Natural Psychedelics _ ________________________________________________________________________
Psilocybin is a prodrug that metabolizes to psilocin, a hallucinogenic tryptamine that acts at serotonin 2A receptors [67; 68; 69; 70]. Although this seems to be the primary site of action, it is thought that psilocybin may also act on other pathways in humans. Some brain imaging suggests that it may have activity at serotonin 1A receptors as well. It seems to have little affinity for dopamine receptors [10; 69; 116]. The hallucinogenic effects of psilocybin involve visual, auditory, tactile, and other illusions, as well as changes in time and space perception. Some patients have reported recurrent drug-like experiences, mostly visual in nature, that occurred more than 24 hours after the last dose of psilocybin. These flashbacks lasted for seconds to minutes and were considered mild in nature [66; 71; 72; 73; 74; 75; 76; 77; 78]. Clinical Effects Psilocybin has been evaluated in a number of small prospective studies. The evidence to date suggests that it may be beneficial for some people, although the benefits vary and it is unclear how these benefits compare to standard therapies. Anxiety Small studies on the use of psilocybin for anxiety suggest that, when used in combination with psychotherapy, it may reduce symptoms of anxiety in some patients for up to six months when compared with either a niacin placebo or low-dose psilocybin. However, most of this research was not conducted in patients with a specific diagnosis of anxiety at baseline. Rather, patients had anxiety, depression, and/or existential distress related to cancer. These studies used psilocybin 0.2–0.43 mg/kg, provided either as one or two doses [71; 73;
According to the U.S. Department of Veterans Affairs, psilocybin-assisted psychotherapy may reduce depression severity and lead to sustained remission for some participants at 12 months compared to wait list controls, but these benefits were
not observed when psilocybin-assisted psychotherapy was compared to intensive psychotherapy and daily escitalopram. (https://www.hsrd.research.va.gov/publications/esp/ psychedelics-mh-brief.pdf. Last accessed June 16, 2023.) Level of Evidence : Low Substance Use Disorder There is significant interest in the use of psilocybin as a treatment for various forms of addiction and substance use disorder, including alcohol, tobacco, and opioids. Clinical research in this area is very limited and has mostly involved small, uncontrolled exploratory studies. The highest quality study to date was conducted in patients with alcohol dependence. This study, which enrolled 93 patients, suggests that psilocybin may be modestly beneficial for further reducing alcohol intake when compared with diphenhydramine. However, it did not increase rates of total abstinence, and it is unclear if it would be beneficial in patients with more severe alcohol use disorder. In this study, psilocybin was provided as a single dose of 25 mg per 70 kg in the fourth week and a single dose of 25–40 mg per 70 kg in the eighth week [86]. Other Uses There has also been some early research on the use of psilocybin for a variety of other mental health conditions, including demoralization and obsessive-compulsive disorder, as well as for the general improvement of psychological well-being. However, the available research is limited and inconclusive. Safety The use of nonstandardized psilocybin mushrooms has been associated with multiple cases of toxicity. For example, seizures, myocardial infarction, and acute kidney failure have been reported in some patients [11; 87; 88]. There is also a growing body of literature on the adverse effects of purified psilocybin. Most clinical research agrees that the most common side effects noted at therapeutic doses are headache, nausea, anxiety, and transient elevations in blood pressure and heart rate. The increases in heart rate and blood pressure seem to peak at about two hours and last for approximately six hours after use [73; 86]. Unlike iboga, psilocybin has not been associated with QT interval prolongation [73; 89].
79; 80; 117]. Depression
The largest study conducted to date enrolled 59 patients and compared psilocybin 25 mg, taken as two separate doses three weeks apart, to escitalopram 20 mg daily for six weeks. The patients in this study were also receiving psychological support. The study found that psilocybin and escitalopram were equally effective for reducing symptoms of depression. Additionally, 57% of patients taking psilocybin achieved remission, compared with 28% of those taking escitalopram. However, it is unclear if these effects persisted beyond the six- week time period [81]. Small clinical studies also indicate that taking psilocybin as an adjunct to psychotherapy reduces symptoms of depression in some patients for up to 12 months when compared to baseline, delayed treatment, niacin placebo, or low-dose psilocybin. However, most of this research was not conducted in patients with a specific diagnosis of depression. Rather, patients had anxiety, depression, and/or existential distress related to cancer. Psilocybin was given as a single dose of 0.2–0.43 mg/ kg or 10 mg and 25 mg given seven days apart [71; 73; 79; 80; 82; 83; 84; 85; 117; 118].
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