The Psychedelic Pharmacy: A Paradigm Shift in Mental Health Treatment

The use of psychedelic substances in ritual healing experiences reaches far back into human history. Ancient cultures from all over the world used different psychoactive compounds as a means of therapy: The ancient Greeks drank a concoction that contained a fungus with lysergic acid diethylamide (LSD)–like alkaloids to facilitate seasonal religious rites; members of a pre-Incan civilization in Bolivia took psilocybin, the active ingredient found in magic mushrooms; and Native Americans used mescaline from the peyote cactus in ritualistic prayer ceremonies.¹

The use of these psychoactive compounds in antiquity did not go unnoticed by investigators in more modern times. From the 1940s through the 1960s, research dedicated to examining the potential therapeutic benefits of psychedelics was in full swing in the United States. But with the 1970 passage of the Controlled Substances Act and the subsequent creation of federal drug schedules, most psychedelics were placed into Schedule I and were deemed to have no medical benefit, effectively ending any funding opportunities and the ability to study them.

However, psychedelic research has gained more support over the past several years in what has commonly been referred to as a psychedelic renaissance. Studies looking into psychedelics for the treatment of various mental health conditions are now taking place at prestigious universities across the country. The FDA has also recently signaled that it is on board. The federal agency put out a draft guidance in June 2023 to highlight considerations for clinical trials with psychedelics and has granted breakthrough therapy designation to 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, and LSD.^2-5

As psychedelic medicine continues to gain recognition and inch closer toward FDA approval, what role will pharmacists have to play in its integration into treatment plans? Pharmacists, who are the most accessible members of health care teams and medication experts, are well positioned to be an authority on the topic of psychedelic medicine and provide education not only to their patients but to the wider health care community as well. And although their part in this has not yet been firmly established, it will undoubtedly be a crucial one.

“I think pharmacists are going to have to ensure that they are comfortable with the use of psychedelics,” Olga Hilas, PharmD, MPH, professor of pharmacy practice at St John’s University in Queens, New York, said. “I believe there’s going to be a number of pharmacists who may be seeking out further specialized professional training programs in this area, similar to what we saw with cannabis. I do think that after feeling comfortable with understanding the different pharmacology, the different evidence-based uses and potential benefits and risks, they’re going to be critical as the medication experts in being able to relay information to both health care professionals and patients as to what is safe and appropriate use and being supportive in the integrative approach to health care.”

Breakthroughs on the Horizon

With the FDA’s acceptance of a new drug application (NDA) from Lykos Therapeutics for MDMA to treat patients with posttraumatic stress disorder (PTSD), psychedelic therapies may be approved in the near future. The NDA from Lykos, which was also awarded priority review, was assigned a Prescription Drug User Fee Act date of August 11, 2024.⁶ MDMA, commonly known as ecstasy, is an entactogen: a psychoactive compound that’s characterized by its ability to increase self-awareness. Although MDMA isn’t considered a psychedelic in the traditional sense, it does share some common properties with other classical psychedelics. Research has shown that MDMA, combined with therapy, can lead to significant reductions in symptoms of PTSD and depression.⁷ Other possible clinical applications include the treatment of patients with anxiety disorders, obsessive-compulsive disorder, substance use disorders, and eating disorders.⁸ MDMA is poised to be the first psychedelic approved by the FDA, but it is not the only compound on the verge of a breakthrough.

Psilocybin is also being looked at as a potential treatment for some mental health disorders. The psychoactive compound is a serotonergic hallucinogen found in hundreds of mushroom species all over the world. The substance, which is converted in the body into psilocin (4-hydroxy-N,N-dimethyltryptamine), alters perception and mood and produces vivid hallucinations.⁹ It has been demonstrated to reduce symptoms of depression and anxiety and has shown promising results in treating patients with alcohol use disorder and helping with end-of-life mood disorders in patients with advanced-stage cancer.¹⁰ Compass Pathways, a leading company researching psilocybin, has completed some of the largest studies on the psychedelic to date. The company’s investigational treatment, called COMP360, is a synthesized formulation of psilocybin. It has shown to reduce symptoms of treatment-resistant depression and other psychiatric disorders, such as PTSD and anorexia nervosa.¹¹

