[In-depth] Serotonin and Friends

Posted on May 9, 2024  •  2 minutes  • 416 words

WIP

MDMA (Ecstasy) MDMA primarily exerts its effects by increasing the release of serotonin from the synaptic vesicles into the synaptic cleft, a small gap between neurons where neurotransmitter activity occurs. Here’s how it happens:

Serotonin Transport: MDMA enters serotonin neurons via the serotonin transporter (SERT). Once inside the neuron, MDMA disrupts the vesicular storage of serotonin by interfering with the function of VMAT2 (vesicular monoamine transporter 2), which normally transports serotonin from the cytoplasm into vesicles. Release and Reuptake Inhibition: MDMA causes a reverse transport of serotonin through the SERT, leading to an increased concentration of serotonin in the synaptic cleft. Furthermore, MDMA inhibits the reuptake of serotonin by blocking the SERT, allowing serotonin to remain in the synaptic cleft longer, intensifying and prolonging its effects on postsynaptic receptors. Receptor Activation: The elevated levels of serotonin activate various serotonin receptors, including 5-HT1A, 5-HT2A, and 5-HT2C, which contribute to the mood elevation, emotional closeness, and empathetic feelings associated with MDMA. This broad receptor activation also influences the release of other neurotransmitters like dopamine and norepinephrine, enhancing the psychoactive effects. Downstream Effects: The overall increase in neurotransmitter activity can lead to mood elevation, increased empathy, and euphoria, as well as physiological effects like increased heart rate and blood pressure. LSD (Lysergic Acid Diethylamide) LSD’s effects are primarily attributed to its action on the serotonin 5-HT2A receptor. Here’s the breakdown of its mechanism:

Receptor Binding: LSD is structurally similar to serotonin and binds strongly to the serotonin 5-HT2A receptors on neurons. This receptor is particularly important for its effects on cognition, perception, and the sense of self. Agonist Activity: Unlike other compounds that might only partially activate the receptor, LSD acts as a potent agonist at the 5-HT2A receptor. This means it fully activates the receptor, leading to a significant biochemical and signaling cascade. Psychedelic Effects: The activation of 5-HT2A receptors is known to lead to increased cortical excitation and reduced filtering of sensory information by the thalamus, resulting in the characteristic hallucinations and sensory distortions seen with LSD. Users report altered visual and auditory perceptions, time distortion, and profound changes in their thought processes and mood. Duration of Action: LSD’s effects are notably long-lasting, partly due to its ability to bind to 5-HT2A receptors in a way that causes the receptor to fold over the molecule, trapping it and prolonging its activity. Secondary Effects: While 5-HT2A is the primary target, LSD also affects other serotonin receptors and can influence dopamine pathways, contributing to its complex psychotropic profile.