The buzz around psychedelics for the treatment of post-traumatic stress disorder (PTSD) far exceeds the current supporting evidence, say the authors of a clinical review published online in AJHP.
The qualitative analysis found high-quality evidence that ketamine and methylenedioxymethamphetamine (MDMA), used in conjunction with psychotherapy, may help improve PTSD symptoms. But no such determination could be made for other psychedelics, thanks to a lack of solid evidence on their use in PTSD.
The authors said their results underscore the need for clinicians to continue making care decisions grounded in scientific research and clinical guidelines.
“We wanted to provide pharmacists with a balanced and evidence-based review of what’s known about psychedelics — not just the hype, but the actual clinical data,” said lead author Jennifer E. Thomas, clinical pharmacist at Children’s of Alabama in Birmingham.
Clinical Matters
The ASHP News Center is publishing a series of stories on new research helping shape pharmacy practice.
In the lead: MDMA and ketamine
Thomas and her co-authors started by searching for English-language randomized controlled studies evaluating the use of psychedelic medications for the treatment of PTSD. That yielded a surprise: Only 13 studies, all pertaining to IV ketamine and MDMA-assisted psychotherapy, met the predetermined inclusion criteria.
Co-author Anna Dellarole, clinical operations consultant for Coiled Therapeutics, said the review ultimately excluded lysergic acid diethylamide, dimethyltryptamine, and mescaline because “there’s no double-blind randomized controlled trial that supports their use in PTSD.”
Dellarole and Thomas were both affiliated with Larkin University in Florida when the study was conducted.
Joshua Caballero, associate professor at the University of Georgia College of Pharmacy and a co-author of the report, cautioned against relying on limited studies or anecdotal reports claiming that MDMA-assisted therapy and IV ketamine may ease PTSD symptoms. The report highlighted that psychedelics are inherently difficult to study in a double-blind methodology. The authors also noted that many of the reviewed papers were constrained by small sample sizes, heterogeneous study designs, and high risk of bias.
“Promising does not mean that it’s proven,” Caballero said.
Meeting unique needs of veterans
The researchers also analyzed the demographics of study participants, specifically veterans, to identify factors that may influence clinical outcomes. A 2018 survey cited in the report estimated the incidence of PTSD among active-duty U.S. service members and reserve personnel to be about 10%, compared with a 7% lifetime risk for the general population. Three of the 13 studies in the analysis were conducted primarily in veterans (two with ketamine IV, one with MDMA-assisted therapy).
Dellarole said new research is needed to guide psychedelic treatments for PTSD in veterans and other patient populations. “Type of trauma, comorbidities, other medication regimens, and treatment response might all differ among veterans, and other populations. We haven’t seen that explored yet in the literature,” she said.
Opportunities for pharmacists
As research into psychedelics continues, other necessary aspects of care — U.S. Food and Drug Administration (FDA) approval, federal and state regulations, and standardized treatment guidelines — will likely evolve. As of now, ketamine has been approved for limited medical use, while MDMA remains an illegal Schedule I controlled substance.
The researchers urged pharmacists to remain aware of healthcare trends and policy shifts and to keep a close eye on pharmaceutical and psychiatric literature, FDA updates, professional organizations, and other trusted sources of information.
“It’s a very fast-moving area,” Caballero said. “Relying on media coverage alone is not enough and could be very risky.”
Potential roles for clinical pharmacists in guiding psychedelic treatment decisions include assessing patients for cardiovascular risks and potential drug interactions, educating the interdisciplinary healthcare team, and complying with risk evaluation and mitigation strategy requirements.
Thomas predicted psychedelics, if approved, will become adjuncts to current therapies, rather than replacements. “These agents should be embedded in a structured, supervised care plan rather than used as stand-alone cures or as first-line therapy,” she said.
Caballero added that each psychedelic should be evaluated individually to account for differences in the drugs’ mechanisms of action, treatment models, evidence base, risk profiles, and regulatory considerations.
“Just because these are all psychedelics does not mean that they’re interchangeable,” he said.
Combining education with empathy
Pharmacists are well-positioned to counsel patients about the proven benefits and risks of psychedelics and to counter misinformation. Safety remains a major concern, as both MDMA and ketamine have been associated with elevated blood pressure and heart rate, among other adverse effects.
“As interesting as it is to think that certain psychedelics could be used as adjunct treatment in patients with treatment-resistant PTSD one day, all the public attention might lead people to prematurely think of these as medications,” said Dellarole. “Pharmacists should have a major role in educating the public on following evidence-based care and sticking to what we know is safe.”
Caballero urged pharmacists to take a non-judgmental approach to patient conversations.
“People are looking for alternative therapies because other treatments have failed. They’re looking for hope,” he pointed out. “We need to provide valid information and give them realistic expectations — without adding any stigma.”
ASHP has a policy on psychedelic assisted therapy.
5-HT2 AGONIST, ENTACTOGEN, AND EMPATHOGEN (PSYCHEDELIC) ASSISTED THERAPY
Source: Council on Therapeutics
- To recognize that psychedelic-assisted therapy (PAT) has demonstrated therapeutic potential and should be further researched; further,
- To recognize that in PAT there is not a standardized product subject to the same regulations as a prescription drug product, and to support the development of standardized formulations of psychedelics that would provide consistent potency and quality; further,
- To encourage state boards of pharmacy, regulatory agencies, and safety bodies with an interest in PAT to promote research best practices and regulatory standards for medication preparation, compounding, and administration to ensure safety and quality; further,
- To advocate that when psychedelics are used for PAT, healthcare providers, including pharmacists, should assess patients for medical, pharmacologic, and psychosocial contraindications prior to use and provide medical assistance as needed.
