Question

Q # 6: Explain the difference between acute (short-term) and chronic (long-term) fat cell related pharmacokinetics?

Q # 7: Compare and contrast endocannabinoids, anandamide, and 2-arachidonoylglycerol.

Q # 8: Compare and contrast the differences between CB1 and CB2 receptors functions and where they are distributed within the central nervous system.

Q # 9: What are the differences between amotivational syndrome, cannabis use disorder, and cannabis withdrawal syndrome?

Q # 10: What are the only clear medicinal uses for prescription (legal use) of marijuana?

Answer 1

A. 8.

The endocannabinoid system has two receptors: CB1 and CB2. Each receptor responds to different cannabinoids, but some cannabinoids can interact with both.The distribution of CB1 and CB2 receptors within the body and brain explains why cannabinoids have certain effects.

CB1 receptors are found throughout the body, but are mostly present in the brain and spinal cord. They are concentrated in brain regions associated with the behaviors they influence.

For example, there are CB1 receptors in the hypothalamus, which is involved with appetite regulation, and the amygdala, which plays a role in memory and emotional processing. CB1 receptors are also found in nerve endings where they act to reduce sensations of pain.

CB2 receptors tend to be found in the peripheral nervous system. They are especially concentrated in immune cells. When CB2 receptors are activated, they work to reduce inflammation. Inflammation is an immune response which is believed to play a role in many diseases and conditions.

A. 10. Medical marijuana can be prescribed for a wide variety of conditions including chronic pain, nausea, multiple sclerosis, epilepsy, and palliative care. Also to treat Cancer, glaucoma, HIV or AIDS, any chronic or debilitating disease or treatment for such diseases, which produces conditions that may be alleviated by the medical use of the marijuana: cachexia; severe pain; severe nausea; seizures, including those that are characteristic of epilepsy; or persistent muscle spasms, including those that are characteristic or multiple sclerosis

A.7.Endocannabinoids are cannabinoids produced naturally within the human body. 2-AG and anandamide are the two major endocannabinoids known.

2-AG is found at higher concentrations in the brain, while anandamide is found at higher concentrations in other areas of the body. Both are capable of binding to CB1 and CB2 receptors, but differ in their affinities for these receptors (i.e. how likely they are to bind to and activate each receptor).

Endocannabinoids are “short-order” neurotransmitters, meaning they are synthesized on demand. In other words, endocannabinoids are only produced when the body signals that they are needed, and their presence is transient.

After being released, endocannabinoids are quickly broken down by enzymes, which include FAAH (fatty acid amide hydrolase) and MAGL (monoacylglycerol lipase)

Endocannabinoids are lipid mediators, isolated from brain and peripheral tissues, which include amides, esters and ethers of long-chain polyunsaturated fatty acids. These compounds exhibit ‘cannabimimetic activity’, that is, they act as ‘THC mimetics’ in a long series of bioassays described in the literature.Anandamide (AEA) shares critical pharmacophores with THC. Thus, together with its congeners it was termed ‘endocannabinoid’ in analogy with the ‘endorphins’, that is, the endogenous ligands of opiate receptors. Another arachidonate derivative, 2-arachidonoylglycerol (2-AG; Figure 1), was shown to mimic THC by functionally activating CB receptors, and together with AEA is the endocannabinoid

endocannabinoids act in the central nervous system not only as modulatory substances (i.e. in an autocrine fashion) like eicosanoids and neuropeptides, but also as neurotransmitters. They are the only neurotransmitters as yet known to act as retrograde synaptic messengers.

On the other hand, AEA has been shown to control the cell choice between growth and death.

2-AG and most of the other congeners of AEA do not seem to play a role in the control of cell fate.

Unlike classical neurotransmitters and neuropeptides, AEA and 2-AG are not stored in intracellular compartments, but are produced on demand by receptor-stimulated cleavage of lipid precursors.

The biological activity of AEA is terminated by its removal from the extracellular space, which occurs through a two-step process: (i) cellular uptake by a high affinity transporter, followed by (ii) intracellular degradation by a fatty acid amide hydrolase

The molecular targets of AEA and 2-AG are the CB1 and CB2 cannabinoid receptors, the non-CB1/non-CB2 cannabinoid receptors, the noncannabinoid receptors and the vanilloid receptors.

endocannabinoids are known in controlling cell patterns during brain development. Recently, endocannabinoids have been shown to inhibit neuronal differentiation in various cellular models in vitro, which correlates with their ability to inhibit adult hippocampal neurogenesis

A. 8.

Cannabis Use Disorder: A problematic pattern of cannabis use leading to clinically significant impairment or distress as manifested by at least two of the following occurring in a 12 month period:

1. Cannabis is often taken in larger amounts over a longer period than was intended.

2. There is a persistent desire or insignificant effort to cut down or control cannabis use.

3. A great deal of time is spent in activities necessary to obtain cannabis, use cannabis or recover from its effects.

4. Craving or a strong desire or urge to use cannabis.

5. Recurrent cannabis use resulting in failure to fulfill major role obligations at work, school or home.

6. Continued cannabis use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of cannabis.

7. Important social, occupational or recreational activities are given up or reduced because of cannabis use.

8. Recurrent cannabis use in situations which is physically hazardous.

9. Cannabis use is continued despite knowledge of having persistent or recurrent physical or psychological problems that are unlikely to have been caused or exacerbated by cannabis.

10. Tolerance, as defined by either:

1) A need for markedly increased amounts of cannabis to achieve intoxication and desired effect, or

2) A markedly diminished effect with continued use of the same amount of cannabis.

11. Withdrawal, as manifested by either:

1) The characteristic withdrawal symptoms for cannabis, or

2) A closer related substance is taken to relieve or avoid withdrawal symptoms.

Cannabis Withdrawal	2. Three or more of the following signs and symptoms develop within approximately one week after cessation of heavy, prolonged use:
	1) Irritability, anger or aggression
	2) Nervousness or anxiety
	3) Sleep difficulty (e.g. insomnia, disturbing dreams)
	4) Decreased appetite or weight loss
	5) Restlessness
	6) Depressed mood
	7) At least one of the following physical symptoms causing significant discomfort:
	i. Abdominal pain,
	ii. Shakiness/tremors,
	iii. Sweating,
	iv. Fever,
	v. Chills, or
	vi. Headache
	3. The signs or symptoms cause clinically significant distress or impairment in social, occupational or other important areas of functioning.
	4. The signs and symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.