From shamanic rituals in remote forests to chemical highs cooked up in hippie labs, psychedelic substances have been ingested in myriad contexts over thousands of years. And with interest in the medical value of these drugs now taking off big-time, tripping looks set to finally emerge from the underground and enter the mainstream.
Yet while the increased availability of psychedelics may help turn the tide of various mental health crises, the widespread use of these substances also raises questions over their sustainability. To meet the growing demand, it’s going to be necessary to mass produce psychedelics while minimizing the environmental impact of all those trips – so should we stick to plant-based hallucinogens or invest in synthetic alternatives?
Extracting the magic
By now, even the most straight-laced among us will have heard of psilocybin, the active ingredient in magic mushrooms that has been touted as the next big thing in mental healthcare. Given that the compound occurs naturally in fungi, it seems logical to assume that the simplest and least harmful way to produce the drug is to just grow a load of shrooms.
However, when it comes to the clinical use of psychedelics, precise dosage calculations are essential. You can’t give a patient a drug without knowing how strong it is, and the problem with magic mushrooms is that their potency can vary. Rather than just letting patients eat a bunch of mushies, therefore, scientists have to provide pure psilocybin, which must first be either extracted from a natural source or synthesized.
“The problem with natural extraction, and especially in the case of psilocybin, is that the compound of interest usually accumulates in very, very small amounts. Psilocybin is like one percent of the mushroom,” says Dr Nick Milne, co-founder of Octarine Bio, which develops sustainable methods for producing tryptamine psychedelics and cannabinoids.
“That means you need to cultivate a lot of mushrooms. So the environmental impact of having a huge greenhouse to grow the mushrooms and to extract the compounds [is quite high].” The extraction process itself also involves “some harsh chemical steps,” all of which can quickly cancel out the environmental benefits of using a plant-based starting ingredient.
On the other hand, synthetic pharmaceuticals are often derived from fossil fuels, which is obviously not ideal if sustainability is our goal. “In the case of synthetic psilocybin, the starting ingredient is benzene, which is a crude oil derivative and a fairly nasty chemical,” Milne told IFLScience.
“Then during the manufacturing process, you require things like high temperatures, high pressure and expensive catalysts, and you generate a lot of waste products. You have a lot of problems with your with your waste stream, which is generally why synthetic chemistry is seen as is unsustainable.”
To get around this problem, Milne and his team have developed a method for creating pure psilocybin from genetically altered brewer’s yeast. The process relies on fermentation, and the end product is therefore a kind of happy hybrid between natural and synthetic psilocybin.
“Our starting point is sugar, which comes from plants, so there’s a CO2 benefit [over traditional synthetic chemistry],” says Milne. “We also convert a considerably greater amount of the sugar into our compound of interest [than using mushrooms] - somewhere in the range of five to ten percent. Also, because you're doing it in a fermentation vessel – which is vertical as opposed to horizontal – you save on the land footprint.”
“Broadly speaking, fermentation is a more sustainable option than either synthetic chemistry or natural extension,” insists Milne. The challenge now is to refine the process to convert even more of the sugar into psilocybin in order to provide a truly sustainable source of the drug for clinical use.
Are sacred plants in danger?
Second only to psilocybin as the most talked-about psychedelic these days is N,N-dimethyltryptamine, or DMT for short. For safety and consistency reasons, a synthetic version of the drug is generally used in clinical research, although the substance is famously found in the hallucinogenic Amazonian brew ayahuasca.
Created by blending a jungle vine with other local plants, ayahuasca has been used as a spiritual sacrament and ritual healing adjunct by indigenous communities for many centuries. However, a boom in ayahuasca tourism over the past two decades has led to concerns over unsustainable harvesting practices.
The city of Iquitos in northern Peru, for instance, has become something of an ayahuasca Disneyland, with countless guesthouses and lodges offering the trippy beverage to the hordes of backpackers that arrive each year. This has led to reports of over-harvesting and ayahuasca shortages in the surrounding forest, in addition to the commodification, appropriation, and exploitation of indigenous culture and traditions.
