pain (neuralgia, etc.) also
found no significant pain relief (Lindstrom, et al., 1997, p 43). Receptor studies
indicate that cannabinoids might be useful adjuncts to opioid analgesia (National
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Academy of Sciences, 1999, p 4.8). Improvement in phantom limb pain has been
documented (British Medical Association, 1997, p 43).
A meta-analysis of all cannabinoid trials for analgesia concluded that as well as
having effects on the CNS that limit their use, cannabinoids are no more effective
than codeine as analgesics (Campbell, et al., 2001).
4.6 Other diseases and symptoms
4.6.1 Movement disorders
The endogenous cannabinoid system appears to be intricately involved in normal
physiology, specifically in the control of movement, formation of memories and
appetite control and may be involved in the pathology of several neurological
diseases. The contribution of cannabinoids to Huntington’s disease, Parkinson’s
disease and tremor has been reviewed (Glass, 2001).
4.6.1.1 Dystonia
No controlled study of smoked marihuana in dystonic patients has been
published. However, there was a preliminary open trial (Consroe, et al., 1986,
30: 277-282) of an oral cannabinoid. CBD, administered in five dystonic
patients (100 mg/day rising to 600 mg/day over 6 weeks), showed modest
dose-related improvements in all five, but worsening of tremor and hypokinesia
in 2 patients with co-existing Parkinson’s disease. Results of a double-blind
randomized, placebo- controlled study of a synthetic cannabinoid (nabilone)
showed no significant reduction in dystonia (Fox, et al., 2002).
4.6.1.2 Huntington’s disease
A double-blind, placebo-controlled trial (Consroe, et al., 1991) of oral CBD, 10
mg/kg/day in 15 patients with Huntington’s disease found no beneficial effects of
treatment .
4.6.1.3 Parkinson's disease
There are theoretical reasons from research on brain transmission pathways that
support a role for cannabinoids in the treatment of Parkinsonism. However, the
one published clinical trial of smoked marihuana (1 g cigarettes containing 2.9%
THC) involving five cases of idiopathic Parkinson’s disease (Frankel, et al., 1990,
53: 436) found no improvement in tremor after the patients smoked marihuana,
whereas all subjects benefited from the administration of levodopa and
apomorphine. A small randomized clinical trial of the synthetic cannabinoid,
nabilone, in seven patients with Parkinson’s disease found that the treatment
reduced levodopa-induced dyskinesia (Sieradzan, et al., 2001).
4.6.1.4 Tourette's syndrome
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Four case histories suggest that smoked marihuana use can reduce tics in
Tourette’s patients (National Academy of Sciences, 1999, p 4.32). In one report of
3 patients, it is hypothesized that beneficial effects of marihuana might have been
due to anxiety-reducing properties of marihuana rather than to a specific anti-tic
effect (Sandyk, et al., 1988, p 444-445). A randomized, double-blind, placebo
controlled trial of single oral doses of THC (5, 7.5 or 10 mg) in 12 patients with
Tourette’s syndrome showed plasma concentration-related improvements in
control of tics and obsessive-compulsive behaviour, with no serious side effects;
although transient, mild side effects were noted in five patients (Muller-Vahl, et
al., 2002). A related study showed that in contrast to healthy marihuana users,
single does of THC (5-10 mg) caused no cognitive impairment measured by
objective tests in 12 patients with Tourette’s syndrome (Muller-Vahl, et al.,
2001).
4.6.2 Glaucoma
The high intraocular pressure (IOP) of glaucoma can be reduced by marihuana (oral
or smoked) and there are a few reports from treatment of glaucoma patients (British
Medical Association, 1997, p 55). One reviewer remarks (Green, 1998) that
“smoking of marijuana plant material for the reduction of elevated IOP in glaucoma
is ill-advised, given its toxicological profile.” Research with cannabinoids, including
the discovery of ocular cannabinoid receptors, could lead to improved agents for
glaucoma treatment (Jarvinen, et al., 2002).
