Psychedelics for Chronic Pain? The Problem and The Unmet Need

Neurmodulation isn't just for mental health

TL;DR

• The ‘lesion’ in Chronic Pain is neurological, not anatomical

• Current treatment options are not great, and the unmet need is large

• like depression, anxiety, and PTSD, Chronic Pain has a structural component (neural circuitry) and an affective/cognitive/emotional/conceptual component

• Neuroplastic changes created the problem, neuroplastic changes can resolve the problem

Chronic Pain: The Case for Psychedelics

If you’re reading this, you already know… psychedelics have the potential to radically improve mental health outcomes.

Why?

Conditions of the mind/soul/consciousness/neural circuits are stubborn as hell.

They are highly complex, highly individualized, and often survival strategies that we employed earlier in our lives, so we’ve had them for a bit.

Psychedelics open a therapeutic window that, when combined with human connection, guidance, and integration, allows for the innate capacity to heal and restore function to take place.

From a clinical science perspective, we might say the conditions the psychedelic medicine community is focused on are disruptions of regulatory networks.

Chief among them is depression, substance abuse, anxiety, and PTSD.

Let’s add chronic pain to the mix.

Researchers at UC San Diego published “Chronic pain and psychedelics: a review and proposed mechanism of action”

Barb Bauer of the Psychedelic Science Review had a nice summary of the main gist:

In proposing their hypothesis for how psychedelics act as analgesics, the authors reviewed three concepts:

1) The mechanism of action of psychedelics at serotonin receptors (primarily 5-HT2A).

2) The downstream effects of psychedelics in the body leading to modulation of gene expression and inflammation.

3) Changes in brain functional connectivity (FC) brought on by psychedelics.

I am gonna get a bit more meta and propose that psychedelics, as Rolland Griffiths put it, have transdiagnostic capacity via what I am thinking of as Neuro-conceptual Modulation, and it is this feature that makes psychedelics attractive as a potential treatment for chronic pain.

What is Chronic Pain?

This is probably a flummoxing proposition for many—why would compounds that act on neural pathways via serotonin receptors have any role in pain located at some part of the body???

In my experience, most people living with chronic pain and most professionals working with chronic pain view the condition as long-standing tissue damage.

That is, the belief that low back pain, for example, must be caused by damage to the vertebra, disc, nerve, muscle, or soft tissue at the site of pain.

As a general rule of thumb, this is true in cases of acute pain. However, in pain conditions with no inciting incident or that have persisted longer than a few weeks, we need to look elsewhere for the cause.

Where should we look?

The nervous system.

Without getting into the weeds, you can think of chronic pain as a maladaptive form of neuroplasticity.

We invoke neuroplastic changes as the reason we see improvements in psychedelic therapy, but it goes both ways. As prominent pain scientist, Lorimer Mosely is known to say, “Neuroplasticity got you into this mess, and neuroplasticity will get you out of it.”

I think most people understand that the results of a trauma “rewire” the brain in a maladaptive way, and over time this maladaptation becomes more and more entrenched.

Well, chronic pain works in a similar fashion. For a host of factors, some people cannot “unlearn” pain.

Central Sensitization

In painful conditions that extend beyond the normal healing time, the nervous system develops a heightened capacity to produce pain in a process called Central Sensitization.

So even though the pain is experienced at a certain part of the body, perhaps with certain movements (which reinforces the idea that the pain is the result of local tissue damage), the culprit is, in fact, the result of neuroplastic changes in the brain and spinal cord.

I admit that my passion and enthusiasm for this topic perhaps outweigh my ability to succinctly and convincingly explain it so if you are keen, I recommend the below brief TED talk from Lorimer Moseley, who, despite looking like an amateur magician with a creepy facial hair is, in fact, Oxford-trained and widely respected pain researcher.

How Big is the Chronic Pain Problem?

Chronic pain not only resembles Treatment-Resistant Depression, PTSD, and addiction as maladaptive neuroplastic changes but in two other important factors: the difficulty, often futility of treatment, and the scale of the problem.

From JAMA:

"The National Academy of Sciences estimated in 2010 that more than 100 million American individuals experienced chronic unrelieved pain"

From the CDC:

"In 2016, an estimated 20.4% (50 million) of U.S. adults had chronic pain and 8.0% (19.6 million) of U.S. adults had high-impact chronic pain. Both were more prevalent among adults living in poverty, adults with less than a high school education, and adults with public health insurance."

