How Psychoactive Compounds Work
Psychoactive compounds change how we perceive and interpret reality. But how do they work?
Psychedelics (LSD and DMT)
Psychedelics, many known as “party” drugs, primarily interact with serotonin receptors, especially the 5-HT2A subtype. Human studies have shown that blocking this receptor dampens the psychedelic effects, while animal research links 5-HT2A activation to changes in behavior. The compounds can cause changes in perception, hallucinations, and dissociation.
Neuroimaging suggests these substances acutely reduce connectivity in the default mode network (DMN). The DMN is associated with self-referential thinking—the “ego” in Sigmund Freud’s psychoanalytic theory. However, psychedelic compounds also increase connectivity between other networks. The reshuffling of connections may explain the benefits reported by some users.
Psychedelics’ biological effects also extend beyond altering senses. Some compounds display anti-inflammatory and immune-modulating properties, both of which are attributed to symptoms of depression. Additionally, psychedelics can restore emotional sensitivity diminished by conditions like depression.
Other Psychoactive Compounds
To understand the effects of psychedelics, it’s helpful to contextualize how other psychoactive compounds affect the brain.
Alcohol
Alcohol is a popular and legal drug that affects various receptors in the brain, including GABA and opioid receptors. It enhances GABAergic neurotransmission activity, inhibiting the brain’s excitatory NMDA receptors. This results in sedation, relaxation, and decreased inhibition. Alcohol also affects dopamine and serotonin pathways, contributing to its euphoric effects. The World Health Organization (WHO) has stated that no consumption of alcohol is free from health risks. Other health agencies consider varying levels of alcohol consumption as generally safe.
Cannabis
Cannabis, also known as marijuana, weed, pot, Mary Jane, among other euphemisms, is now a legal recreational drug in many states in the United States. The primary psychoactive component of cannabis, THC, activates cannabinoid CB1 and CB2 receptors. By binding to these receptors, THC reduces the release of neurotransmitters and interacts with the brain’s reward pathway, similar to opioids. This activation of CB1 receptors results in euphoria, relaxation, altered perception, and cognition. It is sometimes prescribed to treat pain and other medical conditions.
Opioids (e.g., morphine, codeine, heroin)
Opioids, such as morphine and codeine, act on opioid receptors in the brain, specifically the mu, kappa, and delta receptors. By activating these receptors, opioids stimulate the brain’s reward pathway and increase dopamine levels. This activation leads to analgesia (pain relief), euphoria, sedation, and respiratory depression. Opioids can also cause dependence due to their effects on the brain’s reward system. Medical opioids are prescribed to treat pain.
Benzodiazepines (e.g., diazepam, lorazepam)
Benzodiazepines primarily act on GABA receptors in the central nervous system. They enhance the inhibitory effects of GABA, a neurotransmitter that reduces neuronal activity. This leads to anxiolytic (anti-anxiety), sedative, muscle relaxant, and anticonvulsant effects. They are prescribed to treat anxiety disorders.
Stimulants (e.g., caffeine, amphetamines, cocaine)
Stimulants increase dopamine, norepinephrine, and/or serotonin in the brain by affecting the reuptake transporters and vesicles responsible for the reabsorption and storage of these neurotransmitters. Additionally, stimulants act as adrenergic agonists, further enhancing their effects. The increased neurotransmitter levels lead to euphoria, increased wakefulness, attention, and, with chronic use, an increased risk of psychosis. Legal stimulants are used to increase alertness and treat attention-related disorders.
The exact differences between psychedelic and non-psychedelic compounds are still unclear. Nevertheless, as with unregulated supplements, psychoactive compounds “…have not been evaluated by the Food and Drug Administration. [These] products are not intended to diagnose, treat, cure, or prevent any disease.”
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Wikipedia contributors. (2024, January 23). Id, ego, and superego. In Wikipedia, The Free Encyclopedia. Retrieved 23:39, January 23, 2024, from https://en.wikipedia.org/w/index.php?title=Id,_ego_and_superego&oldid=1198207888