4.6.3 Bronchial asthma
While cannabinoids are bronchodilators, there have been very few studies of the
bronchodilator effect in asthmatic patients. A double-blind, placebo-controlled study
of smoked marihuana (2% THC), oral THC (15 mg) and isoprenaline (0.5%) in 14
asthmatic subjects showed reversal of experimental bronchospasm by
bronchodilation which was almost equivalent (Tashkin, et al., 1976). However,
tolerance to this effect developed after several weeks (Tashkin, et al., 1976).
Another single-blind investigation of smoked marihuana (0.9 and 1.9% THC) found
that it caused significant and prolonged bronchodilation, but tachycardia occurred
with the higher dose (Vachon, et al., 1976). It is clear that smoked marihuana is not
suitable for chronic use in asthma because of bronchial irritation from various
components of smoke (British Medical Association, 1997, p 60).
4.6.4 Hypertension
Cannabinoids cause postural hypotension, but tolerance to the cardiovascular effects
develops rapidly and together with adverse effects would preclude their consideration
as a treatment for long-term use in hypertension (British Medical Association, 1997,
p 64).
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4.6.5 Psychiatric disorders
Cannabis has been advocated as a treatment for anxiety, depression, sleep disorders
and alcohol and opiate withdrawal symptoms (Iverson, 2000, p 172). Use is
anecdotal and occurred before modern psychotherapeutic agents became available.
One anecdote concerns relief of depression by smoking marihuana, with much faster
mood alteration than from amitriptyline, a conventional antidepressant that usually
takes some weeks to take effect (Grinspoon, et al., 1993). Trials for treatment of
chemotherapy-induced nausea with cannabinoids have mentioned some
antidepressant effect (Regelson, et al., 1976). However, these are offset by the
potential for severe psychological side effects.
Anecdotal information and some animal studies suggest that cannabinoids may be
useful in treatment of opiate withdrawal, but there are no clinical studies to support
this indication (British Medical Association, 1997, p 64).
4.6.6 Alzheimer’s disease
Two possible indications for cannabinoid treatment in Alzheimer’s are to stimulate
appetite (i.e., to combat food refusal) and improve behaviour. Although oral THC
(dronabinol, Marinol®) has been investigated in 11 patients and showed efficacy
(Volicer, et al., 1997), there are concerns about the known THC effects on memory
of healthy adults in this condition in which memory is already diminishing. There
are also obvious concerns about the fire hazards of smoking marihuana in cognitively
impaired patients.
5.0 Contraindications
Marihuana is contraindicated in any patient who has a history of hypersensitivity to any
cannabinoid or to smoking. Marihuana should not be used in patients with a history of psychotic
disorders, particularly schizophrenia.
6.0 Warnings
The dose of marihuana is difficult to estimate and is affected by source of plant material, its
processing and by different smoking techniques. These include depth of inhalation and breathholding
and the number and frequency of puffs as well as how much of the cigarette is smoked.
Smoking should be gradual and should cease if the patient begins to feel disoriented or agitated.
Experienced smokers are able to “titrate” their dose, but naïve smokers should take great care
and be supervised.
Marihuana can produce physical and psychological dependence and has the potential for abuse.
The drug has complex effects in the CNS. These can result in cognitive and memory impairment,
mood changes, altered perception and decreased impulse control. Patients should be supervised
when administration s initiated.
Any patient experiencing a psychotic reaction to marihuana should stop taking the drug
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immediately and be kept under observation until the normal mental state is regained.
Occupational hazards: Patients using marihuana should be warned not to drive or perform
hazardous tasks such as operating heavy machinery because impairment of mental alertness and
physical coordination may decrease their ability to perform such tasks. Such impairment can last
for over 24 hours after using due to the long half-life of THC.
Pregnancy: Use of marihuana during pregnancy should be avoided as there is evidence of long
term development problems in children exposed to marihuana in utero.
Lactation: Cannabinoids are excreted in human milk and may be absorbed by the nursing baby.
Because of potential risks to the child, nursing mothers should not use marihuana.
