_________________________________________________________________________ Natural Psychedelics
Clinical Effects Depression
to normal after 30 minutes [16; 21; 32]. The hallucinations that occur with ayahuasca can last for several hours and may cause disorientation, delusion, agitation, and dissociation [16; 21; 110]. Some of the more serious adverse effects reported with use have included convulsions, coma, and psychosis. However, due to the anecdotal nature of many of these reports, it is unclear if ayahuasca was the cause or if there were other precipitating factors [25; 33; 34; 35]. Interactions Some of the alkaloids in ayahuasca, such as harmine and harmaline, have been shown to inhibit cytochrome P450 (CYP) 2D6 and 3A4 in laboratory research. Although this effect has not been confirmed in humans, ayahuasca should be used with caution in patients taking drugs that are substrates of these enzymes [36]. Because DMT, harmaline, and harmine all have serotonergic effects, or the ability to enhance the serotonergic effects of other substances, ayahuasca should be used with caution in patients taking serotonergic drugs. In fact, there has been at least one case report of serotonin syndrome in a patient who was stabilized on fluoxetine 20 mg daily and consumed ayahuasca 100 mL [25; 37]. Serotonin syndrome occurs when high levels of serotonin build up in the body, typically due to the use of multiple drugs that increase serotonin levels. Although this is a rare occurrence, serotonin syndrome can be life-threatening. Symptoms include shivering, diarrhea, muscle rigidity, tremors, fever, severe headache, altered mental status, and seizures. Although many drugs may have minor serotonergic activity, the drug classes most commonly associated with serotonin syndrome include: • Monoamine oxidase inhibitors (MAOIs) • Selective serotonin reuptake inhibitors (SSRIs) • Selective serotonin-norepinephrine reuptake inhibitors (SNRIs) • Tricyclic antidepressants (TCAs) • Atypical antipsychotics The risk for serotonin syndrome increases with the addition of each serotonergic drug to any drug regimen. However, the risk is highest when MAOIs are used in combination with other serotonergic drugs. This is because MAOIs inhibit the breakdown of serotonin, perpetuating the effects of other serotonergic agents. Many herbs and supplements can also increase the risk for serotonin syndrome and should be included in patient risk evaluations.
To date, evidence on the use of ayahuasca for depression is limited to very small, low-quality trials, most of which were conducted in Mexico. In one trial of 29 patients with moderate- to-severe treatment-resistant depression, taking a single dose of ayahuasca 1 mL/kg moderately improved symptoms of depression after seven days when compared with placebo. The response rate with ayahuasca was two- to three-fold greater than that seen with placebo [23]. Two small, open-label trials in patients with recurrent major depressive disorder show that taking a single dose of ayahuasca 2.2 mL/kg improved symptoms of depression when compared with baseline [26; 27].
The U.S. Department of Veterans Affairs asserts that ayahuasca use may be associated with a short-term reduction in depression symptoms and suicidality. (https://www.hsrd.research.va.gov/ publications/esp/psychedelics-mh-brief.pdf.
Last accessed June 16, 2023.) Level of Evidence : Low
Prolonged Grief Disorder One observational study in patients with prolonged grief disorder found that taking part in a retreat including four to nine ceremonial ayahuasca experiences was associated with moderately reduced grief severity when compared with baseline. About 50% of the patients at the retreat attributed a sense of healing to the ayahuasca [19]. There is no prospective clinical research evaluating ayahuasca for this purpose. Substance Use Disorder There is interest in the use of ayahuasca for multiple forms of substance use disorder, including alcohol, opioids, cannabis, and mixed substances. However, no prospective clinical research has evaluated its use for this indication. Observational research in patients with multiple self-reported addictions has found that taking ayahuasca twice during a four-day group-counseling retreat is associated with improved feelings of hopefulness, empowerment, mindfulness, and quality of life for up to six months after the retreat. Use of alcohol, tobacco, and cocaine, but not cannabis or opioids, may also decrease [28]. Safety Ayahuasca has been associated with a number of adverse effects, ranging from mild to severe. The most common adverse effects reported with use include gastrointestinal upset, mydriasis, slurred speech, tingling, trembling, and sweating [21; 23; 26; 27; 30; 31]. It can also cause transient elevations in blood pressure and heart rate that typically return
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MDTX1625
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