LSD is most likely the third psychedelic candidate that will receive approval, although it’s probably a bit further off than MDMA and psilocybin. The drug was first synthesized in 1938 by the medicinal chemist Albert Hofmann. It produces a positively experienced state of derealization and depersonalization, audio-visual synesthesia, and changes in interpretations of perceptions.¹² Recent study results on the therapeutic effects of LSD have found that it can reduce symptoms of anxiety, depression, and cluster headaches and can help with alcohol and nicotine use disorders.¹³ Biotechnology company Mind Medicine’s lead candidate, MM120, is a tartrate salt form of LSD and was given breakthrough therapy designation by the FDA on March 7, 2024. Findings from studies conducted by the company demonstrated that LSD reduces key symptoms of generalized anxiety disorder.⁵

“It’s exciting to be working with drugs of this class that are so very novel compared with the other drugs that we use for mental health,” Paul R. Hutson, PharmD, MS, director of the Transdisciplinary Center for Research in Psychoactive Substances at the University of Wisconsin-Madison School of Pharmacy, said. Hutson, who is also a professor of pharmacy, is currently conducting research on the safety and novel therapeutic uses of psilocybin for depression and substance use disorder as well as the use of MDMA for PTSD.

“The promise is there,” Hutson added. “They seem to be working very well for some people and in some cases for a rather long time. But we don’t know the best way to dose the drugs yet. The studies that are looking at depression are using 1 dose and seeing a response, probably enough to get them to FDA approval. But we still don’t know how best to dose it, whether we should be giving it at the particular level of a psychedelic experience, whether we should be giving boosters every 6 months or a year, or whether we should be giving 3 doses routinely instead of 1. I think people should understand that there’s still a great deal more to learn about how we should best give these drugs and to whom we should be giving them.”

The Role of the Pharmacist

After a long hiatus, research on psychedelic medicine is now progressing rapidly and could open a new paradigm in the treatment of patients with mental health conditions. Although there is still much to be learned, the potential for these new therapies to help millions of people with mental health issues looks promising. As trusted members of health care teams, pharmacists will be key players in their successful adoption.

“I see pharmacists needing to adapt their roles to ensure that there is safe and appropriate use of these substances in various health care settings,” Hilas said. “Some pharmacists may work directly with other health care professionals to integrate psychedelics into their practices and therapeutic care plans for individuals while others may become involved with the development of dosing and monitoring protocols. Overall, I think many pharmacists will be participating more on the educational and awareness side, where they’re going to be responsible for providing counseling to patients who will be receiving psychedelic care.”

Educating patients—particularly those who are apprehensive about using psychedelics—will be an area where pharmacists can use their skills. Hilas explained that pharmacists will need to be up to date on the latest research so they can explain to patients how psychedelics work, the purpose of psychedelic treatments, terminology, and how they fit into the overall treatment plan. Part of that job is also working to erase the negative stigmas that have clung to psychedelics since they were made illegal at the federal level. Pharmacists can accomplish this by providing supportive and nonjudgmental counseling, actively listening to patients, and being empathetic.

“Find out first what their concern is, what the question is, whether they are concerned about being addicted to the psychedelic or the effects it has for a short time [that make] it very diffcult to control your thoughts, and address them specifically,” Hutson said. “And [do] not to just say that ‘You don’t have to worry about that’ or ‘It’s not a problem’ but be very specific in addressing their concerns.”

Pharmacists will also play a vital role in establishing protocols for patient screening, counseling, and follow-up care for psychedelics. Hutson said that screening is important because individuals with certain psychiatric conditions, such as schizophrenia and bipolar disorder, are at increased risk of being harmed by high doses of psychedelics. He added that some patients may have had prior negative experiences with psychedelics and that pharmacists can work with them on any questions they may have. Pharmacists—especially those certified in psychiatric practice—could also provide the therapy that is a crucial component of psychedelic medicine, though Hutson noted that criteria for licensing would first need to be established.

