Thinking Back and Looking Forward, Good Neighbor Pharmacy Is Ready for the Next 40 Years

Lauren Biscaldi is the Managing Editor of Drug Topics. 

The Total Pharmacy Solutions Summit is back and better than ever: On October 22, join community pharmacy thought leaders online for a day of education, conversation, and insights centered around the theme of 

From 9 AM to 3 PM, join this virtual Summit and tune into sessions where attendees will learn tips and tricks in areas such as innovative test-to-treat strategies, the ins and outs of AI optimized pricing, and the latest updates on COVID-19 booster vaccines and treatments. Attendees who participate in the live event on October 22 are also eligible to earn 3 live CE credits via 3 accredited sessions, including one on avoiding medication errors and another covering best practices around controlled substances. Both of these CE sessions are accredited by 

Pharmacists, pharmacy support staff, and owners and operators across the independent and community pharmacy space—as well as pharmacy professionals interested in independent pharmacy—are all encouraged to attend.

most recent Total Pharmacy Solutions Summit

 took place on April 30, 2022. Speakers from across the industry came together to share their insights on the latest topics affecting independent pharmacy practitioners across the country and included Paige Clark, RPh, vice president of pharmacy programs and policy at Prescryptive Health; Lisa Faast, PharmD, founder and CEO of DiversifyRx; and Steven F. Moore, PharmD, vice president of Condo Pharmacy, who delivered the day’s Keynote Address.

Please join us for the Total Pharmacy Solutions Summit on Saturday, October 22, 2022 from 9 AM to 3 PM EST. Visit the 

 today to pre-register and secure your spot at the event.

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Health plans use updated evidence when revising their specialty drug coverage policies, but those updates tend to focus on health technology assessments, randomized clinical trials, and systematic reviews/meta-analyses and not real-world evidence studies and economic evaluations, according to a recent review 

Journal of Managed Care + Specialty Pharmacy

“The mismatch between the evidence developed by researchers and the evidence cited by health plans suggests that health plan officials may not find much of the available evidence to be of value when formulating coverage policies,” James D. Chambers, Ph.D., one of the authors of the paper told 

. “Going forward, we should aim for greater alignment. This may require product manufacturers to engage earlier, and more often, with health plans when developing evidence generation programs for their products.” Chambers is associate professor of medicines, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center in Boston.

Researchers at the Institute for Clinical Research and Health Policy Studies reviewed the citations of clinical and economic evidence plans included in their drug coverage policies between August 2017 and August 2019. They identified drug-indication pairs (e.g., infliximab for rheumatoid arthritis) and examined the frequency with which plans reissued these policies between these two time points and the frequency with which plans altered coverage criteria or updated the cited evidence.

Researchers selected 20 drug-indication pairs and they performed a literature search of PubMed to identify the evidence available, including randomized controlled trials, real-world evidence studies, other clinical studies, economic studies, technology assessments and treatment guidelines. They then compared the literature search with evidence cited in coverage policies.

They identified 4,597 coverage policies that plans made available in both August 2017 and August 2019, of which plans reissued 4,468 (97%). Of the reissued policies, 17% revised coverage criteria and 84% revised the evidence cited, and 15% of reissued policies revised both their coverage criteria and the evidence cited, 2% revised only their coverage criteria, and 69% revised only the cited evidence. A total of 14% of policies revised neither the coverage criteria nor the evidence cited.

For drugs approved no earlier than August 2014, plans cited randomized controlled trials and other clinical studies most comprehensively (7% and 5%, respectively); for drugs approved from August 2009 to August 2014, plans cited clinical guidelines and evidence synthesis studies most comprehensively (8% and 5%, respectively); and for drugs approved before August 2009, plans cited health technology assessments most comprehensively (4%).

“Our study indicates that the evidence cited in coverage policies evolves over a product’s life cycle. Plans tended to cite RCTs and other clinical studies for recently approved products and cite clinical treatment guidelines and evidence syntheses for products on the market for longer,” researchers wrote.

