There are 2,500 to 3,500 species of flowering plants Various uses around the world and in history included:

• Medicinal value
• Poisons
• Psychoactive
• Religious ceremonies
• Magic
• Initiation into puberty
• Escape reality
• Fashionable
• Social pleasure

Psychoactive substances are found in various parts of the plant:

• Resin
• Fleshy fruit
• Stems
• Leaves
• Seeds
• Roots

Psychoactive substances can be introduced into the body by:

• Eating
• Drinking (teas)
• Smoking
• Inhalation
• Ointments
• Enemas

The plant contains two parts:

• Cannabis
• Humulus (hop plant)

Resin used as a preservative and as a natural flavor in beer

Marijuana is also known as cannabis, hashish, hemp and marijuana. It is a Source of:

• Strong fiber for rope and paper
• Nutritious fruit
• Industrial oil
• Medicine

Cannabis Sativa is a fiber plant. Cannabis Indica is a resin plant. There are Male and female plants Female plants are better resin producers.

Resin contains:

• Hallucinogenic compounds called cannabinoids
• Delta-1 Tetrahydrocannabinol, also known aso Delta-1-THC
• THC a Major active compound in the cannabis plant

How is it used?

Leaves and flowering tips are dried

• Smoked
• Consumed as tea
• Mixed into food

Resin from flowering heads:

• Smoked
• Mixed with tobacco
• Alcohol extract (cannabis oil) is mixed with tobacco and smoked

Marijuana had been used in Folk Medicine in Europe:

• Germany - to treat seizures, aid in childbirth
• Poland - for toothache (seeds put on hot stones and vapors inhaled)
• Czechoslovakia - to treat fever
• Russia - to treat jaundice
• Serbia - as an aphrodisiac

60 cannabinoids have been isolated from the hemp plant and there are naturally occurring cannabinoids in most species called endocannabinoids, in a similar fashion as endorphins (opiates) have been found.

There are two main receptors for cannabinoids in humans

• CB1(in brain) if stimulated produces Euphoria, Impaired short term memory and sense of time
• CB2 (in spleen, peripheral sites) if stimulated produces Immunosuppressant activity/Not psychoactive

Marijuana - Not a single drug but a complex mixture of over 400 chemicals

• Dried flowering tops and leaves of the plant have THC concentration 0.5% - 5% in the past, now up to 20 – 25%
• Hashish – dried cannabis resin and flowerso THC concentration, 2 - 8% or higher
• Hash oil – extraction of THC from hashish with an organic solvento THC concentration 15 - 50%

Routes of marijuana administration:

• Joints Average is 500 mg of marijuana inside of rolling papers: 20% - 50% of the THC makes it into the bloodstream
• Blunts (marijuana in hollowed out cigar)6 times the amount of marijuana: 20% of the THC makes it into the bloodstream
• Pipes Stone, ceramic or glass: 50% of the THC makes it into the bloodstream
• Water pipes/ Bongs – most efficient 90% of the THC makes it into the bloodstream

Typical joint has 0.5 - 1 gram cannabis

• THC concentration 5 - 150mg
• 20 to 70% of THC is delivered in the smoke 2 - 3 mg THC can produce a brief high
• Lipid soluble so deposited into fat tissue
• 80 probable biologically inactive metabolites of THC
• 11-hydroxy - THC is the primary active metabolite
• THC is eliminated in the feces and 33% in the urine

THC mechanism of action:
Peripheral and central effect
Low dose: Mixture of depression and stimulation
High dose:CNS depression

Oral use:

• Psychoactive effects slowed to about one hour
• Absorption is erratic
• High is less intense, but lasts longer than if smoked

IV use:

• Water insoluble so cannot be injected

SMOKING:

• three cannabis joints will cause you to inhale the same amount of toxic chemicals as a whole packet of cigarettes.

