Natural Psychedelics _ ________________________________________________________________________
• Peyote: This cactus contains the psychedelic chemical mescaline. • Salvia divinorum : The leaf of this herb contains salvinorin A, a psychedelic chemical. When potency concerns are raised, many people immediately consider the impact on therapeutic and psychedelic effects. However, variable potency can also lead to the development of significant and unexpected adverse effects that do not occur consistently with each use. There are many case reports of whole psychedelic plants causing serious adverse effects and even death in people with a history of use [119]. Therapeutic Dosing versus Microdosing As might be expected, psychedelic substances have traditionally been used in doses that are intended to exert a hallucinogenic effect. Most often, psychedelics are taken in single doses or isolated doses taken weeks or months apart from each other. Similar doses are also used in clinical research and tend to be considered “therapeutic” doses for these chemicals. However, there has been interest in the use of very small doses that are not expected to exert a hallucinogenic effect. These small doses, referred to as microdoses, are not strictly defined, but are often about 10% of the amount that would be expected for a “medium to high” single therapeutic dose, taken either every three days or two to four times per week [9; 12]. The theory behind this dosing strategy is that regular use of nonpsychedelic doses will boost mood and energy and reduce anxiety without causing a hallucinogenic high. Unfortunately, any research on this theory is very limited and most publications provide only anecdotal reports. Currently, people who utilize this dosing strategy have self-selected for this use and have determined their own dosing regimen. Thus, this form of treatment is thought to be particularly prone to response expectancy and a placebo effect [9; 13]. Microdosing with psilocybin mushrooms may be particularly difficult, as concentrations of the psychedelic substance can vary widely between mushrooms. These concentrations can also change depending on whether the mushroom has been processed in any way. Many people aiming to microdose have ended up taking much larger doses than intended, leading to hallucinations, paranoia, and increased blood pressure and heart rate. Even when doses are correctly measured, there is limited information on the short- and long-term safety of this practice [9; 12].
NATURAL PSYCHEDELICS
AYAHUASCA (DMT) Ayahuasca is a psychotropic drink that is used for therapeutic and religious rituals in several Amazonian countries, including Brazil, Peru, Colombia, and Ecuador. The word ayahuasca is based on the Quechua language and comes from aya , meaning spirit or soul, and huasca , meaning rope or vine [14; 15; 16; 17; 18; 19; 20]. Ayahuasca is most commonly brewed by boiling the vine of Banisteriopsis caapi with the leaves of Psychotria viridis . In some cases, other plants, such as Diplopterys cabrerana and other Psychotria species, may be used as the source of leaves, or the leaves may be excluded entirely. Regardless of the specific ingredients used, ayahuasca brews contain DMT, a known psychedelic chemical. Some other constituents, including harmine and tetrahydroharmine, may act to enhance the psychedelic effects of DMT [19; 21; 22; 23; 24]. DMT is classified as a Schedule I controlled substance by the DEA [121]. In addition to ayahuasca’s historical use in rituals, there has also been growing interest in its use as a therapeutic agent for various mental health disorders. In fact, some resorts and clinics in Mexico, where ayahuasca is legal, now offer ayahuasca-based retreats. The exact contents of ayahuasca change with each brew, and the concentration of its therapeutic constituents can vary significantly. Most tested preparations of ayahuasca have been found to contain DMT in quantities ranging from 0.088 mg/ mL to 2.687 mg/mL and harmine in quantities ranging from 0.14 mg/mL to 4.44 mg/mL [24]. This wide variability from batch to batch would be expected to significantly alter any therapeutic or adverse effects that occur with use. Mechanism of Action DMT is a serotonin (5-HT) 2A, 2C, and 1A receptor agonist in the central nervous system (CNS). Harmine is a reversible inhibitor of monoamine oxidase (MAO)-A. This is thought to enhance the effect of DMT by inhibiting its metabolism in the gastrointestinal tract and allowing larger quantities to reach the CNS. Another constituent, tetrahydroharmine, has demonstrated activity as a selective inhibitor of serotonin reuptake, which may also produce neurologic effects [25]. However, there is limited reliable research on the actual effects of ayahuasca in humans. The available literature suggests that any effects may be dose- and patient-dependent. Some animal research suggests that low doses may produce stimulant effects, whereas high doses may reduce CNS activity. A small study in humans suggests that baseline mental health diagnoses may alter the outcomes of ayahuasca use [120].
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