Researchers cited several limitations, including a reliance on health plans’ publicly available coverage policies. They said that plans may not fully report the evidence that they review. Additionally, the suggested that the study may not be generalizable to other U.S. commercial health plans or to public healthcare payers (e.g., Medicaid and Medicare). They also did not investigate how newly cited studies affected plan decision making.

This article originally appeared on Formulary Watch.

However, researchers found that only a small percentage of plans use available real-world evidence studies and economic evaluations in their coverage policies.

Adjustments in Drug Coverage Criteria in Health Plans Based on New Evidence

When the FDA approved Opzelura as a treatment for nonsegmental vitiligo in July, the agency heralded the whitish cream as the “first FDA-approved pharmacologic treatment to address regimentation in vitiligo patients.” Opzelura had been previously approved as treatment for atopic dermatitis.

Opzelura contains ruxolitinib, an inhibitor of Janus-activated kinases (JAKs) and, more specifically, the JAK1 and JAK2 (there is also JAK3 and tyrosine kinase 2 in the JAK family of enzymes). The Janus kinases are believed to play a key role in orchestrating the complicated signaling pathways for cytokines and growth factors.

Ruxolitinib may have some company. A number of other JAK inhibitors are under investigation as treatments for vitiligo, an autoimmune disordered characterized by whitish areas of skin that are the result of a loss of melanocytes. Melanocytes produce melanin, a dark skin pigment.

 about advances in vitiligo treatment listed five JAK inhibitors as candidates for vitiligo treatment. Even so, the FDA-approved label for Opzelura has a pointed reminder that the relationship between the JAKs and their inhibition and vitiligo isn’t entirely understood. The label says that the “relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.”

Here are six JAK inhibitors discussed in the 

 is a JAK1 and JAK3 that is the active ingredient in Xeljanz. The review article says that five- to 10-milligram (mg) doses once or twice a day have shown some effectiveness as treatment for vitiligo. But review also mentions side effects from the oral version, including infections, cancer and cytopenia, and it suggests that a topical version may therefore be preferred. The review discusses positive results from a small (11 patients) trial of a tofacitinib cream.

 is a JAK1 and JAK2 inhibitor that is the active ingredient in Olumiant. The review article says that there has been a case report of repigmentation in vitiligo in patients taking four-mg doses of baricitinib as a treatment for rheumatoid arthritis. According to the review, there is a 

 underway evaluating baricitinib in combination with phototherapy as a treatment for vitiligo.

 also known provisionally as ATI-50002, is a JAK1 and JAK3 inhibitor. It is also under investigation as a treatment for alopecia areata,

, also known provisionally as PF-06651600, is a JAK3 and tyrosine kinase inhibitor. It is being evaluated in a clinical trial as a treatment for vitiligo along with another experimental agent, 

, a JAK1 and tyrosine kinase inhibitor that has the provisional code name of PF-0670084.

Pfizer put out a press release earlier this month to announce that the FDA had accepted its application for ritlecitinib as a treatment for alopecia areata and that the FDA is expected to make an approval decision during the second quarter of next year.

In June, Pfizer issued a press release trumpeting the phase 2 trial results for oral brepocitinib as a treatment for psoriatic arthritis, plaque psoriasis, ulcerative colitis, alopecia areata and hidradenitis suppurativa.

 is a spleen tyrosine kinase inhibitor as a well as a JAK inhibitor. According to the federal government’s clinical trial database, clinicaltrials.gov, 

 as a vitiligo treatment was completed in 2020 but no results are posted on the clinicaltrials.gov. Researchers are also evaluating cerdulatinib as a cancer drug and, more specifically, as an agent might be used to treat patients with non-Hodgkin lymphoma and peripheral T-cell lymphoma.

This article originally appeared on Managed Healthcare Executive.

A recent review article lists six other JAK inhibitors that might be used as treatments for vitiligo in addition to ruxolitinib, the active ingredient in recently approved Opzelura.

