If this author was being pedantic, they might be tempted to point out errors or sloppiness in this piece, which include…

• “In short, it is not the substances alone but their combination with the broader sequence of psychotherapy with trained psychiatrists and psychotherapists that ensures the therapeutic benefit.” While this is almost received wisdom among many in the psychedelics space, it has not been borne out in research just yet. Indeed, as the FDA’s draft guidance notes, “the contribution of the psychotherapy component to any efficacy observed with psychedelic treatment has not been characterized”.
• Claims that several states in the U.S. have “begun approving psychedelic therapies for a range of conditions” conflate therapy with the licensed facilitation of non-medical services as seen in Oregon and (soon) Colorado. These contexts are again conflated later when they’re referred to as “medically supervised use”.
• The fact that a “bad trip” is discussed as a potential adverse outcome of microdosing is odd, given that microdoses tend to be sub-perceptual. Meanwhile, the potential risks of chronic 5-HT2B agonism isn’t discussed at all.

But, overall, this is a largely informative piece for the average reader which does a good job of capturing growing levels of interest in psychedelics from researchers and users alike.

It’s also helpful in outlining the central concern of many regulators: the ‘risk’ that non-medical use outpaces, or proves more accessible than, offerings that are the product of clinical trials and medical research. Of course, the most consequential element is whether, or how, regulators choose to react to this perceived risk.

European Drug Report Briefly Discusses Psychedelics

In a similar spirit, the European Monitoring Centre for Drugs and Drug Addiction’s (EMCDDA) European Drug Report also covered psychedelics, choosing to focus on the “possible adverse consequences of growing interest in the therapeutic potential of psychedelic drugs”.

While the agency acknowledges that “some research appears promising”, it warns that the considerable media attention afforded to these studies “may encourage greater experimental use of these substances without medical support, potentially putting some vulnerable individuals at risk of suffering adverse consequences.” The report also mentions evidence of ‘unregulated programmes’ being operated in the EU, alluding to retreats.

FDA Issues Draft Guidance on Psychedelic Trials

Last Friday the FDA issued its first draft guidance on clinical trials with psychedelic drugs. The 14-page document presents non-binding guidance, or “considerations”, that psychedelic drug developers would be wise to heed.

Interestingly, unlike UNODC, FDA doesn’t include dissociative anaesthetics like ketamine in its definition of ‘psychedelics’, perhaps due to the fact that ketamine is already FDA approved.

One element of the guidance has caused a stir among psychedelic researchers and practitioners:

“The therapist monitoring the session can usually deduce the treatment assignment by observing the subject’s behavior. Therefore, it is preferable that the in-session monitor is not involved in post-session psychotherapy because their knowledge of the treatment could bias the delivery of subsequent therapy.”

This suggestion, the FDA thinks, might help reduce bias in assessing efficacy. But it flies in the face of received wisdom among many psychedelic therapists (and non-psychedelic therapists, for that matter).

We covered this topic in much more detail back in March, when FDA’s Tiffany Farchione addressed participants at ECNP in France and mentioned this potential guidance. While it wasn’t a significant portion of her presentation, it piqued this author’s interest:

Where Regulators and Researchers Disagree

One of the points raised by FDA’s Farchione got me thinking. As aforementioned, Farchione suggested that sponsors might reduce potential biases by having post-treatment therapy conducted by a different person than the in-session monitor.

This approach struck me as out of kilter with what a number of researchers had mentioned throughout the meeting, prior to Farchione’s presentation.

Gerhard Gründer, who leads a psilocybin for depression study funded by the German government (see our November 2020 coverage), believes that “if you administer a psychedelic there’s a special relationship between the therapist and the patient”. Gründer shared emails from two patients in his trial to illustrate his point, with one patient writing: “I am infinitely grateful to you, […] I cherish you in deep friendship, not as therapists but as people.”

The most important factor in the efficacy of psychotherapy is the alliance between patient and therapist(s), he said, adding that “we may lose efficacy” if we separate the therapists who psychologically support the administration of psychedelics from “true psychotherapists.” Gründer was emphatic: this alliance “cannot be delegated for a couple of days to someone to administer the drug”.

Elsewhere, during a question and answer period, David Erritzoe discussed how the responsibility of the therapist in managing the very difficult (and sometimes possibly false, dream-like) material that may emerge during a psychedelic session is “immense”, “massive”.

Upon hearing the FDA’s proposal of having a different person conduct the post-drug integration sessions, I wondered how this might work given Erritzoe’s experiences. How might a therapist who did not witness the psychedelic session take on this “immense” task?

Perhaps this is why psychedelic drug developers and researchers alike have not adopted this element in their study designs.

This mismatch between FDA advice and our current (presumed) ‘best practice’ of psychedelic therapy perhaps points to a larger piece of context that is always worth remembering: the FDA does not regulate psychotherapy. Given this fact, it’s not surprising (or sinister) that the agency is looking to disaggregate the drug effect from the psychotherapy, or psychological support.

It does continue to generate friction and challenges, though, for psychedelic drug developers who walk a fine line between satisfying the FDA that they have taken adequate steps to reduce bias and provide a valid comparison to something, and maintaining key elements of psychedelic-assisted therapy that are presumed to drive its safety and efficacy.

Gründer’s advice (or, plea) to regulators: “Don’t just look at curves. Listen to the patients and to the therapists!”

A 60-day public comment period is now underway, meaning you can take umbrage to this suggestion—and any of the others—via the Federal Register.

Elsewhere, the Royal Australian & New Zealand College of Psychiatrists (RANZCP) released a Clinical Memorandum on the therapeutic use of psychedelics this month, ahead of the limited rescheduling of psilocybin- and MDMA-assisted therapy in Australia next week.