Psychedelic Stacking Comes Into Focus

Nobody thinks twice about mixing coffee with psychedelics. All you do is microdose some psilocybin with your cup of Joe and you can really jump-start your day. Maybe even mix your psilocybin microdose in with some with your non-psychedelic mushroom tea for a sort of double whammy effect.

People are also not concerned about mixing chocolate with psychedelics. There are dozens of chocolate products with psilocybin mixed in, available in brightly packaged and sometimes advertised on websites by models in provocative poses.

And as much as consumers believe these combinations with chocolate and coffee enhance the psychedelic experience, they can actually make things worse. 

Both coffee and chocolate contain caffeine, one of the most widely used psychoactive substances in the world, thought to affect the same part of the brain as cocaine. Some dark chocolates can contain as much as 160 mg of caffeine per 100g of chocolate.

One study found that individuals—both adults and adolescents—who consume high doses of caffeine frequently report psychiatric symptoms and disorders, mainly anxiety and mood disorders, but also behavioral alterations. Caffeine intoxication can include anxiety, agitation, restlessness, insomnia, gastrointestinal disturbances, tremors, tachycardia, psychomotor agitation, and, in some cases, death. 

Caffeine is unregulated and even available as a powder. The Food and Drug Administration warns that just one teaspoon of pure powdered caffeine can contain the same amount of caffeine as 28 cups of coffee.

Stacking Psychedelics

But generally speaking, stacking psychedelics with other substances (especially psilocybin with chocolate, to cover the bitter taste of a raw magic mushroom), has become more popular. One study found that psilocybin users were more likely than LSD users to combine psilocybin with other substances, even when microdosing. Some psilocybin consumers stack their magic mushroom with other non-psychedelic mushrooms, such as Lion’s Mane and niacin, according to the study. People who stacked psilocybin with other substances like these were less likely to drink alcohol or smoke cigarettes as well. But they did use cannabis. 

Mixing hallucinogens with opioids can be deadly. In fact, another study found that mixing ketamine and heroin created a particularly high number of fatalities. Researchers noted that many people combined substances like opioids and hallucinogens to reduce unwanted effects from one or both drugs.

But with the prevalence of new formulations and new ways of using psychedelics being created in various labs, and being brought to clinical trials, often hailed as the next generation of pharmaceuticals is beginning a quest for different psychedelics being stacked together for a new therapeutic experience?

According to Mindset Pharma’s Chief Scientific Officer, Joseph Araujo, responding via email to questions from Psychedealia, there currently is little data from well-controlled studies specifically examining the interaction between psychedelic drugs and opioids, but there are data both in the scientific literature as well as from case reports that describe potential interactions of various psychoactive drugs and psychedelics. “Psychedelics of the serotonin hallucinogenic classes as well as several phenethylamines have well established serotoninergic activating effects, which are generally non-specific for receptor subclass,” Araujo wrote. “Thus there has been concern that combining these psychedelics with other drugs that “activate” serotonergic pathways may result in serotonin toxicity, which can be life-threatening.”

The current data suggest that the risk may vary by specific psychedelic drugs, but deaths have been reported with certain combinations, such as antidepressant drugs and 5-methoxy-N, N-dimethyltryptamine (DMT).

“Some drugs inhibit serotonergic receptors, and combining those drugs with psychedelics may result in a reduced or absent psychedelic effect,” Araujo wrote.

Asked if two different psychedelic substances can be used in a single therapeutic session—such as ketamine and psilocybin, or MDMA and psilocybin—Araujo wrote that, again, there is limited data from well-controlled clinical studies to answer this question today. “Certainly, there are

likely to be relatively safe combinations, particularly if the mechanism of action of the two psychedelic substances differ,” he wrote. “But the efficacy of combining treatments is not yet established. Combining drugs with similar mechanisms of action is more likely to result in effects consistent with an overdose, such as serotonin toxicity.”

Serotonin toxicity is a potentially life-threatening drug-induced condition caused by too much serotonin in the synapses of the brain. Patients with serotonin toxicity have a combination of neuromuscular, autonomic, and mental status symptoms.

In 2016, an FDA warning stated that opioids interact with migraine medications to cause serotonin toxicity. Modern antidepressants, such as Zoloft and Prozac, primarily work by increasing levels of serotonin in the brain, making them more dangerous to take with psilocybin.

There are other pharmaceutical interventions that are safe but can mimic serotonin toxicity.

Much more research is needed.

Caffeine Connection

In the meantime, researchers are finding out that maybe caffeine isn’t so bad when taken with your daily microdose. 

Yes, there is more caffeine in coffee than in chocolate. But there is another psychoactive substance in chocolate in higher concentrations than caffeine that researchers have found to be intriguing and possibly helpful for human health—theobromine.

A recent study highlighted the potential of theobromine, which may act as an antitumoral, anti-inflammatory, or cardiovascular protector molecule without the undesirable side effects described for caffeine. Theobromine could be considered a safe and natural alternative in the treatment of some human diseases and may serve as a lead compound for the development of novel drugs, according to the study.

For now, psychedelics consumers buying from the black market are doing what they have been doing for years, especially during the rave days of the past: Either “candy flipping” (taking LSD together with MDMA, increasing the effects of MDMA) or “hippie flipping” (taking magic mushrooms and MDMA, reportedly to counter the anxiety effects of psilocybin). 

There will always be risks in combining psychedelics with any other opioid substance. People sometimes seek a higher high—or are simply not using their best judgment. One example from 2011: One death presumed to be a heroin overdose occurred with a combined consumption of 10 psilocybin mushrooms.

The Centers for Disease Control and Prevention (CDC) reported that, in 2019, 50 percent of drug overdoses involved multiple drugs (though only MDMA was the only psychedelic on their list).

Ultimately, large studies examining specific interactions are lacking, but necessary for advancing the medicinal psychedelic industry, according to Araujo. “Anyone considering taking any psychedelic drug in combination with other drugs should consult a medical practitioner prior to experimentation,” he wrote. “Given the uncontrolled nature of the underground drug market, it is often impossible to confirm the identity and/or the purity of a psychedelic substance, which further increases risk.”

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