Cannabinoids

Question 1

Plant origin of cannabinoids

Answer 1

flowering hemp

Use psychoactive properties from sticky resin of flowering females

Question 2

Marijuana and Hashish

Answer 2

bud and small leaves of flowering plant ~4-5% THC

Concentrated from resin gland ~20% THC

Question 3

Pharmacokinetics of THC

Answer 3

Smoked - Time to peak - 3-5 min
Oral - Time to peak - 1 hr

1/2 life: 2-30 hrs
Very lipophilic (adipocytes and blood lipoproteins)
Demonstrate depot binding

Question 4

Function of Endocannainoid System

Answer 4

THC found in the ff areas:
Cerebral Cortex - higher cognitive fxn
Cerebellum - movement
Basal Ganglia - movement
Spinal Cord - peripheral sensation including pain
Hypothalamus - appetite
Hippocampus - memory, learning, stress
Medulla - Nausea, vomiting, chemoreceptor trigger zone

Activated by marijuana

Question 5

Cellular responses to endocannabinoids

Answer 5

Release from cell is triggered by Ca

• occurs by diffusion (not by conventional synaptic release)
• works by Ca influx causing conversion of endocannabinoid from hydrophilic state to lipophilic state, allowing diffusion

Receptors

• CB1 (neural) –> primary mechanism
• CB2 (immune)
• G-protein coupled metabotripic receptor
• located both pre- and post-synaptically
• primary cellular effects - affect fxning of many other NT systems (Ach, DA, NE, 5-HT, Glut, GABA) (inhibit NT release)

Question 6

Mechanism of action

Answer 6

Termination of signaling by

1) reuptake
2) by FAAH (fatty acid hydrolase) - causes enzymatic breakdown

Question 7

Behavioral Effects of Marijuana

Answer 7

4 Stages

1) buzz - lightheaded
2) high
- euphoria/loss of inhibitions OR dysphoria with naive dose or with high dose)
3) stoned
- relaxed and calm
- mildly hallucinogenic (perceive lights and color differently, slowing of time)
- cloudy thinking
- inability to concentrate
4) come down - symptoms subside

Question 8

Physiological Effects of Marijuana

Answer 8

Vasodilation - feel warm, red eyes
Increased HR
Increased appetite

Question 9

Understanding THC by studying cannabinoid pathways - CB1 blockers

Answer 9

• Hyperalgesia
• Loss of appetite
• Memory problems
  especially spatial memory and story recall

BOTH upregulating and downregulating endocannabinoid system affects memory

Question 10

Reward and Reinforcement - Self-admin studies

Answer 10

primates only self-administer THC if they start with a lower dose
Response is abolished in the presence of CB1 antagonists

Question 11

Reward and Reinforcement - Place Conditioning Studies

Answer 11

Rats show place preference if given a low dose and are given their first dose in their “home” cage
They show aversion with high doses
Response is abolished in the presence of CB1 antagonists

Question 12

Reward and Reinforcement - THC and Reward Pathway

Answer 12

THC stimulated DA release from VTA cells into NAc
There’s a close association between endocannabinoid system and endogenous opioid system
- Mu antagonists infused into VTA block opiate-induced and THC-induced DA release into the NAc
- opiate antagonists –> decreased self-admin of THC by primates
- conditioned place preference is abolished in Mu-KO’s

Question 13

Proof of CB1 Density decrease and Desensitization with THC

Answer 13

one chemical stains for receptors and shows desensitization
the other chemical CB1 distribution
Not as bad as other drugs we studied

Question 14

Marijuana Tolerance

Answer 14

Less evidence of tolerance to THC than other drugs we’ve discussed (particularly at the cellular/molecular level)
Humans show behavioral tolerance: ex. can improve on task performance in the presence of the drug

Question 15

Marijuana Dependence

Answer 15

Humans - only a mild abstinence syndrome

- irritability, poor sleep, loss of appetite, mild anxiety