A Biotech Startup Won a Patent to Combine Elements of Weed and Psychedelics
It’s based on the theory that the benefits of psychedelic plants and fungi come from a combination of chemicals working together
Whether aiming to enhance spiritual growth or brighten the music at Lollapalooza, people have been combining cannabis and psilocybin “magic” mushrooms recreationally for ages. But a small biotech startup called CaaMTech Inc. just became the first to patent the idea.
The patent covers a whole range of cannabinoids — chemical compounds produced by marijuana plants, such as THC or CBD — mixed with a bevy of chemicals related to psilocybin mushrooms. It details myriad formulations, including dried powder, pills, gummies, and edibles, with a blanket of proposed applications for psychological disorders. The company, based in the Seattle suburb of Issaquah, hopes investors will want to license these formulations, which each combine a cannabinoid with a psilocybin derivative, either to treat mental health or entertain a yet-to-exist recreational market. The U.S. Patent and Trademark Office awarded the patent in mid-January.
“The single drug will often behave differently than combinations of the drugs,” CaaMTech CEO and co-founder Andrew Chadeayne, PhD, told Future Human. “You get to fill in sort of the spectrum of different things.”
Separately, both cannabis and psilocybin are being explored by researchers to treat mental health disorders. A 2020 review in BMC Psychiatry examined 13 studies using cannabinoids to treat mental health disorders and found “encouraging, albeit embryonic, evidence for medicinal cannabis in the treatment of a range of psychiatric disorders,” including anxiety, depression, and post-traumatic stress disorder.
However, based on the limited data and few well-designed clinical trials available, the evidence was “too weak” to recommend giving cannabis to patients. The evidence for psilocybin and mental health is stronger. A meta-analysis in the Journal of Psychoactive Drugs published in January 2020 underlined the large effect size and few side effects of psilocybin for end-of-life anxiety and depression.
In the 1950s, anecdotal reports of people eating mushrooms and alleviating their depression and anxiety led to scientists testing psilocybin in a lab. However, the amount of chemicals in each mushroom can vary widely, and today, researchers can’t give patients an unmeasured amount of a drug — at least, not if they want approval from the Food and Drug Administration (FDA). So most modern studies involving psychedelic drugs use a purified, single compound. But few studies have looked at the effect these drugs may have when paired together.
While the cannabinoid and psilocybin patent is CaaMTech’s first to be approved, the company has filed more than 110 psychedelic-related patent applications since 2017 and plans to develop more treatments that involve combining drugs that work on serotonin receptors. The idea is based on the theory that the benefits of psychedelic plants and fungi don’t come from a single compound within them, such as THC, but from a combination of chemicals working together. Scientists who study how drugs work in the brain call this the entourage effect.
The entourage effect isn’t universally accepted among scientists, but the strongest evidence for it exists in cannabis. For decades, researchers believed that THC was the only molecule responsible for marijuana’s psychoactive effects. Then, scientists discovered that CBD and other compounds produced by cannabis plants resulted in different physical and mental effects when applied at different ratios.
For example, one study suggested weed high in THC but low in CBD may trigger more intoxication in people compared to marijuana with an equal amount of both. Some strains of weed seem to be better for sleep, others for pain, and some scientists attribute the difference to these ratios. In one 2018 study in Biochemical Pharmacology, researchers applied pure THC versus a preparation of cannabis flowers soaked in ethanol to mice with breast cancer. They found the mixture treated tumors better than the purified drug product. Some cannabinoids can trigger cell death in tumors, according to a 2019 review, but most of this research is in petri dishes and animals, not humans.
In 2018, U.K.-based pharmaceutical company GW Pharmaceuticals became the first company to win FDA approval for an epilepsy drug made from cannabis plants. Called Epidiolex, it’s a proprietary mixture of CBD, terpenes, and other cannabinoids rather than a single substance.
There is also some evidence that the entourage effect exists in psychedelics. For example, ayahuasca is a South American decoction of multiple rainforest plants: some that contain the psychedelic drug DMT and others that contain another drug called a monoamine oxidase inhibitor, or MAOI. On their own, these substances don’t produce much of a psychoactive effect because DMT is not active orally — the body breaks it down too fast to have any effect. But combining them allows the MAOI to prevent the breakdown of DMT and creates a long-lasting psychedelic experience.
Even so, Peter Cogan, PhD, an associate professor of pharmaceutical sciences at Regis University, has analyzed some of the most well-known entourage effect studies and dismissed the phenomenon as “hodge-podge hashish,” adding “such claims in the scientific and lay literature has fostered their misrepresentation and abuse by a poorly regulated industry.”
In 2020, New Zealand researchers looked at how cannabinoids and terpenes interact at CB1 and CB2 receptors — where drugs like THC have their most direct effects — and detected no synergy. That is, combining the chemicals didn’t produce a greater impact. This doesn’t rule out the entourage effect entirely, but it suggests that if these compounds are working together, it’s probably not at these receptors.
CaaMTech is working to characterize obscure psychedelics, and Chadeayne believes understanding these drugs on an atomic level will shed more light on the entourage effect. It has also been testing whether cannabinoid molecules and psilocybin analogs work synergistically at the brain’s serotonin 2A receptor, which is involved with depression.
To test the theory, CaaMTech built cellular assays using hamster cells coupled to a fluorescent molecule, which lights up in a way that a computer can then measure how much activity is going on in the cell. If combining two drugs produces much more activity than either would alone, then it follows that each substance is making the other more effective. Based on the lab’s preliminary data, which has yet to be peer-reviewed, putting a cannabinoid and a psilocybin derivative together creates significantly more synergy.
Proof that this combination produces a greater effect is only the beginning. Further research is needed to determine whether that effect is beneficial in some way. Matthew Baggott, PhD, a neuroscientist who has been studying psychedelics for 30 years, notes that making a combination drug comes with certain tradeoffs. “One of the considerations with these possible preparations with multiple ingredients is that you gain convenience, but you lose some ability to adjust the doses of the individual ingredients,” he says. “And that can be a big downside if the exact dose matters and varies from person to person.”
While the entourage effect may be one motive for testing combinations of psilocybin and cannabinoids in treatments, there is also a business motive: It’s not possible to patent THC or psilocybin on their own — these drugs exist in nature and have been known to science for decades — but it is possible to patent a combination of the two. Getting FDA approval for a combination for such a drug may be another matter, as regulatory bodies may be more interested in single drugs.
“If it works well enough that you can treat people with it, then it is probably a good strategy to just go for the pure chemical because that’s what the system is set up for,” Baggott says. “And it’s much, much harder to get approval for something that’s kind of a stew of different compounds.”
For this reason, there may be more interest in using CaaMTech’s patent to create a recreational drug that combines cannabinoids and psilocybin than one approved to treat mental health disorders.
Another alternative, which wouldn’t require FDA approval, is licensing this combo to therapists who enroll in Oregon’s upcoming psilocybin therapy program, which was approved by voters during the last election. Florida, Hawaii, and Connecticut are also considering similar laws that would also establish programs for people to take psychedelics in therapy.
Even if this cannabis/psilocybin patent doesn’t deliver the moon for CaaMTech, “understanding natural psychedelics and psychoactive drugs and learning how these combinations work together is going to be important from a purely scientific standpoint,” Chadeayne says. “What we’re doing is trying to give [people] the tools to go and figure out what products or recreational products are going to be the best for folks. And I’m sure that the way to do that is to know what the drugs are and how much.”