Other JAK Inhibitor Options for Treating Vitiligo

 Let’s talk about some individuals and communities, individuals within racial and ethnic groups or who are from foreign countries. The statistics show that they have lower rates of vaccination against flu and other recommended vaccines. How can pharmacists help in that regard? Who can they partner with to reach some of these hard-to-reach populations?

Randy McDonough, PharmD, MS, BCGP, BCPS, FAPhA:

 Mitch, I appreciate that question. One thing COVID-19 taught us is that we have some health disparities as far as who’s getting access to vaccines. The other thing we learned is that we didn’t know who those patients were unless we worked with certain stakeholders within the community. It became more of a community-wide response vs a pharmacy response. We’ve learned to work with our local public health department, our social services department, senior citizen centers, and churches to identify individuals who otherwise may have access problems to vaccines.

We’re not only working with those groups but coordinating efforts to get to those groups, whether through remote clinics or even getting to homebound patients. I’m not just a community pharmacy that provides care to the patients who use my pharmacy. I’m a community pharmacy in the true sense that we’re a community-wide responder to patients who don’t even use our practice. We help provide solutions to the community to reach those hard-to-reach patients.

 Randy articulated that very well. One silver lining of COVID-19 has been the relationship that pharmacies have developed with their local health departments. There are certainly some great examples of pharmacy and public health working together, and we hope that collaboration continues well beyond COVID-19 and into the future. That’s very important.

The other thing I wanted to mention is that with some of these populations in underserved areas, there’s a combination of vaccine hesitancy and mistrust coupled with access. I have a good friend who’s an African American pharmacist in inner-city Richmond. We’ve had numerous conversations over the last year. She said, “My patients trust me. I have no problem convincing them that they need to come in and be vaccinated. The problem is having them come in because a lot of them have transportation issues.” To Randy’s point, it’s a community-wide effort to increase confidence and access. It’s across the board, and it takes a village. It isn’t just the pharmacist. It’s the pastors, barbers, and public health. It’s across the board.

 That’s a great point, John. Randy hit on it earlier when he was talking about those outreach efforts. We leave the pharmacy and go somewhere. Two things have happened that are going to help us close the gap. One is COVID-19 got more pharmacies involved in vaccination than were involved before. Our independents [pharmacies] stepped up in California and across the board. A lot of our [independent pharmacies are in] rural areas. California has some rural areas and some areas that are underserved. We now have pharmacies giving an array of vaccines that they weren’t before. That’s No. 1, and that’s definitely helping us do that.

The second is going out to where they are. If you aren’t where they are, go to where they are. One thing we did very well before COVID-19 was flu outreach. We’d set up at a church, in a parking lot, or at a health fair. We have to get back to that and get other vaccines involved. We now have portable electronic systems. It used to always be that we couldn’t enter the information in the registry because we were in a park. Now Wi-Fi is everywhere. You can get access and get that information in there so we can expand the number of vaccines we could give in all locations. If it isn’t your pharmacy, go to where they are.

 Jeff, that’s a great point. As all 3 of you have mentioned, we’ve got models where that has worked successfully, and models where working with public health has opened some doors for communities. Through COVID-19, we saw the test of the immunization neighborhood. It isn’t just a theory. It could work and benefit communities. That’s the important part of building on that model.

Videos

Key opinion leaders discuss disparities across varying patient demographics concerning access to vaccines.

Disparities in Public Access to Vaccines Across Patient Demographics

 Studies have shown that some patients can benefit from the influenza vaccine. Who are those patients? How should pharmacists identify and communicate with those patients?

 Most pharmacies have a significant number of patients with diabetes in their population, and certainly folks who have other chronic diseases, such as heart disease and asthma. Smokers could also benefit. Anyone can benefit from the seasonal flu vaccine, but certainly those populations could benefit and should protect themselves against serious disease.