Costs of Chronic Pain

Again from JAMA:

"The estimated cost was $560 billion to $635 billion per year, composed of direct health care costs ($261 billion to $300 billion), days of work missed ($11.6 billion to $12.7 billion), hours of work missed ($95.2 billion to $96.5 billion), and lower wages ($190.6 billion to $226.3 billion.) The cost of pain was more than that of heart disease and cancer treatments."

No, Walter, things are very, very fucked here.

Current Treatment

Persistent Low back pain is one of the leading reasons people go to their doctor. Depending on a HUGE variety of factors, someone might leave with advice to take Advil, undergo x-rays or MRI, or get a prescription for Physical Therapy.

The problem is that when pain persists, the variety of treatment options and expert opinions expand drastically, and decisions are made, and advice is given without any real scientific rationale. People end up with surgery, injections, physical therapy, chiropractic, acupuncture, massage, etc. again, without any real scientific guidance.

Many people will experience episodes of persistent pain, most will resolve, and many will go through a gauntlet of treatments that kinda-sorta give relief, but the vast majority of interventions and explanations for the persistent symptoms will identify some sort of tissue damage or abnormality as the culprit.

The challenge of addressing the root cause of chronic pain, that is, the maladaptive neuroplasticity, is that it takes time and requires a skilled therapist and continuous effort. To make it even more challenging, it requires the patient to update their conceptualization, beliefs, understanding, and actions.

In short, it is a lot like psychotherapy.

This is why I am bullish on the use of psychedelics for chronic pain.

Neuro-Conceptual Modulation

I made up this phrase, but I have a feeling that there’s already a term for it. I’ll try my best to flesh it out because I think this is a useful framework for psychedelic-assisted therapy for pain as well as other conditions.

Psychedelics promote neurological flexibility (neuroplasticity) and psychological flexibility.

I have the sense that most people get that the ‘wiring’ of neural circuits is implicated in everything we do, feel, behave, believe, etc. Every movement, concept, word, belief, taste, smell, etc., and everything that we experience is produced/associated with a pattern of neural activity called neurotags.

But what I think is less appreciated is the beliefs, conceptualizations, priors, and understanding we have about ourselves, reality, the nature of consciousness, also feedback upon the neurotags themselves.

The belief that we have about our condition, whether it is depression or persistent pain, impacts the durability of the condition.

Since our beliefs and understanding are stored in patterns of neural activity, an agent that has the capacity to disrupt these patterns and allow a window of malleability can change both the structure of these connections and the beliefs, conceptualizations, priors, and understanding we have.

This is what I mean by neuro-conceptual modulation.

I hope you’re still with me.

A more reductive perspective might argue that the neuro-conceptual stuff is bologna (I will never get over the spelling of bologna) and that the psychedelic capacity to treat chronic pain comes from descending inhibition mediated by 5-HT activation and, as the UCSD authors suggest reducing inflammation and functional connectivity changes.

To which I would say:

It depends on how you look at it, and they are not mutually exclusive.

Back to the UCSD Paper:

“Given the accumulating evidence of altered brain FC in chronic pain states, the ability of psychedelics to disrupt established brain connection patterns is perhaps the most intriguing potential analgesic mechanism for psychedelics. Should this prove to be the case, combining psychedelics with more traditional therapeutic modalities could result in synergistic therapeutic benefits. Potential psychedelic co-therapeutic modalities include MVF therapy, physical therapy, nerve blocks, neuromodulation techniques or others with the goal of reversing some of the neuroplastic changes that resulted in the chronic pain state.”

The Opportunity

Without getting overzealous about the potential for psychedelics to change the world and treat every ailment, I think that serious exploration into Psychedelic Assisted Therapy directed at Chronic pain in conjunction with physical therapy and pain education deserves a close look.

With the understanding that Chronic Pain is both a neurological and a conceptual/cognitive condition, research into psychedelics for pain should consider following in the footsteps of MDMA and Psilocybin assisted therapies, and when it comes time for clinical research, including Therapeutic Pain Science Education in conjunction with preparation and integration sessions, I am convinced will yield results for chronic pain.