7.0 Precautions
7.1 General
The risk/benefit ratio of marihuana should be carefully evaluated in patients with the
following medical conditions, because of individual variation in response and tolerance to
its effects as well as the difficulty in dosing noted in section 3.0:
• Marihuana should be used with caution in patients with cardiac disorders because
of occasional hypotension, possible hypertension, syncope, or tachycardia.
• Smoked marihuana is not recommended in patients with respiratory insufficiency
such as asthma or chronic obstructive pulmonary disease.
• Marihuana should be used with caution in patients with a history of substance
abuse, including alcohol abuse or dependence, because they may be more prone to
abuse marihuana, which itself, is a frequently abused substance.
• Patients with mania, depression, or schizophrenia should be under careful
psychiatric monitoring if marihuana is taken, because it may exacerbate these
illnesses.
• Marihuana should be used with caution in patients receiving concomitant therapy
with sedatives, hypnotics or other psychoactive drugs because of the potential for
additive or synergistic CNS effects.
• Patients should be advised of the negative effects on memory and to report any
mental or behavioural changes that occur after using marihuana.
7.2 Dependence and withdrawal
Tolerance, psychological and physical dependence may occur with prolonged use of
marihuana. Tolerance to cardiovascular effects occurs quickly, but the dependence is
slower to develop and appears more likely with higher, more frequent dosing.
7.3 Special populations
Marihuana should be used with caution in pregnant, pediatric and elderly patients,
because there is insufficient knowledge about its use in these patient populations and the
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potential for harm is likely to outweigh benefits (see Warnings, Pregnancy and
Lactation).
7.4 Drug interactions
THC and CBD are metabolized by the cytochrome P450 system and in vitro human
microsomal studies have suggested a potential for interaction with other drugs. CBD has
been shown to inhibit formation of THC metabolites catalyzed by CYP 3A with less
effect on CYP 2C9. For this reason there is concern that in patients undergoing multiple
drug therapy, such as treatment of AIDS or cancer, clinically significant drug interactions
might occur. However, both with dronabinol and smoked marihuana clinically
significant interactions have not been detected. Protein binding is another possible source
of interaction and patients exposed to marihuana should be monitored for a change in
dosing requirements if they are taking other drugs that are highly protein-bound.
7.5 Drug screening tests
Because of the long half-life of elimination of cannabinoids and their metabolites, drug
screening tests can be positive long after using marihuana (weeks with some tests).
8.0 Adverse Effects
This section includes known cannabis-related effects (e.g., cardiac) as well as effects related to
smoking (e.g., respiratory).
8.1 Carcinogenesis, mutagenesis and respiratory tract
The only epidemiological study in relatively young health maintenance organization
(HMO) clients found an increased number of men with prostate cancer in smokers of
cannabis and other non-tobacco materials. In this study, limited by the demographics of
the HMO clientele and the low marihuana exposures, there were no other associations
found between marihuana use and other cancers (Sidney, et al., 1997). A case control
study (Zhang, et al., 1999) suggested that marihuana use may increase the risk of head
and neck cancer with a strong dose-response pattern. The risk was increased 36-fold in
those using both marihuana and tobacco compared to non-smoking controls. There has
also been a rise in the number of cancers of the respiratory and digestive systems that are
rare in young patients and are attributed to marihuana smoking (Hyman, 1999; Hall, et
al., 1998). In addition there are many cellular and molecular studies that provide strong
evidence that smoked marihuana is carcinogenic (National Academy of Sciences, 1999, p
3.41).
Epidemiological studies have found mild pulmonary function changes in heavy cannabis
smokers, including reduction of forced expiratory volume in 1 second (FEV1), increase in
airway resistance and decrease in airway conductance (Bloom, et al., 1987; Roth et al.,
1998; Tashkin, et al., 1987). Heavy chronic smokers presented with symptoms of
bronchitis, including wheezing, production of phlegm and chronic cough and it may be a
risk factor for chronic obstructive pulmonary disease in later life (Hall, et al., 1998;
Taylor, et al., 2002). All changes were most evident in heavy chronic users, defined as
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those who smoked more than 3 joints per day for 25 years (Sidney et al., 1997; Tashkin,
1999). The effects on the respiratory tract defence system may increase the risk of
infection in chronic users (Denning, 1991). Thus although additional epidemiological
studies are required to determine the potential causal relationship between marihuana use
and the development of respiratory infection and/or cancer, evidence is mounting that
habitual smoking of marihuana has a number of adverse effects on the respiratory and
immune systems (see below) that may be clinically relevant (Tashkin, et al., 2002).
