Cannabis Flashcards
1964 Gaoni & Mechoulam
isolate THC from hashish and determine that it is the chemical in cannabis that causes “high”
1988 Devane & Howlett
discover the location of the CB1 receptor (rat brain) – the target of THC
Rimonabant
CB1 antagonist drug for obesity approved in Europe
Why was rimonabant pulled from the market?
side effects of anxiety and suicidality
the most abundant G-protein coupled receptor in the brain
CB1 receptors
CB1 receptors are activated by
endocannabinoids and THC (present throughout the brain at different levels)
Areas with highest density of endocannabinoids:
cingulate cortex, hippocampus, amygdala, cerebellum, hypothalamus, periaqueductal grey- pain, and area postrema in medulla- vomiting
CB2 also known as…
“peripheral cannabinoid receptors”- because they are highly expressed in the body & are especially immune cells
the receptor that is principally involved in anti-inflammatory and immunosuppressive actions
the CB2 receptor
the receptor that mediates most of the psychoactive effects of cannabinoids
the CB1 receptor
The cannabinoid system is…
the brain’s equalizer- modulating the intensity of every neuronal signal (only made where they are needed and are eliminated quickly- balance and equalize neuron activity)- Always acting in concert with another neurotransmitter
Agonists of CB1 receptor
endocannabinoids and THC
Endocannabinoids
- Appetite stimulant
- Reduces pain (part of descending pathway)
- Promotes learning & memory
THC (Tetrahydrocannabinol)
- Long-lasting – acute effects last for hours, accumulates in fat tissues and remains in body for weeks
- Appetite stimulant & anti-emetic
- Reduces pain (analgesic) and muscle spasticity
- Impairs learning & memory
- Hallucinations (sensory & time distortion)
- Psychosis
early cannabis use (by age 15) confers greater risk for…
schizophrenia outcomes than later cannabis use (by age 18)
Cannabis tolerance is caused by
downregulation of CB1 receptors
CB1 & CB2 are both…
GPCRs NOT ION CHANNELS
Cannabis use disorder affects
30% of those who use cannabis
4 Medical Uses of Cannabis, THC and CBD
- Nabiximol - (Sativex)
- Cannabidiol – (Epidiolex)
- THC as dronabinol (Marinol)
- Nabilone
Nabiximol (Sativex)
- (mouth spray) 1:1 THC:CBD
- Reduces muscle spasticity and pain that accompanies multiple sclerosis.
- Reduces pain in cancer patients
Cannabidiol (Epidiolex)
- is approved to treat childhood epilepsy
- we are not sure what it does, looks like it acts at CB1 receptor (mechanism of action is not really clear because it has many drug targets)- not selective
THC as dronabinol (Marinol)
- approved to treat anorexia in HIV/AIDS
- treat nausea and vomiting induced by chemotherapy
Nabilone
(A synthetic analog)
- used to treat anorexia in AIDS; nausea, vomiting with chemo
- It is used off label for the treatment of chronic pain/neuropathic pain and fibromyalgia.
effects of drugs that block the CB1 receptor
- promote weight loss
The 2 most prevalent endocannabinoids in the brain:
- Anandamide
- 2-AG