 To John’s point, it also helps to customize the message rather than say that everyone 6 months and older should get the flu vaccine. Say, “You’re a smoker, which increases your risk of pneumococcal pneumonia. You have diabetes, which increases your risk of more severe disease. Or you have cardiopulmonary or endocrine,” all these different things. You can customize it, then it becomes a recommendation for them, not for everyone. Also, we can’t forget that pregnancy is still in there as well. Make sure our pregnant patients know that they should be vaccinated. That has been a constant struggle that ob-gyns [obstetrician-gynecologists] and pharmacists have faced.

 Mitch, that’s part of doing the gap analysis of the patient when they come in. You’ve done your job to get them to come into the pharmacy to pick up their medications through a medication synchronization program. Before they came in, you were doing a full review of their medications and looking at whether there’s a gap in their medications, and vaccines would be 1 of those gaps. Which vaccine are they eligible for, and why should they be getting that? That’s when you can have that conversation and say, “You’re a high-risk patient, and this is why this vaccine is important.” [That way] before they come in to pick up the medication or set up the service, they know in advance that they’re going to come in and do this and have that conversation with the pharmacist. If we do that over and over, I guarantee that we’ll increase the vaccination rates of patients.

 To that point, I saw a recent number that said 9 of 10 people coming into a community pharmacy had some type of vaccine need. Mitch, correct me if I’m wrong. You may have told me that. I’m trying to emphasize the opportunity there.

 There are a lot of missed opportunities that are great opportunities for that discussion and impact. Have any of you utilized some of the recent publication work that was put out in terms of heart disease prevention or heart attack prevention and flu? Any insights from that work that you want to share with the audience on how you communicate that to your patients?

 There’s a positive bias toward literature. We like to find the studies that support our beliefs. Fortunately for flu, a lot of studies support our beliefs, and one that we’ve always known is around cardiovascular disease. We certainly see that patients who have congestive heart failure can decompensate and get multiorgan system failure and go into respiratory distress and die in the ICU [intensive care unit]. We know that cardiovascular disease and flu is linked.

We’re also seeing evidence that shows more of a direct benefit beyond preventing the disease. The recent meta-analysis that you referred to showed that the flu vaccine had a 34% lower risk of major cardiovascular events. If you got the flu vaccine, you’re less likely to have a major heart attack or decompensation in the hospital. The primary effect is very likely prevention of flu, but it didn’t explain all of it. There’s also the secondary effect. Even for people who got influenza, we’ve discussed throughout the presentation that it has effects beyond preventing flu but also preventing severe disease. We’ll continue to see more evidence that the flu vaccine prevents not only flu but also complications in those who get the flu. That’s a strong benefit from using the flu vaccine.

 Jeff, one of the groups you mentioned was pregnant individuals. Is there any specific time during pregnancy that an individual should get vaccinated? What’s your guidance for the audience?

 We used to say to avoid the first trimester. Not that there was ever any evidence that teratogenicity was going on, but it was one of those recommendations. Since then, for many years, we made it very easy. You can vaccinate them in any trimester. It’s unlike a Tdap [tetanus, diphtheria, pertussis] vaccination, where you’re trying to time the vaccine to the development of antibodies for the developing fetus. It’s different for influenza. Any time during pregnancy is appropriate. Of course, it’s best to give it before they deliver or at least a bit further from delivery, so they can get the benefit for both the mom and potentially for the baby, but more for mom than baby for influenza.

The expert panel identifies patient populations who can benefit most from influenza vaccination.

Identifying Patient Populations Benefiting Most From Influenza Vaccination

Full data from the 13-week trial of the iLet insulin-only bionic pancreas details the improvements in glycemic control achieved with use of the bionic pancreas in adults and children with 

 aged from as young as 6 years old and up to 79 years of age.

With funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDKD), results of the 13-week, randomized trial suggest use of BetaBionic’s iLet bionic pancreas was associated with greater reductions in HbA1c than standard care, with those using a bionic pancreas experience a greater percentage of time in range as well.

“In this multicenter, randomized trial involving adults and children with type 1 diabetes, the use of the insulin-only configuration of a bionic pancreas was associated with a lower glycated hemoglobin level, a lower mean glucose level, an increase of 2.6 hours per day in the target glucose range, and less time in a hyperglycemic state without an increase in the incidence of hypoglycemia as assessed by continuous glucose monitoring,” wrote investigators.

