Drugs of abuse

Question 1

Cocaine

Answer 1

Blocker of dopamine transporter, norepinephrine transporter and serotonin transporter.

MOA: dopamine is released into the cleft to eventually be removed by dopamine transporter, that reuptake the dopamine into presynaptic neurons. Cocaine blocks the dopamine transporter so the effect of cocaine is that the neuron will signal with same frequency but since dopamine is not taken up against it will stay in the cleft for longer and keep activating receptors in the postsynaptic neuron and this is what causes the rewarding effect.
The behavioral effects are very similar to those of amphetamines although the duration is shorter.

Unwanted effects: tachycardia, vasoconstriction, tremors, cardiac arrest, and psychosis.

Question 2

Amphetamine

Answer 2

-Enhance the release of dopamine and norepinephrine from synaptic vesicles.
-Inhibit the reuptake of neurotransmitter by blocking dopamine transporter and norepinephrine transporter. (competitive inhibitors on the transporters).
-Inhibit MAO (which normally breaks down monoamines), potentiating the effects of amphetamine.

Unwanted effects: restlessness, aggressive behavior, acute schizophrenic attack, and tolerance.

Question 3

MDMA

Answer 3

MDMA primarily induces release of serotonin from presynaptic neurons into the synaptic cleft. It enters the presynaptic neuron through serotonin reuptake transporters . Once inside the neuron, MDMA displaces serotonin from vesicular storage sites and promotes its release into synaptic cleft. Increases 5-HT signaling, leading to feelings of empathy, euphoria, and mild hallucinations.

Unwanted effects: acute hyperthermia and increased ADH secretion (overhydration but then don’t pee as much so this can cause problems). There are also aftereffects of MDMA, such as depression, anxiety, irritability/aggression, ‘the mid-week blues.’

Question 4

Nicotine

Answer 4

Acts as an agonist on the nictinoc Ach receptors in the ventral tegmental area (VTA), from which dopaminergic neurons project to the nucleus accumbuns – reward pathway.
Nicotinic Ach receptors are located both pre and post synaptically, causing respectively enhanced transmitter release and neuronal excitation. Nicotine increases the firing rate and phasic activity of VTA dopaminergic neurons.

Side-effects: nausea/vomit (nACh-R in stomach), tolerance, psychological dependence, and physical dependence.

Question 5

Opioids

Answer 5

Agonist at opioid receptors.
Opioids act through the Gai pathway; this decreases AC activity -> decreases cAMP ->decreases PKA activity. -> this inhibition of PKA leads to decreased phosphorylation of various target proteins and ion channels, resulting in changes in neuronal excitability and neurotransmitter release.

Opioids have euphoric and sedative effects. Morphine and heroin are primary examples of opioids.

Adverse effects: tolerance, respiratory depression, psychological and physical dependence.

Question 6

Ethanol (psychedelic drug)

Answer 6

Ethanol acts as a general anaesthetic.
Ethanol enhances the activity of inhibitory neurotransmitter GABA by increasing GABA-ergic transmission. Activation of GABA leads to hyper polarization of neurons, reducing their excitability.
Ethanol Inhibits the activity of the excitatory neurotransmitter glutamate, primarily by blocking NMDA glutamate receptors.

At low doses, ethanol is a stimulant and increases reward.

Adverse effect: slurred speech, decreased motor coordination, decreased intellectual performance, neurotoxicity, nausea, and addiction.

Question 7

Dependence thus involves both psychological and physiological components and can be considered as a four-stage process around which dependent individuals recycle:

Answer 7

1) Initiation. Drug exposure produces positive subjective effects (euphoria).
2) Maintenance. The person wants to keep the euphoria feeling, so drug taking becomes compulsive.
3) Withdrawal. Signifying that dependence has developed. Appears if the person stops taking the drug.
4) Craving –> Relapse.