Suicide and depression are serious public health issues. Our existing treatments are not as successful as we may like. Suicide is becoming more prevalent. Innovative and successful depression therapies are urgently needed.
Some psychedelics may have the ability to prevent suicidality. Overcoming the stigma associated with their use will be a challenge for both patients and doctors. The widespread acceptance of medical marijuana is still being hindered by a similar problem.
Psilocybin is a promising psychedelic that is present in more than 75 different species of mushrooms, the most well-known of which is Psilocybe Mexicana, also known as the "Magic Mushroom." After intake, psilocybin transforms spontaneously into psilocin, which is more lipid-soluble and the hallucinogenic substance. According to recent PET research, psilocin's capacity to activate the 5HT2A serotonin receptor is what causes it to have its psychoactive effects. Although some authors claim positive outcomes in clinical trials for the treatment of addiction, depression, post-traumatic stress disorder, and death anxiety, psilocybin has so far only shown modest efficacy.
A variety of tryptophan-derived beta-carbolines, including harmane and harmine, are also present in numerous species of the Psilocybe mushroom and may similarly have beneficial effects on brain function. Why do beta-carbolines play a key role in the effects of psilocybe mushrooms? Beta-carbolines have a strong inhibitory effect on the monoamine oxidase enzyme, which deactivates psilocin. Any plant or fungus that displays this behaviour is remarkable. The Psilocybe produces a wide range of various natural products via special pathways that diverge from the same building block, i.e., tryptophan, resulting in the production of dissimilar compounds, all of which directly or indirectly contribute to the same pharmacological effects.
Why would anyone anticipate that psilocybin would be effective in the treatment of depression given what is inside the fungus? Actually, no one ever anticipated that a 5HT2A agonist like psilocybin could be helpful for treating mental illness.
It is important to recognise the function of 5HT2A receptors in the brain in order to comprehend why that is the case. Schizophrenia, depression/anxiety, and drug addiction, for instance, may all be caused by anomalies in the structure and operation of the 5HT2A receptors. Medications that inhibit 5HT2A receptors are used to treat certain diseases. Let me repeat that final point: Psilocybin functions exactly the opposite of medications used to treat sadness and anxiety!
Perhaps the effects of beta-carbolines are what give the Psilocybe mushroom its health benefits. In a recent animal study, the beta-carbolines harmane and harmaline had an impact similar to an antidepressant. When other medications have failed to control major depressive episodes, medications that block monoamine oxidase have been utilised for many years. They all have a bad side effect known as the "Cheese Effect," which is why they are not commonly given today. Foods containing the amino acid tyramine, which is present in beer, cheese, and wines, can cause a person taking beta-carboline or any monoamine oxidase inhibitor's blood pressure to rise sharply, resulting in hypertensive crisis, stroke, and death.
A cultural shift
The adoption of psychedelics for therapeutic reasons has been made possible by the approval of formerly banned medications for medical use. Recent events, such as the legalisation of marijuana and the FDA's recent rescheduling of esketamine1 (the first legal psychedelic) for the treatment of TRD, underscore this societal shift (Krupitsky & Grinenko, 1997).
The way we treat and handle mental illnesses may soon change as a result of the accelerated speed of research and the quickly expanding amount of information. Research on a wide range of illnesses is now possible because to the resurgence of interest in psychedelics. Studies exploring the use of psychedelics in the treatment of Alzheimer's disease, anorexia nervosa, obsessive-compulsive disorder (OCD), and addictions (to alcohol, tobacco, crack cocaine, and other substances) are either planned or currently underway.
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