PSYCHEDELICS SUBSTANCES

• A psychiatrist named Humphrey Osmond first used the term Psychedelic in 1957.
• The word is derived from the Greek words psyche, meaning "mind", and deloun, meaning "to manifest".
• Humans have used psilocybin and mescaline for ceremonies, healing and spiritual rituals for millennia.
• Temples built for mushroom "deities" in indigenous cultures in Mexico and Guatemala date back to 7000 BC.
• Records of the Greek "Eleusinian Mysteries" indicate that psychedelics were used in ceremonial rituals.

3. The modern-day use of psychedelics 

• The modern-day use of psychedelics is commonly associated with the German chemist Arthur Heffter isolating mescaline from the peyote cactus in 1897.
• In 1938, while investigating compounds related to ergotamine (one of the ergot alkaloids) the Swiss chemist Albert Hofmann accidentally contaminated himself with a small dose of LSD, he experienced what was likely the world's first "acid trip".
• On a hunch, he synthesised LSD in 1943 and with further testing, found LSD to be extremely potent and physiologically relatively safe.

4. War on drugs

• Between 1947 and 1967, LSD was widely used as a therapeutic catalyst in psychotherapy.
• The Harvard Psilocybin Project, founded by psychologist Timothy Leary, further proselytised LSD and psilocybin which led to the increasing recreational use of these substances.
• Around this time, medical concerns and the Vietnam War prompted the conservative Richard Nixon administration to criminalise the use of psychedelics and other psychoactive drugs.
• This "war on drugs" stopped all medical use and pushed recreational use underground.
• Media campaigns in the 1960s and 1970s further stigmatised the use of all psychoactive drugs.

5. Drugs work in the body

• Users of psychedelic substances report changes in perception, somatic experience, and mood, through processing and entheogenic experiences.
• Perceptual distortions most commonly include the visual domain.
• An intriguing phenomenon called synaesthesia may occur, where the sensory modalities cross and the user may hear colour or see sounds.
• About half of the ingested psilocybin is absorbed via the digestive tract.
• In the body, psilocybin is converted to psilocin, which is then metabolised in the liver.
• LSD is completely absorbed in the digestive tract and then metabolised in the liver.
• Classical psychedelics boost brain serotonin levels.
• Psilocybin's therapeutic effects require a trip that is mediated by the activation of serotonin receptors.
• A recent case report published in the American Journal of Psychiatry demonstrated that robust and sustained antidepressant effects can occur even in the absence of psilocybin's psychedelic effects.
• This finding, if replicated in larger trials, will have major implications for people with treatment-resistant depression. They can then get better without having to endure a trip.
• Modern neuroimaging suggests that psychedelics are neither stimulants nor depressants of brain activity.
• Instead, they increase the crosstalk between different brain networks and this correlates with the subjective effects of psychedelics.

6. The harm of the substances

• Death due to direct toxicity of LSD, psilocybin or mescaline has not been reported despite 50-plus years of recreational use.
• An overdose requires cardiac monitoring and supportive management in a low-stimulus and reassuring environment.
• Synthetic psychedelics (such as 25INBOMe) have been associated with acute cardiac, central nervous system, limb ischaemia, as well as serotonin syndrome.
• There have also been reports of death attributed directly to synthetic psychedelic use.
• The psychological effects of psychedelics depend on the interaction between the drug and the user's mindset (together called a set) and the environmental setting.
• People with a personal or family history of psychosis are strongly discouraged from experimenting with psychedelics.
• There is also no evidence that psychedelics cause physiological or psychological dependence nor has any withdrawal syndrome been identified.
• Tension headaches are common in the 24 hours after use and offset by the use of simple analgesics.
• This said, brief and self-limiting psychotic episodes can occur when a user is intoxicated with psychedelics, particularly LSD.
• They are more common among first-time users and those with a personal or family history of psychiatric illness.
• Users describe these experiences as a bad trip and they are more likely to occur in unfavourable environments.

7. Psychedelics used to treat neuropsychiatric disorders

• In November 2022, the results from a phase-II psilocybin trial were published in the New England Journal of Medicine.
• The trial found that a single 25 mg dose of psilocybin reduced depression scores over three weeks in people with treatment-resistant depression.
• Adverse events included headache, nausea, and dizziness which occurred in 77 per cent of the participants.
• Suicidal ideation, suicidal behaviour and self-injury occurred in all dose groups (1 mg, 10 mg and 25 mg).
• In 2017, the U.S. Food and Drug Administration (FDA) designated the use of 3, 4 methylenedioxy methamphetamine, also known as MDMA, to be the breakthrough therapy in the treatment of post-traumatic stress disorder (PTSD).
• Under its expanded access program the FDA has allowed a small number of people particularly those seriously ill with PTSD and who have not responded to other treatments to use MDMA.
• Recently, the U.S. non-profit Multidisciplinary Association for Psychedelic Studies (MAPS) also announced positive results from its observational study on MDMA-assisted therapy for patients with PTSD, echoing the findings of its phase III MDMA trial, published in Nature Medicine in May 2021.
• In 2018, the FDA granted breakthrough therapy status to psilocybin for treatment-resistant depression as well. 

8. The usage of psychedelics

• Although recent findings are encouraging, there remains uncertainty about where the psychedelic renaissance will take us.
• Psychedelic substances provide an intriguing avenue through which one can probe the broader constructs of creativity, spirituality and consciousness aside from their therapeutic effects.
• While not a panacea, psychedelic substances have certainly reinvigorated clinical and research interests and have added to psychiatry's ever-expanding therapeutic armamentarium.
• If larger phase III trials establish their safety and therapeutic efficacy, the FDA and other regulatory bodies may clear these agents for routine clinical use.