Cannabis Flashcards
What is the emergent view of cannabis?
Only one lineage, produces phytocannabinoid chemotypes like THC and CBD
The experience you have is chemical-dependent
What is synthesized in the head of trichomes?
Phytocannabinoids, terpenes
What does cannabis extraction produce?
Resin for second generation cannabis products
How can cannabis be extracted?
Solvent or solventless extraction
Super-critical extration
What is the goal of cannabis extraction?
To obtain high purity or a single isolated compound
How do we calculate THC percentage?
% is mg per g (1/1000)
15% = 150 mg/1 g = 150/1000mg = 0.15
What types of chemicals are found in cannabis?
Psychoactive, non-psychoactive, synthetic
What form are most chemicals in the cannabis plant?
Their acid form
What is THC acid?
Psychoactive
What is CBD acid?
Anti-oxidant, anti-convulsant, anti-inflammatory, anti-anxiety, anti-psychotic, and neuro-protective
What does personalized cultivar selection do?
Tailor the therapeutic effect to the disease and individual
What are the forms of cannabis administration?
Inhalation, ingestion, oral-sub-lingual, topical
How do we optimize absorption?
THCA -> THC by heat or pressure
How is cannabis smoke compared to cigarette smoke?
Similar levels of tar, CO, acetaldehyde, acetone, benzene, toluene, benzopyrene, HCN
Poorer filtration of cannabis smoke, more irritation = toking and choking
Linked to increased risk of chronic cough, bronchitis, no link to lung cancer or COPD
What types of administration may reduce harmful components and irritation of smoking?
Water bongs
Dabs
What do you use to smoke cannabis?
Joints
Pipes
Bongs
Vaporizers
What is the effect of ingesting cannabis?
Slower onset of effect
Less predictability of action
More user control
Where is cannabis distributed?
Brain
Liver
THC is very fat-soluble and easily crosses the BBB
When do the peak effects of cannabis occur?
After 15-60 minutes
What is cannabis metabolized by?
Liver CYP450
Also metabolized in the lungs and stomach
Long half-life
How long does it take to metabolize cannabis?
2-12 hours
What is the first-pass metabolite of cannabis?
11-hydroxy-delta9-THC
How is cannabis excreted?
In the kidney
What are the endogenous CBR ligands?
Arachidonoyl ethanolamide (AEA)
2-arachidonoylglycerol (2-AG)
Where is CB1 expressed?
In the CNS (basal ganglia, cerebellum, hippocampus, cortex, amygdala)
Eyes
Pancreas
Liver
Skin
Uterus
Testes
Where is CB2 expressed?
Immune cells
Spleen Tonsils
What are the brain effects of cannabis intoxication?
Affected appetite, sex, and sleep
Inhibited memory encoding and retrieval
Impaired coordination
Enhanced sensory perception
Time seems long and drawn out
Analgesia
What are the behavioral and psychological effects of cannabis intoxication?
Euphoria
Well-being
Talkativeness
Laughter
Relaxation
Lethargy
What are the immune effects of cannabis intoxication?
Immune function modulated
What are the cardiovascular effects of cannabis intoxication?
Elevated heart rate
Elevated blood pressure
Dilated blood vessels to the skin and eye
What are the GI effects of cannabis intoxication?
Increased hunger and thirst
Reduced abnormally high gastric secretions and GI inflammation
Involved in insulin modulation and energy metabolism
What are the reproductive effects of cannabis intoxication?
Involved in sperm production, fertilization, transport of the fertilized egg in the fallopian tube, implantation of the egg in the uterus, development of the fetus, and initiation of suckling in newborns
May decrease sperm count and cause irregular menstrual cycles
Inconsistent effects of libido
What is the mechanism behind pleasure, reward, giggles, and enhanced perceptions during cannabis use?
High CB1 expression in the hippocampus, cerebellum, basal ganglia, hypothalamus, and cortex
What is the mechanism of analgesia following cannabis use?
CB1-mediated blockage of pain neurotransmission
How does cannabis act as a stimulant?
The dose-dependent heart rate increase, skin vessels dilate flushing warmth temp decreases, salivary gland vessels constrict drying mouth, and eye vessels dilate leading to red, bloodshot eyes.
What is the mechanism of energy metabolism, increased appetite, and thirst during cannabis use?
CB1 in the hypothalamus, pancreas, and liver
Why are there reduced gastric secretions and GI inflammation during cannabis use?
Low endocannabinoids are linked to irritable bowel syndrome
What does CB1 in the hypothalamus influence?
Sex drive, sperm production, fertilization, implantation, fetal development, and suckling in newborns
Modulates DA and 5-HT release
What are the cellular mechanisms of action of cannabinoids?
Retrograde signaling
A neurotransmitter binds to the post-synaptic receptor
Binding causes retrograde release of the cannabinoids AEA and 2AG into the synapse
Cannabinoids bind to receptors on the presynaptic membrane
Once bound, cannabinoids inhibit the release of neurotransmitters such as glutamate, GABA, and dopamine from the presynaptic neuron
What do cannabinoids modulate the release of?
Other neurotransmitters
What does cannabis bind to?
CB1/2
Transient receptor potential cation channels
5HT2 sub-type receptors
What is CB1/2 linked to?
Gi/o
What type of channel is TRPV1/2?
