Gus Alva, MD

Guidance for Clinicians on Patient Questions About Psychedelics, With Gus Alva, MD

General clinicians should take patient questions about psychedelic therapies seriously and respond with balanced, nonjudgmental information, even if they lack detailed expertise, according to Gus Alva, MD, psychiatrist and medical director of ATP Clinical Research. He emphasized that inquiries often reflect unmet treatment needs rather than curiosity alone.

“It's really important that if a clinician just dismisses the question, they might then push the patient towards [a] less safe, unsupervised route, and that would be catastrophic in and of itself,” Alva told 

. “It's important for generalists also to know what is approved versus what is experimental.”

He cited ketamine, which is used off-label for treatment-resistant depression, and intranasal esketamine (Spravato), which has received approval from the Food and Drug Administration (FDA) under a Risk Evaluation and Mitigation Strategy. In contrast, agents such as psilocybin, MDMA, LSD, DMT, and ibogaine remain investigational and are generally accessible only through clinical trials or limited research settings.

He encouraged clinicians to screen for features that may increase risk, including histories of bipolar disorder, psychosis, or cardiovascular disease, when patients express interest in psychedelic therapies. These considerations are particularly relevant given reports of patients seeking treatment through retreat centers or other unregulated providers, he said.

“That would actually expose individuals to additional risks,” Alva noted.

Alva also recommended that generalists familiarize themselves with local research programs and referral pathways. Although most clinicians will not deliver psychedelic-assisted therapy, awareness of legitimate clinical trial options can help guide patients appropriately. He emphasized that many individuals pursuing these therapies have experienced partial response or failure with standard treatments, including antidepressants or psychotherapy, and may have higher symptom burden.

Providing clear, evidence-based information while acknowledging uncertainty may help clinicians support patient decision-making. According to Alva, clinicians should focus on understanding why patients are interested, assessing safety considerations, and maintaining open communication. He added that this approach can help strengthen trust while ensuring that patients receive guidance grounded in current evidence and regulatory status.

spoke with Alva in light of the White House executive order issued on April 18, 2026, that directs federal agencies to accelerate psychedelic research for serious mental illness.

 The order, signed by President Donald Trump, outlines steps for prioritizing review of psychedelic compounds, facilitating access under the Right to Try framework, and supporting collaborative research efforts involving federal agencies, academic centers, and the private sector. With federal efforts accelerating psychedelic research, the field may be moving closer to establishing these agents as therapeutic options for patients with mental illness.

“It doesn't mean that every generalist is going to have to become now a psychedelic expert or therapist or clinician, but we should be able to figure out why [our] patients [are] asking about it who have high-risk features and provide non-judgmental information, as well as referring appropriately,” Alva said. “[This] subsequently will help strengthen the therapeutic relationship of the individual with their provider.”

Watch parts 1 and 2 of our interview with Alva here: 

White House Order Accelerates Psychedelic Research for Mental Illness, With Gus Alva, MD

Psychiatry Infrastructure Lags Psychedelic Momentum, With Gus Alva, MD

Relevant disclosures for Alva include Teva Pharmaceuticals, Otsuka America Pharmaceuticals, AbbVie Inc., Axsome Therapeutics, Janssen Pharmaceuticals, and more.

O’Neil G. Accelerating Medical Treatments for Serious Mental Illness. The White House. Published on April 18, 2026. Accessed April 20, 2026. 

https://www.whitehouse.gov/presidential-actions/2026/04/accelerating-medical-treatments-for-serious-mental-illness/

Kotkiewicz J. Fact Sheet: President Donald J. Trump is Accelerating Medical Treatments for Serious Mental Illness. The White House. Published April 18, 2026. 

https://www.whitehouse.gov/fact-sheets/2026/04/fact-sheet-president-donald-j-trump-is-accelerating-medical-treatments-for-serious-mental-illness/

Videos

Alva outlines how general clinicians should address patient questions on psychedelic therapies, including risks, approvals, and referral pathways.


