Psychedelic medicines such as psilocybin, MDMA, ketamine, and LSD have been shown to have a significant impact on conditions such as major depressive disorder, generalized anxiety disorder, and post-traumatic stress disorder in clinical trials.
The development of psychedelic medicine is completely revolutionizing our approach to mental health care, explained Sa'ed Al-Olimat, PharmD, co-founder, Psychedelic Pharmacists Association, during a presentation at the American Pharmacists Association (APhA) 2024 Annual Meeting & Exposition in Orlando, Florida.1 Although still classified as illegal in most states and jurisdictions, the legal status of psychedelics has also been changing in states such as Oregon and Colorado, with more changes on the horizon with
“We're observing a lot of regulatory changes take place that are very inclusive, and spotlight psychedelics as a positive thing versus a device to trip or escape. With that also comes the cultural shifts we're experiencing. Many people are interested in exploring new paths toward healing through their traumas, and access to psychedelic education is rapidly trending,” said Al-Olimat in
Much of this shift toward greater sociocultural acceptance of psychedelics as medicine has come about because of the mental health crisis the country faced during the COVID-19 pandemic, which has continued to result in challenges relating to access to psychiatric care due to the high national demand. However, even before the pandemic the prevalence of mental health conditions in the United States was significant, with 1 in 5 adults reporting experiencing mental illness each year, based on data from a study published in Psychiatric Services in March 2012.2
Al-Olimat explained further that a survey of 36,309 US adults found the 12-month and lifetime prevalence of major depressive disorder (MDD) was 10.4% and 20.6%, respectively. Additionally, post-traumatic stress disorder (PTSD) affects approximately 5% of the US population each year, based on data from a 2018 study published in JAMA Psychiatry.1
“Our current mental health landscape could definitely be better,” Al-Olimat said during the session. “When we look at treating those struggling with MDD, PTSD, or generalized anxiety disorder [GAD], usually our first line approach outside of psychotherapy… are just dispensing of traditional antidepressants, or [selective serotonin reuptake inhibitors (SSRIs)] and [serotonin and norepinephrine reuptake inhibitors (SNRIs)]. However, it's important to look at the efficacy and dissect that.”1
For example, Al-Olimat noted that a significant counseling point with patients on SSRIs and SNRIs is their lag effect, as it can take 2 to 4 weeks before any potential therapeutic effects become noticeable. Patients in need of treatment may not experience the effects of the SSRI for a couple of weeks.1
“When people are struggling day in, day out, and it is true depression, some of them can't wait for it to maybe work. Additionally, in some clinical trials, where they compare antidepressants head to head with placebo, they found that there is only 15% to 18% better efficacy,” Al-Olimat said during the session. “So yes, that's better than placebo. But should that really be our first-line approach?”1
Additionally, Al-Olimat noted that in a recent meta-analysis called the STAR*D Trial, investigators followed patients throughout their treatment regimen with antidepressants and found that at every step of care, there were decreases in treatment effectiveness and higher rates of relapse. “People just weren't necessarily getting better,” Al-Olimat said during the session.1
Additionally, for patients with PTSD, 35% to 47% of individualsdo not respond to antidepressant treatment. Further, common adverse effects of SSRIs and SNRIs can have an impact on patient adherence, as they can include nausea, changes in appetite, weight loss or gain, sexual dysfunction, fatigue and drowsiness, agitation, myalgia, anxiety, excessive sweating, headache, insomnia, dry mouth, vomiting, diarrhea and constipation, and dizziness.1
“The biggest thing I'm wanting to get across is that there's a need for innovation in this space. We've had tremendous strides in oncology, immunology, advanced cardiology, and there are some newer compounds aimed to treat those with depression, anxiety, and PTSD, but what if there could be more,” Al-Olimat said during the session. He explained further that pushing adherence of SSRIs and SNRIs may beg the question of whether adherence to these medications is truly beneficial for patients in the long term.1
What psychedelic medicine offers that is unique comparatively with SSRIs and SNRIs is the opportunity to process memories and experiences while in a supportive setting with trained health care professionals. According to Al-Olimat, the goal of these sessions will likely not be to entirely eliminate a patient’s depression, but instead to process a piece of the puzzle that may be contributing to that depression.1
“It's [like] talking to aspects of the subconscious,” Al-Olimat said during the session. “It's about long-lasting habit change and really nailing down these changes and perspectives and seeing how that fits into the greater schema of your day to day activities and living.”1
Al-Olimat noted that one common analogy that gets used by researchers when discussing an impact of psychedelic medicine on the mind is the imagery of sledding down a hill.1
“They talk about a snowy hill, and depression is when you're going through the same motions, the same thought patterns, and when you're at the top of the hill and you want to slide down, you've made these deep grooves where you're always going to fall,” Al-Olimat said during the session. “What psychedelics can possibly offer is that fresh coat of snow, so that when people want to sled down it afterwards, they can take a new path. This reflects the idea of [psychedelics supporting] neuroplasticity, which allows the brain to be in a more malleable state.”1
With a greater level of neuroplasticity, Al-Olimat noted that efforts to change habits can have a stronger and more long lasting effect.1
Al-Olimat explained further that psychedelics as a term generally encompass the following drugs: ketamine, 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, and LSD. Ketamine, which blocks NMDA receptors, inhibits GABA release, which increases glutamate release. AMPA receptors are then activated resulting in ion influx, triggering BDNF release. BDNF then activates TrkB receptors, which facilitates further enhanced synaptic plasticity.1
“The one thing I love about ketamine is that it is an approved compound, so it is accessible legally under clinical supervision for folks to use off label to try and work through their depression and a variety of other mental health disorders,” Al-Olimat said during the session.1 He explained further that a single low dose of ketamine was shown to have rapid antidepressant effects in patients with treatment-resistant moderate-to-severe depression when compared to a placebo control. Additionally, improvements in depression severity were significant at 24 hours after ketamine infusion and generally maintained for several days (n=47).1,3
In another study published in the American Journal of Psychiatry in 2019, investigators found that 11 participants (27%) met response criteria and 2 (5%) achieved remission after a single infusion, with repeated infusions doubling the antidepressant response (n=39) for some patients. In total, 23 participants (58%) met antidepressant response criteria and 9 (23%) achieved remission in that study.1,4
For MDMA,
“MDMA is essentially a psychedelic amphetamine. It's unique in that it binds to SERT, gets uptake into the presynaptic neuron, releases monoamines into the synaptic cleft,” Al-Olimat said in the interview with Pharmacy Times. “With that, it activates the 5HT2A receptor, which is considered the psychedelic switch. With that activation, we also see the enhanced glutamatergic activity which can really lead to BDNF release, and neurogenesis and neuroplasticity.”
