Drugs of abuse 1: General drugs & Cannabis Flashcards
Why are certain drugs abused?
They induce euphoria (feeling of intense happiness)
How do drugs induce euphoria?
The reward system
- Dopaminergic neurones from the ventral tegmental area (VTA) project to the nucleus accumbens (NAcc)
- Dopamine release at the nucleus accumbens stimulates feelings of reward and happiness
- Essentially this pathway is activated by any stimuli which make you feel happy and rewarded
-
Examples:
- Food
- Money
- Social interaction
-
Examples:
Drugs can also stimulate the reward system in the brain → euphoria
What are the different routes of administration for drugs of abuse?
- Intranasal (snort)
- Oral (eat)
- Inhalational (smoke)
- Intravenous (inject)
Describe how fast the drug would have an effect on the brain with each route of administration.
REMEMBER:
- To have an effect on the brain, the drug needs to enter the systemic circulation
- Arterial part of the circulation as it has to supply the brain
- So the drug which is first absorbed into the bloodstream will reach and have its effect on the brain the fastest
Routes of administration
- Intranasal (snort)
- The drug has to be absorbed through the mucous membranes of the nasal sinuses
- This absorption is slow
- The drug has to be absorbed through the mucous membranes of the nasal sinuses
- Oral (eat)
- The drug has to be absorbed through the walls GI tract
- This absorption is very slow
- The drug has to be absorbed through the walls GI tract
- Inhalational (smoke)
- The drug has to be absorbed through the alveoli
- This absorption is rapid
- The drug has to be absorbed through the alveoli
- Intravenous (inject)
- The drug is injected straight into the veins so doesn’t even need to be absorbed
- Rapid
- The drug is injected straight into the veins so doesn’t even need to be absorbed
Pathway to the brain
Oral, intranasal, IV:
- Once absorbed, the drug enters the venous system
- Or in the case with IV, the drug is directly injected into the venous sytem
- Venous system → RA → RV → lungs → LA → LV → arterial system → brain
- Therefore, the quicker the drug is absorbed into the venous system, the faster the drug will have its effect on the brain
- So out of these 3 routes of administration, fastest → slowest:
- IV → intranasal → oral
Inhalational:
- This is the fastest to have an effect on the brain
- Alveoli → LA → LV → arterial system → brain
- You are skipping the whole venous system → RA → RV part which means that it gets to the lungs faster
What are the different classifications of the drugs of abuse? Give examples for each classification.
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Narcotics/painkillers - opiate-like drugs
- EXAMPLE:
- Heroin
- EXAMPLE:
-
Depressants (‘downers’)
- EXAMPLES:
- Alchohol
- Benzodiazepines (valium)
- Barbiturates
- EXAMPLES:
-
Stimulants (‘uppers’)
- EXAMPLES:
- Cocaine
- Amphetamine (‘speed’)
- Caffeine
- Metamphetamine (‘crystal meth’)
- EXAMPLES:
-
Miscellaneous
-
EXAMPLES:
- Cannabis
- Ecstasy (MDMA)
-
EXAMPLES:
Describe where the drug cannabis comes from.
Cannabis = marijuana
The whole Cannabis sativa plant contains:
- Over 400 compounds - within which there are…
- Over 60 cannabinoids
- Cannabinoids = the active component which acts on cannabinoid receptors in the body
- Highest concentration of cannabinoids in the trichomes (glandular hairs) of the plant
Drug extraction:
- Trichomes are secretory in function
- Substances secreted by plants is known in general as resin
- Hashish is a cannabis concentrate made from the resin of the cannabis plant
- Hash oil is also a cannabis concentrate, where extraction from the plant involves a solvent
State two major cannabinoids.
