What evidence gaps are holding back psychedelic-assisted therapy?

Who is missing from the research? Older adults, adolescents, queer people, and people of color.

The vast majority of psychedelic-assisted therapy trials have studied a narrow slice of humanity. A systematic review of 36 trials with 1,400 participants found that only 19 people (less than 1.4%) were aged 65 or older, and detailed safety data was available for just 10 of them [1]. That means we have almost no evidence on how these treatments work for the growing older adult population who suffer from depression, anxiety, and end-of-life distress. The limited data suggests it is safe—no serious adverse events occurred in those 10 older adults—but the sample is far too small to draw firm conclusions [1].

Adolescents are even more absent. A scoping review covering 25 years of research (2000–2025) found only three trial registrations and one trial plan that included participants under 18, and none of those trials were completed or published [4]. This is a critical gap because many mental health conditions start in adolescence, and medications are often used off-label in this age group without proper evidence. The authors argue for cautious, ethically grounded research starting with older adolescents who have the highest potential benefit [4].

Queer people and people of color are also underrepresented. A scoping review on queer representation found that the vast majority of the literature stigmatizes queer psychedelic use, and only 18 out of over 30,000 captured resources meaningfully addressed the overlap between psychedelics and queerness [5]. Similarly, a qualitative study of BIPOC (Black, Indigenous, and People of Color) therapists found that they face barriers to entering the psychedelic therapy space, and clinical trials have included only small numbers of patients of color [9]. Without this data, we cannot know if psychedelic-assisted therapy works the same way—or safely—across different identities and backgrounds.

How should the therapy actually be delivered? There is no standard protocol.

Psychedelic-assisted therapy is not just a drug—it combines a psychedelic substance with psychological support, including preparation, the dosing session, and follow-up integration. But the 'therapy' part varies enormously between studies. A systematic review of 36 articles found that while 25 mentioned using music, there was no standardized protocol for selecting or using music during sessions [8]. Music is a key part of the 'setting' that shapes the psychedelic experience, yet researchers used different playlists, different lengths, and different genres, making it impossible to compare results across trials or know what works best [8].

The same inconsistency applies to the psychotherapeutic model itself. A review of psychedelic-assisted psychotherapy models found that studies use ad-hoc and adapted therapeutic methods, with no consensus on the therapist's stance, how directive they should be, or what information to give patients before the session [6]. This variability is a major evidence gap because it means we cannot attribute positive outcomes to the drug alone versus the specific therapy approach. Some patients relapse or are less responsive, and the therapeutic context may be a key moderator of efficacy [6].

Even the informed consent process has gaps. A review of 19 informed consent forms from U.S. trials found that while they met federal regulations, they often failed to address the unique vulnerability patients experience while under the effects of psychedelics—such as increased suggestibility and difficulty setting boundaries [7]. This is especially concerning given allegations of sexual misconduct in some early trials [7]. Without better consent processes that explain these altered states, participants may not truly understand what they are agreeing to.

Could genetics explain why some people respond differently? We don't know yet.

A key unanswered question is why some patients have intense, transformative experiences while others have difficult or ineffective sessions. Pharmacogenomics—how a person's genes affect drug metabolism—may be part of the answer, but the evidence is still very limited [3]. Studies suggest that genetic variants in drug-metabolizing enzymes like CYP2D6 can impact the intensity of acute effects for LSD and ibogaine, and that poor metabolizers might need lower doses [3]. For psilocybin and 5-MeO-DMT, it is hypothesized that CYP2D6 status could alter the experience when combined with other drugs, but this is based on preclinical evidence, not human trials [3]. Incorporating genetic testing into future research could help personalize dosing and improve safety, but right now it is a gap, not a standard practice [3].

Can this therapy work outside of tightly controlled research settings?

Even if the evidence gaps on efficacy and safety were filled, there is a huge 'know-do gap'—the typical 17-year lag between research findings and routine clinical practice [2]. Psychedelic-assisted therapy is a multimodal treatment that requires regulatory approvals, specialized clinical training, and changes to how mental health care is delivered [2]. Implementation science methods, such as hybrid study designs that test both effectiveness and real-world feasibility simultaneously, are recommended to accelerate this process without sacrificing safety [2]. Currently, we have almost no data on how to train therapists, set up treatment centers, or ensure equitable access once these therapies are approved [2][10]. Without this implementation evidence, promising treatments may remain unavailable to the people who need them most.

About These Sources

This answer is built on 10 peer-reviewed studies — published from 2022 to 2026, 8 from 2024 or later, 6 in Q1 journals, collectively cited 165 times — selected as the most relevant from 13 studies that passed quality screening, drawn from 58 papers retrieved from a database of over 500 million.

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