MARIJUANA AS MEDICINE

I. Introduction* Knowledge of the medicinal benefits of Cannabis may have only been validated

by science in recent years, but the plant’s origins in medicine stem from as long as 2700 years ago.

* Shen Nung, the “father of medicine”, wrote of the Cannabis plant’s ability to relieve stomach pains, menstrual cramps, muscle soreness, headaches, and more.

* Today, science has not only confirmed many of Shen Nung’s findings, but has discovered a multitude of other ailments and diseases that the plant could help.

* Critics fear the “harmful effects of marijuana”, and as such, create socio-political concepts such as the gateway drug theory in the name of science when there is no credible research to prove such things.

* The LD50 is the dose of a chemical required to kill ½ of the subjects given the substance. These tests are typically performed in rats.

Chemical LD50 mg/kg Body WeightTHC 1270Caffeine 127Acetaminophen 338Naproxen sodium (Ibuprofen) 400Morphine HCl 335Codeine 427

* A search on Entrez/PubMed returns over 18,000 results for the keywords marijuana and Cannabis. When politicians say there is not enough evidence to support medical marijuana, they are biased, or ill-informed by their scientific panel.

* In fairness, it should be recognized there is still a vast wealth of information to be learned from the plant. Most research in the scientific community has been performed with low quality Cannabis strains (NOTE: not all).

* Scientists have discovered the main properties of THC and CBD, the two predominant cannabinoids in marijuana. However, these effects are mitigated by other chemical families, making a predictable breeding regime for medicinal chemical compounds second only to understanding how all these chemicals synergize to create each strains effects.Consider: About 1600 strains + 71 different cannabinoids + over 100

terpenoids + 20 flavones + sugars, fatty acids, etc, with each strain having greater or lesser concentrations of one chemical and not the other!

* Pharmaceutical companies would never attempt to begin trials with whole plant material because of the amount of chemicals involved. FDA requirements involve submitting all available data on drug interactions. Imagine writing

how molecule 1-200 each affect the body, then how 1 and 2 work together, then 1, 2, and 3, and so on. This would take an infinite amount of time.

* GW Pharmaceuticals patents Sativex TM , a spray composed primarily of THC and CBD, but claims to also include “whole plant extracts”. On the GW website they state “We believe very strongly that many of the advantages of using the whole plant come from the inclusion of other components of cannabis [marijuana]," not just THC. "In the cannabis plant, it appears that some of the components added together give better effect. Some components seem to work to counteract some of the side effects of others, and the whole plant is generally well tolerated by humans”.

* The need for selective breeding regimes for medical strains is soon going to be yet another battle patients will have to fight to keep their medicine available in a natural form of which they can grow themselves, and not in pill form that will be patented and sold entirely for profit.

II. Marijuana and Pain:* 76% of medical marijuana users take this medicine for pain* There are many different types of pain, each associated with specific

biochemical pathways in the body. These can include neuropathic, inflammatory, acute, chronic, visceral, etc.

Hyperalgesia – enhancement of pain sensitivityAllodynia – pain arising from non-noxious stimuliAnalgesia – pain relief* Cannabinoids serve as antihyperalgesics, prevent allodynia, and serve as

analgesics.* A review article briefly describes the effects of cannabinoids in nociception =

pain.1. Suppression of behavioral and neurophysiological responses to all types of nociceptive stimuli tested2. High potency (effects observed at ~ 75 mg/kg).

3. High efficacy (typically > 80% reduction in response to noxious stimulation)

4. Effects CB1 receptor-mediated.5. Suppression of both wide-dynamic range neurons (respond to

touch and pain) and nociceptive specific neurons (respond to pain only).

6. No suppression of low-threshold mechanoreceptive neurons (respond to

touch only).7. Spinal and thalamic neurons affected similarly.

8. Behavioral analgesic time course and potency correlated with neuronal

suppression of nociceptive stimulus-evoked activity.9. Suppression of windup (a model of central sensitization that

is observed in chronic pain).

10. Suppression of increased spontaneous firing following injection of complete

Freund’s adjuvant, an inflammatory agent.

* Walker, JM and SM Huang. “ Cannabinoid Analgesia”. Pharmacology & Therapeutics 95(2002).

* Marijuana inhibits pain in a similar fashion to opiate pain medicines, but with important differences.