Psychiatry currently lacks the infrastructure and trained workforce required to safely deliver 

 at scale, despite accelerating policy and research momentum, according to Gus Alva, MD, psychiatrist and medical director of ATP Clinical Research. Speaking in the context of recent federal efforts to expand access and research, Alva emphasized that adaptability exists within the field, but implementation capacity remains limited.

He noted that patients with risk factors such as bipolar disorder, psychosis vulnerability, or cardiovascular disease may require careful screening, including detailed psychiatric and family histories and trauma-informed assessments. Current trial protocols, he explained, rely on highly trained therapists, often requiring > 100 hours of specialized preparation.

“The reality is that we right now don't have a therapist pool in the US that would be able to actually fill in this particular slot,” Alva said. “Bear in mind also that these sessions require about 6 to 8 hours of dosing with facilitators, as well as medical backup…physical space, and integration sessions that are done before and after.”

He highlighted integration expertise as central to potential benefit, noting that clinicians must help patients process experiences during a period of heightened neuroplasticity. He also emphasized the importance of safety protocols, including contingency planning for difficult psychological responses, emergent suicidality, psychotic symptoms, or cardiovascular events.

Alva’s comments follow the April 18 executive order signed by President Donald J. Trump directing federal agencies to accelerate research and regulatory pathways for investigational psychedelic therapies.1,2 Alva cautioned that infrastructure development must keep pace with policy changes.

“What this executive order basically brought to the surface is that the way or the conduit for actually exploring psychedelics is going to become a little bit easier,” he said.

According to Alva, the executive order may help address persistent treatment gaps in major depressive disorder (MDD) or PTSD, where many patients do not achieve remission with current therapies. However, he raised concerns about applying Right to Try pathways to Schedule I psychedelics without sufficient safeguards. Although he characterized expanded clinical trial activity as necessary, he emphasized that premature adoption without adequate training, monitoring, and infrastructure could introduce risks.

“[A] training pipeline would certainly be one of the requisites that we'd be looking at,” Alva said.

Watch part 1 of our interview with Alva here: 

Alva discusses infrastructure gaps, training demands, and unmet psychiatric need amid accelerated policy momentum for psychedelic therapies.

A White House executive order issued April 18, 2026, directs federal agencies to accelerate psychedelic research for 

. Signed by President Donald Trump, the order outlines steps for prioritizing review of psychedelic compounds, facilitating access under the Right to Try framework, and supporting collaborative research efforts involving federal agencies, academic centers, and the private sector.

The policy calls on the Food and Drug Administration (FDA) to issue National Priority Vouchers for eligible psychedelic therapies with Breakthrough Therapy designation and instructs the Drug Enforcement Administration to help establish pathways for clinician and researcher access to Schedule I investigational agents. It also allocates ≥ $50 million through federal collaboration to support research programs and directs interagency data-sharing efforts, including coordination with the Department of Veterans Affairs, to expand clinical trial participation and real-world evidence generation. Additional provisions address expedited review and potential rescheduling of products containing Schedule I substances after successful phase 3 trials.

 spoke with Gus Alva, MD, psychiatrist and medical director of ATP Clinical Research, to assess the scientific rationale, emerging evidence, and clinical considerations surrounding psychedelic therapies. Alva highlighted proposed mechanisms centered on 5-HT2A receptor activation and downstream neuroplastic effects.

“What's novel about psychedelics is that…they're basically opening a window of heightened neuroplasticity,” Alva said. “The reason that this is important is that this might actually help out with creating new associations, new internal models, and thus the brain becoming more responsive to things that are salubrious to it.”

According to Alva, several hypotheses may help explain reported rapid onset and durability signals, including increases in dendritic spine density within the prefrontal cortex and modulation of the default mode network. He noted that these changes may reduce rigid self-referential processing associated with rumination in depressive disorders.

He also referenced the relaxed beliefs under the psychedelics (REBUS) model, which proposes that altered hierarchical processing may allow updating of maladaptive internal models. Despite these theoretical frameworks, Alva emphasized that unanswered questions remain and that cautious interpretation of early findings is warranted.

