Drugs of Abuse - General/Cannabis

Question 1

What is the reason drugs are abused?

Answer 1

They hijack the bodies natural reward pathway

Question 2

Describe the Reward Pathway:

Answer 2

Dopaminergic neurones that originate in the Ventral Tegmental Area (VTA) and project to the Nucleus Accumbens

Question 3

What are the four common routes of Administration of Narcotics?

What is their speed of absorption?

Answer 3

Snort - Mucous membranes of nasal sinuses - Slow absorption

Eat - GI tract - Very slow absorption

Smoke - Small airways and alveoli - Rapid absorption

Inject - Veins - Rapid absorption

Question 4

What is the fastest route of administration for narcotics?

Answer 4

Smoking

• not injecting because lipid-soluble drugs cross into blood easily and enter the left heart, unlike IV which has to go through right heart and lungs
• smoking gets to brain quicker

Question 5

What are the four main classes of Drugs of Abuse?

Give some examples for each:

Answer 5

Narcotics/Painkillers - Opiates like Heroin

Depressants - Alcohol, Benzodiazepines (Valium), Barbiturates

Stimulants - Cocaine, Amphetamines (Speed), Caffeine, Nicotine

Misc. - Cannabis, Ecstasy (MDMA)

Question 6

What is an Alkaloid?

Answer 6

Any class of nitrogenous organic compounds of plant origin which have pronounced physiological actions on humans.

They include many drugs (morphine, quinine) and poisons (atropine, strychnine)

Question 7

What is the plant that Cannabis comes from:

Answer 7

Cannabis sativa

Every part contains active cannabinoids

Question 8

What is the most potent cannabinoid?

Answer 8

delta-9-tetrahydrocannabinol (Δ9-THC)

Question 9

What is ‘the other’ potent cannabinoid (there are over 60 in total)?

Answer 9

Cannabidiol - seems to protect against some of the negative aspects of Δ9-THC

Anti-psychotic to some degree

Question 10

Why is Cannabis believed to be more pro-psychotic than previously?

Answer 10

Production has aimed to increase the concentration of Δ9-THC whilst reducing things like Cannabidiol, so you get less of its anti-psychotic effects

Question 11

What are the major routes of Cannabis administration?

(availabilities)

Answer 11

Oral - 5-15% - Delayed onset/slow absorption first pass metabolism

Inhalation - 25-35%

Question 12

How long do the peak effects of Cannabis last in the brain?

Why?

Answer 12

Couple of hours

Brain is highly perfused so it will reach the brain quickly but also leave quickly

Question 13

Describe the concentrations of Cannabis in different body compartments over time:

Answer 13

Due to its high Lipid Solubility it builds up in the fat but takes a while to get there because adipose tissue is poorly perfused

Question 14

How long after the dose do the effects of Cannabis last?

Answer 14

~30 days

Slow leakage into the bloodstream from the Adipose due to its high lipid solubility

Question 15

Why does measuring the concentration of Δ9-THC give a poor indication of the degree of intoxication?

Answer 15

Because one of Δ9-THC’s main metabolites is 11-hydroxy-THC which is more potent. It is produced in the liver and excreted into bile. It can be reabsorbed from the GI tract into the blood and exert its effects of intoxication (enterohepatic cycling)

The value also does not give an indication of how much is stored in fat

Question 16

What are the two cannabinoid receptors?

Answer 16

CB1 - found in the brain

CB2 - peripheral cannabinoid receptors that are found on immune cells

Question 17

What is the mechanism of the Cannabinoid receptors?

Answer 17

G-protein coupled - negatively coupled with Adenylate cyclase

This is why cannabis is a depressant

Question 18

What is the name of one of the endogenous substances that binds to Cannabinoid receptors?

Answer 18

Anandamide

Question 19

How does Cannabis cause Euphoria?

Answer 19

The Reward pathways are inhibited by default due to GABA actions on the VTA neurones

Δ9-THC binds to the CB1 receptors on the GABAergic neurones that inhibit the VTA preventing it from permanently firing, so the VTA will remain active and Dopaminergic neurones will continue to fire leading to euphoria

Question 20

Why may Schizophrenia and Psychosis be seen in chronic Cannabis users?

Answer 20

THC thought to interact with the Anterior Cingulate Cortex - Performance monitoring and Behavioural adjustment.

Hypoactivity is seen here in chronic users so behavioural performance adjustment is impaired

Question 21

Why does Cannabis give you the ‘munchies’?

Answer 21

Lateral hypothalamus is involved in appetite - has Orexinergic and Melanin Concentrating Hormone neurones that cause hunger

Cannabis inhibits the GABAergic neurones that have inhibitory influence over MCH neurones

Also seems to directly simulate Orexin production (appetite-stimulating hormone/neurotransmitter)

Question 22

Why does Cannabis have an immunosuppressive effect?

Answer 22

Causes a decrease in B-cell and T-cell number and decreases the cytolytic activity of NK cells

• Causes significant immunosuppression in chronic users

Question 23

What are some common effects of Cannabis use?

Answer 23

Stimulated Appetite

Memory loss

Impaired psychomotor performance

Psychosis

Immunosuppression

Tachycardia/Vasodilation

Question 24

How does Cannabis cause memory loss?

Answer 24

Cannabis affects the limbic regions (depressive effects on the hippocampus in particular will lead to amnestic effects)

BDNF (brain-derived neurotrophic factor) is an important peptide in the hippocampus that allows the formation of memories

Cannabis decreases the effects of BDNF

Question 25

Why does Cannabis impair psychomotor performance?

Answer 25

It causes depression of the cerebral cortex

Question 26

Where can vasodilation often be seen with Cannabis use?

Answer 26

In the eyes - bloodshot

Question 27

What is the significance of the medulla having low CB1 receptor expression?

Answer 27

Medulla is responsible for controlling cardio-respiratory function

Low CB1 expression means Cannabis can’t really influence this

You cannot therefore overdose on Cannabis to the point where you can kill yourself

Question 28

What will upregulation of CB receptors in adipocytes lead to?

How can this be used pharmacologically?

Answer 28

Obesity

• Dronabinol and Nabilone THC like CB agonists can be used as anti-emetics, to reduce nausea with chemotherapy, and loss of appetite in AIDS patients

Question 29

How can CB receptors be utilised to treat Obesity?

Answer 29

CB antagonists like Rimonabant can be used

(It was removed after evidence emerged it increased depression and suicidal tendencies - a common problem with anti-obesity drugs)

Question 30

How can CB receptors be utilised in treating MS?

Answer 30

Sativex is a combination drug of THC and CBD that has been shown to reduce symptoms in adult MS patients with moderate to severe spasticity