_________________________________________________________________________ Natural Psychedelics
Interactions Ibogaine can cause serotonergic effects and should be used with caution in patients taking other serotonergic agents [48]. Additionally, ibogaine is a substrate of CYP2D6, suggesting that its metabolism may be altered by drugs that inhibit or induce this enzyme [45; 59]. In fact, one clinical study found that paroxetine, a CYP2D6 inhibitor, can delay the metabolism of ibogaine [65]. Taking paroxetine 20 mg daily increased exposure to ibogaine and its metabolite, noribogaine, by twofold [65]. Considering that paroxetine is also a serotonergic drug, it is important that patients avoid the use of these chemicals in combination. Because ibogaine has been reported to cause QT interval prolongation, it should be used with caution in patients taking drugs that are known to prolong the QT interval. Summary Although there is growing interest in the use of ibogaine for substance use disorder, there is no prospective clinical research supporting its use for any medical purpose. As its use has also been associated with serious adverse effects, it should not be recommended as a treatment option. The whole iboga plant should be avoided, as there is no research on its safety or effectiveness and its use has been associated with reports of death. PSILOCYBIN MUSHROOMS The term “magic mushrooms” refers to various mushrooms that contain a psychedelic chemical called psilocybin. Most of these mushrooms are in the genus Psilocybe . However, there are also other mushrooms that contain psilocybin, including certain species in the genera Conocybe , Galerina , Gymnopilus , Inocybe , Panaeolus , Pholiotina , and Pluteus . These mushrooms have a history of traditional use for religious and spiritual rituals. However, they are also well known for their popular use as recreational drugs [10; 11; 66]. As mentioned, psilocybin can comprise 0.37% to 1.3% of the dry mushroom and there is high variability in the total psilocybin content for psilocybin mushrooms sold in various venues [9; 10; 11]. Psilocybin is classified as a Schedule I controlled substance by the DEA, though its use has been decriminalized in some states/cities [121]. Mechanism of Action Purified psilocybin has recently been the focus of an extensive amount of laboratory and clinical research. Although there is limited information available on the use of psilocybin mushrooms, information on the safety and effectiveness of psilocybin is increasing rapidly.
One observational study in patients in withdrawal due to opioid dependence has found that taking ibogaine 25–55 mg/ kg, given in multiple doses over 24 to 96 hours, is associated with a reduction in addiction severity, drug use, and feelings of depression for 12 months after treatment [52]. An additional observational study has found that providing ibogaine as part of a one-week detoxification protocol for opioid use is associated with the elimination or significant reduction of withdrawal symptoms in 80% of patients. Additionally, cravings and opioid use were modestly reduced [53]. One observational report evaluated the effects of ibogaine in patients with mixed substance use disorder—these patients primarily had cocaine use disorder, but some also used alcohol, tobacco, and cannabis. A single dose of ibogaine was associated with 5.5 months of self-reported abstinence; multiple doses of ibogaine were associated with 8.4 months of self-reported abstinence. It is important to note, however, that these patients had already been required to maintain abstinence for 30 days prior to treatment, which may have increased the success rate [113]. There are no prospective clinical studies that have evaluated the use of ibogaine for any purpose. The reports discussed here represent anecdotal evidence and should be interpreted with caution. Safety All known safety information is specific to ibogaine, as opposed to the whole plant. In general, ibogaine is known to cause multiple adverse effects, which may range from mild to very severe. The most common adverse effects reported with pure ibogaine are ataxia, confusion, diarrhea, headache, nausea, and vomiting. Multiple case reports have also associated the use of ibogaine with ventricular arrhythmias, cardiac arrest, and QT interval prolongation. QT interval prolongation progressed to torsades de pointes in some cases. In many of these reports, the patients had no prior history of heart disease [46; 47; 48; 54; 55; 56; 57; 58; 59; 60; 114]. There have also been multiple reports of death after ibogaine use. Although the exact cause of death is unclear in these cases, most reports provide objective data, such as serum ibogaine levels, that suggest ibogaine may have been a contributing factor [50; 52; 61; 62; 115]. There are also at least two reports of death occurring after the use of the iboga plant. In one case, the patient reported taking one teaspoon of iboga root in addition to methadone and diazepam and died 12 hours after ingestion [44]. In the other case, the patient consumed an unknown quantity of a powder that was labelled as iboga [63]. In both cases, ibogaine was detected in postmortem serum.
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