Na+/Ca_ channels
Pleiotropic signaling which as multiple downstream targets and effects
What causes tolerance to cannabis?
Regular use of marijuana will cause metabolic, cellular, and behavioral tolerance
Faster metabolism, reduced CB1 receptor expression
What are the symptoms of cannabis tolerance?
Reduced high, hypothermic, cardiovascular, analgesic, locomotor, and immune effects
What is cannabis withdrawal like?
Mild burn out
If withdrawal symptoms occur, they are not severe
Chronic users will retain higher levels of residual metabolites with eases withdrawal with elimination over months
What are the acute adverse effects of cannabis?
Green-out
Higher THC impairs learning, memory, concentration via hippocampal effects, inhibits LTP
Psychosis
Anxious, paranoid
Heart rhythm complications
Pesticide contamination
Decreased attention, reaction time, hand-eye coordination, and concentration may affect driving ability but stoned drivers may be defensive drivers
What is green-out?
Vomiting, nausea, complicated 5-HT signaling
Anti-5-HT effects account for the anti-emetic activity vs. chemo
What is psychosis?
Hallucinations, delusions of control, grandiosity
Can you fatally OD on cannabis?
No, not a single case of fatal overdose is caused by cannabis
Risk assessment is low compared to alcohol and tobacco
What would a person need to consume to fatally OD on cannabis?
Ingest 400 t0 mg THC capsules in less than 4 hours
Spray 133 mL of 30 mg/mL THC oil in the mouth in less than 3 hours
Smoke 35 0.5 g 15% THC flower in less than 2 hours
What are the long-term health risks of cannabis?
Increased risk of chronic cough, bronchitis
Reduced ability for egg implantation, increases miscarriage rates
Suppressed LH release, impaired ovulation, low birth rate
Lowered testosterone, sperm count, more abnormal sperm, increased side-swimming sperm
Most effects appear to be reversible
What is the gateway drug hypothesis?
The younger teens are when they first use alcohol, tobacco, and/or cannabis, the more often they use these drugs, the more likely they are to use other drugs and possibly become dependent
What does smoking cannabis increase the incidence of?
Increased long-term cough and bronchitis incidence
What does combustion generate?
Carcinogens
How does vaping deliver de-carbed chemicals?
Without burning
Select the chemical composition of vape smoke by controlling the temperature
What temperature does THC vaporize at?
157°C
What does vaping contain less of?
Combustion products
What is unique about volcano administration?
Results in similar THC delivery while reducing CO delivery
What is the entourage effect?
Selecting for certain chemicals
What is the mechanism of reinforcement of cannabis?
Through CB1-mediated inhibition of GABA release in the VTA = disinhibition of DA-ergic VTA to NAc neurons
How much does 8 mg of inhaled THC increased DA levels in humans?
136% 45-85 minutes post-administration
Does consuming cannabis orally increase DA?
No
What does striatal DA release by THC may underlie?
Schizophrenia
How does cannabis cause bloodshot eyes?
Noradrenaline causes narrowing of blood vessels
Anandamide relaxes those blood vessels
Anandamide is dependent on CB1 receptor and nitric oxide
CBD induces relaxation of arteries
What are the munchies?
Result from hunger signaling
Increase smell, olfaction sensitivity
Increased pleasure when eating = induces DA release
How does hunger signaling work?
Olfactory afferent information coming in via bi-polar mitral neurons
Inhibitory GABA-ergic interneurons project to mitral neuron soma
Glu-ergic neuron expressing CB1 pre-synaptic receptors triggers inhibitory GABA-ergic interneurons in the main olfactory bulb
What is the mechanism of enhanced olfactory sensitivity?
Glu-ergic inputs trigger GABA-ergic firing
Sets baseline mitral afferent firing to the brain
What do endocannabinoids naturally reduce in relation to olfaction?
GABA-ergic interneuron firing leading to increases transmission through mitral cells
What do disinhibition of afferent inputs and increased afferent inputs to the brain do?
Hypersensitizes smell which causes animals to feed
How do we study a physiological process?
Gene/protein knock-outs
What is the physiological mechanism linked to munchies behaviour?
Anterior olfactory nucleus + piriform cortex = centrifugal Glu-ergic input to the MOB
Cortical feedback projections to the MOB regulate foo intake via CB1 signaling
What are the pro-appetite effects of cannabis?
Increased olfactory sensitivity triggers feeding
Users report greater pleasure from food
Appetite-related hormones are modulated by cannabinoids
What are the anti-emetic activity of cannabinoids?
Primary signal is 5HT3R-mediated in the medulla by afferent input from the gut
THC inhibits 5HT release in the medulla via pre-synaptic CB1
THC binds and decreases the activity of 5HT3 receptors
CBD is an agonist at 5HT1a auto-receptors, prevents 5HT release, also antagonizes 5HT3R
What are the acute adverse effects of cannabis use?
Bad driving = affects mostly automated tasks like staying in your lane relative to attention tasks like reversing, doubles risk of severe injury/death, synergistic effect when combined with alcohol
Contamination with toxins can cause severe bleeding
Cancer
What might cannabinoids protect?
Cells from oxidative stress
How do we detect and test for cannabinoids?
Colorimetric-ELISA or dipsticks
Immunoassays, lateral flow
Gas chromatography-mass spectrometry
Roadside screening tests are usually lateral flow assays