Since initial data demonstrated feasibility of the system, the prospect of the iLet bionic pancreas has been looked upon by many as the next great advance in diabetes technology. The current trial was conducted with an interest in exploring the technology against usual care for improving glycemic control among patients with type 1 diabetes.

A 13-week, multicenter, parallel-group, unblinded, randomized trial, the trial people aged 6-79 years of age with type 1 diabetes to receive the bionic pancreas with insulin aspart or insulin lispro or to standard care, which was defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring. Conducted at 16 centers in the US, the trial had a primary outcome of interest of HbA1c at 13 weeks and a secondary outcome of interest of percentage of time in a target glucose range below 54 mg/dL.

A total of 326 individuals were identified for inclusion in the trial between January 4, 2021, and July 7, 2021, with 219 randomized to the bionic pancreas group and 107 randomized to standard care. This cohort had an observed range of HbA1c from 5.5-13.1% at baseline.

Upon analysis, results indicated the mean HbA1c decreased from 7.9% at baseline to 7.2% at week 13 in the bionic pancreas group and did not change in the standard-care group, which remained at 7.7% at both time points (adjusted between-group difference: -0.5 percentage points [95% CI, -0.6 to -0.3]; 

 <.001 for noninferiority). When assessing the secondary outcome of interest, results indicated the percentage of time in target glucose range below 54 mg/dL did not differ significantly between either group (adjusted difference, 0.0 percentage points [95% CI, −0.1 to 0.04]; 

In safety analyses, results indicated the rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic pancreas group compared to 10.8 events per 100 participant-years (

=.39). Investigators highlighted there were also no episodes of diabetic ketoacidosis occurred in either arm of the trial.

“In this 13-week, multicenter, randomized trial, adults and children with type 1 diabetes who had been randomly assigned to automated glycemic control with a bionic pancreas had lower glycated hemoglobin levels than participants in the standard-care group, who were using insulin therapy augmented by continuous glucose monitoring,” investigators added.

This article originally appeared on Endocrinology Network.

1.  Bionic Pancreas Research Group. Multicenter, randomized trial of a bionic pancreas in type 1 diabetes. 

. 2022 Sep 29;387(13):1161-1172. doi: 10.1056/NEJMoa2205225.

The iLet Bionic Pancreas was associated with improved glycemic control and time in target glucose range compared to standard care in a cohort of people with type 1 diabetes aged 6-79 years of age.

Improved Glycemic Control, Time in Target Range Found with iLet Bionic Pancreas

Ms. Hester is Content Specialist with Contemporary OB/GYN and Contemporary Pediatrics.

Did you miss the top stories on Drug Topics® this month? Catch up on these noteworthy stories today.

Women and CBD: Increased Interest, but Caution Is Warranted

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Considering comorbidities is just as important as lowering patient HbA1c.

How Pharmacists Can Address Vaccine Hesitancy for the Flu and Beyond

Address vaccine hesitancy at your pharmacy to encourage patients and their families to get vaccinated against COVID-19, flu, and more.

FDA Approves Voquezna for Helicobacter pylori Infection in Adults

This new treatment option copackages 3 drugs for optimal treatment.

Mitigating Costs of Cancer Treatment: The Role of Pharmacists

Cancer care is expensive, but pharmacists can help.

FDA, Medtronic Alert Users to Cybersecurity Risk with MiniMed 600 Systems

The risk could allow unauthorized users to change insulin levels.

Impact of Laws on Pediatric Opioid Prescriptions

Are prescription cap laws for opioids effective for children and teenagers?

Maternal Vaccination Cut the Risk of COVID-19 Hospitalization for Infants

Infants of fully vaccinated mothers had fewer cases of hospitalization from COVID-19 than those unvaccinated.

Waste Problem Shows COVID-19 Vaccines Aren’t Just a Dime a Dozen

When it comes to the COVID-19 vaccine, independent pharmacies are being set up to fail by federal health partners.