Δ9-Tetrahydrocannabinol (Δ9-THC)
- This is the most potent cannbinoid
Cannabidiol
- This moderates some of the negative effects of Δ9-THC
- Protective in function
Describe how the dose of cannabinoids extracted from a Cannabis sativa plant has changed over time. Describe the effect this has on the drug user
Before (60s and 70s):
- From a plant you would be able to extract 10mg of Δ9-THC
Nowadays:
- Various forms of the Cannabis sativa plant have been farmed so that a higher dose of Δ9-THC can be exracted from them - 150-300mg
Increase in Δ9-THC dose = more powerful drug effect
- However, these farmed forms of the plants also have a lower proportion of cannabidiol
- Increased the amount of Δ9-THC at the expense of cannabidiol
- This means that you have essentially lost the protective effect of cannabidiol
Increase in Δ9-THC dose leads to increase in negative effects
- Δ9-THC has negative effects so it makes sense that increase in dose leads to increase in negative effects
- However, the decrease in the proportion of cannabidiol with an increased dose of Δ9-THC means you have reduced protection against the negative effects → increased negative effects
NOTE: Long term cannabis use is associated with decreased performance
What are the main routes of administration of cannabis?
Oral
- Bioavailability: 5-15%
- This is due to first pass metabolism (in GI tract, liver)
- Slow absorption through GI tract → delayed onset
Inhalation
- Bioavailability: 25-30%
- When you inhale a drug, you lose 50% of it through exhalation (i.e. when you exhale)
-
Of that 50% which isn’t lost, you need to inhale deep enough for the drug to reach the alveoli and be absorbed into the bloodstream
- The deeper you inhale, the more drug will reach the alveoli before you have to exhlae again
NOTE: Bioavailability = proportion of unchanged drug that reaches the systemic circulation
Describe the pharmacokinetics of cannabis.
- Cannabis is very lipid soluble
- Fat (adipose tissue) is poorly perfused - receives 2% of CO
- Therefore, cannabis slowly accumulates in fatty tissues as fatty acid conjugates
-
Slow accumulation due to poor perfusion
- Takes time for blood to reach fatty tissue
-
Accumulation due to poor perfusion
- Drug does not get as much opportunity to diffuse back into the bloodstream via fatty tissue**
-
Slow accumulation due to poor perfusion
- Ratio of cannabis concentration - fat : plasma
- 104 : 1
- REMEMBER:
- Cannabis does slowly leak back into the bloodstream
- This allows drug clearance
How long do the effects of cannabis last in the body?
30 days
- This is because cannabis accumulates in fatty tissues and leaks slowly back into the bloodstream, allowing clearance
What is the correlation like between plasma cannabinoid concentration and degree of intoxication?
Poor correlation
- This is due to the accumulation of cannabis in fatty tissue
- 60% of brain content is lipid
- This lipid has a structural function
- It is not available to be metabolised for energy so this proportion stays the same
- Cannabis can accumulate in the fatty tissue in the brain and leak out to affect the brain → intoxication
- Cannabis is much more concentrated in the brain than in the plasma - therefore poor correlation
How is cannabis excreted?
NOTE: THC (Δ9-THC) is the major component (cannabinoid) in the cannabis taken nowadays
- Liver converts THC → 11-hydroxy-THC (more potent)
- 11-hydroxy-THC can be conjugated with bile and be excreted
- So 65% excreted via GI tract
- BUT:
- Intestinal bacteria hydrolyses the bile conjugate, releasing the free drug (THC)
- Since THC is very lipid soluble, it can diffuse back into the blood → enterohepatic recycling
- 25% excreted in the urine
Where does cannabis act in the body?
Cannabis acts on cannabinoid (CB) receptors
-
CB1
- Found centrally
- Hippocampus
- Cerebellum
- Cerebral cortex
- Basal ganglia
- Found centrally
-
CB2
- Found peripherally
- Immune cells - major location but found elsewhere
- Found peripherally
NOTE: These receptors are found as part of the endocannabinoid system in the body, which is involved in a wide variety of physiological processes
What endogenous substance act on the CB receptors?
Anandamide - an endocannabinoid