One study even found that ayahuasca tourism in Iquitos may contribute to jaguar poaching, as unscrupulous merchants try to convince visitors that trinkets made of jaguar body parts enhance the ayahuasca experience. Obviously, this is not the case, and there is no evidence to suggest that any indigenous group has ever held such a belief.
Fortunately, more responsible approaches are applied elsewhere in South America, with ayahuasca-using syncretic churches in Brazil – such as Santo Daime and União do Vegetal – adopting sustainable cultivation methods to ensure the plant does not suffer from over-harvesting or other forms of abuse. On the whole, the ayahuasca vine is not considered to be under threat, although anyone planning to ingest the brew is advised to look into how their supply has been sourced and what impact this has had on indigenous Amazonian communities and the rainforest as a whole.
A similar story is unfolding in West Africa, where the hallucinogenic root bark of the iboga shrub has been ceremonially ingested for many years. More recently, the active ingredient – called ibogaine – has attracted interest around the world due to its apparent ability to eliminate cravings and withdrawal symptoms in people suffering from opioid addiction.
Over-harvesting of the plant due to an ever-growing export market has led to major concerns about shortages in Gabon and Cameroon, where iboga has traditionally been used. To overcome this issue, researchers have created a synthetic version of ibogaine called 18-methoxycoronaridine (18-MC), which has shown promise as a treatment for substance abuse disorders in early trials. It’s worth mentioning, however, that neither ibogaine nor 18-MC have been subjected to large-scale clinical trials, and major concerns over their safety and efficacy are yet to be addressed.
For toad’s sake
Next up in our fantasy-inducing pharmacopeia is an incredibly potent psychedelic compound called 5-MeO-DMT, which is most famously found in the poisonous glandular secretions of the Sonoran Desert toad. Though this milky amphibian goo can be deadly when eaten, smoking the slime is reported to deliver a knockout punch to the ego, resulting in an empyreal experience that transcends the filters and restrictions of our everyday consciousness.
Sounds pretty awesome – unless you happen to be the toad, that is. The species has already disappeared entirely from California and conservationists are highly concerned about its survival throughout the rest of its territory – so the last thing it needs is to be harassed by people who want to get high on its defensive juice.
"In Mexico, the toads hang out by the roads at night because insects are attracted by lights on the roads. So the easiest way to collect them is to just go for a drive, pick up some toads, drop them in your truck, drive them somewhere and press the glands,” explains Dr Anya Ermakova, a psychedelic researcher and conservation biologist.
“Then in practice, people just dump them randomly rather than returning them to where they collected them from. This is very harmful, not just because of the stress to the toad and removing their protection from predators, but also because toads are territorial animals that like to live in a particular area where they have fought off other toads,” Ermakova told IFLScience. “So relocating them reduces their survival, while mixing different subpopulations of toads could potentially spread pathogens,” such as the deadly chytrid fungus that has already caused numerous amphibious species to become extinct.
To protect the toads, conservationists are now encouraging people to make their own synthetic 5-MeO-DMT, which is actually relatively simple to do. Numerous chemists have published their own methods for manufacturing the compound, and these artificial versions are increasingly being used in clinical research.
In most cases, the process involves the use of various catalysts and solvents to turn mexamine – which is created from the hormone melatonin – into 5-MeO-DMT. As with most synthetic chemistry, this transformation is not without its environmental impact and does involve some harmful steps.
However, scientists are continually looking for ways to make the process more sustainable. For instance, a recent study found that the drug could be synthesized with 99.86 percent purity using a solvent that is derived from sugar.
According to Ermakova, synthetic 5-MeO-DMT is also much safer than toad slime as the potency of the creatures’ excretions tends to be inconsistent and varies with the seasons. She’s currently working with a team of researchers at King’s College London on two clinical studies into the compound’s potential to treat depression and alcoholism, with the synthetic version being used in both trials.
And while the chemistry behind this manufactured psychedelic may not be 100 percent sustainable, it is getting greener all the time. It’s certainly preferable to going down the toad road.