Take a look back at our most popular news from September 2022.

September Month in Review: Top Stories on Drug Topics®

COVID-19 vaccination has been associated with an increase in menstrual cycle length of less than 1 day, based on a large international study.

The study, which was funded by the National Institutes of Health and published in the 

, gathered data from almost 20,000 people across the world who had received any of the 9 different COVID-19 vaccinations. In most participants, menstrual cycle length saw an increase after the vaccine was administered.

“These findings provide additional information for counseling women on what to expect after vaccination,” said Diana Bianchi, MD, director of National Institute of Child Health and Human Development. “Changes following vaccination appear to be small, within the normal range of variation, and temporary.”

This change in cycle is under 8 days, making it fit within the normal range of variation. While not concerning from a professional standpoint, the study authors noted that even minor changes in bodily function surrounding fertility may cause concern and increase vaccine hesitancy.

Data was gathered from a fertility tracking app called Natural Cycles, where women voluntarily provided information on menstrual cycles and body temperature. Over 19,000 individuals participated, with almost 15,000 being vaccinated against COVID-19 while over 4500 were not.

Over 30% of participants were from the United Kingdom, while about 30% were from the United States and Canada, and almost 35% from Europe. Participants were included if they had received any of the following vaccinations: Pfizer-BioNTech, Moderna, AstraZeneca, Covishield, Janssen/Johnson & Johnson, Sputnik, Covaxin, Sinopharm, and Sinovac.

The study period lasted at least 4 consecutive cycles, with at least 3 before vaccination and at least 1 after vaccination being studied. In the cycle after vaccination, vaccinated individuals experienced an average increase of less than 1 day, increasing by about 70% of a day after the first dose and about 55% after the second dose.

Over 1300 participants experienced an increase in cycle length greater than 8 days, making up 6.2% of those vaccinated and 5% of those unvaccinated. This increase was mostly likely in younger woman who had experienced longer circle length prior to vaccination.

The authors recommended further studies to observe other potential physical changes, along with the reasons these changes occur.

This article originally appeared on Contemporary Pediatrics.

1. Study confirms link between COVID-19 vaccination and temporary increase in menstrual cycle length. National Institutes of Health. September 27, 2022. Accessed September 27, 2022. 

https://www.nih.gov/news-events/news-releases/study-confirms-link-between-covid-19-vaccination-temporary-increase-menstrual-cycle-length

In a recent study, participants who had received a COVID-19 vaccine saw an average increase in menstrual cycle length of less than 1 day.

Increased Menstrual Cycle Length Tied to COVID-19 Vaccine

Indian researchers compared a biosimilar of ranibizumab (Lupin) with Lucentis (Genentech) and reported the therapeutic equivalence, safety, and favorable immunogenicity profile of the biosimilar formulation in patients with age-related macular degeneration (AMD).

Ramandeep Singh, MD, lead author from the Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh, India, reported the findings.

Singh and colleagues conducted a prospective, double-blind, 19-center phase-III study that included 202 patients with neovascular AMD. The patients were randomized (1:1) to receive an intravitreal injection of either the biosimilar formulation of ranibizumab or Lucentis 0.5 mg once monthly for 3 months.

The primary endpoint was the percentage of patients who lost fewer than 15 letters of best-corrected visual acuity (BCVA) compared with baseline The investigators assessed the adverse events, the ophthalmic examination and systemic examinations, and vital parameters. The immunogenicity assessment was based on evaluation of anti-drug antibodies, the investigators described.

Comparison of the Biosimilar and Lucentis

Of the 202 patients, 174 patients (86.14%) completed the study; those patients were evenly divided between the 2 groups.

“The proportion of patients losing fewer than 15 letters from the baseline BCVA score in the study eye was comparable between the two groups,” the authors reported.

Analysis of the 2 groups showed that the 2 drugs were comparable in the percentages of patients who lost fewer than 15 letters of BCVA and the numbers of adverse events.

