Exam 3: Marijuana

(Pharmacokinetics):

Smoked THC is ______ absorbed by the ____ and _____ levels rise quickly

easily; lungs; blood plasma

(Pharmacokinetics):

When marijuana is administered orally, does it have a fast time course of onset?

No - it is far slower than smoking.

How much longer can marijuana last in the body when taken orally vs. smoked?

It can affect you for 5+ hours to over a day.

How are marijuana metabolites excreted?

In feces and urine

Why does it take so long for marijuana to be completely eliminated from the body?

THC persists in FAT tissue. The elimination half life is 20-30 hours, therefore it can be detected in urine for up to two weeks.

What are the acute physiological effects of marijuana?

Bloodshot eyes, dry mouth, munchies, increased heart rate, increased blood flow, muscle relaxation, drowsiness

What are the behavioral/psychological effects of Marijuana?

Euphoria/disinhibition, increased laughter, relaxation, stress relief, impaired reaction time, alterations of perceptions (for ex: time slows)

What are the mechanisms of action for cannabinoids?

THC binds to the CB1 or CB2 receptor (metabatropic)

Where is CB1 receptors found?

In the brain, especially in the Basal Ganglia, Hippocampus, and Cerebellum

Where is CB2 found?

Primarily in the periphery tissues and immune system.

What do presynaptic CB1 receptors on nerve terminals do?

When activated, they have an inhibitory effect on NT release on the presynaptic neuron: including ACh, DA, NE, 5-HT, GABA, and Glutumate.

What is the effect of THC on the amygdala?

THC creates panic/paranoia.

What is the effect of THC on the Basil Ganglia?

It slows reaction time.

What is the effect of THC on the brainstem?

It has anti-nausea effects.

What is the effect of THC on the Cerebellum?

Impaired coordination.

What is the effect of THC on the Hippocampus?

Impaired memory

What is the effect of THC on the Hypothalamus?

Increased appetite

What is the effect of THC on the neocortex?

Altered thinking, judgement, and sensation

What is the effect of THC on the Nucleus Accumbens?

Euphoria

What is the effect of THC on the Spinal Cord?

Altered Pain Sensitivity

What is the evidence to show that acute behavioral and physiological effects of marijuana are at least partially mediated by CB1 receptors?

In those who have had treatment with rimonabant, a CB1 receptor antagonist, intoxication is significantly inhibited!

Endocannabinoids (Endogenous Cannabinoids) are cannabinoid receptor ______ synthesized by the body.

Agonists

What are the two endogenous Cannabinoids?

Anandamide and 2-AG

Why is it significant that Anandamide and 2-AG are NOT lipid soluble?

Because they are lipid soluble, they cannot be stored in vesicles of traditional neurotransmitters, therefore they are synthesized and released when needed.

What happens in the body that signals the body to synthesize and release Anandamide and 2-AG?

There is a rise in intracellular CA2+ Levels.

While both 2-AG and Anandamide are agonists at CB1 and CB2 receptors, what is the difference between them?

2-AG is a FULL agonist at CB1 and CB2 receptors, vs. Anandamide which is a PARTIAL agonist.

What does it mean that endocannabinoids function as retrograde messengers?

Endocannabinoids are synthesized and released by the postsynaptic neuron and they bind to the CB receptors on the PREsynaptic neuron, therefore inhibiting and reducing the release of NTS like gaba, etc.

THC is a _______ agonist at the CB1 receptor.

partial

How do we know that THC only partially agonises and has partial effects?

Rodents self administer a full CB1 agonist.

CB1 receptors are involved in which two brain systems?

The brain’s reward system and the endogenous opioid system.

True or False: Cannabinoid reinforcement is dependent on CB1 receptor mediated activation of the VTA dopamine neurons that project to the NACC and release Dopamine.

True

True or false: Alcohol and Cannabinoids have the same effect of DA release with the inhibition of GABA

True

Explain how cannabinoids work on GABAergic neurons in the VTA.

Presynaptic CB1 receptors are located on GABAergic neurons and THC will come and partially activate the neurons, therefore inhibiting GABA release, and increase DA in the NAc.

True or False: Cannabis tolerance is dose dependent

True

What form of Cannabinoid is used to treat childhood seizure disorders?

Cannabidiol (CBD); it is NOT intoxicating or dependence producing.

Is CBD a cannabinoid receptor agonist?

NO. it can act as a negative allosteric modulator of CB1 Receptiors. CBD inhibits the breakdown of endogenous cannabinoids, which enhances the activity of the endocannabinoid system.

Brain imaging shows that THC promotes regional brain activation and enhanced local blood flow. Does CBD do the same?

No, decreases the activation in the regions THC is regularly activated in.

Oral administration of marijuana

A) results in a shorter duration of action of the drug than smoking

B) Yields low but consistent levels of drug in the body

C) Results in a longer duration of action of the drug

D) Is an easy way to regulate the amount of drug entering the body

C

Which statement regarding CB1 cannabinoid receptors is false?

A) It is expressed in many brain regions

B) It is an ionotropic receptor

C) plays a role in the intoxicating effects of marijuana

D) Presynaptic CB1 receptors on nerve terminals have an inhibitory effect on transmitter release

D) All of the above

B

_______ increases regional brain activation and blood flow in some brain regions, while _______ has the opposite effect.

A) THC; CBD

B) CBD; THC

C) Methylphenidate; Hemp

D) Hemp; Methylphenidate

The development of tolerance to cannabis

A) involves down-regulation of CB1 receptors

B) involves up-regulation of CB1 receptors

C) occurs in response to moderate cannabis use

D) occurs in response to heavy chronic cannabis use

E) Both A and D

E

Why is THC less reinforcing than opioids and other highly abused drugs?

THC is only a partial agonist at CB1 receptors.

Which of the following has been found in brain imaging studies of long term cannabis users?

A) reduced gray matter volume in several brain areas

B) Down regulation of cortical CB1 receptors in many brain areas

C) DA system abnormalities

D) All of the above

D