Lec 5-Drugs of abuse (3) Flashcards
1
Q
Magic mushrooms
A
- Liberty cap (Psilocybe semilanceata) Psilos= bald; Cybe= head
- Fly agaric (Amanita muscaria) contains ibotenic acid and its derivative muscimol
2
Q
Russian roulette with mushrooms
A
3
Q
Cannabis- pharmacology and toxicity
A
- Pharmacology
- Widely used, active ingredient- tetrahydrocannabinol (THC)
- Plant alkaloid, from cannabis sativa
- Euphoric, amnesic
- Useful antiemetic (Cancer chemotherapy, e.g. nabilone)
- Tolerance develops to THC
- Withdrawal, only serious in heavy users (anxiety and agitation)
- Toxicity
- Heavy use leads to cannabinoid psychosis, delusions, paranoia
4
Q
CB1R binding sites
A
- Hippocampus
- Entorhinal cortex
- If you weigh this one receptor, it will be more abundant than all other receptors in the brain
5
Q
Cannabis- mechanism
A
- Binds to own receptors CB1R in brain CB2R in a periphery
- Lots of CB1R in the limbic system and mesolimbic nuclei
- Endogenous ligands ‘anandamide’ Arachidonic acid (AA) derivative Arachidonyl etholamine(AEA) & 2-arachidonyl glycerol (2-AG)
- G-coupled CB-1 receptors on inhibitory (GABA) presynaptic terminals
- Activation leads to profound depression of GABA release
- In VTA this leads to DA release in NAc
6
Q
Cannabis- mechanism- hCB1 cannabinoid receptor
A
- GPCR
- 7 transmembrane proteins
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7
Q
Volatile substances
A
- Pharmacology
- Acts similarly to anaesthetics, altering neuronal membrane stability
- Abusers appear drunk, but effect wear off in 30 minutes
- Toxicology
- significant risk of sudden death due to cardiac arrest or blood O2 depletion (amyl nitrate, butane)
- Peripheral and central neuropathy (hexane)
- Hearing and sight loss (toluene)
- Bone marrow damage (benzene)
8
Q
Anticonvulsants- pharmacology and toxicity
A
- Pharmacology
- Gabapentin, pregabalin
- Abusers appear drunk
- Toxicology
- Significant risk of sudden death due to co-administration with heroin and other drugs
- Big increase in prescription since 2013
- 3% of prison population prescribed one of these drugs- twice rate in wider community
9
Q
Synthetic cannabinoids
A
- “Legal highs” e.g. JWH-018 appeared first in 2008
- Full agonist at CB1R and CB2R
- Synthetic cannabinoid receptor agonist (SCRAs)
- Sold as black mamba or exodus damnation; Spice
- Produces hypothermia, bradycardia
- Very potent (Sub-nanomolar affinity at CBR 0.06e10-9 (Ic50))- very high
- Addictive, strong withdrawal response
10
Q
Synthetic cannabinoids- mechanism
A
- Binding at type 1 cannabinoid receptor CB1R
- Highly lipophilic (long-acting)
- EC50 often long, driving massive CB1R activity
- Effects on GABA inhibition
- Toxicity: abulia, psychosis, hypothermia, catatonic state (stupor, mutism, unresponsiveness)
- Catalepsy- maintenance of an uncomfortable, rigid posture (a feature of catatonia)
- Produce a parkinsonian state in basal ganglia, massive inhibition of movement pathways= zombie-like movement
11
Q
Mephedrone
A
- Aka M-cat or miaow-miaow; 4-methylmethcathinone (4-MMC)
- A 1930s drug, very popular in 2012
- Euphoric, stimulant, decreased hostility, similar to Kat (contains cathinone)
- Mechanism 500% increase, DA in NAc 950% 5-HT increase
- Side effect- Bruxism- grinding of teeth; Malignant hyperthermia
12
Q
Mephedrone- mechanism
A
- DA + 5HT transporter
- Block
- Reversal
- Direct displacement
13
Q
Methylenedioxyprrovalerone
A
- Aka Super-coke or cloud-9
- Developed in 1969- popular now
- Stimulant, euphoric no entactogenic qualities
- Mechanism- it is an NDRI
14
Q
Methylenedioxypyrovalerone- mechanism
A
- DAT and NET block by MDPV
15
Q
Bath salts
A
- Stimulant, euphoric, propsychotic
- Mechanism- often a mix of MDPV and mephedrone or other amphetamine-like agents
- Side effect- can be dangerous- may cause violent behaviour and florid psychosis