He described the current evidence base as promising but heterogeneous. Randomized trials of psilocybin for treatment-resistant depression (TRD), including studies in 

, have shown meaningful symptom reductions several weeks after dosing versus active comparators. Phase 3 trials of MDMA-assisted therapy for PTSD have also reported reductions in Clinician-Administered PTSD Scale scores with signals of durability.

However, he noted key limitations in interpretation, including difficulty maintaining blinding due to noticeable psychoactive effects and challenges separating drug effects from the structured psychotherapy embedded in treatment protocols. He also highlighted safety concerns, including potential cardiotoxicity associated with ibogaine and its evaluation in highly selected cohorts. He said these factors underscore the need for rigorous study designs, standardized safety monitoring, and longer-term follow-up.

Alva noted that the executive order’s emphasis on accelerating research and collaboration may expand trial participation and evidence generation. He added that clinicians should monitor evolving regulatory and clinical developments while maintaining focus on patient safety, infrastructure requirements, and therapist training as psychedelic therapies continue to be evaluated.

Following an April 18 executive order, Gus Alva, MD, discusses psychedelic mechanisms, evidence, and clinical considerations for psychiatry.

The annual 2025 Southern California Psychiatry Conference (So Cal Psych), held July 11-12 in Huntington Beach, California, brings together regional clinical experts to deliver evidence-based insights. Sessions will not only cover novel therapeutic agents, including the newly approved xanomeline‑trospium for schizophrenia, but also explore mood disorders, digital therapeutics, long‑acting injectables, and neuromodulation.

As psychiatry continues to evolve mechanistically and technologically—with muscarinic receptor modulators, glutamatergic and GABAergic agents, neuromodulation, and metabolic-focused treatments, So Cal Psych offers the most up-to-date, hands-on education and insights. Attendees will engage in practical learning through case-based presentations, device demonstrations, and expert panels aimed at facilitating real-world clinical implementation.

Gus Alva, MD, DFAPA, is the medical director of ATP Clinical Research in Orange, CA, and serves as chair of the upcoming 2025 Southern California Psychiatry Conference for his second year. 

sister site, Psychiatry Times, caught up with Alva during the meeting to learn more about what attendees have to look forward to, including a deep dive into cutting-edge neuropsychiatric care, strategically bookended by sessions on muscarinic agonism’s role in schizophrenia and advances in treating Alzheimer’s disease.

: What is the significance of muscarinic agonism in schizophrenia and Alzheimer's, and how will this be addressed in the meeting?

The reason that this is so important is that as we commence with our sessions on schizophrenia, we need to recall it's a chronic, disabling brain disorder that affects maybe about 1% of the population. It's got multiple symptoms where individuals can't trust what they think or feel, and as a consequence of that, we definitely know there's an overlap with Alzheimer's disease. In fact, the term schizophrenia comes from the Greek for "splitting up the mind," and that very first session is going to entail some interesting themes, specifically tied in with an M1/M4 agonist called xenomeline, just to give everybody a good historical backdrop. Xenomeline was found to improve psychosis and behavioral disturbances in those suffering from Alzheimer's disease. As a consequence, the thought was, hey, this might actually be something useful for individuals with schizophrenia.

Unfortunately, the early points of xenomeline exploration were met with a lot of side effects, including salivation, sweating, and GI distress, all of which were likely attributed to the non-selective stimulation of muscarinic receptors beyond the M1/M4 agonism, predominantly M2 and M3 in the periphery. So, although xenomeline was not statistically significant in showing improvement in cognition, it did show a reduction in vocal outbursts, suspiciousness, delusions, agitation, and hallucinations—themes we'll be touching on in the last session of our meeting.

What can attendees expect to learn from sessions on mood disorders and digital therapeutics?