“I’m encouraged with the current literature on psychedelic treatments supporting certain mental health conditions,” Hilas said. “I think with time and with health care professionals such as pharmacists, who are at the forefront in the community and in other settings, we’ll be able to better inform the public about why these medications with these perceived euphoric effects can, if dosed appropriately, be used therapeutically to help individuals with certain conditions. I think with pharmacists’ participation and engagement with both the public and other health care professionals, we can certainly bring attention to the positives and not have the stigma or perceptions of psychedelics from over the years overshadow the potential future values.”

READ MORE: Mental and Behavioral Health Resource Center

References

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2. FDA issues first draft guidance on clinical trials with psychedelic drugs. News release. FDA. June 23, 2023. Accessed March 13, 2024. https://www.fda.gov/news-events/press-announcements/fda-issues-first-draft-guidance-clinical-trials-psychedelic-drugs

3. FDA grants breakthrough therapy designation for MDMA-assisted therapy for PTSD, agrees on special protocol assessment for phase 3 trials. News release. Multidisciplinary Association for Psychedelic Studies. August 26, 2017. Accessed March 13, 2024. https://maps.org/news/media/press-release-fda-grants-breakthrough-therapy-designation-for-mdma-assisted-psychotherapy-for-ptsd-agrees-on-special-protocol-assessment-for-phase-3-trials/

4. Compass Pathways receives FDA breakthrough therapy designation for psilocybin therapy for treatment-resistant depression. News release. Compass. October 23, 2018. Accessed March 13, 2024. https://compasspathways.com/compass-pathways-receives-fda-breakthrough-therapy-designation-for-psilocybin-therapy-for-treatment-resistant-depression/

5. MindMed receives FDA breakthrough therapy designation and announces positive 12-week durability data from phase 2b study of MM120 for generalized anxiety disorder. News release. Mind Medicine. March 7, 2024. Accessed March 13, 2024. https://ir.mindmed.co/news-events/press-releases/detail/137/mindmed-receives-fda-breakthrough-therapy-designation-and-announces-positive-12-week-durability-data-from-phase-2b-study-of-mm120-for-generalized-anxiety-disorder

6. Lykos Therapeutics announces FDA acceptance and priority review of new drug application for MDMA-assisted therapy for PTSD. News release. Lykos Therapeutics. February 9, 2024. Accessed March 13, 2024. https://www.prnewswire.com/news-releases/lykos-therapeutics-announces-fda-acceptance-and-priority-review-of-new-drug-application-for-mdma-assisted-therapy-for-ptsd-302058901.html

7. Mitchell JM, Bogenschutz M, Lilienstein A, et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021;27(6):1025-1033. doi:10.1038/s41591-021-01336-3

8. Yazar-Klosinski BB, Mithoefer MC. Potential psychiatric uses for MDMA. Clin Pharmacol Ther. 2017;101(2):194-196. doi:10.1002/cpt.565

9. Strauss D, Ghosh S, Murray Z, Gryzenhout M. An overview on the taxonomy, phylogenetics and ecology of the psychedelic genera Psilocybe, Panaeolus, Pluteus and Gymnopilus. Front For Glob Change. 2022;5. doi:10.3389/ffgc.2022.813998

10. Ziff S, Stern B, Lewis G, Majeed M, Gorantla VR. Analysis of psilocybin-assisted therapy in medicine: a narrative review. Cureus. 2022;14(2):e21944. doi:10.7759/cureus.21944

11. Compass Pathways announces publication of positive data from treatment-resistant depression phase 2 clinical trial of COMP360 psilocybin alongside antidepressants in Nature journal, Neuropsychopharmacology. News release. Compass. July 17, 2023. Accessed March 13, 2024.https://compasspathways.com/compass-pathways-announces-publication-of-positive-data-from-treatment-resistant-depression-phase-2-clinical-trial-of-comp360-psilocybin-alongside-antidepressants-in-nature-journal-neuropsychopharmac

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13. Liechti ME. Modern clinical research on LSD. Neuropsychopharmacology. 2017;42(11):2114-2127. doi:10.1038/npp.2017.86