“The effects of long-term exposure to cannabinoids have been extensively investigated and the consequences in terms of tolerance, sensitization and

dependence are now well known” (Tanda and Goldberg,2003). “Contrary to opioids, a clear-cut abstinence syndrome has been rarely reported for Cannabis, presumably

because of the long half-life of cannabinoids, which precludes the emergence of abrupt abstinence symptoms” (Compton et al.,1990, 1996; Smith, 2002). “Somatic

signs of spontaneouswithdrawal from chronic D9-THC are difficult to observe in rodents, pigeons, dogs and

monkeys, even at high cannabinoid doses “(Diana et al., 1998; Aceto et al.,2001)

* Addiction and the concept of Down Regulation: When individuals abuse opiate based drugs (morphine, heroin, oxycotin), their bodies will slowly adapt by doing one of two things:

1. Reduce production of the naturally occurring substances (endorphins)2. Reduce the number of receptors that recognize these chemicals and thus create

a response in the cell/tissue.3. Our body’s opiates are produced in specific brain regions and cell types, which

eventually shrink, stop working, and sometimes die, from continual outside application of synthetic opiates. This is why addiction is so great in opiates.

* There are mixed reviews on the addictive potential of marijuana. Contradictory research exists between whether down regulation occurs in the cannabinoid system. Furthermore, several researchers have proposed that cannabinoid pain relief, as well as other effects from the plant, can be activated by non receptor mechanisms, and other receptors besides CB1 and CB2

* It is important to realize that ANYTHING can be addicting:A) Sex, chocolate, gambling, racing, and many other behaviors that don’t involve drugs have been characterized as addictive in some people, characterized by increased dopamine and/or serotonin.B) It is important that we, as medical marijuana patients, carry ourselves appropriately in society, as evidence to the untruthfulness of the stereotypes our government has made on “pot heads”.

* Cannabinoids act on receptors in the Central Nervous System, both in the spinal cord and brain, in many of the same areas as opiates. However, additional cannabinoid receptors are found in the immune system.A) The immune system produces many chemicals involved in inflammation

and disease. Inflammation on its own can cause pain, but also potentiate neuropathic and visceral (organ) pain.

B) The immune system may protect us, but it is a double-edged sword, in that it also harms us as well.

C) Not only do cannabinoids inhibit inflammatory pain, but they also reduce inflammation in many complex chemical interactions.1. CBG and CBC, the other two main cannabinoids besides THC and CBD,

block the production of a large class of inflammatory molecules associated with muscle and organs

2. Quercitin, a flavanoid, was found to be anticarcinogenic and considered to be a powerful prevention tool for inflammatory disease (CHP. 7 Medical Uses of Cannabis and Cannabinoids, Geoffrey Guy, 2004).

3. THC has 20x the anti-inflammatory activity of acetylsalicylic acid, and twice that of hydrocortisone (Evans, 1991).

4. β-caryophyllene, the most common sesquiterpenoid in cannabis, demonstrates anti-inflammatory effects (Mediavilla, 1997)

5. TNF-α, a chemical produced by immune cells, induces and maintains inflammation. It is associated with rheumatoid arthritis and MS. THC reduces TNFα.

6. Cannflavin A is a flavone unique to cannabis, found to be an inhibitor of PGE2, 30x more potent than aspirin in human rheumatoid synovial cells, also shown to inhibit cyclooxygenase (COX) and lipoxygenase more potently than THC (Evans et al, 1987).

7. Apigenin is another abundant flavanoid in marijuana with anti-inflammatory effects. Furthermore, it has powerful antioxidant properties important in the treatment of MS.

8. CBD has anti-inflammatory efficacy at doses lower than aspirin.

III. Conclusions* The cannabinoids are less toxic than over-the-counter pain relievers, as well as

prescription pain medicines.* Cannabinoids produce the main effects of smoked or eaten marijuana, but are

mitigated by the activities of terpenoids and flavanoids. For this reason, pharmaceutical companies will have a difficult and expensive task in trying to make a pill that can be as safe and effective as marijuana.

* Marijuana acts in a similar fashion in the body to opiates, but has proven to be far less addicting than conventional pain medicines.

* Not only is cannabis more effective in treatment of some types of neuropathic pain, but also has the added benefit of potent anti-inflammatory molecules

that inhibit inflammation from a wide spectrum of diseases and disorders.