A tourist shows heads of peyote at the desert near the town of Real de 14, in San Luis Potosi State, ... [+]
Mescaline (3,4,5-trimethoxyphenethylamine)—the magical alkaloid found in the peyote cactus (Lophophora williamsii) and similar cacti—could be the next vital ingredient in psychedelic drug formulations.
Recent surprising data supports mescaline’s potential to treat disorders such as depression, anxiety, post-traumatic stress disorder (PTSD), as well as alcohol and drug use disorders. Researchers believe it could unlock a novel arsenal to battle otherwise difficult-to-treat conditions.
Why Mescaline Synthesis?
Vancouver, British Columbia-based XPhyto Therapeutics (CSE: XPHY; OTC: XPHYF; FSE: 4XT) is developing mescaline synthesis processes, which could lead to controlled microdoses, given the company’s expertise in transdermal patches, sublingual strips, and similar delivery systems.
The company announced last week that its Good Manufacturing Practices (GMP) mescaline synthesis program in North America is on track for completion in late Q3 2021.
XPhyto Therapeutics CEO Hugh Rogers explained why realistically, synthesis processes are key to standardization when dealing with a complex plant such as peyote and similar cacti, and we can learn from the mistakes of modernizing cannabis or psilocybin extracts.
“There was an expectation in the cannabis industry that there would be a significant supply of pharmaceutical-grade cannabinoids,” Rogers says. “I don’t think that was the case.” Unwanted plant material could be bypassed via synthesis processes that lead to purified, safer compound delivery systems. Easily controllable microdoses could provide more benefits.
XPhyto Therapeutics Corp. CEO Hugh Rogers.
“And if you look at psychedelics like mescaline, if you want to scale it, medicalize it, and modernize it, you have to synthesize it, using a biotechnology process on an industrial scale,” he continues. “We don’t think that we’ll ever get to a point where—at least in the mainstream—people will be consuming peyote cactus. From a regulatory perspective, it’s too complex as a multi-compound plant extract through the FDA or Health Canada. It also gets very complicated from a drug delivery perspective.”
How is drug formulation even possible given mescaline’s restrictive legal status as a Schedule III substance in Canada? Professor Raimar Löbenberg is overseeing XPhyto’s current focus on mescaline and other psychedelics, with the intent of converting them into therapeutic drug formulations. He is the founder of the Drug Development and Innovation Centre at the University of Alberta and the former president of the Canadian Society for Pharmaceutical Sciences. Löbenberg has unique licenses through Health Canada—making him one of the few scientists in North America to enjoy such a status. This gives XPhyto a very competitive edge.
Rogers explained that it’s nearly impossible to scale the mass production of raw peyote without utilizing synthesis processes. “What we see in mescaline, is an opportunity to enter the market—at least participate in the market—by being a wholesaler of mescaline for R&D, for clinical research, for clinical use. That’s the opportunity.”
Look at the rampant mental health issues in North America, especially post-pandemic: depression, anxiety, addiction, and trauma. “It’s everywhere,” Rogers says. “I see the potential for microdosing. [Mescaline] very much has the potential to replace other forms of therapeutics like SSRIs. It also has the potential to replace something like alcohol.” Rogers explained that recent research explores whether mescaline could improve neuroplasticity or neurogenesis, creating positive changes in your brain.
XPhyto’s success is partly due to the expertise of its flagship German subsidiary, Vektor Pharma TF GmbH. XPhyto also developed a sped-up, 25-minute PCR COVID-19 test.
Last month, Xphyto participated in a syndicated broadcast report aired on NetworkNewsAudio (NNA), specifically covering the progress of mescaline drug formulation development.
How Can Mescaline Help?
Published recently in ACS Pharmacology & Translational Science, researchers gathered promising results about mescaline’s effects in data collected from 452 adults. The same study sample was published in the Journal of Psychopharmacology. Most adults who participated, 68–86 percent, reported subjective improvement following their most memorable mescaline experience. Nearly half of the participants consumed the San Pedro cactus, and nearly a quarter of them consumed peyote.
The participants who reported an improvement in their psychiatric conditions were much more likely to experience acute psychological factors such as mystical reports, psychological insight, and ego dissolution compared to those who said they did not have improvements.
It’s transformative psychological changes seen in mescaline experiences that are believed to help some people to overcome severe depression and other disorders. This unique mechanism is believed to improve psychological flexibility—including the ability to cope with changes in circumstances. This could be useful to help people make major life decisions, such as quitting alcohol or cigarettes.
Gabby Agin-Liebes, PhD
Lead author Gabby Agin-Liebes, PhD is a clinical psychologist and currently a National Institute on Drug Abuse T32 Research Fellow in Substance Use Disorders Treatment and Services Research at the University of California San Francisco. One of her goals is to develop therapies to restore dysregulated reward systems involved in addiction.
“I consider this particular finding quite interesting and pretty remarkable,” Agin-Liebes says in an email. “While the rigor and implications of these data are limited by several study design characteristics, such as the absence of a control group and possible participant self-selection biases, these findings are exciting. They suggest that mescaline holds meaningful potential as an aid in psychotherapy, psychiatric medicine, and personal/psychospiritual development.”
Agin-Liebes explained that due to legal restraints associated with the Controlled Substances Act, officials essentially hit the pause button on human clinical research with classic serotonergic psychedelics—up until recently. “The majority of the human clinical research conducted over the last two decades has focused on psilocybin and DMT-containing ayahuasca, with far fewer studies with LSD, and virtually no human laboratory trials with mescaline," she says. “Preclinical research [e.g., in rodents] has advanced our understanding of mescaline’s basic pharmacological mechanisms, but we continue to lack a more complex empirical understanding of mescaline's psychological effects, and the findings of our study indicate that these psychological effects could potentially be very impactful.”
Agin-Liebes explained that because of the half-life of mescaline—quite longer than psilocybin, with total duration of effects lasting 8–12 hours—the compound may have specific benefits: “For some psychiatric conditions that are more intractable, and for those patients presenting with more severe symptoms, the longer duration could enable a greater therapeutic window and opportunity for shifting entrenched psychological patterns,” she says. “Our findings also contribute interesting data regarding the potential of mescaline for treating PTSD. No studies have examined the use of classic psychedelics (psilocybin, ayahuasca, LSD, mescaline) to directly target PTSD, so this is an interesting preliminary finding. Mescaline is also unique in its phenomenological effects, as it possesses both psychedelic (sensory alterations and spiritually salient experiences) and empathogenic (emotional connection/openness, relatedness) features, and may be uniquely therapeutic for this reason.”
A Long, Complex History
While the use of mescaline-rich cacti strictly allowed in the US for legitimate religious organizations, that could shift quickly. North America has been home to Indigenous peyotism practices for thousands of years. "Bona fide religious ceremonies" involving peyote buttons are tolerated in the US, such as the Native American Church, and a few states in southwest America provide various exemptions.
Due to the sacred nature of peyote cacti, some Indigenous associations fought to exclude peyote from psychedelic decriminalization efforts—with fears of the sacred experience being exploited for recreational purposes.
Peyote is also an endangered species, providing another reason why synthesis could be a more ethical approach. Peyote buttons also take years to mature. Fortunately, there are a number of organizations who launched conservation efforts: Indigenous Peyote Conservation Initiative, RiverStyx, Cactus Conservation Institute, and Centro Nierika.
This push towards decriminalizing psychedelic substances is a big factor to the viability and potential of bioscience companies such as XPhyto. Given that the FDA considers psychedelics to be breakthrough therapy for treating severe depression, there is endless potential here.