8.2 Immune system
The effects of marihuana smoking on the immune system are inconclusive. Among
patients suffering from AIDS, the increased mortality and reports of opportunistic
bacterial and fungal infections associated with marihuana use cause concern. Reviews
suggest (Cabral, 2001; Klein, 2001) that such patients may be exposed to more pathogens
or that the immune system is suppressed by marihuana (National Academy of Sciences,
1999, p 3.39).
8.3 Reproductive and endocrine systems
Results of human epidemiological studies have been conflicting; some report reduced
birth weight (Zuckerman, et al., 1989) and others no effect on birth weight (Shiono, et al.,
1995) among women who smoked cannabis during pregnancy. There appears to be some
long-term effects on development of children born to mothers who used marihuana
during pregnancy. Two longitudinal investigations over 20 years (Fried, 2002),
confirmed by a third (Richardson, et al., 2002), suggest that such in utero exposure
impacts negatively on attentional behaviour and visual analysis/hypothesis testing but not
on standardized derived IQ scores. In later years these behavioural effects have a negative
influence on aspects of executive function. Also, frequent maternal cannabis use may be
a weak risk factor for sudden infant death syndrome (SIDS) (Scragg, et al., 2001).
There is little information concerning transfer of cannabinoids and their metabolites in
human milk (Chao, et al., 1976; Perez-Reyes, et al., 1982). However, in habitual maternal
users of marihuana the above influences in development and behaviour would also be
relevant. In a case-control study (Astley, et al., 1990), exposure to marihuana from the
mother’s milk, during the first month postpartum, appeared to be associated with a
decrease in infant motor development at one year of age.
8.4 Cardiovascular effects
The most consistent acute physiological effect of smoking marihuana is dose-related
tachycardia (Trouve, et al., 1999). While cardiovascular changes have not usually been a
problem for healthy young users, the tachycardia induced by cannabis smoking may be
problematic to those already suffering from cardiac disorders or angina (National
Academy of Sciences 1999 p 3.44). It was found that inhalation of cannabis smoke
reduces the amount of exercise required to cause an attack by 50% (Aronow, et al.,
1974). Recently, marihuana has been associated with an increased relative risk of
nonfatal myocardial infarction in the first hour following smoking (Mittleman, et al.,
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2001). This may be due to increasing myocardial oxygen demand from the increase in
heart rate following cannabis use. However, other drug use could confound reports
(Hollister, 1998).
Cannabis is known to cause postural hypotension immediately after smoking (Merritt, et
al., 1982). It also causes peripheral vasodilatation, which can impact on body
temperature perception and is involved in characteristic conjunctival reddening. The
mechanisms for those effects on the autonomic nervous system are not understood
(National Academy of Sciences, 1999p 3.44).
Chronic marihuana smoking appears to induce tolerance to the cardiac accelerating
effect. In fact, after about 8 days of constant dosing with equivalent of 10 mg of THC per
day (equivalent to 100 mg of marihuana containing 10% THC), bradycardia with
hypotension (decrease in supine blood pressure) was observed (Chesher, et al., 1999).
THC and smoked marihuana poses health risks to people with cardiovascular disease
because of the resulting increased cardiac work, increased catecholamine levels,
carboxyhemoglobin and postural hypotension (Trouve, et al., 1999; Jones, 2002; Sidney,
2002).
AIDS patients may be at risk of cardiovascular effects from interactions of their antiviral
drugs, such as ritonavir, which has been shown to cause plasma lipid abnormalities that
increase risk of cardiovascular events (Purnell, et al., 2000). As this patient population
may use cannabis for weight gain or other amelioration of symptoms, the additional
cardiovascular effects from the marihuana should be considered in risk assessment.
