Lecture 56: Marijuana Flashcards
Where can we find cannabinoids and receptors naturally?
Cannabinoids are endogenously produced
Cannabinoid receptors very common in the brain
What is the main psychoactive ingredient in marijuana?
Delta-9-tetrahydrocannabinol
Also THCV and Cannabidiol
What is the major active metabolite?
OH-THC (11-delta-9-THC)
Major inactive ingredient?
THC-COOH
Is marijuana a gateway drug?
O’Brien is skeptical because kids just kind of uses whatever is available
What are the desirable effects of marijuana?
- Euphoria “high”
- Anxiolysis “mellowing out”
- antiemetic (used for chemo patients)
- Analgesic
- muscle relaxant
- increased appetite lol
- anti convulsant/inflammation
- bronchodilation
- cancer cell apoptosis?
- reduction of intraocular tension (because of CB receptors in retina)
What are the toxic effects?
- balance/orientation
- loss of motivation, memory, perception and even consciousness
- Xerostomia, hypohydrosis, hypertension, tachycardia
- Conjunctival irritation
- Bronchopulmonary irritation
- endocrine changes
- Decreased Immunomodulation
- Testicular germ cell tumors?
- decrease sperm
What is the percentage of marijuana dependence?
9% of those exposed
-less addictive than other drugs
What is marijuana withdrawal syndrome?
Lack of physical complaints Dysphoria Anorexia Irritability Anxiety Nonspecific somatic complaints (what happens to frequent users)
When do the psychotropic effects of marijuana kick in?
Psychotropic effects kick in after a LAG in plasma level after inhalation
When is the peak effect of marijuana?
Les than 10 minutes when inhaled
2.5 hours after ingested
What is the distribution of marijuana in body?
Marijuana is lipophilic
-redistributed in fatty tissues and in chronic users could be intermittently released back into circulation over a motnh longer
How do you detect marijuana?
Immunoassay in urine
Sensitive threshold = 50 ng/ml
Does not discriminate THC from metabolites
Urine levels are NOT correlated with time and amount used…unlike plasma
Single join leads to positive urine test up to 96 hours
What are peak plasma levels of marijuana?
100ng/ml
What is a potential drug for marijuana withdrawal?
- Nabilone
- Sativex
- Buspirone
- Dronabinol
What are examples of synthetic marijuana (for therapy)?
Dronabinol (Marinol)
Nabilone (Cesamet)
What are the significant cannabinoid receptors?
CB1: brain, fat cells, liver, duodenum, muscle
CB2: lymphocytes > macrophages > cytokines
Where are CB1 receptors located?
Dense in the parts of the brain that control emotion -basal ganglia -cerebellum -hippocampus -NAcc -middle prefrontal cortex -parietal cortex Moderately dense in -amygdala, spinal cord, brainstem
What are types of ENDOGENOUS CANNABINOIDS?
- Annandamaide
2. 2-arachidonoyl-glycerol (2-AG)
What is the MOA of THC?
Binds to cannabinoid receptors (Gi) located on GABA interneurons
Elicits dopamine release in NAcc
How do endocannabinoid, dopamine and opioids interact in body?
- Rimonabant (CB1 antagonist) prevents morphine-induced conditioned place preference (not FDA approved because of severe mood side effects)
- Naloxone precipitates opiate withdrawal in cannabinoid dependent rats
- naloxone blocks cannabinoid-induced analgesia (because cannabinoid is also has a Gi receptor)
What are the key characteristics of pharmacotherapy in relation to marijuana?
- No medication has been consistently effective or approved by any national regulatory authority
- Buspirone is the only medication to date that has shown efficacy for cannibs dependence in a controlled clinical trial
- Laboratory and open-label trials suggest that dronabinol the COMT inhibitor entacapone, and lithium may warrant further study
- Pre-clinical studies suggest the potential of fatty acid amide hydrolase (FAAH) inhibitors such as URB597, endocannabinoid-metabolizing enzymes and nicotinic alpha 7 receptor antagonists such as methyllycaconitine (MLA)
What is the association between endocannabinoids and obesity? Significance
Endocannabinoids and cannabinoids
-induce appetite
-reduce satiety
-stimulate lipogenesis
-increase hedonic reward value of palatable food
CB1 antagonists should have opposite effects…
What is the therapeutic potential of CB1 antagonists?
Can be used to treat ADDICTION and OBESITY
1. Can block the direct reinforcing effects of THC
2. Can block the motivational effects of most drugs of abuse
Example: Rimonabant
3. Shown to prevent types of addiction of nicotine but was canceled because of severe depression side effect
