Cannibus And Hallcinogen Abuse Flashcards
MOA of cannabis
Agonists for the CB1 and CB2 receptors
- agonists for CB1 also releases inhibition of dopaminergic signaling in the VTA (reward system increases and mild hallucinations)
CB1/CB2 receptors work by
1) inhibiting neuronal cells via Gi/Go coupling = decreased Adenylate Cyclase and cAMP
2) inhibits voltage-gated Ca2+ channels
3) stimulates potassium channels
* any of these 3 can occur separately or in conjunction*
What is the psychoactive component of cannabis?
Delta-9-tetrahydrocannabinol
- THC
How do endongenous cannabinoids induce their effects?
anandamide
By retrograde signaling via the anandamide transporter on the post synaptic cells
- leaves post synaptic cell (usually in response to overstimulation), leaves and binds to CB receptors on presynaptic cells and enters presynaptic cells
Where are CB1/CB2 located?
CB1 = centrally located - corticolimbic pathway
- basal ganglia
- cerebellum
- nucleus accumbens
- PAG
- hypothalamus
- cerebellum
CB2 = peripheral located
- spleen
- tonsils
- thymus
- blood cells
- mast cells
Why is cannibals considered the lowest risk substance abuse substance?
Because CB1 receptors are NOT found in the medulla
- lowest risk of respiratory depression
Effects of agonism of CB1
Agonism of CB1 receptors
- physical relaxation
- hyperphagia
- tachycardia
- decreased coordination
- decreased nausea
- minor pain modulation
- mild hallucinations
Medical uses for THC
Almost all are due to CB1 receptor agonism
- Stimulate appetite for AIDS and cancer patients
- reduces seizure frequency in epileptic patients (especially children)
- decreases interocular pressure in glaucoma
- reduces pain
- reduces nausea in cancer
Mechanism of chronic THC use
Down regulates CB1 receptors
- tolerance
Leads to loss of motivation and sense of boredom
- also decreased IQ if used in adolescence
In addition to CB1/2 agonism , what is another common indirect effect of THC?
Indirectly Increases GABA singling in hippocampus
- leads to short-term memory capacity, muscle weakness and impaired motor control
Cannabis intoxication symptoms
Euphroia
Apathy
Fear/distrust/panic
Increased appetite
Hallucinations
Social withdrawal
Dry mouth
Sedation
Tachycardia
Conjunctival congestion (red blood shot eyes) - most sensative
Pharmacokinetics of cannibus
Smoked = rapidly dissolved, maximum effects = 1 hr, easily excreted
Oral = slowly dissolved, maximum effects = 3+ hrs, slowly excreted
- more likely to experience OD/intoxication
*distributes in adipose tissue very easily, therefore THC is slowly released into bloodstream over 5 weeks in chronic users. (Positive test doesn’t always mean immediate./acute use)
“Dabbing”
Oral use of Butane hash oil (BHO)
- 75% of THC content (5-10% in smoking normal weed)
Really dangerous because terpenes in the BHO are degraded into methacolein-> acute lung injury if it gets into the lungs
- also found in some vaping and e-cigarettes
Tolerance and withdrawal of cannabis
Develops rapidly and with chronic use
- usually disappears rapidly however
- younger patients are more prone
Symptoms
- restlessness
- irritability
- agitation
- insomnia
- sleep EEG disturbance
- nausea/cramping
- decrease appetite and weight loss
- pain
Treatment of cannabis withdrawal
No antidote
- treat symptoms (zolpidem = sleep disturbances, Gabapentin = depression, busprion = anxiety)
CBT and contingency management therapies are 1st line also
Lysergic Acid Diethylamide (LSD) MOA
Partial agonism of 5-HT(2a)
- mediates serotonin, dopamine and NE systems
Is very strong at inducing psychosis-like symptoms
- so strong that in fact to test antipsychotics efficacy, patients are often put in and LSD-induced psychosis
