Psychedelics, among the oldest psychoactive agents used for religious or mystical experiences, were accidentally discovered in 1943 after LSD's synthesis in 1937. Banned in 1966 due to political and social factors, research remained limited until a 'Psychedelic renaissance' in the 1990s reconsidered their therapeutic value. This article reviews their history, pharmacology via 5-HT2A receptor agonism, and psychological effects, comparing proposed therapeutic uses—for depression, PTSD, anxiety, addiction, neurodegenerative and autoimmune diseases—to potential harms like tolerance, hallucinogen persisting perception disorder, and psychosis. The analysis concludes that therapeutic benefits significantly outweigh harms, warranting further research and clinical trials across countries and cultures for legal clinical approval.
Ketamine, an anesthetic and dissociative drug, can lead to addiction and severe withdrawal symptoms. It alters brain networks, particularly the prefrontal cortex, hippocampus, and mesolimbic pathway, affecting decision-making, memory, and reward processing. The drug's addictive potential involves neurotransmitter systems, specifically glutamate and dopamine, and neuroadaptive changes during withdrawal. Low-dose ketamine may also alter cortisol secretion and dysregulate the hypothalamic-pituitary-adrenal (HPA) axis, which may relate to its repurposing as a fast-acting antidepressant. Side effects include heart and blood vessel instability, respiratory depression, liver injury, and hallucinations. Understanding these neurobiological processes is essential for developing treatments for ketamine addiction and managing withdrawal.