Desired effects of the user:

• Sense of well being
• Relaxation
• Euphoria
• Modified level of consciousness
• Altered perceptions
• Intensified sensory experiences
• Altered time sense
• Sexual disinhibition

Marijuana consumption has the following effects:

• Psychomotor effects
• Behavioral effects
• Cognitive effects

Psychomotor effects:

• Object distance distortion
• Object outlines distorted
• Inability to make rapid judgment
• Slowed reaction time
• Impaired tracking behavior
• Slowed time perception

All are dose-related

Behavioral effects:

• “Amotivational Syndrome” - Little scientific evidence for the existence of this

Tolerance to marijuana was supposed to be a manifestation of desensitization of brain cells, and in addition to contributing to the supposed dependence liability this desensitization of brain cells was supposed to create an amotivational syndrome characterized by apathy and inactivity. The hypothesis was that this desensitization would impede normal brain operations and render individuals somewhat sluggish and unmotivated. The hypothesis has been challenged on both behavioral and pharmacological grounds.

• Increased focus on taste
• Increased appetite (street slang - ”munchies”)
• Dry mouth

Cognitive effects may be due to a reduction in blood flow to the brain - seen even 30 days after last use in heavy smokers. (A study in February 2005 found increase blood flow – indicative of narrowed arteries; much like those seen in hypertension.)o Impaired short-term memory, Especially verbal IQ

• Impaired attention
• Impaired integration of complex information

Chronic marijuana user – “College was the best 6 years of my life.”/ Evidence of brain damage is equivocal in the chronic user

British Medical Journal 2006:

• 2.9% prevalence of cannabis in the driving population2.5% of fatal crashes
• 2.7% prevalence of alcohol in a similar population28.6% of fatal crashes

Addiction?

9% of those who ever used become dependent; Dependence associated with gradual increase in use. No scientific evidence that it is a “gateway” drug

Withdrawal difficult to demonstrate: 10 hour onset and 5 day duration

• Anxiety
• Mental clouding
• Insomnia
• Anorexia
• Irritability
• Tremor
• Depression
• Headache
• Craving

Very similar to nicotine withdrawal, except there is weight loss in marijuana and weight gain in nicotine withdrawal.

71% of marijuana users relapse to marijuana use within 6 months after achieving initial 2 weeks of abstinence

Mental health issues have been seen to co-occur in users.

• Transient panic and anxiety
• Depersonalization
• Bizarre behavior
• Delusions
• Hallucinations
• Acute mania
• Acute paranoia
• Depression (possibly)
• Psychosis (possibly)
• Aggression

Depression? Mixed evidence from a variety of research studies

Psychosis? Inconclusive research; 2005 research in Biological Psychiatry described a common gene that makes cannabis five times more likely to trigger schizophrenia; 25% of the population have this gene15% of this group are likely to develop psychotic conditions if exposed to cannabis early in life.

Arseneault et al concluded that heavy cannabis use (regular and long-term) contributes as one of many factors, forming a “causal constellation” of factors including psychological vulnerability and genetics.

The self medication hypothesis has been discounted

Aggression: Using is associated with decrease aggression unless taken in periods of high stress

CARDIOVASCULAR SYSTEM: Increase heart rate

• Marijuana alone 29-36 beat/min increase
• Marijuana & cocaine 49 beat/min increase
• Decrease blood pressure
• Increase myocardial infarction risk

PULMONARY Tracheitis (inflammation of the trachea)

3 cannabis cigarettes = 20 tobacco cigarettes with significantly more carcinogens

MISCELLANEOUS:

• Questionable effect on fetus –probably due to polypharmacy (use of multiple medications)
• Decrease effectiveness of SSRI anti-depressants
• Increase drowsiness if used with tricyclic antidepressants
• Heavy sedation if used with benzodiazepines
• Alcohol toxicity causes vomiting due to an increase in acetaldehyde. Marijuana anti-emetic effect can suppress the chemo-trigger point and lead to severe alcohol toxicity
• Multiple cavities in youth?Dry mouth and eating sweets?

Lethal doses of marijuana are not known

Medical ses

• Difficult to determine doses if smoked
• Significant adverse effects associated with any smoked medication, especially if to be used in a hospital setting
• Relieve nausea Most trials used dronabinol and not smoked marijuana; however, in trials that compared the two, dronabinol was more effective.

The U.S. Food and Drug Administration (FDA) has given the green light to Valeant Pharmaceuticals International to bring the synthetic cannabinoid drug nabilone (Cesamet) back to market after 17 years. Nabilone is also sold in Canada.