8.5 Central nervous system
According to the Marinol® (oral THC) product monograph, the most commonly
encountered CNS events in controlled clinical trials were drowsiness, dizziness and
transient impairment of sensory and perceptual functions (Compendium of
Pharmaceuticals and Specialties, 2003). Psychotropic effects were observed in most
patients; these included the “high” (easy laughing, elation, heightened awareness) in 24%
of the THC group. Five percent of patients in the THC group and none in the placebo
group experienced weakness or sluggishness, hallucinations, memory lapse and ataxia.
Other events reported were dry mouth, paresthesias, visual distortions (all at 3%),
paranoia, depersonalization (each 2%) and disorientation with confusion (1%).
8.5.1 Cognition
Marihuana impairs cognition involving short-term memory, attention and
concentration. The digit span task has been used to estimate the effects of
cannabis on recent memory, but results have been inconsistent. Differences may
be due to the dosage used (% THC), the smoking procedure or whether the digit
span task assesses forward or backward recall (Heishman, et al., 1989).
Methodological issues have contributed to difficulties in assessing the effects of
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chronic use (Pope Jr, et al., 1995). However, overall, studies suggest that chronic
users of marihuana suffer varying degrees of cognitive impairment that can be
long lasting (Hollister, 1998). Cannabis intoxication significantly impairs the
ability to learn and recall word lists or short stories. Recent studies comparing 51
long-term marihuana smokers (mean age 24 years) with nonsmoking and shortterm
user controls have confirmed that deficits in attention and memory occur
with heavy cannabis use, and that these continue beyond the period of intoxication
and are cumulative with longer periods of use (Solowij, et al., 2002).
8.5.2 Psychomotor performance
Cannabis exposure impairs psychomotor performance and patients must be
warned not to drive after smoking marihuana. The period of time to abstain from
operating complex machinery depends on the dose, the disease being treated and
the patient’s age and gender. Individuals are affected differently by prolonged
exposure to marihuana and there is some evidence of greater effects on
adolescents. Discrimination of marihuana’s effects from the normal effects of
aging on cognition and performance has not been fully researched (Solowij, et al.,
1999). Performance impairment appears to be less among people who are heavy
users of cannabis compared to occasional users (National Academy of Sciences,
1999, p 3.8). It has been suggested that, unlike alcohol, cannabis users are aware
of their level of intoxication and compensate to become hyper-cautious, resulting
in decrease of speed, decreased frequency of overtaking as well as an increase in
following distance (Gieringer, 1988). Others disagree with this assertion
(Moskowitz, 1985).
8.5.3 Behavioural effects
8.5.3.1 Psychiatric disorders
It is noted in the Marinol® (dronabinol, oral THC) product monograph
(Compendium of Pharmaceutical and Specialties, 2003) that this drug should
be used with caution and careful psychiatric monitoring in patients with mania,
depression or schizophrenia because Marinol® may exacerbate these illnesses.
This reflects the IOM report (National Academy of Sciences, 1999, p 3.23,
3.29) and also the knowledge that psychiatric disorders are associated with
substance dependence and are risk factors for drug abuse.
Acute toxic reactions such as nausea, anxiety, paranoia and disorientation often
occur in naïve marihuana smokers but are uncommon in regular users (Noyes
Jr, et al., 1975). The triggering of psychosis by marihuana has not been
definitively established, but it appears that cannabis is frequently used by
psychotic patients (Hollister, 1998). Heavy cannabis smoking, and even lighter
use in susceptible individuals, can produce an acute psychosis including
anxiety, agitation, amnesia, delusions, hallucinations and hypomanic symptoms
(Australian Commonwealth Government, Department of Health and Ageing,
1994).