The numbers of patients who lost fewer than 15 letters, the investigators explained, were within the predefined equivalence margin (intention-to-treat population, 1.0%; 95% CI, -3.3% to 5.4% and per protocol population: 1.2%; 95% CI, -3.2% to 6.4%).

Eleven patients (10.89%) in the biosimilar group and 19 (18.81%) patients in the Lucentis group had at least one treatment-emergent adverse event.

The immunogenicity incidence, ie, the proportion of patients with positive anti-drug antibodies, was numerically lower in the biosimilar group (4.95%) than in the Lucentis group (12.87%).

The investigators concluded that biosimilar ranibizumab showed therapeutic equivalence, desirable safety, and favorable immunogenicity profile compared with Lucentis.

1. Singh R, Chauhan R, Saxena A, et al. A prospective, randomized, parallel group, double blind, multicenter study to compare the efficacy, safety and immunogenicity of Lupin's Ranibizumab with Lucentis in patients with neovascular age-related macular degeneration. 

. 2022;70(8):3008-3014. doi: 10.4103/ijo.IJO_2118_21

The authors noted that the proportion of patients losing fewer than 15 letters from the baseline BCVA score in the study eye was comparable between the two groups.

Efficacy and Safety of Ranibizumab and Lucentis for Wet AMD Compared

Lysergic acid diethylamide (LSD) and psilocybin are serotonergic psychedelics that are candidates for the treatment of psychiatric disorders.

 Both agents stimulate serotonin 5-HT2A receptors; LSD also acts at dopamine D13-3 receptors, and the active metabolic of psilocybin (psilocin) inhibits the serotonin transporter.

 The similarities, acute effects, and dose equivalence of these agents in humans remains unclear.

 directly compared the acute subjective, autonomic, and endocrine effects of LSD and psilocybin at 2 doses and placebo within the same participants. The acute subjective effects of these agents were assessed with validated psychometric instruments, and pharmacokinetic data were obtained over 24 hours. The investigators performed a double-blind, placebo-controlled crossover study with 5 experimental test sessions (placebo, LSD 100 µg, LSD 200 µg, psilocybin 15 mg, psilocybin 30 mg), with a washout period of at least 10 days between sessions.

The authors recruited 28 healthy participants; their mean age was 35 years and 50% were male. Exclusion criteria were: age less than than 25 years or greater than 65 years, pregnancy, family history of major psychiatric disorders in first-degree relatives, current psychotropic medication use, acute or chronic physical illness, tobacco smoking of more than 10 cigarettes/day, lifetime illicit drug use exceeding 10 times (except use of tetrahydrocannabinol [THC], the principal psychoactive cannabinoid of cannabis), or illicit drug use in the past 2 months or during the study period. In terms of previous drug use, 11 participants had previously used LSD and 6 had previously used psilocybin; 13 had previously used a stimulant; and 10 participants had no history of noncannabis illicit drug use. LSD was administered as an oral solution and psilocybin as an oral capsule. A double-dummy method was used such that participants received 6 capsules and 2 solutions at each test session.

Each test session lasted 25 hours and was conducted in a calm hospital room. Abstinence from illicit drugs was verified with a urine drug screen. Outcomes were repeatedly assessed for 24 hours. Standardized meals were served. An investigator was present in the room during the acute effect phase and remained in a room next to the participant for up to 24 hours. Subjective effects were assessed repeatedly using visual analogue scales (VAS), the Adjective Mood Rating Scale (AMRS), the 5 Dimensions of Altered States of Consciousness scale (5D-ASC), and the Mystical Effects Questionnaire(MEQ). Effect durations were assessed using the classic pharmacokinetic-pharmacodynamic link module. Blood pressure, heart rate, and temperature were repeatedly measured. Adverse effects were assessed 1 hour before and 12 and 24 hours after drug administration. Plasma LSD and psilocybin concentrations, and cortisol, prolactin, oxytocin, and brain-derived neurotrophic factor (BDNF) measurements were also obtained at multiple time points. Pharmacokinetic parameters were estimated using noncompartmental methods. Peak drug effects (minimum, maximum, or change from baseline) were determined for repeated measures, then analyzed using repeated-measures analysis of variance.

