Cannabis Pharmacology Flashcards
What can Medical Marijuana do?
- Reduces intraocular pressure
- Control of nausea and vomiting
- Anticonvulsant
- Appetite stimulant
- Withdrawal from depressants and opioids
- Analgesic
Epidiolex (Cannabidol)
- By FDA on June 25th, 2018
- Seizures, spasticity, neuropathic pain
Dronabinol (Marinol)
- Nausea, vomiting for patients in cancer
Nabilone (Cesamet)
Nausea, vomiting for patients in cancer
Nabiximols (Sativex)
Neuropathic pain, spasticity in patients with mutliple sclerosis
Tetrahydrocannabinol (THC)
- Partial agonist
- Targets CB1/CB2
Cannabidiol (CBD)
- Non-psychotropic, low affinity for CB1/CB2
- Anxiety, cognition, movement disorders, and pain
- Decreases THC clearance * (likely by CYP inhibition)
CBN
- THC metabolite
- CB2-selective partial agonist
CBG
- THC/CBD Precursor
- CB1/2 antagonist
Tetrahydrocannabinol (THC) - Pscyhoactive
- Low toxicity (LD50 = 1270 mg/kg in adult male rats)
- Low solubility, high lipophilicity (Log P > 6000 by shake flask, 2.9 ug/mL in H20)
- No documented overdose fatalities * from THC*
What are the potential positive effects of cannabis use?
- Euphoria
- Relaxation
- Laughing
- > appreciation for music
What are the potential negative effects of cannabis use?
- Anxiety, fear, paranoia, or panic
- Hallucinations (rare)
- Dissipate with time
What are the acute effects of cannabis?
- Dry mouth
- Stimulated appetite (munchies)
- Antiemetic (low doses)
- Nausea and vomiting (high doses)
- Increased heart rate
- Orthostatic hypotension
- Dilate blood vessels (red eyes)
- Impaired:
- Attention
- Short term memory
- Some complex cognitive processes
- Motor abilities
What are the long term effects of cannabis?
Impaired cognition
* Attention
* Memory
* Problem Solving
* Mental flexibility
Where does cannabis alter brain functioning on neuroimaging?
- Prefrontal cortex
- Cerebellum
- Hippocampus
What are some symptoms of cannabis withdrawal?
- Sleep difficulties
- Insomnia
- Feeling angry and/or aggressive and/or irritable
- Feeling anxious, “nervous”
Marijuana
- Marijuana is fat soluble
- Effects may persist or reoccur for 12-24 hours
What is the PK of marijuana?
- Absorption directly through the lungs
- Peak concentrations occur 30-60 minutes later
- Duration: 2-4 hours
What is the PK of THC?
- Lipid-soluble and can deposit in the tissues of fatty organs such as the brain, lungs, kidneys, and liver
- Even when blood levels of THC are zero, levels of THC in other organs can be substantial
- Most metabolites (by liver) are excreted slowly through the feces and urine (first pass metabolism)
What is the MOA of THC?
- Main target is the presynaptic endocannabinoid CB1 receptor
- Presynaptic inhibition of GABA neurons
- Disinhibition of dopamine neurons
- Increase dopamine release
What are the receptors, endocannabinoids, and enzymes of the Endocannabinoid System?
- Receptors: Cannabinoid Receptor 1 (CB1) and Cannabinoid Receptor 2 (CB2)
- Endocannabinoids: Anandamide, 2- Arachidonoylglycerol (2-AG)
- Enzymes: Fatty acid amide hydrolase (FAAH)
Where is CB1 expressed?
CNS
Where is CB2 expressed?
Peripheral immune cells
How does CB1 interact with the brain?
- Dose and time dependent
- Pscyhoactive and reinforcing effects
- Euphoria: Increased dopamine in reward center
What is a possible treatment for cannabis use disorder (CUD)?
- No strong evidence for any medication
- No approved medications for CUD
- N-acetylcysteine (glutamate)