The drug, similar to the THC medication, Marinol, was originally marketed by Eli Lilly and Co. but withdrawn from the market in 1989. It is now approved by the FDA for treatment of vomiting and nausea caused by chemotherapy and is listed as a Schedule II controlled substance.

• Increase appetite: Dronabinol does appear to work; No controlled studies in smoked marijuana
• Smoked and oral form increased weight (fat not lean body mass)Annals 2003;
• Decrease muscle spasm Suggested for multiple sclerosis: only Anecdotal information
• Decrease intraocular (eye) pressureo Better preparations available for the control of intraocular pressure as seen in glaucoma
• Decrease chronic pain- also Anecdotal

NIDA study at University of Arizona (Dr.Malan)Compound am1241o Acts on CB2 receptorsPain relief without the central nervous system side effects such as sleepiness and anxiety

• Anticonvulsant First used in the 1940’s for the treatment of seizures/ Better therapeutic agents today; University of Saskatchewan (8/2004) showed one dose of THC in rats could decrease grand mal seizures, but multiple doses lead to an increase in convulsions.
• 2004 - Israeli soldiers suffering from combat stress were treated with cannabis to relieve their symptomso PTSD trials are ongoing
• August 2004 issue of Cancer Research article by Guzmano THC may inhibit genes that make protein, vascular endothelial growth factor (VEGF) This protein stimulates the growth of blood vessels in tumors
• Sativex Whole plant medicinal cannabis extract
• Produced by Bayer and GW pharmaceuticals and approved for use in Canada for multiple sclerosis and neuropathic pain (2005); Contains THC and nabidiolex, not delta - THC; Phase 3 trials in multiple sclerosis patients showed that sublingual spray was safe and effective for symptom relief
• Journal of Psychopharmocology: Marijuana may have a benefit in treating bipolar disorder Cannabidiol (a cannabinoid found in cannabis) has a calming effect; THC prevented severe highs and lows
• The main active ingredient in marijuana is more effective at blocking an enzyme that causes the brain damage common to Alzheimer’s disease than approved drugs already on the market, according to researchers from the Scripps Research Institute.o low doses of THC inhibits an enzyme that breaks down acetylcholine, needed for learning and memory.
• The drug also appears to prevent the formation of fibrils, which damage healthy brain tissue.
• Bowel study backs cannabis drugs – Gastroenterology 2005o People with inflammatory bowel disease had an abundant number of a type of cannabinoid receptors in their body.
• They believe this is part of the body’s attempt to dampen down the inflammation and that giving a drug that binds to these receptors could boost this.
• When people have Crohn’s disease or ulcerative colitis - collectively known as inflammatory bowel disease or IBD - their immune system goes into overdrive, producing inflammation in different areas of the digestive tract.

Overall problems of use:

• Mode of administration: No smoking in hospitals
• No standard dose of smoked marijuana
• Smoke is hazardous in and of itself
• Smoking may impair immune system response
• Difficulty concentrating on complex tasks
• Slowed reaction times
• Tolerance develops quickly
• Effect is 4 - 6 hrs
• Chronic bronchitis can develop
• Pharyngitis (inflammation of the pharynx) can develop
• Large airway obstruction can be seen
• Acute panic reactions can develop
• Acute paranoia can develop
• Heart rate increases 20 - 100% for 2 - 3 hrs
• Decreased blood pressure seen with use

Canada July 2003 the Canadian government started to deliver to physicians marijuana seeds in order to treat 582 approved patients – so that the patients can start to grow the plants themselves; A bag of 30 seeds will cost $20.

There are; however, some questions in relation to this:

• will US border patrol increase activity?
• Counter to the Canadian government’s policy of urging people to stop smoking;
• Fall 2004, pharmacies in British Columbia started to sell marijuana for medicinal purposes without a prescription; A pilot project of the national health service
• Strong criticism of the proposal has come from patients:cost is $110 an ounce and it is “lousy pot”, “tastes like lumber”

Netherlands: Government made medical marijuana legal in September 2003

Source: NY OASAS