Psilocybin, on the other hand, is a 5-HT2A receptor agonist that is considered a “classical psychedelic.” Following consumption, the prodrug psilocybin is converted to the active psilocin, which binds to 5-HT2A receptors, increasing glutamatergic activity in the prefrontal cortex. The AMPA receptors are then activated and BDNF is released, according to Al-Olimat. Psilocybin is naturally occurring and is found in various species of “magic mushrooms,” with indications for treatment-resistant depression, MDD, suicidality, GAD, PTSD, and substance use disorder.
“One thing I really appreciate about psilocybin is that it is found in nature,” Al-Olimat said during the session. “I mushroom farm, mainly oyster mushrooms and lion's mane, and I follow some Reddit threads, and someone took a picture of their garden pot in their front yard, and somehow psilocybin mushrooms were growing out of their garden pot. So, they're all around us.”
Studies have demonstrated that psilocybin-assisted therapy has substantial, rapid, and enduring antidepressant effects in patients with MDD, lasting at least 4 weeks with 71% of participants (n=17) showing significant improvement. Additionally, the effectiveness of psilocybin therapy after a single or a few administrations offers a considerable advantage over daily antidepressant medication, indicating a promising approach for treating MDD. Furthermore, psilocybin's rapid antidepressant effects are comparable to those of ketamine, although with longer-lasting therapeutic benefits.1,5
Notably, in addition to psilocybin, MDMA, and ketamine,
“We need more trained pharmacists and other clinicians available as this becomes legalized,” Al-Olimat said during the session. “We also know that specialty pharmacy will be utilized… for the logistical handling of psilocybin and MDMA.”
Additionally, Al-Olimat noted that many patients are beginning to explore these therapeutics due to media coverage and public interest in these medicines, so pharmacists trained in psychedelic medicines will become increasingly valuable as a resource for accurate information for patients who may be interested.
“I believe that pharmacists can also be trained and equipped to support the dose facilitation of these medicines, as well as support the preparation and integration process before and after the administration day,” Al-Olimat said during the session. “Then, of course, as [pharmaceutical (pharma)] companies continue adopting, researching, and studying psychedelic compounds, more novel agents will come to the fore, and there will be roles in the pharma industry for pharmacists.”
Al-Olimat noted that for pharmacists who are interested in learning more about the role of the pharmacist in psychedelic medicine both now and in the future, the Psychedelic Pharmacists Association is a valuable resource. In a
“The Psychedelic Pharmacists Association is a professional nonprofit focused on connecting pharmacists that are passionate and curious about psychedelics,” Al-Olimat said during the panel discussion. “Additionally, the aim of our association is to educate all stakeholders—patients, providers, and pharmacists—about what psychedelics are, what they can offer, and risks and benefits—everything there is to know about psychedelics.”
Al-Olimat explained further during the panel discussion that no one will advocate on behalf of pharmacists for their inclusion in the standard of care for psychedelics. For that reason, the Psychedelic Pharmacists Association has been working to address this topic with organizations such as MAPS PBC, which has recently been renamed Lykos Therapeutics, as well as with state legislatures.
“[We’re] getting ourselves out there to those key decision makers. So, for example, having calls with like MAPS PBC, who [submitted an NDA to the FDA for] MDMA-assisted psychotherapy. Making sure that they know that, ‘Hey, we're more than just specialty pharmacy, we're more than just dispensing. There are so many more avenues that we as a profession can take.’ But we need to be seen and heard about that,” Al-Olimat said during the panel discussion. “It also means for different states legalization efforts [that we are] getting involved in some of the decision making there, because there's going to be federal legalization, which will happen, but then there's also the state by state approach that is really the ‘Wild West.’ Being able to make sure that pharmacists can have a role, or at least the pharmacist perspective is included in the decision making, that's an utmost priority.”
REFERENCES
1. Al-Olimat S. From Stigma to Science: Psychedelics and Pharmacist Care. American Pharmacists Association 2024 Annual Meeting & Exposition; March 22-25, 2024; Orlando, Florida.
2. One in five U.S. adults had a diagnosable mental disorder in the past year, survey finds. Psychiatr Serv. 2012;63(3):296. doi:10.1176/appi.ps.2012p296
3. Murrough JW, Iosifescu DV, Chang LC, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013;170(10):1134-1142. doi:10.1176/appi.ajp.2013.13030392
4. Phillips JL, Norris S, Talbot J, et al. Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial. Am J Psychiatry. 2019;176(5):401-409. doi:10.1176/appi.ajp.2018.18070834
5. Davis AK, Barrett FS, May DG, et al. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2021;78(5):481-489. doi:10.1001/jamapsychiatry.2020.3285