After the first session, we speak about bipolar disorder and characteristics associated with the condition, preceded by a non-CE talk led by Dr. Jerry Maguire. It's important that people remember acetylcholine is important for mood. Quite a while ago, we figured out that there are overriding factors that tie back to acetylcholine in depression. Contrary to M1/M4 agonism, M1 antagonism may provide a nice avenue for correcting mood in unipolar and bipolar depression.

Then we'll discuss digital therapeutics—a new modality in medicine. We've known about remote physiological monitoring and remote therapeutic monitoring, but now we're looking at smart applications on phones and tools like watches that might help our patients benefit more with the challenges they face. We'll speak about major depressive disorder and the advances within the glutamatergic system. Acetylcholine is deeply involved here too. The M1 receptor is coupled to the NMDA receptor, and antagonizing it might evoke a rapid response in individuals with depression.

We'll review those mechanisms and discuss newer agents coming out soon. We'll also touch on manipulating potassium channels, the opioid system, and incretins—which Dr. Roger McIntyre will address in his keynote speech, tying metabolic and neuropsychiatric states.

: What other clinical challenges will the meeting address on day two?

Day two will begin with difficult-to-treat depression. It's important to distinguish that from treatment-resistant depression. We'll look beyond pharmacological modalities to include augmentation strategies, quicker-acting agents, and neuromodulation. We'll have a great discussion on vagal nerve stimulation through a non-CE product theater, followed by a session on long-acting injectables to improve adherence in schizophrenia.

We'll also address postpartum depression and the use of neurosteroids, tying into the GABAergic pathway, glutamate, and acetylcholine. Finally, we’ll talk about the continuum of Alzheimer's disease and advances with monoclonal antibodies, as well as how to manage agitated or psychotic symptoms in later stages.

: What are some key takeaways you hope clinicians walk away with?

The overall takeaway points that we hope get threaded through every participant are that it's not difficult to stay up to date with the latest findings. Session 1 is a great refresher on why it makes sense to adopt new tools for treating schizophrenia. We now have an M1/M4 agonist for adults with schizophrenia that is not an antipsychotic. This helps de-stigmatize schizophrenia and move away from black box warnings, metabolic issues, and extrapyramidal symptoms.

Session 2 will offer a comprehensive look at bipolar disorder, including diagnostic and treatment updates from DSM-IV to DSM-5. Session three will explore digital therapeutics, including smartphone tools for schizophrenia and depression. Session 4 will dive into advanced treatment options for unipolar depression, from glutamate and GABA to potassium channels and GLP-1 agonists. Session five will focus on tardive dyskinesia and how to properly manage it. We'll close with more about long-acting injectables and cognition in the aging brain, rounding out 2 full days of highly applicable, up-to-date information for clinicians.

Our faculty—Dr. Jonathan Meyer, Chelsea Monroe, Melanie Barrett, Deb York, Yvette Elpedio, Saeed Jacob, Jacob Hene, Dr. Alex Alba, Dr. Jason Kellogg, Dr. Elon Melnick, Dr. Roger McIntyre, Dr. Gerald McGuire, and myself—are all thrilled to be part of this effort. I’m so happy to be here. Thank you for joining us.

This transcript has been edited for clarity. Relevant disclosures for Alva include Teva Pharmaceuticals, Otsuka America Pharmaceuticals, AbbVie Inc., Axsome Therapeutics, Janssen Pharmaceuticals, and more.

Articles

The 2025 Southern California Psychiatry Conference will focus on the latest advancements in psychiatry, including novel therapeutic agents, digital therapeutics, and neuromodulation. Key topics include the role of muscarinic agonism in schizophrenia and Alzheimer's, mood disorders, and digital therapeutics. The conference will also address difficult-to-treat depression, postpartum depression, and Alzheimer's disease management. Attendees will benefit from case-based presentations, device demonstrations, and expert panels. The event aims to provide clinicians with practical, up-to-date knowledge to enhance real-world clinical implementation and improve patient outcomes.

Discover cutting-edge insights on schizophrenia, mood disorders, and digital therapeutics at the 2025 Southern California Psychiatry Conference.