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8.5.3.2 Schizophrenia
Self-reported use of cannabis in childhood has been associated with an
increased risk of developing schizophrenia and this risk was related to
frequency of marihuana exposure (Zammit, et al, 2002). A cohort study of
over 1000 children, followed to age 26 from birth, showed a three-fold
increased risk of psychotic disorders in cannabis users and suggested that
cannabis exposure among psychologically vulnerable adolescents should be
strongly discouraged (Arseneault, 2002, p 1212-1213). Heavy marihuana use
can aggravate symptoms and cause more relapses (Alleback, 1999; National
Academy of Sciences, 1999, p 3.29). Follow-up studies confirm the increased
risk of poor prognosis in psychosis for those using marihuana (Caspari, 1999;
van Os, et al., 2002). Individuals with schizophrenia or with a family history of
this disorder are likely to be at greater risk of suffering adverse psychiatric
effects from marihuana (Johns, 2001).
8.5.3.3 Amotivational syndrome
This syndrome is used to describe young people who show little interest in
school, work or other goal-oriented activity as well as withdrawing from social
activities. While it is an ill-defined condition, this is a common feature of
chronic intoxication with many different psychoactive drugs and when the
chronic intoxication is treated or “cured” the behaviour improves. There is no
convincing evidence to show a casual relationship between marihuana smoking
and such behavioural characteristics (National Academy of Sciences, 1999, p
3.31).
8.5.3.4 Dependence and tolerance
Tolerance to most of the effects of marihuana can develop after a few doses
and it also disappears rapidly (National Academy of Sciences, 1999, p 3.8). In
normal subjects tolerance develops to mood, intraocular pressure, EEG
changes, psychomotor performance, antiemetic effects (Jones, et al., 1976) as
well as to cardiovascular effects (Compton, et al., 1990). The dynamics of
tolerance differs for different effects (Pertwee, 1991). Tolerance to some of the
cannabis effects develops both when THC is administered orally (30 mg four
times a day) and when a roughly equivalent dose was given by smoking
(Haney, et al., 1999) (3.1% cigarette, 5 x 10 second puffs). Both groups
became tolerant to the “high”, but there was no diminution of the appetite
stimulating effect from either route of administration.
There is evidence that cannabis dependence occurs with chronic heavy
recreational use. Some individuals report problems in controlling such use
despite resulting personal difficulties (Australian Commonwealth Government,
Department of Health and Ageing, 1994; Stephens, et al., 1993). Dependence is
unlikely to be problematic when cannabis is used therapeutically although
-22-
withdrawal effects may be uncomfortable (British Medical Association, 1997,
p 67). These include restlessness, anxiety, mild agitation, irritability, tremor,
insomnia and EEG/ sleep disturbance, nausea, diarrhea and cramping.
Withdrawal has been studied in subjects, including adolescents who smoked
marihuana recreationally (Crowley, et al., 1998). These effects are considered
mild compared to the physical “syndromes” experienced with alcohol or opiate
withdrawal (Jones, et al., 1976) and the pattern of withdrawal is less clear than
for these drugs (Smith, 2002).
9.0 Overdose/Toxicity
The LD50 is estimated to be 20,000 to 40,000 times the amount in one marihuana cigarette
(approximately 1500 lb) smoked in a period of 15 minutes (Annas, 1997). Marihuana is not a
completely benign agent and it has a variety of physiological effects, but aside from the hazards
consequent to smoking, the adverse effects are within the range tolerated for other medications
(National Academy of Sciences, 1999, p3.49). Cannabis often produces unwanted effects,
typically dizziness, sedation, intoxication, clumsiness, dry mouth, lowered blood pressure or
increased heart rate (Robson, 2001). The rare acute complications (such as panic attacks,
psychosis, convulsions, etc.) that present to the Emergency Department can be managed with
conservative measures (Seldon, et al., 1990). As is stated for overdose with Marinol®
(Compendium of Pharmaceuticals and Specialties, 2003), signs and symptoms with smoked
marihuana are an extension of the psychotomimetic and physiologic effects of THC. If disturbing
psychiatric symptoms occur at the prescribed dosage, the patient should be closely observed in a
quiet environment and supportive measures, including reassurance, should be used.
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