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
OD effects of LSD
Is pretty rare and requires very large doses
- induces cardiovascular collapse
What hallucinogen has no withdrawal/tolerance/dependence?
LSD
LSD intoxication syndrome
Symptoms
- mydriasis
- tachycardia
- sweating
- palpations
- blurring of vision
- tremors/mild seizures
- lack of coordination
- psychosis symptoms
usually lasts a while (4-5 hrs after last use)
Treatment:
- supportive counseling
- benzos = seizures and NE effects
- antipsychotics = psychosis symptoms
Methylendioxymethamphetamine (MDMA/ecstasy) MOA
Reverses SERT receptors (now are efflux receptors)
- Increases extracellular concentrations of serotonin in mass
- causes depletion of serotonin concentrations = depression/crash
does not impair intellectual capacities
is similar to amphetamines, which does this same mechanism, but for DAT receptors instead
MDMA intoxication and toxic symptoms
- # 1 killer = hyperthermia and dehydration
- results in extreme drinking of water = hyponatremia = seizures/coma/death*
Symptoms
- seizures
- serotonin syndrome*
- mydriasis
- tachycardia
- sweating
- palpitations
- blurring of vision
- bruxism
- tremors
- lack of coordination
Withdrawal MDMA symptoms
Increased aggression and depression are the only two mainly
- due to depletion of serotonin amounts
Phencyclidine (PCP) MOA
Antagonist of NMDA glutamate receptors
- VERY potent at inducing psychotic symptoms
- also causes very bizarre responses to stimuli and sometimes catatonia
What hypothesis of schizophrenia is supported but he MOA of PCP?
Glutamatergic hypothesis of schizophrenia
PCP intoxication and OD symptoms
VERY violent = key feature
Symptoms
- belligerence
- impulsiveness
- impaired judgement
- nystagmus
- ataxia
- seizures/coma
- hyperacusis
- muscle rigidity/catatonia
- no/ very reduced pain responses
Death symptoms:
- cardiovascular toxicity (heart attack)
- neurological toxicity (coma/seizures)
- rhabdomyolysis and hyperthermia
Treatment of PCP OD/toxicity
NO antidote
place patient in non-stimulating environment (+/-) restraints
Acidification of urine via IV vitamin C
- theorized to increase elimination of the PCP
Antipsychotics (treat psychosis)
