Psychedelics are having a moment. Clinical trials have found promising results regarding the efficacy of MDMA to treat PTSD, magic mushrooms to treat depression, and ketamine to treat OCD. Silicon Valley entrepreneurs have been touting the powers of LSD microdosing to increase productivity and creativity. And ayahuasca retreats—where people ingest the Amazonian hallucinogen in shamanic ceremonies—are gaining popularity among Americans.
But these substances’ benefits don’t make them risk-free—especially not outside the supervision of a doctor or therapist, says James Giordano, professor of neurology and biochemistry at Georgetown University Medical Center. The risks and benefits of psychedelics depend on the drug, the dose, the frequency with which you take it, the purity, and whether you mix it with other drugs. In general, Giordano recommends sticking to a microdose or, at most, a low dose (see how much this is for each drug below) and waiting at least 10-14 days between doses (except for ayahuasca, where up to three consecutive days pose minimal risk).
So, how harmful are psychedelics, really? Here’s what you need to know about five of the most popular psychedelics recently enlisted for therapeutic purposes.
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MDMA
MDMA, the active ingredient in ecstasy and molly (though it’s not always present in these drugs), has been shown to help those with various mental health issues including anxiety and eating disorders. However, in these studies, MDMA is in pure form and administered at small doses during therapy sessions, says Giordano. Typically, patients are kept at the facility afterward for monitoring.
In recreational settings, MDMA can lead to overheating, dehydration, overhydration, and kidney failure. At high doses, it puts you at risk for serotonin syndrome, characterized by a high fever that can incur brain damage, a rapid heart rate that can cause cardiac arrest, profound anxiety, changes in blood pressure, and a tremor resembling a “wet dog shake,” Giordano says.
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Very high doses of MDMA have been shown to damage serotonin receptors, which are involved in mood regulation, in rats, says Enzo Tagliazucchi, a neuroscientist studying psychedelics at the University of Buenos Aires and the Brain and Spine Institute in Paris. While the specific neural consequences haven’t been established in humans, research suggests that people who have used lots of MDMA for a long time have lower cognitive abilities. Due to its effects on serotonin receptors, repeated high doses of MDMA can increase your risk for depression and anxiety, Tagliazucchi adds.
Because serotonin is involved in melatonin regulation, MDMA can also disrupt your circadian rhythm so that you don’t go through full sleep cycles, Giordano tells me. Some are very sensitive to this effect: Giordano dealt with one patient who could not sleep for a week after one rave. Others find that MDMA causes them difficulty peeing or an overactive bladder—usually after long-term use, but some are extremely sensitive to this effect in a short amount of time as well.
If you’re going to take MDMA, Giordano recommends sticking to a low dose, not redosing, not mixing it with other drugs, and staying hydrated (but not excessively; RollSafe recommends 1-2 cups of Gatorade/hour).
Small dose: (your weight in kg + 10) mg
Microdose: It’s not recommended to microdose MDMA because you may get few effects and still experience a comedown or hangover.
LSD
Musicians and other artists have sworn by LSD—best known for its alteration of visual and auditory perception, as well as thought patterns—as an aid for their creative processes, and people in other professions have begun microdosing it for work. One small study also found it effective for anxiety reduction in those dealing with life-threatening illnesses.
At high doses, LSD, like MDMA, can trigger serotonin syndrome, Giordano says. Still, the main risks are psychological. LSD at repeated high doses can cause the networks of neurons in your brains to reorganize, leading to what’s colloquially known as “acid brain,” characterized by foggy headedness and flashbacks.
Some users of hallucinogens experience Hallucinogen Persisting Perception Disorder (HPPD), which involves periodic flashbacks to hallucinations long after a trip, Tagliazucchi tells me. A 2011 study in Drug and Alcohol Dependence found that 60.6 percent of 2,679 regular hallucinogen users had experienced “drug-free visual experiences that resembled hallucinogen effects,” though only 4.2 percent of the participants had the chronic flashbacks characteristics of HPPD.