Both doses of LSD and the 30-mg psilocybin dose produced comparable subjective effects, based on VAS and 5D-ASC outcomes. There was significantly greater ego dissolution and a trend toward greater anxiety with 200 µg versus 100 µg LSD. Psilocybin 15 mg had significantly lower effects than psilocybin 30 mg and both LSD doses, based on VAS and 5D-ASC outcomes. Both LSD doses had significantly increased “emotional excitation” on the AMRS compared with psilocybin. There were no differences in subjective effects of LSD or psilocybin based on sex.

Both LSD and psilocybin significantly increased systolic and diastolic blood pressure, temperature, and pupil diameter compared with placebo. Psilocybin 30 mg produced significantly greater increases in blood pressure and temperature compared with psilocybin 15 mg and both doses of LSD. By contrast, both LSD doses produced a greater increase in pulse compared with both psilocybin doses and placebo. Psilocybin produced greater impairments in pupil contraction compared with LSD. Both LSD and psilocybin increased the total acute (0-12 hours) adverse effect score compared with placebo. Subacute (12-24 hours) adverse effect scores were significantly greater with LSD 200 µg LSD and psilocybin 30 mg compared with placebo. The most common adverse effects were headaches. Five participants had 9 flashback episodes within 72 hours. No severe adverse events were observed.

Both LSD doses had significantly longer effect durations (10-11 versus 6-7 hours) and earlier onset of effects (0.4-0.6 versus 0.8 hours) compared with both psilocybin doses. The elimination half-life values were about 4 hours for LSD and 2.5 hours for psilocybin. Both LSD and psilocybin significantly increased plasma cortisol, prolactin, and oxytocin levels, but neither affected BDNF levels. Both LSD and psilocybin showed linear pharmacokinetics, which were not influenced by body weight.

In terms of blinding, no clear distinction between LSD and psilocybin could be made after the session or at study end point. Participants correctly identified the psychedelic and dose in about 60% of sessions, compared with 96% for placebo.

The authors investigated and directly compared the acute effects of LSD and psilocybin in healthy participants in a well-blinded study. They concluded that psilocybin 15 mg exerted clearly weaker subjective effects, and both agents had dose-dependent effect durations (significantly longer for LSD), stimulant autonomic effects, and increased endocrine parameters. Body weight had no influence on blood concentrations. The investigators noted the data further supported the notion that states of consciousness alteration induced by LSD and psilocybin are more likely dose-dependent rather than substance-dependent. In addition, they concluded the differences in the pharmacological profiles of LSD and psilocybin do not relevantly influence subjectively experienced effects of both psychedelics.

Study strengths included the within-subjects design and the use of well-characterized, fixed dosing. The primary study limitations were the use of a highly controlled setting and the participation of healthy participants only.

This study supports dose finding for research and psychedelic-assisted therapy. Psilocybin 20 mg is likely equivalent to LSD 100 µg. There was no evidence for qualitative differences in altered states of consciousness, except for a shorter duration of action for psilocybin.

This article originally appeared on Psychiatric Times. 

1. Carhart-Harris R, Giribaldi B, Watts R, et al. 

Trial of psilocybin versus escitalopram for depression.

2. Griffiths RR, Johnson MW, Carducci MA, et al. 

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial.

Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial.

LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: a qualitative study of acute and sustained subjective effects.

5. Rickli A, Moning OD, Hoener MC, Liechti ME. 

Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens.

Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects.

In a well-blinded study, researchers investigated and directly compared the acute effects of LSD and psilocybin in healthy participants.

Improved Glycemic Control, Time in Target Range Found with iLet Bionic Pancreas

September Month in Review: Top Stories on Drug Topics®

Increased Menstrual Cycle Length Tied to COVID-19 Vaccine

Efficacy and Safety of Ranibizumab and Lucentis for Wet AMD Compared

The Effects of Psychedelics in Healthy Participants