What a long, strange trip it’s been. ~ American musical group The Grateful Dead in the song “Truckin'” (1970)
Humans have a decided fondness for mind-altering substances. Contrary to the indication of Grateful Dead posters, a bear won’t eat a psychedelic mushroom, as it cannot bear the disorientation.
Psychotropic drug use affects glia. Any chemical compound that registers with the brain affects glia, and so is psychotropic to some degree.
Nicotine acts on the acetylcholine receptor, caffeine on the adenosine receptor. Both receptors are expressed in glia. Glia have receptors matching those of neurons, but it is glia, not neurons, that make sense of the world as part of the mind-brain.
Tetrahydrocannabinol (THC), the psychoactive ingredient of cannabis, mimics endocannabinoid neurotransmitters, inciting release of internal stores of calcium in astrocytes, causing calcium waves that psychically massage into a dreamlike state.
Ingested alcohol affects calcium-binding proteins, cause astrocyte calcium release. Alcohol also causes reactive oxygen species release, the same apoptotic kiss of cell death used to fight infections, which explains why alcohol is an antiseptic. Apoptotic kisses to astrocytes are a hoary practice of the Collective to stay stupid in pursuit of pleasure.
Opioids affect a variety of receptors throughout the brain: with the hippocampus, amygdala, and claustrum figuring prominently. Opioid receptors are ancient in evolutionary terms. They were already present with the origin of jawed vertebrates over 450 million years ago. This explains both broad receptivity and the highly addictive nature of opium.
Usually, habitual use of psychoactive agents represses the natural cellular dynamics of receptor production via artificial supply. Near-constant induced receptor activity causes a cell to manufacture less of the receptor; hence addition by feeling a deficit when the unnatural supply is withdrawn.
Cocaine owes its addictiveness to merrily stimulating reward pathways by inhibiting serotonin, norepinephrine, and dopamine reuptake. The mood elevation that cocaine yields by allowing these neurotransmitters to slosh around for too long gives way to irritability and depression when drug use is stopped.
When the artificial stimulation of neurotransmitters is withdrawn, cell signaling is diminished. Withdrawal symptoms nag until natural receptor production can recover.