Marihuana Flashcards
Cannabis Sativa
Plant that is dried and smoked as marihuana
Marihuana
General Term to describe dried plant products of the cannabis plant, contains 0.5-11% THC
THC(Tetrahydrocannabinol)
Main active ingredient in marihuana and dronabinol
Cannabinoid
Chemical class of terpines found only in cannabis plant
Hashish
The dried sticky concentrated resin from the plant that contains 3.6% THC but can be as high as 28 %
Sinsemilla
The buds and flowering tops of female plants, average 7.5 THC but up to 24%
Ganja
From India, Dried tops of female plants, varied concentrations
Bhang
Weakest form, made from remainder of plant, ground into powder
Blunt
Tobacco pipe that has been emptied of tobacco and filled with marihuana
- Can have synergistic effects with nicotine
- Tobacco paper allows it to burn slower
- Looks more commonplace and acceptable
- Brings more of the smoke to the user
Cannabis vs Tobacco
Cannabis use has increased
Tobacco use decreased
Potency Marihuana
THC and CBD content increases over the years
Cannabinol
Metabolite of THC, and is a weak agonist to the CB receptor
Cannabidiol (CBD)
- Not psychoactive
- 5-HT agonist
- Contributes to anxiolytic effects
- Potent anticancer properties such as promoting cell death and decreasing cell migration and invasion
- Low affinity for CB1 but acts as an indirect agonist
- Potentiates THC effects by upregulating the number of CB1 receptors or through another CB1 mechanism
- May increase duration of effect of THC by inhibiting Cytochrome P-450 and 2C enzymes
C indica vs C sativa
- Indica has a higher CBD:THC ratio that is 4-5 times higher than sativa
Higher ratios tend to cause less anxiety as CBD is a cannabinoid receptor antagonist
Synthetic THC has almost no levels of CBD or CBN which explains differential effects
THC distribution in joint
20-40% Mainstream
40-50% Sidestream
20-30% Destroyed by burning
10-15% Cigarette Butt
Absorption
Plasma levels peak quickly after smoking
Rapid absorption into brain immediately after smoking and then redistributed in 30 minutes
Oral absorption is slow and incomplete
First pass effect causes more production of metabolites
Metabolism
Primary metabolite is 11-OH-THC, which is active and more potent
Converted to THC-OOH and is screened in urine
Highly lipid soluble and stored in fat
THC half life is 20-30 hours, but metabolite half life is 30-60 hours or more!
Time Course of Effects
Subjective effects peak after 10-30 minutes
Mild hallucinogenic with some depressant and disinhibiting effects
Renders person into highly suggestible state
Physiological Effects
Increased heart rate- interferes with reflexes that maintain cardiovascular homeostasis Increased workload to the heart Decreased bloodflow to the brain Dry mouth and throat No consistent effect on blood pressure Reddening of the eyes
Effects of Recreational Marihuana Use
Cognitive impairments- especially in those who smoked before 16
Deficits in processing speed, attention, memory and executive function
Higher impulsivity
Altered Brain Structure- Greatest in early users, lower white matter integrity associated with higher impulsivity
Early onset- smoked more marihuana more frequently
Experienced Users: Low Doses
High
i. initially stimulating with mild tension
ii. Pleasant feeling of well being
iii. Introspective and tranquil
Experienced Users: Moderate Doses
Induces sedation and sleep Reduces the amount of REM sleep Sense of well being and dreamy state Perceptions are distorted Increased sexual thoughts- explains why people report better sexual experience Can be suppressed more easily than ethanol Slowed time perception Short term memory impaired Analgesia
Experienced Users: High Doses
Paranoid Ideation and panic
Psychomotor effects
Tracking a moving object harder due to inability to sustain attention and concentration
- Complex tasks involving memory and cognitive function are most sensitive
Effects can linger for 24 hours
Simulated Flyers: Placebo vs 20 mg THC- THC subjects had more significant errors
Receptors
CB1 binding in CNS
CB2 binding in the peripheral system
Binding sites the highest in frontal cortex, basal ganglia, cerebellum, and hippocampus
Located within ascending dopamine pathway, increase DA in mesolimbic area
- Most prevalent receptor in the brain
- Receptor sites are coupled to Guanine nucleotide binding regulatory proteins (G-coupled)
Metabolic Tolerance
None
Pharmacologic Tolerance
Cannabinoid induced down regulation and desensitization of CB receptors
Rapid receptor internalization following agonist binding and receptor activation
- Marihuana is a weak agonist, so uninportant
Reverse Tolerance
Experienced users anticipate and therefore enhance symptoms
Physical Dependence
Human dosing every 4 hours for 10-20 days Withdrawal signs peak at 8 hours Symptoms irritability restlessness nausea vomiting sleep disturbances agression loss of appetite Signs diminish after 3 days Readministering THC relieves symptoms
Marihuana vs Tobacco
Products of smoke Decreases testosterone level and reduces the sperm count lower birth weights panic reactions tachycardia Impairs function of immune system
Passive Inhalation
Being in a room and inhaling secondhand smoke
Used in a defense in court
Need to be in a condensed room for 20 minutes before it shows up in urine test
Impaired Driving
4000 more potent than alcohol in reducing performance
Brain Damage
- No cases of cerebral atrophy due to chronic smoking have been found
Poor performance in radial arm maze due to permanent changes in hippocampal neurons
primate studies showed no permanent neuronal changes
Drug Interactions
Used in combination with other drugs
Slows absorption of alcohol- prolongs it effects
Speeds absorption of cocaine, leads to significant increases in heart rate and panic
May be used to potentiate effects of other drugs like cocaine
Dronabinol
FDA Approved
Used for chemotherapy
Appetite stimulation
Side effects: Dizzy, warm feeling, stomach pain, memory loss
Efficacy is modest compared to other drugs without psychoactive side effects
Nabilone
Synthetic Cannabinoid approved to treat nausea and vomiting, adjunct for treating neuropathic pain
Approved for use in wasting syndrome
Suppress activity in vomiting cemter
Canabidiol (Epidiolex)
Natural chemical in cannabis
Pure extract has unique pharmacology
Accounts for 40% of cannabinoids in marihuana
FDA orphan status for treating dravet syndrome- childhood epilepsy
Low affinity for CB1 and CB2 receptors
Acts as a direct antagonist to the receptor antagonist
Potentiate THC by increasing CB1 receptor density
Inverse agonist of CB2 receptor
Charlotte’s Web
Variant in marihuana that is high in CBD, low in THC
Not popular among older users because it lacks the psychoactive effects
Appears to be effective in reducing childhood seizures, anxiety, depression
Endocannabinoid System- Medical Applications
Target for wasting syndrome, pain, wasting syndrome and obesity
- Chronic overstimulation of EC –> stimulation in CB1 receptor–> Increase in appetite
- CB1 antagonists can counteract this
Rimonaband
Selective CB1 Inverse agonist
- Treated obesity
Removed for suicidal side effects
Synthetic Cannabis
Herbal product marketed as natural incense
Thought to contain a mixture of legal herbs, but labs found synthetic cannabinoids
Cannabinoids not found but metabolites found in urine
- Produces high tolerance and high dependence
Increased risk for psychotic reactions
Chemical composition still unknown
Legalization
Schedule I Cannabis, but oral THC is Schedule II
Decriminalization now sought
Perceived Risk vs Use
Inversely Related
