@theclinic

Methamphetamine (C10H15N), also known as meth or crystal meth, is a colourless liquid at room temperature. It is more commonly encountered as the hydrochloride salt (C10H15N.HCl), which is a white solid under standard conditions. It is a central nervous system stimulant, and is used as a recreational drug.

Methamphetamine acts as an agonist at trace amine-associated receptor 1 (TAAR1), resulting in the release of cyclic adenosine monophosphate. This causes dopamine and noradrenaline transporters to reverse the movement of dopamine and noradrenaline through them; instead of taking them up from the synapse, it releases them from the cell. Furthermore, it inhibits monoamine oxidase (MAO), which normally breaks down dopamine and noradrenaline.

The resultant increase in dopamine and noradrenaline in the synapse causes the corresponding receptors on the postsynaptic membrane to be stimulated to a greater extent, resulting in feelings of euphoria, increased alertness, and a raised heart rate.

Methamphetamine, however, has a high risk of addiction. The high levels of dopamine and noradrenaline can result in tolerance by the body as the postsynaptic neuron reduces the number of receptors to modulate the stimulus. A protein called ΔFosB is also produced in the neurons, resulting in the increased transcription of certain genes, producing addictive behaviour.

As ΔFosB is degraded much more slowly than related proteins, it accumulates upon regular consumption of methamphetamine, resulting in increasing levels of addiction.

Methamphetamine also produces a range of side effects such as loss of appetite, dry skin, acne, insomnia, irregular heartbeat, psychosis, scratching of the skin, as well as loss of teeth. An overdose can also result in tremors, hyperthermia, cerebral haemorrhaging, kidney failure, circulatory collapse, coma, and death. (Below: before/after methamphetamine consumption)

It has been used as a treatment for attention-deficit hyperactivity disorder and obesity, albeit rarely due to its significant drawbacks compared to other existing treatments for these conditions. One of its isomers, levomethamphetamine (below left), is also used in nasal decongestant sprays as it results in vasoconstriction. Unlike its optical isomer, dextromethamphetamine (below right), it does not result in addiction and dependence.

Methamphetamine can be easily synthesised from the condensation of phenylacetone with methylamine, followed by reductive amination:

Serotonin (C10H12N2O), also known as 5-hydroxytryptamine (5-HT), is a white solid that is slightly soluble in water under standard conditions. Like dopamine (Day 44), it is an important neurotransmitter that regulates vital processes in the body.

In the brain, serotonin is largely produced in the neurons of raphe nuclei, which are found in the brain stem. It regulates perceptions of resource availability, which can affect bodily functions and sensations such as mood, appetite, digestion, and sleep.

Serotonin is released from the presynaptic neuron into the synaptic cleft via the fusing of serotonin-containing vesicles with the presynaptic membrane. It then binds to 5-HT receptors on the postsynaptic membrane. 

There are many different subtypes of 5-HT receptors, and each produces a different cellular response upon binding of serotonin. For example, the binding of serotonin to 5-HT2A receptors results in psychedelia, whereas the binding of serotonin to 5-HT3 receptors results in vomiting.

Due to the diverse functions of serotonin in different cells, many classes of drugs, such as anxiolytics, antidepressants, antiemetics, and antimigraine drugs, are designed to target the serotonin system. 

For example, selective serotonin reuptake inhibitors (SSRIs), such as sertraline (Zoloft) inhibit the reuptake of serotonin into the presynaptic membrane from the synaptic cleft. This increases the concentration of serotonin in the synaptic cleft, and the increased binding of serotonin to the 5-HT receptors. This results in an anxiolytic, antidepressive effect.

On the other hand, drugs such as ondansetron act on the receptors themselves; they act as antagonists to 5-HT3 receptors, preventing serotonin from binding to it. As a result, there is a reduction in nausea and vomiting, which are common side-effects in chemotherapy. Hence, such antiemetics are useful and are often co-administered together with chemotherapeutic agents.

In the human body, tryptophan is first hydroxylated via the action of tryptophan hydroxylase to produce 5-hydroxytryptophan, which is then decarboxylated by aromatic amino acid decarboxylase to produce serotonin.