People who overdose on LSD can even full-on trip for several days, Giordano says. They may also experience derealization, or a complete disconnection from reality, which can be traumatic, particularly if it returns in the form of flashbacks.
Because it can put people out of touch with reality, those on LSD may do dangerous things like run in front of cars and jump out windows. If you’re going to take it, he strongly recommends taking it under the supervision of a sober tripsitter.
Small dose: .0003 mg/kg body weight
Microdose: .006 mg (1/16 of a tab)
Magic Mushrooms
Psilocybin mushrooms, or shrooms, also disrupt visual and auditory processing, potentially causing hallucinations, and can help people think outside the box. They can also bring emotions, both positive and negative, to the surface. Perhaps for the latter reason, they’ve shown success in alleviating depression and anxiety.
Similar to LSD, high doses of magic mushrooms can lead to serotonin syndrome, derealization, extended trips, and risky behavior, Giordano says. In the long-term, regular high doses can also reorganize neural networks, potentially leading to chronic flashbacks or cognitive impairment. Don’t take a lot or take it alone.
Small dose: .3 mg mushrooms/kg body weight
Microdose: .2 mg
Ketamine
Ketamine, originally used as a sedative by surgeons, dentists, and veterinarians, has been making its way into nightclubs—and clinical trials, where it’s proven promising for treating depression, alcohol dependence, and heroin addiction.
The effects of ketamine are extremely dose-dependent, Giordano tells me. A high dose can put you in a “K-hole,” where you’re temporarily paralyzed and dissociated from your body. In the worst cases, it can cause respiratory or cardiac arrest, seizures, coma, or brain death. It can be fatal.
In the long term, ketamine can become addictive because it acts on the excitatory neurotransmitter glutamate, while most psychedelics’ potential for addiction is low, Tagliazucchi says. It can also change the membranes of your neurons and the way their receptors function, leading to depression, mood swings, and cognitive impairment, Giordano says.
At a low dose, these risks are diminished, but it’s difficult to predict how susceptible you are to them, since everybody metabolizes ketamine differently, Giordano adds. People who take low doses of ketamine often describe distorted visual perception and the ability to arrive at insights. Microdoses may produce the insights without the sensory disruption. Either way, because it’s so unpredictable, Giordano recommends enlisting supervision if you’re going to take ketamine.
Low dose: .7mg/kg body weight under the tongue or 1.4 mg/kg taken orally
Microdose: .02 mg under the tongue, .2 mg orally
Ayahuasca
Sometimes called “the medicine” by shamans and other enthusiasts, ayahuasca—which can cause visual and auditory hallucinations, epiphanies, and profound spiritual experiences—is often viewed as a harmless substance. And many times, it is—at low doses, Giordano says. However, high doses carry many of the same risks as other psychedelics, including serotonin syndrome, derealization, and extended trips. Like LSD and mushrooms, it could lead to neural network reorganization resulting in foggy headedness and flashbacks after excessive, long-term use.
Because people often don’t feel the effects of ayahuasca the first few times, they may be tempted to up their dose. However, it’s better to keep the dose the same the first few times because it may need several chances to block your MAO enzymes so that all the DMT can reach your brain.
Low dose: This varies drastically based on the brew and how much DMT it contains, so find a reputable facility and talk to the people serving it.
Microdose: You don’t really microdose ayahuasca; you wouldn’t feel much.
The bottom line? “Usually, the advice is to start low and go slow,” Giordano says. “The thing that becomes problematic is higher doses repeatedly, because what that can do is that can disrupt brain chemistry in a more stable and durable manner.”
“When psychedelics are researched, they’re using it primarily as a therapeutic intervention against a defined psychiatric or psychological condition,” he adds. “They’re not saying, ‘These drugs are safe. Go out and use them like it’s 1968.’”
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